A key step toward understanding psychiatric disorders that disproportionately impact female mental health is delineating the emergence of sex-specific patterns of brain organisation at the critical transition from childhood to adolescence. Prior work suggests that individual differences in the spatial organisation of functional brain networks across the cortex are associated with psychopathology and differ systematically by sex.

We aimed to evaluate the impact of sex on the spatial organisation of person-specific functional brain networks.

We leveraged person-specific atlases of functional brain networks, defined using non-negative matrix factorisation, in a sample of n = 6437 youths from the Adolescent Brain Cognitive Development Study. Across independent discovery and replication samples, we used generalised additive models to uncover associations between sex and the spatial layout (topography) of personalised functional networks (PFNs). We also trained support vector machines to classify participants’ sex from multivariate patterns of PFN topography.

Sex differences in PFN topography were greatest in association networks including the frontoparietal, ventral attention and default mode networks. Machine learning models trained on participants’ PFNs were able to classify participant sex with high accuracy.

Sex differences in PFN topography are robust, and replicate across large-scale samples of youth. These results suggest a potential contributor to the female-biased risk in depressive and anxiety disorders that emerge at the transition from childhood to adolescence.

Antibiotics overuse leads to bacterial resistance. The biomarker procalcitonin rises with bacterial pneumonias and remains normal in viral respiratory tract infections. Its use can distinguish between these etiologies and thus guide antibiotics use. We aimed to quantify the effect of procalcitonin use on clinical decision-making.

A retrospective study, spanning a year at a tertiary care center, where 348 patients hospitalized with aspiration pneumonia and 824 with non-aspiration pneumonia were evaluated with regards to procalcitonin use, the length of stay (LOS) and antibiotics prescribing practices. Descriptive statistics and univariate analyses were applied to the ensemble data. Subsets of cases were manually reviewed and analyzed with descriptive statistics. P < 0.05 indicated statistical significance.

21% of both the aspiration and non-aspiration pneumonia cases had procalcitonin checked. In the ensemble analyses, a check of procalcitonin was more likely to happen in prolonged hospitalizations with aspiration pneumonia. The LOS was statistically the same regardless of procalcitonin results (elevated or normal) for both the aspiration and non-aspiration pneumonia cohorts. The overall use of antibiotics was not affected by the procalcitonin results. After excluding two extreme outliers, the per-person antibiotics cost was not affected by the procalcitonin results. Detailed chart reviews of 33 cases revealed that for the vast majority, the procalcitonin results were not used by clinicians to guide the duration of antibiotics use.

Despite its promise as a biomarker for antibiotics stewardship, procalcitonin results appeared to not be utilized by clinicians as a decision-making tool in the management of pneumonia.

To quantify the impact of patient- and unit-level risk adjustment on infant hospital-onset bacteremia (HOB) standardized infection ratio (SIR) ranking.

A retrospective, multicenter cohort study.

Infants admitted to 284 neonatal intensive care units (NICUs) in the United States between 2016 and 2021.

Expected HOB rates and SIRs were calculated using four adjustment strategies: birthweight (model 1), birthweight and postnatal age (model 2), birthweight and NICU complexity (model 3), and birthweight, postnatal age, and NICU complexity (model 4). Sites were ranked according to the unadjusted HOB rate, and these rankings were compared to rankings based on the four adjusted SIR models.

Compared to unadjusted HOB rate ranking (smallest to largest), the number and proportion of NICUs that left the fourth quartile (worst-performing) following adjustments were as follows: adjusted for birthweight (16, 22.5%), birthweight and postnatal age (19, 26.8%), birthweight and NICU complexity (22, 31.0%), birthweight, postnatal age and NICU complexity (23, 32.4%). Comparing NICUs that moved into the better-performing quartiles after birthweight adjustment to those that remained in the better-performing quartiles regardless of adjustment, the median percentage of low birthweight infants was 17.1% (Interquartile Range (IQR): 15.8, 19.2) vs 8.7% (IQR: 4.8, 12.6); and the median percentage of infants who died was 2.2% (IQR: 1.8, 3.1) vs 0.5% (IQR: 0.01, 12.0), respectively.

Adjusting for patient and unit-level complexity moved one-third of NICUs in the worst-performing quartile into a better-performing quartile. Risk adjustment may allow for a more accurate comparison across units with varying levels of patient acuity and complexity.

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.

We evaluated SARS-CoV-2 anti-nucleocapsid (anti-N) seroconversion and seroreversion rates, risk factors associated with SARS-CoV-2 seroconversion, and COVID-19 risk perceptions among academic healthcare center employees in a rural state.

Among employees aged ≥18 years who completed a screening survey (n = 1,377), we invited all respondents reporting previous COVID-19 (n = 85; 82 accepted) and a random selection of respondents not reporting previous COVID-19 (n = 370; 220 accepted) to participate. Participants completed surveys and provided blood samples at 3-month intervals (T0, T3, T6, T9). We used logistic regression to identify risk factors for seropositivity at T0.

