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Pre-diagnostic deficits in social motivation are hypothesized to contribute to autism spectrum disorder (ASD), a heritable neurodevelopmental condition. We evaluated psychometric properties of a social motivation index (SMI) using parent-report item-level data from 597 participants in a prospective cohort of infant siblings at high and low familial risk for ASD. We tested whether lower SMI scores at 6, 12, and 24 months were associated with a 24-month ASD diagnosis and whether social motivation’s course differed relative to familial ASD liability. The SMI displayed good internal consistency and temporal stability. Children diagnosed with ASD displayed lower mean SMI T-scores at all ages and a decrease in mean T-scores across age. Lower group-level 6-month scores corresponded with higher familial ASD liability. Among high-risk infants, strong decline in SMI T-scores was associated with 10-fold odds of diagnosis. Infant social motivation is quantifiable by parental report, differentiates children with versus without later ASD by age 6 months, and tracks with familial ASD liability, consistent with a diagnostic and susceptibility marker of ASD. Early decrements and decline in social motivation indicate increased likelihood of ASD, highlighting social motivation’s importance to risk assessment and clarification of the ontogeny of ASD.
The rapid spread of coronavirus disease 2019 (COVID-19) required swift preparation to protect healthcare personnel (HCP) and patients, especially considering shortages of personal protective equipment (PPE). Due to the lack of a pre-existing biocontainment unit, we needed to develop a novel approach to placing patients in isolation cohorts while working with the pre-existing physical space.
To prevent disease transmission to non–COVID-19 patients and HCP caring for COVID-19 patients, to optimize PPE usage, and to provide a comfortable and safe working environment.
An interdisciplinary workgroup developed a combination of approaches to convert existing spaces into COVID-19 containment units with high-risk zones (HRZs). We developed standard workflow and visual management in conjunction with updated staff training and workflows. The infection prevention team created PPE standard practices for ease of use, conservation, and staff safety.
The interventions resulted in 1 possible case of patient-to-HCP transmission and zero cases of patient-to-patient transmission. PPE usage decreased with the HRZ model while maintaining a safe environment of care. Staff on the COVID-19 units were extremely satisfied with PPE availability (76.7%) and efforts to protect them from COVID-19 (72.7%). Moreover, 54.8% of HCP working in the COVID-19 unit agreed that PPE monitors played an essential role in staff safety.
The HRZ model of containment unit is an effective method to prevent the spread of COVID-19 with several benefits. It is easily implemented and scaled to accommodate census changes. Our experience suggests that other institutions do not need to modify existing physical structures to create similarly protective spaces.
Stingray envenomation is a marine injury suffered by ocean goers throughout the world. No prospective studies exist on the various outcomes associated with these injuries.
The aim of this study was to perform a prospective, observational study of human stingray injuries to determine the natural history, acute and subacute complications, prevalence of medical evaluation, and categories of medical treatment.
This study prospectively studied a population of subjects who were injured by stingrays at Seal Beach, California (USA) from July 2012 through September 2016 and did not immediately seek emergency department evaluation. Subjects described their initial injury and provided information on their symptoms, medical evaluations, and medical treatment for the injury at one week and one month after the injury. This information was reported as descriptive statistics.
A total of 393 participants were enrolled in the study; 313 (80%) of those completed the one-week follow-up interview and 279 (71%) participants completed both the one-week and one-month follow-up interviews. Overall, 234 (75%) injuries occurred to the foot. One hundred sixty-three (52%) patients had complete resolution of their pain within one week and 261 (94%) had either complete resolution or improvement of pain by one month. Sixty-eight (22%) subjects reported being evaluated by a physician and a total of 49 (17%) subjects reported antibiotic treatment for their wound. None of the subjects required parenteral antibiotics or hospital admission.
The majority of stingray victims recover from stingray injury without requiring antibiotics. A subset of subjects will have on-going wound pain after one month. The need for parenteral antibiotics or hospital admission is rare.
Clinical high-risk states for psychosis (CHR) are associated with functional impairments and depressive disorders. A previous PRONIA study predicted social functioning in CHR and recent-onset depression (ROD) based on structural magnetic resonance imaging (sMRI) and clinical data. However, the combination of these domains did not lead to accurate role functioning prediction, calling for the investigation of additional risk dimensions. Role functioning may be more strongly associated with environmental adverse events than social functioning.
We aimed to predict role functioning in CHR, ROD and transdiagnostically, by adding environmental adverse events-related variables to clinical and sMRI data domains within the PRONIA sample.
