Asymptomatic bacteriuria (ASB) treatment is a common form of antibiotic overuse and diagnostic error. Antibiotic stewardship using the inappropriate diagnosis of urinary tract infection (ID-UTI) measure has reduced ASB treatment in diverse hospitals. However, critical access hospitals (CAHs) have differing resources that could impede stewardship. We aimed to determine if stewardship including the ID-UTI measure could reduce ASB treatment in CAHs.

From October 2022 to July 2023, ten CAHs participated in an Intensive Quality Improvement Cohort (IQIC) program including 3 interventions to reduce ASB treatment: 1) learning labs (ie, didactics with shared learning), 2) mentoring, and 3) data-driven performance reports including hospital peer comparison based on the ID-UTI measure. To assess effectiveness of the IQIC program, change in the ID-UTI measure (ie, percentage of patients treated for a UTI who had ASB) was compared to two non-equivalent control outcomes (antibiotic duration and unjustified fluoroquinolone use).

Ten CAHs abstracted a total of 608 positive urine culture cases. Over the cohort period, the percentage of patients treated for a UTI who had ASB declined (aOR per month = 0.935, 95% CI: 0.873, 1.001, P = 0.055) from 28.4% (range across hospitals, 0%-63%) in the first to 18.6% (range, 0%-33%) in the final month. In contrast, antibiotic duration and unjustified fluoroquinolone use were unchanged (P = 0.768 and 0.567, respectively).

The IQIC intervention, including learning labs, mentoring, and performance reports using the ID-UTI measure, was associated with a non-significant decrease in treatment of ASB, while control outcomes (duration and unjustified fluoroquinolone use) did not change.

Obstructive sleep apnea (OSA) is associated with worse outcomes in stroke, Alzheimer’s disease (AD) and Parkinson’s disease (PD), but diagnosis is challenging in these groups. We aimed to compare the prevalence of high risk of OSA based on commonly used questionnaires and self-reported OSA diagnosis: 1. within groups with stroke, AD, PD and the general population (GP); 2. Between neurological groups and GP.

Individuals with stroke, PD and AD were identified in the Canadian Longitudinal Study of Aging (CLSA) by survey. STOP, STOP-BAG, STOP-B28 and GOAL screening tools and OSA self-report were compared by the Chi-squared test. Logistic regression was used to compare high risk/self-report of OSA, in neurological conditions vs. GP, adjusted for confounders.

We studied 30,097 participants with mean age of 62.3 years (SD 10.3) (stroke n = 1791; PD n = 175; AD n = 125). In all groups, a positive GOAL was the most prevalent, while positive STOP was least prevalent among questionnaires. Significant variations in high-risk OSA were observed between different questionnaires across all groups. Under 1.5% of individuals self-reported OSA. While all questionnaires suggested a higher prevalence of OSA in stroke than the GP, for PD and AD, there was heterogeneity depending on questionnaire.

The wide range of prevalences of high risk of OSA resulting from commonly used screening tools underscores the importance of validating them in older adults with neurological disorders. OSA was self-reported in disproportionately small numbers across groups, suggesting that OSA is underdiagnosed in older adults or underreported by patients, which is concerning given its increasingly recognized impact on brain health.

As part of the Research Domain Criteria (RDoC) initiative, the NIMH seeks to improve experimental measures of cognitive and positive valence systems for use in intervention research. However, many RDoC tasks have not been psychometrically evaluated as a battery of measures. Our aim was to examine the factor structure of 7 such tasks chosen for their relevance to schizophrenia and other forms of serious mental illness. These include the n-back, Sternberg, and self-ordered pointing tasks (measures of the RDoC cognitive systems working memory construct); flanker and continuous performance tasks (measures of the RDoC cognitive systems cognitive control construct); and probabilistic learning and effort expenditure for reward tasks (measures of reward learning and reward valuation constructs).

