Pharmacokinetics and safety of repeated oral dosing of acetaminophen in adult horses.

BACKGROUND: There are no published studies on the pharmacokinetics of acetaminophen at the dosage used clinically (20 mg/kg), nor has the safety of multiple doses in horses been investigated. OBJECTIVE: Define the pharmacokinetic parameters of oral acetaminophen at 20 mg/kg in adult horses as a single dose, and twice daily for 14 days to assess the safety of multiple dosing. STUDY DESIGN: Pharmacokinetic study, multiple dose safety study. METHODS: Eight healthy Thoroughbred geldings were given acetaminophen (20 mg/kg; 500 mg tablets) orally as a single dose followed by doses every 12 h for 14 days. Serial blood samples were collected for determination of plasma acetaminophen concentrations using high performance liquid chromatography with ultraviolet detection. Serum biochemical analysis, gastroscopy and liver biopsy were examined during the safety study. RESULTS: Following a single dose, mean maximum concentration (Cmax ) was 16.61 µg/mL at 1.35 h (Tmax ), and drug concentration was below the lower limit of detection in most horses by 24 h. Elimination half-life (T1/2 ) was 2.78 h. No significant accumulation was noted following multiple doses. Average Cmax of acetaminophen following multiple oral dosing was 15.85 µg/mL, with a Tmax of 0.99 h and T1/2 of 4 h. Serum activities of sorbitol dehydrogenase were significantly decreased and total bilirubin concentrations were significantly increased following the last dose. No statistically significant changes were noted in gastroscopy scores. MAIN LIMITATIONS: Only one dose level (20 mg/kg) was studied, sample size was small and only a single breed and sex was used, with no pretreatment liver biopsies. CONCLUSION: This study described the pharmacokinetics of acetaminophen following single and multiple 20 mg/kg oral doses in adult horses and demonstrated the safety of acetaminophen with multiple oral dosing over 14 days. The summary is available in Portuguese - see Supporting information.

Extracorporeal shockwave therapy raises mechanical nociceptive threshold in horses with thoracolumbar pain.

BACKGROUND: Although extracorporeal shockwave therapy (ESWT) is a common treatment for horses with back pain, effects on mechanical nociceptive threshold (MNT) and multifidus muscle cross sectional area (CSA) in the spine are unknown. OBJECTIVES: To evaluate effects of ESWT on spinal MNT and multifidus muscle CSA in horses with thoracolumbar pain. STUDY DESIGN: Non-randomised trial. METHODS: Thoracolumbar spines of 12 horses with thoracolumbar pain were radiographed to document existing pathology. Each horse received three ESWT treatments, 2 weeks apart (days 0, 14, 28). Palpation scores were documented (days 0, 45 and 65). Ultrasonographic CSA of left and right multifidus muscles was recorded at T12, T14, T16, T18, L3 and L5 (days 0, 45 and 65). MNT was measured at the same spinal sites every 7 days (day 0-56). RESULTS: Mechanical nociceptive threshold in 10/12 horses (83%) was greater at each time point compared with day 0 (P < 0.05). Mechanical nociceptive threshold increased at all time points at six sites in 2/12 (16%), at five sites in 3/12 (25%), at four sites in 4/12 (33%) and at one site in 1/12 (8%; P < 0.05). Mechanical nociceptive threshold average per cent  increase from day 0 to 56 was 64% for the thoracic region (T12-T18) and 29% for the lumbar region (L3-L5). There was no statistical difference in MNT from day 35 to 56 (P = 0.25). A bimodal analgesic trend was observed following ESWT. Degree of radiographic change was not associated with response to treatment. No significant change in multifidus muscle CSA was observed. MAIN LIMITATIONS: Small study size and lack of control group. CONCLUSIONS: Three treatments of ESWT 2 weeks apart raised MNT over a 56-day period in horses with back pain, but did not influence change in CSA of the multifidus muscle. While ESWT appears justifiable for analgesia, physiotherapeutic techniques may be necessary in conjunction for concurrent muscle rehabilitation.

PD-L1 and immune infiltrates are differentially expressed in distinct subgroups of gastric cancer.

