M. Duz

Exhaled breath condensate hydrogen peroxide and pH for the assessment of lower airway inflammation in the horse

Measurement of hydrogen peroxide (H(2)O(2)) concentration and pH in exhaled breath condensate (EBC) is useful for detection and monitoring of asthma in humans. In contrast, limited information on the use of these parameters for the investigation of lower airway inflammation (LAI) is available for horses. Aims of the current study were to investigate the intra- and inter-day variations of EBC H(2)O(2) concentration and pH in horses and establish any relationship(s) with LAI. Both intra- and inter-day variability of EBC H(2)O(2) concentration were large, while those of pH were small. No significant difference in the intra-day or inter-day H(2)O(2) concentrations or pH measurements were found in control or LAI horses, except for inter-day H(2)O(2) concentration in horses with LAI (p=0.019). There was no significant difference in EBC pH or H(2)O(2) concentration between control and LAI horses, however a trend for a reduced pH in horses with LAI was observed.

Stabling causes a significant increase in the pH of the equine airway

Regulation of pH homeostasis in the equine lung is poorly understood. Measurement of exhaled breath condensate (EBC) pH provided a simple, highly repeatable and noninvasive method for the longitudinal investigation of changes in airway pH in response to environmental changes. Stabling of horses was found to lead to a small (approximately 100-200 parts/billion) but significant (P < 0.001) increase in ambient ammonia concentration when compared to pasture. This increase in exposure to ambient ammonia concentration was associated with significant (P = 0.002) increases in EBC pH and exhaled ammonia (P = 0.013). Stable feed/bedding management type had no effect on EBC pH or exhaled ammonia concentration, while ambient ammonia concentration was influenced by stable management type.

Investigation of Single and Paired Measurements of Adrenocorticotropic Hormone for the Diagnosis of Pituitary Pars Intermedia Dysfunction in Horses

Background Paired measurement of ACTH concentration may be more reliable than a single measurement. Hypothesis/Objectives To determine whether the mean of 2 measurements of ACTH concentration is more reliable in assessing pituitary pars intermedia dysfunction (PPID) than a single measurement. Animals Paired ACTH measurements were performed on (1) 148 occasions from 124 horses being investigated for PPID, (2) 90 occasions from 76 horses with PPID that were receiving treatment with pergolide, and (3) 63 occasions from 50 horses in which there was no clinical suspicion of PPID. Histologic examination of the pars intermedia was performed in 67 of the untreated horses. Methods Outcome of testing using single and the mean of paired samples was compared directly and both methods were compared against histology, which was considered the gold standard. Results Paired ACTH measurement altered binary classification as healthy or diseased in 6 of 211 cases, all off which had equivocal initial ACTH concentrations between 20 and 39 pg/mL. Using histology as the gold standard, optimal sensitivity and specificity for diagnosing PPID were 69.4 and 80.9%, respectively, for a single measurement and 72.2 and 76.2%, respectively, for paired measurements. The area under the receiver operating characteristic curve was 0.72 and 0.73 for single and paired measurements compared with histopathologic diagnosis, respectively. Conclusions and Clinical Importance Paired measurement of ACTH concentration offers no advantage over a single measurement.

Assessment of the impact of collection temperature and sampler design on the measurement of exhaled breath condensate pH in healthy horses

The pH measurement of exhaled breath condensate (EBC) may provide a non-invasive method of assessing the lower airways of horses but the methodology used may influence findings. The aim of this study was to investigate the effect of two sampling devices and three methods of condensation surface cooling (ethanol slush, -100°C; dry ice, -75°C; water ice, 0°C) on EBC pH. Each method was tested 30 times using six healthy ponies. Sample pH was determined before and after de-aeration with argon for 10 min. Sampler design was found to significantly affect pH. Samples collected as a liquid had a significantly higher pH than samples frozen during collection (P<0.05). De-aeration resulted in significantly higher pH (P<0.05) with less variation. This study has shown that device design and condensation surface temperature will influence EBC pH, which will prevent a direct comparison of results when different methodologies are used.

