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.

Growing evidence suggests that direct oral anticoagulants (DOACs) may be suitable for cerebral venous thrombosis (CVT). The optimal strategy regarding lead-in parenteral anticoagulation (PA) prior to DOAC is unknown.

In this post hoc analysis of the retrospective ACTION-CVT study, we compared patients treated with DOACs as part of routine care: those given “very early” DOAC (no PA), “early” (<5 days PA) and “delayed” (5–21 days PA). We compared baseline characteristics and outcomes between the very early/early and delayed groups. The primary outcome was a composite of day-30 CVT recurrence/extension, new peripheral venous thromboembolism, cerebral edema and intracranial hemorrhage.

Of 231 patients, 11.7% had very early DOAC, 64.5% early (median [IQR] 2 [1–2] days) and 23.8% delayed (5 [5–6] days). More patients had severe clinical/radiological presentations in the delayed group; more patients had isolated headaches in the very early/early group. Outcomes were better in the very early/early groups (90-day modified Rankin Scale of 0–2; 94.3% vs. 83.9%). Primary outcome events were rare and did not differ significantly between groups (2.4% vs. 2.1% delayed; adjusted HR 1.49 [95%CI 0.17–13.11]).

In this cohort of patients receiving DOAC for CVT as part of routine care, >75% had <5 days of PA. Those with very early/early initiation of DOAC had less severe clinical presentations. Low event rates and baseline differences between groups preclude conclusions about safety or effectiveness. Further prospective data will inform care.

Adolescence is marked by a sharp increase in the incidence of depression, especially in females. Identification of risk for depressive disorders (DD) in this key developmental stage can help prevention efforts, mitigating the clinical and public burden of DD. While frequently used in diagnosis, nonverbal behaviors are relatively understudied as risk markers for DD. Digital technology, such as facial recognition, may provide objective, fast, efficient, and cost-effective means of measuring nonverbal behavior.

Here, we analyzed video-recorded clinical interviews of 359 never-depressed adolescents females via commercially available facial emotion recognition software.

We found that average head and facial movements forecast future first onset of depression (AUC = 0.70) beyond the effects of other established self-report and physiological markers of DD risk.

Overall, these findings suggest that digital assessment of nonverbal behaviors may provide a promising risk marker for DD, which could aid in early identification and intervention efforts.

Individuals in a depressive episode and healthy controls exhibit robust differences on affect dynamics captured with ecological momentary assessment (EMA). However, few studies have explored affect dynamics in individuals in remission from depression, and results have been mixed.

A community sample of 18-year-olds (N = 345) completed diagnostic interviews and EMA probing emotions and low interest/motivation 5× daily for 2 weeks. Affect home base, variability, and inertia were compared across currently depressed, remitted, and never-depressed groups.

Both depression groups had a higher negative affect (NA) and low interest/motivation home base, lower positive affect (PA) home base, greater variability of NA, PA, and low interest/motivation, and greater NA and low interest/motivation inertia than never-depressed participants. Additionally, the currently depressed group had a higher sad home base specifically, greater variability across most negative emotions and low interest/motivation, and greater low interest/motivation inertia than the remitted group. The currently depressed and remitted groups did not differ in anxious, upset, or PA home base, anxious or PA variability, and inertia of all negative emotions and PA.

Findings suggest that a number of abnormalities in emotion and reward functioning persist after a depressive episode resolves, however, the tendency to experience higher levels of sadness, greater range of a variety of negative emotions, and more variable and persistent low interest/motivation are exacerbated during depressive episodes. Conversely, greater intensity and persistence of some negative emotions (anxiety, upset) and blunted positive emotions appear to equally characterize depression in both the symptomatic and remitted state.

To (1) understand the role of antibiotic-associated adverse events (ABX-AEs) on antibiotic decision-making, (2) understand clinician preferences for ABX-AE feedback, and (3) identify ABX-AEs of greatest clinical concern.

Focus groups.

Academic medical center.

Medical and surgical house staff, attending physicians, and advanced practice practitioners.

Focus groups were conducted from May 2022 to December 2022. Participants discussed the role of ABX-AEs in antibiotic decision-making and feedback preferences and evaluated the prespecified categorization of ABX-AEs based on degree of clinical concern. Thematic analysis was conducted using inductive coding.

