Our objective was to evaluate the association of antioxidant intake and the inflammatory potential of the diet with functional decline in older men. A diet history questionnaire was used to collect dietary intake data from men aged ≥ 75 years (n 794) participating in the Concord Health and Aging in Men Project cohort study. Intake of vitamins A, C, E and Zn were compared with the Australian Nutrient Reference Values to determine adequacy. The Energy-adjusted Dietary Inflammatory Index (E-DIITM) was used to assess the inflammatory potential of the diet. Physical performance data were collected via handgrip strength and walking speed tests, and activities of daily living (ADL) and instrumental activities of daily living (IADL) questionnaires, at baseline and 3-year follow-up (n 616). Logistic regression analysis was used to identify associations between diet and incident poor physical function and disability. Both poor antioxidant intake and high E-DII scores at baseline were significantly associated with poor grip strength and ADL disability at 3-year follow-up. No significant associations with walking speed or IADL disability were observed. Individual micronutrient analysis revealed a significant association between the lowest two quartiles of vitamin C intake and poor grip strength. The lowest quartiles of intake for vitamins A, C, E and Zn were significantly associated with incident ADL disability. The study observed that poor antioxidant and anti-inflammatory food intake were associated with odds of developing disability and declining muscle strength in older men. Further interventional research is necessary to clarify the causality of these associations.

OBJECTIVES/GOALS: In triple negative breast cancer (TNBC), obesity is associated with poor outcomes. Adipose stem cells (ASCs) from obese patients (obASCs) secrete higher levels of adipokines compared to ASCs from lean individuals. Leptin, one of these adipokines, has been implicated in many cancers. This study seeks to examine the role of leptin signaling in TNBC. METHODS/STUDY POPULATION: Previous work in conjunction with a collaborating lab has shown that leptin signaling promotes metastasis and increased expression of epithelial-mesenchymal transition (EMT) markers in triple negative breast cancer cell lines. This project expands upon this work through using both patient-derived cell lines and and patient-derived xenografts (PDX), and examines the role of leptin signaling both in vitro and in vivo. To determine the effects of obesity upon a PDX model of TNBC, a high fat diet was used to induce obesity in vivo. A pharmacological inhibitor of the leptin receptor was used to test the requirement for leptin signaling both in vivo and in vitro. RESULTS/ANTICIPATED RESULTS: Exposure to conditioned media harvested from obASCs increased the percentage of TNBC cells that expressed cancer stem cell markers, whereas exposure to an inhibitor of the leptin receptor decreased the percentage of cells with cancer stem cell markers. PDX tumors implanted into mice with diet-induced obesity had an increased volume compared to tumors implanted into lean controls. Further analysis will be conducted on metastasis, circulating tumor cells, and survival in both lean and obese mice. DISCUSSION/SIGNIFICANCE: Understanding the complex signaling events in the obese tumor microenvironment is essential, as these molecular differences may contribute to different outcomes for obese and lean individuals with triple negative breast cancer. Therefore, study of the crosstalk between obASCs and TNBC cells is critical.

Diet has direct and indirect effects on health through inflammation and the gut microbiome. We investigated total dietary inflammatory potential via the literature-derived index (Dietary Inflammatory Index (DII®)) with gut microbiota diversity, composition and function. In cancer-free patient volunteers initially approached at colonoscopy and healthy volunteers recruited from the medical centre community, we assessed 16S ribosomal DNA in all subjects who provided dietary assessments and stool samples (n 101) and the gut metagenome in a subset of patients with residual fasting blood samples (n 34). Associations of energy-adjusted DII scores with microbial diversity and composition were examined using linear regression, permutational multivariate ANOVA and linear discriminant analysis. Spearman correlation was used to evaluate associations of species and pathways with DII and circulating inflammatory markers. Across DII levels, α- and β-diversity did not significantly differ; however, Ruminococcus torques, Eubacterium nodatum, Acidaminococcus intestini and Clostridium leptum were more abundant in the most pro-inflammatory diet group, while Akkermansia muciniphila was enriched in the most anti-inflammatory diet group. With adjustment for age and BMI, R. torques, E. nodatum and A. intestini remained significantly associated with a more pro-inflammatory diet. In the metagenomic and fasting blood subset, A. intestini was correlated with circulating plasminogen activator inhibitor-1, a pro-inflammatory marker (rho = 0·40), but no associations remained significant upon correction for multiple testing. An index reflecting overall inflammatory potential of the diet was associated with specific microbes, but not overall diversity of the gut microbiome in our study. Findings from this preliminary study warrant further research in larger samples and prospective cohorts.

