The changing treatment of arthritis

Reproduced with permission from Australian Prescriber The document attached has been archived with permission from the publisher/copyright holder.Leslie G. Cleland, Susanna M. Proudman, Michael J. James and Peter Penglis

Is equine colic seasonal? Novel application of a model based approach

BACKGROUND: Colic is an important cause of mortality and morbidity in domesticated horses yet many questions about this condition remain to be answered. One such question is: does season have an effect on the occurrence of colic? Time-series analysis provides a rigorous statistical approach to this question but until now, to our knowledge, it has not been used in this context. Traditional time-series modelling approaches have limited applicability in the case of relatively rare diseases, such as specific types of equine colic. In this paper we present a modelling approach that respects the discrete nature of the count data and, using a regression model with a correlated latent variable and one with a linear trend, we explored the seasonality of specific types of colic occurring at a UK referral hospital between January 1995–December 2004. RESULTS: Six- and twelve-month cyclical patterns were identified for all colics, all medical colics, epiploic foramen entrapment (EFE), equine grass sickness (EGS), surgically treated and large colon displacement/torsion colic groups. A twelve-month cyclical pattern only was seen in the large colon impaction colic group. There was no evidence of any cyclical pattern in the pedunculated lipoma group. These results were consistent irrespective of whether we were using a model including latent correlation or trend. Problems were encountered in attempting to include both trend and latent serial dependence in models simultaneously; this is likely to be a consequence of a lack of power to separate these two effects in the presence of small counts, yet in reality the underlying physical effect is likely to be a combination of both. CONCLUSION: The use of a regression model with either an autocorrelated latent variable or a linear trend has allowed us to establish formally a seasonal component to certain types of colic presented to a UK referral hospital over a 10 year period. These patterns appeared to coincide with either times of managemental change or periods when horses are more likely to be intensively managed. Further studies are required to identify the determinants of the observed seasonality. Importantly, this type of regression model has applications beyond the study of equine colic and it may be useful in the investigation of seasonal patterns in other, relatively rare, conditions in all species

Epidemiology of impaction colic in donkeys in the UK

BACKGROUND: Colic (abdominal pain) is a clinical condition of serious concern affecting the welfare and survival of donkeys at the Donkey Sanctuary in the UK. One of the most commonly reported causes is due to impacted ingesta in the large intestine ("impaction colic"). However little is known about the incidence of, or risk factors for, this condition. Here we describe the epidemiology of colic in donkeys, specifically impaction colic. We focus on temporal aspects of the disease and we identify environmental and management related risk factors for impaction colic in UK donkeys. RESULTS: There were 807 colic episodes in the population of 4596 donkeys between January 1(st )2000 and March 31(st )2005. The majority (54.8%) of episodes were due to a suspected or confirmed diagnosis of impaction of the gastrointestinal tract. The mortality risk for all colics (51.1%) was higher than reported in other equids. The incidence rate of all colics (5.9 episodes per 100 donkeys per year) and of impaction colic (3.2 episodes) was similar to that in horses. A retrospective matched case-control study of all impaction colics from January 2003 (193) indicated that older donkeys, those fed extra rations and those that previously suffered colic were at increased risk of impaction. Lighter body weight, musculo-skeletal problems, farm and dental disease were also significantly associated with a diagnosis of impaction colic. CONCLUSION: To our knowledge this is the first study to estimate the incidence rate of colic in a large population of donkeys in the UK. In contrast to other equids, impaction was the most commonly reported cause of colic. We identified several risk factors for impaction colic. Increasing age, extra rations and previous colic are known risk factors for colic in other equids. Results support the hypothesis that dental disease is associated with impaction colic. Musculo-skeletal problems may be associated with colic for various reasons including change in amount of exercise or time at pasture. Other associated factors (weight and farm) are the subject of further research. Identification of risk factors for impaction colic may highlight high risk donkeys and may allow intervention strategies to be introduced to reduce the incidence of the disease

Turbulence Fluctuations and New Universal Realizability Conditions in Modelling

General turbulent mean statistics are shown to be characterized by a variational principle. The variational functionals, or ``effective actions'', have experimental consequences for turbulence fluctuations and are subject to realizability conditions of positivity and convexity. An efficient Rayleigh-Ritz algorithm is available to calculate approximate effective actions within PDF closures. Examples are given for Navier-Stokes and for a 3-mode system of Lorenz. The new realizability conditions succeed at detecting {\em a priori} the poor predictions of PDF closures even when the classical 2nd-order moment realizability conditions are satisfied.Comment: 4 pages, LaTeX (Version 2.09), 3 figures, Postscript, Submitted to Phys. Rev. Let

Fluctuations in the Irreversible Decay of Turbulent Energy

A fluctuation law of the energy in freely-decaying, homogeneous and isotropic turbulence is derived within standard closure hypotheses for 3D incompressible flow. In particular, a fluctuation-dissipation relation is derived which relates the strength of a stochastic backscatter term in the energy decay equation to the mean of the energy dissipation rate. The theory is based on the so-called ``effective action'' of the energy history and illustrates a Rayleigh-Ritz method recently developed to evaluate the effective action approximately within probability density-function (PDF) closures. These effective actions generalize the Onsager-Machlup action of nonequilibrium statistical mechanics to turbulent flow. They yield detailed, concrete predictions for fluctuations, such as multi-time correlation functions of arbitrary order, which cannot be obtained by direct PDF methods. They also characterize the mean histories by a variational principle.Comment: 26 pages, Latex Version 2.09, plus seceq.sty, a stylefile for sequential numbering of equations by section. This version includes new discussion of the physical interpretation of the formal Rayleigh-Ritz approximation. The title is also change