Four focus groups were conducted (n = 15). Six themes were identified. (1) ABX-AE risks during initial prescribing influence the antibiotic prescribed rather than the decision of whether to prescribe. (2) The occurrence of an ABX-AE leads to reassessment of the clinical indication for antibiotic therapy. (3) The impact of an ABX-AE on other management decisions is as important as the direct harm of the ABX-AE. (4) ABX-AEs may be overlooked because of limited feedback regarding the occurrence of ABX-AEs. (5) Clinicians are receptive to feedback regarding ABX-AEs but are concerned about it being punitive. (6) Feedback must be curated to prevent clinicians from being overwhelmed with data. Clinicians generally agreed with the prespecified categorizations of ABX-AEs by degree of clinical concern.

The themes identified and assessment of ABX-AEs of greatest clinical concern may inform antibiotic stewardship initiatives that incorporate reporting of ABX-AEs as a strategy to reduce unnecessary antibiotic use.

Adolescence is a key developmental period for the emergence of psychopathology. Reward-related brain activity increases across adolescence and has been identified as a potential neurobiological mechanism of risk for different forms of psychopathology. The reward positivity (RewP) is an event-related potential component that indexes reward system activation and has been associated with both concurrent and family history of psychopathology. However, it is unclear whether the RewP is also associated with higher-order psychopathology subfactors and whether this relationship is present across different types of reward.

In a sample of 193 adolescent females and a biological parent, the present study examined the association between adolescent and parental psychopathology subfactors and adolescent RewP to monetary and social reward.

Results indicated that the adolescent and parental distress subfactors were negatively associated with the adolescent domain-general RewP. The adolescent and parental positive mood subfactors were negatively associated with the adolescent domain-general and domain-specific monetary RewP, respectively. Conversely, the adolescent and parental fear/obsessions subfactors were positively associated with the adolescent domain-general RewP. The associations between parental and adolescent psychopathology subfactors and the adolescent RewP were independent of each other.

The RewP in adolescent females is associated with both concurrent and parental psychopathology symptoms, suggesting that it indexes both severity and risk for higher-order subfactors.

Although risk markers for depressive disorders (DD) are dynamic, especially during adolescence, few studies have examined how change in risk levels during adolescence predict DD onset during transition to adulthood. We compared two competing hypotheses of the dynamic effects of risk. The risk escalation hypothesis posits that worsening of risk predicts DD onset beyond risk level. The chronic risk hypothesis posits that persistently elevated risk level, rather than risk change, predicts DD onset.

Our sample included 393 girls (baseline age 13.5–15.5 years) from the adolescent development of emotions and personality traits project. Participants underwent five diagnostic interviews and assessments of risk markers for DD at 9-month intervals and were re-interviewed at a 6-year follow-up. We focused on 17 well-established risk markers. For each risk marker, we examined the prospective effects of risk level and change on first DD onset at wave six, estimated by growth curve modeling using data from the first five waves.

For 13 of the 17 depression risk markers, elevated levels of risk during adolescence, but not change in risk, predicted first DD onset during transition to adulthood, supporting the chronic risk hypothesis. Minimal evidence was found for the risk escalation hypothesis.

Participants who had a first DD onset during transition to adulthood have exhibited elevated levels of risk throughout adolescence. Researchers and practitioners should administer multiple assessments and focus on persistently elevated levels of risk to identify individuals who are most likely to develop DD and to provide targeted DD prevention.

The report examined reciprocal within-person associations among maternal depressive symptoms and offspring depressive, anxiety and irritability symptoms from early childhood to adolescence using a random intercept cross-lagged panel model (RI-CLPM).

Participants were 609 mother–child dyads participating in the Stony Brook Temperament Study. Child and maternal internalizing symptoms were assessed every 3 years from ages 3 to 15 using maternal report on the Child Behavior Checklist (CBCL) and Diagnostic Inventory for Depression, respectively.

At the between-person level, maternal depressive symptoms, and child depressive, anxiety, and irritability symptoms were all positively associated with one another. At the within-person level, greater within-person child anxiety symptoms at age 3 predicted both greater child anxiety and depressive symptoms at age 15 via greater child anxiety from ages 6 to 12, and greater within-person child irritability at age 3 predicted greater maternal depressive symptoms at age 15 via greater child irritability from ages 6 to 12.

Findings reveal novel within-person developmental pathways from early childhood internalizing problems to later internalizing problems in both the child and mother. Intervention and prevention efforts should thus focus on early identification and prevention of childhood internalizing symptoms to reduce negative effects on both child and parent symptoms.

This study leveraged machine learning to evaluate the contribution of information from multiple developmental stages to prospective prediction of depression and anxiety in mid-adolescence.

