Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).

PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).

PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

Physical health checks in primary care for people with severe mental illness ((SMI) defined as schizophrenia, bipolar disorders and non-organic psychosis) aim to reduce health inequalities. Patients who decline or are deemed unsuitable for screening are removed from the denominator used to calculate incentivisation, termed exception reporting.

To describe the prevalence of, and patient characteristics associated with, exception reporting in patients with SMI.

We identified adult patients with SMI from the UK Clinical Practice Research Datalink (CPRD), registered with a general practice between 2004 and 2018. We calculated the annual prevalence of exception reporting and investigated patient characteristics associated with exception reporting, using logistic regression.

Of 193 850 patients with SMI, 27.7% were exception reported from physical health checks at least once. Exception reporting owing to non-response or declining screening increased over the study period. Patients of Asian or Black ethnicity (Asian: odds ratio 0.72, 95% CI 0.65–0.80; Black: odds ratio 0.86, 95% CI 0.76–0.97; compared with White) and women (odds ratio 0.90, 95% CI 0.88–0.92) had a reduced odds of being exception reported, whereas patients diagnosed with ‘other psychoses’ (odds ratio 1.19, 95% CI 1.15–1.23; compared with bipolar disorder) had increased odds. Younger patients and those diagnosed with schizophrenia were more likely to be exception reported owing to informed dissent.

Exception reporting was common in people with SMI. Interventions are required to improve accessibility and uptake of physical health checks to improve physical health in people with SMI.

Evaluate Department of Defense (DoD) antimicrobial stewardship programs (ASPs) by assessing the relationship between key clinical outcome metrics (antibiotic use, incidence of resistant pathogens, and incidence of Clostridioides difficile infections) and CDC Core Element (CE) adherence.

Retrospective, cross-sectional study of DoD hospitals in 2018 and 2021

National Healthcare Safety Network Standardized Antimicrobial Administration Ratios (SAARs) were used to measure antibiotic use and microbiology results to evaluate four types of pathogen incidence. A novel CE scoring approach used scores to quantitatively assess relationships with CE adherence and outcome metrics using correlation and regression models. Assessments were repeated with 2021 data for Priority CE adherence and to conduct adjusted regressions for CEs and Priority CEs controlling for categorical bed size.

Compared to 2022 national data, DoD hospitals in 2021 had a similar proportion of facilities with a SAAR statistically significantly > 1.0. Leadership, Action, and Tracking CEs followed a more normal score distribution, while Reporting and Education were somewhat left-skewed. Unadjusted models often showed a positive relationship with higher CE scores associated with worse outcomes for the SAAR and pathogen incidence. Adjusted models indicated that procedural CEs, particularly Priority Reporting, were associated with better ASP-related outcomes.

CEs should be more quantitatively assessed. Results provide initial evidence to prioritize procedural CE implementation within the DoD; however, additional investigation for structural CEs is needed. Patient outcome data should be collected as an important indicator of ASP performance.

The presence of an intraluminal thrombus in acutely symptomatic carotid stenosis is thought to represent a high-risk lesion for short-term stroke reccurrence though evidence on natural history and treatment is lacking, leading to equipoise and much variation in practice. The objective of this study was to map these variations in practice (medical management and timing of revascularization), determine the considerations that influence clinician decision-making in this condition and gather opinions that inform the development and design of future trials in the area.

This was a mixed-methods study using both quantitative survey methods and qualitative interview-based methods. International perspectives were gathered by distributing a case-based survey via the “Practice Current” section of Neurology: Clinical Practice and interviewing international experts using established qualitative research methods.

The presence of an intraluminal thrombus significantly increased the likelihood of using a regimen containing anticoagulation agents (p < 0.001) in acutely symptomatic carotid stenosis in the case-based survey. Themes that emerged from qualitative interview analysis were therapeutic uncertainty regarding anticoagulation, decision to reimage, revascularization choices and future trial design and anticipated challenges.

Results of this study demonstrate a preference for anticoagulation and delayed revascularization after reimaging to examine for clot resolution, though much equipoise remains. While there is interest from international experts in future trials, further study is needed to understand the natural history of this condition in order to inform trial design.

In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.

A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.

