Posttraumatic stress disorder (PTSD) is often chronic and impairing. Mechanisms that maintain symptoms remain poorly understood because of heterogenous presentation. We parsed this heterogeneity by examining how individual differences in stress-symptom dynamics relate to the long-term maintenance of PTSD.

We studied 7,308 trauma-exposed World Trade Center responders who self-reported PTSD symptoms and stressful life events at annual monitoring visits for up to 20 years (average = 8.8 visits; [range = 4–16]). We used multilevel structural equation models to separate the stable and time-varying components of symptoms and stressors. At the within-person level, we modeled stress reactivity by cross-lagged associations between stress and future symptoms, stress generation by cross-lagged associations between symptoms and future stress, and autoregressive effects represented symptom persistence and stress persistence. The clinical utility of the stress-symptom dynamics was evaluated by associations with PTSD chronicity and mental health care use.

Stress reactivity, stress generation, and symptom persistence were significant on average (bs = 0.03–0.16). There were significant individual differences in the strength of each dynamic (interquartile ranges = 0.06–0.12). Correlations among within-person processes showed some dynamics are intertwined (e.g. more reactive people also generate stress in a vicious cycle) and others represent distinct phenotypes (e.g. people are reactive or have persistent symptoms). Initial trauma severity amplified some dynamics. People in the top deciles of most dynamics had clinically significant symptom levels across the monitoring period and their health care cost 6–17× more per year than people at median levels.

Individual differences in stress-symptom dynamics contribute to the chronicity and clinical burden of PTSD.

The Clinical and Translational Science Awards (CTSA) Program supports a national network of medical research institutions working to expedite the development of treatments and interventions. High-performing translational teams (TTs) involving inter-institutional collaborations are critical for advancing these evidence-based approaches. However, management of these complex teams can be difficult, and tailored project management may help TTs overcome the unique challenges they face.

We conducted qualitative interviews with 14 dedicated project managers (PMs) from six CTSAs to learn more about their experiences with TTs. Information derived from the thematic analysis of the data was used to identify barriers and facilitators for effective project management.

Barriers included a lack of institutional support, communication issues, pushback, role confusion, and a need for agility. Facilitators included transparent communication, supportive team environments, shared leadership with autonomy, and opportunities for professional development. The PMs interviewed for this study provided descriptions of their work that depicted a more expansive view of project management than the more traditional approach focused on meeting deadlines and managing deliverables.

Our findings have been used to inform development, training, and guidance for an innovative project management resource, the Project Management Innovation Center of Excellence (PROMICE) recently launched at the UW-Madison Institute for Clinical and Translational Research (ICTR). Through the development of a dedicated career path, PROMICE recognizes the value that PMs bring to translational science and provides the support that they need to be innovative, leading their teams to success.

Traumatic brain injury (TBI) is a prevalent cause of long-term morbidity in children and adolescents and can lead to persistent difficulties with social and behavioral function. TBI may impact brain structures that support social cognition, social perception, and day-to-day social interactions—termed the social brain network (SBN). We examined differences in links among the SBN and regions of interest from other neural networks thought to support social outcomes, i.e., the default mode network (DMN) and salience network (SN). Furthermore, we examined how differences in co-activation among the SBN and these other key networks were associated with ratings of social and day-to-day adaptive outcomes.

Participants included children and adolescents with moderate to severe TBI (msTBI; n=11, Mage=11.78, 6 male), complicated-mild TBI (cmTBI; n=12, Mage=12.59, 9 male), and orthopedic injury (OI; n=22, Mage=11.69, 15 male). Participants underwent resting-state functional MRI on a 3Tesla Siemens Prisma scanner. Parents rated their child’s social and adaptive function on the Child Behavior Checklist (CBCL) and Adaptive Behavior Assessment System-Third Edition (ABAS-3). Resting-state connectivity was assessed using the CONN Toolbox, including preprocessing, denoising, and alignment to the participants’ processed T1 MPRAGE sequence followed by seed-to-voxel analysis using a SBN mask and targeted regions of interest within the DMN and SN. Individual-level r-to-z correlations were extracted from resulting clusters of co-activation with the SBN mask and exported into SPSSv28.0 for integration with behavioral data.

