Early life stress is associated with earlier emergence of permanent molars.

Exposure to adversity can accelerate biological aging. However, existing biomarkers of early aging are either costly and difficult to collect, like epigenetic signatures, or cannot be detected until late childhood, like pubertal onset. We evaluated the hypothesis that early adversity is associated with earlier molar eruption, an easily assessed measure that has been used to track the length of childhood across primates. In a preregistered analysis (n = 117, ages 4 to 7 y), we demonstrate that lower family income and exposure to adverse childhood experiences (ACEs) are significantly associated with earlier eruption of the first permanent molars, as rated in T2-weighted magnetic resonance images (MRI). We replicate relationships between income and molar eruption in a population-representative dataset (National Health and Nutrition Examination Survey; n = 1,973). These findings suggest that the impact of stress on the pace of biological development is evident in early childhood, and detectable in the timing of molar eruption.

The Age of Reason: Functional Brain Network Development during Childhood.

Human childhood is characterized by dramatic changes in the mind and brain. However, little is known about the large-scale intrinsic cortical network changes that occur during childhood because of methodological challenges in scanning young children. Here, we overcome this barrier by using sophisticated acquisition and analysis tools to investigate functional network development in children between the ages of 4 and 10 years ([Formula: see text]; 50 female, 42 male). At multiple spatial scales, age is positively associated with brain network segregation. At the system level, age was associated with segregation of systems involved in attention from those involved in abstract cognition, and with integration among attentional and perceptual systems. Associations between age and functional connectivity are most pronounced in visual and medial prefrontal cortex, the two ends of a gradient from perceptual, externally oriented cortex to abstract, internally oriented cortex. These findings suggest that both ends of the sensory-association gradient may develop early, in contrast to the classical theories that cortical maturation proceeds from back to front, with sensory areas developing first and association areas developing last. More mature patterns of brain network architecture, controlling for age, were associated with better visuospatial reasoning abilities. Our results suggest that as cortical architecture becomes more specialized, children become more able to reason about the world and their place in it.SIGNIFICANCE STATEMENT Anthropologists have called the transition from early to middle childhood the "age of reason", when children across cultures become more independent. We employ cutting-edge neuroimaging acquisition and analysis approaches to investigate associations between age and functional brain architecture in childhood. Age was positively associated with segregation between cortical systems that process the external world and those that process abstract phenomena like the past, future, and minds of others. Surprisingly, we observed pronounced development at both ends of the sensory-association gradient, challenging the theory that sensory areas develop first and association areas develop last. Our results open new directions for research into how brains reorganize to support rapid gains in cognitive and socioemotional skills as children reach the age of reason.

Daily fluctuations in young children's persistence.

Children's behavior changes from day to day, but the factors that contribute to its variability are understudied. We developed a novel repeated measures paradigm to study children's persistence by capitalizing on a task that children complete every day: toothbrushing (N = 81; 48% female; 36-47 months; 80% white, 14% Multiracial, 10% Hispanic, 2% Asian, 1% Black; 1195 observations collected between January 2019 and March 2020). Children brushed longer on days when their parents used more praise (d = .23) and less instruction (d = -.22). Sensitivity to mood, sleep, and parent stress varied across children, suggesting that identifying the factors that shape an individual child's persistence could lead to personalized interventions.

Children Persist Less When Adults Take Over.

Children need to learn to persist through challenges, yet adults sometimes step in to solve problems for them. Here, we looked at how adult taking over related to children's persistence. In an observational study (N = 34, ages 4-8), we found that parents who took over more often during a challenging puzzle task rated their children as dispositionally less persistent. To establish whether taking over can cause reduced persistence, we ran two preregistered experiments (N = 150, ages 4-5). Children assigned to a taking over condition persisted less on a subsequent task compared to those in a teaching or a baseline condition. Reframing the context did not ameliorate the negative impact of taking over. The results suggest that taking over impairs children's persistence.

Clinical and economic burden of pre-emptive therapy of cytomegalovirus infection in hospitalized allogeneic hematopoietic cell transplant recipients.

