Outcomes of an adapted prolonged exposure psychotherapy for people with early phase psychosis, substance misuse, and a history of adversity: the PE + trial.

BACKGROUND: Several adversity-focused treatment trials have reported improvements to adversity sequelae (e.g., PTSD symptoms) and decreases in psychotic symptoms among individuals with psychotic disorders. Yet, no trials have examined the impact of adversity-focused treatment on substance use or examined the outcomes among an early phase psychosis population. These gaps in both the research literature and clinical practice have resulted in less knowledge about the outcomes of adversity-focused treatment at this stage of illness, including the impact on substance use. METHODS: The outcomes of an adapted prolonged exposure protocol (PE+) among an early phase psychosis population were examined using a multiple-baseline design. Nineteen adults with a psychotic disorder, current substance misuse, and a history of adversity were recruited from an early psychosis program. Participants were randomized to treatment start time and participated in a 15-session course of PE + therapy. Ten assessments were completed focusing on primary outcomes (i.e., adversity sequelae, negative psychotic symptoms, substance misuse) and secondary outcomes (i.e., functioning, hopelessness, experiential avoidance). The Reliable Change Index (RCI) was used to establish whether there were clinically significant changes to primary or secondary outcomes. RESULTS: Half or more of treatment completers experienced clinically significant changes to most domains of adversity sequelae, no participants experienced improvements in negative psychotic symptoms, and substance misuse increased for several participants. In terms of secondary outcomes, functioning and experiential avoidance were improved for a number of participants, while hopelessness decreased for only one participant. Participants reported high satisfaction with the PE + treatment, and exposure and coping skills were rated as the most helpful elements of treatment. CONCLUSIONS: Reductions in adversity sequelae were observed following PE + treatment, suggesting that adversity-focused treatment may be beneficial for an early psychosis population. Yet, few positive changes to psychotic symptoms or substance use were observed. Further integrating treatment strategies for psychosis and substance use into PE + may be required to effectively treat the links between psychosis, adversity sequelae, and substance use. Future studies should make efforts to integrate substance use strategies into adversity treatment trials for people with psychotic disorders. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04546178; registration posted 11/09/2020, https://clinicaltrials.gov/ct2/show/NCT04546178?term=NCT04546178&draw=2&rank=1 .

Diagnostic performance and radiation dose of reduced vs. standard scan range abdominopelvic CT for evaluation of appendicitis.

OBJECTIVE: To compare the diagnostic performance and radiation dose of reduced vs. standard scan range CT in diagnosing appendicitis. METHODS: We retrospectively evaluated 531 consecutive adults who underwent emergency contrast-enhanced CT for abdominal pain or suspected appendicitis between July 2018 and March 2019. One hundred eighty-one young adults (mean age, 26 ± 6 years) were imaged from L2 to the symphysis pubis (reduced protocol). A total of 350 older patients (mean age, 55 ± 17 years) and those with a wider differential diagnosis were imaged from the diaphragm to the ischium (standard protocol). The reference standard was histopathology (surgical cases) or 3 months of medical record follow-up (nonsurgical cases). Sensitivity, specificity, and accuracy were calculated. Mean dose-length products (DLP) were compared (t-test). Using an anthropomorphic phantom, organ doses were measured on CT scanners with (scanner 1) and without (scanner 2) automatic voltage selection; effective radiation doses were calculated. RESULTS: The frequency of appendicitis was 57/181 (31.5%) and 80/350 (22.9%) in the reduced and standard groups, respectively. Results of the reduced and standard protocols respectively were as follows (95% CI in parentheses): sensitivity, 98.2% (90.4-99.9%) and 100.0 (95.3-100.0%); specificity, 99.2% (95.6-100.0%) and 99.6% (97.9-100.0%); accuracy, 97.8% and 97.4%; mean DLPs, 363 ± 191mGy∙cm and 633 ± 591mGy∙cm (p < 0.0001). Phantom-based measurements of effective dose were 47% lower on scanner 1 (4.64 vs. 2.48 mSv) and 26% lower on scanner 2 (4.68 vs. 3.45 mSv) with the reduced protocol. CONCLUSION: For young adults with clinically suspected appendicitis, a reduced scan range CT protocol is as sensitive, specific, and accurate as a standard scan range CT and imparts significantly less radiation dose. KEY POINTS: • A reduced scan range CT protocol in young adults with high suspicion of appendicitis demonstrates similar diagnostic performance as a full-range abdominopelvic CT in undifferentiated adult patients. • The reduced scan range CT protocol imparts significantly less radiation dose: 57% based on dose-length product data and 26-47% based on anthropomorphic phantom data.

