Systematic Review of Nonsteroidal Anti‐Inflammatory Drug‐Induced Adverse Effects in Dogs

The aim of this systematic review was to identify, assess, and critically evaluate the quality of evidence of nonsteroidal anti‐inflammatory drug (NSAID)‐induced adverse effects in dogs. Original prospective studies published in peer‐reviewed journals in English (1990–2012) that reported data on the safety of NSAIDs administration in dogs were searched. For each study, design type (I, II, III, or IV) and assessment of quality (+, Ø, ?) were rated. For each drug, quantity and consistency rating (***, **, *) and strength of evidence (high, moderate, low, or extremely low) were identified and evaluated. The strength of evidence was defined in terms of how applicable and relevant the conclusions were to the target population. Sixty‐four studies met the inclusion criteria. Thirty‐five (55%) research studies and 29 (45%) clinical trials were identified. A high strength of evidence existed for carprofen, firocoxib, and meloxicam; moderate for deracoxib, ketoprofen, and robenacoxib; and low for etodolac. Quality and consistency rating were as follows: carprofen (***/***), deracoxib (**/***), etodolac (*/unable to rate), firocoxib (***/**), ketoprofen (**/***), meloxicam (***/***), and robenacoxib (**/**), respectively. Adverse effects were detected in 35 studies (55%) and commonly included vomiting, diarrhea, and anorexia. Three studies (5%) reported a power analysis related to adverse effects of ≥80%. In randomized, placebo‐controlled, blinded studies (n = 25, 39%), the incidence of adverse effects was not statistically different between treated and control dogs. Finally, most studies were not appropriately designed to determine the safety of NSAIDs, and involved a healthy nongeriatric population of research dogs.     

Efficacy of Spironolactone on Survival in Dogs with Naturally Occurring Mitral Regurgitation Caused by Myxomatous Mitral Valve Disease

Background: Spironolactone, an aldosterone antagonist, has been demonstrated to decrease mortality in human patients when added to other cardiac therapies. Hypothesis: Spironolactone in addition to conventional therapy increases survival compared with conventional therapy in dogs with naturally occurring myxomatous mitral valve disease (MMVD). Animals: Between February 2003 and March 2005, 221 dogs were recruited in Europe. Nine dogs were excluded from analysis, leaving 212 dogs with moderate to severe mitral regurgitation (MR) caused by MMVD (International Small Animal Cardiac Health Council classification classes II [n = 190] and III [n = 21]). Methods: Double‐blinded, field study conducted with dogs randomized to receive either spironolactone (2 mg/kg once a day) or placebo in addition to conventional therapy (angiotensin converting enzyme inhibitor, plus furosemide and digoxin if needed). Primary endpoint was a composite of cardiac‐related death, euthanasia, or severe worsening of MR. Results: Primary endpoint reached by 11/102 dogs (10.8%) in the spironolactone group (6 deaths, 5 worsening) versus 28/110 (25.5%) in control group (14 deaths, 8 euthanasia, 6 worsening). Risk of reaching the composite endpoint significantly decreased by 55% (hazard ratio [HR] = 0.45; 95% confidence limits [CL], 0.22–0.90; log rank test, P= .017). Risk of cardiac‐ related death or euthanasia significantly reduced by 69% (HR = 0.31; 95% CL, 0.13–0.76; P= .0071). Number of dogs not completing the study for cardiac and other miscellaneous reasons similar in spironolactone (67/102) and control groups (66/110). Conclusion and Clinical Importance: Spironolactone added to conventional cardiac therapy decreases the risk of reaching the primary endpoint (ie, cardiac‐related death, euthanasia, or severe worsening) in dogs with moderate to severe MR caused by MMVD.     

Randomized Placebo‐Controlled Clinical Trial of a Chewable Formulation of Amlodipine for the Treatment of Hypertension in Client‐Owned Cats

Background

There is an unmet clinical need for a cat‐specific formulation of amlodipine to treat hypertensive cats.

Objectives

To assess the efficacy of chewable amlodipine tablets in reducing systolic blood pressure (SBP) in cats diagnosed with systemic arterial hypertension.

Animals

Seventy‐seven client‐owned cats with systemic hypertension were included (median age 14 years).