This study investigates the association of PD-L1 expression and immune cell infiltrates and their impact on clinical outcome, in addition to their overlap with microsatellite instability (MSI), HER2 and ATM molecular subgroups of gastric cancer (GC). PD-L1 membrane expression on tumour cells (TC) and infiltrating immune cells (IC), CD3 + T-lymphocytes, CD8+ cytotoxic T-cells, ATM and HER2 were assessed by immunohistochemistry (IHC) in the ACRG (Asian Cancer Research Group) GC cohort (N = 380). EBV status was determined using in situ hybridization and MSI status was performed using PCR and MLH1 IHC. The PD-L1 segment was associated with increased T-cell infiltrates, while the MSI-high segment was enriched for PD-L1, CD3, and CD8. Multivariate analysis confirmed PD-L1 positivity, high CD3 and high CD8 as independent prognostic factors for both disease-free survival and overall survival (all p < 0.05). Patients with MSI-high tumours had better overall survival by both univariate and multivariate analysis. The ATM-low and HER2-high subgroups differed markedly in their immune profile; the ATM-low subgroups enriched for MSI, PD-L1 positivity and CD8 + T-cells, while the HER2 segment was enriched for MSS, with no enrichment for immune markers. Hence, we demonstrate a molecular profiling approach that can divide GC into four molecular subgroups, namely ATM-low, HER2-high, PD-L1 positive and MSI-high with differing levels of immune infiltrates and prognostic significance which may help to stratify patients for response to targeted therapies.

Pharmacokinetics of firocoxib after intravenous administration of multiple consecutive doses in neonatal foals.

The purpose of this study was to determine the pharmacokinetic profile of intravenous firocoxib in neonatal foals. Six healthy foals were administered 0.09 mg/kg firocoxib intravenously once a day for 7 days. Blood was collected for plasma firocoxib analysis using high-performance liquid chromatography with fluorescence detection at times 0 (day 1 of study only) and 0.08, 0.25, 1, 2, 4, 6, 8, 16 and 24 hr on dose numbers 1, 5 and 7. Blood was also collected immediately prior to doses 3, 4, 5 and 7. Final samples were collected at 36, 48, 72 and 96 hr following the final dose. Noncompartmental analysis using the trapezoidal method with linear interpolation revealed a moderate half-life (15.9 ± 9.1 hr) with a large volume of distribution at steady state (1.79 ± 0.57 L/kg) and a clearance (96.0 ± 59.2 ml h-1  kg-1 ) that was more rapid than that observed in adult horses.

Seroprevalence of Borrelia burgdorferi in Horses Presented for Coggins Testing in Southwest Virginia and Change in Positive Test Results Approximately 1 Year Later.

BACKGROUND: Lyme disease can affect people, dogs, and horses, but it remains poorly understood, especially in the horse. Determining the seroprevalence of Borrelia burgdorferi in horses in different geographic areas will enable better understanding of the epidemiology of the disease, thus improving diagnosis and treatment of affected animals. HYPOTHESIS: To determine the seroprevalence of B. burgdorferi in horses in southwest Virginia. ANIMALS: Horses presented for routine Coggins testing from January 2013 to January 2014 had additional blood drawn for Lyme Multiplex Assay testing. METHODS: Of 492 samples collected, 250 samples were analyzed using the Lyme Multiplex Assay. Of the 83 horses that had positive test results to at least 1 outer surface protein (Osp), 63 were available for follow-up testing 5-17 months later (June 2014). RESULTS: Thirty-three percent of horses had positive results for antibodies to at least 1 Osp. Horses with a positive outer surface protein F (OspF) result were older (14.5 ± 0.79) than horses with a negative OspF result (11.6 ± 0.53). Of the horses available for follow-up testing, 63% had the same result as that of the initial test. There was no difference in test result between initial and follow-up testing. CONCLUSIONS: Horses seropositive to B. burgdorferi are common in Virginia, and older horses are more likely to have a positive test result for OspF than younger horses. Follow-up testing indicated that the majority of horses that were positive on initial testing did not have a different test result 5-17 months later.

Impact of KRAS codon subtypes from a randomised phase II trial of selumetinib plus docetaxel in KRAS mutant advanced non-small-cell lung cancer.

BACKGROUND: Selumetinib (AZD6244, ARRY-142886)+docetaxel increases median overall survival (OS) and significantly improves progression-free survival (PFS) and objective response rate (ORR) compared with docetaxel alone in patients with KRAS mutant, stage IIIB/IV non-small-cell lung cancer (NSCLC; NCT00890825). METHODS: Retrospective analysis of OS, PFS, ORR and change in tumour size at week 6 for different sub-populations of KRAS codon mutations. RESULTS: In patients receiving selumetinib+docetaxel and harbouring KRAS G12C or G12V mutations there were trends towards greater improvement in OS, PFS and ORR compared with other KRAS mutations. CONCLUSION: Different KRAS mutations in NSCLC may influence selumetinib/docetaxel sensitivity.

