Not All Stroop-Type Tasks Are Alike: Assessing the Impact of Stimulus Material, Task Design, and Cognitive Demand via Meta-analyses Across Neuroimaging Studies.

The Stroop effect is one of the most often studied examples of cognitive conflict processing. Over time, many variants of the classic Stroop task were used, including versions with different stimulus material, control conditions, presentation design, and combinations with additional cognitive demands. The neural and behavioral impact of this experimental variety, however, has never been systematically assessed. We used activation likelihood meta-analysis to summarize neuroimaging findings with Stroop-type tasks and to investigate whether involvement of the multiple-demand network (anterior insula, lateral frontal cortex, intraparietal sulcus, superior/inferior parietal lobules, midcingulate cortex, and pre-supplementary motor area) can be attributed to resolving some higher-order conflict that all of the tasks have in common, or if aspects that vary between task versions lead to specialization within this network. Across 133 neuroimaging experiments, incongruence processing in the color-word Stroop variant consistently recruited regions of the multiple-demand network, with modulation of spatial convergence by task variants. In addition, the neural patterns related to solving Stroop-like interference differed between versions of the task that use different stimulus material, with the only overlap between color-word, emotional picture-word, and other types of stimulus material in the posterior medial frontal cortex and right anterior insula. Follow-up analyses on behavior reported in these studies (in total 164 effect sizes) revealed only little impact of task variations on the mean effect size of reaction time. These results suggest qualitative processing differences among the family of Stroop variants, despite similar task difficulty levels, and should carefully be considered when planning or interpreting Stroop-type neuroimaging experiments.

Prediction of depressive symptoms severity based on sleep quality, anxiety, and gray matter volume: a generalizable machine learning approach across three datasets.

BACKGROUND: Depressive symptoms are rising in the general population, but their associated factors are unclear. Although the link between sleep disturbances and depressive symptoms severity (DSS) is reported, the predictive role of sleep on DSS and the impact of anxiety and the brain on their relationship remained obscure. METHODS: Using three population-based datasets (N = 1813), we trained the machine learning models in the primary dataset (N = 1101) to assess the predictive role of sleep quality, anxiety problems, and brain structural (and functional) measurements on DSS, then we tested our models' performance in two independent datasets (N = 378, N = 334) to test the generalizability of our findings. Furthermore, we applied our model to a smaller longitudinal subsample (N = 66). In addition, we performed a mediation analysis to identify the role of anxiety and brain measurements on the sleep quality and DSS association. FINDINGS: Sleep quality could predict individual DSS (r = 0.43, R2 = 0.18, rMSE = 2.73), and adding anxiety, contrary to brain measurements, strengthened its prediction performance (r = 0.67, R2 = 0.45, rMSE = 2.25). Importantly, out-of-cohort validations in other cross-sectional datasets and a longitudinal subsample provided robust similar results. Furthermore, anxiety scores, contrary to brain measurements, mediated the association between sleep quality and DSS. INTERPRETATION: Poor sleep quality could predict DSS at the individual subject level across three datasets. Anxiety scores not only increased the predictive model's performance but also mediated the link between sleep quality and DSS. FUNDING: The study is supported by Helmholtz Imaging Platform grant (NimRLS, ZTI-PF-4-010), the Deutsche Forschungsgemeinschaft (DFG, GE 2835/2-1, GE 2835/4-1), the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)-Project-ID 431549029-SFB 1451, the programme "Profilbildung 2020" (grant no. PROFILNRW-2020-107-A), an initiative of the Ministry of Culture and Science of the State of Northrhine Westphalia.

Sex differences in functional cortical organization reflect differences in network topology rather than cortical morphometry.

Differences in brain size between the sexes are consistently reported. However, the consequences of this anatomical difference on sex differences in intrinsic brain function remain unclear. In the current study, we investigate whether sex differences in intrinsic cortical functional organization may be associated with differences in cortical morphometry, namely different measures of brain size, microstructure, and the geodesic distance of connectivity profiles. For this, we compute a low dimensional representation of functional cortical organization, the sensory-association axis, and identify widespread sex differences. Contrary to our expectations, sex differences in functional organization do not appear to be systematically associated with differences in total surface area, microstructural organization, or geodesic distance, despite these morphometric properties being per se associated with functional organization and differing between sexes. Instead, functional sex differences in the sensory-association axis are associated with differences in functional connectivity profiles and network topology. Collectively, our findings suggest that sex differences in functional cortical organization extend beyond sex differences in cortical morphometry.

