Evidence-based medicine in equine clinical practice

The principles of Evidence-Based Medicine (EBM) have been well documented in the medical literature, with many examples of the successful application of these principles to the clinical environment. Despite this widespread acceptance of these principles throughout the medical profession, there has been resistance to adopt such an approach in the veterinary profession. To date, there are. few examples in the literature of the application of the principles of evidence-based medicine to either clinical or scientific research. The aim of this study was to design a series of investigations of equine diseases, and implement them at three private equine hospitals. A variety of study designs were used, providing different classes of evidence when using the classification system proposed by Yusuf et al. (1998). The main focus of this investigation was to ascertain whether it was possible to apply the ethos of EBM to the veterinary profession, and provide good quality research and evidence form private practice. It was found that 85.6% of horses (95% c.l. 81.3 to 89.3) treated for septic arthritis were successfully discharged from the hospital, with 65% of these horses (95% C.l. 57.9 to 71.6) able to return to their previous level of athletic function. When considering those horses treated for septic digital tenosynovitis, 87.8% survived to be discharged from the hospital. However, the prognosis for future soundness was poorer than that achieved following resolution of septic arthritis, with only 50% of horses treated for septic digital tenosynovitis able to return to their previous level of athletic function. Racing Thoroughbreds, both neonates and mature horses, were identified as an important subset of the population. It was found that the occurrence of septic arthritis in neonatal Thoroughbreds significantly reduced the likelihood of those foals going on to make at least one start on a racecourse, with those foals being 3.5 times less likely to start on a racecourse when compared to their siblings. In contrast, when considering mature Thoroughbred racehorses it was found that the occurrence of septic arthritis did not affect the likelihood that they would make at least one start on a racecourse when compared to their siblings, or be able to achieve an Official Rating awarded by the British Horseracing Board's handicappers equal to, or higher than, either the highest rating achieved prior to the onset of sepsis in cases in which horses had raced previously, or equal to the highest rating achieved by their siblings. In a controlled, randomised trial it was found that 31.6% (95% c.l. 17.5 to 48.7) of horses wearing a belly band following an exploratory laparotomy developed incisional complications, compared with 76.6% (95% c.I. 62.0 to 87.7) of horses where no belly band was used. If a belly band was used following an exploratory laparotomy, the risk of developing post-operative incisional complications was reduced by 45% compared to those cases where no belly band was used. Following a clinical audit of elective surgical procedures at three private equine hospitals, there was found to be a higher rate of post-operative complications, when compared to results reported in both the medical and small animal veterinary literature. It was concluded that it was possible to apply the ethos of EBM to the veterinary profession, and provide good quality research and evidence from research performed in private practice. However, in order to be able to achieve sufficient case numbers to provide answers that are directly relevant to practice-based clinical situations, multi-centre studies are likely to be the best way forward

The Miseducation of Welfare Reform: Denying the Promise of Postsecondary Education

When Congress enacted “welfare reform” in 1996, decades of progress in assisting low-income mothers obtain a college education in order to escape poverty was nearly eradicated. The federal welfare reform law strongly discouraged states from incorporating postsecondary education into their welfare reform programs and focused instead on “work-first” policies. As a direct result, hundreds of thousands of low-income mothers across the country were forced to drop out of college and find jobs in order to comply with strict “work-first” welfare rules. Despite the pressure imposed by the federal law, the State of Maine persevered in its effort to make college a reality for low-income mothers. Advocates in Maine were adamant that welfare reform policies focus on raising families out of poverty and endeavor to change the position of women in the labor market in order to relieve poverty for low-income single mothers. These farsighted views, embodied in the Maine Parents as Scholars program, have paid off for welfare recipients and for the state, with dividends. As the welfare reform law expires, Congress has the opportunity to reverse course and support states in providing access to postsecondary education for welfare recipients. In this paper, we will reveal how “work-first” ideology pushed the merits of postsecondary education for low-income women to the background despite the well-known, intimate relationship between higher education and women\u27s earnings, employment, and well-being. We will highlight the innovative approach taken in Maine to overcome the pressures of the federal welfare reform law and report on positive outcomes for Maine welfare recipients who were able to access higher education despite federal restrictions. Finally, we will explore the current Congressional proposals for renewing the welfare reform law in a manner more conducive to allowing low-income mothers access to education

A Single Tri-Epitopic Antibody Virtually Recapitulates the Potency of a Combination of Three Monoclonal Antibodies in Neutralization of Botulinum Neurotoxin Serotype A.