Toward individualized prediction of seizure recurrence: Hippocampal neuroimaging features in a cohort of patients from a first seizure clinic.

PURPOSE: We performed an exploratory analysis of electroencephalography (EEG) and neuroimaging data from a cohort of 51 patients with first seizure (FS) and new-onset epilepsy (NOE) to identify variables, or combinations of variables, that might discriminate between clinical trajectories over a one-year period and yield potential biomarkers of epileptogenesis. METHODS: Patients underwent EEG, hippocampal and whole brain structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS) within six weeks of the index seizure, and repeat neuroimaging one year later. We classified patients with FS as having had a single seizure (FS-SS) or having converted to epilepsy (FS-CON) after one year and performed logistic regression to identify combinations of variables that might discriminate between FS-SS and FS-CON, and between FS-SS and the combined group FS-CON + NOE. We performed paired t-tests to assess changes in quantitative variables over time. RESULTS: Several combinations of variables derived from hippocampal structural MRI, DTI, and MRS provided excellent discrimination between FS-SS and FS-CON in our sample, with areas under the receiver operating curve (AUROC) ranging from 0.924 to 1. They also provided excellent discrimination between FS-SS and the combined group FS-CON + NOE in our sample, with AUROC ranging from 0.902 to 1. After one year, hippocampal fractional anisotropy (FA) increased bilaterally, hippocampal radial diffusivity (RD) decreased on the side with the larger initial measurement, and whole brain axial diffusivity (AD) increased in patients with FS-SS; hippocampal volume decreased on the side with the larger initial measurement, hippocampal FA increased bilaterally, hippocampal RD decreased bilaterally and whole brain AD, FA and mean diffusivity increased in the combined group FS-CON + NOE (corrected threshold for significance, q = 0.017). CONCLUSION: We propose a prospective, multicenter study to develop and test models for the prediction of seizure recurrence in patients after a first seizure, based on hippocampal neuroimaging. Further longitudinal neuroimaging studies in patients with a first seizure and new-onset epilepsy may provide clues to the microstructural changes occurring at the earliest stages of epilepsy and yield biomarkers of epileptogenesis.

Long-acting injectable antipsychotic (LAI) prescribing trends during COVID-19 restrictions in Canada: a retrospective observational study.

BACKGROUND: The COVID-19 pandemic has had significant impacts on how mental health services are delivered to patients throughout Canada. The reduction of in-person healthcare services have created unique challenges for individuals with psychotic disorders that require regular clinic visits to administer and monitor long-acting injectable antipsychotic medications. METHODS: To better understand how LAI usage was impacted, national and provincial patient-level longitudinal prescribing data from Canadian retail pharmacies were used to examine LAI prescribing practices during the pandemic. Prescribing data on new starts of medication, discontinuations of medications, switches between medications, antipsychotic name, concomitant medications, payer plan, gender and age were collected from January 2019 to December 2020 for individuals ≥18-years of age, and examined by month, as well as by distinct pandemic related epochs characterized by varying degrees of public awareness, incidence of COVID-19 infections and public health restrictions. RESULTS: National, and provincial level data revealed that rates of LAI prescribing including new starts, discontinuations and switches between LAI products remained highly stable (i.e., no statistically significant differences) throughout the study period. CONCLUSIONS: Equal numbers of LAI new starts and discontinuations prior to and during the pandemic suggests prescribing of LAI antipsychotics, for those already in care, continued unchanged throughout the pandemic. The observed consistency of LAI prescribing contrasts with other areas of healthcare, such as cardiovascular and diabetes care, which experienced decreases in medication prescribing during the COVID-19 pandemic.

Are There Therapeutic Benefits of Cannabinoid Products in Adult Mental Illness?

