Paul S. Morley

Continuous Low-Dose Oral Chemotherapy for Adjuvant Therapy of Splenic Hemangiosarcoma in Dogs

BACKGROUND Hemangiosarcoma (HSA) is a highly metastatic and often rapidly fatal tumor in dogs. At present, conventional adjuvant chemotherapy provides only a modest survival benefit for treated dogs. Continuous oral administration of low-dose chemotherapy (LDC) has been suggested as an alternative to conventional chemotherapy protocols. Therefore, we evaluated the safety and effectiveness of LDC using a combination of cyclophosphamide, etoposide, and piroxicam as adjuvant therapy for dogs with stage II HSA. HYPOTHESIS We hypothesized that oral adjuvant therapy with LDC could be safely administered to dogs with HSA and that survival times would be comparable to those attained with conventional doxorubicin (DOX) chemotherapy. ANIMALS Nine dogs with stage II splenic HSA were enrolled in the LDC study. Treatment outcomes were also evaluated retrospectively for 24 dogs with stage II splenic HSA treated with DOX chemotherapy. METHODS Nine dogs with stage II splenic HSA were treated with LDC over a 6-month period. Adverse effects and treatment outcomes were determined. The pharmacokinetics of orally administered etoposide were determined in 3 dogs. Overall survival times and disease-free intervals were compared between the 9 LDC-treated dogs and 24 DOX-treated dogs. RESULTS Dogs treated with LDC did not develop severe adverse effects, and long-term treatment over 6 months was well-tolerated. Oral administration of etoposide resulted in detectable plasma concentrations that peaked between 30 and 60 minutes after dosing. Both the median overall survival time and the median disease-free interval in dogs treated with LDC were 178 days. By comparison, the overall survival time and disease-free interval in dogs treated with DOX were 133 and 126 days, respectively. CONCLUSIONS Continuous orally administered LDC may be an effective alternative to conventional high-dose chemotherapy for adjuvant therapy of dogs with HSA.

Characteristics of biosecurity and infection control programs at veterinary teaching hospitals

OBJECTIVE To characterize biosecurity and infection control practices at veterinary teaching hospitals located at institutions accredited by the AVMA. DESIGN Cross-sectional survey. POPULATION 50 biosecurity experts at 38 veterinary teaching hospitals. PROCEDURES Telephone interviews were conducted between July 2006 and July 2007, and questions were asked regarding policies for hygiene, surveillance, patient contact, education, and awareness. Respondents were also asked their opinion regarding the rigor of their programs. RESULTS 31 of 38 (82%) hospitals reported outbreaks of nosocomial infection during the 5 years prior to the interview, 17 (45%) reported > 1 outbreak, 22 (58%) had restricted patient admissions to aid mitigation, and 12 (32%) had completely closed sections of the facility to control disease spread. Nineteen (50%) hospitals reported that zoonotic infections had occurred during the 2 years prior to the interview. Only 16 (42%) hospitals required personnel to complete a biosecurity training program, but 20 of the 50 (40%) respondents indicated that they believed their hospitals ranked among the top 10% in regard to rigor of infection control efforts. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that differences existed among infection control programs at these institutions. Perceptions of experts regarding program rigor appeared to be skewed, possibly because of a lack of published data characterizing programs at other institutions. Results may provide a stimulus for hospital administrators to better optimize biosecurity and infection control programs at their hospitals and thereby optimize patient care.

Parathyroid Hormone An Anabolic Treatment for Osteoporosis.

Osteoporosis is a disease characterised by low bone mass, structural deterioration of bone and increased risk of fracture. The prevalence, and cost, of osteoporosis is increasing dramatically with our ageing population and the World Health Organization now considers it to be the second-leading healthcare problem. All currently approved therapies for osteoporosis (eg., estrogen, bisphosphonates, calcitonin and selective estrogen receptor modulators) are anti-resorptive agents that act on osteoclasts to prevent further bone loss. A new class of bone anabolic agent capable of building mechanically strong new bone in patients with established osteoporosis is in development. While the parathyroid hormone (PTH) is classically considered to be a bone catabolic agent, when delivered intermittently at low doses PTH potently stimulates cortical and trabecular bone growth in animals humans. The native hPTH-(1-84) and its osteogenic fragment, hPTH-(1-34), have already entered Phase III clinical trials. Understanding the mechanism of PTHs osteogenic actions has led to the development of smaller PTH analogues which can also build mechanically normal bone in osteopenic rats. These new PTH analogues are promising candidates for treating osteoporosis in humans as they are as efficacious as hPTH-(1-84) and hPTH-(1-34), but there is evidence that they may have considerably less ability to induce hypercalcemia, the major side effect of PTH therapy. In addition to treating osteoporosis, PTHs may be used to promote fracture healing, to restore bone loss in immobilized patients, or following excessive glucocorticoid or prolonged spaceflight, and to treat psoriasis.

