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Clostrididioides difficile is associated with adverse clinical outcomes and increased morbidity, mortality, length of hospital stay, and health-care costs.Areas Covered: We searched relevant papers...

Multilocus sequence typing (MLST) is a low-resolution but rapid genotyping method for Clostridioides difficile. Whole-genome sequencing (WGS) has emerged as the new gold standard for C. difficile typing, but cost and lack of standardization still limit broad utilization. In this study, we evaluated the potential to combine the portability of MLST with the increased resolution of WGS for a cost-saving approach to routine C. difficile typing. C. difficile strains from two New York City hospitals (hospital A and hospital B) were selected. WGS single-nucleotide polymorphism (wgSNP) was performed using established methods. Sequence types (ST) were determined using PubMLST, while wgSNP analysis was performed using the Bionumerics software. An additional analysis of a subset of data (hospital A) was made comparing the Bionumerics software to the CosmosID pipeline. Cost and turnaround time to results were compared for the algorithmic approach of MLST followed by wgSNP versus direct wgSNP. Among the 202 C. difficile isolates typed, 91% (n = 185/203) clustered within the representative ST, showing a high agreement between MLST and wgSNP. While clustering was similar between the Bionumerics and CosmosID pipelines, large differences in the overall number of SNPs were noted. A two-step algorithm for routine typing results in significantly lower cost than routine use of WGS. Our results suggest that using MLST as a first step in routine typing of C. difficile followed by WGS for MLST concordant strains is a less technically demanding, cost-saving approach for performing C. difficile typing than WGS alone without loss of discriminatory power.

In 2016, the WHO included haemoglobin values within normal ranges as a diagnostic criterion for Polycythaemia Vera (PV). Since then, concerns have arisen that a large number of patients are undergoing unnecessary screening for PV. To address this issue, we estimated the prevalence of JAK2 p.V617F in individuals with elevated haemoglobin or haematocrit and developed and validated a screening algorithm for PV. A total of 15,366 blood counts performed in seven non-consecutive days were reviewed, of which 1001 were selected for subsequent JAK2 p.V617F mutation screening. Eight (0.8%) new JAK2 p.V617F-mutated cases were detected. From ROC curves, a two-step algorithm was developed based on the optimal cut-off for the detection of the JAK2 p.V617F mutation. The algorithm was prospectively validated in an independent cohort of 15,298 blood counts. A total of 1595 (10.4%) cases met the criterion for haemoglobin or haematocrit, of whom 581 passed to step 2 (3.8% of the total). The JAK2 p.V617F mutation was detected in 7 of the 501 patients tested, which accounts for 0.04% of the total cohort and 0.4% of patients with erythrocytosis. In conclusion, this data show that our two-step algorithm improves the selection of candidates for JAK2 p.V617F testing.

Background: Fast identification of Candida glabrata is important, because empirical antifungal therapy for fungemia with C. glabrata and non-C. glabrata varies. We proposed an algorithm for rapid presumptive diagnosis to identify fungemia with C. glabrata using earlier or only growth from anaerobic bottles and longer time to positivity (TTP) in blood cultures.Methods: Positivity and TTP using the BacT/Alert 3D system (bioMerieux Inc, USA) with resin bottles (FA Plus and FN Plus) were analyzed in 215 candidemia patients from June 2014 to June 2016 in a university- affiliated hospital in Korea.Results: A higher proportion of earlier or only growth from anaerobic bottles was observed in C. glabrata (38.8%, 7/18) than in C. albicans (7.6%, 8/105), C. parapsilosis (10.5%, 4/138), and C. tropicalis (9.2%, 5/54) (P=0.006). The mean (±standard deviation) TTP for C. glabrata was 41.7 h (±16.3 h) compared with 26.7 h (±15.9 h) for C. albicans, 33.4 h (±8.4 h) for C. parapsilosis, and 23.1 h (±17.3 h) for C. tropicalis (P31.4 h.Conclusion: This two-step algorithm in the BacT/Alert 3D system could be the basis for an initial empirical antifungal therapy for fungemia with C. glabrata prior to final identification. (Ann Clin Microbiol 2018;21:23-27)

