Identifying persons with HIV (PWH) at increased risk for Alzheimer’s disease (AD) is complicated because memory deficits are common in HIV-associated neurocognitive disorders (HAND) and a defining feature of amnestic mild cognitive impairment (aMCI; a precursor to AD). Recognition memory deficits may be useful in differentiating these etiologies. Therefore, neuroimaging correlates of different memory deficits (i.e., recall, recognition) and their longitudinal trajectories in PWH were examined.

We examined 92 PWH from the CHARTER Program, ages 45–68, without severe comorbid conditions, who received baseline structural MRI and baseline and longitudinal neuropsychological testing. Linear and logistic regression examined neuroanatomical correlates (i.e., cortical thickness and volumes of regions associated with HAND and/or AD) of memory performance at baseline and multilevel modeling examined neuroanatomical correlates of memory decline (average follow-up = 6.5 years).

At baseline, thinner pars opercularis cortex was associated with impaired recognition (p = 0.012; p = 0.060 after correcting for multiple comparisons). Worse delayed recall was associated with thinner pars opercularis (p = 0.001) and thinner rostral middle frontal cortex (p = 0.006) cross sectionally even after correcting for multiple comparisons. Delayed recall and recognition were not associated with medial temporal lobe (MTL), basal ganglia, or other prefrontal structures. Recognition impairment was variable over time, and there was little decline in delayed recall. Baseline MTL and prefrontal structures were not associated with delayed recall.

Episodic memory was associated with prefrontal structures, and MTL and prefrontal structures did not predict memory decline. There was relative stability in memory over time. Findings suggest that episodic memory is more related to frontal structures, rather than encroaching AD pathology, in middle-aged PWH. Additional research should clarify if recognition is useful clinically to differentiate aMCI and HAND.

Among people with HIV (PWH), the apolipoprotein e4 (APOE-e4) allele, a genetic marker associated with Alzheimer’s disease (AD), and self-reported family history of dementia (FHD), considered a proxy for higher AD genetic risk, are independently associated with worse neurocognition. However, research has not addressed the potential additive effect of FHD and APOE-e4 on global and domain-specific neurocognition among PWH. Thus, the aim of the current investigation is to examine the associations between FHD, APOE-e4, and neurocognition among PWH.

283 PWH (Mage=50.9; SDage=5.6) from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study completed comprehensive neuropsychological and neuromedical evaluations and underwent APOE genotyping. APOE status was dichotomized into APOE-e4+ and APOE-e4-. APOE-e4+ status included heterozygous and homozygous carriers. Participants completed a free-response question capturing FHD of a first- or second-degree relative (i.e., biologic parent, sibling, children, grandparent, grandchild, uncle, aunt, nephew, niece, half-sibling). A dichotomized (yes/no), FHD variable was used in analyses. Neurocognition was measured using global and domain-specific demographically corrected (i.e., age, education, sex, race/ethnicity) T-scores. t-tests were used to compare global and domain-specific demographically-corrected T-scores by FHD status and APOE-e4 status. A 2x2 factorial analysis of variance (ANOVA) was used to model the interactive effects of FHD and APOE-e4 status. Tukey’s HSD test was used to follow-up on significant ANOVAs.

Results revealed significant differences by FHD status in executive functioning (t(281)=-2.3, p=0.03) and motor skills (t(278)=-2.0, p=0.03) such that FHD+ performed worse compared to FHD-. Differences in global neurocognition by FHD status approached significance (t(281)=-1.8, p=.069). Global and domain-specific neurocognitive performance were comparable among APOE-e4 carriers and noncarriers (ps>0.05). Results evaluating the interactive effects of FHD and APOE-e4 showed significant differences in motor skills (F(3)=2.7, p=0.04) between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups such that the FHD+/APOE-e4- performed worse than the FHD-/APOE-e4+ group (p=0.02).