Can Psychedelic Use Benefit Meditation Practice? Examining Individual, Psychedelic, and Meditation-Related Factors.

Introduction: Meditation practice and psychedelic use have attracted increasing attention in the public sphere and scientific research. Both methods induce non-ordinary states of consciousness that may have significant therapeutic benefits. Thus, there is growing scientific interest in potential synergies between psychedelic use and meditation practice with some research suggesting that psychedelics may benefit meditation practice. The present study examined individual, psychedelic-related, and meditation-related factors to determine under what conditions meditators perceive psychedelic use as beneficial for their meditation practice. Method: Participants (N = 863) who had reported psychedelic use and a regular meditation practice (at least 3 times per week during the last 12 months) were included in the study. To accommodate a large number of variables, machine learning (i.e., elastic net, random forest) was used to analyze the data. Results: Most participants (n = 634, 73.5%) found psychedelic use to have a positive influence on their quality of meditation. Twenty-eight variables showed significant zero-order associations with perceived benefits even following a correction. Elastic net had the best performance (R2 = .266) and was used to identify the most important features. Across 53 variables, the model found that greater use of psychedelics, intention setting during psychedelic use, agreeableness, and exposure to N,N-Dimethyltryptamine (N,N-DMT) were most likely to be associated with the perception that psychedelics benefit meditation practice. The results were consistent across several different approaches used to identify the most important variables (i.e., Shapley values, feature ablation). Discussion: Results suggest that most meditators found psychedelic use to have a positive influence on their meditation practice, with: 1) regularity of psychedelic use, 2) the setting of intentions for psychedelic use, 3) having an agreeable personality, and 4) reported use of N,N-DMT being the most likely predictors of perceiving psychedelic use as beneficial. Longitudinal designs and randomized trials manipulating psychedelic use are needed to establish causality.

Regional patterns of human cortex development correlate with underlying neurobiology.

Human brain morphology undergoes complex changes over the lifespan. Despite recent progress in tracking brain development via normative models, current knowledge of underlying biological mechanisms is highly limited. We demonstrate that human cortical thickness development and aging trajectories unfold along patterns of molecular and cellular brain organization, traceable from population-level to individual developmental trajectories. During childhood and adolescence, cortex-wide spatial distributions of dopaminergic receptors, inhibitory neurons, glial cell populations, and brain-metabolic features explain up to 50% of the variance associated with a lifespan model of regional cortical thickness trajectories. In contrast, modeled cortical thickness change patterns during adulthood are best explained by cholinergic and glutamatergic neurotransmitter receptor and transporter distributions. These relationships are supported by developmental gene expression trajectories and translate to individual longitudinal data from over 8000 adolescents, explaining up to 59% of developmental change at cohort- and 18% at single-subject level. Integrating neurobiological brain atlases with normative modeling and population neuroimaging provides a biologically meaningful path to understand brain development and aging in living humans.

Pyrazine-bridged polymetallic copper-iridium clusters.

Single crystals of the mol-ecular compound, {Cu20Ir6Cl8(C21H24N2)6(C4H4N2)3]·3.18CH3OH or [({Cu10Ir3}Cl4(IMes)3(pyrazine))2(pyrazine)]·3.18CH3OH [where IMes is 1,3-bis-(2,4,6-trimethylphen-yl)imidazol-2-yl-idene], with a unique heterometallic cluster have been prepared and the structure revealed using single-crystal X-ray diffraction. The mol-ecule is centrosymmetric with two {Cu10Ir3} cores bridged by a pyrazine ligand. The polymetallic cluster contains three stabilizing N-heterocyclic carbenes, four Cl ligands, and a non-bridging pyrazine ligand. Notably, the Cu-Ir core is arranged in an unusual shape containing 13 vertices, 22 faces, and 32 sides. The atoms within the trideca-metallic cluster are arranged in four planes, with 2, 4, 4, 3 metals in each plane. Ir atoms are present in alternate planes with an Ir atom featuring in the peripheral bimetallic plane, and two Ir atoms featuring on opposite sides of the non-adjacent tetra-metallic plane. The crystal contains two disordered methanol solvent mol-ecules with an additional region of non-modelled electron density corrected for using the SQUEEZE routine in PLATON [Spek (2015 ▸). Acta Cryst. C71, 9-18]. The given chemical formula and other crystal data do not take into account the unmodelled methanol solvent mol-ecule(s).

Machine-Learning-Based Prediction of Client Distress From Session Recordings.