We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.

The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.

Motor neuron disease (MND) is a progressive, fatal, neurodegenerative condition that affects motor neurons in the brain and spinal cord, resulting in loss of the ability to move, speak, swallow and breathe. Acceptance and commitment therapy (ACT) is an acceptance-based behavioural therapy that may be particularly beneficial for people living with MND (plwMND). This qualitative study aimed to explore plwMND’s experiences of receiving adapted ACT, tailored to their specific needs, and therapists’ experiences of delivering it.

Semi-structured qualitative interviews were conducted with plwMND who had received up to eight 1:1 sessions of adapted ACT and therapists who had delivered it within an uncontrolled feasibility study. Interviews explored experiences of ACT and how it could be optimised for plwMND. Interviews were audio recorded, transcribed and analysed using framework analysis.

Participants were 14 plwMND and 11 therapists. Data were coded into four over-arching themes: (i) an appropriate tool to navigate the disease course; (ii) the value of therapy outweighing the challenges; (iii) relevance to the individual; and (iv) involving others. These themes highlighted that ACT was perceived to be acceptable by plwMND and therapists, and many participants reported or anticipated beneficial outcomes in the future, despite some therapeutic challenges. They also highlighted how individual factors can influence experiences of ACT, and the potential benefit of involving others in therapy.

Qualitative data supported the acceptability of ACT for plwMND. Future research and clinical practice should address expectations and personal relevance of ACT to optimise its delivery to plwMND.

1. (1) To understand the views of people living with motor neuron disease (plwMND) and therapists on acceptance and commitment therapy (ACT) for people living with this condition.

2. (2) To understand the facilitators of and barriers to ACT for plwMND.

3. (3) To learn whether ACT that has been tailored to meet the specific needs of plwMND needs to be further adapted to potentially increase its acceptability to this population.

Most evidence on suicidal thoughts, plans and attempts comes from Western countries; prevalence rates may differ in other parts of the world.

This study determined the prevalence of suicidal thoughts, plans and attempts in high school students in three different regional settings in Kenya.

This was a cross-sectional study of 2652 high school students. We asked structured questions to determine the prevalence of various types of suicidality, the methods planned or effected, and participants’ gender, age and form (grade level). We provided descriptive statistics, testing significant differences by chi-squared and Fisher's exact tests, and used logistic regression to identify relationships among different variables and their associations with suicidality.

The prevalence rates of suicidal thoughts, plans and attempts were 26.8, 14.9 and 15.7%, respectively. These rates are higher than those reported for Western countries. Some 6.7% of suicide attempts were not associated with plans. The most common method used in suicide attempts was drinking chemicals/poison (18.8%). Rates of suicidal thoughts and plans were higher for older students and students in urban rather than rural locations, and attempts were associated with female gender and higher grade level – especially the final year of high school, when exam performance affects future education and career prospects.

Suicidal thoughts, plans and attempts are prevalent in Kenyan high school students. There is a need for future studies to determine the different starting points to suicidal attempts, particularly for the significant number whose attempts are not preceded by thoughts and plans.

Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.

Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.

Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).

Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.

Evidence-based central-line–associated bloodstream infection (CLABSI) prevention guidelines recommend the use of an antiseptic scrub to disinfect needleless connectors before device access. Guideline noncompliance may render disinfection ineffective. The goal of this study was to observe needleless-connector disinfection practices and to identify perceived facilitators and barriers to best practices of needleless-connector access.

A human factors mixed-methods study involving nursing focus groups of perceived barriers and facilitators and clinical observations of compliance with instructions and protocols for use of 3.15% chlorhexidine gluconate/70% isopropyl alcohol (CHG/IPA) and 70% isopropyl alcohol (IPA) antisepsis products for central venous access device (CVAD) needleless-connector disinfection was conducted in intensive care units (ICUs) at 2 academic medical centers.

Access to the antiseptic product and lesser workload were identified as best-practice facilitators. Barriers were the time required per needleless-connector access and knowledge deficits. Of the 48 observed access events, 77% resulted in needleless-connector disinfection. The observed mean needleless-connector scrubbing times when using IPA were substantially below the recommended time. Drying time after product use was negligible.

