How Does Housing Influence Bovine Respiratory Disease in Dairy and Veal Calves?

Bovine respiratory disease (BRD) is a leading cause of morbidity and mortality in young cattle. Housing factors that lead to poor ventilation and stagnant air are often considered the primary reasons for high levels of endemic disease. This article reviews the literature from the past 40 years in order to determine which housing factors have been associated with respiratory disease. Penning strategy and its affect on calf respiratory health were most commonly studied. The wide variation in disease definitions and quality of reporting make drawing conclusions from the available literature extraordinarily difficult.

Considerations for analysis of time-to-event outcomes subject to competing risks in veterinary clinical studies.

In veterinary medicine, prospective clinical trials are increasingly utilized to address questions regarding effectiveness of therapies and patient prognosis. A large number of these trials involve time-to-event (TTE) endpoints, which require special methods of analysis to handle data in which not all subjects are observed to have the event of interest. Analyses and interpretation of the results can be further complicated when an endpoint of interest is not observed in some patients because they incur a competing risk, such as death from an unrelated cause. Competing risks have been the source of confusion in many epidemiologic analyses leading to the potential for misinterpretation. In this article, we review key considerations for the TTE analysis in the setting of competing risks. We briefly review standard TTE tools, namely Kaplan-Meier survival curves and Cox regression. In the setting of outcomes with competing risks, we provide guidance on the appropriate analysis techniques, such as cumulative incidence curves, to estimate the risk of an event of interest. We also describe a common pitfall of treating competing risks as censoring in Kaplan-Meier survival curve analysis, which can overestimate the event rate of interest. We describe two common regression methods that examine associated risk factors in the presence of competing risks and highlight the different research questions these methods address. This article provides an introductory overview and illustrates concepts with examples from veterinary trials and with example data sets.

Survey of cat owners on features of, and preventative measures for, feline scratching of inappropriate objects: a pilot study.

Objectives The objective of this study was to collect preliminary data on relevant features and preventative measures of feline inappropriate scratching. Preliminary data could then be used to inform future randomized controlled studies. Methods A paper questionnaire was distributed to 140 cat-owning clients of a small animal practice. The response rate was 82.9%. Questions related to features of inappropriate and designated items scratched, frequency of the behavior and how owners attempted to modify the behavior. The frequency of scratching was ranked and analyzed with repeated-measures models for differences between features of items. The effectiveness of techniques to modify scratching was analyzed with Student's t-tests comparing frequencies of scratching between cats of survey participants who did and did not use specific techniques. Results Scratching of inappropriate items was reported for 83.9% of cats. Most cats (81.5%) scratched chairs or other furniture and 64.1% scratched carpet. The frequency of scratching inappropriate items was significantly influenced by type and material of the items scratched, with furniture and carpet, and fabric and carpet, respectively, being scratched most often. Most cats (76.1%) had a designated scratching item. The frequency of scratching designated items was significantly influenced by type, with cats using scratching posts and other items more often than scratch pads. Owners used a variety of punishment- and reward-based techniques to stop inappropriate scratching and encourage scratching of designated items; only one technique was found to have a significant effect, with the frequency of scratching designated items being significantly lower in cats that were placed near the item. Conclusions and relevance Furniture covered with fabric was an object frequently scratched. Fabric should be further investigated as a potential material to encourage desired scratching behavior. Scratch pads appeared less desired than scratching posts. Punishment was a common strategy to deter scratching but did not appear to influence the frequency of scratching.

Sample size and number of outcome measures of veterinary randomised controlled trials of pharmaceutical interventions funded by different sources, a cross-sectional study.

