Early intervention in psychosis (EIP) services improve outcomes for young people, but approximately 30% disengage.

To test whether a new motivational engagement intervention would prolong engagement and whether it was cost-effective.

We conducted a multicentre, single-blind, parallel-group, cluster randomised controlled trial involving 20 EIP teams at five UK National Health Service (NHS) sites. Teams were randomised using permuted blocks stratified by NHS trust. Participants were all young people (aged 14–35 years) presenting with a first episode of psychosis between May 2019 and July 2020 (N = 1027). We compared the novel Early Youth Engagement (EYE-2) intervention plus standardised EIP (sEIP) with sEIP alone. The primary outcome was time to disengagement over 12–26 months. Economic outcomes were mental health costs, societal costs and socio-occupational outcomes over 12 months. Assessors were masked to treatment allocation for primary disengagement and cost-effectiveness outcomes. Analysis followed intention-to-treat principles. The trial was registered at ISRCTN51629746.

Disengagement was low at 15.9% overall in standardised stand-alone services. The adjusted hazard ratio for EYE-2 + sEIP (n = 652) versus sEIP alone (n = 375) was 1.07 (95% CI 0.76–1.49; P = 0.713). The health economic evaluation indicated lower mental healthcare costs linked to reductions in unplanned mental healthcare with no compromise of clinical outcomes, as well as some evidence for lower societal costs and more days in education, training, employment and stable accommodation in the EYE-2 group.

We found no evidence that EYE-2 increased time to disengagement, but there was some evidence for its cost-effectiveness. This is the largest study to date reporting positive engagement, health and cost outcomes in a total EIP population sample. Limitations included high loss to follow-up for secondary outcomes and low completion of societal and socio-occupational data. COVID-19 affected fidelity and implementation. Future engagement research should target engagement to those in greatest need, including in-patients and those with socio-occupational goals.

Traumatic brain injury (TBI), mental health conditions (e.g., posttraumatic stress disorder [PTSD]), and vascular comorbidities (e.g., hypertension, diabetes) are highly prevalent in the Veteran population and may exacerbate age-related changes to cerebral white matter (WM). Our study examined (1) relationships between health conditions—TBI history, PTSD, and vascular risk—and cerebral WM micro- and macrostructure, and (2) associations between WM measures and cognition.

We analyzed diffusion tensor images from 183 older male Veterans (mean age = 69.18; SD = 3.61) with (n = 95) and without (n = 88) a history of TBI using tractography. Generalized linear models examined associations between health conditions and diffusion metrics. Total WM hyperintensity (WMH) volume was calculated from fluid-attenuated inversion recovery images. Robust regression examined associations between health conditions and WMH volume. Finally, elastic net regularized regression examined associations between WM measures and cognitive performance.

Veterans with and without TBI did not differ in severity of PTSD or vascular risk (p’s >0.05). TBI history, PTSD, and vascular risk were independently associated with poorer WM microstructural organization (p’s <0.5, corrected), however the effects of vascular risk were more numerous and widespread. Vascular risk was positively associated with WMH volume (p = 0.004, β=0.200, R2 = 0.034). Higher WMH volume predicted poorer processing speed (R2 = 0.052).

Relative to TBI history and PTSD, vascular risk may be more robustly associated with WM micro- and macrostructure. Furthermore, greater WMH burden is associated with poorer processing speed. Our study supports the importance of vascular health interventions in mitigating negative brain aging outcomes in Veterans.

We sought to compare patient outcomes between carbapenem-resistant Enterobacterales (CRE) and carbapenem-susceptible Enterobacterales (CSE) infections at our academic medical center.

We conducted a retrospective cohort study of adult patients with a positive culture of E. coli, E. cloacae, K. aerogenes, K. oxytoca, and/or K. pneumoniae admitted at UK HealthCare (January 1, 2010–December 31, 2019). Based on the type of pathogen on the date of the first culture (index date), patients were included in the CRE (i.e., exposed) group, or the CSE (comparator) group. Exclusion criteria were age < 18 years old, pregnancy, endocarditis, osteomyelitis, necrotizing fasciitis, or cystic fibrosis. We evaluated the impact of CRE vs CSE on a composite outcome of 30-day of all-cause mortality or discharge to hospice using Kaplan–Meier survival curves and Cox proportional hazard regression with inverse probability of treatment weights (IPTW).

