The Bethesda ERCP Skills Assessment Tool (BESAT) can reliably differentiate endoscopists of different experience levels.

Background and study aims The Bethesda ERCP Skill Assessment Tool (BESAT) is a video-based assessment tool of technical endoscopic retrograde cholangiopancreatography (ERCP) skill with previously established validity evidence. We aimed to assess the discriminative validity of the BESAT in differentiating ERCP skill levels. Methods Twelve experienced ERCP practitioners from tertiary academic centers were asked to blindly rate 43 ERCP videos using the BESAT. ERCP videos consisted of native biliary cannulation and sphincterotomy and were recorded from 10 unique endoscopists of various ERCP experience (from advanced endoscopy fellow to > 10 years of ERCP experience). Inter-rater reliability, discriminative validity, and internal structure validity were subsequently assessed. Results The BESAT was found to reliably differentiate between endoscopists of varying levels of ERCP experience with experienced ERCPists scoring higher than novice ERCPists in 11 of 13 (85%) instrument items. Inter-rater reliability for BESAT items ranged from good to excellent (intraclass correlation range: 0.86 to 0.93). Internal structure validity was assessed with item-total correlations ranging from 0.53 to 0.83. Conclusions Study findings demonstrate that the BESAT, a video-based ERCP skill assessment tool, has high inter-rater reliability and has discriminative validity in differentiating novice from expert ERCP skill. Further investigations are needed to determine the role of video-based assessment in improving trainee learning curves and patient outcomes.

Characteristics of Very Young Patients Undergoing Total Hip Arthroplasty: A Contemporary Assessment.

Background: This study aims to compare indications, patient characteristics, hospital factors, and complication rates between total hip arthroplasty (THA) patients aged 30 years or younger and those older than 30 years using a large national database. Methods: The Premier Healthcare Database was utilized to identify primary THA patients from 2015 to 2021 who were aged ≤30 or >30 years. Patient demographics, hospital factors, and primary indications were compared for each cohort. Rates of complications and readmissions were assessed for each cohort by primary indication. Differences were assessed through univariate analysis. Results: Overall, 539,173 primary THA patients were identified (age ≤30: 1849; >30: 537,234). Compared to the >30 cohort, the ≤30 cohort was more likely to be male (56.5% vs 44.9%, P < .001) and non-White (34.0% vs 14.2%, P < .001). The most common indications for THA in the ≤30 cohort were osteonecrosis (49.3%), osteoarthritis (17.8%), and congenital hip deformities (16.0%), and in the >30 cohort, they were osteoarthritis (77.0%), other arthritis (11.3%), and osteonecrosis (5.4%). Patients aged ≤30 years had lower rates of respiratory failure (0.16% vs 0.57%, P < .001), acute renal failure (0.32% vs 1.72%, P < .001), and urinary tract infection (0.38% vs 1.11%, P = .003) than those aged >30 years, but higher rates of wound dehiscence (0.59% vs 0.29%, P = .015) and transfusion (3.68% vs 2.21%, P < .001). There were no differences in 90-day readmission rates (P = .811) or 90-day in-hospital death (P = .173) between cohorts. Conclusions: Younger patients undergoing THA differed significantly in indication, patient characteristics, and hospital factors compared to the older population on univariate analysis. Despite differences in indications, the cohorts did not differ markedly with regard to complication rates in this study.

A cost-effectiveness analysis of avelumab plus best supportive care versus best supportive care alone as first-line maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma in Taiwan.

