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To evaluate the clinical impact of an antimicrobial stewardship program (ASP) on high-risk pediatric patients.
Retrospective cohort study.
Free-standing pediatric hospital.
This study included patients who received an ASP review between March 3, 2008, and March 2, 2017, and were considered high-risk, including patients receiving care by the neonatal intensive care (NICU), hematology/oncology (H/O), or pediatric intensive care (PICU) medical teams.
The ASP recommendations included stopping antibiotics; modifying antibiotic type, dose, or duration; or obtaining an infectious diseases consultation. The outcomes evaluated in all high-risk patients with ASP recommendations were (1) hospital-acquired Clostridium difficile infection, (2) mortality, and (3) 30-day readmission. Subanalyses were conducted to evaluate hospital length of stay (LOS) and tracheitis treatment failure. Multivariable generalized linear models were performed to examine the relationship between ASP recommendations and each outcome after adjusting for clinical service and indication for treatment.
The ASP made 2,088 recommendations, and 50% of these recommendations were to stop antibiotics. Recommendation agreement occurred in 70% of these cases. Agreement with an ASP recommendation was not associated with higher odds of mortality or hospital readmission. Patients with a single ASP review and agreed upon recommendation had a shorter median LOS (10.2 days vs 13.2 days; P < .05). The ASP recommendations were not associated with high rates of tracheitis treatment failure.
ASP recommendations do not result in worse clinical outcomes among high-risk pediatric patients. Most ASP recommendations are to stop or to narrow antimicrobial therapy. Further work is needed to enhance stewardship efforts in high-risk pediatric patients.
OBJECTIVES/SPECIFIC AIMS: 1.Identify barriers to pursuing research for physician trainees 2.Develop a sustainable pipeline of physician-scientists at Duke 3.Coordinate physician-scientist development programs across the School of Medicine under one central Office 4.Provide infrastructure and resources for all physician-scientists 5.Increase the number of MDs and MD/PhDs who pursue, succeed, and are retained in research METHODS/STUDY POPULATION: To establish a baseline understanding of the needs and concerns of physician-scientist trainees at Duke, we conducted focus groups using a standardized interview guide and thematic analysis. Findings from these focus groups were used to develop a framework for support, leading to the creation of the Office of Physician-Scientist Development (OPSD) housed centrally within the Duke School of Medicine. The OPSD integrates programs and resources for multiple populations including medical students, residents, fellows, junior faculty, and faculty mentors. Pipeline programs will also be developed to enhance research engagement in targeted student populations prior to medical school. RESULTS/ANTICIPATED RESULTS: A total of 45 students and faculty participated in the focus groups and structured interviews (1st year medical student, n=11; 4th year medical students, n=11; residents/fellows, n=13; junior faculty, n=11). While participants raised a number of specific issues, one key message emerged: non-PhD MDs in basic research felt they lacked opportunities for directed training. Moreover, they felt the need to teach themselves many critical skills through trial and error. This has led to perceptions that they cannot compete effectively with PhDs and MD-PhD scientists for research funding and positions. Consensus recommendations included: better guidance in choosing mentors, labs, and projects; central resource for information relevant to physician scientists; training specifically tailored to physician scientists conducting laboratory-based research; improved infrastructure and well-defined training pathways; and assistance with grant preparation. To-date, over 90 students, residents, and fellows have been identified who identify as laboratory-based physician scientists. Additional efforts are underway to identify and characterize the broader range of physician-scientist students and trainees at Duke. DISCUSSION/SIGNIFICANCE OF IMPACT: Our planning study revealed specific steps forward toward developing a robust community of physician-scientists at Duke. As a first step, the Dean of the School of Medicine has appointed an Associate Dean of Physician-Scientist Development to oversee a new Office of Physician-Scientist Development (OPSD) being launched in December of 2018. The OPSD will offer four primary programs. 1) A concierge mentoring program will assist new trainees in identifying research areas of interest and mentors. Trainees will receive periodic contact to provide additional support as needed and promote success. 2) A physician-scientist training program is being created to provide training specific to laboratory research skills as well as career and professional development training to complement existing clinical and translational research programs. 3) Integrated training pathways will provide additional mentored research training for those pursuing research careers. Pathways will capitalize on existing resources from R38 programs, while pursuing additional R38 and R25 support. 4) An MD-Scientist funding program has been developed to provide additional research funding and protected time for students pursuing a second research year. Through the support and programming offered by the OPSD, we anticipate decreased perceptions of barriers to pursuing a physician-scientist career and increased satisfaction with training opportunities. Over time, we expect such support to increase the number of MD students pursuing research as a career and the number of residents, fellows, and MD junior faculty remaining in research careers.