The sample comprised 286 cognitively healthy participants who completed novel versions of all 7 tasks via an online recruitment platform, Prolific, in the summer of 2022. The mean age of participants was 38.6 years (SD = 14.5, range 18-74), 52% identified as female, and stratified recruitment ensured an ethnoracially diverse sample. Excluding time for instructions and practice, each task lasted approximately 6 minutes. Task order was randomized. We estimated optimal scores from each task including signal detection d-prime measures for the n-back, Sternberg, and continuous performance task, mean accuracy for the flanker task, win-stay to win-shift ratio for the probabilistic learning task, and trials completed for the effort expenditure for reward task. We used parallel analysis and a scree plot to determine the number of latent factors measured by the 7 task scores. Exploratory factor analysis with oblimin (oblique) rotation was used to examine the factor loading matrix.

The scree plot and parallel analyses of the 7 task scores suggested three primary factors. The flanker and continuous performance task both strongly loaded onto the first factor, suggesting that these measures are strong indicators of cognitive control. The n-back, Sternberg, and self-ordered pointing tasks strongly loaded onto the second factor, suggesting that these measures are strong indicators of working memory. The probabilistic learning task solely loaded onto the third factor, suggesting that it is an independent indicator of reinforcement learning. Finally, the effort expenditure for reward task modestly loaded onto the second but not the first and third factors, suggesting that effort is most strongly related to working memory.

Our aim was to examine the factor structure of 7 RDoC tasks. Results support the RDoC suggestion of independent cognitive control, working memory, and reinforcement learning. However, effort is a factorially complex construct that is not uniquely or even most strongly related to positive valance. Thus, there is reason to believe that the use of at least 6 of these tasks are appropriate measures of constructs such as working memory, reinforcement learning and cognitive control.

Eliciting perceived cognitive complaints is a routine part of a clinical neuropsychological evaluation, presumably because complaints are informative of underlying pathology. However, there is no strong empirical support that subjective cognitive impairment (SCI) is actually related to objective cognitive impairment as measured by neurocognitive tests. Instead, internalizing psychopathology is thought to predominately influence the endorsement of SCI. Specifically, individuals with greater symptoms of depression and anxiety, when accounting for comorbidities, have a higher disposition to overestimate their degree of cognitive impairment as compared to objective testing. Yet, there are few existing studies that have determined which factors influence both SCI and the discrepancy between subjective and objective cognitive impairment in general outpatient populations. The current study examined the relationship between subjective and objective cognitive impairment in a clinically diverse sample of outpatients. We additionally explored the associations between SCI and relevant intrapersonal factors including internalizing psychopathology, number of medical comorbidities, and demographics. Finally, we quantified the degree of discrepancy between subjective and objective impairment and examined this discrepancy in relation to the intrapersonal factors.

The sample comprised 142 adult women and men (age range 18–79 years) seen in an outpatient neuropsychology clinic for a diverse range of referral questions. Scores on the cognition portion of the WHO Disability Assessment Schedule (WHODAS 2.0) were used to index SCI. A composite score from 14 measures across various domains of cognitive functioning served as an objective measure of cognitive functioning. Internalizing psychopathology was measured via a standardized composite of scores from screening measures of anxiety and depression. Medical comorbidities were indexed by the number of different ICD diagnostic categories documented in patients' medical records. Demographics included age, sex, race, and years of formal education. Objective-subjective discrepancy scores were computed by saving standardized residuals from a linear regression of neurocognitive test performance on the WHODAS 2.0 scores.

A hierarchical linear regression revealed that objective cognitive impairment was not significantly related to SCI (p > .05), explaining less than 2% of the variance in SCI ratings. Likewise, participants' demographics (age, sex, education, race) and number of comorbidities were not significantly related to their SCI ratings, explaining about 6% of the variance. However, participants' level of internalizing psychopathology was significantly associated with SCI (F[10, 131] = 4.99, p < .001), and explained approximately 20% of the variance in SCI ratings. Similarly, the degree of discrepancy between subjective and objective cognitive impairment was primarily influenced by internalizing psychopathology (F[9, 132] = 5.20, p < .001, R2 = 21%) and largely unrelated to demographics and number of comorbidities, which explained about 6% of the variance.

These findings are consistent with prior research suggesting that SCI may be more indicative of the extent of internalizing psychopathology rather than actual cognitive impairment. Taken together, these results illuminate potential treatment and diagnostic implications associated with assessing perceived cognitive complaints during a neuropsychological evaluation.