BACKGROUND: Patients with locally advanced or metastatic urothelial carcinoma have limited treatment options and a poor prognosis. The JAVELIN Bladder 100 trial showed that avelumab as first-line maintenance plus best supportive care significantly prolonged overall survival and progression-free survival versus best supportive care alone in patients with locally advanced or metastatic urothelial carcinoma that had not progressed with first-line platinum-containing chemotherapy. AIMS: We assessed whether avelumab plus best supportive care is a cost-effective treatment option versus best supportive care alone in this patient group in Taiwan. METHODS AND RESULTS: A partitioned survival model was used to estimate the costs and effects of avelumab plus best supportive care versus best supportive care alone over a 20-year time horizon from the perspective of Taiwan's National Health Insurance Administration. Patient-level data from JAVELIN Bladder 100 on efficacy, safety, utility, and time on treatment were analyzed to provide parameters for the model. Log-normal and Weibull distributions were used for overall survival and progression-free survival, respectively. Costs of healthcare resources, drug acquisition, adverse events, and progression were identified through publicly available data sources and clinician interviews. The model estimated total costs, life years, and quality-adjusted life years. In the modeled base case, avelumab plus best supportive care increased survival versus best supportive care alone by 0.79 life years (2.93 vs. 2.14) and 0.61 quality-adjusted life years (2.15 vs. 1.54). The incremental cost-effectiveness ratio for avelumab plus best supportive care versus best supportive care alone was NT$1 827 680. Most (78%) of the probabilistic sensitivity analyses fell below three times the gross domestic product per capita. Scenario analysis indicated that life year and quality-adjusted life year gains were most sensitive to alternative survival extrapolations for both avelumab plus best supportive care and best supportive care alone. CONCLUSION: Avelumab first-line maintenance therapy combined with best supportive care was determined as a cost-effective treatment strategy for patients in Taiwan diagnosed with locally advanced or metastatic urothelial carcinoma that had not progressed with platinum-containing chemotherapy.

Medicaid Patients Undergo Total Joint Arthroplasty at Lower-Volume Hospitals by Lower-Volume Surgeons and Have Poorer Outcomes.

BACKGROUND: Medicaid insurance coverage among patients undergoing total hip arthroplasty (THA) or those undergoing total knee arthroplasty (TKA) has been associated with worse postoperative outcomes compared with patients without Medicaid. Surgeons and hospitals with lower annual total joint arthroplasty (TJA) volume have also been associated with worse outcomes. This study sought to characterize the associations between Medicaid insurance status, surgeon case volume, and hospital case volume and to assess the rates of postoperative complications compared with other payer types. METHODS: The Premier Healthcare Database was queried for all adult patients who underwent primary TJA from 2016 to 2019. Patients were divided on the basis of their insurance status: Medicaid compared with non-Medicaid. The distribution of annual hospital and surgeon case volume was assessed for each cohort. Multivariable analyses were performed accounting for patient demographic characteristics, comorbidities, surgeon volume, and hospital volume to assess the 90-day risk of postoperative complications by insurance status. RESULTS: Overall, 986,230 patients who underwent TJA were identified. Of these, 44,370 (4.5%) had Medicaid. Of the patients undergoing TJA, 46.4% of those with Medicaid were treated by surgeons performing ≤100 TJA cases annually compared with 34.3% of those without Medicaid. Furthermore, a higher percentage of patients with Medicaid underwent TJA at lower-volume hospitals performing ≤500 cases annually, 50.8% compared with 35.5% for patients without Medicaid. After accounting for differences among the 2 cohorts, patients with Medicaid remained at increased risk for postoperative deep vein thrombosis (adjusted odds ratio [OR], 1.16; p = 0.031), pulmonary embolism (adjusted OR, 1.39; p < 0.001), periprosthetic joint infection (adjusted OR, 1.35; p < 0.001), and 90-day readmission (adjusted OR, 1.25; p < 0.001). CONCLUSIONS: Patients with Medicaid were more likely to undergo TJA performed by lower-volume surgeons at lower-volume hospitals and had higher rates of postoperative complications compared with patients without Medicaid. Future research should assess socioeconomic status, insurance, and postoperative outcomes in this vulnerable patient population seeking arthroplasty care. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Prospective Longitudinal Assessment of Health-related Quality of Life in Patients With Brain Metastases Undergoing Radiation Therapy.