Antimicrobial selection and dosing in the treatment of wounds in the United Kingdom

REASONS FOR PERFORMING STUDY Antimicrobial stewardship within the veterinary profession is recognised by governing and professional bodies as being important; the attitudes and behaviour of veterinary surgeons merit investigation. OBJECTIVES To investigate levels of protected antimicrobial use and accuracy of antimicrobial dosing in a common clinical scenario in equine practice. STUDY DESIGN Retrospective cohort study. METHODS Antimicrobial use was evaluated retrospectively in 113 cases subsequently referred to a single referral hospital for the treatment of limb wounds over a 20-month period. Antimicrobial classification (first-line, alternative or protected) was made according to guidelines produced by the British Equine Veterinary Association. These guidelines also served as the reference for recommended dose rates. RESULTS Systemic antimicrobials were administered prior to referral in 94/113 (83.2%) horses, of which 8 (8.5%) received the protected third or fourth generation cephalosporins or fluoroquinolones. Forty-eight of 87 (55.2%) horses for which complete dosing data were available received antimicrobials at ≤90% of the recommended dose. Practitioners who held a postgraduate clinical qualification or worked in purely equine practice were no more or less likely to use protected antimicrobials (P = 0.06 and P = 0.64, respectively) or administer inadequate doses (P = 0.75 and P = 0.85, respectively). Veterinary surgeons with more experience were less likely to use protected antimicrobials (P<0.001); however, with the small case numbers, this finding should be interpreted with caution. Heavier horses were more likely to be under-dosed (P<0.002). CONCLUSIONS This study highlights the administration of certain classes of antimicrobials in situations where their use is unlikely to be justified. If these findings reflect more general attitudes and behaviour then greater awareness of, and compliance with, recommendations for responsible antimicrobial use are required among equine practitioners. Bodyweight ought to be measured or estimated using validated objective techniques prior to systemic medications being administered.

Effect of flunixin meglumine and firocoxib on ex vivo cyclooxygenase activity in horses undergoing elective surgery

OBJECTIVE To evaluate ex vivo cyclooxygenase (COX) inhibition and compare in vitro and ex vivo COX-1 inhibition by flunixin meglumine and firocoxib in horses. ANIMALS 4 healthy horses for in vitro experiments and 12 healthy horses (6 males and 6 females; 5 Thoroughbreds, 5 Warmbloods, and 2 ponies) undergoing elective surgery for ex vivo experiments. PROCEDURES 12 horses received flunixin meglumine (1.1 mg/kg, IV, q 12 h) or firocoxib (0.09 mg/kg, IV, q 24 h). Blood samples were collected before (baseline) and 2 and 24 hours after NSAID administration. Prostanoids (thromboxane B2, prostaglandin E2, and prostaglandin E metabolites) served as indicators of COX activity, and serum drug concentrations were measured by use of high-performance liquid chromatography. An in vitro coagulation-induced thromboxane B2 assay was used to calculate drug concentration-COX-1 inhibition curves. Effect of time and treatment on COX activity was determined. Agreement between in vitro and ex vivo measurement of COX activity was assessed with Bland-Altman analysis. RESULTS At 2 and 24 hours after NSAID administration, COX-1 activity was reduced, compared with baseline activity, for the flunixin meglumine group only and relative COX-1 activity was significantly greater for the firocoxib group, compared with that for the flunixin meglumine group. There was no significant change in COX-2 activity after surgery for either group. Bland-Altman analysis revealed poor agreement between in vitro and ex vivo measurement of COX-1 activity. CONCLUSIONS AND CLINICAL RELEVANCE Compared with flunixin meglumine, firocoxib had COX-1-sparing effects ex vivo in equine patients that underwent elective surgery.

Disease and pharmacologic risk factors for first and subsequent episodes of equine laminitis: A cohort study of free-text electronic medical records

Electronic medical records from first opinion equine veterinary practice may represent a unique resource for epidemiologic research. The appropriateness of this resource for risk factor analyses was explored as part of an investigation into clinical and pharmacologic risk factors for laminitis. Amalgamated medical records from seven UK practices were subjected to text mining to identify laminitis episodes, systemic or intra-synovial corticosteroid prescription, diseases known to affect laminitis risk and clinical signs or syndromes likely to lead to corticosteroid use. Cox proportional hazard models and Prentice, Williams, Peterson models for repeated events were used to estimate associations with time to first, or subsequent laminitis episodes, respectively. Over seventy percent of horses that were diagnosed with laminitis suffered at least one recurrence. Risk factors for first and subsequent laminitis episodes were found to vary. Corticosteroid use (prednisolone only) was only significantly associated with subsequent, and not initial laminitis episodes. Electronic medical record use for such analyses is plausible and offers important advantages over more traditional data sources. It does, however, pose challenges and limitations that must be taken into account, and requires a conceptual change to disease diagnosis which should be considered carefully.