BACKGROUND: Randomised controlled trials (RCTs) are a key component of the veterinary evidence base. Sample sizes and defined outcome measures are crucial components of RCTs. To describe the sample size and number of outcome measures of veterinary RCTs either funded by the pharmaceutical industry or not, published in 2011. METHODS: A structured search of PubMed identified RCTs examining the efficacy of pharmaceutical interventions. Number of outcome measures, number of animals enrolled per trial, whether a primary outcome was identified, and the presence of a sample size calculation were extracted from the RCTs. The source of funding was identified for each trial and groups compared on the above parameters. RESULTS: Literature searches returned 972 papers; 86 papers comprising 126 individual trials were analysed. The median number of outcomes per trial was 5.0; there were no significant differences across funding groups (p = 0.133). The median number of animals enrolled per trial was 30.0; this was similar across funding groups (p = 0.302). A primary outcome was identified in 40.5% of trials and was significantly more likely to be stated in trials funded by a pharmaceutical company. A very low percentage of trials reported a sample size calculation (14.3%). CONCLUSIONS: Failure to report primary outcomes, justify sample sizes and the reporting of multiple outcome measures was a common feature in all of the clinical trials examined in this study. It is possible some of these factors may be affected by the source of funding of the studies, but the influence of funding needs to be explored with a larger number of trials. Some veterinary RCTs provide a weak evidence base and targeted strategies are required to improve the quality of veterinary RCTs to ensure there is reliable evidence on which to base clinical decisions.

Sponsorship bias and quality of randomised controlled trials in veterinary medicine.

BACKGROUND: Randomised controlled trials (RCTs) are considered the gold standard form of evidence for assessing treatment efficacy, but many factors can influence their reliability including methodological quality, reporting quality and funding source. The aim of this study was to examine the relationship between funding source and positive outcome reporting in veterinary RCTs published in 2011 and to assess the risk of bias in the RCTs identified. METHODS: A structured search of PubMed was used to identify feline, canine, equine, bovine and ovine clinical trials examining the efficacy of pharmaceutical interventions published in 2011. Funding source and outcomes were extracted from each RCT and an assessment of risk of bias made using the Cochrane risk of bias tool. RESULTS: Literature searches returned 972 papers, with 86 papers (comprising 126 individual RCTs) included in the analysis. There was found to be a significantly higher proportion of positive outcomes reported in the pharmaceutical funding group (P) compared to the non-pharmaceutical (NP) and 'no funding source stated' (NF) groups (P = 56.9%, NP = 34.9%, NF = 29.1%, p < 0.05). A high proportion of trials had an unclear risk of bias across the five criteria examined. CONCLUSIONS: We found evidence that veterinary RCTs were more likely to report positive outcomes if they have pharmaceutical industry funding or involvement. Consistently poor reporting of trials, including non-identification of funding source, was found which hinders the use of the available evidence.

Clinical Trials in Veterinary Medicine: A New Era Brings New Challenges.

Randomized clinical trials (RCTs) are among the most rigorous ways to determine the causal relationship between an intervention and important clinical outcome. Their use in veterinary medicine has become increasingly common, and as is often the case, with progress comes new challenges. Randomized clinical trials yield important answers, but results from these studies can be unhelpful or even misleading unless the study design and reporting are carried out with care. Herein, we offer some perspective on several emerging challenges associated with RCTs, including use of composite endpoints, the reporting of different forms of risk, analysis in the presence of missing data, and issues of reporting and safety assessment. These topics are explored in the context of previously reported veterinary internal medicine studies as well as through illustrative examples with hypothetical data sets. Moreover, many insights germane to RCTs in veterinary internal medicine can be drawn from the wealth of experience with RCTs in the human medical field. A better understanding of the issues presented here can help improve the design, interpretation, and reporting of veterinary RCTs.

In veterinary trials reporting and communication regarding randomisation procedures is suboptimal.