Of 17,839 hospitalized patients, 128 and 6,953 patients were included in the CRE and CSE groups, respectively. Baseline differences existed in sex-assigned-at-birth, admission source, time-to-index culture, and infection type/severity. Most CRE index cultures observed (76%) only exhibited resistance to ertapenem. IPTW-adjusted HR [95% CI] of composite outcome was 0.99 [0.65, 1.51] after 30 days. Follow-up analysis in patients with carbapenem-non-susceptible Enterobacteralesbloodstream infections on index yielded an HR of 1.38 [0.85, 2.24].

Risk of composite outcome was not estimated to differ between patients with CRE and CSE in the overall analysis. Although follow-up analysis identified an increased risk, we cannot statistically distinguish this from a null effect.

Family members of people experiencing a first-episode psychosis (FEP) can experience high levels of carer burden, stigma, emotional challenges, and uncertainty. This indicates the need for support and psychoeducation. To address these needs during the COVID-19 pandemic, we developed a multidisciplinary, blended, telehealth intervention, incorporating psychoeducation and peer support, for family members of FEP service users: PERCEPTION (PsychoEducation for Relatives of people Currently Experiencing Psychosis using Telehealth, an In-person meeting, and ONline peer support). The aim of the study was to explore the acceptability of PERCEPTION for family members of people who have experienced an FEP.

Ten semi-structured interviews were conducted online via Zoom and audio recorded. Maximum variation sampling was used to recruit a sample balanced across age, gender, relatives’ prior mental health service use experience, and participants’ relationship with the family member experiencing psychosis. Data were analysed by hand using reflexive thematic analysis.

Four themes were produced: ‘Developing confidence in understanding and responding to psychosis’; ‘Navigating the small challenges of a broadly acceptable and desirable intervention’; ‘Timely support enriches the intervention’s meaning’; and ‘Dealing with the realities of carer burden’.

Broadly speaking, PERCEPTION was experienced as acceptable, with the convenient, safe, and supportive environment, and challenges in engagement being highlighted by participants. Data point to a gap in service provision for long-term self-care support for relatives to reduce carer burden. Providing both in-person and online interventions, depending on individuals’ preference and needs, may help remove barriers for family members accessing help.

Paliperidone palmitate 3-monthly (PP3M) has been tested in 1-year controlled studies. The aim of this study was to examine the relapse outcomes with PP3M monotherapy at 3 years in patients with schizophrenia.

This was an observational, non-interventional study of patients started on PP3M according to their clinical need. All patients had a diagnosis of schizophrenia (ICD-10 F20) and were between 18 and 65 years of age. The study took place in a mental health facility in South East London, UK.

Among the 166 patients who started PP3M, 97 (58%) met inclusion criteria and were observed for 36 months. In total, five patients (5%) experienced a relapse (defined as step-up in clinical care) while on PP3M. There were no relapses between months 18 and 36. Of the original 97 patients, 56 (58%) remained on PP3M monotherapy at 3 years, and 71 (73%) remained on either PP3M or paliperidone palmitate one-monthly. Reasons for discontinuation of PP3M included patient refusal (n = 11, 33% of discontinuations) and adverse effects in (n = 8, 24%).

PP3M is a highly effective monotherapy treatment for reducing relapse in people with schizophrenia.

Research indicates that Veterans with a history of traumatic brain injury (TBI) are at increased risk for dementia. Although the precise mechanisms underlying this relationship are poorly understood, remote TBI may exacerbate normal age-related changes to cerebral white matter (WM) and result in cognitive decline. However, Veterans commonly experience a constellation of mental (e.g., post-traumatic stress disorder [PTSD] and depression) and vascular (e.g., diabetes, hypertension, obesity) health conditions that have also been implicated in pathologic cerebral WM and cognitive aging trajectories. Therefore, the present study sought to (1) clarify the effects of remote TBI within the context of PTSD, depression, and vascular risk on WM micro- and macrostructure, and (2) explore if WM integrity is associated with cognition in a sample of Vietnam-Era Veterans.