A community sample (N = 374; 53.5% male) of children and their families completed tri-annual assessments across ages 3–15. The feature set included several important risk factors spanning psychopathology, temperament/personality, family environment, life stress, interpersonal relationships, neurocognitive, hormonal, and neural functioning, and parental psychopathology and personality. We used canonical correlation analysis (CCA) to reduce the large feature set to a lower dimensional space while preserving the longitudinal structure of the data. Ablation analysis was conducted to evaluate the relative contributions to prediction of information gathered at different developmental periods and relative to previous disorder status (i.e. age 12 depression or anxiety) and demographics (sex, race, ethnicity).

CCA components from individual waves predicted age 15 disorder status better than chance across ages 3, 6, 9, and 12 for anxiety and 9 and 12 for depression. Only the components from age 12 for depression, and ages 9 and 12 for anxiety, improved prediction over prior disorder status and demographics.

These findings suggest that screening for risk of adolescent depression can be successful as early as age 9, while screening for risk of adolescent anxiety can be successful as early as age 3. Assessing additional risk factors at age 12 for depression, and going back to age 9 for anxiety, can improve screening for risk at age 15 beyond knowing standard demographics and disorder history.

Preschool psychiatric symptoms significantly increase the risk for long-term negative outcomes. Transdiagnostic hierarchical approaches that capture general (‘p’) and specific psychopathology dimensions are promising for understanding risk and predicting outcomes, but their predictive utility in young children is not well established. We delineated a hierarchical structure of preschool psychopathology dimensions and tested their ability to predict psychiatric disorders and functional impairment in preadolescence.

Data for 1253 preschool children (mean age = 4.17, s.d. = 0.81) were drawn from three longitudinal studies using a similar methodology (one community sample, two psychopathology-enriched samples) and followed up into preadolescence, yielding a large and diverse sample. Exploratory factor models derived a hierarchical structure of general and specific factors using symptoms from the Preschool Age Psychiatric Assessment interview. Longitudinal analyses examined the prospective associations of preschool p and specific factors with preadolescent psychiatric disorders and functional impairment.

A hierarchical dimensional structure with a p factor at the top and up to six specific factors (distress, fear, separation anxiety, social anxiety, inattention-hyperactivity, oppositionality) emerged at preschool age. The p factor predicted all preadolescent disorders (ΔR2 = 0.04–0.15) and functional impairment (ΔR2 = 0.01–0.07) to a significantly greater extent than preschool psychiatric diagnoses and functioning. Specific dimensions provided additional predictive power for the majority of preadolescent outcomes (disorders: ΔR2 = 0.06–0.15; functional impairment: ΔR2 = 0.05–0.12).

Both general and specific dimensions of preschool psychopathology are useful for predicting clinical and functional outcomes almost a decade later. These findings highlight the value of transdiagnostic dimensions for predicting prognosis and as potential targets for early intervention and prevention.

Adolescence is a key developmental period for the emergence of psychiatric disorders. However, there is still no consensus on the core mechanisms of dysfunction in youth. Neurobiological sensitivity to unpredictable threat has been associated with several psychiatric disorders in adults. The present study examined adolescent defensive motivation (startle reflex) and attention (event-related potentials) in anticipation of unpredictable threat in relation to both adolescent and maternal (i.e. familial risk) internalizing and externalizing spectra.

The sample included 395 15-year-old adolescents and their biological mothers. Adolescent startle potentiation and probe P300 suppression (indicating increased attention to threat) were measured in anticipation of predictable and unpredictable threat. Adolescent and maternal lifetime history of psychiatric disorders were assessed via semi-structured diagnostic interviews, and confirmatory factor analysis was used to model internalizing and externalizing spectra.

The adolescent internalizing spectrum was positively associated with adolescent startle potentiation and probe P300 suppression to unpredictable threat. Conversely, the adolescent externalizing spectrum was negatively associated with adolescent P300 suppression to unpredictable threat. The maternal internalizing spectrum was positively associated with adolescent startle potentiation to unpredictable threat and P300 suppression to both predictable and unpredictable threat. The maternal externalizing spectrum was negatively associated with adolescent startle potentiation to unpredictable threat and P300 suppression to both predictable and unpredictable threat. Adolescent and maternal internalizing and externalizing spectra were independently related to adolescent startle potentiation and P300 suppression.

Adolescent neurobiological sensitivity to unpredictable threat is associated with both personal history and familial risk for the internalizing and externalizing spectra.

Life stress and blunted reward processing each have been associated with the onset and maintenance of major depressive disorder. However, much of this work has been cross-sectional, conducted in separate lines of inquiry, and focused on recent life stressor exposure, despite the fact that theories of depression posit that stressors can have cumulative effects over the lifespan. To address these limitations, we investigated whether acute and chronic stressors occurring over the lifespan interacted with blunted reward processing to predict increases in depression over time in healthy youth.

