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The coronavirus disease 2019 (COVID-19) pandemic continues to cause significant morbidity and mortality worldwide. Since a large portion of the world’s population is currently unvaccinated or incompletely vaccinated and has limited access to approved treatments against COVID-19, there is an urgent need to continue research on treatment options, especially those at low cost and which are immediately available to patients, particularly in low- and middle-income countries. Prior in vitro and observational studies have shown that fluoxetine, possibly through its inhibitory effect on the acid sphingomyelinase/ceramide system, could be a promising antiviral and anti-inflammatory treatment against COVID-19.
Objectives
The aim of this sudy was to test the potential antiviral and anti-inflammatory activities of fluoxetine against SARS-CoV-2 in a K18-hACE2 mouse model of infection, and against several variants of concern in vitro, and test the hypothesis of the implication of ceramides and/or their derivatives hexosylceramides.
Methods
We evaluated the potential antiviral and anti-inflammatory activities of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and against variants of concern in vitro, i.e., SARS-CoV-2 ancestral strain, Alpha B.1.1.7, Gamma P1, Delta B1.617 and Omicron BA.5.
Results
Fluoxetine, administrated after SARS-CoV-2 infection, significantly reduced lung tissue viral titres (Figure 1) and expression of several inflammatory markers (i.e., IL-6, TNFα, CCL2 and CXCL10) (Figure 2). It also inhibited the replication of all variants of concern in vitro. A modulation of the ceramide system in the lung tissues, as reflected by the increase in the ratio HexCer 16:0/Cer 16:0 in fluoxetine-treated mice, may contribute to explain these effects (Figure 3).
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Conclusions
Our findings demonstrate the antiviral and anti-inflammatory properties of fluoxetine in a K18-hACE2 mouse model of SARS-CoV-2 infection, and its in vitro antiviral activity against variants of concern, establishing fluoxetine as a very promising candidate for the prevention and treatment of SARS-CoV-2 infection and disease pathogenesis.
Changes in executive function (EF) occur during adolescence with several factors (e.g., parenting styles, socioeconomic status) influencing the development of EF abilities. These changes are important as EF has been strongly linked with a range of outcomes including academic achievement, job performance, and social–emotional well-being. However, few studies have examined variability in EF trajectories during this critical developmental period, or trajectories in samples known to have specific impairments with EF, such as adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD). The present study examined differential trajectories of three domains of parent-rated EF in 302 adolescents (167 males; Mage = 13.17 years) with and without ADHD (53.6% with ADHD) from grade 8 to 10. The study also explored whether adolescent ADHD, parent ADHD, and parents’ own EF predicted EF trajectories in addition to the longitudinal relation between trajectories and academic outcomes. Findings suggest that adolescence is marked by significant variability in EF development due to factors such as ADHD status, parent ADHD, and parent EF ability. Additionally, adolescents who displayed poor EF abilities throughout middle and high school had significantly lower grade point averages and poorer parent-, teacher-, and self-reported academic outcomes. Implications for interventions targeting EF deficits among adolescents with and without ADHD are discussed.
Evidence suggests that suicide stigma (i.e. negative attitudes towards persons affected by suicide/suicidality) and suicide normalisation (i.e. liberal attitudes towards suicide) are both associated with increased suicide risk. Despite conceptual similarities and potential interaction, suicide stigma and suicide normalisation have usually been investigated separately. We used cross-sectional data from a community sample to test the association between suicide stigma and suicide normalisation as well as to identify their respective determinants and consequences.
Methods
Participants were N = 3.269 adults recruited from an established online-panel using quotas to reflect the composition of the German general population with regard to age, gender, education and region. We collected information about suicide stigma, suicide normalisation, intentions to seek help for suicidality, current suicidality, suicide literacy, negative mood and socio-demographic variables. We used regression modelling to determine the association between suicide stigma and suicide normalisation as well as to identify their determinants and consequences.