Baseline clinical, environmental and sMRI data collected in 92 CHR and 95 ROD samples were trained to predict lower versus higher follow-up role functioning, using support vector classification and mixed k-fold/leave-site-out cross-validation. We built separate predictions for each domain, created multimodal predictions and validated them in independent cohorts (74 CHR, 66 ROD).
Models combining clinical and environmental data predicted role outcome in discovery and replication samples of CHR (balanced accuracies: 65.4% and 67.7%, respectively), ROD (balanced accuracies: 58.9% and 62.5%, respectively), and transdiagnostically (balanced accuracies: 62.4% and 68.2%, respectively). The most reliable environmental features for role outcome prediction were adult environmental adjustment, childhood trauma in CHR and childhood environmental adjustment in ROD.
Findings support the hypothesis that environmental variables inform role outcome prediction, highlight the existence of both transdiagnostic and syndrome-specific predictive environmental adverse events, and emphasise the importance of implementing real-world models by measuring multiple risk dimensions.
Aiming to study the rough-wall turbulent boundary layer structure over differently arranged roughness elements, an experimental study was conducted on flows with regular and random roughness. Varying planform densities of truncated cone roughness elements in a square staggered pattern were investigated. The same planform densities were also investigated in random arrangements. Velocity statistics were measured via two-component laser Doppler velocimetry and stereoscopic particle image velocimetry. Friction velocity, thickness, roughness length and zero-plane displacement, determined from spatially averaged flow statistics, showed only minor differences between the regular and random arrangements at the same density. Recent a priori morphometric and statistical drag prediction methods were evaluated against experimentally determined roughness length. Observed differences between regular and random surface flow parameters were due to the presence of secondary flows which manifest as high-momentum pathways and low-momentum pathways in the streamwise velocity. Contrary to expectation, these secondary flows were present over the random surfaces and not discernible over the regular surfaces. Previously identified streamwise-coherent spanwise roughness heterogeneity does not seem to be present, suggesting that such roughness heterogeneity is not necessary to sustain secondary flows. Evidence suggests that the observed secondary flows were initiated at the front edge of the roughness and sustained over irregular roughness. Due to the secondary flows, local turbulent boundary layer profiles do not scale with local wall shear stress but appear to scale with local turbulent shear stress above the roughness canopy. Additionally, quadrant analysis shows distinct changes in the populations of ejection and sweep events.
Childhood trauma (CT) is associated with an increased risk of mental health disorders; however, it is unknown whether this represents a diagnosis-specific risk factor for specific psychopathology mediated by structural brain changes. Our aim was to explore whether (i) a predictive CT pattern for transdiagnostic psychopathology exists, and whether (ii) CT can differentiate between distinct diagnosis-dependent psychopathology. Furthermore, we aimed to identify the association between CT, psychopathology and brain structure.
We used multivariate pattern analysis in data from 643 participants of the Personalised Prognostic Tools for Early Psychosis Management study (PRONIA), including healthy controls (HC), recent onset psychosis (ROP), recent onset depression (ROD), and patients clinically at high-risk for psychosis (CHR). Participants completed structured interviews and self-report measures including the Childhood Trauma Questionnaire, SCID diagnostic interview, BDI-II, PANSS, Schizophrenia Proneness Instrument, Structured Interview for Prodromal Symptoms and structural MRI, analyzed by voxel-based morphometry.
(i) Patients and HC could be distinguished by their CT pattern with a reasonable precision [balanced accuracy of 71.2% (sensitivity = 72.1%, specificity = 70.4%, p ≤ 0.001]. (ii) Subdomains ‘emotional neglect’ and ‘emotional abuse’ were most predictive for CHR and ROP, while in ROD ‘physical abuse’ and ‘sexual abuse’ were most important. The CT pattern was significantly associated with the severity of depressive symptoms in ROD, ROP, and CHR, as well as with the PANSS total and negative domain scores in the CHR patients. No associations between group-separating CT patterns and brain structure were found.
These results indicate that CT poses a transdiagnostic risk factor for mental health disorders, possibly related to depressive symptoms. While differences in the quality of CT exposure exist, diagnostic differentiation was not possible suggesting a multi-factorial pathogenesis.
The current study aimed to investigate availability and placement of healthy and discretionary (less healthy) food in supermarkets in Victoria, Australia, and examine variation by supermarket chain and area-level socio-economic disadvantage.
