Mixed methods investigation of the use of telephone triage within UK veterinary practices for horses with abdominal pain: A Participatory action research study.

BACKGROUND: Telephone triage is an integral part of modern patient care systems in human medicine, and a key component of veterinary practice care systems. There is currently no published research on telephone triage within the veterinary profession. OBJECTIVE: To investigate current approaches to telephone triage of horses with abdominal pain (colic) in veterinary practice and develop new resources to support decision-making. STUDY DESIGN: Participatory action research using mixed-methods approach. METHODS: An online survey assessed current approaches to telephone triage of horses with colic in UK veterinary practices. Structured group and individual interviews were conducted with four equine client care (reception) teams on their experiences around telephone triage of colic. Evidence-based resources, including an information pack, decision flow chart and recording form, were developed and implemented within the practices. Participant feedback was obtained through interviews six months after implementation of the resources. RESULTS: There were 116 participants in the online survey. Management and client care staff (53/116) felt less confident giving owner advice (p<0.01) and recognising critical indicators (p = 0.03) compared to veterinary surgeons and nurses (63/116). Thirteen themes were identified in the survey relating to owner advice; exercise and owner safety were most frequently mentioned, but conflicting guidance was often given. Fourteen client care staff were interviewed. They were confident recognising colic during a telephone conversation with an owner and identified the most common signs of critical cases as sweating and recumbency. The new resources received positive feedback; the decision flow chart and information on critical indicators were identified as most useful. After resource implementation, there was an increase in confidence in recognising critical cases and giving owners advice. MAIN LIMITATIONS: Limited sample population. CONCLUSIONS: This study described existing approaches to telephone triage, identified variations in advice given, and worked with client care teams to develop new resources to aid decision-making.

BEVA primary care clinical guidelines: Analgesia.

Primary care guidelines provide a reference point to guide clinicians based on a systematic review of the literature, contextualised by expert clinical opinion. These guidelines develop a modification of the GRADE framework for assessment of research evidence (vetGRADE) and applied this to a range of clinical scenarios regarding use of analgesic agents. Key guidelines produced by the panel included recommendations that horses undergoing routine castration should receive intratesticular local anaesthesia irrespective of methods adopted and that horses should receive NSAIDs prior to surgery (overall certainty levels high). Butorphanol and buprenorphine should not be considered appropriate as sole analgesic for such procedures (high certainty). The panel recommend the continuation of analgesia for 3 days following castration (moderate certainty) and conclude that phenylbutazone provided superior analgesia to meloxicam and firocoxib for hoof pain/laminitis (moderate certainty), but that enhanced efficacy has not been demonstrated for joint pain. In horses with colic, flunixin and firocoxib are considered to provide more effective analgesia than meloxicam or phenylbutazone (moderate certainty). Given the risk of adverse events of all classes of analgesic, these agents should be used only under the control of a veterinary surgeon who has fully evaluated a horse and developed a therapeutic, analgesic plan that includes ongoing monitoring for such adverse events such as the development of right dorsal colitis with all classes of NSAID and spontaneous locomotor activity and potentially ileus with opiates. Finally, the panel call for the development of a single properly validated composite pain score for horses to allow accurate comparisons between medications in a robust manner.

Misoprostol is superior to combined omeprazole-sucralfate for the treatment of equine gastric glandular disease.