One-way ANOVAs used to examine group differences in social and adaptive outcome revealed significant group differences in CBCL Social Competence (F=4.49, p=.019) and all composite scores on the ABAS-3 (Fs=3.78 to 5.17, ps=.031 to .010). In each domain, children with msTBI were rated as having elevated difficulties relative to cmTBI or OI, whereas cmTBI and OI groups did not differ. Connectivity also differed significantly between groups, with children with OI demonstrating greater connectivity between the SBN and the anterior cingulate cortex of the SN (t=5.19, p(FDR)<.0001) and posterior cingulate cortex of the DMN (f=4.30, p(FDR)<.001) than children with msTBI. Children with cmTBI also showed greater connectivity between the SBN and left temporal pole of the DMN (t=7.45, p(FDR)<.000001) than children with msTBI. Degree of connectivity between the SBN and posterior cingulate was significantly positively correlated across all domains of adaptive function (rs=.451 to .504, ps=.010 to .003), whereas degree of connectivity between the SBN and left temporal pole was strongly positively related to Social Competence (a=.633, p=.006) and conceptual adaptive skills on the ABAS (A=.437, p=.037).

Our findings provide insights into the neural substrates of social and adaptive morbidity after pediatric TBI, particularly msTBI, by linking alterations in connectivity among the SBN, DMN, and SN with measures of social and adaptive outcome. While the posterior cingulate was broadly associated with adaptive outcome, the temporal pole was particularly strongly associated with social competence. This may reflect the diverse functions and high degree of interconnectivity of the posterior cingulate, which contributes to various cognitive and attentional processes, relative to the strong amygdala/limbic connections of the temporal pole.

The stria terminalis (ST) is a white matter tract with connections to limbic and autonomic brain structures that is implicated in affective functioning. Recent works suggests that ST functional integrity and connectivity is associated with faster responses to emotional cues (Dzafic et al., 2019) and may be influenced by environmental factors including socioeconomic status (SES) and childhood adversity (Banihashemi et al., 2020). The role of the ST in the experience of more daily affective experiences, such as depressive symptoms, remains unexplored. Therefore, the present study examined the role of the ST and SES, as assessed by household income, in the relationship between age and depressive symptoms in typically developing children and adolescents.

Participants include 64 typically developing children and adolescents age 8-21 (Mage=13.27, SD=3.15) who participated in an ongoing study of development of neurocognitive and social-cognitive skills. Participants completed imaging on a 3Tesla MR Siemens PRISMA scanner. Tractography was executed via ENIGMA tract-based spatial statistics to quantify WM integrity and provided values for mean fractional anisotropy (mFA) of the ST. Depressive symptoms were measured with the Behavior Assessment Scale for Children-Third Edition (BASC-3) parent report scale, and annual family income was obtained per parent report. Mediation and moderation analyses were conducted using Process version 4.1 (Hayes, 2022) in SPSS version 28. As depression symptoms are often higher in early adolescence than later, we examined the indirect effect of age on depressive symptoms through ST mFA and evaluated this relationship at different levels of family income.

Age was associated with lower levels of depressive symptoms (b=-.98, t=-2.18, p<.05), whereas greater right ST mFA was associated with higher levels of depressive symptoms (b=42.05, t=2.50, p<.05). Right ST mFA explained significant variance in the relationship between age and parent-reported depression (ab=.13, 95% CI [.02, .29]). The conditional indirect effect of family income was significant for children with annual family incomes between 25-50k (effect=.16, 95% CI [.01, .38]) and 75-100k (effect=.13, 95% CI [.001, .31]), but not for 100k+ (effect=.11, 95% CI [-.05, .33]).