Cross-sectional supermarket audit. Measures included: (i) proportion of shelf space (in square metres) allocated to selected healthy and discretionary food and beverages; (ii) proportion of end-of-aisle, checkout and island bin displays containing discretionary food and beverages and (iii) proportion of space within end-of-aisle, checkout and island bin displays devoted to discretionary food and beverages.
Metropolitan areas of Melbourne and Geelong, Australia. Assessment: June–July 2019.
Random sample of 104 stores, with equal numbers from each supermarket group (Coles, Woolworths, Aldi and Independent stores) within strata of area-level socio-economic position.
Proportion of shelf space devoted to selected discretionary foods was greater for Independent stores (72·7 %) compared with Woolworths (65·7 %), Coles (64·8 %) and Aldi (63·2 %) (all P < 0·001). Proportion of shelf space devoted to selected discretionary food for all Coles, Woolworths and Aldi stores was 9·7 % higher in the most compared with the least disadvantaged areas (P = 0·002). Across all stores, 90 % of staff-assisted checkout displays and 50 % of end-of-aisle displays included discretionary food. Aldi was less likely to feature discretionary food in end-of-aisle and checkout displays compared with other supermarket groups.
Extensive marketing of discretionary food in all Australian supermarket chains was observed, which is likely to strongly influence purchasing patterns and population diets. Findings should be used to inform private and public sector policies to reduce marketing of discretionary food in supermarkets.
Prevention of severe mental disorders, and especially the indicated prevention, has become a main topic in psychiatric research and, consequently, a matter of ethical debates. Neuropsychiatric disorders, however, form a most heterogeneous group of disorders that, among others, strike first in different age groups, differ in outcome and in availability as well as safety of treatments, have more or less understood different aetiologies and are subject to different degrees of stigmatisation and discrimination. And, although the main focus and critic are on the accuracy of prediction and the safety of treatment, concerns and arguments vary with the different characteristics of the considered disorder.
Taking endogenous psychoses as an example, costs and benefits of an early detection, of an early intervention and of prevention research in the prodromal or premorbid phase will be reviewed. It will be argued that the best way to adhere to the major ethical principles in medicine - autonomy, nonmaleficence, beneficence and fairness - in research and clinical practice will have to be reassessed continuously against the background of the current state of knowledge as well as the public opinion. Thereby, great care has to be given to ensuring that the great expected ‘common good’ will not overcome an individual patient's right to his or her own good and that, especially in patients more vulnerable to misuse, i.e., minors and those already impaired in their decision-making capacity, autonomy is given priority.
This guidance paper from the European Psychiatric Association (EPA) aims to provide evidence-based recommendations on early intervention in clinical high risk (CHR) states of psychosis, assessed according to the EPA guidance on early detection. The recommendations were derived from a meta-analysis of current empirical evidence on the efficacy of psychological and pharmacological interventions in CHR samples. Eligible studies had to investigate conversion rate and/or functioning as a treatment outcome in CHR patients defined by the ultra-high risk and/or basic symptom criteria. Besides analyses on treatment effects on conversion rate and functional outcome, age and type of intervention were examined as potential moderators. Based on data from 15 studies (n = 1394), early intervention generally produced significantly reduced conversion rates at 6- to 48-month follow-up compared to control conditions. However, early intervention failed to achieve significantly greater functional improvements because both early intervention and control conditions produced similar positive effects. With regard to the type of intervention, both psychological and pharmacological interventions produced significant effects on conversion rates, but not on functional outcome relative to the control conditions. Early intervention in youth samples was generally less effective than in predominantly adult samples. Seven evidence-based recommendations for early intervention in CHR samples could have been formulated, although more studies are needed to investigate the specificity of treatment effects and potential age effects in order to tailor interventions to the individual treatment needs and risk status.
Research on at-risk states of psychosis has mainly aimed to predict conversion. Yet as a considerable number of patients does not to progress to this outcome during the investigated observation periods, the course of these non-converters (NC) is of major interest, particularly with regard to preventive interventions and treatment.
To analyze the psychopathological and functional in 18-month non-converters.
Data were derived from the prospective multicenter European Prediction of Psychosis Study with an 18-month follow-up period. Participants had to fulfill ultra-high risk criteria and/or the COGDIS criterion, which is based on a set of cognitive basic symptoms. Psychopathology was assessed with the Structure Interview for Prodromal Syndromes (SIPS), including the Global Assessment of Functioning Scale (GAF) and a short version of the Schizophrenia Proneness Instrument (SPI-A).
All total and subscale scores improved significantly during follow-up. However, a more detailed analysis revealed that a considerable part of the patients showed no improvement or even a worsening of psychopathology and function.