Methods

The study was randomized, double‐blinded, and placebo‐controlled. Forty‐two cats received 0.125–0.50 mg/kg amlodipine once daily for 28 days; 35 cats received placebo. After 28 days all cats continued with amlodipine for 2–3 months in an open‐label phase. Blood pressure was measured using high definition oscillometry. A responder was defined as a cat showing a decrease of SBP to <150 mmHg at 28 days or a decrease from baseline ≥15%.

Results

Sixty‐one cats completed the study. The responder rate was 63% in amlodipine group and 18% in placebo group. Cats receiving amlodipine were 7.9 (95% CI 2.6–24.1) times more likely to be classified as responders when compared to those receiving placebo (P < .001). From a mean (±SD) baseline value of 181 (±12) mmHg, SBP decreased to 154 (±17) mmHg with amlodipine and to 170 (±21) mmHg with placebo (P < .001). The voluntary acceptance rate of amlodipine formulation was 73%.

Conclusions and Clinical Importance

The chewable amlodipine tablet effectively reduced SBP compared with placebo in hypertensive cats, and was well‐tolerated. It can be used concomitantly with angiotensin‐converting enzyme inhibitors and in cats with chronic kidney disease.     

Participatory Policy Making by Dairy Producers to Reduce Anti‐Microbial use on Farms

Pressures for more responsible use of anti‐microbial (AM) medicines in food animals are likely to increase from policymakers and the food industry, including retailers. To address this challenge, participatory approaches to welfare interventions and disease prevention may also be necessary alongside more conventional regulatory measures. This article describes the process of enabling groups of dairy producers to use a participatory policy making approach to develop an AM stewardship policy. The policy includes measures agreed to by all producers for more responsible use of AMs, whilst maintaining or improving dairy herd health and welfare. This process provided a unique opportunity for collaboration and dialogue between producers, veterinarians, industry and researchers. Its participatory nature encouraged comprehensive learning for all involved. This integration of science with producers’ knowledge and experience led to credible and practical recommendations designed to deliver real and lasting change in AM use. The multidisciplinary nature of this research marks a significant contribution to embedding social science skills and approaches into the veterinary sphere. As an initial step in creating better understanding of how participatory approaches with farmers can be applied in a UK context and more widely, this work serves as a pilot for promoting more responsible use of veterinary medicines in other livestock species.     

Quality of Life Measurement in Prospective Studies of Cancer Treatments in Dogs and Cats

Background

Quality of life (QOL) is an important consideration in healthcare decision‐making for pets with cancer. To determine the effect of disease and treatment on pet QOL, this important variable should be objectively measured as an outcome in veterinary cancer studies.

Objectives

To determine the prevalence and methodology of QOL measurement in a sample of recently published reports of prospective studies evaluating cancer treatments in client‐owned dogs and cats; to characterize reporting of QOL outcomes and to identify article characteristics associated with QOL measurement.

Methods

English‐language reports of prospective studies of cancer treatments in dogs and cats published from 2008 to 2013 were identified using medical research databases combined with a hand‐searching strategy. Data pertaining to general article characteristics and QOL measurement were abstracted and summarized.

Results

Reports of 144 eligible studies were identified. QOL was measured in 16 (11.1%) studies, with 8 (5.6%) reporting the results. All studies that measured QOL reported using unvalidated instruments, or did not report how QOL was assessed. Only 1 study provided sufficient information for QOL measurements to be replicated. Recently published articles (2011–2013) were significantly more likely to report measuring QOL, compared with earlier articles.

Conclusions

Quality of life of pets undergoing cancer treatment is largely unreported and cannot be meaningfully compared across treatments or disease states using the existing literature. Reliable, validated instruments are needed to facilitate the measurement and comparison of pet QOL in veterinary cancer research. Consistent reporting practices could improve transparency and interpretation of QOL results.     

24‐Hour Kinetics of Cardiac Troponin‐T Using a “High‐Sensitivity” Assay in Thoroughbred Chuckwagon Racing Geldings after Race and Associated Clinical Sampling Guidelines

Background

A “high‐sensitivity” cardiac troponin‐T (hscTnT) assay recently has been validated for use in horses and is a specific biomarker of myocardial damage. Postexercise release kinetics of cTnT utilizing the hscTnT assay have yet to be established in horses.

Objectives

To determine: (1) cTnT release kinetics in racing Thoroughbreds after a high‐intensity 5/8th mile Chuckwagon race; (2) the effects of age on pre‐ and postrace cTnT concentrations; and (3) sampling guidelines for clinicians evaluating horses presenting after exercise.

