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The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis.
Methods
Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank. Both datasets had information on cannabis use.
Results
In both samples, schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use in the EU-GEI cases or controls or UK Biobank cases. It was associated with lifetime and daily cannabis use among UK Biobank participants without psychosis, but the effect was substantially reduced when CUD PRS was included in the model. In the EU-GEI sample, regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS (OR daily use high-potency cannabis adjusted for PRS = 5.09, 95% CI 3.08–8.43, p = 3.21 × 10−10). We found no evidence of interaction between schizophrenia PRS and patterns of cannabis use.
Conclusions
Regular use of high-potency cannabis remains a strong predictor of psychotic disorder independently of schizophrenia PRS, which does not seem to be associated with heavy cannabis use. These are important findings at a time of increasing use and potency of cannabis worldwide.
One century after its initial excavation, this article presents the first absolute chronology for the settlement of Karanis in Egypt. Radiocarbon dates from crops retrieved from settlement structures suggest that the site was inhabited beyond the middle of the fifth century AD, the time at which it was previously believed to have been abandoned. These dates add to the complex picture of population fluctuations and the remodelling and reuse of structures at Karanis. Two dates reach into the middle of the seventh century, placing the abandonment of the site in a period of political and environmental transition that changed the physical and social landscape of the Fayum region and beyond.
The knowledge, skills, and abilities needed for clinical research professionals (CRPs) are described in the Joint Task Force (JTF) for Clinical Trial Competencies Framework as a basis for leveled educational programs, training curricula, and certification. There is a paucity of literature addressing team science competencies tailored to CRPs. Gaps in training, research, and education can restrict their capability to effectively contribute to team science.
Materials/Methods:
The CRP Team Science team consisted of 18 members from 7 clinical and translational science awarded institutions. We employed a multi-stage, modified Delphi approach to define “Smart Skills” and leveled team science skills examples using individual and team science competencies identified by Lotrecchiano et al.
Results:
Overall, 59 team science Smart Skills were identified resulting in 177 skills examples across three levels: fundamental, skilled, and advanced. Two examples of the leveled skillsets for individual and team competencies are illustrated. Two vignettes were created to illustrate application for training.
Discussion:
This work provides a first-ever application of team science for CRPs by defining specific individual and team science competencies for each level of the CRP career life course. This work will enhance the JTF Domains 7 (Leadership and Professionalism) and 8 (Communication and Teamwork) which are often lacking in CRP training programs. The supplement provides a full set of skills and examples from this work.
Conclusion:
Developing team science skills for CRPs may contribute to more effective collaborations across interdisciplinary clinical research teams. These skills may also improve research outcomes and stabilize the CRP workforce.
The number of patient preference studies in health has increased dramatically. There is growing use of patient preferences in a wide variety of contexts, including health technology assessment. Patient preference studies can help inform decision makers on the needs and priorities of patients and the tradeoffs they are willing to make about health technologies.
Methods
This International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force included international experts, health preference researchers and others from diverse backgrounds, including regulatory, health technology assessment, medicine, patient advocacy, and the pharmaceutical industry. The report underwent two rounds of written reviews by ISPOR Preferences Special Interest Group members until a final consensus was reached. The Task Force focused on developing a roadmap that would: (i) apply to the wide variety of preference methods, (ii) identify key domains to guide researchers and other stakeholders in making patient preference studies more useful to decision makers, and (iii) detail important questions to guide researchers conducting preference studies and those critically appraising them.
Results
This Task Force report provides a novel roadmap that invites patient-preference researchers to work with decision makers, patients and other stakeholders to do even more to ensure that studies are useful and impactful. The ISPOR Roadmap consists of five key elements: (i) Context; (ii) Purpose; (iii) Population; (iv) Method; and (v) Impact. In this report, we define these five elements and provide good practices on how patient-preference researchers can actively contribute to increasing the usefulness and impact of patient preference studies in decision-making. We also present a set of key questions that can support researchers and other stakeholders in assessing efforts that promote preference studies’ intended and unintended impact.