Our first analysis of course on non-converters shows that a high proportion of patients improved. In the light of results from retrospective studies, however, this improvement has to be interpreted with caution, as the observation period does not allow to determine the proportion of outpost syndromes, i.e. precursors of a later prodrome. Furthermore, a considerable portion of our sample worsened functionally and/or symptomatically. With regard to retrospective schizophrenia related results, very long observation periods may be needed to characterize the patterns of course in subpsychotic syndromes.
The aim of this guidance paper of the European Psychiatric Association is to provide evidence-based recommendations on the early detection of a clinical high risk (CHR) for psychosis in patients with mental problems. To this aim, we conducted a meta-analysis of studies reporting on conversion rates to psychosis in non-overlapping samples meeting any at least any one of the main CHR criteria: ultra-high risk (UHR) and/or basic symptoms criteria. Further, effects of potential moderators (different UHR criteria definitions, single UHR criteria and age) on conversion rates were examined. Conversion rates in the identified 42 samples with altogether more than 4000 CHR patients who had mainly been identified by UHR criteria and/or the basic symptom criterion ‘cognitive disturbances’ (COGDIS) showed considerable heterogeneity. While UHR criteria and COGDIS were related to similar conversion rates until 2-year follow-up, conversion rates of COGDIS were significantly higher thereafter. Differences in onset and frequency requirements of symptomatic UHR criteria or in their different consideration of functional decline, substance use and co-morbidity did not seem to impact on conversion rates. The ‘genetic risk and functional decline’ UHR criterion was rarely met and only showed an insignificant pooled sample effect. However, age significantly affected UHR conversion rates with lower rates in children and adolescents. Although more research into potential sources of heterogeneity in conversion rates is needed to facilitate improvement of CHR criteria, six evidence-based recommendations for an early detection of psychosis were developed as a basis for the EPA guidance on early intervention in CHR states.
Surface based MRI methods are a promising approach for the identification of cerebral shape alterations in schizophrenia . In particular, investigating gyrification might offer important evidence for disturbed neurodevelopmental mechanisms in schizophrenia.
The present study is the first to compare on a vertex - wise basis mean curvature as a sensitive parameter for the identification of local gyrification changes in first episode schizophrenia.
54 patients with first-episode schizophrenia and 54 healthy control subjects underwent high-resolution T1-weighted MRI scans. Surface extraction and mean curvature calculation was performed using the Freesurfer Software package. Statistical cortical maps were created to estimate gyrification differences between groups.
A significantly increased gyrification was detected in patients relative to controls in a large right parahippocampal-lingual cortex area. A further analysis of cortical thickness of this cluster revealed concurrent significant reduced cortical thickness in patients.
This is the first study to reveal an aberrant gyrification of the medial surface in first episode schizophrenia on basis of a vertex - wise analysis of local gyrification changes of the entire cortex. Both affected areas, the parahippocampal and the lingual cortex, are of high pathophysiological relevance for schizophrenia. Thus, our data provided new in vivo evidence for an early maturational deficit of these cortical areas in schizophrenia .
The human endocannabinoid system interacts with various neurotransmitter systems and the endocannabinoid anandamide was found significantly elevated in CSF and inversely correlated to psychopathology (Giuffrida et al. 2004) providing a link to the neurobiology of schizophrenia. While delta-9-tetrahydrocannabinol, the psychoactive compound of Cannabis sativa, shows psychedelic properties, the major herbal cannabinoid compound cannabidiol was suggested recently a re-uptake inhibitor of anandamide. In addition potential antipsychotic properties have been hypothezised.
We performed an explorative, 4-week, double-blind, controlled clinical trial on the effects of purified cannabidiol in acute schizophrenia compared to the antipsychotic amisulpride. The antipsychotic properties of both drugs were the primary target of the study. Furthermore, side-effects and anxiolytic capabilities of both treatments were investigated.
42 patients fulfilling DSM-IV criteria of acute paranoid schizophrenia or schizophreniform psychosis participated in the study. Both treatments were associated with a significant decrease of psychotic symptoms after 2 and 4 weeks as assessed by BPRS and PANSS. However, there was no statistical difference between both treatment groups. In contrast, cannabidiol induced significantly less side effects (EPS, increase in prolactin, weight gain) when compared to amisulpride.
Cannabidiol proved substantial antipsychotic properties in acute schizophrenia. This is in line with our suggestion of an adaptive role of the endocannabinoid system in paranoid schizophrenia, and raises further evidence that this adaptive mechanism may represent a valuable target for antipsychotic treatment strategies.
