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The success of a democratic society depends, Rawls thought, on members having a shared sense of justice, a common basis for reasoning about what is right. Otherwise, disagreements born from conflicts of interest and identity – and associated “distrust and resentment” – will have corrosive effects on social cooperation. But can we reasonably hope for a broadly shared sense of justice? Religious and philosophical pluralism arguably leave hope for an overlapping consensus on a conception of justice sufficient to cabin those corrosive effects. But what about the pluralism of conceptions of justice themselves? I argue that, even on favorable assumptions about people and social cooperation, we should expect serious disagreement about conceptions of justice and the forms of democracy they recommend, as well as conflicts between and among the interests and identities of citizens who endorse those competing conceptions. Even on these favorable assumptions, then, we have reason to worry – as I think Rawls always did – about the fragility of democracy.
Although anesthesiology and endocrinology are two distinct branches of medicine, some recent breakthrough treatments have brought together both medical specialties, particularly those concerned with surgical sciences and critical care. Related to the use of various traditional surgical techniques, the lack of newer and safer drugs, the lack of monitoring tools, and the scarcity of critical care services in the past, managing patients with various endocrine disorders has always been perceived as being more difficult by practicing anesthesiologists.
Health technology assessment (HTA) organizations vary in terms of how they conduct assessments. We assess whether and to what extent HTA bodies have adopted societal and novel elements of value in their economic evaluations.
After categorizing “societal” and “novel” elements of value, we reviewed fifty-three HTA guidelines. We collected data on whether each guideline mentioned each societal or novel element of value, and if so, whether the guideline recommended the element’s inclusion in the base case, sensitivity analysis, or qualitative discussion in the HTA.
The HTA guidelines mention on average 5.9 of the twenty-one societal and novel value elements we identified (range 0–16), including 2.3 of the ten societal elements and 3.3 of the eleven novel value elements. Only four value elements (productivity, family spillover, equity, and transportation) appear in over half of the HTA guidelines, whereas thirteen value elements are mentioned in fewer than one-sixth of the guidelines, and two elements receive no mention. Most guidelines do not recommend value element inclusion in the base case, sensitivity analysis, or qualitative discussion in the HTA.
Ideally, more HTA organizations will adopt guidelines for measuring societal and novel value elements, including analytic considerations. Importantly, simply recommending in guidelines that HTA bodies consider novel elements may not lead to their incorporation into assessments or ultimate decision making.
This study aimed to investigate general factors associated with prognosis regardless of the type of treatment received, for adults with depression in primary care.
We searched Medline, Embase, PsycINFO and Cochrane Central (inception to 12/01/2020) for RCTs that included the most commonly used comprehensive measure of depressive and anxiety disorder symptoms and diagnoses, in primary care depression RCTs (the Revised Clinical Interview Schedule: CIS-R). Two-stage random-effects meta-analyses were conducted.
Twelve (n = 6024) of thirteen eligible studies (n = 6175) provided individual patient data. There was a 31% (95%CI: 25 to 37) difference in depressive symptoms at 3–4 months per standard deviation increase in baseline depressive symptoms. Four additional factors: the duration of anxiety; duration of depression; comorbid panic disorder; and a history of antidepressant treatment were also independently associated with poorer prognosis. There was evidence that the difference in prognosis when these factors were combined could be of clinical importance. Adding these variables improved the amount of variance explained in 3–4 month depressive symptoms from 16% using depressive symptom severity alone to 27%. Risk of bias (assessed with QUIPS) was low in all studies and quality (assessed with GRADE) was high. Sensitivity analyses did not alter our conclusions.
When adults seek treatment for depression clinicians should routinely assess for the duration of anxiety, duration of depression, comorbid panic disorder, and a history of antidepressant treatment alongside depressive symptom severity. This could provide clinicians and patients with useful and desired information to elucidate prognosis and aid the clinical management of depression.
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.
Quality-adjusted life-years (QALYs) and disability-adjusted life-years (DALYs) are commonly used in cost-effectiveness analysis (CEA) to measure health benefits. We sought to quantify and explain differences between QALY- and DALY-based cost-effectiveness ratios, and explore whether using one versus the other would materially affect conclusions about an intervention's cost-effectiveness.
We identified CEAs using both QALYs and DALYs from the Tufts Medical Center CEA Registry and Global Health CEA Registry, with a supplemental search to ensure comprehensive literature coverage. We calculated absolute and relative differences between the QALY- and DALY-based ratios, and compared ratios to common benchmarks (e.g., 1× gross domestic product per capita). We converted reported costs into US dollars.