PWH with FHD exhibited worse neurocognitive performance within the domains of executive functioning and motor skills, however, there were no significant differences in neurocognition between APOE-e4 carriers and noncarriers. Furthermore, global neurocognitive performance was comparable across FHD/APOE-e4 groups. Differences between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups in motor skills were likely driven by FHD status, considering there were no independent effects of APOE-e4 status. This suggests that FHD may be a predispositional risk factor for poor neurocognitive performance among PWH. Considering FHD is easily captured through self-report, compared to blood based APOE-e4 status, PWH with FHD should be more closely monitored. Future research is warranted to address the potential additive effect of FHD and APOE-e4 on rates of global and domain-specific neurocognitive decline and impairment over time among in an older cohort of PWH, where APOE-e4 status may have stronger effects.

Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.

The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (<50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, and

relevant imaging covariates (i.e., intracranial volume or mean cortical thickness).

APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps>0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps<0.05). There were no APOE by race interactions for any MTL structures (ps>0.10).

Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.

The Beta-lactam Comprehensive Allergy Management Program (CAMP) was implemented to facilitate complete beta-lactam allergy history documentation in the electronic medical record (EMR) and increase beta-lactam utilization. The study objective was to assess the rate of complete allergy histories and days of antimicrobial therapy (DOT) before versus after CAMP implementation.

Quasi-experimental study with interrupted time-series analysis.

Non-teaching, urban, and community medical center within a multi-hospital health system.

Adult inpatients with a beta-lactam allergy receiving antimicrobial therapy.

The multidisciplinary CAMP team screened, interviewed, and collected allergy history details of adult inpatients with a beta-lactam allergy receiving antimicrobial therapy starting January 4, 2021. Patients were stratified as high, moderate, or low risk of IgE-mediated allergy and referred to an allergist for skin testing or drug challenge. The EMR was updated with interview details and drug challenge or skin test results. The primary endpoint was rate of complete allergy history documentation before (12/1/18–4/1/19) compared to after (1/4/21–5/1/21) program implementation. The secondary endpoint was days of inpatient beta-lactam therapy. Implementation logistics, de-labeling rate, and antimicrobial therapy changes were evaluated.

The program evaluated 392 individuals, with 184 and 208 patients comprising the pre- and post-intervention groups, respectively. The post-intervention period was associated with an increase of 19.8% in complete allergy histories (0.359 PPc; R2 0.26; p = 0.002) and 9.34 beta-lactam DOT per 1,000-days-present (1.106 PPc; R2 0.194; p = 0.009).

Implementation of a comprehensive beta-lactam allergy management program was associated with higher rates of complete beta-lactam allergy history and beta-lactam use.

Many male prisoners have significant mental health problems, including anxiety and depression. High proportions struggle with homelessness and substance misuse.

This study aims to evaluate whether the Engager intervention improves mental health outcomes following release.

The design is a parallel randomised superiority trial that was conducted in the North West and South West of England (ISRCTN11707331). Men serving a prison sentence of 2 years or less were individually allocated 1:1 to either the intervention (Engager plus usual care) or usual care alone. Engager included psychological and practical support in prison, on release and for 3–5 months in the community. The primary outcome was the Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM), 6 months after release. Primary analysis compared groups based on intention-to-treat (ITT).

In total, 280 men were randomised out of the 396 who were potentially eligible and agreed to participate; 105 did not meet the mental health inclusion criteria. There was no mean difference in the ITT complete case analysis between groups (92 in each arm) for change in the CORE-OM score (1.1, 95% CI –1.1 to 3.2, P = 0.325) or secondary analyses. There were no consistent clinically significant between-group differences for secondary outcomes. Full delivery was not achieved, with 77% (108/140) receiving community-based contact.

Engager is the first trial of a collaborative care intervention adapted for prison leavers. The intervention was not shown to be effective using standard outcome measures. Further testing of different support strategies for prison with mental health problems is needed.

Exposure to aerosol spray generated by high-speed handpieces (HSHs) and ultrasonic scalers poses a significant health risk to oral health practitioners from airborne pathogens. Aerosol generation varies with different HSH designs, but to date, no study has measured this.

We measured and compared aerosol generation by (1) dental HSHs with 3 different coolant port designs and (2) ultrasonic scalers with no suction, low-volume evacuation (LVE) or high-volume evacuation (HVE). Measurements used a particle counter placed near the operator’s face in a single-chair, mechanically ventilated dental surgery. Volume concentrations of aerosol, totaled across a 0.3–25-µm size range, were compared for each test condition.

