Prospective evaluation of an assessment tool for technical performance of duodenoscopes.

OBJECTIVE: While single-use and detachable-tip duodenoscopes have been recently developed to overcome risks of infection transmission, there are no reliable tools to objectively assess their technical performance. We evaluated the reliability and validity of a newly developed tool to assess the technical performance of reusable duodenoscopes. METHODS: An assessment tool was developed to measure duodenoscope performance based on three distinct criteria: maneuverability, mechanical/imaging characteristics and ability to perform requisite interventions. The assessment tool was tested prospectively on duodenoscopes used in endoscopic retrograde cholangiopancreatography (ERCP) procedures at nine academic medical centers over a 6-month period. The main outcome was reliability of the duodenoscope assessment tool, which was estimated using Cronbach's coefficient alpha (α). The secondary outcome was validity of the assessment tool. RESULTS: The assessment tool evaluated technical performance of reusable duodenoscopes in 1080 ERCP procedures. Indications were biliary in 92.8% and pancreatic in 7.2% procedures. The overall Cronbach's coefficient α for maneuverability was 0.81, assessment of mechanical/imaging characteristics was 0.92, and ability to perform requisite interventions was 0.87. On multiple linear regression analysis, prolonged procedure duration, older patient age and pancreatic interventions were significantly positively associated with higher (worse) scores. CONCLUSIONS: The newly developed assessment tool appears reliable and valid for evaluating the technical performance of duodenoscopes. Registration: ClinicalTrials.gov Identifier: NCT04004533.

Simplifying Resect and Discard Strategies for Real-Time Assessment of Diminutive Colorectal Polyps.

BACKGROUND & AIMS: During endoscopy, the resect and discard strategy, if performed with high confidence, can be used to determine histologic features of diminutive colorectal polyps (5 mm or less). These polyps can then be removed and discarded without pathology assessment. However, the complexities of real-time optical assessment and follow-up management have provided challenges to widespread use of this approach. We aimed to determine the outcomes of simple alternative strategies, in which all diminutive polyps can be resected and discarded. METHODS: We collected data from 2 previous studies that used narrow-band imaging to assess polyps, performed at 5 medical centers (1658 patients with 2285 diminutive polyps; 15 endoscopists). We compared 3 resect and discard strategies: the currently used optical strategy, which relies on high confidence optical assessment of all diminutive polyps; a location-based strategy that classifies all recto-sigmoid diminutive polyps a priori as hyperplastic and all polyps proximal to the recto-sigmoid colon a priori as neoplastic; and a simplified optical strategy, in which all recto-sigmoid diminutive polyps are classified as hyperplastic unless confidently assessed as neoplastic, and all polyps proximal to the recto-sigmoid colon are classified as neoplastic unless confidently assessed as hyperplastic polyps. The primary outcome was the agreement of the surveillance interval calculated for each strategy with the surveillance interval determined by pathology analysis. RESULTS: The proportion of surveillance intervals that agreed with pathology-based surveillance recommendations was slightly higher when the optical strategy was used compared to the location-based strategy or simplified optical strategy (94% vs 89% and 90%, respectively; P < .001). When the 5-10 year recommendations for patients with low-risk polyps were applied as a 10-year surveillance interval, all 3 strategies resulted in surveillance interval agreement compared to pathology above 90% (the quality benchmark). Use of the simplified or location-based strategy could have avoided pathology analysis for 77% of all polyps, compared to 59% if the optical strategy was used (P < .001). In addition, a higher proportion of patients could receive recommendations immediately after colonoscopy with use of the simplified or location based strategy (65%) compared to the optical strategy (40%) (P < .001). CONCLUSION: A location-based and a simplified optical resect and discard strategy produced surveillance recommendations that were in agreement with those from pathology analysis for at least 90% of patients, assuming a 10-year surveillance interval for patients with low-risk polyps. These strategies could further reduce the number of pathology examinations and provide more patients with immediate surveillance recommendations. Optical assessment might be reduced or might not be required for resect and discard. Clintrials.gov no: NCT01935180 and NCT01288833.

Cassandra: An open source Monte Carlo package for molecular simulation.

Cassandra is an open source atomistic Monte Carlo software package that is effective in simulating the thermodynamic properties of fluids and solids. The different features and algorithms used in Cassandra are described, along with implementation details and theoretical underpinnings to various methods used. Benchmark and example calculations are shown, and information on how users can obtain the package and contribute to it are provided. © 2017 Wiley Periodicals, Inc.