Results
Suicide stigma and suicide normalisation were inversely associated so that higher suicide stigma scores were linked to lower suicide normalisation. More suicide stigma was associated with reduced intentions to seeking professional help, increased willingness to seek help from family and friends and lower odds to experience current suicidality, however the association between suicide stigma and intentions to seek professional help diminished after controlling for confounding variables. Increased suicide normalisation was linked to reduced intentions to seek help from professionals or family and friends, as well as higher odds to experience current suicidality, even after controlling for confounding variables.
Conclusions
Our findings suggest that interventions to reduce public suicide stigma are at risk to unintentionally increase suicide normalisation, which appears to be a key barrier to seeking help for suicidality. Future research should therefore identify strategies to improve attitudes towards persons affected by suicidality that avoid normalisation, i.e. do not convey the message of suicide as an acceptable solution for difficult life situations. One strategy with great potential to safely reduce public suicide sigma could be interventions that stimulate interpersonal contact with affected persons sharing their recovery story.
ABSTRACT IMPACT: Identifying factors associated with opioid overdoses will enable better resource allocation in communities most impacted by the overdose epidemic. OBJECTIVES/GOALS: Opioid overdoses often occur in hotspots identified by geographic and temporal trends. This study uses principles of community engaged research to identify neighborhood and community-level factors associated with opioid overdose within overdose hotspots which can be targets for novel intervention design. METHODS/STUDY POPULATION: We conducted an environmental scan in three overdose hotspots’‘ two in an urban center and one in a small city’‘ identified by the Rhode Island Department of Health as having the highest opioid overdose burden in Rhode Island. We engaged hotspot community stakeholders to identify neighborhood factors to map within each hotspot. Locations of addiction treatment, public transportation, harm reduction programs, public facilities (i.e., libraries, parks), first responders, and social services agencies were converted to latitude and longitude and mapped in ArcGIS. Using Esri Service Areas, we will evaluate the service areas of stationary services. We will overlay overdose events and use logistic regression identify neighborhood factors associated with overdose by comparing hotspot and non-hotspot neighborhoods. RESULTS/ANTICIPATED RESULTS: We anticipate that there will be differing neighborhood characteristics associated with overdose events in the densely populated urban area and those in the smaller city. The urban area hotspots will have overlapping social services, addiction treatment, and transportation service areas, while the small city will have fewer community resources without overlapping service areas and reduced public transportation access. We anticipate that overdoses will occur during times of the day when services are not available. Overall, overdose hotspots will be associated with increased census block level unemployment, homelessness, vacant housing, and low food security. DISCUSSION/SIGNIFICANCE OF FINDINGS: Identifying factors associated with opioid overdoses will enable better resource allocation in communities most impacted by the overdose epidemic. Study results will be used for novel intervention design to prevent opioid overdose deaths in communities with high burden of opioid overdose.
We investigated whether the type of antipsychotic treatment has an impact on patients’ subjective quality of life (QoL).
In a prospective naturalistic long-term study, 374 patients meeting ICD-10 criteria for schizophrenia or schizoaffective disorder were examined biannually over a two-year period with regards to QoL, psychopathology, social functioning, use of medical and psychosocial services, compliance, side effects and current neuroleptic treatment. QoL was assessed by the Berliner Lebensqualitätsprofil (BeLP), an adaption of the Lancashire Quality of Life Profile. First examination took place two weeks around discharge from a psychiatric clinic. At study entry, all participants were receiving neuroleptic medication of either quetiapine, risperidone or olanzapine. Mixed regression analysis taking into account the unbalanced panel structure of the data and adjusted for selection bias by means of propensity scores were used for data analysis.
Overall quality of life improved continuously during the two years observed period regardless of the type of neuroleptic. A small, but significant difference emerged when comparing quetiapine monotherapy treatment with olanzapine monotherapy or with a combination treatment of conventional and atypical antipsychotics. QoL of patients treated with olanzapine was generally worse than that of patients treated with quetiapine but improved slightly more over the course of time. In total time and type of medication explained only small proportions of variance in QoL.
Type of neuroleptic had only marginal impact on the subjective QoL of our sample. In order to explain changes in quality of life, research on social and individual factors seems to be more promising.