HSH drilling and scaling produced significantly high aerosol levels (P < .001) with total volume concentrations 4.73×108µm3/m3 and 4.18×107µm3/m3, respectively. For scaling, mean volume of aerosol was highest with no suction followed by LVE and HVE (P < .001). We detected a negative correlation with both LVE and HVE, indicating that scaling with suction improved operator safety. For drilling, simulated cavity preparation with a 1-port HSH generated the most aerosol (P < .01), followed by a 4-port HSH. Independent of the number of cooling ports, lack of suction caused higher aerosol volume (1.98×107 µm3/m3) whereas HVE significantly reduced volume to −4.47×105 µm3/m3.

High concentrations of dental aerosol found during HSH cavity preparation or ultrasonic scaling present a risk of infection, confirming the advice to use respiratory PPE. HVE and LVE both effectively reduced aerosol generation during scaling, whereas the new aerosol-reducing ‘no air’ function was highly effective and can be recommended for HSH drilling.

The COVID-19 pandemic presented a challenge to established seed grant funding mechanisms aimed at fostering collaboration in child health research between investigators at the University of Minnesota (UMN) and Children’s Hospitals and Clinics of Minnesota (Children’s MN). We created a “rapid response,” small grant program to catalyze collaborations in child health COVID-19 research. In this paper, we describe the projects funded by this mechanism and metrics of their success.

Using seed funds from the UMN Clinical and Translational Science Institute, the UMN Medical School Department of Pediatrics, and the Children’s Minnesota Research Institute, a rapid response request for applications (RFAs) was issued based on the stipulations that the proposal had to: 1) consist of a clear, synergistic partnership between co-PIs from the academic and community settings; and 2) that the proposal addressed an area of knowledge deficit relevant to child health engendered by the COVID-19 pandemic.

Grant applications submitted in response to this RFA segregated into three categories: family fragility and disruption exacerbated by COVID-19; knowledge gaps about COVID-19 disease in children; and optimizing pediatric care in the setting of COVID-19 pandemic restrictions. A series of virtual workshops presented research results to the pediatric community. Several manuscripts and extramural funding awards underscored the success of the program.

A “rapid response” seed funding mechanism enabled nascent academic-community research partnerships during the COVID-19 pandemic. In the context of the rapidly evolving landscape of COVID-19, flexible seed grant programs can be useful in addressing unmet needs in pediatric health.

Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.

To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.

This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.

The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.

Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.

Longitudinal studies are needed to examine the association between maternal depression, trauma and childhood mental health in conflict-affected settings.

To examine maternal depressive symptoms, trauma-related adversities and child mental health by using a longitudinal path model in conflict-affected Timor-Leste.

Women were recruited in pregnancy. At wave 1, 1672 of 1740 eligible women were interviewed (96% response rate). The final sample comprised 1118 women with complete data at all three time points. Women were followed up when the index child was aged 18 months (wave 2) and 36 months (wave 3). Measures included the Edinburgh Postnatal Depression Scale, lifetime traumatic events and the Child Behaviour Checklist. A longitudinal path analysis examined associations cross-sectionally and in a cross-lagged manner across time.

Maternal depressive symptom score was associated with child mental health (cross-sectional association at wave 2, β = 0.35, P < 0.001; cross-sectional association at wave 3, β = 0.33, P < 0.001). The maternal depressive symptom score at wave 1 was associated with child mental health at wave 2 (β = 0.12, P < 0.001), and the maternal depressive symptom score at wave 2 showed an indirect association with child mental health at wave 3 (indirect standardised coefficient 0.23, P < 0.001). There was a time-lagged relationship between child mental health at wave 2 and maternal depression at wave 3 (β = 0.08, P = 0.02).

Maternal depressive symptoms are longitudinally associated with child mental health, and traumatic events play a role. Maternal depression symptoms are also affected by child mental health. Findings suggest the need for skilled assessment for depression, trauma-informed maternity care and parenting support in a post-conflict country such as Timor-Leste.