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OBJECTIVES/SPECIFIC AIMS: The objective of this research was to assess the clinical impact of simulation-based team leadership training on team leadership effectiveness and patient care during actual trauma resuscitations. This translational work addresses an important gap in simulation research and medical education research. METHODS/STUDY POPULATION: Eligible trauma team leaders were randomized to the intervention (4-hour simulation-based leadership training) or control (standard training) condition. Subject-led actual trauma patient resuscitations were video recorded and coded for leadership behaviors (primary outcome) and patient care (secondary outcome) using novel leadership and trauma patient care metrics. Patient outcomes for trauma resuscitations were obtained through the Harborview Medical Center Trauma Registry and analyzed descriptively. A one-way ANCOVA analysis was conducted to test the effectiveness of our training intervention versus a control group for each outcome (leadership effectiveness and patient care) while accounting for pre-training performance, injury severity score, postgraduate training year, and days since training occurred. Association between leadership effectiveness and patient care was evaluated using random coefficient modeling. RESULTS/ANTICIPATED RESULTS: Sixty team leaders, 30 in each condition, completed the study. There was a significant difference in post-training leadership effectiveness [F(1,54)=30.19, p<.001, η2=.36] between the experimental and control conditions. There was no direct impact of training on patient care [F(1,54)=1.0, p=0.33, η2=.02]; however, leadership effectiveness mediated an indirect effect of training on patient care. Across all trauma resuscitations team leader effectiveness correlated with patient care (p<0.05) as predicted by team leadership conceptual models. DISCUSSION/SIGNIFICANCE OF IMPACT: This work represents a critical step in advancing translational simulation-based research (TSR). While there are several examples of high quality translational research programs, they primarily focus on procedural tasks and do not evaluate highly complex skills such as leadership. Complex skills present significant measurement challenges because individuals and processes are interrelated, with multiple components and emergent nature of tasks and related behaviors. We provide evidence that simulation-based training of a complex skill (team leadership behavior) transfers to a complex clinical setting (emergency department) with highly variable clinical tasks (trauma resuscitations). Our novel team leadership training significantly improved overall leadership performance and partially mediated the positive effect between leadership and patient care. This represents the first rigorous, randomized, controlled trial of a leadership or teamwork-focused training that systematically evaluates the impact on process (leadership) and performance (patient care).
Major depressive disorder (MDD) is a leading cause of disease burden worldwide, with lifetime prevalence in the United States of 17%. Here we present the results of the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the clinical importance of achieving congruence between combinatorial pharmacogenomic (PGx) testing and medication selection for MDD.
1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were enrolled and randomized 1:1 to a Treatment as Usual (TAU) arm or PGx-guided care arm. Combinatorial PGx testing categorized medications in three groups based on the level of gene-drug interactions: use as directed, use with caution, or use with increased caution and more frequent monitoring. Patient assessments were performed at weeks 0 (baseline), 4, 8, 12 and 24. Patients, site raters, and central raters were blinded in both arms until after week 8. In the guided-care arm, physicians had access to the combinatorial PGx test result to guide medication selection. Primary outcomes utilized the Hamilton Depression Rating Scale (HAM-D17) and included symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17<7) at the fully blinded week 8 time point. The durability of patient outcomes was assessed at week 24. Medications were considered congruent with PGx test results if they were in the ‘use as directed’ or ‘use with caution’ report categories while medications in the ‘use with increased caution and more frequent monitoring’ were considered incongruent. Patients who started on incongruent medications were analyzed separately according to whether they changed to congruent medications by week8.
At week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Remission rates, response rates, and symptom reductions continued to improve in the guided-treatment arm until the 24week time point. Congruent prescribing increased to 91% in the guided-care arm by week 8. Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.
Combinatorial PGx testing improves short- and long-term response and remission rates for MDD compared to standard of care. In addition, prescribing congruency with PGx-guided medication recommendations is important for achieving symptom improvement, response, and remission for MDD patients.
Funding Acknowledgements: This study was supported by Assurex Health, Inc.
Electron and proton microprobes, along with electron backscatter diffraction (EBSD) analysis were used to study the microstructure of the contemporary Al–Cu–Li alloy AA2099-T8. In electron probe microanalysis, wavelength and energy dispersive X-ray spectrometry were used in parallel with soft X-ray emission spectroscopy (SXES) to characterize the microstructure of AA2099-T8. The electron microprobe was able to identify five unique compositions for constituent intermetallic (IM) particles containing combinations of Al, Cu, Fe, Mn, and Zn. A sixth IM type was found to be rich in Ti and B (suggesting TiB2), and a seventh IM type contained Si. EBSD patterns for the five constituent IM particles containing Al, Cu, Fe, Mn, and Zn indicated that they were isomorphous with four phases in the 2xxx series aluminium alloys including Al6(Fe, Mn), Al13(Fe, Mn)4 (two slightly different compositions), Al37Cu2Fe12 and Al7Cu2Fe. SXES revealed that Li was present in some constituent IM particles. Al SXES mapping revealed an Al-enriched (i.e., Cu, Li-depleted) zone in the grain boundary network. From the EBSD analysis, the kernel average misorientation map showed higher levels of localized misorientation in this region, suggesting greater deformation or stored energy. Proton-induced X-ray emission revealed banding of the TiB2 IM particles and Cu inter-band enrichment.