Animals

Samples were obtained from 38 Thoroughbred geldings aged 5–16 years before racing and immediately, 2, 3, 4, 6, 12, and 24 hour postrace.

Methods

Prospective, observational study with convenience sampling. A fifth‐generation hscTnT assay was used for plasma sample analysis, and concentrations were compared at all time‐points. Correlations were determined between cTnT concentrations and age. Biochemistry analysis was performed to assess rhabdomyolysis, renal failure, and exercise‐induced dehydration.

Results

All horses with measureable cTnT concentrations had significant postexercise increases in cTnT with a median peak (8.0 ng/L) at 3‐hour postrace. All horses had peak postexercise cTnT concentrations 2‐ to 6‐hour postrace ≤ the 99th percentile upper reference limit of 23.2 ng/L, after which all cTnT concentrations decreased until returning to baseline by 12–24 hours. There was no correlation over time between cTnT concentrations and age.

Conclusions and Clinical Importance

In racing Thoroughbreds completing short‐duration, high‐intensity Chuckwagon races, cTnT concentrations are expected to be increased 2‐ to 6‐hour postrace and to decrease by 12–24 hours while remaining ≤23.2 ng/L throughout. This study contributes to establishing guidelines for clinical use of the hscTnT assay in exercising horses.     

The effects of transportation stress on Japanese quail (Coturnix Coturnix japonica) fed corn‐based diet in comparison with wheat‐based diet supplemented with xylanase and phytase

Harvesting, handling and transporting quails to the slaughterhouses, other farms and laboratories might covertly reduce their welfare. The aim of this study was to evaluate the effects of two major sources of energy in poultry nutrition on reducing transportation stress in Japanese quail (Coturnix Coturnix japonica). Male quails (n = 60) were divided into two groups. The first group was fed corn‐based diet, and the second was fed wheat‐based diet supplemented with xylanase and phytase. At the end of the experiment (day 35), quails were subjected to 80 km of transportation. Immediately on arrival and after 24 h, heterophil counts, lymphocyte counts and H:L ratios were measured. On arrival, H counts were lower, L counts were higher, and H:L ratios were lower for corn‐fed group. After 24 h, wheat‐fed group showed lower increment of H counts, greater increment of L counts and also decrement of H:L ratios rather than corn‐fed group which showed increment of H:L ratios. However, these ratios were still lower in corn‐fed group. Results indicate that corn‐based diets can help Japanese quail to better resist transportation stress, although it seems that feeding wheat‐based diets supplemented with xylanase and phytase could have positive effects for coping better with stress after journeys.     

Utility of Transesophageal Echocardiography for Transcatheter Occlusion of Patent Ductus Arteriosus in Dogs: Influence on the Decision‐Making Process

Background: Appropriate device selection for transcatheter occlusion of patent ductus arteriosus (PDA) is essential to procedural success. Objectives: To determine if transesophageal echocardiography (TEE) influences device selection for PDA occlusion and to report benefits, limitations, and complications associated with TEE. Animals: Twenty‐two client‐owned dogs with left‐to‐right shunting PDA. Methods: PDA dimensions were obtained via transthoracic echocardiography (TTE) and then TEE followed by angiography. Based solely on information from TTE and angiography, an initial device type and size were selected. After initial device selection, TEE measurements were disclosed and changes in device selection were recorded. After device release, angiography, TEE, or both were performed to assess occlusion. Results: An Amplatz canine duct occluder (ACDO) was securely positioned and released in 21 dogs and an embolization coil was deployed in 1 dog. Based on TEE evaluation, initial selected device type was unchanged but ACDO size was changed in 3 dogs. TEE was utilized throughout the procedure allowing real time visualization of device deployment, release and assessment of closure in 17 dogs. No complications occurred related to TEE. Complete PDA closure was achieved in all dogs. Conclusions and Clinical Importance: TEE provided anatomic information regarding PDA morphology that closely approximated angiographic ductal dimensions while aiding in device deployment, release and confirmation of closure. We conclude that TEE provides complementary anatomical and intraprocedural information and is well tolerated in dogs.     