Agricultural workers are immersed in environments associated with increased risk for adverse psychiatric and neurological outcomes. Agricultural work-related risks to brain health include exposure to pesticides, heavy metals, and organic dust. Despite this, there is a gap in our understanding of the underlying brain systems impacted by these risks. This study explores clinical and cognitive domains, and functional brain activity in agricultural workers. We hypothesized that a history of agricultural work-related risks would be associated with poorer clinical and cognitive outcomes as well as changes in functional brain activity within cortico-striatal regions.

The sample comprised 17 agricultural workers and a comparison group of 45 non-agricultural workers recruited in the Northern Colorado area. All participants identified as White and non-Hispanic. The mean age of participants was 51.7 years (SD = 21.4, range 18-77), 60% identified as female, and 37% identified as male. Participants completed the National Institute of Health Toolbox (NIH Toolbox) and Montreal Cognitive Assessment (MoCA) on their first visit. During the second visit, they completed NIH Patient-Reported Outcomes Measurement Information System (PROMIS) measures and underwent functional magnetic resonance imaging (fMRI; N = 15 agriculture and N = 35 non-agriculture) while completing a working memory task (Sternberg). Blood oxygen-level dependent (BOLD) response was compared between participants. Given the small sample size, the whole brain voxel-wise group comparison threshold was set at alpha = .05, but not otherwise corrected for multiple comparisons. Cohen’s d effect sizes were estimated for all voxels.

Analyses of cognitive scores showed significant deficits in episodic memory for the agricultural work group. Additionally, the agricultural work group scored higher on measures of self-reported anger, cognitive concerns, and social participation. Analyses of fMRI data showed increased BOLD activity around the orbitofrontal cortex (medium to large effects) and bilaterally in the entorhinal cortex (large effects) for the agricultural work group. The agricultural work group also showed decreased BOLD activity in the cerebellum and basal ganglia (medium to large effects).

To our knowledge, this study provides the first-ever evidence showing differences in brain activity associated with a history of working in agriculture. These findings of poorer memory, concerns about cognitive functioning, and increased anger suggest clinical relevance. Social participation associated with agricultural work should be explored as a potential protective factor for cognition and brain health. Brain imaging data analyses showed increased activation in areas associated with motor functioning, cognitive control, and emotion. These findings are limited by small sample size, lack of diversity in our sample, and coarsely defined risk. Despite these limitations, the results are consistent with an overall concern that risks associated with agricultural work can lead to cognitive and psychiatric harm via changes in brain health. Replications and future studies with larger sample sizes, more diverse participants, and more accurately defined risks (e.g., pesticide exposure) are needed.

Deficits in cognitive ability are common among patients with schizophrenia. The MATRICS Consensus Cognitive Battery (MCCB) was designed to assess cognitive ability in studies of patients diagnosed with schizophrenia and has demonstrated high test-retest reliability with minimal practice effects, even in multi-site trials. However, given the motivational challenges associated with schizophrenia, it is unknown whether performance on MCCB tasks affects performance at later stages of testing. The goal of this study was to determine whether there are differences between people with and without schizophrenia in how their performance on individual MCCB tasks influences their performance throughout the battery.

The sample comprised 92 total participants including 49 cognitively healthy comparison participants and 43 outpatients diagnosed with schizophrenia. The mean age of participants was 44.2 years (SD = 12.0, range 21–69) and 61% identified as male. The Trail Making Test, Brief Assessment of Cognition in Schizophrenia, Hopkins Verbal Learning Test – Revised, Letter-Number Span, and Category Fluency from the MCCB were administered in the same order at 2 different sites and studies from 2016–2022. The autocorrelation between t-scores for task scores within each participant was computed and then compared between control and outpatient participants to determine if there are differences between groups. Group mean t-scores for each task were also compared between groups.

We found no significant difference in autocorrelations across MCCB tasks between healthy comparison participants and outpatients. However, mean performance in all tasks was lower for the outpatient group than for the healthy comparison group. None of the tasks used stood out as having significantly lower mean scores than other tasks for either group.

