Background: Tracheal aspirate bacterial cultures are routinely collected in mechanically ventilated children for the evaluation of ventilator-associated infections (VAIs). However, frequent bacterial colonization of endotracheal and tracheostomy tubes contribute to the marginal performance characteristics of the test for diagnosing VAI. Published literature characterizing drivers of culture collection and the predictive value of positive cultures are limited. Methods: This single-center, retrospective cohort study included children admitted to the pediatric intensive care unit who were receiving mechanical ventilation for at least 48 hours and had 1 or more semiquantitative tracheal aspirate cultures collected between September 1, 2019, and August 31, 2020. Indications for culture collection were determined through medical record review and included fever, hypothermia, tracheal secretion changes, radiographic pneumonia, increased oxygen requirement, and/or increased positive end-expiratory pressure (PEEP). A positive culture was defined as moderate or heavy growth of a noncommensal bacterial organism. A purulent Gram stain was defined as detection of moderate or many white blood cells. Diagnosis of VAI was based on treating-clinician documentation and was ascertained through medical record review. Logistic regression accounting for clustering by patient was performed to estimate the association between indications for culture collection and (1) culture positivity, (2) purulent Gram stain, and (3) diagnosis of VAI. Results: In total, 625 tracheal aspirate cultures were performed in 261 unique patients. Common indications for culture collection included isolated fever or hypothermia (n = 124, 20%), fever with an increase in oxygen requirement or PEEP (n = 71, 11%), isolated increase in oxygen requirement or PEEP (n = 67, 11%), or isolated secretion change (n = 54, 9%) (Figure 1). Overall, 230 cultures (37%) were positive and 218 (35%) Gram stains were purulent. There were no associations between culture indications and a positive culture. Presence of isolated fever was negatively associated with a purulent Gram stain (odds ratio [OR], 0.49; 95% CI, 0.30–0.81; P = .005); otherwise, there were no associations between indication and purulent Gram stain. Finally, in a multivariable model, odds of VAI diagnosis increased with both the number of indications for culture collection and purulent Gram stain, but not with positive culture (Figure 2). Conclusions: Number and type of clinical signs were not associated with tracheal aspirate culture positivity or purulence on Gram stain, but they were associated with a clinical diagnosis of VAI. These findings suggest that positive tracheal aspirate cultures may not aid clinicians in the diagnosis of VAI, and they highlight the opportunity for improved diagnostic stewardship.

Funding: No

Disclosures: None

Figure 1.

Figure 2.

The aim of this review is to present the current options for cardiac output (CO) monitoring in children undergoing cardiac surgery. Current technologies for monitoring identified were a range of invasive, minimally invasive, and non-invasive technologies. These include pulmonary artery catheter, transoesophageal echocardiography, pulse contour analysis, electrical cardiography, and thoracic bioreactance. A literature search was conducted using evidence databases which identified two current guidelines; the NHS Greater Glasgow and Clyde guideline and Royal College of Anaesthetics Guideline. These were appraised using the AGREE II tool and the evidence identified was used to create an overview summary of each technological option for CO monitoring. There is limited evidence regarding the accuracy of modalities available for CO monitoring in paediatric patients during cardiac surgery. Each technology has advantages and disadvantages; however, none could be championed as the most beneficial. Furthermore, a gold standard for CO monitoring has not yet been identified for paediatric populations, nor is it apparent whether one modality is preferable based on the available evidence. Additional evidence using a standardised method for comparing CO measurements should be conducted in order to determine the best option for CO monitoring in paediatrics. Furthermore, cost-effectiveness assessment of each modality should be conducted. Only then will it be possible for clear, evidence-based guidance to be written.

