Antipsychotic (AP) medication in individuals at clinical high risk for psychosis (CHR-P) is not routinely recommended by clinical guidelines but is commonly prescribed. Since little is known about the predictors of AP inception in CHR-P, we analyzed data from two observational cohorts.

To avoid baseline predictors being confounded by previous treatment, participants were selected for analysis from the 764 participants at CHR-P enrolled in NAPLS-2 and the 710 enrolled in NAPLS-3 by excluding those with lifetime histories of AP use. Baseline clinical variables available in both studies were employed as predictors of subsequent AP inception over the next 6 months in univariable and multivariable analyses.

Preliminary analyses indicated no important effects of sample. The final combined population included 79 AP inception participants and 580 participants who did not have AP inception. The AP medications most commonly prescribed were risperidone, aripiprazole, and quetiapine. Univariable analyses identified seven significant predictors of AP inception. The final logistic regression model including these variables was highly significant (χ2 = 36.53, df = 7, p = <0.001). Three variables (current major depression, fewer education years, and current benzodiazepine use) emerged as significant independent predictors of AP inception.

This study is the first to determine baseline characteristics that predict subsequent AP initiation in CHR-P. Some AP use in CHR-P appears to be intended as augmentation of antidepressant treatment for comorbid major depression. Some prescribers may not have detected the attenuated positive symptoms characteristic of CHR-P since their severity did not significantly predict AP inception.

Haemolysis is developing prominence in the setting of supporting increasingly complex children with heart failure with a ventricular assist device. The goal of this study is to better characterise haemolysis and its implications in children supported with pulsatile ventricular assist devices.

This is a single-centre retrospective review of 44 children who were supported by Berlin Heart EXCOR between January 2006 and June 2020. Patients were divided into major haemolysers and non-major haemolysers. Major haemolysers were defined as patients with lactate dehydrogenase > 500U/L (2.5x the upper limits of normal) with either total bilirubin > 2mg/dL (with predominantly indirect hyperbilirubinemia) or anaemia out of proportion to the clinical scenario more than three days following implantation of the ventricular assist device(s). Patient demographics, ventricular assist device factors, and outcomes, including end-organ function and mortality, were compared between major haemolysers and non-major haemolysers.

Forty-four patients supported by the Berlin EXCOR were included in the analytic cohort of the study: 27 major haemolysers and 17 non-major haemolysers. Major haemolysis was more common in those supported with single-ventricle ventricular assist device (i.e., VAD in the context of functionally univentricular anatomy) compared to those with biventricular hearts, p = 0.01. There were no patients with an isolated left ventricular assist device or isolated right ventricular assist device in our analytic cohort of 44 patients. Of the 19 patients with single-ventricle ventricular assist device, 84% (16/19) were major haemolysers. Of the 25 patients with a biventricular assist device, 44% (11/25) were major haemolysers. Major haemolysers and non-major haemolysers had a body surface area of 0.28 and 0.40, respectively (p = 0.01). Overall, survival to discharge from the hospital was 66% (n = 29/44). Survival to discharge from the hospital was 52% (14/27) in major haemolysers versus 88% (15/17) in non-major haemolysers, p = 0.02. Only 3 of the 27 with major haemolysis had severe haemolysis, that is, lactate dehydrogenase > 2000 and bilirubin above 10. Non-major haemolysers had a better improvement in creatinine clearance during ventricular assist device support, p < 0.0001. (During the same era of this study, 22 patients who were supported with Berlin Heart were excluded from the analytic cohort because they did not have any recorded measurement of lactate dehydrogenase. Seventeen of these 22 patients had no clinical evidence of haemolysis. Survival to discharge from the hospital in this excluded cohort was 86% [19/22].)

Major haemolysis in patients with pulsatile ventricular assist device is more likely with single-ventricle ventricular assist device support and smaller body surface area.

Negative symptoms are a key feature of several psychiatric disorders. Difficulty identifying common neurobiological mechanisms that cut across diagnostic boundaries might result from equifinality (i.e., multiple mechanistic pathways to the same clinical profile), both within and across disorders. This study used a data-driven approach to identify unique subgroups of participants with distinct reward processing profiles to determine which profiles predicted negative symptoms.

Participants were a transdiagnostic sample of youth from a multisite study of psychosis risk, including 110 individuals at clinical high-risk for psychosis (CHR; meeting psychosis-risk syndrome criteria), 88 help-seeking participants who failed to meet CHR criteria and/or who presented with other psychiatric diagnoses, and a reference group of 66 healthy controls. Participants completed clinical interviews and behavioral tasks assessing four reward processing constructs indexed by the RDoC Positive Valence Systems: hedonic reactivity, reinforcement learning, value representation, and effort–cost computation.

k-means cluster analysis of clinical participants identified three subgroups with distinct reward processing profiles, primarily characterized by: a value representation deficit (54%), a generalized reward processing deficit (17%), and a hedonic reactivity deficit (29%). Clusters did not differ in rates of clinical group membership or psychiatric diagnoses. Elevated negative symptoms were only present in the generalized deficit cluster, which also displayed greater functional impairment and higher psychosis conversion probability scores.