Beyond histograms: efficiently estimating radial distribution functions via spectral Monte Carlo.

Despite more than 40 years of research in condensed-matter physics, state-of-the-art approaches for simulating the radial distribution function (RDF) g(r) still rely on binning pair-separations into a histogram. Such methods suffer from undesirable properties, including subjectivity, high uncertainty, and slow rates of convergence. Moreover, such problems go undetected by the metrics often used to assess RDFs. To address these issues, we propose (I) a spectral Monte Carlo (SMC) quadrature method that yields g(r) as an analytical series expansion; and (II) a Sobolev norm that assesses the quality of RDFs by quantifying their fluctuations. Using the latter, we show that, relative to histogram-based approaches, SMC reduces by orders of magnitude both the noise in g(r) and the number of pair separations needed for acceptable convergence. Moreover, SMC reduces subjectivity and yields simple, differentiable formulas for the RDF, which are useful for tasks such as coarse-grained force-field calibration via iterative Boltzmann inversion.

Cost-effectiveness of colorectal cancer screening in Germany: current endoscopic and fecal testing strategies versus plasma methylated Septin 9 DNA.

BACKGROUND AND STUDY AIMS: Colorectal cancer (CRC) screening strategies in Germany include guaiac-based fecal occult blood testing (gFOBT) starting at age 50 and a switch to colonoscopy at age 55 or continued gFOBT testing, but screening utilization is limited. Blood-based biomarkers, such as methylated Septin 9 DNA ( (m) SEPT9), may improve screening rates. We performed a cost-effectiveness analysis of current and emerging CRC screening strategies in Germany. METHODS: Using a validated Markov model, we compared annual gFOBT for ages 50 through 54 followed by biennial testing until age 75 (FOBT) or by colonoscopy at ages 55 and 65 (FOBT/COLO 55,65), substitution of fecal immunochemical testing (FIT) for gFOBT (FIT, FIT/COLO 55,65), and annual or biennial plasma (m) SEPT9 testing. We also considered persons who utilize only colonoscopy and varied age at colonoscopy utilization. RESULTS: The current strategies were more effective and less costly than no screening. FIT was more effective and less costly than (m) SEPT9 testing. FIT/COLO 55,65 cost €12 200 per quality-adjusted life-years gained in comparison with FIT. (m) SEPT9-based screening was cost-effective in comparison with no screening but was dominated by other cost-saving strategies. Differential screening utilization and adherence greatly affected incremental results between strategies. In probabilistic analyses, FIT was preferred in 49 % and FIT/COLO 55,65 in 47 % of iterations. CONCLUSION: Currently available CRC screening strategies in Germany, including hybrid fecal testing/colonoscopy, are likely to be cost-saving. Current strategies appear superior to (m) SEPT9-based screening. The impact of blood-based biomarkers is likely to depend on utilization and adherence as much as on test performance characteristics and cost.

Colorectal cancer screening--optimizing current strategies and new directions.

The first evidence that screening for colorectal cancer (CRC) could effectively reduce mortality dates back 20 years. However, actual population screening has, in many countries, halted at the level of individual testing and discussions on differences between screening tests. With a wealth of new evidence from various community-based studies looking at test uptake, screening-programme organization and the importance of quality assurance, population screening for CRC is now moving into a new realm, promising better results in terms of reducing CRC-specific morbidity and mortality. Such a shift in the paradigm requires a change from opportunistic, individual testing towards organized population screening with comprehensive monitoring and full-programme quality assurance. To achieve this, a combination of factors--including test characteristics, uptake, screenee autonomy, costs and capacity--must be considered. Thus, evidence from randomized trials comparing different tests must be supplemented by studies of acceptance and uptake to obtain the full picture of the effectiveness (in terms of morbidity, mortality and cost) the different strategies have. In this Review, we discuss a range of screening modalities and describe the factors to be considered to achieve a truly effective population CRC screening programme.

Capsule colonoscopy increases uptake of colorectal cancer screening.