Natural language processing (NLP) is a subfield of machine learning that may facilitate the evaluation of therapist-client interactions and provide feedback to therapists on client outcomes on a large scale. However, there have been limited studies applying NLP models to client outcome prediction that have (a) used transcripts of therapist-client interactions as direct predictors of client symptom improvement, (b) accounted for contextual linguistic complexities, and (c) used best practices in classical training and test splits in model development. Using 2,630 session recordings from 795 clients and 56 therapists, we developed NLP models that directly predicted client symptoms of a given session based on session recordings of the previous session (Spearman's rho =0.32, p<.001). Our results highlight the potential for NLP models to be implemented in outcome monitoring systems to improve quality of care. We discuss implications for future research and applications.

Inter- and intra-subject similarity in network functional connectivity across a full narrative movie.

Naturalistic paradigms, such as watching movies during functional magnetic resonance imaging, are thought to prompt the emotional and cognitive processes typically elicited in real life situations. Therefore, naturalistic viewing (NV) holds great potential for studying individual differences. Previous studies have primarily focused on using shorter movie clips, geared toward eliciting specific and often isolated emotions, while the potential behind using full narratives depicted in commercial movies as a proxy for real-life experiences has barely been explored. Here, we offer preliminary evidence that a full narrative movie (FNM), that is, a movie covering a complete narrative arc, can capture complex socio-affective dynamics and their links to individual differences. Using the studyforrest dataset, we investigated inter- and intra-subject similarity in network functional connectivity (NFC) of 14 meta-analytically defined networks across a full narrative, audio-visual movie split into eight consecutive movie segments. We characterized the movie segments by valence and arousal portrayed within the sequences, before utilizing a linear mixed model to analyze which factors explain inter- and intra-subject similarity. Our results show that the model best explaining inter-subject similarity comprised network, movie segment, valence and a movie segment by valence interaction. Intra-subject similarity was influenced significantly by the same factors and an additional three-way interaction between movie segment, valence and arousal. Overall, inter- and intra-subject similarity in NFC were sensitive to the ongoing narrative and emotions in the movie. We conclude that FNMs offer complex content and dynamics that might be particularly valuable for studying individual differences. Further characterization of movie features, such as the overarching narratives, that enhance individual differences is needed for advancing the potential of NV research.

Longitudinal increases in mindfulness practice quality are associated with changes in psychological outcomes and not vice versa - a brief report.

With research on mindfulness increasing exponentially, it is important to clarify factors that may influence the success of this approach. We examined the construct of mindfulness meditation practice quality using longitudinal data drawn from a randomized controlled trial testing low-dose mindfulness practices with novice mindfulness practitioners from the general population (N = 48). Results suggest that increases in mindfulness practice quality over time are associated with improvements in psychological outcomes (anxiety, stress, and mindfulness), but not vice versa. Findings join previous research supporting the notion that mindfulness practice quality is an important element of mindfulness training in higher-dose programs as well as low-dose and self-help mindfulness programs and practices. Therefore, this research contributes to finding further support of the importance of mindfulness practice quality as a cause of improvement in psychological distress. This needs to be explored further in future research.

Association Between Parental Problematic Internet Use and Adolescent Depression.

We examined the association between parental problematic internet use (PIU) and adolescent depression and whether this association varied based on internet-related rules. We recruited adolescents ages 13-18 and their parent using national Qualtrics panels (N = 4592 dyads). Measures included the Problematic and Risky Internet Use Screening Scale (PRIUSS-3), the Patient Health Questionnaire (PHQ-9), and the internet specific parenting practice scale (ISPPS). Parental PIU was associated with symptoms of adolescent depression, including suicidal ideation, even when controlling for adolescent PIU (ß = 0.35, 95% CI [0.32, 0.38]). Time-related rules moderated this association in a non-linear way where the association was strongest when time-related rules were unclear / mid-range. The moderation effect was linear for content-related rules, where stricter rules were associated with a weaker association between parent PIU and adolescent depression. Results support clinicians assessing parent PIU when treating depressed adolescents and engaging parents in monitoring their adolescents' internet use content.

Incorporating Individual-Level Treatment Effects and Outcome Preferences Into Personalized Blood Pressure Target Recommendations.

