Antimicrobial stewardship in companion animal practice: an implementation trial in 135 general practice veterinary clinics.

BACKGROUND: Antimicrobial stewardship programmes (ASPs) have been widely implemented in medical practice to improve antimicrobial prescribing and reduce selection for multidrug-resistant pathogens. OBJECTIVES: To implement different antimicrobial stewardship intervention packages in 135 veterinary practices and assess their impact on antimicrobial prescribing. METHODS: In October 2018, general veterinary clinics were assigned to one of three levels of ASP, education only (CON), intermediate (AMS1) or intensive (AMS2). De-identified prescribing data (1 October 2016 to 31 October 2020), sourced from VetCompass Australia, were analysed and a Poisson regression model fitted to identify the effect of the interventions on the incidence rates of antimicrobial prescribing. RESULTS: The overall incidence rate (IR) of antimicrobial prescribing for dogs and cats prior to the intervention was 3.7/100 consultations, which declined by 36% (2.4/100) in the implementation period, and by 50% (1.9/100) during the post-implementation period. Compared with CON, in AMS2 there was a 4% and 6% reduction in the overall IR of antimicrobial prescribing, and a 24% and 24% reduction in IR of high importance antimicrobial prescribing, attributable to the intervention in the implementation and post-implementation periods, respectively. A greater mean difference in the IR of antimicrobial prescribing was seen in high-prescribing clinics. CONCLUSIONS: These AMS interventions had a positive impact in a large group of general veterinary practices, resulting in a decline in overall antimicrobial use and a shift towards use of antimicrobials rated as low importance, with the greatest impact in high-prescribing clinics.

Overcoming challenges in extracting prescribing habits from veterinary clinics using big data and deep learning.

Understanding antimicrobial usage patterns and encouraging appropriate antimicrobial usage is a critical component of antimicrobial stewardship. Studies using VetCompass Australia and Natural Language Processing (NLP) have demonstrated antimicrobial usage patterns in companion animal practices across Australia. Doing so has highlighted the many obstacles and barriers to the task of converting raw clinical notes into a format that can be readily queried and analysed. We developed NLP systems using rules-based algorithms and machine learning to automate the extraction of data describing the key elements to assess appropriate antimicrobial use. These included the clinical indication, antimicrobial agent selection, dose and duration of therapy. Our methods were applied to over 4.4 million companion animal clinical records across Australia on all consultations with antimicrobial use to help us understand what antibiotics are being given and why on a population level. Of these, approximately only 40% recorded the reason why antimicrobials were prescribed, along with the dose and duration of treatment. NLP and deep learning might be able to overcome the difficulties of harvesting free text data from clinical records, but when the essential data are not recorded in the clinical records, then, this becomes an insurmountable obstacle.

Using natural language processing and VetCompass to understand antimicrobial usage patterns in Australia.

BACKGROUND: Currently there is an incomplete understanding of antimicrobial usage patterns in veterinary clinics in Australia, but such knowledge is critical for the successful implementation and monitoring of antimicrobial stewardship programs. METHODS: VetCompass Australia collects medical records from 181 clinics in Australia (as of May 2018). These records contain detailed information from individual consultations regarding the medications dispensed. One unique aspect of VetCompass Australia is its focus on applying natural language processing (NLP) and machine learning techniques to analyse the records, similar to efforts conducted in other medical studies. RESULTS: The free text fields of 4,394,493 veterinary consultation records of dogs and cats between 2013 and 2018 were collated by VetCompass Australia and NLP techniques applied to enable the querying of the antimicrobial usage within these consultations. CONCLUSION: The NLP algorithms developed matched antimicrobial in clinical records with 96.7% accuracy and an F1 Score of 0.85, as evaluated relative to expert annotations. This dataset can be readily queried to demonstrate the antimicrobial usage patterns of companion animal practices throughout Australia.

Protein interaction network (PIN)-based breast cancer subsystem identification and activation measurement for prognostic modeling.

Genome-wide gene expression information has been very useful for understanding cancer at the molecular level. In particular, breast cancer has been widely studied by utilizing a large amount of transcriptome data. Although statistical selection of differentially expressed genes, e.g., PAM50, has been successful to classify breast cancer subtypes, understanding breast cancer in terms of biological functions or pathways is still limited. Thus, it is essential to develop a tailored model that unravels breast cancer mechanisms by identifying disease-specific functional units of biological pathways and apply the model for breast cancer prognosis. In this paper, a systematic characterization of breast cancer functional units or 'subsystems' is presented. We propose a novel concept of decomposing biological pathways into subsystems by utilizing protein interaction network, pathway information, and RNA-seq data. Subsystem activation score (SAS) was developed to measure the degree of activation for each subsystem and each patient. This method revealed distinctive genome-wide activation patterns or landscape of subsystems that are differentially activated among samples and among breast cancer subtypes. Then, we used SAS information for prognostic modeling by performing the classification and regression tree (CART) analysis. Eleven subgroups of patients, defined by 10 most significant subsystems, were identified with the maximal discrepancy in survival outcome. Our model not only defined patient subgroups with similar survival outcomes, but also provided patient-specific decision paths determined by subsystem activation status, suggesting functionally informative gene sets of breast cancer.

