Neurobehavioral risk factors influence prevalence and severity of hazardous substance use in youth at genetic and clinical high risk for psychosis

BackgroundElevated rates of alcohol, tobacco, and cannabis use are observed in both patients with psychotic disorders and individuals at clinical high risk for psychosis (CHR-P), and strong genetic associations exist between substance use disorders and schizophrenia. While individuals with 22q11.2 deletion syndrome (22qDel) are at increased genetic risk for psychosis, initial evidence suggests that they have strikingly low rates of substance use. In the current study, we aimed to directly compare substance use patterns and their neurobehavioral correlates in genetic and clinical high-risk cohorts.MethodsData on substance use frequency and severity, clinical symptoms, and neurobehavioral measures were collected at baseline and at 12-month follow-up visits in two prospective longitudinal cohorts: participants included 89 22qDel carriers and 65 age and sex-matched typically developing (TD) controls (40.67% male, Mage = 19.26 ± 7.84 years) and 1,288 CHR-P youth and 371 matched TD controls from the North American Prodrome Longitudinal Study-2 and 3 (55.74% male; Mage = 18.71 ± 4.27 years). Data were analyzed both cross-sectionally and longitudinally using linear mixed effects models.ResultsControlling for age, sex, and site, CHR-P individuals had significantly elevated rates of tobacco, alcohol, and cannabis use relative to TD controls, whereas 22qDel had significantly lower rates. Increased substance use in CHR-P individuals was associated with increased psychosis symptom severity, dysphoric mood, social functioning, and IQ, while higher social anhedonia was associated with lower substance use across all domains at baseline. These patterns persisted when we investigated these relationships longitudinally over one-year. CHR-P youth exhibited significantly increased positive psychosis symptoms, dysphoric mood, social functioning, social anhedonia, and IQ compared to 22qDel carriers, and lower rates of autism spectrum disorder (ASD) compared to 22qDel carriers, both at baseline and at 1 year follow-up.ConclusionIndividuals at genetic and CHR-P have strikingly different patterns of substance use. Factors such as increased neurodevelopmental symptoms (lower IQ, higher rates of ASD) and poorer social functioning in 22qDel may help explain this distinction from substance use patterns observed in CHR-P individuals

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

A Public Health Perspective on Screening for Psychosis Within General Practice Clinics.

Screening for major mental illness in adolescents and young adults has lagged behind screening for physical illness for a myriad of reasons. Existing pediatric behavioral health screening tools screen primarily for disorders of attention, disruptive behaviors, depression, and anxiety. A few also screen for substance use and suicide risk. Although it is now possible to reliably identify young people at imminent risk for a psychotic disorder, arguably the most severe of mental illnesses, general practitioners (GP) rarely screen for psychotic symptoms or recognize when to refer patients for a specialized risk assessment. Research suggests that barriers such as inadequate knowledge or insufficient access to mental health resources can be overcome with intensive GP education and the integration of physical and mental health services. Under the lens of two public health models outlining the conditions under which disease screening is warranted, we examine additional evidence for and against population-based screening for psychosis in adolescents and young adults. We argue that systematic screening within general health settings awaits a developmentally well-normed screening tool that includes probes for psychosis, is written at a sufficiently low reading level, and has acceptable sensitivity and, in particular, specificity for detecting psychosis and psychosis risk in both adolescents and young adults. As integrated healthcare models expand around the globe and psychosis-risk assessments and treatments improve, a stratified screening and careful risk management protocol for GP settings could facilitate timely early intervention that effectively balances the benefit/risk ratio of employing such a screening tool at the population level

Recent Updates on Predicting Conversion in Youth at Clinical High Risk for Psychosis.