Lack of access to the disinfection product, emergency situations, and high workload were barriers to needleless-connector disinfection. Observed scrubbing and drying times were shorter than recommended, especially for IPA wipes. These needleless-connector disinfection deficits may increase the risk of CLABSI. Ongoing education and periodic competency evaluation of needleless-connector disinfection, improvement of supply management, and staffing workload are required to imbed and sustain best practices. Further study involving a larger sample size in diverse patient populations is warranted.

The Stricker Learning Span (SLS) is a computer-adaptive word list memory test specifically designed for remote assessment and self-administration on a web-based multi-device platform (Mayo Test Drive). Given recent evidence suggesting the prominence of learning impairment in preclinical Alzheimer’s disease (AD), the SLS places greater emphasis on learning than delayed memory compared to traditional word list memory tests (see Stricker et al., Neuropsychology in press for review and test details). The primary study aim was to establish criterion validity of the SLS by comparing the ability of the remotely-administered SLS and inperson administered Rey Auditory Verbal Learning Test (AVLT) to differentiate biomarkerdefined groups in cognitively unimpaired (CU) individuals on the Alzheimer’s continuum.

Mayo Clinic Study of Aging CU participants (N=319; mean age=71, SD=11; mean education=16, SD=2; 47% female) completed a brief remote cognitive assessment (∼0.5 months from in-person visit). Brain amyloid and brain tau PET scans were available within 3 years. Overlapping groups were formed for 1) those on the Alzheimer’s disease (AD) continuum (A+, n=110) or not (A-, n=209), and for 2) those with biological AD (A+T+, n=43) vs no evidence of AD pathology (A-T-, n=181). Primary neuropsychological outcome variables were sum of trials for both the SLS and AVLT. Secondary outcome variables examined comparability of learning (1-5 total) and delay performances. Linear model ANOVAs were used to investigate biomarker subgroup differences and Hedge’s G effect sizes were derived, with and without adjusting for demographic variables (age, education, sex).

Both SLS and AVLT performances were worse in the biomarker positive relative to biomarker negative groups (unadjusted p’s<.05). Because biomarker positive groups were significantly older than biomarker negative groups, group differences were attenuated after adjusting for demographic variables, but SLS remained significant for A+ vs A- and for A+T+ vs A-T- comparisons (adjusted p’s<.05) and AVLT approached significance (p’s .05-.10). The effect sizes for the SLS were slightly better (qualitatively, no statistical comparison) for separating biomarker-defined CU groups in comparison to AVLT. For A+ vs A- and A+T+ vs A-T- comparisons, unadjusted effect sizes for SLS were -0.53 and -0.81 and for AVLT were -0.47 and -0.61, respectively; adjusted effect sizes for SLS were -0.25 and -0.42 and for AVLT were -0.19 and -0.26, respectively. In secondary analyses, learning and delay variables were similar in terms of ability to separate biomarker groups. For example, unadjusted effect sizes for SLS learning (-.80) was similar to SLS delay (.76), and AVLT learning (-.58) was similar to AVLT 30-minute delay (-.55) for the A+T+ vs AT- comparison.

Remotely administered SLS performed similarly to the in-person-administered AVLT in its ability to separate biomarker-defined groups in CU individuals, providing evidence of criterion validity. The SLS showed significantly worse performance in A+ and A+T+ groups (relative to A- and A-T-groups) in this CU sample after demographic adjustment, suggesting potential sensitivity to detecting transitional cognitive decline in preclinical AD. Measures emphasizing learning should be given equal consideration as measures of delayed memory in AD-focused studies, particularly in the preclinical phase.

Mayo Test Drive (MTD): Test Development through Rapid Iteration, Validation and Expansion, is a web-based multi-device (smartphone, tablet, personal computer) platform optimized for remote self-administered cognitive assessment that includes a computer-adaptive word list memory test (Stricker Learning Span; SLS; Stricker et al., 2022; Stricker et al., in press) and a measure of processing speed (Symbols Test: Wilks et al., 2021). Study aims were to determine criterion validity of MTD by comparing the ability of the MTD raw composite and in-person administered cognitive measures to differentiate biomarkerdefined groups in cognitively unimpaired (CU) individuals on the Alzheimer’s continuum.