Characteristics of non-carious cervical lesions--an ex vivo study using micro computed tomography.

The aetiology of non-carious cervical lesions (NCCLs) is not well understood and still controversial. The aim of this ex-vivo study was to examine the morphological characteristics of NCCLs for clinical evidence of enamel loss above the cemento-enamel junction (CEJ) as suggested by the abfraction theory. Fifty extracted human teeth with various types of NCCLs were collected and scanned by micro computed tomography. The reconstructed three-dimensional models were evaluated from multiple aspects, including longitudinal cross-section series. The location of internal line angle and proximal exits of the lesions were evaluated in relation to the level of CEJ. The coronal margins of the lesions were inspected for evidence of enamel loss above the CEJ using the bucco-lingual longitudinal sectional images. Coronal margins of the lesions were located along and/or under the CEJ for all of the 50 samples. In most of the lesions, regardless of lesion type, the proximal exits and internal line angles were located below the CEJ. This study did not detect clinical evidence of enamel loss above the occlusal margin of NCCLs as would have been expected according to the general abfraction mechanism.

Stress distribution of three NiTi rotary files under bending and torsional conditions using a mathematic analysis.

AIM: To compare and evaluate the stress distribution of three NiTi instruments of various cross-sectional configurations under bending or torsional condition using a finite-element analysis model. METHODOLOGY: Three NiTi files (ProFile, ProTaper and ProTaper Universal) were scanned using Micro-CT to produce a three-dimensional digital model. The behaviour of the instrument under bending or torsional loads was analysed mathematically in software (ABAQUS V6.5-1), taking into consideration the nonlinear mechanical characteristic of NiTi material. RESULTS: ProFile showed the greatest flexibility, followed by ProTaper Universal and ProTaper. The highest stress was observed at the surface near the cutting edge and the base of (opposing) flutes during cantilever bending. Concentration of stresses was observed at the bottom of the flutes in ProFile and ProTaper Universal instruments in torsion. The stress was more evenly distributed over the surface of ProTaper initially, which then concentrated at the middle of the convex sides when the amount of angular deflection was increased. CONCLUSION: Incorporating a U-shaped groove in the middle of each side of the convex-triangular design lowers the flexural rigidity of the origin ProTaper design. Bending leads to the highest surface stress at or near the cutting edge of the instrument. Stress concentration occurs at the bottom of the flute when the instrument is subjected to torsion.

Measurement of glycoprotein IIb/IIIa blockade by flow cytometry with fluorescein isothiocyanate-conjugated crotavirin, a member of disintegrins.

The blockade of platelet membrane glycoprotein IIb/IIIa by a monoclonal antibody, 7E3, was measured by flow cytometry using a fluorescein isothiocyanate-conjugated disintegrin, FITC-crotavirin, as the probe. After treatment of platelets with 7E3 or 7E3 F(ab')2, there is a good correlation between the inhibition of platelet aggregation and the blockade of FITC-crotavirin's binding to platelets. The content of glycoprotein IIb/IIIa for the subsequent binding of FITC-crotavirin to the 7E3-pretreated platelets highly correlated to the extent of glycoprotein IIb/IIIa, remaining available. It was evidenced by the observation that the sum of glycoprotein IIb/IIIa occupation by 7E3 and that of FITC-crotavirin approached the total amount of glycoprotein IIb/IIIa expressed on the platelet membrane. This indicates that the percentage inhibition of FITC-crotavirin's binding at the saturation dose reflects the extent of glycoprotein IIb/IIIa blockade by 7E3. At the saturation binding concentration (5 micrograms/ml), FITC-crotavirin did not displace platelet bound 7E3. Gating the light-scattering profile for platelets, the binding of FITC-crotavirin to platelet glycoprotein IIb/IIIa could be easily determined in diluted whole blood by direct stain method. The available unoccupied glycoprotein IIb/IIIa of platelets in the 7E3 or 7E3 F(ab')2-pretreated whole blood were measured by flow cytometry at the saturation binding dose of FITC-crotavirin (4 micrograms/ml) and the data showed that the higher deconcentration of antibody added into whole blood, the lower debinding of FITC-crotavirin to platelets. This technique may provide an alternative rapid method for measuring the blockade of glycoprotein IIb/IIIa by 7E3, a promising anti-thrombotic agent, thus providing a monitoring method for adjusting the therapeutic dose of 7E3 or its related derivatives.