A position statement developed by the Canadian Psychiatric Association's (CPA) Research Committee and approved by the CPA's Board of Directors on May 13, 2020.

Ultrasound and CT in the Diagnosis of Appendicitis: Accuracy With Consideration of Indeterminate Examinations According to STARD Guidelines.

OBJECTIVE. The objective of our study was to determine the accuracy of ultrasound (US) and CT in diagnosing appendicitis at our institution while taking into account the number of indeterminate examinations in accordance with the Standards for Reporting Diagnostic Accuracy (STARD) guidelines. MATERIALS AND METHODS. We retrospectively evaluated 790 patients who underwent US, CT, or both for evaluation of suspected appendicitis between May 1, 2013, and April 30, 2015. Patient characteristics and US and CT examination results were recorded. The reference standard was histopathology or 3 months of medical record follow-up if surgery was not performed; 3 × 2 tables were generated, and sensitivity, specificity, overall test yield, and accuracy were calculated according to STARD guidelines. For surgical cases, time to surgery (one-way ANOVA) was compared among patients who underwent US alone, CT alone, or both US and CT. RESULTS. A total of 473 of 562 US examinations had indeterminate findings (overall test yield, 15.8%); sensitivity and specificity in the 89 diagnostic examinations were 98.5% and 54.2%, respectively. Thirteen of 522 CT examinations were indeterminate (overall test yield, 97.5%); sensitivity and specificity in the remaining 509 CT examinations were 98.9% and 97.2%, respectively. Taking indeterminate studies into account, the accuracy was 13.7% for US and 95.6% for CT. The negative appendectomy rates were 17.7% (11/62) for US and 3.3% (9/276) for CT (p = 0.0002). Time to surgery was longer for patients who underwent US and CT (mean ± SD, 17.7 ± 8.9 hours) than US alone (12.9 ± 6.4 hours; p = 0.002) but was not longer for patients who underwent CT alone (16.3 ± 8.4 hours; p = 0.45). CONCLUSION. At our institution, a large proportion of US examinations are indeterminate for appendicitis. CT is the preferred first-line imaging test for evaluating appendicitis in nonobstetric adult patients.

A Retrospective Study of the Clinical Characteristics Associated with Alcohol and Cannabis use in Early Phase Psychosis.

OBJECTIVE: Alcohol and cannabis misuse are common in patients with early phase psychosis (EPP); however, research has tended to focus primarily on cannabis misuse and EPP outcomes, with a relative lack of data on alcohol misuse. This retrospective cross-sectional EPP study investigated the relationship between cannabis, alcohol, and cannabis combined with alcohol misuse, on age, gender, psychotic, depressive and anxiety symptom severity, and social/occupational functioning, at entry to service. METHODS: Two-hundred and sixty-four EPP patients were divided into 4 groups based on substance use measured by the Alcohol, Smoking and Substance Involvement Screening Test: (1) no to low-level cannabis and alcohol misuse (LU), (2) moderate to high alcohol misuse only (AU), (3) moderate to high cannabis misuse only (CU), and (4) moderate to high alcohol and cannabis misuse (AU + CU). RESULTS: We found significant between group differences in age (with the AU group being the oldest and AU + CU group the youngest) as well as gender (with the CU group having the highest percentage of men). There were also group differences in positive psychotic symptoms (lowest in AU group), trait anxiety (highest in AU + CU group), and social/occupational functioning (highest in AU group). Further regression analyses revealed a particularly strong relationship between AU + CU group and trait anxiety (3-fold increased odds of clinical trait anxiety for combined misuse of alcohol and cannabis compared to non/low users). CONCLUSIONS: This study demonstrates the unique demographic and clinical characteristics found in the EPP population at entry to care associated with alcohol and cannabis misuse both separately and in combination. This work highlights the importance of including the assessment of alcohol misuse in addition to cannabis misuse in future treatment guidelines and research.

Epilepsy as a Network Disorder (2): What can we learn from other network disorders such as dementia and schizophrenia, and what are the implications for translational research?