BACKGROUND: There are no shared decision-making frameworks for selecting blood pressure (BP) targets for individuals with hypertension. This study addressed whether results from the SPRINT (Systolic Blood Pressure Intervention Trial) could be tailored to individuals using predicted risks and simulated preferences. METHODS AND RESULTS: Among 8202 SPRINT participants, Cox models were developed and internally validated to predict each individual's absolute difference in risk from intensive versus standard BP lowering for cardiovascular events, cognitive impairment, death, and serious adverse events (AEs). Individual treatment effects were combined using simulated preference weights into a net benefit, which represents a weighted sum of risk differences across outcomes. Net benefits were compared among those above versus below the median AE risk. In simulations for which cardiovascular, cognitive, and death events had much greater weight than the AEs of BP lowering, the median net benefit was 3.3 percentage points (interquartile range [IQR], 2.0-5.7), and 100% of participants had a net benefit favoring intensive BP lowering. When simulating benefits and harms to have similar weights, the median net benefit was 0.8 percentage points (IQR, 0.2-2.2), and 87% had a positive net benefit. Compared with participants at lower risk of AEs from BP lowering, those at higher risk had a greater net benefit from intensive BP lowering despite experiencing more AEs (P<0.001 in both simulations). CONCLUSIONS: Most SPRINT participants had a predicted net benefit that favored intensive BP lowering, but the degree of net benefit varied considerably. Tailoring BP targets using each patient's risks and preferences may provide more refined BP target recommendations.

[Prediction and timely identification of postpartum depression: results of the longitudinal RiPoD study in the context of the literature]. / Vorhersage und frühzeitige Identifikation einer postpartalen Depression: Ergebnisse der longitudinalen RiPoD-Studie im Kontext der Literatur.

The first 4-6 weeks after childbirth are defined as the onset time for postpartum depression (PPD). Despite this known time frame there are significant gaps in the identification and treatment of PPD. The risk for postpartum depression (RiPoD) study investigated specific risk factors and predictors of postpartum psychological adjustment processes and the results are presented within the framework of a state of the art review of research. The dynamic neuroplastic changes in the maternal brain during pregnancy and the postpartum period appear to be closely linked to peripartum hormone fluctuations, which jointly influence the development of postpartum mood disorders. Hormonal risk factors such as baby blues and premenstrual syndrome have been found to have a bearing on PPD. The combination of these two factors predicts the risk of PPD with 83% sensitivity within the first week postpartum. Follow-up digital monitoring of symptom development in the first 6 weeks postpartum has enabled an accurate identification of women with PPD. Understanding the interaction between hormone fluctuations, neuroplasticity and psychiatric disorders should be an important target for future research. Early identification and diagnosis of PPD can be easily integrated into the clinical routine and everyday life.

The uniqueness of human vulnerability to brain aging in great ape evolution.

Aging is associated with progressive gray matter loss in the brain. This spatially specific, morphological change over the life span in humans is also found in chimpanzees, and the comparison between these great ape species provides a unique evolutionary perspective on human brain aging. Here, we present a data-driven, comparative framework to explore the relationship between gray matter atrophy with age and recent cerebral expansion in the phylogeny of chimpanzees and humans. In humans, we show a positive relationship between cerebral aging and cortical expansion, whereas no such relationship was found in chimpanzees. This human-specific association between strong aging effects and large relative cortical expansion is particularly present in higher-order cognitive regions of the ventral prefrontal cortex and supports the "last-in-first-out" hypothesis for brain maturation in recent evolutionary development of human faculties.

Design and Optimization of Selectivity-Tunable Toll-like Receptor 7/8 Agonists as Novel Antibody-Drug Conjugate Payloads.

Toll-like receptors 7 and 8 are involved in modulating the adaptive and innate immune responses, and their activation has shown promise as a therapeutic strategy in the field of immuno-oncology. While systemic exposure to TLR7/8 agonists can result in poor tolerance, combination therapies and targeted delivery through antibody-drug conjugates (ADCs) can help mitigate adverse effects. Described herein is the identification of a novel and potent series of pyrazolopyrimidine-based TLR7/8 agonists with tunable receptor selectivity. Representative agonists from this series were successfully able to induce the production of various proinflammatory cytokines and chemokines from human peripheral blood mononuclear cells. Anti-HER2-25 and anti-HER2-26 ADCs made from this class of payloads demonstrated mechanism-based activation of TLR7/8 in a THP1/N87 coculture system.

Markers of Biological Brain Aging Mediate Effects of Vascular Risk Factors on Cognitive and Motor Functions: A Multivariate Imaging Analysis of 40,579 Individuals.