TAG depleted remnants of postprandial chylomicrons are a risk factor for atherosclerosis. Recent studies have demonstrated that in the fasted state, the majority of chylomicrons are small enough for transcytosis to arterial subendothelial space and accelerate atherogenesis. However, the size distribution of chylomicrons in the absorptive state is unclear. This study explored in normolipidaemic subjects the postprandial distribution of the chylomicron marker, apoB-48, in a TAG-rich lipoprotein plasma fraction (Svedberg flotation rate (Sf>400), in partially hydrolysed remnants (Sf 20–400) and in a TAG-deplete fraction (Sf<20), following ingestion of isoenergetic meals with either palm oil (PO), rice bran or coconut oil. Results from this study show that the majority of fasting chylomicrons are within the potentially pro-atherogenic Sf<20 fraction (70–75 %). Following the ingestion of test meals, chylomicronaemia was also principally distributed within the Sf<20 fraction. However, approximately 40 % of subjects demonstrated exaggerated postprandial lipaemia specifically in response to the SFA-rich PO meal, with a transient shift to more buoyant chylomicron fractions. The latter demonstrates that heterogeneity in the magnitude and duration of hyper-remnantaemia is dependent on both the nature of the meal fatty acids ingested and possible metabolic determinants that influence chylomicron metabolism. The study findings reiterate that fasting plasma TAG is a poor indicator of atherogenic chylomicron remnant homoeostasis and emphasises the merits of considering specifically, chylomicron remnant abundance and kinetics in the context of atherogenic risk. Few studies address the latter, despite the majority of life being spent in the postprandial and absorptive state.
The main question that Firestone & Scholl (F&S) pose is whether “what and how we see is functionally independent from what and how we think, know, desire, act, and so forth” (sect. 2, para. 1). We synthesize a collection of concerns from an interdisciplinary set of coauthors regarding F&S's assumptions and appeals to intuition, resulting in their treatment of visual perception as context-free.
Exposures to antioxidants (AO) are associated with levels of C-reactive protein (CRP), but the pattern of evidence is mixed, due in part to studying each potential AO, one at a time, when multiple AO exposures might affect CRP levels. By studying multiple AO via a composite indicator approach, we estimate the degree to which serum CRP level is associated with serum AO level. Standardised field survey protocols for the US National Health and Nutrition Examination Survey (NHANES) 2003–2006 yielded nationally representative cross-sectional samples of adults aged 20 years and older (n 8841). NHANES latex-enhanced nephelometry quantified serum CRP levels. Liquid chromatography quantified serum concentrations of vitamins A, E and C and carotenoids. Using structural equations, we regressed CRP level on AO levels, and derived a summary estimate for a composite of these potential antioxidants (CPA), with covariates held constant. The association linking CPA with CRP was inverse, stronger for slightly elevated CRP (1·8≤CRP<10 mg/l; slope= −1·08; 95 % CI −1·39, −0·77) and weaker for highly elevated CRP (≥10 mg/l; slope= −0·52; 95 % CI −0·68, −0·35), with little change when covariates were added. Vitamins A and C, as well as lutein+zeaxanthin, were prominent contributors to the composite. In these cross-sectional data studied via a composite indicator approach, the CPA level and the CRP level were inversely related. The stage is set for more confirmatory longitudinal or intervention research on multiple vitamins. The composite indicator approach might be most useful in epidemiology when several exposure constructs are too weakly inter-correlated to be studied via formal measurement models for underlying latent dimensions.
To determine whether use of contact precautions on hospital ward patients is associated with patient adverse events
Individually matched prospective cohort study
The University of Maryland Medical Center, a tertiary care hospital in Baltimore, Maryland
A total of 296 medical or surgical inpatients admitted to non–intensive care unit hospital wards were enrolled at admission from January to November 2010. Patients on contact precautions were individually matched by hospital unit after an initial 3-day length of stay to patients not on contact precautions. Adverse events were detected by physician chart review and categorized as noninfectious, preventable and severe noninfectious, and infectious adverse events during the patient’s stay using the standardized Institute for Healthcare Improvement’s Global Trigger Tool.