Contrary to the equifinality hypothesis, results suggested one global reward processing deficit pathway to negative symptoms independent of diagnostic classification. Assessment of reward processing profiles may have utility for individualized clinical prediction and treatment.

Cognitive sequelae are reported in 20-25% of patients following SARS-CoV-2 infection. It remains unclear whether post-infection sequelae cluster into a uniform cognitive syndrome. In this cohort study, we characterized post-COVID neuropsychological outcome clusters, identified factors associated with cluster membership, and examined 6-month recovery trajectories by cluster.

The Mayo Clinic Institutional Review Board approved study protocols. Informed consent was obtained from all participants. Participants (> 18 years old) were recruited from a hospital-wide registry of Mayo Clinic Florida patients who tested positive for SARS-CoV-2 infection from July 2020 to Feb 2022. We abstracted participant health history and COVID-19 disease severity (NIAID score) from the electronic health record and retrieved Area Deprivation Index (ADI) scores as a measure of neighborhood socioeconomic disadvantage. We assessed objective cognitive performance with the CNS Vital-Signs (CNSVS) and subjective neuropsychological symptoms with the Neuropsych Questionnaire-45 (NPQ-45). Results were used as input features in a K-means clustering analysis to derive neurophenotypes. Chi-square and analysis of variance (AnOvA) tests were used to identify clinical and sociodemographic factors associated with cluster membership. Participants repeated the CNS Vital Signs, NPQ-45, as well as the Medical Outcomes Survey (MOS SF-36) and a posttraumatic stress disorder (PTSD) checklist (PCL-C 17) 6 months following initial testing. Repeated-measures ANOVA was used to assess change in neurocognitive performance over time by cluster. Significance was set at P < 0.05.

Our cohort consisted of 205 participants (171 ambulatory, 34 hospitalized) who completed post-acute outcome assessment a mean of 5.7 (± 3.8) weeks following testing positive for SARS-CoV-2. K-means clustering with elbow method fitting identified three subgroups (see figure). The first cluster (N = 31) is characterized by executive dysfunction, greater socioeconomic disadvantage, and higher rates of obesity. The second cluster (N = 32) is characterized by memory and speed impairment, higher COVID severity, prevalent anosmia (70%), and greater severity of memory complaints, depression, anxiety, and fatigue. The third and largest cluster (N = 142) is absent cognitive impairment. Approximately 39% of participants completed the 6-month outcome assessment (N=79). Regardless of cluster membership, verbal memory, psychomotor speed, and reaction time scores improved over time. Regardless of timepoint, cluster 1 (dysexecutive) showed lower scores on cognitive flexibility and complex attention and cluster 2 (memory-speed impaired) showed lower scores on verbal memory, psychomotor speed, and reaction time. Modeling of cluster by timepoint interactions showed a steeper slope of improvement in complex attention and cognitive flexibility in cluster 1 (dysexecutive). Cluster 3 (normal) showed significant improvement in fatigue while cluster 2 (memory-speed impaired) continued to report moderate-severe fatigue, worse medical outcomes, and higher PTSD symptom severity scores at six months.

Most participants were cognitively normal or experienced cognitive recovery following SARS-CoV-2 infection. The 25-30% of participants who showed cognitive impairment cluster into two different neurophenotypes. The dysexecutive phenotype was associated with socioeconomic factors and medical comorbidities that are non-specific to COVID-19, while the amnestic phenotype was associated with COVID-19 severity and anosmia. These results suggest that cognitive sequelae following SARS-CoV-2 infection are not uniform. Deficits may be influenced by distinct patient- and disease-specific factors, necessitating differentiated treatment approaches.

Early Intervention (EI) services aim to reduce progression to chronic illness for patients with schizophrenia. The Lambeth Early Onset study (2002) demonstrated reduced hospitalisation at 18 months for patients exposed to EI services. This study assesses the durability of these benefits at 5 years.

Hospital use in the LEO cohort was assessed by case note review.