The cohort was primarily direct patient caregivers (205/302; 67.9%), white (278/302; 92.1%), and female (212/302; 70.2%). At T0, 86/302 (28.4%) participants were seropositive. Of the seronegative participants, 6/198 (3.0%), 6/183 (3.3%), and 14/180 (7.8%) had seroconverted at T3, T6, and T9, respectively. The overall seroreversion rate was 6.98% at T9. At T0, nursing staff (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.08, 5.19) and being within six feet of a non-household member outside of work (OR, 2.91; 95% CI, 1.02, 8.33) had significantly higher odds of seropositivity. Vaccination (OR, 0.05; 95% CI, 0.02, 0.12) and face mask use (OR, 0.36; 95% CI, 0.17, 0.78) were protective.

The seroconversion and seroreversion rates were low among participants. Public health and infection prevention measures implemented early in the COVID-19 pandemic – vaccination, face mask use, and social distancing – were associated with significantly lower odds of SARS-CoV-2 seropositivity among participants.

BrighT STAR was a diagnostic stewardship collaborative of 14 pediatric intensive care units (PICUs) across the United States designed to standardize and reduce unnecessary blood cultures and study the impact on patient outcomes and broad-spectrum antibiotic use. We now examine the implementation process in detail to understand how sites facilitated this diagnostic stewardship program in their PICUs.

A multi-center electronic survey of the 14 BrighT STAR sites, based on qualitative data about the implementation process collected during the primary phase of BrighT STAR.

14 PICUs enrolled in BrighT STAR.

Site leads at each enrolled site.

An electronic survey guided by implementation science literature and based on data collected during BrighT STAR was administered to all 14 sites after completion of the primary phase of the collaborative.

10 specific tasks appear critical to implementing blood culture diagnostic stewardship, with variability in site-level strategies employed to accomplish those tasks. Sites rated certain tasks and strategies as highly important. Strategies used in top-performing sites were distinct from those used in lower-performing sites. Certain strategies may link to drivers of culture overuse and represent key targets for changing clinician behavior.

BrighT STAR offers important insights into the tasks and strategies used to facilitate successful diagnostic stewardship in the PICU. More work is needed to compare specific strategies and optimize stewardship outcomes in this complex environment.

Blood Culture Improvement Guidelines and Diagnostic Stewardship for Antibiotic Reduction in Critically Ill Children (Bright STAR). NCT03441126. https://www.clinicaltrials.gov/study/NCT03441126?term=Bright%20STAR&aggFilters=status:com&checkSpell=false&rank=1

Estimate the risk for household transmission of Methicillin-Resistant Staphylococcus aureus (MRSA) following exposure to infected family members or family members recently discharged from a hospital.

Analysis of monthly MRSA incidence from longitudinal insurance claims using the Merative MarketScan Commercial and Medicare (2001–2021) databases.

Visits to inpatient, emergency department, and outpatient settings.

Households with ≥2 family members enrolled in the same insurance plan for the entire month.

We estimated a monthly incidence model, where enrollees were binned into monthly enrollment strata defined by demographic, patient, and exposure characteristics. Monthly incidence within each stratum was computed, and a regression analysis was used to estimate the incidence rate ratio (IRR) associated with household exposures of interest while accounting for potential confounding factors.

A total of 157,944,708 enrollees were included and 424,512 cases of MRSA were identified. Across all included enrollees, exposure to a family member with MRSA in the prior 30 days was associated with significantly increased risk of infection (IRR: 71.03 [95% CI, 67.73–74.50]). After removing enrollees who were hospitalized or exposed to a family member with MRSA, exposure to a family member who was recently discharged from the hospital was associated with increased risk of infection (IRR: 1.44 [95% CI, 1.39–1.49]) and the risk of infection increased with the duration of the family member’s hospital stay (P value < .001).

Exposure to a recently hospitalized and discharged family member increased the risk of MRSA infection in a household even when the hospitalized family member was not diagnosed with MRSA.

Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.

Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.

Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).

Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.

Compare the effectiveness of multiple mitigation measures designed to protect nursing home residents from infectious disease outbreaks.

Agent-based simulation study.

Simulation environment of a small nursing home.

We collected temporally detailed and spatially fine-grained location information from nursing home healthcare workers (HCWs) using sensor motes. We used these data to power an agent-based simulation of a COVID-19 outbreak using realistic time-varying estimates of infectivity and diagnostic sensitivity. Under varying community prevalence and transmissibility, we compared the mitigating effects of (i) regular screening and isolation, (ii) inter-resident contact restrictions, (iii) reduced HCW presenteeism, and (iv) modified HCW scheduling.

Across all configurations tested, screening every other day and isolating positive cases decreased the attack rate by an average of 27% to 0.501 on average, while contact restrictions decreased the attack rate by an average of 35%, resulting in an attack rate of only 0.240, approximately half that of screening/isolation. Combining both interventions impressively produced an attack rate of only 0.029. Halving the observed presenteeism rate led to an 18% decrease in the attack rate, but if combined with screening every 6 days, the effect of reducing presenteeism was negligible. Altering work schedules had negligible effects on the attack rate.

Universal contact restrictions are highly effective for protecting vulnerable nursing home residents, yet adversely affect physical and mental health. In high transmission and/or high community prevalence situations, restricting inter-resident contact to groups of 4 was effective and made highly effective when paired with weekly testing.