Background An estimated 15% of hospitalized patients are asymptomatic carriers of C. diff. Inappropriate testing can lead to over diagnosis, treatment, isolation & substantial financial penalties. Ours is a rural 310 bed hospital with nurse driven C. diff test ordering protocol. Due to inadvertent test ordering, we had an uptick in the HO-CDI incidence with rates as high as 0.94 per 1000 patient days in 2017. In order to streamline testing, we initiated an infection preventionist(IP) led diagnostic stewardship program which was implemented in two phases in 2017-2019 Methods The phase 1 involved daily review by IPs regarding the legitimacy of PCR order for minimum 3 loose stools in 24 hours, use of laxatives, presence of symptoms.There were concerns nationally that then CDI risk adjustment model from NHSN in 2017 does not optimally account for the impact of specific CDI testing methods used by individual hospitals on CDI SIRs. Hence, in Jan 2018 NHSN’s MDRO/CDI Protocol stated “Results of the final test that are placed in the patient’s medical record should be used to determine whether event meets the CDI LabID defn”.This led to phase 2 in mar 2019 which involved two step testing which started with C diff PCR assay with positive test reflexed to the toxin A/B assay. Results During the first phase, and a full year of the protocol in 2018, the number of completed PCR tests decreased to 626 (compared to 940 PCR tests in 2016) with an 34% decrease. In the year following implementation of the Diagnostic Stewardship, HO CDI decreased from 60 in 2017 to 43 events in 2018 with a reduction of 28%. Subsequently, HO CDI further decreased in 2019 to 28 with a reduction of 35%. Since the start of the project in 2017, HO CDI have decreased 54% in total. The reduction in 314 C diff PCR tests in the first year[2017-2018] led to a savings of $8300 in lab supplies. No readmissions with C difficile infection documented within 30 days on patients who did not meet the criterion for testing. Significant decrease in the usage of C difficile antibiotics. After the start of the two step test, we have seen a precipitous drop in our HO-CDI rates to less than 0.3 per 1000 pt days by the end of 2019. Quarterly comparison of HO CDI incidence for 2017-2020 HO CDI incidence before and following phase 1 and phase 2 interventions C. difficile antibiotic use trends during intervention period Conclusion IP run diagnostic stewardship programs with two step tests are highly successful in streamlining testing and in discriminating infection from colonization Disclosures All Authors: No reported disclosures

OBJECTIVES/GOALS: In 2017, new guidelines recommended multi-step algorithms for CDI diagnosis, and clinical centers rapidly implemented changes despite limited pediatric data. We assessed a multi-step algorithm using NAAT followed by EIA for ability to differentiate symptomatic CDI from colonization in children. METHODS/STUDY POPULATION: We prospectively enrolled pediatric patients with cancer, cystic fibrosis, or inflammatory bowel disease who were not being tested or treated for CDI and obtained a stool sample for NAAT. If positive by NAAT (colonized), EIA was performed. Children with symptomatic CDI who tested positive by NAAT via the clinical laboratory were also enrolled and EIA performed on residual stool. A functional cell cytotoxicity neutralization assay (CCNA) was performed in addition. RESULTS/ANTICIPATED RESULTS: Of the 138 asymptomatic children enrolled, 24 (17%) were colonized. An additional 37 children with symptomatic CDI were enrolled. Neither EIA positivity (41% versus 21%, P = 0.11) or CCNA positivity (49% versus 46%, P = 0.84) were significantly different between symptomatic versus colonized children. When both EIA and CCNA were positive, children were more commonly symptomatic than colonized (33% versus 13%, P = 0.04). DISCUSSION/SIGNIFICANCE OF IMPACT: A multi-step testing algorithm with NAAT and EIA failed to differentiate symptomatic CDI from colonization in our pediatric cohort. As multi-step algorithms are moved into clinical care, pediatric providers will need to be aware of the continued limitations in diagnostic testing.