The present study revealed a significant, positive relationship between white matter integrity in the right ST and parent-reported depressive symptoms in healthy children and young adults. Finding extend on prior work implicating the ST in threat responsivity (Dzafic et al., 2019). Moreover,results suggest the role of the ST in the relationship between age and depression depends on level of family income, such that ST mFA explains more variance at lower income levels, and is no longer significant for children from families with income greater than 100k. These findings support the notion that environmental stressors (such as lower family income) may strengthen ST pathways via activity-dependent plasticity and repeated, coordinated activation (Rinaman et al., 2011). Future studies should examine these brain-behavior associations, as they may replicate in a larger sample, with more nuanced indicators of environmental stress.

The increasing complexity of social stress may be especially threatening to mental health during childhood and adolescence. One's skills in effectively coping with this stress may contribute to symptoms of pediatric anxiety and depression, a growing, significant, and pervasive public health concern. In addition to strategic skills, individual differences in coping may reflect differences in brain structure, including the white matter pathways that integrate frontal lobe networks with those involved in social functioning. Identifying the neurological substrates underlying anxiety and depression is an important way to delineate mechanisms underlying development of these disorders. Deterministic automated-fiber quantification (AFQ) is a technique that removes potential error from manual tracking of white matter, segregating tracts into distinct nodes—diminishing the effect of crossing fibers—and quantifying the number of fibers in a tract, allowing for assessment of connectivity across regions. Collectively, this investigation aims to quantify the interplay between anxiety, depression, coping with social stress, and white matter microstructure in children and adolescents.

Ninety-two healthy children and adolescents (8-17 years old; n=53 female, Mage=12.96; n=39 male, Mage=12.31) and a parent rated symptoms of anxiety and depression using the Behavior Assessment System for Children (BASC-III). Coping and stress reactivity were assessed using the Responses to Stress Questionnaire, Social Stress version. Children and adolescents also completed 64-direction DTI in a Siemens 3T Prisma scanner. White matter microstructure was quantified using AFQ; Fractional anisotropy (FA) values were extracted for 18 tracts, comprised of 100 nodes each.

Mean levels of parent- and self-reported anxiety and depression fell within the normative range, and children reported mild- to moderate social stress. Higher levels of social stress were associated with increased parent reported anxiety (r=.294, p=.002) and parent- and self-reported depression (r=.481, p<.001; r=.211, p=.034, respectively). Anxiety and depression were not significantly related to white matter microstructure; however, several specific links with coping were noted. Use of secondary control coping (e.g., cognitive restructuring) was associated with higher FA of the bilateral inferior fronto-occipital fasciculi (left IFOF r=.228, p=.027; right IFOF r=.299, p=.003) and left inferior longitudinal fasciculus (r=.269, p=.009); use of primary control coping (e.g., problem solving) was associated with higher FA of the bilateral uncinate fasciculi (left UF r=.216, p=.036; right UF r=.207, p=.045). Furthermore, use of primary and secondary control coping were associated with fewer symptoms of anxiety and depression, whereas greater use of disengagement coping (e.g., wishful thinking) was associated with more depressive symptoms.

These findings highlight links among white matter microstructure in tracts integrating frontal with temporal and occipital regions, and adoption of adaptive (i.e., primary and secondary control) coping responses. This may suggest that strong connections between brain regions supports more of a modulatory than a neglecting coping strategy. Finding also replicate extant literature on the ties between coping style and psychosocial distress. Given that coping responses are amenable to intervention, capitalizing on these brain-behavior links during ongoing neuromaturation is worthy of future research, with a goal of reducing symptoms of anxiety and depression via the brain's support of adaptive coping.

Limited data exist regarding treatment of invasive group A streptococcal (GAS) infections, including safety and efficacy of oral (PO) step-down therapy. We sought to describe current prescribing practices and clinical outcomes for patients with GAS bacteremia across a large health system, including a prespecified subset of patients who stepped down to PO antibiotics.