Pharmacokinetics and safety of firocoxib after oral administration of repeated consecutive doses to neonatal foals.

The purpose of this study was to determine the pharmacokinetics and safety profile of firocoxib in neonatal foals. Seven healthy foals were administered 0.1 mg/kg firocoxib orally q24 h for nine consecutive days, commencing at 36 h of age. Blood was collected for firocoxib analysis using high-pressure liquid chromatography with fluorescence detection at 0 (dose #1 only), 0.25, 0.5, 1, 2, 4, 8, 16, and 24 h after doses 1, 5, and 9. For all other doses (2, 3, 4, 6, 7, and 8), blood was collected immediately prior to the next dose (24 h trough). Elimination samples (36, 48, 72, 96, 120, and 144 h) were collected after dose 9. Safety was assessed via physical examinations, body weight measurements, gastroscopy, complete blood count, plasma biochemistry and urinalysis. Firocoxib was rapidly absorbed following oral administration with minimal accumulation after repeat dosing. After the final dose, the terminal half-life was approximately 11 h. Firocoxib was below the limit of detection (<2.5 ng/mL) in plasma 72 h after the final dose. No significant abnormalities were found on blood analyses, urinalysis, or gastroscopy. This study demonstrated that firocoxib is absorbed in neonatal foals with no demonstrable adverse effects after repeated doses of 0.1 mg/kg.

Pharmacokinetics of pioglitazone after multiple oral dose administration in horses.

Pioglitazone is a thiazolidinedione class of antidiabetic agent with proven efficacy in increasing insulin sensitivity in humans with noninsulin-dependent diabetes mellitus, a syndrome of insulin resistance sharing similarities with equine metabolic syndrome. The purpose of this study was to determine the pharmacokinetics of pioglitazone in adult horses following multiple oral dose administration. Pioglitazone hydrochloride (1 mg/kg) was administered orally for 11 doses at 24-h intervals, and plasma samples were collected. Initially, a pilot study was performed using one horse; and thereafter the drug was administered to six horses. Samples were analyzed by liquid chromatography with tandem mass spectrometry, and pharmacokinetic parameters were calculated using noncompartmental modeling. The maximum plasma concentration was 509.1 ± 413.5 ng/mL achieved at 1.88 ± 1.39 h following oral administration of the first dose, and 448.1 ± 303.5 ng/mL achieved at 2.83 ± 1.81 h (mean ± SD) following the eleventh dose. Apparent elimination half-life was 9.94 ± 4.57 and 9.63 ± 5.33 h after the first and eleventh dose, respectively. This study showed that in healthy horses, pioglitazone administered at a daily oral dose of 1 mg/kg results in plasma concentrations and total drug exposure approximating, but slightly below, those considered therapeutic in humans.

A survey of aged horses in Queensland, Australia. Part 2: Clinical signs and owners' perceptions of health and welfare.

OBJECTIVE: To describe the prevalence and risk factors for clinical signs of disease and owner-reported health or welfare issues of aged horses in Queensland, Australia. METHODS: Owners of horses were contacted via an equestrian organisation in Queensland and asked to complete a questionnaire about their horses aged 15 years and older, to gain information about clinical signs observed in the horse and disease history. Owners were asked to identify health or welfare issues they felt were important in aged horses. RESULTS: Owners were able to identify many clinical signs of disease, with 83% of horses having at least one reported clinical sign of disease. Muscle stiffness (33%), lameness (28%), ocular discharge (22%), change in hair coat (22%) and skin problems (21%) were the most commonly reported signs. Increasing age was a risk factor for the presence of clinical signs of disease. Ponies had an increased risk of both laminitis and hirsutism, whereas Thoroughbreds had an increased risk of stereotypies, wounds, weight loss and musculoskeletal signs. Owners reported a known disease or disorder in their horses less frequently than the clinical signs of disease. Owners reported weight loss (28%), arthritis/lameness (24%) and teeth/dental care (18%) as the most important health issues, followed by welfare issues (8%). CONCLUSION: Owners demonstrated concern for the health and welfare of their aged horses, but the lack of appropriate recognition of the significance of clinical signs and limited veterinary care suggest a need for increased client communication and veterinarian-client interaction.

Osseous spinal pathology and epaxial muscle ultrasonography in Thoroughbred racehorses.