PURPOSE OF REVIEW: This review highlights recent advances in the prediction and treatment of psychotic conversion. Over the past 25&nbsp;years, research into the prodromal phase of psychotic illness has expanded with the promise of early identification of individuals at clinical high risk (CHR) for psychosis who are likely to convert to psychosis. RECENT FINDINGS: Meta-analyses highlight conversion rates between 20 and 30% within 2-3&nbsp;years using existing clinical criteria while research into more specific risk factors, biomarkers, and refinement of psychosis risk calculators has exploded, improving our ability to predict psychotic conversion with greater accuracy. Recent studies highlight risk factors and biomarkers likely to contribute to earlier identification and provide insight into neurodevelopmental abnormalities, CHR subtypes, and interventions that can target specific risk profiles linked to neural mechanisms. Ongoing initiatives that assess longer-term (&gt; 5-10&nbsp;years) outcome of CHR participants can provide valuable information about predictors of later conversion and diagnostic outcomes while large-scale international biomarker studies provide hope for precision intervention that will alter the course of early psychosis globally

Emotional and stigma-related experiences relative to being told one is at risk for psychosis

OBJECTIVE: Despite the appeal of early intervention in psychosis, there is concern that identifying youth as having high psychosis risk (PR) may trigger stigma. This study employed a pre-post design to measure change in PR participants\u27 emotions about PR upon being told of their PR status and according to whether this was the first time receiving this information. METHODS: Participants (n = 54) identified as at PR via structured interview rated their emotions about PR before and after being told they were at PR. Qualitative analyses explored the valence of participant reflections on being given this information. RESULTS: Participants reported significantly less negative emotion after being told of their PR status (p \u3c .001), regardless of whether they were hearing this for the first time (p = .72). There was no change in positive emotions or the predominant belief that they should keep their PR status private. Most participants commented positively about the process of feedback but negatively about its impact on their self-perceptions and/or expectations of others\u27 perceptions of them. CONCLUSION: This is the first study to collect pre-post data related to being told one is at PR and to examine quantitative and qualitative responses across and within individuals. For a majority of participants, clinical feedback stimulated negative stereotypes even as it relieved some distress. To actively address internalized stigma, clinicians providing feedback to PR youth must attend to the positive and negative impacts on how youth think about themselves as well as how they feel

T70. IDENTIFYING YOUTH AT CLINICAL HIGH RISK: WHAT\u27S THE EMOTIONAL IMPACT?...The 2019 Congress of the Schizophrenia International Research Society, April 10-14, 2019, Orlando, Florida

Background In spite of advances in early intervention in major mental illness, concerns linger regarding the risks of identifying youth as at clinical high risk (CHR) for psychosis. In particular, stigma in this population has been associated with increased emotional distress, social withdrawal, non-engagement in treatment, and suicide risk. Being told one has a CHR syndrome may be one source of stigma, yet no prior studies have conducted assessments both before and after people are given this feedback. Within the context of a larger study of stigma, we compared emotional responses to the CHR concept assessed before and after feedback by study clinicians. Notably, some participants had been already told of their risk prior to study entry whereas others had not. We expected different reactions to study feedback in these two groups. An informed discussion of risk might reduce stigma in those already worried about psychosis whereas it might increase stigma for those considering their risk for the first time. Thus, we predicted a small decrease in negative emotions following feedback in the first group, a small increase in the second, and no significant change in negative emotions for the group as a whole. Methods Fifty-seven CHR participants ages 12–35 were interviewed both before and after receiving formal clinical feedback about their risk status and eligibility for the study. This feedback typically included elements of psychoeducation and information about treatment options. In each interview participants were asked 1) the degree to which they felt 12 emotions in relation to risk for psychosis or schizophrenia, 2) whether they thought it was better to not tell anyone about psychosis risk. We analyzed pre-post change using general linear modeling with group (those told before study entry and those first told in the study context) as a between-subjects variable and the time between pre and post interviews as a covariate. Results Stigma was a significant concern in this sample as the vast majority of participants endorsed It is better that I not tell people that I am at-risk, both before and after feedback (75% pre to 71% post, McNemar test, p = 0.75). However, contrary to our hypothesis, participants experienced a significant decline in negative emotions (embarrassed, different, angry, ashamed, sad, worried; F= 20.7, p \u3c0.001) post- vs. pre-feedback, even controlling for the significant effects of time (M = 16 days between assessments; F= 3.7, p =0.033). This was true for those who reported already having been told that they were at risk for psychosis (N = 35; F = 20.0, p \u3c 0.001) as well as for those who were first told they were at risk in the context of the study (F =4.0, p = 0.038). Strikingly, a third of this latter group continued to report not having been told they were at risk even immediately after feedback. Additionally, in the larger group, ten believed that they already had schizophrenia and two maintained this belief even after being told that they did not. Discussion This is the first study to assess emotional aspects of stigma in CHR youth both before and after formal feedback about their psychosis risk. In contrast to concerns, feedback provided in the context of specialized early psychosis programs may actually reduce distress in these youth. The fact that the number of days between assessments did not fully account for the significant changes in negative emotions suggests that these changes were unlikely to be due to time alone. Importantly, participants\u27 varied impressions of what they had been told or whether they were at risk suggest that feedback is not the only factor influencing self-identification and stigma