Among eleven published CEAs reporting both QALYs and DALYs, seven focused on pharmaceuticals and infectious disease, and five were conducted in high-income countries. Four studies concluded that the intervention was “dominant” (cost-saving). Among the QALY- and DALY-based ratios reported from the remaining seven studies, absolute differences ranged from approximately $2 to $15,000 per unit of benefit, and relative differences from 6–120 percent, but most differences were modest in comparison with the ratio value itself. The values assigned to utility and disability weights explained most observed differences. In comparison with cost-effectiveness thresholds, conclusions were consistent regardless of the ratio type in ten of eleven cases.
Our results suggest that although QALY- and DALY-based ratios for the same intervention can differ, differences tend to be modest and do not materially affect comparisons to common cost-effectiveness thresholds.
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.
Decision-makers in low- and middle-income countries (LMICs) often must prioritize health spending without quantitative benchmarks for the value of their purchases. The Tufts Global Health Cost-Effectiveness Analysis (GH CEA) Registry (healtheconomicevaluation.org/GHCEARegistry/) is a freely-available, curated and standardized dataset designed to address this need.
All indexed English-language articles published between 1995 and 2017 are currently included in the GH CEA Registry. Studies are limited to those reporting cost-effectiveness in terms of cost per disability-adjusted life years (DALYs) averted, a commonly-employed metric in global health. Abstracted data include intervention type, comparator(s), country, funding source, study characteristics (e.g., perspective, time horizon), primary study findings, sensitivity analyses, and disaggregated data on costs and DALYs. Study quality is assessed using a numerical scoring system (from 1-7, higher scores indicating better quality) based on accuracy of findings and comprehensive reporting of methods and results.
To date, 620 articles have been included in the GH CEA Registry. Among LMICs, studies have been conducted primarily in Sub-Saharan Africa (41 percent) or South Asia (34 percent), have focused on communicable diseases (67 percent), and have involved immunization, educational, or pharmaceutical interventions (67 percent). As a priority-setting example, seven percent of interventions from higher-quality studies (ratings of 5 or higher) were reported to be cost-saving (i.e., lower costs and greater DALYs than standard care), two-thirds of which involved primary disease prevention (e.g., immunization, educational or behavioral interventions).
The GH CEA Registry is a new tool for decision-makers in LMICs, particularly those without a formal health technology assessment infrastructure but with a remit for providing access to essential, cost-effective health interventions. New functions are under development, including league tables for priority ranking, a repository for shared models, and tools for enhancing transferability between settings.
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.
In “Contractualism and Utilitarianism,” Scanlon first presents his contractualist theory of moral rightness. According to that theory, elaborated in his subsequent work, conduct is morally wrong just in case it conflicts with “any set of principles for the general regulation of behavior that no one could reasonably reject as a basis for informed, unforced general agreement.” Lying and stealing, for example, are wrong because principles that permit lying or stealing can reasonably be rejected as a basis for such agreement. Intuitively, when you lie or steal, you act in ways that you cannot justify to others.
Scanlon's contractualism shares with other contract theories the concern about justifiability to others. A distinctive feature of Scanlon's view is that, in conducting such mutual justification, the contracting parties themselves use a normative notion of reasonableness. When we reason about right and wrong, we ask ourselves whether a proposed principle is reasonable for others to accept or reject. The notion of reasonableness is distinct from and irreducible to rationality. When I assess a proposed principle for the general regulation of behavior, I do not ask whether compliance with the principle is rationally advantageous – an effective means for achieving my aims. Instead, I ask whether the principle is reasonable to accept or reject.
As Scanlon emphasizes in “Contractualism,” moral contractualism contrasts on this point with Rawls's social-contract theory of justice. In TJ, Rawls observes that different contract theories – those developed by Hobbes, Locke, Rousseau, and Kant, for example – all employ an idea of justification via universal agreement in an “initial situation.” They differ in how they interpret that initial situation. In Rawls's preferred interpretation of the initial situation – the original position – the parties, reasoning under informational constraints, make a rational choice of principles. Each person asks what the most effective way is of advancing his or her good. Parties in the Rawlsian initial choice situation thus make no use of the notion of reasonableness. The original position relies instead on what I will be calling the Rational Advantage Model.
To be clear, Rawls does not suppose that people in a just society (or any society) act solely on the basis of judgments of rational advantage. In a just society, people act in part on the basis of their sense of justice, as specified by a set of principles of justice.
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.