Conclusions
This roadmap can help increase the usefulness and impact of patient preference studies in decision-making by challenging researchers to engage and partner with decision makers, patients and others, and together consider the intended and unintended impacts of patient preference studies on decision-making while actively fostering positive impact.
Aims and auditable outcomes: We aim to ensure 100% patients on clozapine have annual physical health checks. By ensuring all patients prescribed clozapine therapy receive an annual physical health check and medic review, we aim to improve patient safety and prevent serious harm from occurring in cases that could be avoided.
Methods
All patients aged over 18 years prescribed Clozapine, who were under the assessment and treatment service in Eastbourne, were identified using Carenotes, our electronic patient records system.
Results
78% of patients on clozapine had been reviewed by a doctor in the past 12 months. 32% of patients had attended a physical health review within the past 12 months. One patient had not had a medical review for several years.
Conclusion
Our audit has shown that there are no clear guidelines on the long term monitoring of clozapine in regards to physical health reviews and psychiatric assessment. Using best practice it appears annual review should be the minimal standard, however further evaluation of this is recommended at trust level.
In response to these results and the current guidance, we would like to implement the following:
• Create a database for all patients on Clozapine under the care of Eastbourne ATS.
• Create a spreadsheet looked after by one member of admin staff to be updated regularly
• The physical health lead nurse to be informed of physical health checks due by admin
While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis.
Methods
We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case–control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.
We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case–control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case–control status.
Results
Controls (86.1%) and FEPp (75.63%) were most likely to report ‘because of friends’ as their most common RFUC. However, 20.1% of FEPp compared to 5.8% of controls reported: ‘to feel better’ as their RFUC (χ2 = 50.97; p < 0.001). RFUC ‘to feel better’ was associated with being a FEPp (OR 1.74; 95% CI 1.03–2.95) while RFUC ‘with friends’ was associated with being a control (OR 0.56; 95% CI 0.37–0.83). The path model indicated an association between RFUC ‘to feel better’ with heavy cannabis use and with FEPp-control status.
Conclusions
Both FEPp and controls usually started using cannabis with their friends, but more patients than controls had begun to use ‘to feel better’. People who reported their reason for first using cannabis to ‘feel better’ were more likely to progress to heavy use and develop a psychotic disorder than those reporting ‘because of friends’.
OBJECTIVES/GOALS: Team science competencies are not well-defined for nonfaculty staff of Clinical Research Professionals (CRPs) who conduct research. Using an existing framework, our work has determined skills associated with team science competencies as related to CRPs. Our team also outlined examples of those skills on a fundamental, skilled, and advanced level. METHODS/STUDY POPULATION: The team consists of both CRPs and those working in the Team Science space. This team used a modified Delphi approach to determine the skills and leveling examples of each team science competency. The team broke into four groups and was assigned 3-4 competencies each. Each group determined skills needed to support (exhibit, promote) each competency and then described an example of this skill at the fundamental, skilled, and advanced levels. Once each group was finished with their assigned competencies, they were re-assigned to a different group for review and changes. Finally, team science and CRP experts reviewed the skills and levels. RESULTS/ANTICIPATED RESULTS: Our results are a rubric that defines 3-5 practical skills per described competency. These skills are needed to support and promote each competency as a CRP. An additional outcome from this work includes examples of each skill at the fundamental, skilled, and advanced levels in a CRP’s career. Each leveled example is described in a concise, actionable way using Bloom’s taxonomy. This rubric is meant to be easily understood, very useable and able to be used in conjunction with existing CRP competency frameworks. By using Bloom’s taxonomy, we set the stage for future educational programming in Team Science skill-building for clinical research professionals. DISCUSSION/SIGNIFICANCE: Team science concepts and competencies have been increasingly integrated into translational science teams. However, team science competencies related to CRPs have remained largely undefined. Our work helps to define these competencies for CRPs in a practical way. Our rubric fills gaps in, and builds on, existing CRP competency frameworks.