Mayo Clinic Study of Aging CU participants (N=319; mean age=71, SD=11, range=37-94; mean education=16, SD=2, range=6-20; 47% female) completed a brief remote cognitive assessment (∼0.5 months from in-person visit). Brain amyloid and brain tau PET scans were available within 3 years. Overlapping groups were formed for 1) those on the Alzheimer’s disease (AD) continuum (A+, n=110) or not (A-, n=209), and for 2) those with biological AD (A+T+, n=43) or with no evidence of AD pathology (A-T-, n=181). Primary outcome variables were MTD raw composite (SLS sum of trials + an accuracy-weighted Symbols response time measure), Global-z (average of 9 in-person neuropsychological measures) and an in-person screening measure (Kokmen Short Test of Mental Status, STMS; which is like the MMSE). Linear model ANOVAs were used to investigate biomarker subgroup differences and Hedge’s G effect sizes were derived, with and without adjusting for demographic variables (age, education, sex).

Remotely administered MTD raw composite showed comparable to slightly larger effect sizes compared to Global-z. Unadjusted effect sizes for MTD raw composite for differentiating A+ vs. A- and A+T+ vs. A-T- groups, respectively, were -0.57 and -0.84 and effect sizes for Global-z were -0.54 and -0.73 (all p’s<.05). Because biomarker positive groups were significantly older than biomarker negative groups, group differences were attenuated after adjusting for demographic variables, but MTD raw composite remained significant for A+T+ vs A-T- (adjusted effect size -0.35, p=.007); Global-z did not reach significance for A+T+ vs A-T- (adjusted effect size -0.19, p=.08). Neither composite reached significance for adjusted analyses for the A+ vs A- comparison (MTD raw composite adjusted effect size= -.22, p=.06; Global-z adjusted effect size= -.08, p=.47). Results were the same for an alternative MTD composite using traditional z-score averaging methods, but the raw score method is preferred for comparability to other screening measures. The STMS screening measure did not differentiate biomarker groups in any analyses (unadjusted and adjusted p’s>.05; d’s -0.23 to 0.05).

Remotely administered MTD raw composite shows at least similar ability to separate biomarker-defined groups in CU individuals as a Global-z for person-administered measures within a neuropsychological battery, providing evidence of criterion validity. Both the MTD raw composite and Global-z showed greater ability to separate biomarker positive from negative CU groups compared to a typical screening measure (STMS) that was unable to differentiate these groups. MTD may be useful as a screening measure to aid early detection of Alzheimer’s pathological changes.

The Stricker Learning Span (SLS) is a computer-adaptive digital word list memory test specifically designed for remote assessment and self-administration on a web-based multi-device platform (Mayo Test Drive). We aimed to establish criterion validity of the SLS by comparing its ability to differentiate biomarker-defined groups to the person-administered Rey’s Auditory Verbal Learning Test (AVLT).

Participants (N = 353; mean age = 71, SD = 11; 93% cognitively unimpaired [CU]) completed the AVLT during an in-person visit, the SLS remotely (within 3 months) and had brain amyloid and tau PET scans available (within 3 years). Overlapping groups were formed for 1) those on the Alzheimer’s disease (AD) continuum (amyloid PET positive, A+, n = 125) or not (A-, n = 228), and those with biological AD (amyloid and tau PET positive, A+T+, n = 55) vs no evidence of AD pathology (A−T−, n = 195). Analyses were repeated among CU participants only.

The SLS and AVLT showed similar ability to differentiate biomarker-defined groups when comparing AUROCs (p’s > .05). In logistic regression models, SLS contributed significantly to predicting biomarker group beyond age, education, and sex, including when limited to CU participants. Medium (A− vs A+) to large (A−T− vs A+T+) unadjusted effect sizes were observed for both SLS and AVLT. Learning and delay variables were similar in terms of ability to separate biomarker groups.

Remotely administered SLS performed similarly to in-person-administered AVLT in its ability to separate biomarker-defined groups, providing evidence of criterion validity. Results suggest the SLS may be sensitive to detecting subtle objective cognitive decline in preclinical AD.

Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.

In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.

Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.

Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.