The cohort of 148 patients on contact precautions at admission was matched with a cohort of 148 patients not on contact precautions. Of the total 296 subjects, 104 (35.1%) experienced at least 1 adverse event during their hospital stay. Contact precautions were associated with fewer noninfectious adverse events (rate ratio [RtR], 0.70; 95% confidence interval [CI], 0.51–0.95; P=.02) and although not statistically significant, with fewer severe adverse events (RtR, 0.69; 95% CI, 0.46–1.03; P=.07). Preventable adverse events did not significantly differ between patients on contact precautions and patients not on contact precautions (RtR, 0.85; 95% CI, 0.59–1.24; P=.41).
Hospital ward patients on contact precautions were less likely to experience noninfectious adverse events during their hospital stay than patients not on contact precautions.
Infect. Control Hosp. Epidemiol. 2015;36(11):1268–1274
A number of copy number variants (CNVs) have been suggested as
susceptibility factors for schizophrenia. For some of these the data
remain equivocal, and the frequency in individuals with schizophrenia is
To determine the contribution of CNVs at 15 schizophrenia-associated loci
(a) using a large new data-set of patients with schizophrenia
(n = 6882) and controls (n = 6316),
and (b) combining our results with those from previous studies.
We used Illumina microarrays to analyse our data. Analyses were
restricted to 520 766 probes common to all arrays used in the different
We found higher rates in participants with schizophrenia than in controls
for 13 of the 15 previously implicated CNVs. Six were nominally
significantly associated (P<0.05) in this new
data-set: deletions at 1q21.1, NRXN1, 15q11.2 and
22q11.2 and duplications at 16p11.2 and the Angelman/Prader–Willi
Syndrome (AS/PWS) region. All eight AS/PWS duplications in patients were
of maternal origin. When combined with published data, 11 of the 15 loci
showed highly significant evidence for association with schizophrenia
We strengthen the support for the majority of the previously implicated
CNVs in schizophrenia. About 2.5% of patients with schizophrenia and 0.9%
of controls carry a large, detectable CNV at one of these loci. Routine
CNV screening may be clinically appropriate given the high rate of known
deleterious mutations in the disorder and the comorbidity associated with
these heritable mutations.
Chylomicron particles are continually synthesised and secreted from the intestine even in the absence of ingested fat. It is possible that following consumption of low doses of fat the basal level of chylomicron secretion and subsequent metabolism are sufficient to metabolise this fat without an increase in postprandial chylomicron concentrations. To test this hypothesis, healthy male subjects were randomised to receive, on three separate occasions, meals containing a range of doses of fat (average 8·1–19 g) and effects on postprandial lipaemia and chylomicron concentration were determined. Furthermore, to delineate the effect on lipid-rich v. lipid-poor (remnant) forms lipid levels were also determined in a density <1·006 g/ml fraction. Following consumption of the very low dose of fat the postprandial concentration of chylomicrons was unaltered, whereas following the medium dose postprandial chylomicron concentrations were significantly increased. Interestingly, this increase was only detected in the lipid-rich chylomicron fraction, with postprandial levels of chylomicron remnants remaining unchanged. In conclusion, it appears that consumption of what would be considered low to medium doses of fat are not associated with transient postprandial increases in chylomicron remnants in healthy male subjects.
More than 60% of newborns with severe congenital cardiac disease develop perioperative brain injuries. Known risk factors include: pre-operative hypoxemia, cardiopulmonary bypass characteristics, and post-operative hypotension. Infection is an established risk factor for white matter injury in premature newborns. In this study, we examined term infants with congenital cardiac disease requiring surgical repair to determine whether infection is associated with white matter injury. Acquired infection was specified by site – bloodstream, pneumonia, or surgical site infection – according to strict definitions. Infection was present in 23 of 127 infants. Pre- and post-operative imaging was evaluated for acquired injury by a paediatric neuroradiologist. Overall, there was no difference in newly acquired post-operative white matter injury in infants with infection (30%), compared to those without (31%). When stratified by anatomy, infants with transposition of the great arteries, and bloodstream infection had an estimated doubling of risk of white matter injury that was not significant, whereas those with single ventricle anatomy had no apparent added risk. When considering only infants without stroke, the estimated association was higher, and became significant after adjusting for duration of inotrope therapy. In this study, nosocomial infection was not associated with white matter injury. Nonetheless, when controlling for risk factors, there was an association between bloodstream infection and white matter injury in selected sub-populations. Infection prevention may have the potential to mitigate long-term neurologic impairment as a consequence of white matter injury, which underscores the importance of attention to infection control for these patients.