Participants were 245 adolescent girls aged 8–14 years old (Mage = 12.4, s.d. = 1.8) who were evaluated at baseline and two years later. The reward positivity (RewP), an event-related potential measure of reward responsiveness, was assessed at baseline using the doors task. Cumulative lifetime exposure to acute and chronic stressors was assessed two years later using the Stress and Adversity Inventory for Adolescents (Adolescent STRAIN). Finally, depressive symptoms were assessed at both baseline and follow-up using the Children's Depression Inventory.

As hypothesized, greater lifetime acute stressor exposure predicted increases in depressive symptoms over two years, but only for youth exhibiting a blunted RewP. This interaction, however, was not found for chronic stressors.

Lifetime acute stressor exposure may be particularly depressogenic for youth exhibiting a blunted RewP. Conversely, a robust RewP may be protective in the presence of greater acute lifetime stressor exposure.

Awareness of adult separation anxiety (ASA) is growing, but there is a dearth of knowledge about how separation anxiety aggregates in families. We examined the intergenerational associations of separation anxiety and other forms of internalizing problems in an American community sample of 515 predominantly white children and their parents.

Children's separation anxiety (CSA), depression, and other anxiety disorders were modeled as latent factors using diagnoses from interviews and symptom scores from questionnaires completed by mothers, fathers, and children when children were 9 years old and again 3 years later. Parents' separation anxiety was assessed via a questionnaire and parents' other anxiety, depressive, and substance use disorders were assessed with a diagnostic interview when children were nine. Relationships between parents' and children's psychopathology were modeled using s.e.m.

Mothers' and fathers' ASA were related to all three psychopathology factors in offspring, over and above other parental disorders, in concurrent and prospective analyses. CSA was also related to maternal depression concurrently and prospectively and to maternal anxiety prospectively. Of all paternal psychopathology variables, only ASA was significantly related to children's psychopathology in either model.

Results indicate that parental separation anxiety is an important, but non-specific, risk factor for children's psychopathology. The pathway by which this risk is transmitted may be genetic or environmental, and the observed statistical associations likely also encompass child-to-parent effects.

This report examines between- and within-person associations between youth irritability and concurrent and prospective internalizing and externalizing symptoms from early childhood through adolescence. Distinguishing between- and within-person longitudinal associations may yield distinct, clinically relevant information about pathways to multifinality from childhood irritability.

Children’s irritability and co-occurring symptoms were assessed across five waves between ages 3 and 15 years using the mother-reported Child Behavior Checklist (N = 605, 46% female). Parental history of depressive disorders was assessed with a clinical interview.

Results demonstrated that between- and within-person irritability were uniquely associated with concurrent depressive, anxiety, and defiance symptoms, but not ADHD. Prior wave within-person irritability also predicted next wave depressive, anxiety, and defiance symptoms, controlling for prior symptoms; these prospective associations were bidirectional. Child sex and parental depressive disorders moderated associations.

Findings identify pathways from within- and between-person irritability to later internalizing and externalizing psychopathology. Results demonstrate the importance of parsing within- and between-person effects to understand nuanced relations among symptoms over childhood.

Risk factors for depressive disorders (DD) change substantially over time, but the prognostic value of these changes remains unclear. Two basic types of dynamic effects are possible. The ‘Risk Escalation hypothesis’ posits that worsening of risk levels predicts DD onset above average level of risk factors. Alternatively, the ‘Chronic Risk hypothesis’ posits that the average level rather than change predicts first-onset DD.

We utilized data from the ADEPT project, a cohort of 496 girls (baseline age 13.5–15.5 years) from the community followed for 3 years. Participants underwent five waves of assessments for risk factors and diagnostic interviews for DD. For illustration purposes, we selected 16 well-established dynamic risk factors for adolescent depression, such as depressive and anxiety symptoms, personality traits, clinical traits, and social risk factors. We conducted Cox regression analyses with time-varying covariates to predict first DD onset.

Consistently elevated risk factors (i.e. the mean of multiple waves), but not recent escalation, predicted first-onset DD, consistent with the Chronic Risk hypothesis. This hypothesis was supported across all 16 risk factors.

Across a range of risk factors, girls who had first-onset DD generally did not experience a sharp increase in risk level shortly before the onset of disorder; rather, for years before onset, they exhibited elevated levels of risk. Our findings suggest that chronicity of risk should be a particular focus in screening high-risk populations to prevent the onset of DDs. In particular, regular monitoring of risk factors in school settings is highly informative.