REASONS FOR PERFORMING STUDY: The multifidus muscle plays a key role in spinal stabilisation. Multifidus atrophy ipsilateral to the side of osseous pathology has been demonstrated in man and pigs but has not been investigated in horses. OBJECTIVES: To measure cross-sectional area (CSA) left/ right symmetry of equine multifidus ultrasonographically and relate asymmetry of multifidus with osseous spinal pathology in Thoroughbred racehorses. We hypothesised that ipsilateral multifidus CSA would be reduced when osseous pathological changes are present leading to left/right asymmetry in CSA. MATERIALS AND METHODS: Twenty-two racehorses presented for euthanasia for primary reasons other than back pain were examined clinically. Ultrasonographic images on left/right sides were acquired at 5 thoracolumbosacral levels and CSA's of multifidus or sacrocaudalis dorsalis calculated. At necropsy, osseous pathological of the TL spine and pelvis were recorded by spinal level, anatomical site, and graded (0-3) according to severity. The mean typical measurement error in estimating multifidus/sacrocaudalis dorsalis CSA was used to determine the significance of left/right asymmetries. An association between multifidus CSA asymmetry and asymmetrical grading of pathological lesions was sought using Pearson's χ(2) analysis. RESULTS: All horses had significant left/right asymmetry of multifidus CSA at >2 spinal levels, most commonly at L5 with total of 74 sites affected (22 horses). Seventeen horses had severe (grade 3) pathology, 16 of these had ipsilateral atrophy of multifidus/sacrocaudalis dorsalis. There was a significant association between pathological grade and degree of multifidus asymmetry. CONCLUSIONS: Severe osseous pathological changes were common in this population of Thoroughbred racehorses and were associated with measurable left/right asymmetry in multifidus at or close to the level of pathology. POTENTIAL RELEVANCE: Ultrasonography of multifidus may be a useful clinical tool in diagnosis of back problems in horses.

A survey of aged horses in Queensland, Australia. Part 1: management and preventive health care.

OBJECTIVE: To describe management practices and routine preventive care of aged horses in Queensland, Australia, including effects of owner characteristics, affiliation to an equestrian group and retirement of the horse. METHODS: Owners of horses were contacted via Equestrian Australia (EA) and asked to complete a questionnaire about their aged horses (e.g. age, breed, sex and colour); their use and management, including preventive health care; and use of equine healthcare providers. RESULTS: Horses aged 15 years or greater represented one-third of the total horses owned in the population sample. The median age of the horses was 20.7 years (range 15-44 years). Basic husbandry and preventive health care varied depending on demographic region, age of the horse and its use. Affiliation with EA was associated with the breed and use of the horse, but not with management or preventive health care other than frequency of hoof care visits. Retired horses had reduced basic husbandry and preventive health care compared with non-retired horses. There was reduced preventive health care in rural compared with urban areas. The majority (61%) of horses in the current study had not been visited by a veterinarian in the previous 12 months. CONCLUSION: Aged horses constitute a large subgroup of the Australian horse population. Although basic management is at a high level for most aged horses, it appears to be reduced following the horse's retirement and in the more rural areas. There was limited veterinary involvement in preventive healthcare strategies for aged horses, especially in rural areas.

Long-term assessment of horses and ponies post exposure to monensin sodium in commercial feed.

REASONS FOR PERFORMING STUDY: Acute monensin intoxication in equids is well described; however, the long-term effects of sublethal intoxication and ability to return to previous use are less well understood. Long-term observations may allow improved estimation of prognosis in cases of sublethal intoxication. OBJECTIVES: To assess horses and ponies exposed to sublethal amounts of monensin for evidence of chronic sequelae and ability to return to prior/intended use. METHODS: Twenty-nine horses and 8 ponies were assessed utilising serum biochemistry, treadmill exercise stress testing, electrocardiography, and pre- and post exercise echocardiography > or = 6 weeks after ingestion of monensin-contaminated feed. Animals with evidence of monensin-induced cardiomyopathy were re-examined after a period of rest of > or = 11 months. Follow-up information was obtained by owner telephone interview > or = 52 months after exposure. RESULTS: During resting echocardiography, 11 animals had reduced/low-normal left ventricular fractional shortening (FS); an increase in FS in 8 of these animals was measured > or = 11 months later. Six animals had reduced or low-normal FS during post exercise echocardiography. Two horses had ventricular premature depolarisations during exercise. Follow-up information was available for 35 animals: 21 returned to athletic/reproductive use, 13 were retired immediately and one died. Mean FS increased significantly (P < 0.001) between initial and second examination in 15 animals that underwent resting echocardiography on 2 occasions. CONCLUSIONS: Some equids exposed to sublethal doses of monensin may not develop permanent myocardial disease and a return to athletic/reproductive use is possible. POTENTIAL RELEVANCE: Exercise stress testing, echocardiography and electrocardiography may be useful for detection and monitoring of cardiac dysfunction in equids exposed to monensin and determining whether a return to athletic/reproductive use is possible.

