Modeling the impact of 13RS-HB358: HPV vaccination for school entry in a high-prevalence state

Prophylactic cancer vaccination presents novel opportunities to improve the health and well-being of populations. Since the approval of a cervical cancer vaccine against human papillomavirus (HPV) in 2006, only three states have passed legislation adding it to their school-entry schedules of required vaccinations. Despite ample evidence of its safety and efficacy, the vaccine remains controversial, and national vaccination rates among both girls and boys remain low. Risk for HPV-related cancers varies by population, and Appalachian Kentucky has among the highest HPV-related morbidity and mortality in the nation. Annual attempts to pass HPV vaccine legislation in Kentucky have so far failed in the absence of directly targeted quantitative data on the risks and rewards of action vs. inaction. We herein present the first known impact assessment of an HPV vaccine school entry requirement for the state of Kentucky, using a transmission-dynamic model to simulate vaccine scenarios in the context of Kentucky’s high HPV disease burden and unique population characteristics. Our findings suggest that over the lifetime of those first vaccinated after passage, such a policy could prevent approximately 18 thousand cancers and 3 thousand deaths; preserve 18 thousand life-years and more than 34 thousand quality-adjusted life years; and save as much as 1.3 billion USD in the state of Kentucky

TextCode: A Tool to Support Problem Solving Among Novice Programmers

Several tools have been developed to support novices learning to program. Most of them focus on the code and provide features regarding the visualization of the data structures or the debugging. However, in introductory programming courses, students are typically given exercises in the form of a problem written in natural language; and the first challenge they face is understanding the problem, identifying the relevant information, and then translating that information into code. To our knowledge, little attention has been paid to proposing tools targeted at supporting this problem-solving step, even though it is crucial for deriving a correct solution. In this paper, we present an IDE to encourage novices to understand the problem before start coding, decompose it down into subproblems, explore alternative implementations for each subproblem, and arrange these implementations to build a general solution. Finally, the adopted problem-solving approach is discussed

Epidemiological Effectiveness and Cost of a Fungal Meningitis Outbreak Response in New River Valley, Virginia: Local Health Department and Clinical Perspectives.

OBJECTIVE: We evaluated the effectiveness and cost of a fungal meningitis outbreak response in the New River Valley of Virginia during 2012-2013 from the perspective of the local public health department and clinical facilities. The fungal meningitis outbreak affected 23 states in the United States with 751 cases and 64 deaths in 20 states; there were 56 cases and 5 deaths in Virginia. METHODS: We conducted a partial economic evaluation of the fungal meningitis outbreak response in New River Valley. We collected costs associated with the local health department and clinical facilities in the outbreak response and estimated the epidemiological effectiveness by using disability-adjusted life years (DALYs) averted. RESULTS: We estimated the epidemiological effectiveness of this outbreak response to be 153 DALYs averted among the patients, and the costs incurred by the local health department and clinical facilities to be $30,413 and$39,580, respectively. CONCLUSIONS: We estimated the incremental cost-effectiveness ratio of $198 per DALY averted and$258 per DALY averted from the local health department and clinical perspectives, respectively, thereby assisting in impact evaluation of the outbreak response by the local health department and clinical facilities. (Disaster Med Public Health Preparedness. 2018;12:38-46)

Frame-Based Editing: Easing the Transition from Blocks to Text-Based Programming

Block-based programming systems, such as Scratch or Alice, are the most popular environments for introducing young children to programming. However, mastery of text-based programming continues to be the educational goal for stu- dents who continue to program into their teenage years and beyond. Transitioning across the significant gap between the two editing styles presents a difficult challenge in school- level teaching of programming. We propose a new style of program manipulation to bridge the gap: frame-based edit- ing. Frame-based editing has the resistance to errors and approachability of block-based programming while retaining the flexibility and more conventional programming seman- tics of text-based programming languages. In this paper, we analyse the issues involved in the transition from blocks to text and argue that they can be overcome by using frame- based editing as an intermediate step. A design and imple- mentation of a frame-based editor is provided

Outlook for tuberculosis elimination in California: An individual-based stochastic model.

RationaleAs part of the End TB Strategy, the World Health Organization calls for low-tuberculosis (TB) incidence settings to achieve pre-elimination (<10 cases per million) and elimination (<1 case per million) by 2035 and 2050, respectively. These targets require testing and treatment for latent tuberculosis infection (LTBI).ObjectivesTo estimate the ability and costs of testing and treatment for LTBI to reach pre-elimination and elimination targets in California.MethodsWe created an individual-based epidemic model of TB, calibrated to historical cases. We evaluated the effects of increased testing (QuantiFERON-TB Gold) and treatment (three months of isoniazid and rifapentine). We analyzed four test and treat targeting strategies: (1) individuals with medical risk factors (MRF), (2) non-USB, (3) both non-USB and MRF, and (4) all Californians. For each strategy, we estimated the effects of increasing test and treat by a factor of 2, 4, or 10 from the base case. We estimated the number of TB cases occurring and prevented, and net and incremental costs from 2017 to 2065 in 2015 U.S. dollars. Efficacy, costs, adverse events, and treatment dropout were estimated from published data. We estimated the cost per case averted and per quality-adjusted life year (QALY) gained.Measurements and main resultsIn the base case, 106,000 TB cases are predicted to 2065. Pre-elimination was achieved by 2065 in three scenarios: a 10-fold increase in the non-USB and persons with MRF (by 2052), and 4- or 10-fold increase in all Californians (by 2058 and 2035, respectively). TB elimination was not achieved by any intervention scenario. The most aggressive strategy, 10-fold in all Californians, achieved a case rate of 8 (95% UI 4-16) per million by 2050. Of scenarios that reached pre-elimination, the incremental net cost was $20 billion (non-USB and MRF) to$48 billion. These had an incremental cost per QALY of $657,000 to$3.1 million. A more efficient but somewhat less effective single-lifetime test strategy reached as low as $80,000 per QALY.ConclusionsSubstantial gains can be made in TB control in coming years by scaling-up current testing and treatment in non-USB and those with medical risks