The REFLECT Statement: Reporting Guidelines for Randomized Controlled Trials in Livestock and Food Safety: Explanation and Elaboration

Concerns about the completeness and accuracy of reporting of randomized clinical trials (RCTs) and the impact of poor reporting on decision making have been documented in the medical field over the past several decades. Experience from RCTs in human medicine would suggest that failure to report critical trial features can be associated with biased estimated effect measures, and there is evidence to suggest that similar biases occur in RCTs conducted in livestock populations. In response to these concerns, standardized guidelines for reporting RCTs were developed and implemented in human medicine. The Consolidated Standards of Reporting Trials (CONSORT) statement was first published in 1996, with a revised edition published in 2001. The CONSORT statement consists of a 22‐item checklist for reporting a RCT and a flow diagram to follow the number of participants at each stage of a trial. An explanation and elaboration document not only defines and discusses the importance of each of the items, but also provides examples of how this information could be supplied in a publication. Differences between human and livestock populations necessitate modifications to the CONSORT statement to maximize its usefulness for RCTs involving livestock. These have been addressed in an extension of the CONSORT statement titled the REFLECT statement: Methods and processes of creating reporting guidelines for randomized control trials for livestock and food safety. The modifications made for livestock trials specifically addressed the common use of group housing and group allocation to intervention in livestock studies; the use of deliberate challenge models in some trials and the common use of non‐clinical outcomes, such as contamination with a foodborne pathogen. In addition, the REFLECT statement for RCTs in livestock populations proposed specific terms or further clarified terms as they pertained to livestock studies.

Control of EHV-1 viremia and nasal shedding by commercial vaccines.

Equine herpesvirus-1 is a cause of outbreaks of abortion and neurological disease. The pathogenesis of both these diseases depends on establishment of viremia. An experiment was performed to determine the protective efficacy of two commercially available vaccines used with an optimized 3-dose vaccination regime: a modified-live viral (MLV) and a high antigen load killed vaccine licensed for abortion control. The study design was a blinded, randomized challenge trial. Three groups of 8 yearling ponies received one of three treatments: MLV vaccine (Rhinomune, Boehringer Ingelheim Vetmedica, Inc.); killed vaccine (Pneumabort-K, Pfizer Animal Health); or a placebo (control group). Three vaccinations were administered at intervals of 27 and 70 days followed by challenge infection 24 days later. Clinical disease after challenge was significantly reduced in both vaccine groups; the reduction was greater in the MLV vaccine group. Nasal shedding was reduced by at least 1-2 logs in both vaccine groups. The number of days of viremia was significantly reduced in the killed vaccine group only. This study demonstrated that both commercial vaccines significantly suppressed EHV-1 disease and nasal viral shedding, and one vaccine suppressed days of viremia.

A Multi-Institutional Study Evaluating the Diagnostic Utility of the Spec cPL™ and SNAP® cPL™ in Clinical Acute Pancreatitis in 84 Dogs

BACKGROUND Pancreas-specific lipase is reported to aid in diagnosing acute pancreatitis (AP) in dogs but has not been rigorously evaluated clinically. HYPOTHESIS/OBJECTIVES To describe variability of disease in dogs with suspected clinical AP, and to evaluate accuracy of 2 pancreatic-specific lipase immunoassays, Spec cPL (SPEC) and SNAP cPL (SNAP), in diagnosing clinical AP. We hypothesized that SPEC and SNAP provide better diagnostic accuracy than serum amylase or total lipase. ANIMALS A total of 84 dogs; 27 without AP and 57 with clinical signs associated with AP. METHODS Multicenter study. Dogs were prospectively enrolled based upon initial history and physical examination, then retrospectively classified into groups according to the likelihood of having clinical AP by a consensus of experts blinded to SPEC and SNAP results. Bayesian latent class analyses were used to estimate the diagnostic accuracy of SPEC and SNAP. RESULTS The estimates for test sensitivities and specificities, respectively, ranged between 91.5-94.1% and 71.1-77.5% for SNAP, 86.5-93.6% and 66.3-77.0% for SPEC (cutoff value of 200 μg/L), 71.7-77.8% and 80.5-88.0% for SPEC (cutoff value of 400 μg/L), and were 52.4-56.0% and 76.7-80.6% for amylase, and 43.4-53.6% and 89.3-92.5% for lipase. CONCLUSIONS AND CLINICAL IMPORTANCE SNAP and SPEC have higher sensitivity for diagnosing clinical AP than does measurement of serum amylase or lipase activity. A positive SPEC or SNAP has a good positive predictive value (PPV) in populations likely to have AP and a good negative predictive value (NPV) when there is low prevalence of disease.