The increasing global life expectancy brings forth challenges associated with age-related cognitive and motor declines. To better understand underlying mechanisms, we investigated the connection between markers of biological brain aging based on magnetic resonance imaging (MRI), cognitive and motor performance, as well as modifiable vascular risk factors, using a large-scale neuroimaging analysis in 40,579 individuals of the population-based UK Biobank and Hamburg City Health Study. Employing partial least squares correlation analysis (PLS), we investigated multivariate associative effects between three imaging markers of biological brain aging - relative brain age, white matter hyperintensities of presumed vascular origin, and peak-width of skeletonized mean diffusivity - and multi-domain cognitive test performances and motor test results. The PLS identified a latent dimension linking higher markers of biological brain aging to poorer cognitive and motor performances, accounting for 94.7% of shared variance. Furthermore, a mediation analysis revealed that biological brain aging mediated the relationship of vascular risk factors - including hypertension, glucose, obesity, and smoking - to cognitive and motor function. These results were replicable in both cohorts. By integrating multi-domain data with a comprehensive methodological approach, our study contributes evidence of a direct association between vascular health, biological brain aging, and functional cognitive as well as motor performance, emphasizing the need for early and targeted preventive strategies to maintain cognitive and motor independence in aging populations.

Does Spinal Cord Stimulation Improve Sleep Disturbances Independently of Pain Relief in Patients With Chronic Pain? An Explorative, Observational Study.

OBJECTIVES: Chronic pain poses a significant health challenge worldwide and is associated with both disability and reduced quality of life. Sleep disturbances are reported in 67% to 88% of patients with chronic pain. Pain and sleep affect each other reciprocally; we aimed to study this bidirectional relationship in patients treated with spinal cord stimulation (SCS) for chronic pain. Specifically, we investigated whether sleep improves after treatment with SCS and whether this improvement may be mediated by pain reduction. MATERIALS AND METHODS: An observational cohort study was conducted in patients with chronic neuropathic pain treated with SCS at a single neurosurgical department in Denmark. Outcomes were assessed preoperatively and at three, six, and 12 months postoperatively, and thereafter annually. Primary outcomes were pain intensity (numeric rating scale) and insomnia at first follow-up (Insomnia Severity Index). The association between sleep and pain was investigated using linear regression and mediation analysis. RESULTS: Forty-three patients were included in the study. The mean insomnia score was reduced by 25% from 18.1 (SD 6.0) to 13.5 (SD 6.6) (p = 0.0001). Pain intensity was reduced 38% from 7.4 (SD 1.6) to 4.6 (SD 2.1) at the first follow-up (p ≤ 0.0001). Changes in pain and changes in insomnia scores were significantly but weakly associated (regression coefficient = 1.3, 95% CI [0.3; 2.2], p = 0.008, r2 = 15.7%); and changes in pain score were not found to mediate changes in sleep score (ß = -0.02, 95% CI [-0.15; 0.11], p = 0.76). CONCLUSIONS: We found that patients treated with SCS showed significant improvements in both insomnia and pain intensity at first follow-up. Improvements in insomnia and pain intensity were significantly but weakly associated, and improvements in pain intensity score did not mediate improvements in insomnia score. Thus, improvements in self-reported insomnia in patients treated with SCS for chronic pain may predominantly be caused by other factors than reduced pain intensity.

Adolescent maturation of cortical excitation-inhibition balance based on individualized biophysical network modeling.

The balance of excitation and inhibition is a key functional property of cortical microcircuits which changes through the lifespan. Adolescence is considered a crucial period for the maturation of excitation-inhibition balance. This has been primarily observed in animal studies, yet human in vivo evidence on adolescent maturation of the excitation-inhibition balance at the individual level is limited. Here, we developed an individualized in vivo marker of regional excitation-inhibition balance in human adolescents, estimated using large-scale simulations of biophysical network models fitted to resting-state functional magnetic resonance imaging data from two independent cross-sectional (N = 752) and longitudinal (N = 149) cohorts. We found a widespread relative increase of inhibition in association cortices paralleled by a relative age-related increase of excitation, or lack of change, in sensorimotor areas across both datasets. This developmental pattern co-aligned with multiscale markers of sensorimotor-association differentiation. The spatial pattern of excitation-inhibition development in adolescence was robust to inter-individual variability of structural connectomes and modeling configurations. Notably, we found that alternative simulation-based markers of excitation-inhibition balance show a variable sensitivity to maturational change. Taken together, our study highlights an increase of inhibition during adolescence in association areas using cross sectional and longitudinal data, and provides a robust computational framework to estimate microcircuit maturation in vivo at the individual level.