Incidence rate of musculoskeletal injuries and determinants of time to recovery in young Australian Thoroughbred racehorses.

OBJECTIVE: To describe the incidence rate of musculoskeletal (MS) injuries and investigate the factors that influence recovery from MS injury in young Thoroughbred horses in Australia. METHODS: Training and injury data were collected at fortnightly intervals from 14 trainers in New South Wales. Incidence rates were calculated for initial injuries stratified by age-class and sex. Survival analysis methods were used to investigate the time to recovery after the first MS injury (measured as a start in a race or barrier trial). RESULTS: For the 248 racehorses enrolled, there were 428 injuries recorded; 2-year-olds were 2.99-fold more likely than 3-year-olds to sustain an MS injury. The cumulative percentage of horses that had recovered within 6 months was 55%. The time to recovery was longest in horses whose fast gallop speed prior to injury was < 890 m/min. CONCLUSION: This study supports the finding that shin soreness is the most common MS injury in young Australian Thoroughbreds. There was an increased rate of MS injury in 2-year-olds compared with 3-year-olds. However, it was impossible to determine if the increased risk in 2-year-olds was related to age, the start of training or a combination of both. The study also found that horses performing at higher exercise speeds prior to injury were more likely to recover. There was a significant effect of trainer, suggesting that other factors related to trainer may influence the time to the recovery. Additional research is required to understand the determinants of time to recovery.

Profiling training preparation in young Australian Thoroughbred racehorses.

OBJECTIVE: To describe the impact of age, sex, and musculoskeletal (MS) injury on three preparation-level measures of performance: (i) the duration of preparation, (ii) time from the beginning of the preparation until the first start in a race or barrier trial, and (iii) time from the first start until the end of the preparation. METHODS: Daily training and injury data for 2- and 3-year old Thoroughbred racehorses were collected fortnightly from 14 trainers in NSW, Australia. Training data were aggregated into units referred to as 'preparations'. Univariate and multivariate analytical methods were used to examine the associations between the explanatory variables and each of the measures of performance. RESULTS: There were 1274 preparations recorded in 451 horses. Younger horses had a shorter interval from the first start in a race or barrier trial to the end of the preparation. MS injury was not conditionally associated with any of the outcomes. CONCLUSION: MS injuries in young racehorses have limited impact on long-term performance, although care must be taken in interpreting the results because they could be confounded by variables not considered in this analysis. This study also begins to unravel the complicated relationship between age and previous exposure to training, with results supporting the hypothesis that the intensity of training increases with increasing age.

Elapid snake envenomation in dogs in New South Wales: a review.

Elapid snake envenomation in dogs is a commonly occurring yet poorly described clinical entity. Twelve species of dangerously venomous elapid snakes are found in New South Wales that are capable of causing disease in dogs. Geographical distribution of these species varies, as does their venom composition and systemic envenomation syndromes produced in target species. Elapid venom may be divided into the components of prothrombin activating enzymes, lipases and peptidic neurotoxins. Each species of elapid snake may possess venom components that fit any or all of these classifications. The action of these venom components may result in neurotoxic (pre-synaptic and post-synaptic), haemotoxic (red-cell destruction and coagulation disturbance), cardiovascular, myotoxic and secondary nephrotoxic effects. Marked variability may occur in venom composition between and within snake species, resulting in varying toxicity between species and also potentially unreliable clinical syndromes following envenomation. The existence of certain components consistently within the venom of each snake species allows the broad definition of basic pathological processes and clinicopathological changes resulting from snake species-specific envenomation and these are discussed. Diagnosis of snake envenomation is unreliable if based on clinical signs alone and the use of these signs in conjunction with history, physical examination and laboratory investigation, including snake venom detection kits, is recommended. Treatment of systemic envenomation should be undertaken with initial effective first aid and subsequent administration of snake species-specific antivenom.

Effect of hypothermia on recovery from general anaesthesia in the dog.