BACKGROUND: Previous studies have demonstrated a poor response to healing of gastric glandular lesions with oral omeprazole and other medications. OBJECTIVES: To evaluate the efficacy of two novel treatments (misoprostol [M] and combined omeprazole-sucralfate [OS]) in horses for gastric glandular disease. STUDY DESIGN: Prospective, clinical study. METHODS: Sixty-three sports horses with grade >1/4 glandular disease were identified by gastroscopy. Horses received either 5 µg/kg of misoprostol per os BID 1 h prior to feeding or a combination of 4 mg/kg enteric coated omeprazole per os SID and 12 mg/kg sucralfate per os BID where drugs were given 1 h prior to feeding and sucralfate given 60 min after omeprazole; allocation was dependent upon centre. Gastroscopy was repeated at 28-35 days. Evaluators of the gastroscopy images were blinded to the treatments the horses received and images were reviewed independently. RESULTS: The most common presenting sign in both treatment groups was poor performance (Overall - 65.1%; M - 60.5% and OS - 75%). Overall healing (P<0.001; OR = 11 [2.8-45]) and improvement (P = 0.006; OR = 11 [1.9-59]) of lesions were associated with resolution of clinical signs. Misoprostol was shown to be superior to combined omeprazole-sucralfate both for healing (M - 72% [95% CI 43-67] and OS - 20% [95% CI 7-41]; P<0.001) and improvement (M - 98% [95% CI 90-100] and OS - 65% [95% CI 43-83]; P<0.001). MAIN LIMITATIONS: Relatively small, clinical study, reliance on client questionnaire data, clients not blinded to the treatments the horse received, diet could have affected drug pharmacodynamics although mimics clinical practice and no validated scoring system available for glandular lesions. CONCLUSIONS: These results suggest that gastric glandular disease does indeed result in clinical signs. In this population of horses, misoprostol was superior to omeprazole and sucralfate and warrants further evaluation in a large scale, multi-centre trial.

Canine reproductive ultrasound examination for predicting future sperm quality.

The reproductive potential of male animals is commonly evaluated using a breeding soundness examination incorporating B-mode ultrasound examination of the testes and recently Doppler ultrasound examination of the testicular arteries. These techniques may detect testicular normality or pathology, and while some measured parameters are associated with semen quality at the time of ultrasound examination, few studies have investigated the relationship with future semen quality. We hypothesized that B-mode and Doppler ultrasound measurements would correlate with future semen quality. Within two studies, we investigated the relationship between ultrasound measured testicular volume, testicular echogenicity, testicular homogeneity, subjective assessment of the testicular parenchyma, testicular artery resistance index, and pulsatility index with subsequent semen quality. Fifty-five normal fertile dogs of which 29 had stable semen quality and 26 had a subsequent decline in semen quality were examined during a 6-month period commencing 62 days after the ultrasound examination. Statistical analysis showed that no ultrasound parameters were predictive of future total sperm output or percentage live normal sperm. However, mean testicular echogenicity was positively related to future sperm motility (t = 2.202, p = .039). We conclude that quantitative ultrasound assessment of the appearance of the testicular parenchyma has potential for the evaluation of future semen quality in dogs.

Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015.

REASONS FOR PERFORMING STUDY: Equine gastric glandular disease (EGGD) is a common condition, for which the underlying pathophysiology is undetermined. Endoscopic mucosal biopsies have been proposed as a method for adapting therapy. OBJECTIVES: To evaluate diagnostic information obtained from endoscopic mucosal biopsies. STUDY DESIGN: Prospective, experimental study. METHODS: Twenty-one horses undergoing elective humane slaughter were subjected to gross examination of the glandular mucosa. Glandular pathology was graded using EGUS Council guidelines from digital camera images. Mucosal biopsies were obtained using a 'single-bite' (1.8 mm; A and 2.4 mm; B) or 'double bite' technique (2.4 mm; C) using endoscopic biopsy instruments. Tissue was formalin fixed, processed and stained using standard protocols. Inflammatory infiltrates visualised histologically were graded (mild, moderate or severe) and compared with ulcer grade. Full thickness biopsies were also obtained adjacent to the biopsy site and of other visual lesions and inflammatory cell counts were compared with mucosal biopsies using ICC. RESULTS: Full thickness samples were artefact free and allowed visualisation of all layers. Mucosal biopsy samples contained mucosa in all samples, submucosa in 55% (C), 61% (A) and 66% (B) of samples and glands in 50% (B), 66% (A) and 100% (C). Samples from A were too small for histological assessment (33%) and tissue damage was commonly seen in A and B (n = 8 and n = 10) when compared with C (n = 3). Horses with normal glandular appearance (grade 0; n = 7) mostly demonstrated mild gastritis (n = 5). Severe gastritis was identified in mild EGGD (grade 1/2), whilst mild and moderate gastritis was identified in all EGGD grades. There was no histological evidence of ulceration or erosion. There was poor agreement between cell numbers and sampling techniques (ICC<0.29). CONCLUSIONS: These data show lack of ulcerative pathology and instead inflammation in EGGD. Lesion appearance is a poor indicator of underlying severity. Mucosal biopsies offer limited value in predicting underlying disease. Ethical animal research: This study was approved by the University of Nottingham Ethics and Welfare Committee. The study was performed on material collected at an abattoir. SOURCE OF FUNDING: None. Competing interests: None declared.