OBJECTIVES/GOALS: Diverse medication-based studies require longitudinal drug dose information. EHRs can provide such data, but multiple mentions of a drug in the same clinical note can yield conflicting dose. We aimed to develop statistical methods which address this challenge by predicting the valid dose in the event that conflicting doses are extracted. METHODS/STUDY POPULATION: We extracted dose information for two test drugs, tacrolimus and lamotrigine, from Vanderbilt EHRs using a natural language processing system, medExtractR, which was developed by our team. A random forest classifier was used to estimate the probability of correctness for each extracted dose on the basis of subject longitudinal dosing patterns and extracted EHR note context. Using this feasibility measure and other features such as a summary of subject dosing history, we developed several statistical models to predict the dose on the basis of the extracted doses. The models developed based on supervised methods included a separate random forest regression, a transition model, and a boosting model. We also considered unsupervised methods and developed a Bayesian hierarchical model. RESULTS/ANTICIPATED RESULTS: We compared model-predicted doses to physician-validated doses to evaluate model performance. A random forest regression model outperformed all proposed models. As this model is a supervised model, its utility would depend on availability of validated dose. Our preliminary result from a Bayesian hierarchical model showed that it can be a promising alternative although performing less optimally. The Bayesian hierarchical model would be especially useful when validated dose data are not available, as it was developed in unsupervised modeling framework and hence does not require validated dose that can be difficult and time consuming to obtain. We evaluated the feasibility of each method for automatic implementation in our drug dosing extraction and processing system we have been developing. DISCUSSION/SIGNIFICANCE OF IMPACT: We will incorporate the developed methods as a part of our complete medication extraction system, which will allow to automatically prepare large longitudinal medication dose datasets for researchers. Availability of such data will enable diverse medication-based studies with drastically reduced barriers to data collection.

Dietary fibre is believed to provide important health benefits including protection from colorectal cancer. However, the evidence on the relationships with different dietary fibre sources is mixed and little is known about which fibre source provides the greatest benefits. We conducted a dose–response meta-analysis of prospective cohorts to summarise the relationships of different fibre sources with colorectal cancer and adenoma risks. Analyses were restricted to publications that reported all fibre sources (cereals, vegetables, fruits, legumes) to increase comparability between results. PubMed and Embase were searched through August 2018 to identify relevant studies. The summary relative risks (RR) and 95 % CI were estimated using a random-effects model. This analysis included a total of ten prospective studies. The summary RR of colorectal cancer associated with each 10 g/d increase in fibre intake were 0·91 (95 % CI 0·82, 1·00; I2 = 0 %) for cereal fibre, 0·95 (95 % CI 0·87, 1·03, I2 = 0 %) for vegetable fibre, 0·91 (95 % CI 0·78, 1·06, I2 = 43 %) for fruit fibre and 0·84 (95 % CI 0·63, 1·13, I2 = 45 %) for legume fibre. For cereal fibre, the association with colorectal cancer risk remained statistically significant after adjustment for folate intake (RR 0·89, 95 % CI 0·80, 0·99, I2 = 2 %). For vegetable and fruit fibres, the dose–response curve suggested evidence of non-linearity. All fibre sources were inversely associated with incident adenoma (per 10 g/d increase: RR 0·81 (95 % CI 0·54, 1·21) cereals, 0·84 (95 % CI 0·71, 0·98) for vegetables, 0·78 (95 % CI 0·65, 0·93) for fruits) but not associated with recurrent adenoma. Our data suggest that, although all fibre sources may provide some benefits, the evidence for colorectal cancer prevention is strongest for fibre from cereals/grains.

The democratisation of design permits greater stakeholder involvement in what has traditionally been a domain reserved for experts; the design process itself. This is enabled by technological advances in fields such as 3D printing, virtual reality and high-speed peer to peer communication technologies which have fuelled the development of new and innovative design methods. This paper compares and contrasts different approaches to the democratisation of design, and in particular, those that aim to involve wider stakeholders in the design process itself. Three different approaches(design by play, design by generation and crowdsourcing for design) are defined and contextualised within existing design frameworks and their respective suitabilities to democratise different design phases are considered. An exemplar use case of each approach is presented in order to assess how stakeholder engagement is affected by each democratising strategy. The discussion compares and contrasts the approaches with respect to their applicability and utility for different stages of the design process and how the power dynamics of the design process are altered when the different approaches are employed.

Cognitive dysfunction is a symptomatic domain identified across many mental disorders. Cognitive deficits in individuals with major depressive disorder (MDD) contribute significantly to occupational and functional disability. Notably, cognitive subdomains such as learning and memory, executive functioning, processing speed, and attention and concentration are significantly impaired during, and between, episodes in individuals with MDD. Most antidepressants have not been developed and/or evaluated for their ability to directly and independently ameliorate cognitive deficits. Multiple interacting neurobiological mechanisms (eg, neuroinflammation) are implicated as subserving cognitive deficits in MDD. A testable hypothesis, with preliminary support, posits that improving performance across cognitive domains in individuals with MDD may improve psychosocial function, workplace function, quality of life, and other patient-reported outcomes, independent of effects on core mood symptoms. Herein we aim to (1) provide a rationale for prioritizing cognitive deficits as a therapeutic target, (2) briefly discuss the neurobiological substrates subserving cognitive dysfunction, and (3) provide an update on current and future treatment avenues.