Cytomegalovirus (CMV) infection remains a major complication after allogeneic hematopoietic cell transplantation (allo-HCT). We conducted a retrospective study to determine the clinical and economic burden of pre-emptive therapy (PET) for CMV infection in 100 consecutive hospitalized adult CMV positive serostatus allo-HCT recipients and compared their hospitalization cost with allo-HCT recipients hospitalized with graft vs host disease without CMV infection (control group) and across 19 US cancer centers for hospitalized patients with CMV infection between 2012 and 2015 (Vizient database). A total of 192 CMV episodes of PET for CMV infection occurred within 1 year post-HCT. PET consisted of ganciclovir (41% of episodes), foscarnet (40%), and valganciclovir (38%) with the longest average length of stay in foscarnet-treated patients (41 days). The average direct cost per patient admitted for PET was $116 976 (range: $7866-$641 841) compared with $12 496 (range: $2004-$43 069) in the control group (P < .0001). The total direct cost per encounter was significantly higher in patients treated with foscarnet and had nephrotoxicity ($284 006) compared with those who did not ($112 195). The average cost amongst the 19 US cancer centers, including our institution, was $42 327 with major disparities in cost and clinical outcomes. PET for CMV infection is associated with high economic burden in allo-HCT recipients.

Understanding Thyroidectomy Cost Variations Among National Cancer Institute-Designated Cancer Centers.

BACKGROUND: The cost of thyroidectomy varies across the USA, while the causes of this variation are poorly understood. We examined the cost of inpatient thyroidectomy among National Cancer Institute-designated cancer centers nationwide to determine why it differs. METHODS: A retrospective study of inpatient thyroidectomies was performed using the Vizient Clinical Data Base. Fifty-two of 70 eligible hospitals were grouped into five geographic regions (Mid-Atlantic and New England, East Central, South Atlantic, West Central, and Mountain and Pacific). We identified drivers of cost variation in the five geographic regions and used risk adjustment model to evaluate the rationality of cost from each hospital. RESULTS: Male sex, more extended hospital stays, and occurrence of complications were consistently associated with increased costs in all regions. Also, the cost was significantly lower in the Mid-Atlantic and New England region. The higher than expected costs did not correlate well with the case mix index among hospitals (p = 0.289), but the lower than expected costs were more common in high-volume hospitals. The average length of stay was the shortest in high-volume hospitals, which might account for the lower cost in the Mid-Atlantic and New England region; however, the overages of costs still varied widely among hospitals in all regions even if the length of stay was adjusted. CONCLUSIONS: Cost variation may result from both patient-related factors and volume-related practice pattern differences among hospitals. A more standard of care and charge transparency is still needed for patients seeking affordable care at cancer centers.

Early development of letter specialization in left fusiform is associated with better word reading and smaller fusiform face area.

A functional region of left fusiform gyrus termed "the visual word form area" (VWFA) develops during reading acquisition to respond more strongly to printed words than to other visual stimuli. Here, we examined responses to letters among 5- and 6-year-old early kindergarten children (N = 48) with little or no school-based reading instruction who varied in their reading ability. We used functional magnetic resonance imaging (fMRI) to measure responses to individual letters, false fonts, and faces in left and right fusiform gyri. We then evaluated whether signal change and size (spatial extent) of letter-sensitive cortex (greater activation for letters versus faces) and letter-specific cortex (greater activation for letters versus false fonts) in these regions related to (a) standardized measures of word-reading ability and (b) signal change and size of face-sensitive cortex (fusiform face area or FFA; greater activation for faces versus letters). Greater letter specificity, but not letter sensitivity, in left fusiform gyrus correlated positively with word reading scores. Across children, in the left fusiform gyrus, greater size of letter-sensitive cortex correlated with lesser size of FFA. These findings are the first to suggest that in beginning readers, development of letter responsivity in left fusiform cortex is associated with both better reading ability and also a reduction of the size of left FFA that may result in right-hemisphere dominance for face perception.