Our findings suggest that performance on individual MCCB tasks do not affect performance throughout the battery differently between the healthy comparison group and outpatients. This suggests that participants with schizophrenia are not particularly reactive to past performance on MCCB tasks. Additionally, this finding further supports use of the MCCB in this population. Further research is needed to determine whether subgroups of patients and/or different batteries of measures show different patterns of reactivity.

Identifying youths most at risk to COVID-19-related mental illness is essential for the development of effective targeted interventions.

To compare trajectories of mental health throughout the pandemic in youth with and without prior mental illness and identify those most at risk of COVID-19-related mental illness.

Data were collected from individuals aged 18–26 years (N = 669) from two existing cohorts: IMAGEN, a population-based cohort; and ESTRA/STRATIFY, clinical cohorts of individuals with pre-existing diagnoses of mental disorders. Repeated COVID-19 surveys and standardised mental health assessments were used to compare trajectories of mental health symptoms from before the pandemic through to the second lockdown.

Mental health trajectories differed significantly between cohorts. In the population cohort, depression and eating disorder symptoms increased by 33.9% (95% CI 31.78–36.57) and 15.6% (95% CI 15.39–15.68) during the pandemic, respectively. By contrast, these remained high over time in the clinical cohort. Conversely, trajectories of alcohol misuse were similar in both cohorts, decreasing continuously (a 15.2% decrease) during the pandemic. Pre-pandemic symptom severity predicted the observed mental health trajectories in the population cohort. Surprisingly, being relatively healthy predicted increases in depression and eating disorder symptoms and in body mass index. By contrast, those initially at higher risk for depression or eating disorders reported a lasting decrease.

Healthier young people may be at greater risk of developing depressive or eating disorder symptoms during the COVID-19 pandemic. Targeted mental health interventions considering prior diagnostic risk may be warranted to help young people cope with the challenges of psychosocial stress and reduce the associated healthcare burden.

Rapid antigen detection tests (Ag-RDT) for SARS-CoV-2 with emergency use authorization generally include a condition of authorization to evaluate the test’s performance in asymptomatic individuals when used serially. We aim to describe a novel study design that was used to generate regulatory-quality data to evaluate the serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals.

This prospective cohort study used a siteless, digital approach to assess longitudinal performance of Ag-RDT. Individuals over 2 years old from across the USA with no reported COVID-19 symptoms in the 14 days prior to study enrollment were eligible to enroll in this study. Participants throughout the mainland USA were enrolled through a digital platform between October 18, 2021 and February 15, 2022. Participants were asked to test using Ag-RDT and molecular comparators every 48 hours for 15 days. Enrollment demographics, geographic distribution, and SARS-CoV-2 infection rates are reported.

A total of 7361 participants enrolled in the study, and 492 participants tested positive for SARS-CoV-2, including 154 who were asymptomatic and tested negative to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 US states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide.

The digital site-less approach employed in the “Test Us At Home” study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19 and can be adapted across research disciplines to optimize study enrollment and accessibility.

Functional recovery is a treatment goal that goes beyond symptomatic remission and encompasses multiple aspects of schizophrenia patients’ lives, including quality of life, physical, and mental functioning. There is evidence that long-acting injectable (LAI) treatments promote adherence and reduce rehospitalisation and functional decline, which could facilitate patients’ ability to reach functional recovery. Despite this, LAIs are underused in the first-episode (FEP) and early-phase (EP) patient population, due to physician hesitancy and concerns around stigma. A Delphi panel was held to gain expert consensus on an approach to the domains and assessment of functional recovery elements in FEP and EP schizophrenia patients.

A literature review and input from a steering committee of 5 experts in psychiatry informed statements development for a three-round modified Delphi process. Round one was conducted via one-to-one video conference interviews, and the successive rounds were conducted via electronic surveys, which enabled international collaboration. Statements on the different domains and assessment for functional recovery were presented to 17 psychiatrists, practicing in 7 countries (France, Italy, US, Germany, Spain, Denmark, and UK), experienced in the treatment of schizophrenia with LAIs. Several analysis rules determined whether a statement could progress to the next round and specified the level of agreement required to achieve consensus. Measures of central tendency (mode, mean) and variability (interquartile range) were reported back to help panelists look at their previous responses in the context of the overall group.