Introduction: An important challenge physicians face when treating acute heart failure (AHF) patients in the emergency department (ED) is deciding whether to admit or discharge, with or without early follow-up. The overall goal of our project was to improve care for AHF patients seen in the ED while avoiding unnecessary hospital admissions. The specific goal was to introduce hospital rapid referral clinics to ensure AHF patients were seen within 7 days of ED discharge. Methods: This prospective before-after study was conducted at two campuses of a large tertiary care hospital, including the EDs and specialty outpatient clinics. We enrolled AHF patients ≥50 years who presented to the ED with shortness of breath (<7 days). The 12-month before (control) period was separated from the 12-month after (intervention) period by a 3-month implementation period. Implementation included creation of rapid access AHF clinics staffed by cardiology and internal medicine, and development of referral procedures. There was extensive in-servicing of all ED staff. The primary outcome measure was hospital admission at the index visit or within 30 days. Secondary outcomes included mortality and actual access to rapid follow-up. We used segmented autoregression analysis of the monthly proportions to determine whether there was a change in admissions coinciding with the introduction of the intervention and estimated a sample size of 700 patients. Results: The patients in the before period (N = 355) and the after period (N = 374) were similar for age (77.8 vs. 78.1 years), arrival by ambulance (48.7% vs 51.1%), comorbidities, current medications, and need for non-invasive ventilation (10.4% vs. 6.7%). Comparing the before to the after periods, we observed a decrease in hospital admissions on index visit (from 57.7% to 42.0%; P <0.01), as well as all admissions within 30 days (from 65.1% to 53.5% (P < 0.01). The autoregression analysis, however, demonstrated a pre-existing trend to fewer admissions and could not attribute this to the intervention (P = 0.91). Attendance at a specialty clinic, amongst those discharged increased from 17.8% to 42.1% (P < 0.01) and the median days to clinic decreased from 13 to 6 days (P < 0.01). 30-day mortality did not change (4.5% vs. 4.0%; P = 0.76). Conclusion: Implementation of rapid-access dedicated AHF clinics led to considerably increased access to specialist care, much reduced follow-up times, and possible reduction in hospital admissions. Widespread use of this approach can improve AHF care in Canada.

Introduction: Transition to the attending physician role and onboarding at a new workplace are often stressful. Effective initiation is important to individuals as well as departments, hospitals and universities wishing to retain valuable staff. Our aim was to learn about early experiences from the perspective of new staff and apply these findings to develop a new onboarding program. Methods: Following a pilot study of individual interviews, we surveyed and conducted focus group interviews with all attending physicians who had joined our dual site, urban, academic emergency department within three years. We used a mixed quantitative and qualitative approach to collect and analyze data. We applied the data to develop a new needs-based formal onboarding program. Results: 24/36 participated in the survey, 22/36 in focus groups. 95% were 30-39 years old. Newcomers described the existing orientation as too brief, non-specific, and missing essential elements. We identified six onboarding themes: (1)clinical protocols and reference documents, (2)graduated responsibilities, (3)mentorship, (4)relationship building, (5)department structure and culture, and (6)emotions. We formed a committee to develop and implement these initiatives: (1)a new online platform enables easy access to clinical care and orientation documents, (2)a formal mentorship program matches each newcomer with 2 mentors to coach towards goals, navigate department structure and culture, and provide perspective to mitigate strong emotions, (3)adjusting shift and teaching assignments allows newcomers to ease into clinical and academic responsibilities, and (4)our next priority is to improve clarity around academic opportunities, expectations, and advancement. Conclusion: New emergency physicians are highly engaged and provided many insights on their orientation experiences. Using mixed methods, we identified six themes to guide the design and implementation of a program to promote successful integration of newcomers.