OBJECTIVE: We conducted a prospective clinical trial of patients receiving radiation (RT) for brain metastases to identify clinical predictors of pre-RT and post-RT health-related quality of life (hrQoL). MATERIALS AND METHODS: Patients with brain metastases completed overall (European Organisation for Research and Treatment of Cancer QLQ C15-PAL) and brain tumor-specific (QLQ-BN20) hrQoL assessments pre-RT (n=127) and 1 (n=56) and 3 (n=45) months post-RT. Linear and proportional-odds models analyzed patient, disease, and treatment predictors of baseline, 1-, and 3-month hrQoL scores. Generalized estimating equations and repeated measures proportional-odds models assessed predictors of longitudinal hrQoL scores. RESULTS: Most patients underwent stereotactic radiosurgery (SRS) (69.3%) and had non-small-cell lung (36.0%) metastases. Compared with SRS, receipt of whole brain RT was associated with a higher odds of appetite loss (baseline P=0.04, 1 mo P=0.02) and greater motor dysfunction (baseline P=0.01, 1 mo P=0.003, 3 mo P=0.02). Receipt of systemic therapy was associated with better emotional functioning after RT (1 mo P=0.03, 3 mo P=0.01). Compared with patients with breast cancer, patients with melanoma had higher odds of better global hrQoL (P=0.01) and less pain (P=0.048), while patients with lung cancer reported lower physical function (P=0.048) 3 months post-RT. Nonmarried patients had greater odds of higher global hrQoL (1 mo P=0.01), while male patients had lower odds of reporting more hair loss (baseline P=0.03, 3 mo P=0.045). Patients 60 years and above had lower odds of more drowsiness (P=0.04) and pain (P=0.049) over time. CONCLUSIONS: Patients receiving SRS versus whole brain RT and systemic therapy reported better posttreatment hrQoL. In addition, melanoma metastases, nonmarried, male, and older patients with reported better hrQoL in various as well as domains after intracranial RT.

An Application of Random Walk Resampling to Phylogenetic HMM Inference and Learning.

Statistical resampling methods are widely used for confidence interval placement and as a data perturbation technique for statistical inference and learning. An important assumption of popular resampling methods such as the standard bootstrap is that input observations are identically and independently distributed (i.i.d.). However, within the area of computational biology and bioinformatics, many different factors can contribute to intra-sequence dependence, such as recombination and other evolutionary processes governing sequence evolution. The SEquential RESampling ("SERES") framework was previously proposed to relax the simplifying assumption of i.i.d. input observations. SERES resampling takes the form of random walks on an input of either aligned or unaligned biomolecular sequences. This study introduces the first application of SERES random walks on aligned sequence inputs and is also the first to demonstrate the utility of SERES as a data perturbation technique to yield improved statistical estimates. We focus on the classical problem of recombination-aware local genealogical inference. We show in a simulation study that coupling SERES resampling and re-estimation with recHMM, a hidden Markov model-based method, produces local genealogical inferences with consistent and often large improvements in terms of topological accuracy. We further evaluate method performance using empirical HIV genome sequence datasets.

Integrated Counts of Carbohydrate-Active Protein Domains as Metabolic Readouts to Distinguish Probiotic Biology and Human Fecal Metagenomes.

Bowel microbiota is a "metaorgan" of metabolisms on which quantitative readouts must be performed before interventions can be introduced and evaluated. The study of the effects of probiotic Clostridium butyricum MIYAIRI 588 (CBM588) on intestine transplantees indicated an increased percentage of the "other glycan degradation" pathway in 16S-rRNA-inferred metagenomes. To verify the prediction, a scoring system of carbohydrate metabolisms derived from shotgun metagenomes was developed using hidden Markov models. A significant correlation (R = 0.9, p < 0.015) between both modalities was demonstrated. An independent validation revealed a strong complementarity (R = -0.97, p < 0.002) between the scores and the abundance of "glycogen degradation" in bacteria communities. On applying the system to bacteria genomes, CBM588 had only 1 match and ranked higher than the other 8 bacteria evaluated. The gram-stain properties were significantly correlated to the scores (p < 5 × 10-4). The distributions of the scored protein domains indicated that CBM588 had a considerably higher (p < 10-5) proportion of carbohydrate-binding modules than other bacteria, which suggested the superior ability of CBM588 to access carbohydrates as a metabolic driver to the bowel microbiome. These results demonstrated the use of integrated counts of protein domains as a feasible readout for metabolic potential within bacteria genomes and human metagenomes.

The Effects of Radiation and Emitted Light Transport on the Positional Response of 11 cm × 42.5 cm × 5.5 cm NaI(Tl) Detectors.

Experiments were performed with 30 11 cm × 42.5 cm × 5.5 cm NaI(Tl) detectors to better understand their positional response. Spectra were collected using 0.02 to 0.15 MBq point sources of Am, Cs, Co, and Ba positioned on lines parallel and perpendicular to the long axis of the crystal along both the narrow and wide detector faces as well as at different distances from them. A greater density of positions was sampled at the ends of the detector, and repeated measurements were made to examine potential gain drifts during the experiment. Spectroscopic peak counts, spectroscopic pulse heights, and net counts were analyzed. Empirical equations were fit to the aforementioned data for each specific source energy as a function of source position. In addition, a Monte Carlo radiation transport code was used to simulate the expected positionally variable response based solely upon radiation absorption. The simulated radiation transport efficiency functions were compared to the experimental data. The effects of the geometric radiation efficiency, the attenuation and scattering of emitted light within the scintillation crystal, and combined effects such as nonuniformity of the photomultiplier tube, photocathode response, and crystal irregularities were then distinguished. Functions describing each effect were derived. The results suggest potential new corrections to data obtained with large scintillation detectors as well as a novel approach to partial positional gamma-ray detection with minimal collimation, given that the energy resolution is within reason for particular photopeaks.

