This national survey aimed to describe the work settings, characteristics, employment activities, scope, functions, and challenges of the pharmacist workforce responsible for infectious diseases (ID) and antimicrobial stewardship (AMS)-related tasks in the U.S.

An internet-based QualtricsXM survey was distributed to 22,749 unique individuals with potential ID or AMS job responsibilities via email listservs for three national pharmacy organizations, and was open from 9/25/2024 to 10/24/2024. A respondent was considered engaged in ID/AMS activities if they reported involvement in at least one of 14 activities directly related to ID/AMS.

A total of 796 pharmacists with ID or AMS job responsibilities responded (3.5% response rate), with 607 working clinically or administratively in ID or AMS further categorized in four mutually exclusive groups based on formal and informal ID/AMS responsibilities. Respondents were predominantly female (66%), less than 40 years of age (59%) and white (82%). ID-specific training was completed by 41.8%, and 74% reported having student loan debt at graduation. Work-related activities were diverse and most frequently included: staffing or taking calls on weekends related to ID/AMS, AMS, educating learners or healthcare providers about ID-related topics, precepting learners, and conducting ID-related research and/or quality improvement projects. Respondents frequently indicated they lacked adequate job resources.

The results highlight the extensive responsibilities placed on ID/AMS pharmacists to fulfill multiple roles. Pharmacists frequently lack ID-specific training or dedicated time for AMS responsibilities. The workforce is young, suggesting a need for both increased capacity for training programs and strategies for workforce retention.

Major depressive disorder is a prevalent and debilitating mental health condition contributing to a growing global burden. Late-life depression (LLD), affecting individuals over 60 years of age, is further associated with elevated risks for cardiovascular diseases, cognitive decline, and dementia. Treatment responses vary widely, potentially due to underlying neurodegeneration and cellular senescence. We aimed to explore blood-based biomarkers related to Alzheimer’s disease and senescence-associated secretory phenotype (SASP) proteins, seeking to identify biological underpinnings of LLD and their association with response to psychotherapy.

We performed a secondary analysis of the Cognitive Behavioral Therapy for Late-Life Depression (CBTlate) trial in 228 participants aged 60 years and older with a diagnosis of LLD. Depression trajectories were compared using clustering. In participants with available plasma samples, biomarker data were generated post hoc. We assessed associations between biomarkers and depression trajectories, biomarker dynamics, and their ability to predict treatment response.

Two depression trajectories were identified: persistently high stable Geriatric Depression Scale (GDS) scores (hsGDS) and decreasing scores over time (dGDS). The hsGDS group had more severe baseline depression (p = 2.88 × 10−6), anxiety (p = 4.39 × 10−4), and sleep disorders (p = 1.09 × 10−3), and was more likely to have a history of major depression (p = 0.01) and mild cognitive impairment (p = 0.01). Biomarker analysis revealed elevated baseline plasma neurofilament light chain (NfL, p = 2.51 × 10−2) and reduced C-X-C Motif Chemokine Ligand 5 (CXCL5, p = 2.83 × 10−2) in the hsGDS group. Including CXCL5 in predictive models improved trajectory differentiation (p = 3.94 × 10−3).

Cellular aging biomarkers like CXCL5 may improve understanding of LLD and guide personalized therapeutic interventions.

Healthcare workers globally face an elevated risk of mental health conditions. Despite the critical need for mental health support, access remains inconsistent, hindered by both systemic gaps and barriers like stigma and regulatory constraints. Recognizing this unmet need, we established the Staff Mental Health Service (SMHS) in Cambridgeshire, UK, in September 2020. SMHS offers prompt assessments and treatments for healthcare workers across various professional roles.

To assess costs, clinical outcomes and waiting times associated with treatment at the SMHS compared to NHS Talking Therapies (TT), a nationally-delivered primary care mental health service.

A cost-consequence analysis comparing costs and clinical outcomes for a hypothetical cohort of patients (N=1,000) between two options: (1) treatment either at SMHS or TT ; and (2) treatment at TT only. SMHS costs and outcomes were collected from routinely collected patient-level data, while those for TT were informed by published literature. Only costs borne by the health system were assessed; and model outcomes were compared for one treatment period (i.e., from treatment start to discharge).  Primary model outcomes included average total treatment costs (GBP - £); and mean score changes on the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder Assessment (GAD-7) measures for symptoms of depression and anxiety, respectively. Uncertainty in model parameters was explored using deterministic and probabilistic sensitivity analyses. Mean waiting times from referral to initial assessment and first treatment appointment for the SMHS and TT were analysed independently.

Average total treatment costs per patient for the option consisting of treatment at either SMHS or TT was £825 less costly than the option consisting of treatment only at TT (£617 vs £1,442). Main drivers of cost difference included the notably higher cost and average number of appointments associated with treatment at TT. Treatment at either SMHS or TT also led to better patient outcomes on both the PHQ-9 (mean score reductions of 7.2 vs 6.1) and GAD-7 (mean score reductions of 6.3 vs 4.8) scales. Mean waiting times (days) for treatment at SMHS were considerably shorter than at TT: referral to initial assessment (19 vs 25 days); and referral to first treatment appointment (28 vs 53 days).