The Effect of Hetastarch (670/0.75) on Urine Specific Gravity and Osmolality in the Dog

Background: Urine specific gravity (USG) is used clinically to estimate urine osmolality (UOsm). Although USG has been shown to have a linear correlation with UOsm in dogs, the relationship is altered when there are significant numbers of high molecular weight (MW) molecules in the urine.
Hypothesis: USG would no longer predict UOsm in dogs given intravenous hetastarch (670/0.75)(HES).
Animals: Eight healthy employee-owned adult dogs.
Methods: Prospective, controlled experimental study. USG and UOsm were measured every 30 minutes from t=0 minutes to t=360 minutes. Dogs were administered 20mL/kg of either NaCl 0.9% (control group, n=4) or HES (treatment group, n=8) IV over 1 hour starting at t=90 minutes.
Results: There was a decrease in UOsm in both groups starting at t=120 minutes and continuing for the study duration, and there was no significant difference in UOsm between treatment and control groups across all time points. There was an appropriate decrease in USG from t=120 minutes for the control group. In the treatment group, USG increased significantly at t=120 minutes ( P = .0006), t=150 minutes ( P = .0002), and t=180 minutes ( P = .0044). The largest increase in USG occurred at t=150 minutes with a mean USG of 1.070 ± 0.021 (range 1.038-1.104).
Conclusions and clinical importance: Urine specific gravity should not be used to estimate urine solute concentration in dogs following the administration of 20mL/kg of HES. In a clinical setting, the evaluation of USG following this dose of HES may lead to an overestimation of urine concentration.     

Use of CD9 and CD61 for the characterization of AML‐M7 by flow cytometry in a dog*

Acute megakaryoblastic leukaemia (AML‐M7) is a rare myeloproliferative disorder in domestic animals. Recently, thanks to the greater availability of immunophenotype techniques, precise diagnosis is more easily made. The morphological evaluation has its limitations, especially in the study of poorly differentiated cells. Few reports have described AML‐M7 in dogs using flow cytometry. This clinical case points out the utility of flow cytometry in the characterization of AML‐M7 in a 3‐year‐old German Shepherd dog. Flow cytometry investigation has established megakaryocytic lineage involvement by showing the presence of two megakaryocyte/platelet associated antigens (CD9 and CD61). In human medicine CD9 may be used as a platelet and megakaryocyte marker. There is an evidence of cross‐reactivity of human anti‐CD9 monoclonal antibody with canine samples. To our knowledge, the use of CD9 has never been described before, for this purpose in the dog.     

An evidence‐based medicine approach to small animal anaesthetic mortality in a referral practice: the influence of initiating three recommendations on subsequent anaesthetic deaths

ObjectiveTo evaluate anaesthetic death after implementation of recommendations and its risk factors in a small animal practice.Study designObservational cohort study.AnimalsAll cats and dogs anaesthetized at the Centre Hospitalier Vétérinaire des Cordeliers during two periods, from April 15th, 2008 to April 15th, 2010 (period 1) and from June 15th, 2010 to August 24th, 2011 (period 2).MethodsDeath occurring during or before full recovery from anaesthesia was recorded. At the end of period 1, a logistic regression model was generated to describe anaesthetic death and identify risk factors. Potential risk factors in our practice setting were identified, and three recommendations, relating to improving physical status and anaesthetic/analgesic regimen implemented for period 2. The relationship between anaesthetic death and recorded variables were analyzed, and where relevant, compared between periods.ResultsSix thousand two hundred and thirty-one animals underwent general anaesthesia. The overall death rate during period 1 was 1.35% (48 in 3546, 95% CI [1.0–1.7%]) and during period 2 was 0.8% (21 in 2685, 95% CI [0.6–1.2%]). For sick animals (ASA status 3 and over), the overall death rate was 4.8% (45 of 944 95% [CI 3.5–6.4%]) during period 1 and 2.2% (18 of 834 95% CI [1.3–3.5%]) during period 2; this represented a significant decrease in death rate in period 2 (p = 0.002). In period 2, the main factors associated with an increased odds ratio of anaesthetic death were poor health status (ASA physical status classification) and old age. Species, gender, anaesthetic regimen, the nature and urgency of the procedure were not associated with risk.Conclusion and clinical relevanceFollowing evidence based recommendations, the death rate related to anaesthesia was significantly decreased during period 2 compared to period 1. Application of evidence-based medicine may contribute to an effective approach to decrease death rates. Other factors, not monitored in this study, may also have had an impact.