Collecting prospective data on medication adherence, course of illness, course of treatment, cost effectiveness and quality of life among patients with schizophrenia under the German health system.
Methods
The ELAN study was conducted as a multi-centre, non-interventional observation study. 374 patients with a diagnosis of schizophrenia or schizoaffective disorder (ICD-10 F2) who had been discharged with a medication of quetiapine (N=183), olanzapine (N=91) or risperidone (N=100) were included. Follow-up interviews were conducted after 6,12,18 and 24 months. Applied instruments comprised PANSS, MARS-S, EPS-M, AIMS-S, GAF, ZST and a questionnaire for quality of life.
Results
For each follow-up, at least 80% of the original sample could be included. After two years, between 39% and 43% of patients continued to take the drug prescribed at discharge. Only between 4% and 7% of patients received no neuroleptic treatment in the last 6 months, respectively. The variety of drugs used increased during the course. Only small differences could be found regarding the defined outcome measures (PANSS, GAF, rehospitalisation rate) and side effects. Changes in medication were mostly due to insufficient efficacy or side effects. Doctor's recommendations had an important influence on patients’ decisions.
Conclusions
Under conditions of routine treatment, medication adherence was much greater and differences between drugs were smaller than reported in randomised controlled clinical trials. Taking into account the low sample selection bias and the small percentage of lost-to-follow-up subjects, this study provides some new insight into routine clinical treatment and outcomes in patients with schizophrenia.
Stigma against mental illness and the mentally ill is well known. However, stigma against psychiatrists and mental health professionals is known but not discussed widely. Public attitudes and also those of other professionals affect recruitment into psychiatry and mental health services. The reasons for this discriminatory attitude are many and often not dissimilar to those held against mentally ill individuals. In this Guidance paper we present some of the factors affecting the image of psychiatry and psychiatrists which is perceived by the public at large. We look at the portrayal of psychiatry, psychiatrists in the media and literature which may affect attitudes. We also explore potential causes and explanations and propose some strategies in dealing with negative attitudes. Reduction in negative attitudes will improve recruitment and retention in psychiatry. We recommend that national psychiatric societies and other stakeholders, including patients, their families and carers, have a major and significant role to play in dealing with stigma, discrimination and prejudice against psychiatry and psychiatrists.
There are significant differences in psychiatric training across Europe. In the light of the current direction of Europe (without borders with free movement of workforce) it is inevitable to harmonize at least basic standards of psychiatric education across Europe. Ideally by working in partnership with relevant national and international bodies (European Union of Medical Specialists, Board of Psychiatry - UEMS, European Psychiatric Association - EPA and European Federation of Psychiatric Trainees - EFPT). A qualitative data analysis on the most important challenges of psychiatric trainees across Europe, carried out by the EFPT in 2009, revealed several interesting findings which might be of interest not only for trainees, but for all involved in the process of psychiatric education. As the most important issue trainees reported the imperfect structure of the training programs and problems with implementation of new ones. That is why new training programs based on a competency based framework are being developed lately in number of countries (e.g. United Kingdom, Ireland, Netherlands). However, not only the structure of the training and its implementation remains an issue, trainees are concerned also with topics related to working conditions, insufficient training opportunities, lack of supervision, funding and availability of psychotherapy courses, etc. Based on these findings EFPT will undertake specific actions which in cooperation with other organizations shall lead in the future to better postgraduate training opportunities in Europe.
Even if technology and information are omnipresent, they rarely meet harmoniously. Either the lack of sufficient means prevents good information to reach its target or the technology is too complex to integrate flawlessly in the daily workflow.
The use and misuse of information technologies (internet, email, e-learning, social networks) has recently significantly increased among psychiatrists and patients and the changes in behavior of communication and seeking informations are real challenges.
Using the European Federation of Psychiatric Trainees network, the self-questionnaires concerning the usage of information technologies and the local patients-therapists communication were distributed among psychiatric trainees of 31 European countries.
A review of the results of this study, as well as recommendations about netiquette and useful websites for psychiatrists and scientists will be presented in detail.