The sample consisted of 195 male Veterans ages 60-80 (mean age=69.3) enrolled in the Department of Defense-Alzheimer’s Disease Neuroimaging Initiative (DoD-ADNI) study. 102 Veterans met criteria for TBI by sustaining a head-injury that resulted in a loss of consciousness, alteration of consciousness, or post-traumatic amnesia. Current and/or lifetime PTSD was designated by scores >30 on the Clinician-Administered PTSD Scale. The Geriatric Depression Scale was used as a continuous measure of depression. A vascular risk score (0-3) was calculated based on diabetes, hypertension, and obesity (BMI >30 kg/m2). An executive functioning composite was created by averaging sample-specific z-scores for Trail Making Tests (A and B), with higher scores indicating worse performance. Voxelwise analysis of WM microstructure (fractional anisotropy [FA]) was conducted with Tract-Based Spatial Statistics (TBSS), using non-parametric permutation testing with threshold-free cluster enhancement. SPM’s Lesion Segmentation Tool was used to investigate WM macrostructure (WM hyperintensity [WMH] volume). Lesion probability maps were masked to restrict WMH volume calculations to WM. Robust regression using M-estimation and predictive R2 calculated using 10-fold cross-validation examined WMH volume, predictor, and cognitive associations. Age was a covariate in all WM analyses, and education was a covariate in all cognitive analyses.

TBSS analysis revealed widespread, significant negative relationships between vascular risk and FA across numerous WM tracts (p’s<0.05). These associations remained significant after adjusting for TBI history, PTSD, and depression. TBSS identified significant positive relationships between executive functioning performance and FA across similar brain regions (p’s<0.05). Robust regressions revealed that vascular risk significantly predicted WMH volume (p=0.006; ß=0.161; R2=0.093), whereas TBI history, PTSD, and depression did not (p’s=0.107-0.166; ß's=-0.089-0.101). WMH volume significantly predicted executive functioning (p=0.002; ß=0.216; R2=0.105), whereas TBI history, PTSD, depression, and vascular risk did not (p’s=0.123-0.888; ß's=-0.012-0.125).

Our results suggest that vascular health, relative to remote TBI, PTSD, and depression, may be more robustly associated with cerebral WM micro- and macrostructure in older Veterans. Furthermore, poorer WM integrity is associated with poorer cognitive performance. These findings underscore the importance of vascular health interventions in preventing negative brain and cognitive aging outcomes in Veterans, independent of TBI history. Future studies might leverage other neuroimaging modalities (e.g., functional MRI) to further investigate the effects of vascular health on aging in Veterans with a history of TBI.

Frequent and remote cognitive assessment may improve sensitivity to subtle cognitive decline associated with preclinical Alzheimer’s disease (AD). The objective of this study was to evaluate the feasibility and acceptability of repeated remote memory assessment in late middle-aged and older adults.

We recruited participants from a longitudinal aging cohort to complete three medial temporal lobe-based memory paradigms (Object-In-Room Recall [ORR], Mnemonic Discrimination for Objects and Scenes [MDT-OS], Complex Scene Recognition [CSR]) using the neotiv application at repeated intervals over one year. We conducted initial telephone calls to perform screening, consent, and download instructions. Participants were assigned 24 remote sessions on a smartphone or tablet and were alerted via push notification when an assignment was ready to complete. Participants were randomly assigned to: (1) complete memory tests every other week or (2) complete memory tests for multiple days within one week every other month. Each remote session lasts approximately 10 minutes and includes one memory paradigm and brief usability/acceptability questionnaires followed by a delayed retrieval session 90 minutes later. Feasibility metrics examined included participation, retention, compliance, and usability/acceptability.