The standard of treatment for botulism, equine antitoxin, is a foreign protein with associated safety issues and a short serum half-life which excludes its use as a prophylactic antitoxin and makes it a less-than-optimal therapeutic. Due to these limitations, a recombinant monoclonal antibody (mAb) product is preferable. It has been shown that combining three mAbs that bind non-overlapping epitopes leads to highly potent botulinum neurotoxin (BoNT) neutralization. Recently, a triple human antibody combination for BoNT/A has demonstrated potent toxin neutralization in mouse models with no serious adverse events when tested in a Phase I clinical trial. However, a triple antibody therapeutic poses unique development and manufacturing challenges. Thus, potentially to streamline development of BoNT antitoxins, we sought to achieve the potency of multiple mAb combinations in a single IgG-based molecule that has a long serum half-life. The design, production, and testing of a single tri-epitopic IgG1-based mAb (TeAb) containing the binding sites of each of the three parental BoNT/A mAbs yielded an antibody of nearly equal potency to the combination. The approach taken here could be applied to the design and creation of other multivalent antibodies that could be used for a variety of applications, including toxin elimination

MELA: Modelling in Ecology with Location Attributes

Ecology studies the interactions between individuals, species and the environment. The ability to predict the dynamics of ecological systems would support the design and monitoring of control strategies and would help to address pressing global environmental issues. It is also important to plan for efficient use of natural resources and maintenance of critical ecosystem services. The mathematical modelling of ecological systems often includes nontrivial specifications of processes that influence the birth, death, development and movement of individuals in the environment, that take into account both biotic and abiotic interactions. To assist in the specification of such models, we introduce MELA, a process algebra for Modelling in Ecology with Location Attributes. Process algebras allow the modeller to describe concurrent systems in a high-level language. A key feature of concurrent systems is that they are composed of agents that can progress simultaneously but also interact - a good match to ecological systems. MELA aims to provide ecologists with a straightforward yet flexible tool for modelling ecological systems, with particular emphasis on the description of space and the environment. Here we present four example MELA models, illustrating the different spatial arrangements which can be accommodated and demonstrating the use of MELA in epidemiological and predator-prey scenarios.Comment: In Proceedings QAPL'16, arXiv:1610.0769

International Veterinary Epilepsy Task Force Consensus Proposal: Diagnostic approach to epilepsy in dogs

This article outlines the consensus proposal on diagnosis of epilepsy in dogs by the International Veterinary Epilepsy Task Force. The aim of this consensus proposal is to improve consistency in the diagnosis of epilepsy in the clinical and research settings. The diagnostic approach to the patient presenting with a history of suspected epileptic seizures incorporates two fundamental steps: to establish if the events the animal is demonstrating truly represent epileptic seizures and if so, to identify their underlying cause. Differentiation of epileptic seizures from other non-epileptic episodic paroxysmal events can be challenging. Criteria that can be used to make this differentiation are presented in detail and discussed. Criteria for the diagnosis of idiopathic epilepsy (IE) are described in a three-tier system. Tier I confidence level for the diagnosis of IE is based on a history of two or more unprovoked epileptic seizures occurring at least 24 h apart, age at epileptic seizure onset of between six months and six years, unremarkable inter-ictal physical and neurological examination, and no significant abnormalities on minimum data base blood tests and urinalysis. Tier II confidence level for the diagnosis of IE is based on the factors listed in tier I and unremarkable fasting and post-prandial bile acids, magnetic resonance imaging (MRI) of the brain (based on an epilepsy-specific brain MRI protocol) and cerebrospinal fluid (CSF) analysis. Tier III confidence level for the diagnosis of IE is based on the factors listed in tier I and II and identification of electroencephalographic abnormalities characteristic for seizure disorders. The authors recommend performing MRI of the brain and routine CSF analysis, after exclusion of reactive seizures, in dogs with age at epileptic seizure onset 6 years, inter-ictal neurological abnormalities consistent with intracranial neurolocalisation, status epilepticus or cluster seizure at epileptic seizure onset, or a previous presumptive diagnosis of IE and drug-resistance with a single antiepileptic drug titrated to the highest tolerable dose