To evaluate randomisation mechanisms in the veterinary literature, all trials defined as 'randomised' were extracted from five leading veterinary journals for the year 2013. Three blinded investigators evaluated (1) if the random sequence generation was actually non-random, and (2) whether method (CONSORT item 8A) and (3) type of randomisation (CONSORT item 8B) were reported. Trialists were contacted via email to establish (1) willingness to respond to questions on randomisation procedures, (2) whether reporting of randomisation improved following a suggestion to use the CONSORT 2010 guideline. Seven per cent ((95 per cent CI 2 to 12 per cent); 8/114) of the trials defined as 'randomised' explicitly used methods that are considered non-random. Almost half of the trials (49 per cent (40 to 59 per cent); 52/106) did not report any mechanism of randomisation. Only 13 trials (12.3 per cent (6 to 19 per cent); 13/106) reported both items. 39 of 114 (34.2 per cent) trialists contacted were willing to respond to further questions on randomisation mechanisms; 4 (3.5 per cent) trialists were unwilling and 71 (62.3 per cent) trialists did not respond. Email correspondence resulted in a mean clarification of 0.7 items (95 per cent CI 0.4 to 1.0) for the 15 trials for trialists that replied. Improved adherence to CONSORT guidelines and trialists communication is imperative to increase the quality of published evidence in veterinary medicine and to reduce research waste.

Status epilepticus in dogs and cats, part 2: treatment, monitoring, and prognosis.

OBJECTIVE: To discuss current anticonvulsant drug options and advances in treatment of status epilepticus (SE) and to review the prognosis associated with SE. TREATMENT: When treating a patient with SE, the main goals are to halt seizure activity, prevent further seizures, identify the cause of the seizures, and manage any complications. The veterinary literature indicates that benzodiazepines are the most common class of drugs used for the initial treatment of SE. Although many anticonvulsant drugs are currently available for treatment of SE, there is a lack of evidence demonstrating clear benefit to the use of specific therapeutics for benzodiazepine-refractory SE. Several multicenter, randomized, and placebo-controlled clinical trials are currently investigating the efficacy of new drugs, such as fosphenytoin, for use in canine SE. Another active area of research is the investigation of nonpharmacologic methods of seizure treatment including percutaneous vagal nerve stimulation and transcranial ultrasonic neuromodulation. MONITORING: Electroencephalography (EEG) is underutilized in the management of veterinary seizure disorders. However, recent advances in EEG technology may allow for earlier and proactive therapeutic interventions in epileptic patients, provide objective data collection regarding treatment efficacy, and yield insight into the neurologic status of patients with SE. Most importantly, use of EEG in patients with SE will lead to increased recognition of nonconvulsive seizures and nonconvulsive SE. PROGNOSIS: Mortality associated with SE is as high as 25% in dogs due to direct and indirect causes of death. Dogs with seizure disorders have a decreased lifespan compared to the general population, and epileptic dogs with SE have a significantly abbreviated lifespan compared to epileptics that do not experience SE. In people, nonconvulsive SE has a higher morbidity and mortality than convulsive SE, regardless of patient age or underlying diagnosis.

Veterinary homeopathy: systematic review of medical conditions studied by randomised trials controlled by other than placebo.

BACKGROUND: No systematic review has previously been carried out on randomised controlled trials (RCTs) of veterinary homeopathy in which the control group was an intervention other than placebo (OTP). For eligible peer-reviewed RCTs, the objectives of this study were to assess the risk of bias (RoB) and to quantify the effect size of homeopathic intervention compared with an active comparator or with no treatment. METHODS: Our systematic review approach complied fully with the PRISMA 2009 Checklist. Cochrane methods were applied to assess RoB and to derive effect size using standard meta-analysis methods. Based on a thorough and systematic literature search, the following key attributes of the published research were distinguished: individualised homeopathy (n = 1 RCT)/non-individualised homeopathy (n = 19); treatment (n = 14)/prophylaxis (n = 6); active controls (n = 18)/untreated controls (n = 2). The trials were highly diverse, representing 12 different medical conditions in 6 different species. RESULTS: No trial had sufficiently low RoB to be judged as reliable evidence: 16 of the 20 RCTs had high RoB; the remaining four had uncertain RoB in several domains of assessment. For three trials with uncertain RoB and without overt vested interest, it was inconclusive whether homeopathy combined with conventional intervention was more or was less effective than conventional intervention alone for modulation of immune response in calves, or in the prophylaxis of cattle tick or of diarrhoea in piglets. CONCLUSION: Due to the poor reliability of their data, OTP-controlled trials do not currently provide useful insight into the effectiveness of homeopathy in animals.