Introduction: Guidelines recommend serial conventional cardiac troponin (cTn) measurements 6-9 hours apart for non-ST-elevation myocardial infarction (NSTEMI) diagnosis. We sought to develop a pathway based on absolute/relative changes between two serial conventional cardiac troponin I (cTnI) values 3-hours apart for 15-day MACE identification. Methods: This was a prospective cohort study conducted in the two large ED's at the Ottawa Hospital. Adults with NSTEMI symptoms were enrolled over 32 months. Patients with STEMI, hospitalized for unstable angina, or with only one cTnI were excluded. We collected baseline characteristics, Siemens Vista cTnI at 0 and 3-hours after ED presentation, disposition, and ED length of stay (LOS). Adjudicated primary outcome was 15-day MACE (AMI, revascularization, or death due to cardiac ischemia/unknown cause). We analysed cTnI values by 99th percentile cut-off multiples (45, 100 and 250ng/L). Results: 1,683 patients (mean age 64.7 years; 55.3% female; median ED LOS 7 hours; 88 patients with 15-day MACE) were included. 1,346 (80.0%) patients with both cTnI ≤45ng/L; and 58 (3.4%) of the 213 patients with one value≥100ng/L but both <250ng/L or ≤20% change did not suffer MACE. Among 124 patients (7.4%) with one value >45ng/L but both <100ng/L based on 3 or 6-hour cTnI, one patient with Δ<10ng/L and 6 of 19 patients with Δ≥20ng/L were diagnosed with NSTEMI (patients with Δ10-19ng/L between first and second cTnI had third one at 6-hours). Based on the results, we developed the Ottawa Troponin Pathway (OTP) with a 98.9% sensitivity (95%CI 96.7-100%) and 94.6% specificity (95%CI 93.4-95.7%). Conclusion: The OTP, using two conventional cTnI measurements performed 3-hours apart, should lead to better identification of NSTEMI particularly those with values >99th percentile cut-off, standardize management and reduce the ED LOS.

Introduction: Emergency Department Overcrowding (EDOC) is a multifactorial issue that leads to Access Block for patients needing emergency care. Identified as a national problem, patients presenting to a Canadian Emergency Department (ED) at a time of overcrowding have higher rates of admission to hospital and increased seven-day mortality. Using the well accepted input-throughput-output model to study EDOC, current research has focused on throughput as a measure of patient flow, reported as ED length of stay (LOS). In fact, ED LOS and ED beds occupied by inpatients are two “extremely important indicators of EDOC identified by a 2005 survey of Canadian ED directors. One proposed solution to improve ED throughput is to utilize a physician at triage (PAT) to rapidly assess newly arriving patients. In 2017, a pilot PAT program was trialed at Kelowna General Hospital (KGH), a tertiary care hospital, as part of a PDSA cycle. The aim was to mitigate EDOC by improving ED throughput by the end of 2018, to meet the national targets for ED LOS suggested in the 2013 CAEP position statement. Methods: During the fiscal periods 1-6 (April 1 to September 7, 2017) a PAT shift occurred daily from 1000-2200, over four long weekends. ED LOS, time to inpatient bed, time to physician initial assessment (PIA), number of British Columbia Ambulance Service (BCAS) offload delays, and number of patients who left without being seen (LWBS) were extracted from an administrative database. Results were retrospectively analyzed and compared to data from 1000-2200 of non-PAT trial days during the trial periods. Results: Median ED LOS decreased from 3.8 to 3.4 hours for high-acuity patients (CTAS 1-3), from 2.1 to 1.8 hours for low-acuity patients (CTAS 4-5), and from 9.3 to 8.0 hours for all admitted patients. During PAT trial weekends, there was a decrease in the average time to PIA by 65% (from 73 to 26 minutes for CTAS 2-5), average number of daily BCAS offload delays by 39% (from 2.3 to 1.4 delays per day), and number of patients who LWBS from 2.4% to 1.7%. Conclusion: The implementation of PAT was associated with improvements in all five measures of ED throughput, providing a potential solution for EDOC at KGH. ED LOS was reduced compared to non-PAT control days, successfully meeting the suggested national targets. PAT could improve efficiency, resulting in the ability to see more patients in the ED, and increase the quality and safety of ED practice. Next, we hope to prospectively evaluate PAT, continuing to analyze these process measures, perform a cost-benefit analysis, and formally assess ED staff and patient perceptions of the program.