There was no statistically significant difference in terms of ever being admitted at 5 years (OR 1.42; 95% CI 0.550 - 3.68; p=0.468)). Although the mean number of admissions was lower in the EI group: 1.65 (SD = 0.86) versus 1.83 (SD= 0.92), this difference was not significant (coefficient = 0.096; 95% CI -0.550 - 0.742; p=0.770). At 5 years patients assigned to EI used 42.25 days (SD 112.8 days) versus 51.41 days (SD 125 days); coefficient = 6.344; 95% CI -46 - 58.7; p= 0.810. The primary outcome was robust to potentially extreme admission rates for missing subjects on sensitivity analysis.

There is no evidence from these data that EI services statistically significantly reduce hospital use at 5 years follow-up (vis a vis care as usual) despite some interim benefits at 18 months. We only considered a limited number of outcomes and more work needs to be done in this area.

The existence of a frontotemporal dementia phenocopy (phFTD) syndrome remains controversial. Opinions differ on whether the phenocopy presentation represents the neuropsychological manifestation of a mid-life decompensation in vulnerable pre-morbid personalities or an indolent prodrome of behavioral-variant FTD (bvFTD). Literature on this topic is sparse and clinicians and patients have little guidance around prognosis and management.

To describe the demographic, neuropsychological and biomarker profiles of a case series of phFTD patients, attending the memory clinic and review relevant literature.

Retrospective review of all cases diagnosed with phFTD.

Eleven cases were identified (male = 9, female = 2). Mean age 55.8 years. Subjective complaints comprised memory and language difficulties. Collateral reports described apathy, aggression, impulsivity, disinhibition, hyperorality. Function was relatively preserved though motivation or supervision for higher-level tasks was sometimes required. All had non-neurodegenerative MRI and PET scans. Neuropsychological test (NPT) findings predominantly showed executive dysfunction and fluency impairment. A total of 3/11 had non-amnestic memory impairment. Follow-up imaging and NPT were invariably unchanged; 1/11 had a pre-morbid psychiatric diagnosis; 5/11 had unusual personality traits pre-morbidly. Major psychosocial stressors were documented in 7/11. Management consisted of psychosocial interventions to support function and interpersonal relationships.

The literature describes the phFTD syndrome as predominantly affecting males though we include 2 females who meet the criteria. In keeping with our findings, personality traits and psychosocial stressors may be more common in phFTD than bvFTD. More severe symptoms, memory impairment at presentation and C9ORF72 gene mutation may predict eventual progression. Those who do not progress have minimal long-term functional impairment though behavioral symptoms persist.

The authors have not supplied their declaration of competing interest.

Disaster Medicine (DM) is a discipline arising from the marriage of emergency medicine and disaster management. The importance of DM has recently increased, with current wildfire situations throughout the world being examples of mass scale disasters with significant human morbidity and mortality. DM deals with preparedness, mitigation, response, recovery, and prevention of disasters (1).

To develop an educational strategy and reusable format for delivering undergraduate DM courses online. Man-made, weather-related, humanitarian, and technological disasters occur all around the globe annually, yet the majority of medical schools do not have an undergraduate DM program. This project developed an online course structure accessible to medical schools and students throughout the world.

Learning theories and models of learning were used to construct a course layout that encouraged students to be active learners, developed long-term retention strategies, and facilitated assessment for and of learning. This was accomplished through innovative educational modalities, including novel apps and external online resources. The course focuses heavily on outcome-based education with an emphasis on the development of applicable skills. Each lecture is divided into a series of learning objectives to allow students to master concepts sequentially, followed by questions to make use of the “testing effect” (2).

Focused review of current medical education literature reveals that students learn best when given short, outcome-focused “mini-lectures” followed by low-stakes assessment and feedback.

Medical schools without trained DM staff now have access to expert online material developed by educationalists with a focus on skills and knowledge retention.

The transition from adolescent to adult mental health services (AMHS) is associated with disengagement, poor continuity of care and patient dissatisfaction. The aim of this retrospective and descriptive study was to describe the ‘care pathways’ in an independent mental health service when adolescents reach age 18 and to investigate the level of engagement of those who transitioned to independent AMHS.

This is a retrospective, naturalistic and descriptive study in design. All patients discharged from the St Patrick’s Adolescent Mental Health Service aged 17 years and 6 months and older, during a 3-year period between January 2014 and December 2016, were included. Electronic records were used to collect socio-demographic and clinical details and to determine engagement rates in adolescents who transferred to independent adult services.

A total of 180 patients aged over 17 years and 6 months were discharged from the adolescent service. Of these, 45.6% were discharged to their GP, 28.9% to public mental health services and 25.6% to independent mental health services. The majority who transitioned to independent AMHS went to a Young Adult Service, which had high engagement rates at 3 and 12 months post-transition.

In this independent mental health service, less than half of adolescents who reach the transition age are referred onto AMHS. Engagement rates were found to be high among those referred on to a specialised young adult service.