BACKGROUND: Screening colonoscopy effectiveness is hampered by limited adherence by the general population. The present prospective study was performed to evaluate whether adding capsule colonoscopy to the endoscopic screening options increases uptake. METHODS: Invitation letters were sent to 2150 persons above the age of 55 insured with a German medical insurance company in the area of Rinteln, Lower Saxony with a baseline spontaneous annual screening colonoscopy uptake of 1 %. Both capsule or conventional colonoscopy were offered. Interested persons were given information about the two screening options by four local gastroenterologists and examinations were then performed according to screenees' final choice. RESULTS: 154 persons sought further information, and 34 and 90 underwent conventional and capsule colonoscopy, respectively. Colonoscopy uptake was thus increased by the invitation process by 60 % (1.6 % vs. 1 %; p = 0.075), while the option of capsule endoscopy led to a fourfold increase of screening uptake (4.2 % vs. 1 %, p < 0.001). Despite similar age distribution in both sex groups, uptake in men was significantly higher (5.6 % vs. 2.8 %, p = 002). However, overall adenoma yield was not different in both groups. CONCLUSIONS: The present study suggests that offering the option of capsule colonoscopy increases uptake of endoscopic colorectal cancer screening. However, capsule endoscopy sensitivity for adenoma detection needs to be improved.

Reaction Ensemble Monte Carlo Simulation of Complex Molecular Systems.

Acceptance rules for reaction ensemble Monte Carlo (RxMC) simulations containing classically modeled atomistic degrees of freedom are derived for complex molecular systems where insertions and deletions are achieved gradually by utilizing the continuous fractional component (CFC) method. A self-consistent manner in which to utilize statistical mechanical data contained in ideal gas free energy parameters during RxMC moves is presented. The method is tested by applying it to two previously studied systems containing intramolecular degrees of freedom: the propene metathesis reaction and methyl-tert-butyl-ether (MTBE) synthesis. Quantitative agreement is found between the current results and those of Keil et al. (J. Chem. Phys. 2005, 122, 164705) for the propene metathesis reaction. Differences are observed between the equilibrium concentrations of the present study and those of Lísal et al. (AIChE J. 2000, 46, 866-875) for the MTBE reaction. It is shown that most of this difference can be attributed to an incorrect formulation of the Monte Carlo acceptance rule. Efficiency gains using CFC MC as opposed to single stage molecule insertions are presented.

Endoscopic versus surgical therapy for early cancer in Barrett's esophagus: a decision analysis.

BACKGROUND: Esophagectomy for early esophageal adenocarcinoma is associated with increased operative mortality and morbidity, but possibly a decreased recurrence rate compared with endoscopic therapy when using EMR and radiofrequency ablation. OBJECTIVE: To compare the cost-effectiveness of esophagectomy and endoscopic therapy in the treatment of early esophageal adenocarcinoma. DESIGN: Decision analysis model. MAIN OUTCOME MEASUREMENTS: Incremental cost-effectiveness ratio. RESULTS: During the 5-year study period, endoscopic therapy cost $17,000.00 and yielded 4.88 quality-adjusted life years, compared with $28,000.00 and 4.59, respectively, for esophagectomy. Varying the recurrence rates of cancer or Barrett's esophagus metaplasia after endoscopic therapy did not change the overall outcome. The sensitivity analysis demonstrated, however, that the outcome depended on the rate of lymph node involvement and operative mortality. Under the best of circumstances in favor of esophagectomy, such as 2% operative mortality, no reduced quality of life after esophagectomy, and a low 5-year survival rate after recurrence of endoscopic ablation, the risk of positive lymph nodes still needed to exceed 25% before esophagectomy became the preferred treatment option. This threshold is twice as high as the values reported for early submucosal cancer invasion. LIMITATIONS: Limited data are available about the long-term outcome of EMR and radiofrequency ablation. CONCLUSIONS: Endoscopic therapy for early Barrett's esophagus adenocarcinoma is more effective and less expensive than esophagectomy. Even in early esophageal adenocarcinoma with submucosal invasion, endoscopic therapy is a cost-effective alternative to esophagectomy, especially in patients with a high operative risk.

Prospective, randomized comparison of mechanical and electronic radial endoscopic ultrasound systems: assessment of performance parameters and image quality.