Introduction: Creatine kinase (CK) measurement, despite not being recommended for the diagnosis of a Non-ST Elevation Myocardial Infarction (NSTEMI) is still routinely performed in the emergency department (ED) for the workup of NSTEMI. The diagnostic utility of CK among ED patients with suspected NSTEMI is still not well understood. The objectives of this study were to assess: the additional value of CK in NSTEMI diagnosis and the correlation between the highest CK/TNI values and ejection fraction (EF) on follow-up echocardiography among patients with suspected NSTEMI. Methods: This was a prospective cohort study conducted at the Civic and General Campuses of The Ottawa Hospital from March 2014 to March 2016. We enrolled adults (18 years) for whom troponin (TNI) and CK were ordered for chest pain or non-chest pain symptoms within the past 24 hours concerning for NSTEMI and excluded those with suspected ST-Elevation Myocardial Infarction (STEMI). Primary outcome was a 30-day NSTEMI adjudicated by two blinded physicians. Demographics, medical history, and ED CK/TNI values were collected. We used descriptive statistics and report test diagnostic characteristics. Results: Of the 1,663 patients enrolled, 84 patients (5.1%) suffered NSTEMI. The sensitivity and specificity of CK was 30.9% (95%CI 21.1, 40.8) and 91.4% (95%CI 90.0, 92.8) respectively. The sensitivity and specificity of troponin was 96.4% (95%CI 92.4, 100) and 88.1% (95%CI 86.5, 89.7) respectively. Among 3 (0.2%) patients with missed NSTEMI diagnosis with TNI, CK measurements did not add value. The mean CK values were not significantly different between those with normal and abnormal EF on follow-up (132.4 U/L and 146.3 U/L respectively; p=0.44), whereas the mean TNI values were significantly different (0.5 µg/L and 1.3 µg/L respectively; p=0.046). Conclusion: CK measurements neither provide any additional value in the work-up of NSTEMI in the ED nor correlate with EF on follow-up. Discontinuing routine CK measurements would reduce overall costs and improve resource utilization in the ED, and streamline the management of patients in the ED with chest pain.

Arterial wall thickening, stimulated by low-grade systemic inflammation, underlies many cardiovascular events. As diet is a significant moderator of systemic inflammation, the dietary inflammatory index (DIITM) has recently been devised to assess the overall inflammatory potential of an individual’s diet. The primary objective of this study was to assess the association of the DII with common carotid artery–intima-media thickness (CCA–IMT) and carotid plaques. To substantiate the clinical importance of these findings we assessed the relationship of DII score with atherosclerotic vascular disease (ASVD)-related mortality, ischaemic cerebrovascular disease (CVA)-related mortality and ischaemic heart disease (IHD)-related mortality more. The study was conducted in Western Australian women aged over 70 years (n 1304). Dietary data derived from a validated FFQ (completed at baseline) were used to calculate a DII score for each individual. In multivariable-adjusted models, DII scores were associated with sub-clinical atherosclerosis: a 1 sd (2·13 units) higher DII score was associated with a 0·013-mm higher mean CCA–IMT (P=0·016) and a 0·016-mm higher maximum CCA–IMT (P=0·008), measured at 36 months. No relationship was seen between DII score and carotid plaque severity. There were 269 deaths during follow-up. High DII scores were positively associated with ASVD-related death (per sd, hazard ratio (HR): 1·36; 95 % CI 1·15, 1·60), CVA-related death (per sd, HR: 1·30; 95 % CI 1·00, 1·69) and IHD-related death (per sd, HR: 1·40; 95 % CI 1·13, 1·75). These results support the hypothesis that a pro-inflammatory diet increases systemic inflammation leading to development and progression of atherosclerosis and eventual ASVD-related death.

