ABSTRACT IMPACT: Our study will integrate state-of-the-art methods in pathogen genomics, epidemiology, and geospatial analysis to identify both host- and pathogen-factors driving the MDR-TB transmission and the study outcome can inform the design of targeted interventions OBJECTIVES/GOALS: The emergence of multidrug-resistant tuberculosis (MDR-TB) poses serious challenges for the global eradication of tuberculosis. Recent research has shown that transmission is now the dominant driver of MDR-TB. However, our limited understanding of where and among whom MDR-TB is transmitted hampers efforts to control person-to-person spread. METHODS/STUDY POPULATION: We used several analytic approaches to characterize the dynamics of MDR-TB transmission in Shanghai, China. We identified all culture-confirmed MDR cases between 2009-2016 in the city and 1) estimated individual-level risk factors for MDR disease; 2) mapped the TB cases by their home addresses and used a Bayesian spatial disease mapping method to identify regions with an elevated risk of MDR-TB; and 3) we sequenced all MDR isolates to understand whether transmission explained variance in risk that was not attributable to the distribution of individual or location-specific risk variates. RESULTS/ANTICIPATED RESULTS: There were 1034 MDR-TB cases among 16,315 culture-confirmed TB cases during the study period. Bayesian disease mapping identified spatial heterogeneity of MDR-TB and determined four hotspots with an elevated risk of MDR-TB, none of which were fully explained by individual or regional-covariates (Figure 1). Sequencing revealed that more than 40% of the MDR-TB strains were in genomic clusters, indicating recent MDR-TB transmission. Most importantly, MDR-TB cases in three of the four large clades (>8 isolates) were spatially concentrated in three strain-specific hotspots (Figure 2). DISCUSSION/SIGNIFICANCE OF FINDINGS: With the combination of traditional epidemiological tools, geographical, and genomic methods, this study revealed multiple loci of transmission of specific MDR-TB clades within a single city. Identification of where and among whom MDR-TB is transmitted can inform the design of targeted interventions.

Good tools can bring mechanical verification to programs written in mainstream functional languages. We use hs-to-coq to translate significant portions of Haskell’s containers library into Coq, and verify it against specifications that we derive from a variety of sources including type class laws, the library’s test suite, and interfaces from Coq’s standard library. Our work shows that it is feasible to verify mature, widely used, highly optimized, and unmodified Haskell code. We also learn more about the theory of weight-balanced trees, extend hs-to-coq to handle partiality, and – since we found no bugs – attest to the superb quality of well-tested functional code.

Loeys–Dietz syndrome is a connective tissue disorder known to cause aggressive aortopathy in paediatric patients, but it is extremely rare for cardiovascular events to present during infancy. We report the first successful aortic repair in a neonate with LDS presenting in extremis with an early onset, massive aortic aneurysm.

Susan Okin has written an important book on justice and the family. Animated by the experiences that contemporary feminism has sought to articulate, and guided by a principled hostility to the subordination of women that continues to disgrace American life, she argues that the current ordering of domestic life in the United States is unjust and that its alteration ought to be made a matter of public policy.

Families, according to Okin, are not havens in an otherwise heartless world. Instead the current division of domestic labor marks them as the centerpiece of a broader system of inequalities between men and women. Justice condemns those inequalities and commands their remedy through the transformation of our domestic practices. Because the division of domestic labor is so fundamental to injustice, we need in particular to ‘encourage and facilitate’ (171) equal sharing by parents in the responsibilities of child-rearing, and in the more quotidian chores that provide the material foundation of modern domesticity.

OBJECTIVES/SPECIFIC AIMS: Objective: Approximately 86 million people in the US have prediabetes, but only a fraction of them receive proven effective therapies to prevent diabetes. Further, the effectiveness of these therapies varies with individual risk of progression to diabetes. We estimated the value of targeting those individuals at highest diabetes risk for treatment, compared to treating all individuals meeting inclusion criteria for the Diabetes Prevention Program (DPP). METHODS/STUDY POPULATION: METHODS: Using a micro-simulation model, we estimated total lifetime costs and quality-adjusted life expectancy (QALE) for individuals receiving: (1) lifestyle intervention involving an intensive program focused on healthy diet and exercise, (2) metformin administration, or (3) no intervention. The model combines several components. First a Cox proportional hazards model predicted onset of diabetes from baseline characteristics for each pre-diabetic individual and yielded a probability distribution for each alternative. We derived this risk model from the Diabetes Prevention Program (DPP) clinical trial data and the follow-up study DPP-OS. The Michigan Diabetes Research Center Model for Diabetes then estimated costs and outcomes for individuals after diabetes diagnosis using standard of care diabetes treatment. Based on individual costs and QALE, we evaluated NMB of the two interventions at population and individual levels, stratified by risk quintiles for diabetes onset at 3 years. RESULTS/ANTICIPATED RESULTS: Results: Compared to usual care, lifestyle modification conferred positive benefits for all eligible individuals. Metformin’s NMB was negative for the lowest population risk quintile. By avoiding use among individuals who would not benefit, targeted administration of metformin conferred a benefit of $500-$800 per person, depending on duration of treatment effect. When treating only 20% of the population (e.g., due to capacity constraints), targeting conferred a NMB of $14,000-$18,000 per person for lifestyle modification and $16,000-$20,000 for metformin. DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusions: Metformin confers value only among higher risk individuals, so targeting its use is worthwhile. While lifestyle modification confers value for all eligible individuals, prioritizing the intervention to high risk patients when capacity is constrained substantially increases societal benefits.