There is common agreement that many disorders of the central nervous system are 'complex', that is, there are many potential factors that influence the development of the disease, underlying mechanisms, and successful treatment. Most of these disorders, unfortunately, have no cure at the present time, and therapeutic strategies often have debilitating side effects. Interestingly, some of the 'complexities' of one disorder are found in another, and the similarities are often network defects. It seems likely that more discussions of these commonalities could advance our understanding and, therefore, have clinical implications or translational impact. With this in mind, the Fourth International Halifax Epilepsy Conference and Retreat was held as described in the prior paper, and this companion paper focuses on the second half of the meeting. Leaders in various subspecialties of epilepsy research were asked to address aging and dementia or psychosis in people with epilepsy (PWE). Commonalities between autism, depression, aging and dementia, psychosis, and epilepsy were the focus of the presentations and discussion. In the last session, additional experts commented on new conceptualization of translational epilepsy research efforts. Here, the presentations are reviewed, and salient points are highlighted.

Anxiety and Depression in Adult First Seizure Presentations.

OBJECTIVE: To define the prevalence of psychiatric symptoms of anxiety and depression in patients at the time of their first seizure presentation to a neurologist. METHODS: Our pilot study uses a cohort approach with multimodal data (clinical, social, structural [3T magnetic resonance imaging], and functional [electroencephalogram]). We screened 105 patients referred to the Halifax First Seizure Clinic between 2014 and 2016 and 51 controls. All participants completed two screening questionnaires: Neurological Disorders Depression Inventory for Epilepsy and Generalized Anxiety Disorder 7-Item. After applying the exclusion criteria, the study population consisted of 57 patients with unprovoked first seizure and 31 controls. The prevalence of anxiety and depression was based on cutoff scores of >15 and >14 respectively. RESULTS: Unprovoked first seizure patients showed higher prevalence of depression (33%) compared with control (6%) with an odds ratio (OR) of 2.75 (95% confidence interval [CI], 0.72-10.5). There was no significant difference in the prevalence of anxiety between control subjects (9.7%) and unprovoked first seizure patients (23%). Subcategory analysis conducted after diagnosis confirmation revealed significantly increased OR of depression in patients diagnosed with new-onset epilepsy (OR, 11.6; 95% CI, 2.1-64.0) and newly diagnosed epilepsy (OR, 20.0; 95% CI,2.2-181), but not first seizure only patients (OR, 2.2; 95% CI,0.28-17.6) compared with control. CONCLUSIONS: Our study supports a bidirectional relationship between the first seizure and depression. Prevalence rate of depression increased with duration of undiagnosed epilepsy at the time of first clinical assessment.

Heterogeneity in assessing the risk of developing a psychotic disorder given a previous subclinical psychotic-like experience in children and adolescents: A systematic review and meta-analysis.

Psychotic-like experiences (PLEs) are common in the general population. Child and adolescent PLEs are the most prevalent and linked with future psychotic disorders. Significant heterogeneity in PLE assessment has obscured its clinical utility to identify psychosis-prone trajectories and improve clinical outcomes. This meta-analysis aimed to assess i) PLE prevalence in children and adolescents and ii) their relationship with subsequent psychotic disorder while exploring sources of heterogeneity. PubMed, Embase, PsycINFO, and CINAHL databases were searched in August 2023 for population-based longitudinal studies that assessed child or adolescent PLEs and early adulthood psychotic outcomes. Six studies were included (n = 16,560), showing a pooled PLE prevalence of 17.3 %. Child and adolescent PLEs were associated with an increased risk of psychotic disorder in early adulthood (unadjusted OR = 3.80, 95 % CI: 2.31-6.26), with a population attributable fraction of 32.6 %. Significant heterogeneity in the strength of this relationship (I2 = 70 %, p = .01) was related to assessment type (self-report vs. interview). This review contends that interview-based PLE assessments could more accurately identify children or adolescents on a path towards psychosis and are better suited for psychotic risk identification. Further research is needed to elucidate interactions between PLEs and other psychotic risk factors.

The role of referral pathway to early intervention services for psychosis on 2-year inpatient and emergency service use.