Preliminary results showed that a specialised mental health service for healthcare workers was associated with lower costs, better patient outcomes, and shorter waiting times compared to standard treatment options.

None Declared

To determine the association between blood markers of white matter injury (e.g., serum neurofilament light and phosphorylated neurofilament heavy) and a novel neuroimaging technique measuring microstructural white matter changes (e.g., diffusion kurtosis imaging) in regions (e.g., anterior thalamic radiation and uncinate fasciculus) known to be impacted in traumatic brain injury (TBI) and associated with symptoms common in those with chronic TBI (e.g., sleep disruption, cognitive and emotional disinhibition) in a heterogeneous sample of Veterans and non-Veterans with a history of remote TBI (i.e., >6 months).

Participants with complete imaging and blood data (N=24) were sampled from a larger multisite study of chronic mild-moderate TBI. Participants ranged in age from young to middle-aged (mean age = 34.17, SD age = 10.96, range = 19-58) and primarily male (66.7%). The number of distinct TBIs ranged from 1-5 and the time since most recent TBI ranged from 0-30 years. Scores on a cognitive screener (MoCA) ranged from 22-30 (mean = 26.75). We performed bivariate correlations with mean kurtosis (MK) in the anterior thalamic radiation (ATR; left, right) uncinate fasciculus (UF; left, right), and serum neurofilament light (NFL), and phosphorylated neurofilament heavy (pNFH). Both were log transformed for non-normality. Significance threshold was set at p<0.05.

pNFH was significantly and negatively correlated to MK in the right (r=-0.446) and left (r=-0.599) UF and right (r=-0.531) and left (r=-0.469) ATR. NFL showed moderate associations with MK in the right (r=-0.345) and left (r=-0.361) UF and little to small association in the right (r=-0.063) and left (r=-0.215) ATR. In post-hoc analyses, MK in both the left (r=0.434) and right (r=0.514) UF was positively associated with performance on a frontally-mediated list-learning task (California Verbal Learning Test, 2nd Edition; Trials 1-5 total).

Results suggest that serum pNFH may be a more sensitive blood marker of microstructural complexity in white matter regions frequently impacted by TBI in a chronic mild-moderate TBI sample. Further, it suggests that even years after a mild-moderate TBI, levels of pNFH may be informative regarding white matter integrity in regions related to executive functioning and emotional disinhibition, both of which are common presenting problems when these patients are seen in a clinical setting.

To determine the association between in-vivo spectroscopy metabolite data, the local connectome, and markers of initial injury severity (I.e., history of loss of consciousness; LoC) in traumatic brain injury (TBI), in a heterogenous sample of Veterans and non-Veterans with a history of remote mild-to-moderate TBI (I.e., >6 months).

Participants with complete PRESS magnetic resonance spectroscopy (MRS) and diffusion weighted imaging (DWI) data (N = 41) were sampled from a larger multisite study of chronic mild-to-moderate TBI (Nmiid = 38; Nmoderate = 3; 54% with LoC; 46% with multiple TBI). The sample was predominantly male (76%) with ages ranging from 23-59 (M = 36.9, SD = 10.1), with 98% holding at least a high school degree (M = 14.5 years of education, SD = 2.4). Fully tissue-and-relaxation-corrected metabolite concentration estimates in the dorsal anterior cingulate (30x30x30mm voxel) were modeled using Osprey 2.4.0. Total creatine (tCr), total choline (tCho), total N-acetylaspartate (tNAA), glutamate/glutamine (Glx), and myo-inositol (mI) were analyzed. Logistic regression was used to measure the association between metabolites and history of TBI with LoC. Correlational connectometry using the normalized spin distribution function was performed for metabolites associated with LoC, to characterize the local connectome associated with metabolites of interest, controlling for age and sex, and correcting for multiple comparisons (FDR < .050 with 4000 permutations). A profile approach was used to interpret diffusion metrics, contrasting quantitative anisotropy (QA) with fractional anisotropy (FA). Local connectome tracks were then clustered to identify the larger white matter tract.

Glx (p = .008) and tCr (p = .032) were significantly associated with history of TBI with LoC. Increased Glx was associated with increased QA in 11,001 tracks, accounting for 1.4% of the total white matter tracks in the brain. 90% of tracks were identified in bilateral cingulum (33%), bilateral thalamic (13%), bilateral corticospinal (13%), corpus callosum (12%), left arcuate fasciculus (9%), left frontoparietal aslant tracts (6%), and bilateral inferior fronto-occipital fasciculus (4%) tracts. In contrast, FA was not associated with Glx. The same pattern emerged for tCr, with 10,542 tracks identified predominantly in bilateral cingulum (29%), corpus callosum (21%), bilateral corticospinal (15%), bilateral corticostriatal (7%), bilateral medial lemniscus (7%), left cortico-pontine (3%), left thalamic (2%), and bilateral superior longitudinal fasciculus (2%) tracts. Post-hoc exploratory analyses of mean QA across regions of cingulum found that increased QA was associated with self-report measures of headache intensity, fatigue, and perceived change in executive functioning.