OBJECTIVE: To discern the effects of anaesthesia protocols and decreasing core body temperature on time to recovery from general anaesthesia. MATERIALS AND METHODS: Healthy adult dogs undergoing desexing surgery were enrolled. More excitable dogs were premedicated with intramuscular acepromazine and morphine; calmer dogs were not premedicated. Anaesthesia was induced using halothane, isoflurane or sevoflurane delivered by mask, or by intravenous propofol, and maintained in standard fashion using one of the three inhalant agents. Thermostat controlled heat mats were used during surgical preparation and surgery. Oesophageal temperature was recorded throughout surgery. The time from cessation of anaesthetic administration until the dog successfully raised itself to sternal recumbency was considered the time of recovery. RESULTS: Sixty-nine dogs completed the study, 42 males anaesthetised for 60.4 +/- 20.5 min, and 27 females anaesthetised for 85.4 +/- 33.2 min. Oesophageal temperature at the end of surgery was 36.8 +/- 0.80 degrees C. Oesophageal temperature had a significant effect on recovery time, with lower temperatures contributing to slower recoveries. Premedication significantly lengthened recovery times. The choice of induction or maintenance anaesthetic agent had no effect on recovery time. DISCUSSION: Hypothermia is a common complication of general anaesthesia and surgery. Amongst other deleterious effects, it is associated with slower recovery from anaesthesia, likely due to a number of different mechanisms.

Anuric renal failure in a dog after red-bellied black snake (Pseudechis porphyriacus) envenomation.

A case of Red-bellied Black snake envenomation resulting in intravascular haemolytic anaemia, rhabdomyolysis and anuric renal failure is described in the dog. A 12-year-old female desexed Golden Retriever was presented with a 15 hour history of profuse salivation, progressive lethargy, obtundence, inappetence and collapse. Significant findings on clinical examination were pallor, icterus, tachypnoea and dyspnoea with increased respiratory sounds and crackles in all lung fields. Generalised abdominal and muscular pain was apparent and dark red-brown urine was present around the perineal region. A diagnosis of Red-bellied Black snake (Pseudechis porphyriacus) envenomation was made and the dog was treated with intravenous fluid therapy, Tiger/Brown snake antivenom, packed red cell transfusions and Intermittent Positive Pressure Ventilation. Continued clinical deterioration occurred and a diagnosis of acute renal failure secondary to myohaemoglobinuric pigmenturia was made 12 hours after admission. Intensive treatment was attempted with diuresis and volume expansion. Oliguria and subsequent anuria ensued and the dog was euthanased due to a grave prognosis and lack of clinical response to treatment. Necropsy examination revealed muscular necrosis, accumulation of fluid in the thoracic and peritoneal cavities, and marked renal tubular necrosis with intraluminal occlusion secondary to pigmentary casts.

Risk factors for musculoskeletal injuries in 2-year-old Thoroughbred racehorses.

Musculoskeletal injuries (MSI) in racehorses have been identified as the most common cause of lost training days and weeks spent resting at pasture. Several training-, track- and horse-related risk factors have been identified. However, there is no clear understanding of the inter-relationship between these factors. The aim of this longitudinal cohort study was to investigate risk factors for MSI in 2-year-old Thoroughbred racehorses. Australian Thoroughbred trainers were convenience sampled and enrolled in a 27-month longitudinal cohort study. The study population consisted of all 2-year-old Thoroughbred racehorses trained by a participating trainer. Horses were followed from the time of enrollment until the completion of the study or until they were lost to follow-up. Trainers were visited at approximately 14-day intervals to collect training and injury data. Training days were categorised as fast days if the maximum speed during training exceeded 800 m/min. For each horse, the first training period that included one or more fast days was analysed. A multiple logistic regression model was used to determine those horse- and training-related variables that were associated with MSI. Data from 274 horses trained by 14 trainers at five racetracks were analysed. Forty percent of the horses sustained a MSI during their first fast preparation. The average distance trained at speeds >or=800 m/min and the percentages of fast days from the first fast day until the end of the preparation were the only variables associated with MSI. After accounting for these variables there were still significant differences between trainers. This suggests that there are other training-related variables such as the rate of increase in distance trained at speeds >or=800 m/min that may be risk factors for MSI. In addition, other factors such as the level of veterinary involvement and the training centre/racetrack may be risk factors for MSI. More analysis using multi-level modelling is required to determine the relationship between trainer- and track-related risk factors.