The Stanley Medical Research Institute (00-093 to FML) and the Koeln Fortune Program (107/2000 + 101/2001 to FML) funded this study.
A main objective of EPOS is to provide a valid multifactorial model for the prediction of psychosis. One major element of such a model should be the clinical state.
In a European multicentre study, persons fulfilling clinical criteria thought to indicate an increased risk for psychosis (PAR) were assessed amongst others with different psychopathological instruments covering the whole spectrum from basic symptoms to frank psychotic symptoms. Inclusion criteria comprised attenuated positive symptoms (APS), brief limited intermittent psychotic symptoms (BLIPS), cognitive basic symptoms (CogDis) and a combination of family risk and reduced functioning (S&T).
246 PAR were included into the study, mostly by APS or CogDis. Analysis of demographical data showed a high amount of functional impairment, resulting e.g. in low mean GAF scores (51.0 ± 11.8 SD), and of non-psychotic axis-I disorders. In September 2006, the hazard rate for a conversion to psychosis was 15.3 at 12 and 20.0 at 18 months after baseline assessment. According to the inclusion criteria, the highest rate of conversion was observed among PAR with BLIPS. On a dimensional level, a low GAF score was among the best predictors of conversion.
The transition rates of EPOS were in line with recent studies. A first analysis of clinical data supports the notion that the functional state should be an inherent part of any set of clinical risk criteria. Further analysis will consider the contribution of single symptoms or symptom combinations and the impact of symptom duration.
One aim of the European prediction of psychosis study (EPOS) has been to evaluate the clinical course of putatively prodromal patients in terms of psychopathology.
245 patients at risk for psychosis defined by attenuated positive symptoms, brief limited psychotic symptoms, a state/ trait combination or cognitive-perceptive basic symptoms was recruited in six centres in four countries. The Structured Interview for Prodromal Syndromes (SIPS) and the Bonn Scale for the Assessment of Basic Symptoms – Prediction List (BSABS-P) were employed. Follow-up was scheduled after 9 months (t1) and 18 months.
In total, 40 patients developed a psychosis (P). Compared to those without a transition (NP), P showed significantly higher SIPS scores at baseline. The same applied to the BSABS-P sub-scores 'cognitive perception disturbances' and 'cognitive motor disturbances'. The P sub-group developing psychosis after t1 showed no significant change of the SIPS positive (SIPS-P) sub-score or of any BSABS-P score from baseline to t1, whereas all scores improved in the NP group. At t1, SIPS-P and BSABS-P sub-score 'cognitive thought disturbances' were significantly lower in those later becoming psychotic.
Patients at risk showing a transition to psychosis during exhibited a pronounced psychopathology at baseline. Also, the positive symptom scores did not significantly improve during 1st follow-up, whereas those patients with no transition during the complete follow-up showed an improvement of all scores. As EPOS is a naturalistic study, different treatments have been performed in a considerable portion of the patients and association with course awaits further analysis.
After two decades of research, prevention of psychosis becomes increasingly accepted in clinical psychiatry. However, there are still unmet scientific and clinical needs. Therefore, guidance for prediction as well as prevention is required, reflecting their current capabilities, but also their requirements and limitations.
Evaluating the current state of risk estimation and prevention.
Developing clinical recommendations for the prediction and prevention of psychosis.
42 samples, mainly defined by ultra-high risk criteria and/or the basic symptoms criterion ‘COGDIS‘, were included into meta-analyses of prevention, 15 studies into meta-analyses of prevention.
The pooled conversion rate at >4-year follow-up was 37.0% in UHR and 61.3% in COGDIS samples. The 12-month pooled risk ratio was 0.44, the NNT 10. Psychosocial functioning seemed not to improve, however results were inconclusive due to methodological issues of the trials. Both meta-analyses indicated age related differences.
Several recommendations were developed to guide prediction and prevention, emphasizing age-adapted strategies; details will be presented and discussed during the symposium.
Regarding future steps to further improve prediction and thus prevention, neurocognitive and neurobiological parameters of information processing, i.e. mismatch negativity, P300 and processing speed, as well as support vector machine based analysis of structural MRI seem to be most promising. Furthermore, with regard to current developmental models of psychotic disorders, risk should be conceptualized as dynamically modulated over time and thus presumably non-linearly related to future outcome. Therefore, studies need to consider the fluid interplay of risk and resilience factors to advance prediction significantly.