Biosecurity of veterinary practices.

Hospitalization of sick animals tremendously increases their risk of acquiring infections as this congregates animals that are most likely to be shedding infectious agents with animals that often have enhanced susceptibility. In order to provide the best veterinary care possible, veterinarians have an underlying responsibility to minimize the risk of additional harm that might unintentionally befall a patient because of their interventions. This includes minimizing the risk of exposing patients to infectious agents. It is therefore incumbent upon veterinarians to actively manage the risk of nosocomial infections. Nosocomial infections in veterinary hospitals are not solely a patient-care concern; the spread of infectious agents can also significantly impact normal hospital operations, revenue, client confidence, public image, and can even affect the morale of hospital personnel. In some cases nosocomial agents can also be zoonotic. This paper discusses the need for biosecurity programs in veterinary practices, and describes a practical approach for developing biosecurity practices that are tailored to individual facilities.

Efficacy of furosemide for prevention of exercise-induced pulmonary hemorrhage in Thoroughbred racehorses

OBJECTIVE To evaluate the efficacy of furosemide for prevention of exercise-induced pulmonary hemorrhage (EIPH) in Thoroughbred racehorses under typical racing conditions. DESIGN Randomized, placebo-controlled, blinded, crossover field trial. ANIMALS 167 Thoroughbred racehorses. PROCEDURES Horses were allocated to race fields of 9 to 16 horses each and raced twice, 1 week apart, with each of the 2 races consisting of the same race field and distance. Each horse received furosemide (500 mg, IV) before one race and a placebo (saline solution) before the other, with the order of treatments randomly determined. Severity of EIPH was scored on a scale from 0 to 4 after each race by means of tracheobronchoscopy. Data were analyzed by means of various methods of multivariable logistic regression. RESULTS Horses were substantially more likely to develop EIPH (severity score >or= 1; odds ratio, 3.3 to 4.4) or moderate to severe EIPH (severity score >or= 2; odds ratio, 6.9 to 11.0) following administration of saline solution than following administration of furosemide. In addition, 81 of the 120 (67.5%) horses that had EIPH after administration of saline solution had a reduction in EIPH severity score of at least 1 when treated with furosemide. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that prerace administration of furosemide decreased the incidence and severity of EIPH in Thoroughbreds racing under typical conditions in South Africa.

ACVIM Consensus Statement on Therapeutic Antimicrobial Use in Animals and Antimicrobial Resistance

The epidemic of antimicrobial resistant infections continues to challenge, compromising animal care, complicating food animal production and posing zoonotic disease risks. While the overall role of therapeutic antimicrobial use in animals in the development AMR in animal and human pathogens is poorly defined, veterinarians must consider the impacts of antimicrobial use in animal and take steps to optimize antimicrobial use, so as to maximize the health benefits to animals while minimizing the likelihood of antimicrobial resistance and other adverse effects. This consensus statement aims to provide guidance on the therapeutic use of antimicrobials in animals, balancing the need for effective therapy with minimizing development of antimicrobial resistance in bacteria from animals and humans.

Retrospective multicentre study of methicillin-resistant Staphylococcus aureus infections in 115 horses.

REASONS FOR PERFORMING STUDY Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging veterinary and zoonotic pathogen, associated with increasing reports of disease in horses. OBJECTIVES To provide an overview of the characteristics of clinical MRSA infections in horses. METHODS A retrospective case study was performed on 115 horses admitted to 6 participating veterinary teaching hospitals in Canada and the United States between 2000 and 2006, and diagnosed with clinical MRSA infection. Descriptive statistics, univariate and multivariable analyses for community- (CA) vs. hospital-associated (HA) MRSA infections, and survival vs. nonsurvival at discharge were performed. RESULTS The age range of MRSA-infected horses was zero (born in hospital) to 31 years. HA (58/114, 50.9%) and CA infections (56/114, 49.1%) were equally common. Infection of surgical incisions was most frequently reported (44/115, 38.0%). Overall 93/111 (83.8%) cases survived to discharge. Previous hospitalisation and treatment with gentamicin were associated significantly with CA-MRSA, whereas infected incision sites were associated significantly with HA-MRSA. Factors significantly associated with nonsurvival included i.v. catheterisation, CA-MRSA infection and dissemination of infection to other body sites. CONCLUSIONS Equine MRSA infections have a broad range of clinical presentations, appear to be primarily opportunistic and the overall prognosis for survival to discharge is good. POTENTIAL RELEVANCE These results should help direct future research with regard to investigation of risk factors for equine MRSA infection in community and hospital populations.