Digital image analysis of testicular and prostatic ultrasonographic echogencity and heterogeneity in dogs and the relation to semen quality.

A semi-automated ultrasonographic method was developed to measure echogenicity and heterogeneity of the testes and prostate gland and relationships of these measures with semen quality were assessed in 43 fertile dogs. The relationship between animal age and body weight upon the volume of the testes, epididymal tail volume and prostate volume were also established. Mean testicular echogenicity was negatively correlated with the percentage of morphologically normal live spermatozoa (more echogenic testes were associated with fewer normal sperm) but not with any other semen quality measure. Mean testicular heterogeneity was positively correlated with the total spermatozoal output (more heterogenous testes, being those with anechoic parenchyma and prominent echogenic stippling, were associated with greater sperm output) but not with any other semen quality measure. There was no relationship between either mean prostatic echogenicity or mean prostatic heterogeneity and any semen quality measure. There was no relationship between age and any testicular or prostatic parameter; however bodyweight was significantly correlated with total testicular volume, total epididymal tail volume and total prostatic volume. Testicular and prostatic ultrasonographic echogenicity and heterogeneity can be objectively assessed using digital image analysis and testicular echogenicity and heterogeneity may be useful adjunct measurements in a breeding soundness examination.

Reliability of quantitative echocardiography in adult sheep and goats.

BACKGROUND: Echocardiography is a non-invasive method for assessment of the ovine and caprine heart. Complete reference ranges for cardiac dimensions and time indices for both species are not currently available and reliability of these measurements has not been evaluated. The objectives for this study are to report reliability, normal cardiac dimensions and time indices in a large group of adult sheep and goats.Fifty-one adult sheep and forty adult goats were recruited. Full echocardiographic examinations were performed in the standing unsedated animal. All animals underwent echocardiography four times in a 72-hour period. Echocardiography was performed three times by one author and once by another. Images were stored and measured offline. Technique and measurement repeatability and reproducibility and any differences due to animal or day were evaluated. Reference ranges (mean ± 2 standard deviations) were calculated for both species. RESULTS: Majority of the images obtained were of good to excellent quality. Image acquisition was straightforward with 5.4% of animals demonstrating a small scanning window. Reliability was excellent for majority of dimensions and time indices. There was less variation in repeatability when compared with reproducibility and differences were greater for technique than for measurements. Dimensions that were less reliable included those for right ventricular diameter and left ventricular free wall. There were many differences in cardiac dimensions between sheep and goats. CONCLUSIONS: This study has demonstrated that specific reference ranges are required for these two species. Repeatability and reproducibility were excellent for the majority of cardiac dimensions and time indices suggesting that this technique is reliable and valuable for examination of clinical cases over time and for longitudinal research studies.

Reference ranges and reliability of transabdominal ultrasonographic renal dimensions in thoroughbred horses.

The aims of this study were to establish a normal reference range (mean ± 2 SD) and assess reliability of renal dimensions obtained using transabdominal ultrasonography in Thoroughbred horses (n = 7). A minimum of three ultrasonographic cineloops were obtained from each intercostal space and the left paralumbar fossa by two observers daily for three consecutive days. Renal length, width, and thickness and cortex, medulla, and pelvic dimensions were obtained. Measurements were undertaken by both observers, who were unaware of prior measurements, to assess reproducibility and measured on three separate occasions to evaluate short-term measurement repeatability. Measurements from images obtained by both operators were compared to evaluate image repeatability. The left kidney was consistently identified in the left 15th-17th intercostal space and the paralumbar fossa with maximal length in the 16th intercostal space (12.7 ± 2.0 cm) and maximal width in the paralumbar fossa (7.9 ± 1.1 cm). The right kidney was consistently identified in the right 15th-17th intercostal space with maximal length and maximal width in the 15th intercostal space (16.0 ± 0.7 cm and 7.9 ± 1.0 cm). Reproducibility, image repeatability, measurement repeatability were good to excellent, although were less good for the smaller structures. There were no differences in renal dimensions between horses. Overall renal ultrasonography was reliable and a normal reference range for Thoroughbred horses was established. Renal dimensions vary between rib spaces. As repeatability and reproducibility were excellent for renal length and width, it may be prudent to use those measurements in rib spaces where parameters were maximal.