Dietary factors and inflammation markers have been shown to play a role in the development of depression. However, there are very few studies that have explored the association between inflammatory potential of diet and risk of depression. In this study, we examined the association between the dietary inflammatory index (DII), which was developed specifically to measure the inflammatory potential of diet, and risk of depression in the middle-aged cohort of the Australian Longitudinal Study on Women’s Health. A total of 6438 women with a mean age of 52·0 (sd 1·4) years at baseline were followed-up at five surveys over 12 years (2001–2013). Depression was defined as a score of ≥10 on the Center for Epidemiologic Studies Depression-10 scale. The DII score, a literature-derived, population-based dietary index that has been validated against several inflammatory markers, was computed on the basis of dietary intake assessed using a validated FFQ. Generalised estimating equations were used to estimate relative risk (RR) of depression according to DII score. Models were adjusted for energy intake, highest education completed, marital status, menopause status and symptoms, personal illness or injury, smoking status, physical activity, BMI and depression diagnosis or treatment. In total, 1156 women (18 %) had scores≥10 on the CESD scale over the course of 9 years. Women with the most anti-inflammatory diet had an approximately 20 % lower risk of developing depression compared with women with the most pro-inflammatory diet (RRDII quartile 1 v. 4: 0·81; 95 % CI 0·69, 0·96; P trend=0·03). These results suggest that an anti-inflammatory diet is associated with lower risk of depression in middle-aged Australian women.

The dietary inflammatory index (DII) is a new tool to assess the inflammatory potential of the diet. In the present study, we aimed to determine the association between the DII and BMI, waist circumference and waist:height ratio (WHtR). We conducted a cross-sectional study of 7236 participants recruited into the PREvención con DIeta MEDiterránea trial. Information from a validated 137-item FFQ was used to calculate energy, food and nutrient intakes. A fourteen-item dietary screener was used to assess adherence to the Mediterranean diet (MeDiet). Sex-specific multivariable linear regression models were fitted to estimate differences (and 95 % CI) in BMI, waist circumference and WHtR across the quintiles of the DII. All nutrient intakes, healthy foods and adherence to the MeDiet were higher in the quintile with the lowest DII score (more anti-inflammatory values) except for intakes of animal protein, saturated fat and monounsaturated fat. Although an inverse association between the DII and total energy was apparent, the DII was associated with higher average BMI, waist circumference and WHtR after adjusting for known risk factors. The adjusted difference in the WHtR for women and men between the highest and lowest quintiles of the DII was 1·60 % (95 % CI 0·87, 2·33) and 1·04 % (95 % CI 0·35, 1·74), respectively. Pro-inflammatory scores remained associated with obesity after controlling for the effect that adherence to a MeDiet had on inflammation. In conclusion, the present study shows a direct association between the DII and indices of obesity, and supports the hypothesis that diet may have a role in the development of obesity through inflammatory modulation mechanisms.

From a ferrite/martensite cold-rolled microstructure, the interaction between ferriterecrystallization and austenite formation is investigated. It is observed that a slowheating rate promotes the ferrite recrystallization and a homogeneous microstructure,whereas a fast heating rate delays the recrystallization and leads to heterogeneouslydistributed austenite islands.