The current coronavirus disease (COVID-19) pandemic has placed unprecedented strain on underfunded public health resources in the Southeastern United States. The Memphis, TN, metropolitan region has lacked infrastructure for health data exchange.
This manuscript describes a multidisciplinary initiative to create a community-focused COVID-19 data registry, the Memphis Pandemic Health Informatics System (MEMPHI-SYS). MEMPHI-SYS leverages test result data updated directly from community-based testing sites, as well as a full complement of public health data sets and knowledge-based informatics. It has been guided by relationships with community stakeholders and is managed alongside the largest publicly funded community-based COVID-19 testing response in the Mid-South. MEMPHI-SYS has supported interactive Web-based analytic resources and informs federally funded COVID-19 outreach directed toward neighborhoods most in need of pandemic support.
MEMPHI-SYS provides an instructive case study of how to collaboratively establish the technical scaffolding and human relationships necessary for data-driven, health equity-focused pandemic surveillance, and policy interventions.
Obesity in adolescents with intellectual and developmental disabilities) occurs at twice the frequency as their typically developing peers. Typically developing adolescents with obesity have abnormal cardiac function (as measured by strain echocardiography) and cardiac mass, but the effects of obesity on cardiac health in adolescents with Down syndrome or autism spectrum disorder are unknown. The purpose of this study was to evaluate the impact of body mass index on cardiac function in adolescents with Down syndrome or autism.
Methods:
Adolescents (age 12–21 years) with Down syndrome (n = 28), autism (n = 33), and age-/sex-matched typically developing controls (n = 15) received an echocardiogram optimised for strain analysis at a single timepoint. Measures of ventricular function, mass, and size were collected. Regression modelling evaluated the impact of body mass index and intellectual and developmental disabilities diagnosis on these cardiac measures.
Results:
In regression modelling, an elevated body mass index z-score was associated with diminished systolic biventricular function by global strain (left ventricular longitudinal strain β 0.87, P < 0.001; left ventricular circumferential strain β 0.57, p 0.003; right ventricular longitudinal strain β 0.63, P < 0.001). Diminished left ventricular diastolic function by early diastolic strain rate was also associated with elevated body mass index (global longitudinal end-diastolic strain rate β −0.7, P < 0.001). No association was found between traditional (non-strain) measures of systolic and diastolic ventricular function and body mass index z-score.
Conclusions:
Obesity in adolescents with Down syndrome or autism negatively impacts cardiac function as measured by echocardiographic strain analysis that was not detected by traditional parameters.
Psychiatric mother and baby units (MBUs) are recommended for severe perinatal mental illness, but effectiveness compared with other forms of acute care remains unknown.
Aims
We hypothesised that women admitted to MBUs would be less likely to be readmitted to acute care in the 12 months following discharge, compared with women admitted to non-MBU acute care (generic psychiatric wards or crisis resolution teams (CRTs)).
Method
Quasi-experimental cohort study of women accessing acute psychiatric care up to 1 year postpartum in 42 healthcare organisations across England and Wales. Primary outcome was readmission within 12 months post-discharge. Propensity scores were used to account for systematic differences between MBU and non-MBU participants. Secondary outcomes included assessment of cost-effectiveness, experience of services, unmet needs, perceived bonding, observed mother–infant interaction quality and safeguarding outcome.
Results
Of 279 women, 108 (39%) received MBU care, 62 (22%) generic ward care and 109 (39%) CRT care only. The MBU group (n = 105) had similar readmission rates to the non-MBU group (n = 158) (aOR = 0.95, 95% CI 0.86–1.04, P = 0.29; an absolute difference of −5%, 95% CI −14 to 4%). Service satisfaction was significantly higher among women accessing MBUs compared with non-MBUs; no significant differences were observed for any other secondary outcomes.
Conclusions
We found no significant differences in rates of readmission, but MBU advantage might have been masked by residual confounders; readmission will also depend on quality of care after discharge and type of illness. Future studies should attempt to identify the effective ingredients of specialist perinatal in-patient and community care to improve outcomes.