Developmental Correlates of Accelerated Molar Eruption in Early Childhood.

Background: Adversity has been linked to accelerated maturation. Molar eruption is a simple and scalable way to identify early maturation, but its developmental correlates remain unexplored. Thus, we examined whether accelerated maturation as indexed by molar eruption is associated with children's mental health or cognitive skills. Methods: Molar eruption was evaluated from T2-weighted magnetic resonance imaging in 117 children (63 female; ages 4-7 years). Parents reported on child mental health with the Child Behavior Checklist. Children completed standardized assessments of fluid reasoning, working memory, processing speed, crystallized knowledge, and math performance. Relationships between molar eruption and developmental outcomes were examined using linear models, with age, gender, and stress risk as covariates. Results: Earlier molar eruption was positively associated with children's externalizing symptoms (false discovery rate-corrected p [pFDR] = .027) but not internalizing symptoms, and the relationship with externalizing symptoms did not hold when controlling for stress risk. Earlier molar eruption was negatively associated with fluid reasoning (pFDR < .001), working memory (pFDR = .033), and crystallized knowledge (pFDR = .001). The association between molar eruption and both reasoning and crystallized knowledge held when controlling for stress risk. Molar eruption also partially mediated associations between stress risk and both reasoning (proportion mediated = 0.273, p = .004) and crystallized knowledge (proportion mediated = 0.126, p = .016). Conclusions: Accelerated maturation, as reflected in early molar eruption, may have consequences for cognitive development, perhaps because it constrains brain plasticity. Knowing the pace of a child's maturation may provide insight into the impact of a child's stress history on their cognitive development.

Individual differences in T1w/T2w ratio development during childhood.

Myelination is a key developmental process that promotes rapid and efficient information transfer. Myelin also stabilizes existing brain networks and thus may constrain neuroplasticity, defined here as the brain's potential to change in response to experiences rather than the canonical definition as the process of change. Characterizing individual differences in neuroplasticity may shed light on mechanisms by which early experiences shape learning, brain and body development, and response to interventions. The T1-weighted/T2-weighted (T1w/T2w) MRI signal ratio is a proxy measure of cortical microstructure and thus neuroplasticity. Here, in pre-registered analyses, we investigated individual differences in T1w/T2w ratios in children (ages 4-10, n = 157). T1w/T2w ratios were positively associated with age within early-developing sensorimotor and attention regions. We also tested whether socioeconomic status, cognition (crystallized knowledge or fluid reasoning), and biological age (as measured with molar eruption) were related to T1w/T2w signal but found no significant effects. Associations among T1w/T2w ratios, early experiences, and cognition may emerge later in adolescence and may not be strong enough to detect in moderate sample sizes.

Multilayer network associations between the exposome and childhood brain development.

Growing up in a high poverty neighborhood is associated with elevated risk for academic challenges and health problems. Here, we take a data-driven approach to exploring how measures of children's environments relate to the development of their brain structure and function in a community sample of children between the ages of 4 and 10 years. We constructed exposomes including measures of family socioeconomic status, children's exposure to adversity, and geocoded measures of neighborhood socioeconomic status, crime, and environmental toxins. We connected the exposome to two structural measures (cortical thickness and surface area, n = 170) and two functional measures (participation coefficient and clustering coefficient, n = 130). We found dense connections within exposome and brain layers and sparse connections between exposome and brain layers. Lower family income was associated with thinner visual cortex, consistent with the theory that accelerated development is detectable in early-developing regions. Greater neighborhood incidence of high blood lead levels was associated with greater segregation of the default mode network, consistent with evidence that toxins are deposited into the brain along the midline. Our study demonstrates the utility of multilayer network analysis to bridge environmental and neural explanatory levels to better understand the complexity of child development.

Comparison of LACE and HOSPITAL Readmission Risk Scores for CMS Target and Nontarget Conditions.