Applications and implications of direct groundwater velocity measurement at the centimetre scale.

Three projects involving point velocity probes (PVPs) illustrate the advantages of direct groundwater velocity measurements. In the first, a glacial till and outwash aquifer was characterized using conventional methods and multilevel PVPs for designing a bioremediation program. The PVPs revealed a highly conductive zone that dominated the transport of injected substances. These findings were later confirmed with a natural gradient tracer test. In the second, PVPs were used to map a groundwater velocity field around a dipole recirculation well. The PVPs showed higher than expected velocities near the well, assuming homogeneity in the aquifer, leading to improved representations of the aquifer heterogeneity in a 3D flow model, and an improved match between the modelled and experimental tracer breakthrough curves. In the third study, PVPs detected subtle changes in aquifer permeability downgradient of a biostimulation experiment. The changes were apparently reversible once the oxygen source was depleted, but in locations where the oxygen source lingered, velocities remained low. PVPs can be a useful addition to the hydrogeologist's toolbox, because they can be constructed inexpensively, they provide data in support of models, and they can provide information on flow in unprecedented detail.

Two novel aspirin analogues show selective cytotoxicity in primary chronic lymphocytic leukaemia cells that is associated with dual inhibition of Rel A and COX-2.

OBJECTIVES: Non-steroidal anti-inflammatory drugs have been shown to induce apoptosis in primary B-cell chronic lymphocytic leukaemia (CLL) cells, but the molecular mechanisms that underpin this observation have not been fully elucidated. Here, we have analysed the effect two novel aspirin analogues, 2-hydroxy benzoate zinc (2HBZ) and 4-hydroxy benzoate zinc (4HBZ), on primary CLL samples. MATERIALS AND METHODS: Cytotoxic effects of 2HBZ and 4HBZ were analysed in primary CLL cells derived from 52 patients, and normal B- and T-lymphocytes. Mechanisms of action of these agents were also elucidated. RESULTS: Both analogues induced apoptosis in a dose-dependent and time-dependent manner. Apoptosis was associated with activation of caspase-3 that could be partially abrogated by the caspase-9 inhibitor (Z-LEHD.fmk). Importantly, both agents demonstrated preferential cytotoxicity in CLL cells when compared to normal B- and T-lymphocytes. In terms of their molecular mechanisms of action, 4HBZ and 2HBZ inhibited COX-2 transcription and protein expression and this was associated with upstream inhibition of transcription factor Rel A. Co-culture of CLL cells with CD40 ligand-expressing mouse fibroblasts significantly increased COX-2 expression and inhibited spontaneous apoptosis. Importantly, the most potent analogue, 4HBZ, overcame pro-survival effects of the co-culture system and significantly repressed COX-2. Finally, elevated COX-2 expression was associated with poor prognostic subsets and increased sensitivity to 4HBZ. CONCLUSIONS: Our results demonstrate therapeutic potential of 4HBZ and are consistent with a mechanism involving suppression of Rel A nuclear translocation and inhibition of COX-2 transcription.

Repeatability and reproducibility of transabdominal ultrasonographic intestinal wall thickness measurements in Thoroughbred horses.