Anorexia nervosa (AN) is a psychiatric disorder with complex etiology, with a significant portion of disease risk imparted by genetics. Traditional genome-wide association studies (GWAS) produce principal evidence for the association of genetic variants with disease. Transcriptomic imputation (TI) allows for the translation of those variants into regulatory mechanisms, which can then be used to assess the functional outcome of genetically regulated gene expression (GReX) in a broader setting through the use of phenome-wide association studies (pheWASs) in large and diverse clinical biobank populations with electronic health record phenotypes.
Methods
Here, we applied TI using S-PrediXcan to translate the most recent PGC-ED AN GWAS findings into AN-GReX. For significant genes, we imputed AN-GReX in the Mount Sinai BioMe™ Biobank and performed pheWASs on over 2000 outcomes to test the clinical consequences of aberrant expression of these genes. We performed a secondary analysis to assess the impact of body mass index (BMI) and sex on AN-GReX clinical associations.
Results
Our S-PrediXcan analysis identified 53 genes associated with AN, including what is, to our knowledge, the first-genetic association of AN with the major histocompatibility complex. AN-GReX was associated with autoimmune, metabolic, and gastrointestinal diagnoses in our biobank cohort, as well as measures of cholesterol, medications, substance use, and pain. Additionally, our analyses showed moderation of AN-GReX associations with measures of cholesterol and substance use by BMI, and moderation of AN-GReX associations with celiac disease by sex.
Conclusions
Our BMI-stratified results provide potential avenues of functional mechanism for AN-genes to investigate further.
Little is known about mental health problems of children and young people (CYP) involved with public and private law family court proceedings, and how these CYP fare compared to those not involved in these significant disruptions to family life.
Aims
This study examined records of depression/anxiety in CYP involved in public and private law proceedings using linked population-level data across Wales.
Method
Retrospective e-cohort study. We calculated the incidence of primary-care-recorded depression/anxiety among CYP involved in these proceedings and in a comparison group, using Poisson regression. Depression/anxiety outcomes following proceedings were evaluated using pairwise Cox regression, with age- and gender-matched controls of CYP who had no involvement with the courts.
Results
CYP in the public group had twice the risk of depression (adjusted incidence rate ratio aIRR = 2.2; 95% CI 1.9–2.6) and 20% higher risk of anxiety (aIRR = 1.2; 95% CI 1.0–1.5) relative to the comparison group. The private group had 60% higher risk of depression (aIRR = 1.6; 95% CI 1.4–1.7) and 30% higher risk of anxiety (aIRR = 1.3; 95% CI 1.2–1.4). Following private law proceedings, CYP were more likely to have depression (hazard ratio HR = 1.9; 95% CI 1.7–2.1), and anxiety (HR = 1.4; 95% CI 1.2–1.6) than the control group. Following public proceedings, CYP were more likely to have depression (HR = 2.1; 95% CI 1.7–2.5). Incidence of anxiety or depression following court proceedings was around 4%.
Conclusions
Findings highlight the vulnerability of CYP involved in family court proceedings and increased risk of depression and anxiety. Schools, health professionals, social and family support workers have a role to play in identifying needs and ensuring CYP receive appropriate support before, during and after proceedings.
To identify eating occasion-level and individual-level factors associated with the consumption of larger portions in young children and estimate their relative importance.
Design:
Cross-sectional.
Setting:
Data from parent-reported 4-d food diaries in the UK National Diet and Nutrition Survey (2008–2017) were analysed. Multilevel models explored variation in eating occasion size (kJ) within (n 48 419 occasions) and between children (n 1962) for all eating occasions. Eating contexts: location, eating companion, watching TV, and sitting at a table and individual characteristics: age, gender, ethnicity and parental socio-economic status were explored as potential correlates of eating occasion size.
Participants:
Children aged 1·5–5 years.
Results:
Median eating occasion size was 657 kJ (IQR 356, 1117). Eating occasion size variation was primarily attributed (90 %) to differences between eating occasions. Most (73 %) eating occasions were consumed at home. In adjusted models, eating occasions in eateries were 377 kJ larger than at home. Eating occasions sitting at a table, v. not, were 197 kJ larger. Eating in childcare, with additional family members and friends, and whilst watching TV were other eating contexts associated with slightly larger eating occasion sizes.
