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41.
Endoscopic submucosal dissection (ESD) is an established technique for the endoscopic therapy of dysplastic and early cancerous lesions throughout the gastrointestinal tract. The procedure requires both a sophisticated knowledge for lesion characterization and high‐level endoscopic skills. As a result, the learning curve is very steep and, in Japan, it takes years to gain proficiency under the traditional Master‐Apprentice teaching model. At present, as a result of multiple limitations, this training model is not applicable to the USA. Nevertheless, a unique, multipronged, stepwise approach has emerged as a viable pathway to train US endoscopists in ESD. Although this approach deserves refinement, it has already led to the expansion of ESD in the USA, has contributed to the widening of the indications for ESD, and has further developed ESD techniques. Multiple challenges remain, but they can be overcome by active collaboration between Japanese and US endoscopists and professional societies. The robust interest in ESD in the USA has drawn industry attention with a few innovations already coming to fruition and many more in development.  相似文献   
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Background

Payers frequently rely on budget impact model (BIM) results to help determine drug coverage policy and its effect on their bottom line. It is unclear whether BIMs typically overestimate or underestimate real-world budget impact.

Objective

We examined how different modeling assumptions influenced the results of 6 BIMs from the Institute for Clinical and Economic Review (ICER).

Study Design

Retrospective analysis of pharmaceutical sales data.

Methods

From ICER reports issued before 2016, we collected estimates of 3 BIM outputs: aggregate therapy cost (ie, cost to treat the patient population with a particular therapy), therapy uptake, and price. We compared these against real-world estimates that we generated using drug sales data. We considered 2 classes of BIM estimates: those forecasting future uptake of new agents, which assumed “unmanaged uptake,” and those describing the contemporaneous market state (ie, estimates of current, managed uptake and budget impact for compounds already on the market).

Results

Differences between ICER's estimates and our own were largest for forecasted studies. Here, ICER's uptake estimates exceeded real-world estimates by factors ranging from 7.4 (sacubitril/valsartan) to 54 (hepatitis C treatments). The “unmanaged uptake” assumption (removed from ICER's approach in 2017) yields large deviations between BIM estimates and real-world consumption. Nevertheless, in some cases, ICER's BIMs that relied on current market estimates also deviated substantially from real-world sales data.

Conclusions

This study highlights challenges with forecasting budget impact. In particular, assumptions about uptake and data source selection can greatly influence the accuracy of results.  相似文献   
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In cases of suspected violations of rules, regulations or the law by armed forces personnel, investigations are invariably mandatory. Military investigations differ from well-researched civilian criminal investigations. Differing from civilian police detectives, most military investigators – as disciplinary supervisors and military police personnel – have a number of tasks to accomplish, which include leading in combat and ensuring military readiness. Military investigations can lead to substantive negative or positive consequences for military readiness, including mental health, unit cohesion and subjective legal certainty. This impact on unit cohesion and mental health is influenced by any prior history of distress or trauma; military investigations are often preceded by contravention of internal disciplinary acts, complaints and traumatic events. This study explores factors in the differing military and legal systems of Germany and the United Kingdom (UK) that might help military personnel to successfully conduct investigations while ensuring deployment readiness and maintaining human rights.  相似文献   
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Objective: Several biologic therapies are available for the treatment of mild-to-moderate Crohn’s disease (CD). This network meta-analysis (NMA) aimed to assess the comparative efficacy of ustekinumab, adalimumab, vedolizumab and infliximab in the maintenance of clinical response and remission after 1?year of treatment.

Methods: A systematic literature search was performed to identify relevant randomized controlled trials (RCTs). Key outcomes of interest were clinical response (CD activity index [CDAI] reduction of 100 points; CDAI-100) and remission (CDAI score under 150 points; CDAI < 150). A treatment sequence Bayesian NMA was conducted to account for the re-randomization of patients based on different clinical definitions, the lack of similarity of the common comparator for each trial and the full treatment pathway from the induction phase onwards.

Results: Thirteen RCTs were identified. Ustekinumab 90?mg q8w was associated with statistically significant improvement in clinical response relative to placebo and vedolizumab 300?mg. For clinical remission, ustekinumab 90?mg q8w was associated with statistically significant improvement relative to placebo and vedolizumab 300?mg q8w. Findings from sub-population analyses had similar results but were not statistically significant.

Conclusions: The NMA suggest that ustekinumab is associated with the highest likelihood of reaching response or remission at 1?year compared with placebo, adalimumab and vedolizumab. Results should be interpreted with caution because this is a novel methodology; however, the treatment sequence analysis may be the most methodologically sound analysis to derive estimates of comparative efficacy in CD in the absence of head-to-head evidence.  相似文献   

49.
Objective and methods: This paper reviews sources of data typically used in guideline development, available grading systems, their pros and cons, and the methods for evaluating risks of bias in publications, and proposes a revised method for grading evidence and recommendations for use in development of clinical treatment guidelines.

Results: The new World Federation of Societies of Biological Psychiatry (WFSBP) grading system allows guideline developers to follow a multi-step approach of defining levels of evidence, applying criteria for grading (define the acceptability) and the grading of recommendations.

Conclusions: Further, these updated WFSBP recommendations for rating evidence and treatment recommendations provide a grading system that takes into account potential biases in sources of evidence in arriving at final ratings that are likely more clinically meaningful and pragmatic and thus should be used for the development of future treatment guidelines.  相似文献   

50.
A long‐standing question in child language research concerns how children achieve mature syntactic knowledge in the face of a complex linguistic environment. A widely accepted view is that this process involves extracting distributional regularities from the environment in a manner that is incidental and happens, for the most part, without the learner's awareness. In this way, the debate speaks to two associated but separate literatures in language acquisition: statistical learning and implicit learning. Both fields have explored this issue in some depth but, at present, neither the results from the infant studies used by the statistical learning literature nor the artificial grammar learning tasks studies from the implicit learning literature can be used to fully explain how children's syntax becomes adult‐like. In this work, we consider an alternative explanation—that children use error‐based learning to become mature syntax users. We discuss this proposal in the light of the behavioral findings from structural priming studies and the computational findings from Chang, Dell, and Bock's (2006) dual‐path model, which incorporates properties from both statistical and implicit learning, and offers an explanation for syntax learning and structural priming using a common error‐based learning mechanism. We then turn our attention to future directions for the field, here suggesting how structural priming might inform the statistical learning and implicit learning literature on the nature of the learning mechanism.  相似文献   
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