OBJECTIVES/SPECIFIC AIMS: The population of cancer survivors is rapidly growing in the United States. Long term and late effects of cancer, combined with ongoing management of other chronic conditions, make cancer survivors particularly vulnerable to polypharmacy and its adverse effects. We examined patterns of prescription medication use and polypharmacy in a population-based sample of cancer survivors. METHODS/STUDY POPULATION: Using data from the Medical Expenditure Panel Survey (MEPS), we matched cancer survivors (n=5216) to noncancer controls (n=19,588) by age, sex, and survey year. We defined polypharmacy as using 5 or more unique medications. We also estimated proportion of respondents prescribed specific medications within therapeutic classes and total prescription expenditures. RESULTS/ANTICIPATED RESULTS: A higher proportion of cancer survivors were prescribed 5 or more unique medications (64.0%, 95% CI 62.3%–65.8%) compared with noncancer controls (51.5%, 95% CI 50.4%–52.6%), including drugs with abuse potential. Across all therapeutic classes, a higher proportion of newly (≤1 year since diagnosis) and previously (>1 years since diagnosis) diagnosed survivors were prescribed medications compared to controls, with large differences in central nervous system agents (65.8% vs. 57.4% vs. 46.2%), psychotherapeutic agents (25.4% vs. 26.8% vs. 18.3%), and gastrointestinal agents (31.9% vs. 29.6% vs. 22.0%). Specifically, nearly 10% of cancer survivors were prescribed benzodiazepines and/or opioids compared to about 5% of controls. Survivors had more than double prescription expenditures (median $1633 vs. $784 among noncancer controls). Findings persisted similarly across categories of age and comorbidity. DISCUSSION/SIGNIFICANCE OF IMPACT: Cancer survivors were frequently prescribed a higher number of unique medications and inappropriate medications or drugs with abuse potential, increasing risk of adverse drug events, financial toxicity, poor adherence, and drug-drug interactions. Adolescent and young adult survivors appear at increased risk of polypharmacy.

Background: Research to date has focused on the detrimental effects of negative self-images for individuals with social anxiety disorder (SAD), but the benefits of positive self-images have been neglected. Aims: The present study examined the effect of holding a positive versus negative self-image in mind on anxiety, judgement bias and emotion regulation (ER) in individuals with SAD. Method: Forty-two individuals who met the diagnostic criteria for SAD were randomly assigned to either a positive or a negative self-image group. Participants were assessed twice with a week's interval in between using the Reactivity and Regulation Situation Task, which measures social anxiety, discomfort, judgement bias and ER, prior to and after the inducement of a positive or negative self-image. Results: Individuals in the positive self-image group reported less social anxiety, discomfort and distress from social cost when compared with their pre-induction state. They also used more adaptive ER strategies and experienced less anxiety and discomfort after using ER. In contrast, individuals in the negative self-image group showed no significant differences in anxiety, judgement bias or ER strategies before and after the induction. Conclusions: This study highlights the beneficial effects of positive self-images on social anxiety and ER.

Climate change may drive shifts in global agriculture that will affect remaining natural lands, with important consequences for the conservation of species and ecosystems. Wine production is an excellent model for examining this type of impact, because suitable climate is central to product quality and production is centered in Mediterranean climate regions that are all global biodiversity hotspots. Adaptation to climate change in existing vineyards may involve water use to ameliorate heat stress or drought, resulting in additional conservation issues. Global studies of wine, climate, and conservation have highlighted the need for more detailed regional analyses to better understand these complex multiple issues. Here we examine impacts of climate change on winegrape suitability in California and its possible implications for nature conservation and water use. Under two global climate models and two emissions scenarios, winegrape suitability in California is projected to decline overall and to move into undeveloped areas that provide important habitats for native species. Coastal and upslope areas retain and improve in suitability, respectively, while inland areas see the largest losses in suitability. Areas of declining suitability are regions in which heightened water use for vineyard adaptation may lead to declines in stream flow or conflicts with other water uses. Continued growth in global demand for wine and reduced production in areas of declining suitability will drive expansion into newly suitable areas, potentially impacting important species native to California. Existing vineyards in areas of declining suitability will likely need to adapt to remain viable. Advance planning for a changing climate and adaptation options that are not water intensive (e.g. vine orientation, trellising, or varietal switch) will help reduce potential water conservation issues in those areas. (JEL Classifications: Q15, Q54, Q57)