Conclusions:
Eating contexts that vary from one eating occasion to another are more important than demographic characteristics that vary between children in explaining variation in consumed portion sizes in young children. Strategies to promote consumption of age-appropriate portion sizes in young children should be developed, especially in the home environment, in eating contexts such as sitting at the table, eating with others and watching TV.
The ancient city of Gabii—an Italian polity of the first millennium BC and a peer to early Rome—has often been presented as an example of urban decline, a counterpoint to Rome's rise from a collection of hilltop huts to a Mediterranean hegemon. Here the authors draw on the results from recent excavations at Gabii that challenge such simplistic models of urban history. Diachronic evidence documenting activity at the site over the course of 1400 years highlights shifting values and rhythms materialised in the maintenance, transformation and abandonment of different urban components. This complex picture of adaptation and resilience provides a model of ancient urbanism that calls into question outdated narratives of urban success and failure.
Understanding the socio-economic inequalities in dietary intake is crucial when addressing the socio-economic gradient in obesity rates and non-communicable diseases. We aimed to systematically assess the association between socio-economic position (SEP) and dietary intake in Chile.
Design:
We searched for peer-reviewed and grey literature from inception until 31 December 2019 in PubMed, Scopus, PsycINFO, Web of Sciences and LILACS databases. Observational studies published in English and Spanish, reporting the comparison of at least one dietary factor between at least two groups of different SEP in the general Chilean population, were selected. Two researchers independently conducted data searches, screening and extraction and assessed study quality using an adaptation of the Newcastle Ottawa Quality Assessment Scale.
Results:
Twenty-one articles (from eighteen studies) were included. Study quality was considered low, medium and high for 24, 52 and 24 % of articles, respectively. Moderate-to-large associations indicated lower intake of fruit and vegetables, dairy products and fish/seafood and higher pulses consumption among adults of lower SEP. Variable evidence of association was found for energy intake and macronutrients, in both children and adults.
Conclusions:
Our findings highlight some socio-economic inequalities in diets in Chile, evidencing an overall less healthy food consumption among the lower SEP groups. New policies to reduce these inequalities should tackle the unequal distribution of factors affecting healthy eating among the lower SEP groups. These findings also provide important insights for developing strategies to reduce dietary inequalities in Chile and other countries that have undergone similar nutritional transitions.
An adequate intake of PUFA plays a vital role in human health. Therefore, it is important to assess PUFA intakes in different populations and validate them with biomarkers, but only a few small studies are in paediatric populations. We calculated the dietary intake of PUFA and their main food sources in children and assessed associations between PUFA intakes and plasma proportions. Dietary intakes of 7-year-old children (n 8242) enrolled in the Avon Longitudinal Study of Parents and Children were calculated from the parental-completed FFQ. Plasma PUFA were measured in 5571 children 8 months later, and 4380 children had complete dietary and plasma data. The association between dietary and plasma PUFA proportions was estimated using Spearman’s correlation coefficients, quintile cross-classification and Cohen’s κ coefficients. Mean total PUFA intake was 13·2 g/d (sd 4·2), contributing 6·5 % of total energy intake; n-6 PUFA contributed 5·2 % and n-3 PUFA 0·7 %. The n-6:n-3 ratio was 7·9:1. Mean intakes of EPA and DHA were 35·7 mg/d and 49·7 mg/d, respectively. Most n-3 and n-6 PUFA intakes were weakly correlated with their respective plasma lipids (0·07 ≤ r ≤ 0·16, P < 0·001). The correlation between dietary and plasma DHA was stronger though (r = 0·34, P < 0·001), supported by a modest level of agreement between quintiles (k = 0·32). The results indicate that the FFQ was able to reasonably rank the long-chain (LC) PUFA, DHA, in this paediatric population. Public health initiatives need to address the suboptimal ratio of n-6:n-3 PUFA and very low n-3 LC-PUFA intakes in school-age children in the UK.