This retrospective cohort study included adult patients with a positive blood culture for GAS between July 2018 and July 2021. Primary outcomes included frequency of PO step-down, total duration of therapy, duration of intravenous (IV) therapy prior to PO switch, and antimicrobial selection. Secondary outcomes included length of stay (LOS), mortality, adverse events, and clinical failure leading to readmission within 90 days.

In total, 280 patients met inclusion criteria. Of these, 46.7% were stepped down to PO antibiotics. Median total duration of therapy was 15 days. Median duration of IV therapy prior to PO switch was 5 days. The predominant definitive antibiotic choice was a beta-lactam. Median LOS was 5 days. Ninety-day mortality was 16.7%. One patient developed an occluded line and one developed Clostridioides difficile-associated diarrhea within 90 days. Ninety-day readmission due to clinical failure was 12.5%. Among cases of uncomplicated skin and soft tissue source, mortality (6.1% vs 2.4%) and readmission (15.2% vs 16.9%) were similar between definitive IV and PO groups.

Group A streptococcal bacteremia is a severe infection with a high readmission and mortality rate. Use of PO step-down therapy was common with similar readmission and mortality rates compared with definitive IV therapy.

Assess urgent care (UC) clinician prescribing practices and factors associated with first-line antibiotic selection and recommended duration of therapy for sinusitis, acute otitis media (AOM), and pharyngitis.

Retrospective cohort study.

All respiratory UC encounters and clinicians in the Intermountain Health (IH) network, July 1st, 2019–June 30th, 2020.

Descriptive statistics were used to characterize first-line antibiotic selection rates and the duration of antibiotic prescriptions during pharyngitis, sinusitis, and AOM UC encounters. Patient and clinician characteristics were evaluated. System-specific guidelines recommended 5–10 days of penicillin, amoxicillin, or amoxicillin-clavulanate as first-line. Alternative therapies were recommended for penicillin allergy. Generalized estimating equation modeling was used to assess predictors of first-line antibiotic selection, prescription duration, and first-line antibiotic prescriptions for an appropriate duration.

Among encounters in which an antibiotic was prescribed, the rate of first-line antibiotic selection was 75%, the recommended duration was 70%, and the rate of first-line antibiotic selection for the recommended duration was 53%. AOM was associated with the highest rate of first-line prescriptions (83%); sinusitis the lowest (69%). Pharyngitis was associated with the highest rate of prescriptions for the recommended duration (91%); AOM the lowest (51%). Penicillin allergy was the strongest predictor of non–first-line selection (OR = 0.02, 95% CI [0.02, 0.02]) and was also associated with extended duration prescriptions (OR = 0.87 [0.80, 0.95]).

First-line antibiotic selection and duration for respiratory UC encounters varied by diagnosis and patient characteristics. These areas can serve as a focus for ongoing stewardship efforts.

Studies have reported mixed findings regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on pregnant women and birth outcomes. This study used a quasi-experimental design to account for potential confounding by sociodemographic characteristics.

Data were drawn from 16 prenatal cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) program. Women exposed to the pandemic (delivered between 12 March 2020 and 30 May 2021) (n = 501) were propensity-score matched on maternal age, race and ethnicity, and child assigned sex at birth with 501 women who delivered before 11 March 2020. Participants reported on perceived stress, depressive symptoms, sedentary behavior, and emotional support during pregnancy. Infant gestational age (GA) at birth and birthweight were gathered from medical record abstraction or maternal report.

After adjusting for propensity matching and covariates (maternal education, public assistance, employment status, prepregnancy body mass index), results showed a small effect of pandemic exposure on shorter GA at birth, but no effect on birthweight adjusted for GA. Women who were pregnant during the pandemic reported higher levels of prenatal stress and depressive symptoms, but neither mediated the association between pandemic exposure and GA. Sedentary behavior and emotional support were each associated with prenatal stress and depressive symptoms in opposite directions, but no moderation effects were revealed.

There was no strong evidence for an association between pandemic exposure and adverse birth outcomes. Furthermore, results highlight the importance of reducing maternal sedentary behavior and encouraging emotional support for optimizing maternal health regardless of pandemic conditions.