The aims of this study were to assess the repeatability and reproducibility of transabdominal ultrasonography to assess intestinal wall thickness in adult Thoroughbred horses (n = 8). Ultrasonographic cineloops were captured by one examiner from each horse for five consecutive days. During each examination at least three cineloops were obtained for five different intestinal tract locations. Measurements were performed by three separate observers to assess reproducibility and measured on three separate occasions by three observers to evaluate short-term repeatability. The repeatability of measurements from the duodenum (0.3 +/- 0.04 cm), jejunum (0.29 +/- 0.05 cm), ventral colon (0.37 +/- 0.01 cm), and cecum (0.42 +/- 0.03 cm) were good (P > 0.291). The reproducibility of measurements from the duodenum, jejunum, and ventral colon were good (P > 0.394). Reproducibility of measurement of the cecal wall was inadequate (P = 0.01), although the maximum difference between observers was 0.07 cm. It was possible to image all areas on all days, with the exception of the duodenum, which could not be imaged in one horse, on 1 day. Equine intestinal wall measurements are therefore repeatable and reproducible with the exception of reproducibility of the measurements of cecal wall. Although an accepted clinical technique, measurement of cecal wall thickness from intestinal ultrasound images in a clinical setting must be interpreted with care.

Sub-millimolar concentration of the novel phenol-based compound, 2-hydroxy benzoate zinc, induces apoptosis in human HT-1080 fibrosarcoma cells.

OBJECTIVES: To examine the effect of a novel phenolic-based compound, 2-hydroxy benzoate zinc (2HBZ), and acetylsalicylic acid (ASA) on human HT-1080 fibrosarcoma cells. MATERIALS AND METHODS: MTT assay was used to assess cell proliferation while different methods were used to detect apoptosis morphologically and immunohistochemically in Human HT-1080 fibrosarcoma cells. Apoptosis was determined by Annexine-V labelling, and caspase-3 activation. In addition, western blot was used to analyse p21, p53 and Bax and flow cytometry was to analyse the cell cycle. RESULTS: 2HBZ exhibited a more than 5-fold increase in cytotoxic potency when compared with ASA with mean LD50 values of 210 and 1100 lM respectively (P < 0.0001). The cytotoxic effects of 2HBZ were both time- and dosedependent with marked apoptosis being evident only after 24 h at concentrations as low as 200 mM. In contrast, ASA-induced apoptosis was observed only at concentrations in excess of 1000 mM at the same time point. Both 2HBZ and ASA induced caspase-3 activation in the cells, which confirmed that their cytotoxic effects were the result of apoptotic cell death. These findings were further confirmed by immunomorphological studies for the detection of apoptosis including haematoxylineosin, methyl green/pyronin Y staining and scanning electron microscopy. In addition, 2HBZ caused a marked increase in p21, p53 and Bax protein expressions and these effects were associated with an increase in G1 and G2 arrest of the cell cycle and a reduction in S-phase. CONCLUSIONS: These results demonstrate that the novel phenolic compound 2HBZ is a potent apoptosis-inducing agent in HT-1080 cells and warrants further investigation as a potential chemotherapeutic agent in primary cancer cell models.

Effect of left-sided valvular regurgitation on mortality and causes of death among a population of middle-aged and older horses.

The effect of left-sided valvular regurgitation (LSVR) on the mortality of middle-aged and older horses was investigated in a prospective cohort study involving 19 yards and 1153 horses. The horses were examined to determine whether they had a cardiac murmur and its type, and their age, sex, breed type and occupation were recorded. They were followed up at intervals of two years by postal questionnaire, and after four years information on 773 horses was available. There was no significant difference in the mortality of the horses with and without LSVR, but small horses had a significantly higher risk of having LSVR than small ponies (odds ratio [OR] 2.33), and older horses were slightly more likely to have LSVR than young horses (OR 1.07). Twenty-nine per cent of the deaths reported by the owners were due to orthopaedic problems, 23.3 per cent to gastrointestinal problems, and only 7.9 per cent to cardiovascular problems. Orthopaedic problems were the main cause of death in the horses, and gastrointestinal problems were the main cause of death in the ponies.

Ultrasonographic anatomy of the bovine eye.