This study compared the level of education and tests from multiple cognitive domains as proxies for cognitive reserve.
Method:
The participants were educationally, ethnically, and cognitively diverse older adults enrolled in a longitudinal aging study. We examined independent and interactive effects of education, baseline cognitive scores, and MRI measures of cortical gray matter change on longitudinal cognitive change.
Results:
Baseline episodic memory was related to cognitive decline independent of brain and demographic variables and moderated (weakened) the impact of gray matter change. Education moderated (strengthened) the gray matter change effect. Non-memory cognitive measures did not incrementally explain cognitive decline or moderate gray matter change effects.
Conclusions:
Episodic memory showed strong construct validity as a measure of cognitive reserve. Education effects on cognitive decline were dependent upon the rate of atrophy, indicating education effectively measures cognitive reserve only when atrophy rate is low. Results indicate that episodic memory has clinical utility as a predictor of future cognitive decline and better represents the neural basis of cognitive reserve than other cognitive abilities or static proxies like education.
To conduct formative research using qualitative methods among stakeholders of secondary schools to explore their perceptions, barriers and facilitators related to healthy eating and physical activity (PA) among Malaysian adolescents.
Design:
A qualitative study involving eight focus groups and twelve in-depth interviews. Focus groups and interviews were recorded and transcribed verbatim. An inductive thematic analysis approach was used to analyse the data.
Setting:
Four secondary schools in Perak and Selangor states (two urban and two rural schools) in Malaysia.
Participants:
Focus groups were conducted with seventy-six adolescents aged 13–14 years, and in-depth interviews were conducted with four headmasters, four PA education teachers and four food canteen operators.
Results:
Stakeholders thought that adolescents’ misperceptions, limited availability of healthy options, unhealthy food preferences and affordability were important challenges preventing healthy eating at school. Low-quality physical education (PE) classes, limited adolescent participation and teachers’ commitment during lessons were perceived as barriers to adolescents being active at school. Affordability was the main challenge for adolescents from rural schools. Stakeholders perceived that a future school-based intervention should improve the availability and subsidies for healthy foods, provide health education/training for both adolescents and PE teachers, enhance active adolescent participation in PE and develop social support mechanisms to facilitate engagement with PA.
Conclusions:
These findings provide important insights into developing school-based lifestyle interventions to improve healthy eating and strengthening PA of Malaysian adolescents.
OBJECTIVES/GOALS: 1. Understand the association between patient perceptions of care measured by the Interpersonal Processes of Care (IPC) Survey and glycemic control, appointment no-shows/cancellations and medication adherence in patients with type II diabetes. 2. Determine how these relationships differ by race for non-Hispanic White and Black patients. METHODS/STUDY POPULATION: This is a cross-sectional study of a random sample of 100 White and 100 Black Type II diabetic patients followed in Duke primary care clinics and prescribed antihyperglycemic medication. We will recruit through email and phone calls. Enrolled patients will complete the Interpersonal Processes of Care Short Form and Extent of Medication Adherence survey to measure patient perceptions of care (predictor) and medication adherence (secondary outcome). No show appointments and cancellations (secondary outcomes) and most recent hemoglobin A1c (primary outcome) will be collected from the Electronic Medical Record. We will also collect basic demographic information, insurance status, financial security, significant co-morbidities, and number and type (subcutaneous vs oral) of antihyperglycemic medications. RESULTS/ANTICIPATED RESULTS: -The study is powered to detect a 0.6% difference in HbA1c, our primary outcome, between high and low scorers on the Interpersonal Processes of Care subdomains. -We expect that higher patient scores in the positive domains of the IPC survey and lower DISCUSSION/SIGNIFICANCE OF IMPACT: This study will provide information to develop and implement targeted interventions to reduce racial and ethnic disparities in patients with Type II diabetes. We hope to gain information on potentially modifiable factors in patient-provider interactions that can be intervened upon to improve prevention and long-term outcomes in these populations.