Polymorphisms in cytochrome P450 2C19 enzyme and cessation of leflunomide in patients with rheumatoid arthritis

Extent: 9p.Introduction: Rational selection of disease modifying anti-rheumatic drugs in the treatment of rheumatoid arthritis (RA) has many potential advantages, including rapid disease control, reduced long-term disability and reduced overall cost to the healthcare system. Inter-individual genetic differences are particularly attractive as markers to predict efficacy and toxicity, as they can be determined rapidly prior to drug selection. The aims of this study, therefore, were to investigate the association between differences in genes associated with the metabolism, clearance and efficacy of leflunomide with its cessation in a group of rheumatoid arthritis patients who were treated with an intensive contemporary, treat-to-target approach. Methods: This retrospective cohort study identified all individuals who received leflunomide and were enrolled in the Early Arthritis inception cohort at the Royal Adelaide Hospital between 2001 and July 2011. Inclusion criteria were age (>18) and a diagnosis of rheumatoid arthritis. Patients were excluded if a DNA sample was not available, if they withdrew from the cohort or if clinical data were insufficient. Subjects were followed for 12 months or until either another disease modifying antirheumatic drug was added or leflunomide was ceased. The following single nucleotide polymorphisms (SNPs) were determined: CYP2C19*2 (rs4244285), CYP2C19*17 (rs12248560), ABCG2 421C>A (rs2231142), CYP1A2*1F (rs762551) and DHODH 19C>A (rs3213422). The effects of variables on cessation were assessed with Cox Proportional Hazard models. Results: Thirty-three of 78 (42.3%) patients ceased leflunomide due to side effects. A linear trend between cytochrome P450 2C19 (CYP2C19) phenotype and leflunomide cessation was observed, with poor and intermediate metabolizers ceasing more frequently (adjusted Hazard Ratio = 0.432 for each incremental change in phenotype, 95% CI 0.237 to 0.790, P = 0.006). Previously observed associations between cytochrome P450 1A2 (CYP1A2) and dihydro-orotate dehydrogenase (DHODH) genotype and toxicity were not apparent, but there was a trend for ATP-binding cassette sub-family G member 2 (ABCG2) genotype to be associated with cessation due to diarrhea. Conclusions: CYP2C19 phenotype was associated with cessation due to toxicity, and since CYP2C19 intermediate and poor metabolizers have lower teriflunomide concentrations, it is likely that they have a particularly poor risk:benefit ratio when using this drug.Michael D Wiese, Matthew Schnabl, Catherine O’Doherty, Llewellyn D Spargo, Michael J Sorich, Leslie G Cleland and Susanna M Proudma

3-D Perturbations in Conformal Turbulence

The effects of three-dimensional perturbations in two-dimensional turbulence are investigated, through a conformal field theory approach. We compute scaling exponents for the energy spectra of enstrophy and energy cascades, in a strong coupling limit, and compare them to the values found in recent experiments. The extension of unperturbed conformal turbulence to the present situation is performed by means of a simple physical picture in which the existence of small scale random forces is closely related to deviations of the exact two-dimensional fluid motion.Comment: Discussion of intermittency improved. Figure include

Paraphrases and summaries: A means of clarification or a vehicle for articulating a preferred version of student accounts?

The use of group discussions as a means to facilitate learning from experiences is well documented in adventure education literature. Priest and Naismith (1993) assert that the use of the circular discussion method, where the leader poses questions to the participants, is the most common form of facilitation in adventure education. This paper draws on transcripts of facilitation sessions to argue that the widely advocated practice of leader summaries or paraphrases of student responses in these sessions functions as a potential mechanism to control and sponsor particular knowledge(s). Using transcripts from recorded facilitation sessions the analysis focuses on how the leader paraphrases the students’ responses and how these paraphrases or ‘formulations’ function to modify or exclude particular aspects of the students’ responses. I assert that paraphrasing is not simply a neutral activity that merely functions to clarify a student response, it is a subtle means by which the leader of the session can, often inadvertently or unknowingly, alter the student’s reply with the consequence of favouring particular knowledge(s). Revealing the subtle work that leader paraphrases perform is of importance for educators who claim to provide genuine opportunities for students to learn from their experience

The geometry of a vorticity model equation

We provide rigorous evidence of the fact that the modified Constantin-Lax-Majda equation modeling vortex and quasi-geostrophic dynamics describes the geodesic flow on the subgroup of orientation-preserving diffeomorphisms fixing one point, with respect to right-invariant metric induced by the homogeneous Sobolev norm $H^{1/2}$ and show the local existence of the geodesics in the extended group of diffeomorphisms of Sobolev class $H^{k}$ with $k\ge 2$.Comment: 24 page