This study evaluated the utility and performance of the LACE index and HOSPITAL score with consideration of the type of diagnoses and assessed the accuracy of these models for predicting readmission risks in patient cohorts from 2 large academic medical centers. Admissions to 2 hospitals from 2011 to 2015, derived from the Vizient Clinical Data Base and regional health information exchange, were included in this study (291 886 encounters). Models were assessed using Bayesian information criterion and area under the receiver operating characteristic curve. They were compared in CMS diagnosis-based cohorts and in 2 non-CMS cancer diagnosis-based cohorts. Overall, both models for readmission risk performed well, with LACE performing slightly better (area under the receiver operating characteristic curve 0.73 versus 0.69; P ≤ 0.001). HOSPITAL consistently outperformed LACE among 4 CMS target diagnoses, lung cancer, and colon cancer. Both LACE and HOSPITAL predict readmission risks well in the overall population, but performance varies by salient, diagnosis-based risk factors.

Early stressful experiences are associated with reduced neural responses to naturalistic emotional and social content in children.

How do children's experiences relate to their naturalistic emotional and social processing? Because children can struggle with tasks in the scanner, we collected fMRI data while 4-to-11-year-olds watched a short film with positive and negative emotional events, and rich parent-child interactions (n = 70). We captured broad, normative stressful experiences by examining socioeconomic status (SES) and stressful life events, as well as children's more proximal experiences with their parents. For a sub-sample (n = 30), parenting behaviors were measured during a parent-child interaction, consisting of a picture book, a challenging puzzle, and free play with novel toys. We characterized positive parenting behaviors (e.g., warmth, praise) and negative parenting behaviors (e.g., harsh tone, physical control). We found that higher SES was related to greater activity in medial orbitofrontal cortex during parent-child interaction movie events. Negative parenting behaviors were associated with less activation of the ventral tegmental area and cerebellum during positive emotional events. In a region-of-interest analysis, we found that stressful life events and negative parenting behaviors were associated with less activation of the amygdala during positive emotional events. These exploratory results demonstrate the promise of using movie fMRI to study how early experiences may shape emotional, social, and motivational processes.

Individual differences in frontoparietal plasticity in humans.

Neuroplasticity, defined as the brain's potential to change in response to its environment, has been extensively studied at the cellular and molecular levels. Work in animal models suggests that stimulation to the ventral tegmental area (VTA) enhances plasticity, and that myelination constrains plasticity. Little is known, however, about whether proxy measures of these properties in the human brain are associated with learning. Here, we investigated the plasticity of the frontoparietal system by asking whether VTA resting-state functional connectivity and myelin map values (T1w/T2w ratios) predicted learning after short-term training on the adaptive n-back (n = 46, ages 18-25). We found that stronger baseline connectivity between VTA and lateral prefrontal cortex predicted greater improvements in accuracy. Lower myelin map values predicted improvements in response times, but not accuracy. Our findings suggest that proxy markers of neural plasticity can predict learning in humans.

Early childhood stress is associated with blunted development of ventral tegmental area functional connectivity.

Early life stress increases risk for later psychopathology, due in part to changes in dopaminergic brain systems that support reward processing and motivation. Work in animals has shown that early life stress has a profound impact on the ventral tegmental area (VTA), which provides dopamine to regions including nucleus accumbens (NAcc), anterior hippocampus, and medial prefrontal cortex (mPFC), with cascading effects over the course of development. However, little is known about how early stress exposure shifts the developmental trajectory of mesocorticolimbic circuitry in humans. In the current study, 88 four- to nine-year-old children participated in resting-state fMRI. Parents completed questionnaires on their children's chronic stress exposure, including socioeconomic status (SES) and adverse childhood experiences (ACEs). We found an age x SES interaction on VTA connectivity, such that children from higher SES backgrounds showed a positive relationship between age and VTA-mPFC connectivity. Similarly, we found an age x ACEs exposure interaction on VTA connectivity, such that children with no ACEs exposure showed a positive relationship between age and VTA-mPFC connectivity. Our findings suggest that early stress exposure relates to the blunted maturation of VTA connectivity in young children, which may lead to disrupted reward processing later in childhood and beyond.