OBJECTIVES/SPECIFIC AIMS: Costs associated with the treatment of skin diseases accounted for greater than 4% of total US healthcare spending in 2013, an increase of $46 billion (170%) since 2004. Considering the increase in novel treatments and spending, cost-utility analyses (CUAs) may provide a better understanding of costs in dermatology. In this study, we conduct a systematic overview of study quality among CUAs related to dermatology. METHODS/STUDY POPULATION: We queried studies from the Tufts Medical Center Cost-Effectiveness Analysis Registry (www.cearegistry.org), a database supplying information on all peer-reviewed cost-effectiveness analysis through 2014. Database methodology was previously discussed here. We queried studies using keywords from the 24 major skin disease categories (e.g., diseases relating to actinic damage were searched by using “actinic,” “actinic keratosis”). We collected data on study design, reporting methods, and analyzed relevant data stratified by 2 time-periods (1976–2008 and 2009–2014) chosen to encompass a comparable number of studies. RESULTS/ANTICIPATED RESULTS: In total, 42 and 50 studies corresponding to the 2 time-periods were retrieved (representing 14/24 disease categories). Based on the recommended data reporting guidelines for CUAs, study quality remained largely unchanged across the 2 phases. Across the 2 time-periods, a societal perspective was used in 19% and 12% of studies, costs and (quality adjusted life-years) QALYs were discounted in 67% and 72% of studies, a correct (incremental cost-effectiveness ratio) ICER was reported in 67% and 72% of studies, and a sensitivity analysis was included in 88% and 84% of studies, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings suggest the quality of dermatology-related CUAs, as evaluated by recommended data reporting guidelines, to be generally stable during the analyzed time-periods. However, the quality of our results may be limited by the small number of CUAs within dermatology (10/24 disease categories did not have CUAs across any time-period). Moving forward, we encourage researchers within dermatology to pursue additional investigation towards cost-effective practices while adhering closely to recommended quality reporting guidelines for CUAs.

Nickel-titanium (NiTi) alloys combine several remarkable characteristics, among them are shape-memory, superelasticity, great strain recovery, good biocompatibility, and corrosion resistance. These render them well suited to a wide range of medical applications, such as cardiovascular stents, laparoscopy, and dental applications such as NiTi endodontic files (EFs) used for root canal treatment, which are the focus of this work. Unfortunately, fatigue-induced and incidental failure of NiTi EFs is not uncommon, which may lead to severe medical consequences. Here we examine the effects of cobalt coatings with impregnated fullerene-like WS2 nanoparticles on file fatigue and failure. Dynamic x-ray diffraction, nanoindentation and torque measurements all indicate a significant improvement in the fatigue resistance and time to breakage of the coated files, stemming from reduced friction between the file and the surrounding tissue. These methods are possibly applicable to a variety of NiTi-based medical devices where fatigue and consequent failure are of relevance.

Objectives: Research has shown that effectiveness, cost-effectiveness, and severity of illness each play a role in drug reimbursement decisions. However, the role of budget impact in such decisions is less obvious. Policy makers almost always demand a budget impact estimate yet seem reluctant to formally include budget impact as a rationing criterion. Health economists even reject budget impact as a legitimate criterion. For these reasons, it is important to examine its use in rationing decisions, and rationales underlying its use.

Methods: We trace several rationales supporting the use of budget impact through a literature review, supplemented by semistructured interviews with eleven key stakeholders involved in drug reimbursement decisions in the Netherlands.

Results: Budget impact arguments are used in certain instances, although policy makers appear uncomfortable with its use because well described rationales still are lacking. In addition, we identify the following rationales to support budget impact as a rationing criterion: opportunity costs, loss aversion, uncertainty and equal opportunity.

Conclusions: Budget impact plays a role in drug reimbursement decisions and has rationales to support its use. However, policy makers do not easily admit that they consider budget impact and are even reluctant to explicitly use budget impact as a formal criterion. A debate would strengthen the theoretical foundation of budget impact as a legitimate criterion in the context of drug reimbursement decisions. Such discussion of budget impact's role will also enhance policy-makers' accountability.