This study examined the relationship between terminal referral source and subsequent urgent health service use in a Canadian early intervention service (EIS) for psychosis. Administrative health record data of emergency and inpatient mental health service use over a 2-year follow up from entry to EIS were retrospectively analyzed (n = 515). Negative binomial regression models were used to assess for the relationship between referral source and care outcomes. Compared to those referred from primary care services, the rate of urgent health care use was significantly greater for individuals referred to early intervention services from urgent care services while accounting for social and occupational functioning and psychotic symptom severity. Findings suggest that those referred from urgent services may be at an increased risk for subsequent urgent health care use while attending EIS for psychosis. Further research examining this relationship while incorporating additional relevant predictors is needed.

Referral pathways to early intervention services for psychosis and their influence on perceptions of care: An interpretive phenomenological analysis.

AIM: Most young adults experiencing psychosis enter early intervention services (EIS) via inpatient and emergency departments. These experiences are suggested to negatively impact their views of treatment and engagement in EIS. However, limited research has examined the impact of young adults' prior help-seeking experiences on these outcomes. The present study aimed to explore how young adults engaged in EIS have experienced initial help-seeking and make sense of these experiences in the context of their current treatment. METHODS: Using an interpretative phenomenological analysis approach, semi-structured interviews were conducted with 12 young adults (mean age = 24.83) within their first 3-12 months of treatment in EIS. Interviews aimed to examine their experiences of help-seeking and referral to EIS as well as the impact of these experiences on their subsequent perception of, and engagement with EIS. RESULTS: 3 superordinate themes emerged: (1) Navigating the Maze of Healthcare (2) Dignity and (3) Impact of Help-Seeking and Referral Experiences. Participants with referral pathways involving urgent care services described more adversity during their referral pathway and tended to describe help-seeking experiences as contributing to negative views towards EIS and diminished engagement in treatment. CONCLUSIONS: The impact of early negative experiences with healthcare on views towards EIS and engagement is evident in participants' accounts. Sense making was further contextualized by participants' illness insight, degree of recovery, and social support throughout experiences. Emergent themes highlight the need for psychiatric services to emphasize service users' dignity and for EIS to provide opportunities for patients to process past negative mental healthcare experiences to strengthen engagement.

Examining the Complex Mismatch Negativity in Early Phase Psychosis Using the Dual Rule Paradigm.

Using electroencephalography (EEG) to examine the simple mismatch negativity (MMN), a marker of auditory cortex function, has been of great interest in the exploration of biomarkers for psychotic illness. Despite many studies reporting MMN deficits in chronic schizophrenia, there are inconsistent reports of MMN reductions in the early phases of psychotic illness, suggesting the MMN elicited by traditional paradigms may not be a sensitive enough measure of vulnerability to be used as a biomarker. Recently, a more computationally complex measure of auditory cortex function (the complex mismatch negativity; cMMN) has been hypothesized to provide a more sensitive marker of illness vulnerability. The current study employed a novel dual rule paradigm, in which two pattern rules are established and violated, to examine the cMMN in 14 individuals with early phase psychosis (EPP, < 5 years illness) and 15 healthy controls (HC). Relationships between cMMN waveforms, symptom severity, and measures of functioning were explored. We found reductions of cMMN amplitudes at the site of maximal amplitude in EPP (p = .017) with large effect sizes (Hedges' g = 0.96). This study is an early step in the exploration of the cMMN as a biomarker for psychosis. Our results provide evidence that the dual rule cMMN paradigm shows promise as a method for cMMN elicitation that captures more subtle neurofunctional changes in the early stages of illness.

A conceptual framework for the use of neuroimaging to study and predict pharmacoresistance in epilepsy.

Twenty percent to 49% of newly treated patients with epilepsy will develop pharmacoresistance (PR). The mechanisms leading to PR are unclear. There is currently no unifying theory to explain the variety of presentations of PR and the diversity of potential contributing factors. Etiology of seizures seems to play a critical role in at least a subset of PR. Many magnetic resonance imaging (MRI) studies in the advanced stages of epilepsy suggest a strong association between lesions such as hippocampal sclerosis and focal cortical dysplasia and PR. Unfortunately, almost all of these studies are cross-sectional and retrospective. There is a need for a new perspective on the role of preexisting lesions in the evolution of epilepsy and PR. We propose in this article to study a unique population of drug-naive patients with either first seizure or new-onset epilepsy longitudinally with advanced MRI imaging techniques, including magnetic resonance spectroscopy and diffusion tensor imaging. We hope to be able to monitor imaging findings and the development of PR early in the course of the disease in a subset of these patients with temporal lobe epilepsy (TLE). Our goal is to understand the pathogenesis of PR, to dissect changes associated with the development of PR from changes associated with chronic seizures and medication, and ultimately to predict PR at the onset of disease.