Emotional and stigma-related experiences relative to being told one is at risk for psychosis.

OBJECTIVE: Despite the appeal of early intervention in psychosis, there is concern that identifying youth as having high psychosis risk (PR) may trigger stigma. This study employed a pre-post design to measure change in PR participants emotions about PR upon being told of their PR status and according to whether this was the first time receiving this information. METHODS: Participants (n&nbsp;=&nbsp;54) identified as at PR via structured interview rated their emotions about PR before and after being told they were at PR. Qualitative analyses explored the valence of participant reflections on being given this information. RESULTS: Participants reported significantly less negative emotion after being told of their PR status (p&nbsp;&lt;&nbsp;.001), regardless of whether they were hearing this for the first time (p&nbsp;=&nbsp;.72). There was no change in positive emotions or the predominant belief that they should keep their PR status private. Most participants commented positively about the process of feedback but negatively about its impact on their self-perceptions and/or expectations of others perceptions of them. CONCLUSION: This is the first study to collect pre-post data related to being told one is at PR and to examine quantitative and qualitative responses across and within individuals. For a majority of participants, clinical feedback stimulated negative stereotypes even as it relieved some distress. To actively address internalized stigma, clinicians providing feedback to PR youth must attend to the positive and negative impacts on how youth think about themselves as well as how they feel

Neurobehavioral risk factors influence prevalence and severity of hazardous substance use in youth at genetic and clinical high risk for psychosis

BackgroundElevated rates of alcohol, tobacco, and cannabis use are observed in both patients with psychotic disorders and individuals at clinical high risk for psychosis (CHR-P), and strong genetic associations exist between substance use disorders and schizophrenia. While individuals with 22q11.2 deletion syndrome (22qDel) are at increased genetic risk for psychosis, initial evidence suggests that they have strikingly low rates of substance use. In the current study, we aimed to directly compare substance use patterns and their neurobehavioral correlates in genetic and clinical high-risk cohorts.MethodsData on substance use frequency and severity, clinical symptoms, and neurobehavioral measures were collected at baseline and at 12-month follow-up visits in two prospective longitudinal cohorts: participants included 89 22qDel carriers and 65 age and sex-matched typically developing (TD) controls (40.67% male, Mage = 19.26 ± 7.84 years) and 1,288 CHR-P youth and 371 matched TD controls from the North American Prodrome Longitudinal Study-2 and 3 (55.74% male; Mage = 18.71 ± 4.27 years). Data were analyzed both cross-sectionally and longitudinally using linear mixed effects models.ResultsControlling for age, sex, and site, CHR-P individuals had significantly elevated rates of tobacco, alcohol, and cannabis use relative to TD controls, whereas 22qDel had significantly lower rates. Increased substance use in CHR-P individuals was associated with increased psychosis symptom severity, dysphoric mood, social functioning, and IQ, while higher social anhedonia was associated with lower substance use across all domains at baseline. These patterns persisted when we investigated these relationships longitudinally over one-year. CHR-P youth exhibited significantly increased positive psychosis symptoms, dysphoric mood, social functioning, social anhedonia, and IQ compared to 22qDel carriers, and lower rates of autism spectrum disorder (ASD) compared to 22qDel carriers, both at baseline and at 1 year follow-up.ConclusionIndividuals at genetic and CHR-P have strikingly different patterns of substance use. Factors such as increased neurodevelopmental symptoms (lower IQ, higher rates of ASD) and poorer social functioning in 22qDel may help explain this distinction from substance use patterns observed in CHR-P individuals