Neuroimaging Evidence of Major Morpho-Anatomical and Functional Abnormalities in the BTBR T+TF/J Mouse Model of Autism

BTBR T+tf/J (BTBR) mice display prominent behavioural deficits analogous to the defining symptoms of autism, a feature that has prompted a widespread use of the model in preclinical autism research. Because neuro-behavioural traits are described with respect to reference populations, multiple investigators have examined and described the behaviour of BTBR mice against that exhibited by C57BL/6J (B6), a mouse line characterised by high sociability and low self-grooming. In an attempt to probe the translational relevance of this comparison for autism research, we used Magnetic Resonance Imaging (MRI) to map in both strain multiple morpho-anatomical and functional neuroimaging readouts that have been extensively used in patient populations. Diffusion tensor tractography confirmed previous reports of callosal agenesis and lack of hippocampal commissure in BTBR mice, and revealed a concomitant rostro-caudal reorganisation of major cortical white matter bundles. Intact inter-hemispheric tracts were found in the anterior commissure, ventro-medial thalamus, and in a strain-specific white matter formation located above the third ventricle. BTBR also exhibited decreased fronto-cortical, occipital and thalamic gray matter volume and widespread reductions in cortical thickness with respect to control B6 mice. Foci of increased gray matter volume and thickness were observed in the medial prefrontal and insular cortex. Mapping of resting-state brain activity using cerebral blood volume weighted fMRI revealed reduced cortico-thalamic function together with foci of increased activity in the hypothalamus and dorsal hippocampus of BTBR mice. Collectively, our results show pronounced functional and structural abnormalities in the brain of BTBR mice with respect to control B6 mice. The large and widespread white and gray matter abnormalities observed do not appear to be representative of the neuroanatomical alterations typically observed in autistic patients. The presence of reduced fronto-cortical metabolism is of potential translational relevance, as this feature recapitulates previously-reported clinical observations

International Veterinary Epilepsy Task Force recommendations for a veterinary epilepsy-specific MRI protocol

Epilepsy is one of the most common chronic neurological diseases in veterinary practice. Magnetic resonance imaging (MRI) is regarded as an important diagnostic test to reach the diagnosis of idiopathic epilepsy. However, given that the diagnosis requires the exclusion of other differentials for seizures, the parameters for MRI examination should allow the detection of subtle lesions which may not be obvious with existing techniques. In addition, there are several differentials for idiopathic epilepsy in humans, for example some focal cortical dysplasias, which may only apparent with special sequences, imaging planes and/or particular techniques used in performing the MRI scan. As a result, there is a need to standardize MRI examination in veterinary patients with techniques that reliably diagnose subtle lesions, identify post-seizure changes, and which will allow for future identification of underlying causes of seizures not yet apparent in the veterinary literature. There is a need for a standardized veterinary epilepsy-specific MRI protocol which will facilitate more detailed examination of areas susceptible to generating and perpetuating seizures, is cost efficient, simple to perform and can be adapted for both low and high field scanners. Standardisation of imaging will improve clinical communication and uniformity of case definition between research studies. A 6–7 sequence epilepsy-specific MRI protocol for veterinary patients is proposed and further advanced MR and functional imaging is reviewed