Mental health adverse events with cannabis use diagnosed in the Emergency Department: what are we finding now and are our findings accurate?

We have previously reviewed the types and numbers of cannabis-associated adverse events that have mental health presentations that are encountered in the Emergency Department. A particular challenge in examining these events is disentangling cannabis use adverse events from adverse events associated with use of multiple recreational substances. Since that review was published, cannabis legalization for recreational use has greatly expanded world-wide and with these changes in the legal climate has come clearer information around the frequency of adverse events seen in the Emergency Department. However, as we examined the current state of the literature, we also examined some of research designs and the biases that may be impacting the validity of the data in this field. The biases both of clinicians and researchers as well as research approaches to studying these events may be impacting our ability to assess the interaction between cannabis and mental health. For example, many of the studies performed examining cannabis-related admissions to the Emergency Department were administrative studies that relied on front line clinicians to identify and attribute that cannabis use was associated with any particular admission. This narrative review provides an overview on what we currently know about mental health adverse events in the Emergency Department with a focus on the mental health impacts both for those with and without a history of mental illness. The evidence that cannabis use can adversely impact genders and sexes differently is also discussed. This review outlines what the most common adverse events related to mental health with cannabis use are; as well as noting the most concerning but much rarer events that have been reported. Additionally, this review suggests a framework for critical evaluation of this field of study going forward.

Short communication: Prevalence of long-acting injectable antipsychotic use in Canadian early intervention services for psychosis.

The use of long-acting injectable (LAI) antipsychotic drugs for psychotic disorders in Canada has been historically low compared to other jurisdictions despite advantages of LAIs in improving medication adherence and preventing relapse. In response, treatment recommendations were developed in 2013 by the Canadian Consortium for Early Intervention in Psychosis and other Canadian provincial expert groups. The impact of these guidelines needed to be assessed. To document practices in LAI use in early intervention services (EIS) for psychosis, Canadian EIS were surveyed in 2016 (n = 18) and 2020 (n = 12). Trends and descriptive information were examined using repeated cross-sectional survey data. Eight EIS responded to surveys at both time points allowing for longitudinal comparisons. Outcomes of interest included i) LAI use frequency, ii) timing of LAI starts, and iii) factors influencing LAI use. Cross-sectional analysis identified a significant increase in overall LAI usage (24.7% in 2016; 35.1% in 2020). Longitudinal analysis indicated that patients in the second program year saw the greatest increase in LAI use between 2016 and 2020 (25.6% vs. 36.1%), especially among patients under community treatment orders (65.5% vs. 81.5%). Results support increases in LAI use over time, accessibility, awareness, and increasing comfortability among Canadian clinicians.

Interaction of sex and cannabis in adult in vivo brain imaging studies: A systematic review.

Cannabis has been shown to cause structural and functional neurocognitive changes in heavy users. Cannabis use initiation aligns with brain development trajectories; therefore, it is imperative that the potential neurological implications of cannabis use are understood. Males and females reach neurodevelopmental milestones at different rates making it necessary to consider biological sex in all cannabis and brain-based research. Through use of a systamatic review in accordance with PRISMA guidelines, we aimed to understand the interaction between biological sex and cannabis use on brain-based markers. In total, 18 articles containing a sex-based analysis of cannabis users were identified. While the majority of studies (n = 11) reported no sex by cannabis use interactions on brain-based markers, those that reported findings (n = 8) suggest females may be more susceptible to cannabis' neurotoxic effects. Unfortunately, a large portion of the literature was excluded due to no sex-based analysis. In addition, studies that reported no sex differences often contained a reduced number of females which may result in some studies being underpowered for sex-based analyses, making it difficult to draw firm conclusions. Suggestions to improve cannabis and sex-based reseach are proposed.