The ELAN study is a prospective multi centre observational trial on the effectiveness and safety of long-term antipsychotic treatment of people with schizophrenia or schizoaffective disorders with quetiapine in comparison to olanzapine and risperidone under real world treatment conditions.
374 adult persons with schizophrenia or schizoaffective disorder prescribed antipsychotic maintenance therapy with quetiapine, olanzapine or risperidone were included at discharge from inpatient treatment. Psychotropic regimen, psychopathological symptoms, general and cognitive functioning, negative side-effects and quality of life were assessed before discharge and at 6, 12, 18 and 24 month follow-up assessments. Intention-to-treat analyses and crossover analyses were conducted by mixed-effects regression models including random linear time effects and time x treatment effects, controlling for baseline differences and additional psychotropic medication and using propensity scores to control for selection bias.
As indicated by significant linear time effects the patients improved with regard to psychopathological symptoms, general functioning, subjective quality of life and cognitive processing speed. No change of extrapyramidal motor side-effects, body mass index or waist circumference was obtained. The lack of any significant time x treatment interaction effects indicated no differences in the safety or effectiveness between the three antipsychotics. Nevertheless, the average hospital admission rate of patients receiving olanzapine was lower in comparison to patients receiving quetiapine or risperidone.
Training schemes in psychiatry are developed and evaluated by national education policy makers in the majority of European countries. However, the requirements that a training program in psychiatry should meet are also defined on the European level in a form of recommendations by the Board of Psychiatry - European Union of Medical Specialists (UEMS).
Recently, the European Federation of Psychiatric Trainees (EFPT) which represent trainees from more then 30 European countries, reported data pertaining to the structure of training programs and to the evaluation of training programs in 30 European countries. Whereas in the majority of European countries the structure of training programs and methods of assessment of trainees' competencies are partially compatible with one another and with the existing recommendations at the European level, the quality assurance of training programs varies significantly among countries. Regular evaluations of training programs and mentors, however, contribute to the proper implementation of training programs and help that the theoretical training principles are followed through in practice. As quality assurance of training schemes is an important mechanism how to improve the delivery of training programs, it should gain more focus by responsible authorities who structure the psychiatric training on the national and international European level.
The influence of pharmaceutical industry (PI) on clinical practice and research in psychiatry has been considered a serious problem. Strict rules and guidelines were developed to regulate the interactions between doctors and PI. However, there is an ongoing debate whether these were thoroughly implemented in practice and internalized by physicians. The objective of our study was to assess the attitudes and behaviors of trainees in psychiatry and child & adolescent psychiatry toward PI across Europe. Methodologically, a validated questionnaire with additional items was administered to1444 trainees in 20 European countries. The minimum response rate was set at 60%. We found a high variation across countries in number of interactions between trainees and PI representatives; Portugal and Turkey had the highest number of interactions. The majority (59.76%) agreed that interactions with PI representatives have an impact on physicians’ prescribing behavior; whereas only 29.26% and 19.79% agreed interactions with PI representatives and gifts from PI have impact on their own prescribing behavior, respectively. Most of the gifts were considered appropriate by the majority, except tickets to vacation spot and social dinner at a restaurant. Of the sample, 70.76% think they have not been given sufficient training regarding how to interact with PI representatives. Only less than 20% indicated they have guidelines at institutional or national level. In conclusion, there is substantial interaction between trainees and PI across countries. The majority feel inadequately trained regarding professional interaction with PI, and believes they are immune to the influence of PI.
Interactions between the pharmaceutical industry (PI) and psychiatrists have been under scrutiny recently, though there is little empirical evidence on the nature of the relationship and its intensity at psychiatry trainee level. We therefore studied the level of PI interactions and the underlying beliefs and attitudes in a large sample of European psychiatric trainees.
Methods:
One thousand four hundred and forty-four psychiatric trainees in 20 European countries were assessed cross-sectionally, with a 62-item questionnaire.