A two-step algorithm for the dynamic reduction of flexible mechanisms inspired to the IRS method for structures is proposed. The classic Guyan-Iron condensation is first extended to multibody systems by introducing the joint compatibility equations in the equations of motion written in terms of slave and the new class joint-nodes. It is demonstrated that the joint-nodes augment the boundary-nodes, that form subset of nodes with independent displacements. Then, the Miller’s expansion is combined with the extended Guyan-Iron reduction to build a two-step algorithm for the dynamic condensation of flexible multibody systems. Finally, a numerical example is studied to check the accuracy of the proposed method.

This study addresses the global consensus problems of a class of non-linear multi-agent systems with Lipschitz non-linearity and directed communication graphs, by using a distributed consensus protocol based on the relative states of neighbouring agents. A two-step algorithm is presented to construct a protocol, under which a Lipschitz multi-agent system without disturbances can reach global consensus for a strongly connected directed communication graph. Another algorithm is then given to design a protocol that can achieve global consensus with a guaranteed H∞ performance for a Lipschitz multi-agent system subject to external disturbances. The case with a leader–follower communication graph is also discussed. Finally, the effectiveness of the theoretical results is demonstrated through a network of single-link manipulators.

An optical computing system is expected to be a powerful information processing system that takes full advantage of optics, such as parallelism, high speed, and large information capacity. Therefore many suitable optical number systems have been developed by many research to exploit the inherent parallelism of optics to developed parallel arithmetic operations . In this paper we used binary modified signed-digit (BMSD) number system and available recoding method to generate a simplified binary MSD addition/subtraction truth table to obtained a parallel two-step algorithm in which the carry chain was generated during the addition operation and the borrowing chain was generated during the subtraction operation that will be stopped after two steps, the addition and subtraction operations will be completed independent of the number of digits in each operand. Also this paper involve limitation for the minterms that used in the logical processing for the addition/subtraction truth table.

The grating lateral shearing interferometer may achieve ultra-high accuracy absolute testing after eliminating the systemic errors from the interferometer itself and the orthogonality problem between two shearing directions. Aiming at the interferometer, we proposed a two-step algorithm for removing the rotationally asymmetric systemic errors from our shearing setup. This rotation method provides a new approach for acquiring the wavefront aberration by choosing the rotation angles with the minimum decentration and to satisfy the immune of systemic errors at the same time. Simulation and experiment verified that it is more propitious to eliminate the systemic errors when it is applied to our shearing setup.

Objectives: Development and validation of a clinical algorithm to identify infection with group A β-haemolytic streptococci in patients with sore throat, using a clinical score and measurement of C-reactive protein for selected patients.Design: Two phased study. Phase 1: Development of a clinical score from structured clinical records by logistic regression analysis and Bayesian analysis. Phase 2: Prospective validation of the score developed in phase 1.Setting: One GP practice in Germany (two GPs) for development of the score, five German GP practices (six GPs) for validation of the score.Subjects: Consecutive patients aged 16 or older presenting with newly developed sore throat, n=116 (phase 1), n=265 (phase 2).Main outcome measures: Infection by group A β-haemolytic streptococci diagnosed by means of throat swab cultures on selective Columbia agar.Results: Development of a two-step algorithm consisting of a clinical score of four parameters (throat mucosa, uvula, soft palate, tonsils) and near-patient ...