Rare copy number variants (CNVs) are associated with risk of neurodevelopmental disorders characterised by varying degrees of cognitive impairment, including schizophrenia, autism spectrum disorder and intellectual disability. However, the effects of many individual CNVs in carriers without neurodevelopmental disorders are not yet fully understood, and little is known about the effects of reciprocal copy number changes of known pathogenic loci.
We aimed to analyse the effect of CNV carrier status on cognitive performance and measures of occupational and social outcomes in unaffected individuals from the UK Biobank.
We called CNVs in the full UK Biobank sample and analysed data from 420 247 individuals who passed CNV quality control, reported White British or Irish ancestry and were not diagnosed with neurodevelopmental disorders. We analysed 33 pathogenic CNVs, including their reciprocal deletions/duplications, for association with seven cognitive tests and four general measures of functioning: academic qualifications, occupation, household income and Townsend Deprivation Index.
Most CNVs (24 out of 33) were associated with reduced performance on at least one cognitive test or measure of functioning. The changes on the cognitive tests were modest (average reduction of 0.13 s.d.) but varied markedly between CNVs. All 12 schizophrenia-associated CNVs were associated with significant impairments on measures of functioning.
CNVs implicated in neurodevelopmental disorders, including schizophrenia, are associated with cognitive deficits, even among unaffected individuals. These deficits may be subtle but CNV carriers have significant disadvantages in educational attainment and ability to earn income in adult life.
OBJECTIVES/SPECIFIC AIMS: The aim of this study is to determine whether quantitative measures of knee structures including effusion, bone marrow lesions, cartilage, and meniscal damage can improve upon an existing model of demographic and clinical characteristics to classify accelerated knee osteoarthritis (AKOA). METHODS/STUDY POPULATION: We conducted a case-control study using data from baseline and four annual follow-up visits from the osteoarthritis initiative. Participants had no radiographic knee osteoarthritis (KOA) at baseline. AKOA is defined as progressing from no KOA to advance-stage KOA in at least 1 knee within 48 months. AKOA knees were matched 1:1 based on sex to (1) participants who did not develop KOA within 48 months and (2) participants who developed KOA but not AKOA. Analyses were person based. Classification and regression tree analysis was used to determine the important variables and percent of variance explained. RESULTS/ANTICIPATED RESULTS: A previous classification and regression tree analysis found that age, BMI, serum glucose, and femorotibial angle explained 31% of the variability between those who did and did not develop AKOA. Including structural measurements as candidate variables yielded a model that included effusion, BMI, serum glucose, cruciate ligament degeneration and coronal slope and explained 39% of the variability. DISCUSSION/SIGNIFICANCE OF IMPACT: Knee structural measurements improve classification of participants who developed AKOA Versus those who did not. Further research is needed to better classify patients at risk for AKOA.
To determine the effect of mandatory and nonmandatory influenza vaccination policies on vaccination rates and symptomatic absenteeism among healthcare personnel (HCP).
Retrospective observational cohort study.
This study took place at 3 university medical centers with mandatory influenza vaccination policies and 4 Veterans Affairs (VA) healthcare systems with nonmandatory influenza vaccination policies.
The study included 2,304 outpatient HCP at mandatory vaccination sites and 1,759 outpatient HCP at nonmandatory vaccination sites.
To determine the incidence and duration of absenteeism in outpatient settings, HCP participating in the Respiratory Protection Effectiveness Clinical Trial at both mandatory and nonmandatory vaccination sites over 3 viral respiratory illness (VRI) seasons (2012–2015) reported their influenza vaccination status and symptomatic days absent from work weekly throughout a 12-week period during the peak VRI season each year. The adjusted effects of vaccination and other modulating factors on absenteeism rates were estimated using multivariable regression models.