Harnessing Behavioral Economics Principles to Promote Better Surgeon Accountability for Operating Room Cost: A Prospective Study.

BACKGROUND: Operating room (OR) cost accounts for a significant portion of inpatient spending, but most surgeons are unaware of the costs of OR implants and supplies. We leveraged behavioral economics principles and a cost transparency tool to have an impact on discretionary OR spending (disposable supplies). STUDY DESIGN: We performed a single-institution, prospective study, from January to December 2018, across 3 departments: urology, thoracic, and endocrine. Two self-selected procedures per department were subjected to intraoperative supply cost (ISC) feedback via a custom dashboard and monthly email reports. Behavioral economics principles like choice overload, social ranking, and threshold effects were leveraged during study design. The primary outcome of percentage change in the department-level mean ISC, as determined via an interrupted time-series mixed effects model, was compared between the intervention year (2018) and "pre-baseline" (2016) and "baseline" (2017) years. RESULTS: A total of 2,853 procedures and 26 surgeons comprised our analytical sample. Costs decreased in 5 of the 6 procedures in 2018. On average, there was a significant monthly decrease in costs of approximately 0.5% over the study period (p = 0.0004). Post-intervention, there was a nonsignificant additional decrease of 0.6% in monthly cost (p = 0.0648). Overall cost significantly decreased by 20% due to the intervention (p < 0.0001). Similar results were noted on sensitivity analysis. There were no significant changes in the incidence of postoperative complication due to our intervention. CONCLUSIONS: Deployment of a cost feedback tool using behavioral economics principles resulted in a significant decrease in OR spending without negatively affecting complication rate.

Demonstrating value: association of cost and quality outcomes with implementation of a value-driven oncology-hospitalist inpatient collaboration for patients with lung cancer.

The hospitalist model of care has gained favour in many hospital systems for the value, cost-effectiveness and quality of care that hospitalists provide. Hospitalists are experts in high-acuity medical problems of patients and they are intimately knowledgeable about hospital operations that enable efficiency of patient care. This results in tremendous cost-savings for institutions especially since hospitalists are also obligated to be involved in quality and practice improvement initiatives. The University of Texas MD Anderson Cancer Center employs oncology-hospitalists for many of their patients with cancer needing inpatient services. This physician team has expertise in both cancer-related and comorbidity-related reasons for hospitalisation. In September 2015, the thoracic and head and neck medical oncology team started a collaboration with the Oncology Hospitalist team whereby a proportion of patients with thoracic malignancies were directly admitted to hospitalists for inpatient care. To determine the value of this collaboration, a pre- and post- implementation study was done to compare quality outcomes such as readmission rates and length of stay (LOS) between the two groups. Adjusted outcomes showed that readmission rates were similar for both physician groups both at baseline and after implementation of the collaborative (p=0.680 and p=0.840, respectively). Median LOS was similar for both groups at baseline (4 days) and was not significantly different post-implementation (4vs5 days, p=0.07). The adjusted cost of a hospitalisation was also similar for hospitalist encounters and thoracic oncology encounters. This initial study showed that quality of care remained comparable for patients with lung cancer who were admitted to either service. With possibly shorter LOS but comparable readmission outcomes and adjusted cost for patients discharged from the hospitalist service, there is a strong value benefit for the implemented Thoracic Oncology-Hospitalist inpatient collaborative.

Associations between cortical thickness and reasoning differ by socioeconomic status in development.

Although lower socioeconomic status (SES) is generally negatively associated with performance on cognitive assessments, some children from lower-SES backgrounds perform as well as their peers from higher-SES backgrounds. Yet little research has examined whether the neural correlates of individual differences in cognition vary by SES. The current study explored whether relationships between cortical structure and fluid reasoning differ by SES in development. Fluid reasoning, a non-verbal component of IQ, is supported by a distributed frontoparietal network, with evidence for a specific role of rostrolateral prefrontal cortex (RLPFC). In a sample of 115 4-7-year old children, bilateral thickness of RLPFC differentially related to reasoning by SES: thicker bilateral RLPFC positively correlated with reasoning ability in children from lower-SES backgrounds, but not in children from higher-SES backgrounds. Similar results were found in an independent sample of 59 12-16-year old adolescents. Furthermore, young children from lower-SES backgrounds with strong reasoning skills were the only group to show a positive relationship between RLPFC thickness and age. In sum, we found that relationships between cortical thickness and cognition differ by SES during development.