Synthetic approaches to the 2014 new drugs.

New drugs introduced to the market every year represent privileged structures for particular biological targets. These new chemical entities (NCEs) provide insight into molecular recognition and also serve as leads for designing future new drugs. This annual review covers the synthesis of thirty-seven NCEs that were approved for the first time in 2014 and one drug which was approved in 2013 and was not covered in a previous edition of this review.

An HMM-based comparative genomic framework for detecting introgression in eukaryotes.

One outcome of interspecific hybridization and subsequent effects of evolutionary forces is introgression, which is the integration of genetic material from one species into the genome of an individual in another species. The evolution of several groups of eukaryotic species has involved hybridization, and cases of adaptation through introgression have been already established. In this work, we report on PhyloNet-HMM-a new comparative genomic framework for detecting introgression in genomes. PhyloNet-HMM combines phylogenetic networks with hidden Markov models (HMMs) to simultaneously capture the (potentially reticulate) evolutionary history of the genomes and dependencies within genomes. A novel aspect of our work is that it also accounts for incomplete lineage sorting and dependence across loci. Application of our model to variation data from chromosome 7 in the mouse (Mus musculus domesticus) genome detected a recently reported adaptive introgression event involving the rodent poison resistance gene Vkorc1, in addition to other newly detected introgressed genomic regions. Based on our analysis, it is estimated that about 9% of all sites within chromosome 7 are of introgressive origin (these cover about 13 Mbp of chromosome 7, and over 300 genes). Further, our model detected no introgression in a negative control data set. We also found that our model accurately detected introgression and other evolutionary processes from synthetic data sets simulated under the coalescent model with recombination, isolation, and migration. Our work provides a powerful framework for systematic analysis of introgression while simultaneously accounting for dependence across sites, point mutations, recombination, and ancestral polymorphism.

Barking up the wrong treelength: the impact of gap penalty on alignment and tree accuracy.

Several methods have been developed for simultaneous estimation of alignment and tree, of which POY is the most popular. In a 2007 paper published in Systematic Biology, Ogden and Rosenberg reported on a simulation study in which they compared POY to estimating the alignment using ClustalW and then analyzing the resultant alignment using maximum parsimony. They found that ClustalW+MP outperformed POY with respect to alignment and phylogenetic tree accuracy, and they concluded that simultaneous estimation techniques are not competitive with two-phase techniques. Our paper presents a simulation study in which we focus on the NP-hard optimization problem that POY addresses: minimizing treelength. Our study considers the impact of the gap penalty and suggests that the poor performance observed for POY by Ogden and Rosenberg is due to the simple gap penalties they used to score alignment/tree pairs. Our study suggests that optimizing under an affine gap penalty might produce alignments that are better than ClustalW alignments, and competitive with those produced by the best current alignment methods. We also show that optimizing under this affine gap penalty produces trees whose topological accuracy is better than ClustalW+MP, and competitive with the current best two-phase methods.

Evaluating environmental sustainability: an integration of multiple-criteria decision-making and fuzzy logic.

While pursuing economic development, countries around the world have become aware of the importance of environmental sustainability; therefore, the evaluation of environmental sustainability has become a significant issue. Traditionally, multiple-criteria decision-making (MCDM) was widely used as a way of evaluating environmental sustainability, Recently, several researchers have attempted to implement this evaluation with fuzzy logic since they recognized the assessment of environmental sustainability as a subjective judgment Intuition. This paper outlines a new evaluation-framework of environmental sustainability, which integrates fuzzy logic into MCDM. This evaluation-framework consists of 36 structured and 5 unstructured decision-points, wherein MCDM is used to handle the former and fuzzy logic serves for the latter, With the integrated evaluation-framework, the evaluations of environmental sustainability in 146 countries are calculated, ranked and clustered, and the evaluation results are very helpful to these countries, as they identify their obstacles towards environmental sustainability.