Results:
The total number of PI interactions in the preceding two months varied between countries, with least interactions in The Netherlands (M (Mean) = 0.92, SD = 1.44, range = 0–12) and most in Portugal (M = 19.06, SD = 17.44, range = 0–100). Trainees were more likely to believe that PI interactions have no impact on their own prescribing behaviour than that of other physicians (M = 3.30, SD = 1.26 vs. M = 2.39, SD = 1.06 on a 5-point Likert scale: 1 “completely disagree” to 5 “completely agree”). Assigning an educational role to the pharmaceutical industry was associated with more interactions and higher gift value (IRR (incidence rate ratio) = 1.21, 95%CI = 1.12–1.30 and OR = 1.18, 95%CI = 1.02–1.37).
Conclusions:
There are frequent interactions between European psychiatric trainees and the PI, with significant variation between countries. We identified several factors affecting this interaction, including attribution of an educational role to the PI. Creating alternative educational opportunities and specific training dedicated to PI interactions may therefore help to reduce the impact of the PI on psychiatric training.
Both blood- and milk-based biomarkers have been analysed for decades in research settings, although often only in one herd, and without focus on the variation in the biomarkers that are specifically related to herd or diet. Biomarkers can be used to detect physiological imbalance and disease risk and may have a role in precision livestock farming (PLF). For use in PLF, it is important to quantify normal variation in specific biomarkers and the source of this variation. The objective of this study was to estimate the between- and within-herd variation in a number of blood metabolites (β-hydroxybutyrate (BHB), non-esterified fatty acids, glucose and serum IGF-1), milk metabolites (free glucose, glucose-6-phosphate, urea, isocitrate, BHB and uric acid), milk enzymes (lactate dehydrogenase and N-acetyl-β-D-glucosaminidase (NAGase)) and composite indicators for metabolic imbalances (Physiological Imbalance-index and energy balance), to help facilitate their adoption within PLF. Blood and milk were sampled from 234 Holstein dairy cows from 6 experimental herds, each in a different European country, and offered a total of 10 different diets. Blood was sampled on 2 occasions at approximately 14 days-in-milk (DIM) and 35 DIM. Milk samples were collected twice weekly (in total 2750 samples) from DIM 1 to 50. Multilevel random regression models were used to estimate the variance components and to calculate the intraclass correlations (ICCs). The ICCs for the milk metabolites, when adjusted for parity and DIM at sampling, demonstrated that between 12% (glucose-6-phosphate) and 46% (urea) of the variation in the metabolites’ levels could be associated with the herd-diet combination. Intraclass Correlations related to the herd-diet combination were generally higher for blood metabolites, from 17% (cholesterol) to approximately 46% (BHB and urea). The high ICCs for urea suggest that this biomarker can be used for monitoring on herd level. The low variance within cow for NAGase indicates that few samples would be needed to describe the status and potentially a general reference value could be used. The low ICC for most of the biomarkers and larger within cow variation emphasises that multiple samples would be needed - most likely on the individual cows - for making the biomarkers useful for monitoring. The majority of biomarkers were influenced by parity and DIM which indicate that these should be accounted for if the biomarker should be used for monitoring.
Social anxiety disorder (SAD) is characterized by fear of social and performance situations. The consequence of scrutiny by others for the neural processing of performance feedback in SAD is unknown.
Methods
We used event-related functional magnetic resonance imaging to investigate brain activation to positive, negative, and uninformative performance feedback in patients diagnosed with SAD and age-, gender-, and education-matched healthy control subjects who performed a time estimation task during a social observation condition and a non-social control condition: while either being monitored or unmonitored by a body camera, subjects received performance feedback after performing a time estimation that they could not fully evaluate without external feedback.
Results
We found that brain activation in ventral striatum (VS) and midcingulate cortex was modulated by an interaction of social context and feedback type. SAD patients showed a lack of social-context-dependent variation of feedback processing, while control participants showed an enhancement of brain responses specifically to positive feedback in VS during observation.
Conclusions
The present findings emphasize the importance of social-context processing in SAD by showing that scrutiny prevents appropriate reward-processing-related signatures in response to positive performances in SAD.