A consensus was reached (defined a priori as ≥80% agreement) on all 27 statements covering the dimensions, assessment, and level of achieved functional recovery for FEP and EP patients. The following domains are important to consider when assessing functional recovery: depression, aggressive behaviour, social interaction, family functioning, education/employment, sexual functioning, and leisure activities. Additionally, panellists reached consensus that dimensions should be minimally impairing, if present (excluding sexual functioning) and asked about at every encounter with the patient (excluding sexual functioning and leisure activities). In summary, this Delphi panel yielded agreement that functional recovery is multidimensional and should be assessed regularly as part of usual care on an individual patient level in FEP and EP schizophrenia patients.

Lundbeck Otsuka Alliance

Schizophrenia is among the top ten causes of years lost due to disability. Goals of treatment are evolving beyond remission of psychotic symptoms to include physical and mental functioning, quality of life, and long-term functional recovery. Evidence has shown long-acting injectables (LAIs) are beneficial for schizophrenia patients by increasing treatment adherence and decreasing relapse and rehospitalisation. This potentially reduces disease progression and facilitates functional recovery. However, LAIs are underused and often seen as a last resort for first-episode (FEP) and early-phase (EP) patients, due to physicians’ lack of familiarity and stigma.

A three-round modified Delphi panel was held to gain expert consensus on an approach to functional recovery in FEP and EP patients with LAIs. A literature review and input from a steering committee of 5 experts in psychiatry informed the development of statements. Round one was carried out via one-to-one video conference interviews, and the subsequent rounds were conducted via electronic surveys, which enabled international collaboration. Delphi panellists were 17 psychiatrists with schizophrenia treatment experience, practicing in 7 countries (France, Italy, US, Germany, Spain, Denmark, and UK). Several analysis rules determined whether a statement could progress to the next round and specified the level of agreement required to achieve consensus. Measures of central tendencies (mode, mean) and variability (interquartile range) of aggregated responses from the previous round were reported to panelists to understand their response in relation to the group.

There was consensus (defined a priori as ≥80% agreement) on the 8 statements relating to long-term treatment goals and LAI links to functional recovery. LAI treatment in FEP and EP patients increases adherence and reduces treatment burden and functional decline compared to the same and other oral medication. Additionally, there was consensus that LAIs lead to better treatment outcome and functional recovery. Other important factors to achieving functional recovery include patient attitude towards treatment and psychoeducation. Furthermore, consensus was reached that functional recovery and quality of life are linked. In summary, this Delphi panel yielded agreement that functional recovery is a reachable goal for FEP and EP patients and can be enhanced using LAIs.

Lundbeck Otsuka Alliance

Reported childhood adversity (CA) is associated with development of depression in adulthood and predicts a more severe course of illness. Although elevated serotonin 1A receptor (5-HT1AR) binding potential, especially in the raphe nuclei, has been shown to be a trait associated with major depression, we did not replicate this finding in an independent sample using the partial agonist positron emission tomography tracer [11C]CUMI-101. Evidence suggests that CA can induce long-lasting changes in expression of 5-HT1AR, and thus, a history of CA may explain the disparate findings.

Following up on our initial report, 28 unmedicated participants in a current depressive episode (bipolar n = 16, unipolar n = 12) and 19 non-depressed healthy volunteers (HVs) underwent [11C]CUMI-101 imaging to quantify 5-HT1AR binding potential. Participants in a depressive episode were stratified into mild/moderate and severe CA groups via the Childhood Trauma Questionnaire. We hypothesized higher hippocampal and raphe nuclei 5-HT1AR with severe CA compared with mild/moderate CA and HVs.

There was a group-by-region effect (p = 0.011) when considering HV, depressive episode mild/moderate CA, and depressive episode severe CA groups, driven by significantly higher hippocampal 5-HT1AR binding potential in participants in a depressive episode with severe CA relative to HVs (p = 0.019). Contrary to our hypothesis, no significant binding potential differences were detected in the raphe nuclei (p-values > 0.05).

With replication in larger samples, elevated hippocampal 5-HT1AR binding potential may serve as a promising biomarker through which to investigate the neurobiological link between CA and depression.