The purposes of the study were to describe the ultrasonographic appearance and measurements of the normal bovine eye, to compare the measurements to those reported previously for cadaveric eyes and to describe differences between ocular dimensions of Holstein Friesian and Jersey cattle. Sixty transpalpebral ocular ultrasonographic examinations were performed on 30 adult Holstein Friesian cows, and 16 examinations were performed on 8 adult Jersey cows. Transpalpebral ultrasonographic images were obtained with a 10 MHz linear transducer in both horizontal and vertical imaging planes. The ultrasonographic appearance of structures within the bovine eye is similar to that in other species, although the ciliary artery was frequently identified, appearing as a 0.33 +/- 0.04 cm diameter hypoechoic area. The axial length of the globe was significantly greater in Holstein Friesian cattle (3.46 +/- 0.09 cm) compared with Jersey cattle (3.27 +/- 0.19 cm; P = 0.001), although the vitreous depth was smaller in Holstein Friesian cattle (1.46 +/- 0.09 cm) (P = 0.0009). The anterioposterior depth of the lens was significantly greater in Jersey cattle (1.92 +/- 0.11 cm) and the cornea was thinner in Jersey cattle (0.17 +/- 0.02 cm). The appearance and ocular distances for live animals were similar to those reported previously for cadaveric specimens. The knowledge of normal ocular dimensions facilitates the use of ultrasonography in the evaluation of ocular disease in cattle.

Methods and normal values for echocardiography in adult dairy cattle.

OBJECTIVE: The objective of the study was to report normal ultrasonographic appearance and intra-cardiac dimensions in two dairy breeds and to calculate cardiac output (CO) using echocardiography. BACKGROUND: Intra-cardiac dimensions, time indices and CO estimation have not previously been reported in adult cattle. ANIMALS, MATERIALS AND METHODS: Echocardiograms were obtained from healthy adult dairy cows (10 Jersey (J) and 12 Holstein Friesians (HF)) in the body weight range of 400 to 700 kg. Standard echocardiographic images were obtained from the left and right hemithoraces. Velocity time integrals were obtained in order to calculate CO using pulsed wave Doppler of aortic flow in the J cows. Measurements obtained included pulmonary artery and aortic diameters, left and right ventricular diameters (and calculated fractional shortening and left ventricular ejection fraction), left atrial size and time indices assessing valve function. RESULTS: HF cows had significantly (p<0.05) larger pulmonary artery and aortic diameters, larger left atrial diameters and left ventricular internal diameters during diastole, but these were not different when corrected for body weight. Left and right ventricular dimensions, adjusted for body weight, were significantly larger (p=0.02 and p=0.035 respectively) in J cows when compared to HF cows. No differences were noted in the time indices between the two groups. No significant differences were noted in intra-operator variability and the only significant difference in inter-operator variability was in measurement of the pulmonary artery (p=0.03; ICC=0.63). CONCLUSIONS: It is possible to obtain repeatable, reliable echocardiograms in order that meaningful intra-cardiac dimensions can be obtained in adult dairy cattle.

Calcium salicylate-mediated apoptosis in human HT-1080 fibrosarcoma cells.

Salicylates are novel biologically active compounds that exhibit multiple therapeutic activities. The anti-cancer effectiveness of calcium salicylate has been investigated on human HT-1080 fibrosarcoma cell lines at relatively low concentrations (predominantly 0.4 mM) compared to those previously reported. Although low calcium salicylate concentrations did not retard tumour growth progression significantly, as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and time-lapse assays, its cytotoxic characteristics were proven to be prominent by various morphological and immunocytological techniques. The results here demonstrate evidence for approximately 25% apoptosis after treatment with calcium salicylate, which up-regulatd the expression of p53, p21 and Bax, and down-regulated Bcl-2 in HT-1080 cells.

The historical analysis of aspirin discovery, its relation to the willow tree and antiproliferative and anticancer potential.

For several millennia, the willow tree and salicin have been associated with salicylic acid, the key precursor molecule that has contributed to the discovery of acetylsalicylic acid, traded as aspirin. These molecules have been shown to possess phyto- and chemotherapeutic activities as analgesic drugs. In recent decades, aspirin has become the focus of extensive investigation into antiproliferative and anticancer activities. The historical steps that led to the discovery of aspirin, and its antiproliferative and anticancer potential are highlighted in this review.