J Adolesc Health

PurposeTo assess the optimal age at which a one-time HIV screen should begin for adolescents and young adults (AYA) in the United States without identified HIV risk factors, incorporating clinical impact, costs, and cost-effectiveness.MethodsWe simulated HIV-uninfected 12-year-olds in the US without identified risk factors who faced age-specific risks of HIV infection (0.6\u201371.3/100,000PY). We modeled a one-time screen ($36) at age 15, 18, 21, 25, or 30, each in addition to current US screening practices (30$/year-of-life saved (YLS) from the healthcare system perspective. In sensitivity analyses, we varied HIV incidence, screening and linkage rates, and costs.ResultsAll one-time screens detected a small proportion of lifetime infections (0.1\u201310.3%). Compared to current US screening practices, a screen at age 25 led to the most favorable care continuum outcomes at age 25: proportion diagnosed (77% vs. 51%), linked to care (71% vs. 51%), retained in care (68% vs. 44%) and virologically suppressed (49% vs. 32%). Compared to the next most effective screen, a screen at age 25 provided the greatest clinical benefit, and was cost-effective ($96,000/YLS) by US standards (<$100,000/YLS).ConclusionsFor US AYA without identified risk factors, a one-time routine HIV screen at age 25, after the peak of incidence, would optimize clinical outcomes and be cost-effective compared to current US screening practices. Focusing screening on AYA ages 18 or younger is a less efficient use of a one-time screen among AYA than screening at a later age.L30 AI120123/AI/NIAID NIH HHS/United StatesR01 AI042006/AI/NIAID NIH HHS/United StatesR01 HD079214/HD/NICHD NIH HHS/United StatesU38 PS004644/PS/NCHHSTP CDC HHS/United States2019-01-01T00:00:00Z29273141PMC5745059vault:2571

MEDICAL DEVICES DISTINCTIVE FEATURES

Medical devices (MDs) have distinctive features, such as incremental innovation, dynamic pricing, the learning curve and organisational impact, that need to be considered when they are evaluated. This paper investigates how MDs have been assessed in practice, in order to identify methodological gaps that need to be addressed to improve the decision-making process for their adoption. We used the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist supplemented by some additional categories to assess the quality of reporting and consideration of the distinctive features of MDs. Two case studies were considered: transcatheter aortic valve implantation (TAVI) representing an emerging technology and implantable cardioverter defibrillators (ICDs) representing a mature technology. Economic evaluation studies published as journal articles or within Health Technology Assessment reports were identified through a systematic literature review. A total of 19 studies on TAVI and 41 studies on ICDs were analysed. Learning curve was considered in only 16% of studies on TAVI. Incremental innovation was more frequently mentioned in the studies of ICDs, but its impact was considered in only 34% of the cases. Dynamic pricing was the most recognised feature but was empirically tested in less than half of studies of TAVI and only 32% of studies on ICDs. Finally, organisational impact was considered in only one study of ICDs and in almost all studies on TAVI, but none of them estimated its impact. By their very nature, most of the distinctive features of MDs cannot be fully assessed at market entry. However, their potential impact could be modelled, based on the experience with previous MDs, in order to make a preliminary recommendation. Then, well-designed post-market studies could help in reducing uncertainties and make policymakers more confident to achieve conclusive recommendations. © 2017 The Authors. Health Economics published by John Wiley & Sons, Ltd

CREB engages C/EBPδ to initiate leukemogenesis.

cAMP response element binding protein (CREB) is frequently overexpressed in acute myeloid leukemia (AML) and acts as a proto-oncogene; however, it is still debated whether such overactivation alone is able to induce leukemia as its pathogenetic downstream signaling is still unclear. We generated a zebrafish model overexpressing CREB in the myeloid lineage, which showed an aberrant regulation of primitive hematopoiesis, and in 79% of adult CREB-zebrafish a block of myeloid differentiation, triggering to a monocytic leukemia akin the human counterpart. Gene expression analysis of CREB-zebrafish revealed a signature of 20 differentially expressed human homologous CREB targets in common with pediatric AML. Among them, we demonstrated that CREB overexpression increased CCAAT-enhancer-binding protein-δ (C/EBPδ) levels to cause myeloid differentiation arrest, and the silencing of CREB-C/EBPδ axis restored myeloid terminal differentiation. Then, C/EBPδ overexpression was found to identify a subset of pediatric AML affected by a block of myeloid differentiation at monocytic stage who presented a significant higher relapse risk and the enrichment of aggressive signatures. Finally, this study unveils the aberrant activation of CREB-C/EBPδ axis concurring to AML onset by disrupting the myeloid cell differentiation process. We provide a novel in vivo model to perform high-throughput drug screening for AML cure improvement