Understanding the Implementation of Informal Meditation Practice in a Smartphone-Based Intervention: A Qualitative Analysis.

Objectives: Informal practice (i.e., brief meditation practices incorporated spontaneously into daily activities) may be important for increasing the efficacy and accessibility of meditation-based interventions (MedBIs). However, the facilitators and barriers to engaging in informal practice are largely unknown. The current study aimed to investigate factors associated with the implementation of informal practice. Method: Participants were drawn from a randomized trial testing the effects of 5- versus 15-min daily meditation practice in a 4-week smartphone-delivered meditation training. Qualitative interviews on informal practice were conducted with 17 participants (mean age: 37.12 years; 82.35% female; 52.94% non-Latinx White) following the intervention. Given that prior knowledge on this topic is limited, inductive content analysis was utilized to characterize participants' experiences in relation to implementing informal practice. Results: Four overarching categories emerged from the data, namely (a) reported benefits of informal practice, (b) integration of informal practice, (c) perceived barriers to informal practice, and (d) recommended facilitators of informal practice. Conclusion: This study underscores the importance of addressing barriers and facilitators (e.g., providing personalized app features, reminders, social support, and repeating intervention content) to encourage individuals' informal practice. Findings provide suggestions for methods to increase engagement in informal practice, which may, in turn, increase the accessibility and effectiveness of MedBIs. Preregistration: The larger trial from which the qualitative interview participants were drawn was preregistered through clinicaltrials.gov (NCT05229406) and the Open Science Framework (https://osf.io/fszvj/?view_only=039b14ccbf8848bd99808c983070b635). The qualitative analyses reported here were not preregistered.

Knockdowns of CD3zeta Chain in Primary NK Cells Illustrate Modulation of Antibody-Dependent Cellular Cytotoxicity Against Human Immunodeficiency Virus-1.

Multifaceted natural killer (NK) cell activities are indispensable for controlling human immunodeficiency virus (HIV)-1 transmission and pathogenesis. Among the diverse functions of NK cells, antibody-dependent cellular cytotoxicity (ADCC) has been shown to predict better HIV-1 protection. ADCC is initiated by the engagement of an Fc γ receptor CD16 with an Fc portion of the antibody, leading to phosphorylation of the CD3 ζ chain (CD3ζ) and Fc receptor γ chain (FcRγ) as well as downstream signaling activation. Though CD3ζ and FcRγ were thought to have overlapping roles in NK cell ADCC, several groups have reported that CD3ζ-mediated signals trigger a more robust ADCC. However, few studies have illustrated the direct contribution of CD3ζ in HIV-1-specific ADCC. To further understand the roles played by CD3ζ in HIV-1-specific ADCC, we developed a CD3ζ knockdown system in primary human NK cells. We observed that HIV-1-specific ADCC was inhibited by CD3ζ perturbation. In summary, we demonstrated that CD3ζ is important for eliciting HIV-1-specific ADCC, and this dynamic can be utilized for NK cell immunotherapeutics against HIV-1 infection and other diseases.

The Clinical and Economic Burden of Antibiotic Use in Pediatric Patients With Varicella Infection: A Retrospective Cohort Analysis of Real-World Data in England.

BACKGROUND: Varicella is a highly infectious disease, particularly affecting children, that can lead to complications requiring antibiotics or hospitalization. Antibiotic use for varicella management is poorly documented. This study assessed antibiotic use for varicella and its complications in a pediatric population in England. METHODS: Data were drawn from medical records in the Clinical Practice Research Datalink and Hospital Episode Statistics data sets. The study included patients <18 years old with varicella diagnosed during 2014-2018 and 3-month follow-up available. We determined varicella-related complications, medication use, healthcare resource utilization, and costs from diagnosis until 3 months after diagnosis. RESULTS: We identified 114 578 children with a primary varicella diagnosis. Of these, 7.7% (n = 8814) had a varicella-related complication, the most common being ear, nose, and throat related (37.1% [n = 3271]). In all, 25.9% (n = 29 706 of 114 578) were prescribed antibiotics. A higher proportion of patients with complications than without complications were prescribed antibiotics (64.3% [n = 5668 of 8814] vs 22.7% [n = 24 038 of 105 764]). Mean annualized varicella-related costs were £2 231 481 for the study cohort. Overall, antibiotic prescriptions cost approximately £262 007. CONCLUSIONS: This study highlights high antibiotic use and healthcare resource utilization associated with varicella management, particularly in patients with complications. A national varicella vaccination program in England may reduce varicella burden and related complications, medication use, and costs.