OBJECTIVE: Implementation of electronic image technology in endoscopic ultrasonography (EUS) should improve image quality, but systematic data are scarce. The purpose of this study was to compare the image quality and performance of an electronic and a mechanical radial echoendoscope. MATERIAL AND METHODS: Eighty consecutive patients (42 M, mean age 56 years) in a tertiary referral center, without gross pathology (advanced tumors excluded), were prospectively randomized to EUS with the mechanical or electronic echoendoscope. Images from five standardized positions (pancreatobiliary and upper gastrointestinal (GI) tract) were taken by two examiners of differing experience. Time to acquire images was noted. Penetration depth was also measured. Image quality variables (overall quality, contrast, and structure discrimination) were assessed blindly on the basis of randomly shuffled images during three independent evaluations by the same experienced examiner (mean values were taken), using a visual analogue scale (VAS) from 1 (excellent) to 10 (inadequate). RESULTS: Time needed to achieve visualization of the distal common bile duct (CBD) was significantly shorter with the electronic scope (49.7+/-8.6 versus 97.4+/-8.5 s; p<0.001). Image quality with the electronic scope was rated significantly better for all variables assessed, whereas EUS penetration depth was similar in both groups. There were no differences in examiner experience. CONCLUSIONS: Electronic EUS provided better quality images according to the examiner's subjective assessment. An objective advantage was faster identification of the distal CBD.

Investigation of the phase behavior of an embedded charge protein model through molecular simulation.

The phase behavior of an embedded-charge model for lysozyme developed by Carlsson and co-workers (J. Phys. Chem. B 2001, 105, 9040) is investigated using grand canonical transition matrix Monte Carlo simulation. Within this model, protein-protein interactions are approximated through a combination of hard-sphere repulsion, isotropic hydrophobic attraction, and screened electrostatic interactions through a series of embedded point charges located at the positions of charged amino acid groups within lysozyme. Liquid-liquid phase diagrams are constructed for a wide range of solution conditions and compared with experimental data. Our results indicate that the model is generally capable of describing qualitative trends in the evolution of protein phase behavior with variation of pH and ionic strength. From a quantitative perspective, model estimates for both the change in critical temperature with variation of the solution conditions and the critical concentration do not agree with experimental results. We find the width of model coexistence curves to be independent of solution conditions and narrow relative to experimentally obtained phase envelopes. Connections between the value of the second virial coefficient evaluated at the critical temperature and the location of the liquid-liquid phase envelope are also examined.

Endoscopic ultrasonography for upper gastrointestinal submucosal lesions: a cost minimization analysis with an international perspective.

OBJECTIVES: Our prospective clinical study of prospectively compared physicians' management of submucosal tumors (SMTs) with and without endoscopic ultrasound (EUS). It showed that EUS reduced further tests by more than 50%, but it is unclear whether it reduced the overall costs. The aim of this study was to determine whether EUS would reduce costs. METHODS: Based on the data from the clinical study, a decision analysis was created to compare the direct hospital costs for diagnosing SMTs with and without EUS. Cost data from Germany, Canada, Japan, France, and the United States were used. Costs were expressed as a ratio of the cost of esophagogastroduodenoscopy (EGD). Average cost ratios for each procedure were as follows (sensitivity analysis ranges are 95% CIs): EGD = 1; large particle biopsy (LPB) 0.75 (0.22-1.24); endoscopic ultrasound (EUS) 2.0 (1.22-2.79); abdominal ultrasound (US) 0.77 (0.31-1.24); computed tomography (CT) 1.79 (0.64-2.95); magnetic resonance imaging (MRI) 3.54 (1.28-5.79); and ERCP 3.45 (0.82-6.07). RESULTS: Initial inputs show the "no EUS" strategy is less costly when cost data for all countries are averaged (expected cost 2.13 vs 2.71, expressed as a ratio of the cost of EGD]) and for all countries individually except Germany. In descending order, overall management costs were most sensitive to the relative costs of CT and EUS, the cost of LPB, and to the probability of no further testing when the "no EUS" strategy is used. However, threshold analysis showed that changes in only one variable, the ratio of the cost of EUS compared to CT (the "EUS/CT ratio"), were able to shift the optimal strategy from "no EUS" to "EUS." "EUS" becomes less costly only if the EUS/CT cost ratio is <0.85 (i.e., if the cost of EUS is <85% that of CT). If the potential for EUS to reduce severe complications caused by LPB of high risk lesions is incorporated, "EUS" is less costly if this risk is >2% (range 1-5%). CONCLUSIONS: When used to diagnose SMTs, EUS may reduce the need for further tests but not necessarily costs. For this indication, the relative cost of EUS compared with CT is what most limits its potential value as a cost-minimizing test. The costs, economic impact, and hence the relative appropriateness of EUS and other procedures may vary in different health care systems.