Validation of an Improved Computer-Assisted Technique for Mining Free-Text Electronic Medical Records

Background The use of electronic medical records (EMRs) offers opportunity for clinical epidemiological research. With large EMR databases, automated analysis processes are necessary but require thorough validation before they can be routinely used. Objective The aim of this study was to validate a computer-assisted technique using commercially available content analysis software (SimStat-WordStat v.6 (SS/WS), Provalis Research) for mining free-text EMRs. Methods The dataset used for the validation process included life-long EMRs from 335 patients (17,563 rows of data), selected at random from a larger dataset (141,543 patients, ~2.6 million rows of data) and obtained from 10 equine veterinary practices in the United Kingdom. The ability of the computer-assisted technique to detect rows of data (cases) of colic, renal failure, right dorsal colitis, and non-steroidal anti-inflammatory drug (NSAID) use in the population was compared with manual classification. The first step of the computer-assisted analysis process was the definition of inclusion dictionaries to identify cases, including terms identifying a condition of interest. Words in inclusion dictionaries were selected from the list of all words in the dataset obtained in SS/WS. The second step consisted of defining an exclusion dictionary, including combinations of words to remove cases erroneously classified by the inclusion dictionary alone. The third step was the definition of a reinclusion dictionary to reinclude cases that had been erroneously classified by the exclusion dictionary. Finally, cases obtained by the exclusion dictionary were removed from cases obtained by the inclusion dictionary, and cases from the reinclusion dictionary were subsequently reincluded using Rv3.0.2 (R Foundation for Statistical Computing, Vienna, Austria). Manual analysis was performed as a separate process by a single experienced clinician reading through the dataset once and classifying each row of data based on the interpretation of the free-text notes. Validation was performed by comparison of the computer-assisted method with manual analysis, which was used as the gold standard. Sensitivity, specificity, negative predictive values (NPVs), positive predictive values (PPVs), and F values of the computer-assisted process were calculated by comparing them with the manual classification. Results Lowest sensitivity, specificity, PPVs, NPVs, and F values were 99.82% (1128/1130), 99.88% (16410/16429), 94.6% (223/239), 100.00% (16410/16412), and 99.0% (100×2×0.983×0.998/[0.983+0.998]), respectively. The computer-assisted process required few seconds to run, although an estimated 30 h were required for dictionary creation. Manual classification required approximately 80 man-hours. Conclusions The critical step in this work is the creation of accurate and inclusive dictionaries to ensure that no potential cases are missed. It is significantly easier to remove false positive terms from a SS/WS selected subset of a large database than search that original database for potential false negatives. The benefits of using this method are proportional to the size of the dataset to be analyzed.

Prevalence, survival analysis and multimorbidity of chronic diseases in the general veterinarian-attended horse population of the UK

The average age of the global human population is increasing, leading to increased interest in the effects of chronic disease and multimorbidity on health resources and patient welfare. It has been posited that the average age of the general veterinarian-attended horse population of the UK is also increasing, and therefore it could be assumed that chronic diseases and multimorbidity would pose an increasing risk here also. However, evidence for this trend in ageing is very limited, and the current prevalence of many chronic diseases, and of multimorbidity, is unknown. Using text mining of first-opinion electronic medical records from seven veterinary practices around the UK, Kaplan-Meier and Cox proportional hazard modelling, we were able to estimate the apparent prevalence among veterinarian-attended horses of nine chronic diseases, and to assess their relative effects on median life expectancy following diagnosis. With these methods we found evidence of increasing population age. Multimorbidity affected 1.2% of the study population, and had a significant effect upon survival times, with co-occurrence of two diseases, and three or more diseases, leading to 6.6 and 21.3 times the hazard ratio compared to no chronic disease, respectively. Laminitis was involved in 74% of cases of multimorbidity. The population of horses attended by UK veterinarians appears to be aging, and chronic diseases and their co-occurrence are common features, and as such warrant further investigation.

Validation of a digital audio recording method for the objective assessment of cough in the horse.

AIM To validate the use of digital audio recording and analysis for quantification of coughing in horses. MATERIALS AND METHODS Part A: Nine simultaneous digital audio and video recordings were collected individually from seven stabled horses over a 1 h period using a digital audio recorder attached to the halter. Audio files were analysed using audio analysis software. Video and audio recordings were analysed for cough count and timing by two blinded operators on two occasions using a randomised study design for determination of intra-operator and inter-operator agreement. Part B: Seventy-eight hours of audio recordings obtained from nine horses were analysed once by two blinded operators to assess inter-operator repeatability on a larger sample. RESULTS AND CONCLUSIONS Part A: There was complete agreement between audio and video analyses and inter- and intra-operator analyses. Part B: There was >97% agreement between operators on number and timing of 727 coughs recorded over 78 h. The results of this study suggest that the cough monitor methodology used has excellent sensitivity and specificity for the objective assessment of cough in horses and intra- and inter-operator variability of recorded coughs is minimal.