Background The low sensitivity of toxin enzyme immunoassay (EIA) for the diagnosis of Clostridium difficile infection (CDI) motivated many laboratories to add nucleic acid amplification tests (NAAT) to their testing protocol. However, NAAT do not distinguish between colonization and infection, and indiscriminant testing could lead to over treatment of CDI. Methods Active, population-based CDI surveillance has been conducted through the Emerging Infections Program in Bernalillo County, NM since 2011, with test type collected at the individual level since 2014. Community-onset (CO) CDI cases with a first positive test diagnosed by a two-step algorithm (concurrent EIA/GDH, with discordant results reflexed to NAAT) in 2014–2015 were included. We analyzed clinical characteristics and outcomes of patients EIA positive compared with NAAT positive. Demographics, risk factors, treatment, and outcomes were assessed through medical record review. Results Among 1,063 cases, 559 (52.6%) were EIA positive only and 504 (47.4%) were NAAT positive only. Of those with stool collected as a hospital inpatient, 57% were NAAT positive (P < 0.001); this increased from 43.4% if tested the day of admission to 61.4% when tested on day three. Conversely, 38.6% of patients with stool collected in an emergency department were NAAT positive (P = 0.004). Fewer cases with complicated outcomes were NAAT positive (40.7%, P = 0.023). Among those with no documentation of recent antibiotic use, 64.3% were NAAT positive (P < 0.001), and 67.8% of cases with no CDI treatment were NAAT positive (P = 0.005). Only 28.3% percent of cases with recurrent CDI were initially NAAT positive (P < 0.001). Conclusion EIA negative and NAAT positive CO-CDI cases tended to have a milder clinical presentation than those that were EIA positive. This suggests that some patients positive only by NAAT may have mild CDI or be colonized, rather than infected, with C. difficile. These individuals were less likely to have complicated outcomes, have recent documented antibiotic use, be treated for CDI, or have a recurrent CDI episode than those positive by EIA. Longer hospital stay correlated with increased proportion of testing NAAT positive. Providers may benefit from considering testing protocol and clinical correlation when assessing patients with positive C. difficile test results. Disclosures All authors: No reported disclosures.

Emerging Microbes & Infections (2017) 6, e67; doi:10.1038/emi.2017.52; published online 26 July 2017

Treatment of COPD can be simplified with a two-step algorithm according to severity and phenotype http://ow.ly/iJUN306DEHU

The aim of this paper is to evaluate the level of flooding in proximity of sensible targets in urban areas using only one Synthetic Aperture Radar (SAR) image. To this purpose a two-step algorithm is here proposed: first the flooded areas are detected in the SAR image; and then the water level is retrieved by inverting scattering models developed for urban areas and now properly adapted for the case at issue. The retrieval is performed through a local approach where the a-priori knowledge of the target ground truth and two gauges in the premises is required. The approach is tested on a High Resolution (HR) TerraSAR-X image acquired during the flooding occurred in the Gloucestershire in July 2007.

A common method in solving ill-posed problems is to substitute the original problem by a family of well-posed (i.e., with a unique solution) regularized problems. We will use this idea to define and study a two-step algorithm to solve hierarchical fixed point problems under different conditions on involved parameters.

In the information regularization framework by Corduneanu and Jaakkola (2005), the distributions of labels are propagated on a hypergraph for semi-supervised learning. The learning is efficiently done by a Blahut-Arimoto-like two step algorithm, but, unfortunately, one of the steps cannot be solved in a closed form. In this paper, we propose a dual version of information regularization, which is considered as more natural in terms of information geometry. Our learning algorithm has two steps, each of which can be solved in a closed form. Also it can be naturally applied to exponential family distributions such as Gaussians. In experiments, our algorithm is applied to protein classification based on a metabolic network and known functional categories.

We investigate two different initial boundary-value problems for derivative nonlinear Schrödinger equation. The boundary conditions are Dirichlet or generalized periodic ones. We propose a two-step algorithm for numerical solving of this problem. The method consists of Bäcklund type transformations and difference scheme. We prove the convergence and stability in C and H1 norms of Crank–Nicolson finite difference scheme for the transformed problem. There are no restrictions between space and time grid steps. For the derivative nonlinear Schrödinger equation, the proposed numerical algorithm converges and is stable in C1 norm.

The paper proposes an alternative modified two-step algorithm for steady state optimisation and parameter estimation. The aim is to simplify the model optimisation computation in the presence of general inequality constraints. Another advantage is that the existence of a model based optimal solution is ensured during the course of iteration. Optimality properties and convergence conditions are investigated. A simulation study is presented.