The proportion of participants who received influenza vaccination was lower each year at nonmandatory than at mandatory vaccination sites (odds ratio [OR], 0.09; 95% confidence interval [CI], 0.07–0.11). Among HCP who reported at least 1 sick day, vaccinated HCP had lower symptomatic days absent compared to unvaccinated HCP (OR for 2012–2013 and 2013–2014, 0.82; 95% CI, 0.72–0.93; OR for 2014–2015, 0.81; 95% CI, 0.69–0.95).
These data suggest that mandatory HCP influenza vaccination policies increase influenza vaccination rates and that HCP symptomatic absenteeism diminishes as rates of influenza vaccination increase. These findings should be considered in formulating HCP influenza vaccination policies.
There is strong evidence that people born in winter and in spring have a small increased risk of schizophrenia. As this ‘season of birth’ effect underpins some of the most influential hypotheses concerning potentially modifiable risk exposures, it is important to exclude other possible explanations for the phenomenon.
Here we sought to determine whether the season of birth effect reflects gene-environment confounding rather than a pathogenic process indexing environmental exposure. We directly measured, in 136 538 participants from the UK Biobank (UKBB), the burdens of common schizophrenia risk alleles and of copy number variants known to increase the risk for the disorder, and tested whether these were correlated with a season of birth.
Neither genetic measure was associated with season or month of birth within the UKBB sample.
As our study was highly powered to detect small effects, we conclude that the season of birth effect in schizophrenia reflects a true pathogenic effect of environmental exposure.
We examine the role of status quo bias in the ballot wording of social issues that affect the rights of minority groups. We test the salience of this framing bias by conducting an experiment that randomly assigns different ballot wordings for five policies across survey respondents. We find that status quo bias changes the percent of individuals who vote for the ballot measure by 5–8 percentage points with the least informed individuals being the most affected by status quo bias.
The Schistosoma mansoni cercarial elastase (SmCE) has previously been shown to be poorly immunogenic in mice. However, a minority of mice were able to produce antibodies against SmCE after multiple immunizations with crude preparations containing the enzyme. These mice were partially protected against challenge infections of S. mansoni. In the present study, we show that in contrast to the poor immunogenicity of the enzymatically active native form of SmCE derived from a crude preparation (cercarial transformation fluid), immunization of CBA/Ca mice with two enzymatically inactive forms, namely purified native SmCE or a recombinant SmCE fused to recombinant Schistosoma japonicum glutathione S-transferase (rSmCE-SjGST), after adsorption onto aluminum hydroxide adjuvant, induced specific anti-SmCE immunoglobulin G (IgG) in all mice within 2 weeks of the second immunization. The IgG antibody response to rSmCE-SjGST was mainly of the IgG1 subclass. These results suggest that inactive forms of the antigen could be used to obtain the optimum immunogenic effects as a vaccine candidate against schistosomiasis. Mice immunized with the rSmCE-SjGST on alum had smaller mean worm burdens and lower tissue egg counts when compared with adjuvant alone- and recombinant SjGST-injected controls. The native SmCE was antigenically cross-reactive with homologous enzymes of Schistosoma haematobium and Schistosoma margrebowiei.
Objectives: This study examined whether individuals with Parkinson’s disease (PD) are at increased vulnerability for vascular-related cognitive impairment relative to controls. The underlying assumption behind this hypothesis relates to brain reserve and that both PD and vascular risk factors impair similar fronto-executive cognitive systems. Methods: The sample included 67 PD patients and 61 older controls (total N=128). Participants completed neuropsychological measures of executive functioning, processing speed, verbal delayed recall/memory, language, and auditory attention. Cardiovascular risk was assessed with the Framingham Cardiovascular Risk index. Participants underwent brain imaging (T1 and T2 FLAIR). Trained raters measured total and regional leukoaraiosis (periventricular, deep subcortical, and infracortical). Results: Hierarchical regressions revealed that more severe cardiovascular risk was related to worse executive functioning, processing speed, and delayed verbal recall in both Parkinson patients and controls. More severe cardiovascular risk was related to worse language functioning in the PD group, but not controls. In contrast, leukoaraiosis related to both cardiovascular risk and executive functioning for controls, but not the PD group. Conclusions: Overall, results revealed that PD and cardiovascular risk factors are independent risk factors for cognitive impairment. Generally, the influence of cardiovascular risk factors on cognition is similar in PD patients and controls. (JINS, 2017, 23, 322–331)
The development and spread of glyphosate-resistant (GR) horseweed has increased the use of dicamba as an alternative herbicide treatment. Research evaluated suspected glyphosate-resistant horseweed populations from DeKalb (GR-1) and Cherokee (GR-2) counties, Alabama, for response to glyphosate, dicamba, and glyphosate + dicamba. Populations used for resistance determination were tested at rosette and bolt growth stages. Glyphosate resistance evaluation treatments ranged from 0 to 36.0 kg ae ha−1. Data confirmed that GR-1 and GR-2 horseweed populations were 3.0 to 38 times more resistant to glyphosate than the susceptible population, according to population, data type, and growth stage at treatment. GR-1 and GR-2 populations were further evaluated for response to dicamba. Dicamba was applied at 0 to 1.12 kg ai ha−1, both with and without the addition of glyphosate at 1.12 kg ae ha−1. All populations had similar tolerance to dicamba, with the exception of GR-2 treated at the rosette growth stage, which had ~2-fold greater tolerance. When glyphosate was tank-mixed with dicamba, the response of GR populations was similar to that of dicamba alone. Therefore, any potential resistance-management benefit of tank-mixing dicamba with glyphosate may be negated when one is attempting to control GR horseweed. Conversely, adding glyphosate to dicamba drastically enhanced control of the susceptible population at both growth stages.