Of 150 participants recruited, 113 consented and were enrolled into the study (participation rate = 75%). Current retention rate is 75%, with 85/113 currently active (n=73) or completed (n=12). Of the 85 active or completed participants, the mean age is 68.7 (range = 4882), 64% are women, 70% used a smartphone (30% tablet), 84 are cognitively unimpaired and 1 has mild cognitive impairment. The primary threat to retention was participants consenting into the study but never registering in the app or completing their first scheduled assignment. After enrollment, 130 telephone calls were made by study staff to facilitate registration into the app or to remind participants to complete tasks. 74-80% of participants completed delayed retrieval tasks within 30 minutes of push notification, but average retrieval time was 125137 minutes post-learning trials. Regarding acceptability/usability, 94% agreed the application was easy to use, 56% enjoyed completing the mobile memory tests (36% felt neutral), 40% prefer remote mobile memory tests to standard in-person paper and pencil tests, and 50% understood the test instructions. 87% felt the frequency of tests assigned was “just right” (13% “too often”) and 90% felt the test length was “just right” (7% too short, 3% too long). Participants who completed all 24 sessions to date (n=12) all endorsed being “satisfied” or “very satisfied” with the platform and visit schedule, as well as recommended continued use of this type of cognitive testing.

Remote memory assessment using smartphones and tablets is feasible and acceptable for cognitively unimpaired late middle-aged and older adults. Follow-up by study staff was needed to ensure adequate retention. Comprehension of instructions and compliance with completing delayed retrieval tasks within the expected timeframe was lower than expected. These feedback will be incorporated into an updated version of the app to improve compliance and retention. Longitudinal data collection is ongoing and results will be updated with a larger sample. Results will be compared across frequency schedule groups.

The objective of this study was to compare the attitudes and beliefs of PCU physicians leaders in the United States versus Canada regarding the subcutaneous method in the administration of medications and hydration in order to gain a better understanding as to why variations in practice exist.

This survey trial took place from November 2022 to May 2023. The MD Anderson Cancer Center institutional review board in Houston, Texas, approved this study. The participants were the physician leaders of the acute palliative care units (PCUs) in the United States and Canada. The survey comprised questions formulated by the study investigators regarding the perceived comfort, efficiency, and preference of using the subcutaneous versus the intravenous method. The consent form and survey links were emailed to the participants.

Sixteen PCUs were identified in the United States and 15 PCUs in Canada. Nine US and 8 Canadian physicians completed the survey. Physicians in Canada were more likely to use the subcutaneous route for administering opioids, antiemetics, neuroleptics, and hydration. They preferred subcutaneous over intravenous or intramuscular routes (p = 0.017). Canadian physicians felt their nursing staff was more comfortable with subcutaneous administration (p = 0.022) and that it was easier to administer (p = 0.02). US physicians felt the intravenous route was more efficient (p = 0.013).

The study results suggest that exposure to the subcutaneous route influences a physician’s perception. Further research is needed to explore ways to incorporate its use to a greater degree in the US healthcare system.

Trauma is prevalent amongst early psychosis patients and associated with adverse outcomes. Past trials of trauma-focused therapy have focused on chronic patients with psychosis/schizophrenia and comorbid Post-Traumatic Stress Disorder (PTSD). We aimed to determine the feasibility of a large-scale randomized controlled trial (RCT) of an Eye Movement Desensitization and Reprocessing for psychosis (EMDRp) intervention for early psychosis service users.

A single-blind RCT comparing 16 sessions of EMDRp + TAU v. TAU only was conducted. Participants completed baseline, 6-month and 12-month post-randomization assessments. EMDRp and trial assessments were delivered both in-person and remotely due to COVID-19 restrictions. Feasibility outcomes were recruitment and retention, therapy attendance/engagement, adherence to EMDRp treatment protocol, and the ‘promise of efficacy’ of EMDRp on relevant clinical outcomes.

Sixty participants (100% of the recruitment target) received TAU or EMDR + TAU. 83% completed at least one follow-up assessment, with 74% at 6-month and 70% at 12-month. 74% of EMDRp + TAU participants received at least eight therapy sessions and 97% rated therapy sessions demonstrated good treatment fidelity. At 6-month, there were signals of promise of efficacy of EMDRp + TAU v. TAU for total psychotic symptoms (PANSS), subjective recovery from psychosis, PTSD symptoms, depression, anxiety, and general health status. Signals of efficacy at 12-month were less pronounced but remained robust for PTSD symptoms and general health status.

The trial feasibility criteria were fully met, and EMDRp was associated with promising signals of efficacy on a range of valuable clinical outcomes. A larger-scale, multi-center trial of EMDRp is feasible and warranted.