Results provided evidence that multimodal imaging can identify subtle markers of initial TBI severity years after injury. Neurometabolite concentrations were associated with diffuse changes in the local connectome; the pattern of discrepancy between FA and QA was suggestive of reduced potential for neuroplasticity. Exploratory analyses further indicated that variability in white matter density in the cingulum, an important connection for limbic regions, was associated with a range of problems commonly reported in clinical settings, which may be informative for diagnosis and treatment planning.

It has been previously identified that levels of peripheral inflammatory proteins, such as cytokines, are altered in people with schizophrenia spectrum disorders (SSD).

As there is considerable inconsistency in the literature with respect to how inflammatory profiles differ between acute and chronic stages of SSD, a systematic review and network meta-analysis was performed.

Records from CINAHL, the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, and PsycINFO were systematically searched from inception until 31 March 2022 for published studies that had measured levels of inflammatory proteins in cases of SSD and healthy controls. Pairwise and network meta-analyses were performed to determine whether there were significant differences in mean peripheral protein concentrations between acute SSD, chronic SSD, and healthy controls.

After application of the screening process, 215 articles were included for data-analysis. One group of markers were consistently elevated (p<0·05) in both acute and chronic SSD, relative to healthy controls; this group comprised interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), soluble interleukin-2 receptor (sIL-2R), IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, and high sensitivity C-reactive protein (hsCRP). A second group of markers were inconsistently altered between illness stages: IL-2 and interferon (IFN)-γ were significantly elevated (p<0·05) in acute SSD, whilst IL-4, IL-12 and IFN-γ were significantly decreased (p<0·05) in chronic SSD.

These results indicate that a baseline level of inflammatory protein alteration occurs in SSD throughout the course of illness. This was evident from the group of markers that were consistently elevated in acute and chronic SSD (e.g., IL-6), representing possible trait markers. Moreover, superimposed immune activity may occur in acute SSD, given the group of possible state markers that were increased only in acute illness (e.g., IFN-γ). Further research is required to elucidate whether these peripheral changes are reflected within the central nervous system.

None Declared

Although clozapine is the most efficacious medication for treatment-refractory schizophrenia, not all patients will have an adequate response. Optimising clozapine dose using therapeutic drug monitoring could therefore maximise response.

Using individual patient data, we undertook a receiver operating characteristic (ROC) curve analysis to determine an optimal therapeutic range for clozapine levels to guide clinical practice.

We conducted a systematic review of PubMed, PsycINFO and Embase for studies that provided individual participant level data on clozapine levels and response. These data were analysed using ROC curves to determine the prediction performance of plasma clozapine levels for treatment response.

We included data on 294 individual participants from nine studies. ROC analysis yielded an area under the curve of 0.612. The clozapine level at the point of optimal diagnostic benefit was 372 ng/mL; at this level, the response sensitivity was 57.3%, and specificity 65.7%. The interquartile range for treatment response was 223–558 ng/mL. There was no improvement in ROC performance with mixed models including patient gender, age or length of trial. Clozapine dose and clozapine concentration to dose ratio did not provide significantly meaningful prediction of response to clozapine.

Clozapine dose should be optimised based on clozapine therapeutic levels. We found that a range between 250 and 550 ng/mL could be recommended, while noting that a level of >350 ng/mL is the most optimal for response. Although some patients may not respond without clozapine levels >550 ng/mL, the benefits should be weighed against the increased risk of adverse drug reactions.

Young people can receive mental health care from many sources, from formal and informal sectors. Caregiver characteristics/experiences/beliefs may influence whether young people get help and the type of care or support used by their child. We investigate facilitators/barriers to receiving formal and/or informal care, particularly those related to the caregiver’s profile.

We interviewed 1,400 Brazilian primary caregivers of young people (aged 10–19), participants of a high-risk cohort. Caregivers reported on young people’s formal/informal mental health care utilization, and associated barriers and facilitators to care. Data were also collected on youth mental health and its impact on everyday life; and caregiver characteristics—education, socioeconomics, ethnicity, mental health, and stigma. Logistic regression models were used to examine the relationship between caregiver and young people characteristics with formal/informal care utilization.

Persistence and greater impact of youth mental health conditions were associated with a higher likelihood of care, more clearly for formal care. Caregiver characteristics, however, also played a key role in whether young people received any care: lower parental stigma was associated with greater formal service use, and lower socioeconomic class showed higher odds of informal care (mainly from religious leaders).

This study highlights the key role of the caregivers as gatekeepers to child treatment access, particularly parental stigma influencing whether young people received any mental health care, even in a low resource setting. These results help to map barriers for treatment access and delivery for young people, aiming to improve intervention efforts and mental health support.