Disrupted left fusiform response to print in beginning kindergartners is associated with subsequent reading.

Dyslexia is a common neurobiological disorder in which a child fails to acquire typical word reading skills despite adequate opportunity and intelligence. The visual word form area (VWFA) is a region within the left fusiform gyrus that specializes for print over the course of reading acquisition and is often hypoactivated in individuals with dyslexia. It is currently unknown whether atypicalities in this brain region are already present in kindergarten children who will subsequently develop dyslexia. Here, we measured fMRI activation in response to letters and false fonts in bilateral fusiform gyrus in children with and without risk for dyslexia (defined by family history or low scores on assessments of pre-reading skills, such as phonological awareness). We then followed these children longitudinally through the end of second grade to evaluate whether brain activation patterns in kindergarten were related to second-grade reading outcomes. Compared to typical readers who exhibited no risk factors for reading impairment in kindergarten, there was significant hypoactivation to both letters and false-fonts in the left fusiform gyrus in at-risk children who subsequently developed reading impairment, but not in at-risk children who developed typical reading skills. There were no significant differences in letter- or false-font responses in the right fusiform gyrus among the groups. The finding that hypoactivation to print in the VWFA is present in children who subsequently develop reading impairment even prior to the onset of formal reading instruction suggests that atypical responses to print play an early role in the development of reading impairments such as dyslexia.

Amygdala-medial prefrontal cortex connectivity relates to stress and mental health in early childhood.

Early life stress has been associated with disrupted functional connectivity between the amygdala and medial prefrontal cortex (mPFC), but it is unknown how early in development stress-related differences in amygdala-mPFC connectivity emerge. In a resting-state functional connectivity (rs-FC) analysis with 79 four- to seven-year-old children, we found a significant correlation between more adverse experiences and weaker amygdala-mPFC rs-FC. We also found that weaker amygdala-mPFC rs-FC was associated with higher levels of aggressive behavior and attention problems. These findings suggest that the impact of stress on emotional circuitry is detectable in early childhood and that this impact is associated with mental health difficulties. Connectivity in this circuit may be useful as a marker for mental health risk and for tracking the efficacy of early interventions.

What Is the Real Rate of Surgical Site Infection?

PURPOSE: Surgical site infections (SSIs) are associated with patient morbidity and increased health care costs. Although several national organizations including the University HealthSystem Consortium (UHC), the National Surgical Quality Improvement Program (NSQIP), and the National Healthcare Safety Network (NHSN) monitor SSI, there is no standard reporting methodology. METHODS: We queried the UHC, NSQIP, and NHSN databases from July 2012 to June 2014 for SSI after gynecologic surgery at our institution. Each organization uses different definitions and inclusion and exclusion criteria for SSI. The rate of SSI was also obtained from chart review from April 1 to June 30, 2014. SSI was classified as superficial, deep, or organ space infection. The rates reported by the agencies were compared with the rates obtained by chart review using Fisher's exact test. RESULTS: Overall SSI rates for the databases were as follows: UHC, 1.5%; NSQIP, 8.8%; and NHSN, 2.8% (P < .001). The individual databases had wide variation in the rate of deep infection (UHC, 0.7%; NSQIP, 4.7%; NHSN, 1.3%; P < .001) and organ space infection (UHC, 0.4%; NSQIP, 4.4%; NHSN, 1.4%; P < .001). In agreement with the variation in reporting methodology, only 19 cases (24.4%) were included in more than one database and only one case was included in all three databases (1.3%). CONCLUSION: There is discordance among national reporting agencies tracking SSI. Adopting standardized metrics across agencies could improve consistency and accuracy in assessing SSI rates.