Nearly 258 million ha (28%) of the United States is publicly owned land that is managed by federal government agencies. For example, the US Department of Agriculture's Forest Service (USFS) manages over 77 million ha of national forests and grasslands for the benefit of the American public. Given its legal directive to manage multiple uses, it is not surprising that conflicts arise among stakeholders over how this land should be used (Lansky, 1992). The USFS has much discretion in how land is managed, yet must often balance conflicting values of public use and benefit (Nie, 2004). As national priorities, social preferences and public awareness of national forest goods, services and values have changed over time, USFS managers have faced increased pressure to balance consumptive uses with the need for environmental protection. Competing stakeholder demands coupled with increased environmental risks (wildfires, tree diseases and insect epidemics) have resulted in an escalating conservation conflict that is manifested in administrative appeals, lawsuits and a growing distrust of the agency.
Over time, the USFS has embraced new directions and management paradigms to reduce conflict. Some of these have been ecosystem management, adaptive management and now collaborative management (e.g. Holling, 1978; Maser, 1988; Franklin, 1992; Boyce and Haney, 1997; Wondolleck and Yaffee, 2000; Brown et al., 2004). These approaches reflect changing societal values, political pressures and new scientific information.
A persistent conflict has been the logging of trees in national forests and related impacts on forest ecosystems (Lansky, 1992). The USFS’ timber sale programme has supported jobs and community stability through economic development. Logging has also been a mechanism to reduce the risk of wildfire by reducing tree density (fuel for fires) and vertical stand diversity (‘ladder’ fuels; North et al., 2009). However, logging can also negatively affect forest integrity, watershed quality, wildlife, aesthetic and spiritual values of forests (Satterfield, 2002; North et al., 2009).
We conducted a time-series analysis to evaluate the impact of the ASP over a 6.25-year period (July 1, 2008–September 30, 2014) while controlling for trends during a 3-year preintervention period (July 1, 2005–June 30, 2008). The primary outcome measures were total antibacterial and antipseudomonal use in days of therapy (DOT) per 1,000 patient-days (PD). Secondary outcomes included antimicrobial costs and resistance, hospital-onset Clostridium difficile infection, and other patient-centered measures.
During the preintervention period, total antibacterial and antipseudomonal use were declining (−9.2 and −5.5 DOT/1,000 PD per quarter, respectively). During the stewardship period, both continued to decline, although at lower rates (−3.7 and −2.2 DOT/1,000 PD, respectively), resulting in a slope change of 5.5 DOT/1,000 PD per quarter for total antibacterial use (P=.10) and 3.3 DOT/1,000 PD per quarter for antipseudomonal use (P=.01). Antibiotic expenditures declined markedly during the stewardship period (−$295.42/1,000 PD per quarter, P=.002). There were variable changes in antimicrobial resistance and few apparent changes in C. difficile infection and other patient-centered outcomes.
In a hospital with low baseline antibiotic use, implementation of an ASP was associated with sustained reductions in total antibacterial and antipseudomonal use and declining antibiotic expenditures. Common ASP outcome measures have limitations.