Evaluating treatment options for common bovine diseases using published data and clinical experience.

"In this article, the authors describe the sources used by clinicians to obtain information about the efficacy of treatments. The authors discuss how the potential for bias differs by information source and how the ability to assess bias differs by information source. The authors also discuss how the clinical setting and background are important to making decisions about treatments, but clinical impressions of efficacy can be biased. The role of cohort studies, clinical impressions, case reports, case series, pharmacokinetic studies, in vivo studies, narrative review, and opinion are also discussed."

Treatment of mastitis in cattle.

The understanding of mastitis, its cause, and the rationale for treatment or nontreatment of mastitis under various circumstances continues to evolve. This article presents research-based evidence about the use or nonuse of drugs to treat mastitis. Nondrug factors involved in decision making about mastitis, including cow characteristics and the epidemiology of mastitis, are also briefly discussed. This article provides information that helps in the making of knowledgeable, evidence-based decisions about therapy for mastitis. Focus is primarily on the use of antimicrobial drugs.

Clinical evidence for individual animal therapy for papillomatous digital dermatitis (hairy heel wart) and infectious bovine pododermatitis (foot rot).

Data supporting individual animal therapy for papillomatous digital dermatitis (PDD) and infectious pododermatitis (IP) in cattle are available for treatment with multiple drugs in the form of randomized, prospective clinical trials conducted in naturally occurring disease with negative controls and masked subjective evaluators. In the case of PDD, these trials support the use of topical tetracycline and oxytetracycline, lincomycin, a copper-containing preparation, and a nonantimicrobial cream. In individual therapy for IP, trial evidence is available to support systemic treatment with ceftiofur, florfenicol, tulathromycin, and oxytetracycline. However, it was not available for IP standards such as penicillin G, sulfadimethoxine, and tylosin.

Consideration of evidence for therapeutic interventions in bovine polioencephalomalacia.

Randomized, masked, prospective clinical trial evidence for therapeutic intervention in naturally occurring bovine polioencephalomalacia (polio) is nonexistent. This article evaluates the use of thiamine and anti-inflammatories in the therapy of polioencephalomalacia based on available information related to the pathophysiology of the disease, induced models, disease outcome in other species (sheep), and parallels in similar disease in humans.

Clinical pharmacology of analgesic drugs in cattle.

Providing pain relief in cattle is challenging. In the absence of labeled drugs, the Animal Medicinal Drug Use Clarification Act regulates the extralabel drug use of analgesics in cattle within the United States. Given the variety of pharmacokinetic and pharmacodynamic properties of pain-relieving drugs, evidence needs to drive the development of analgesic protocols for cattle during pain-related events. This article reviews the commonly used analgesics investigated in cattle including local anesthetics, nonsteroidal anti-inflammatory drugs, opioids, α2-agonists, N-methyl-d-aspartate receptor antagonists, and gabapentin. These compounds are examined with respect to evidence of analgesia in cattle during pain states.

A review of the expected effects of antimicrobials in bovine respiratory disease treatment and control using outcomes from published randomized clinical trials with negative controls.

Bovine respiratory disease (BRD) remains a major disease from an economic and an animal welfare standpoint in beef production systems. Antimicrobial administration is a mainstay in the control of and therapeutic treatment of acute BRD. Judicious use of antimicrobials remains paramount to ensure efficacy of treatment remains acceptable. A systemic review was conducted in the scientific literature, the objective of which was to present a cumulative review of the data from published randomized clinical trials using a negative control in the treatment and control of BRD and using the number needed to treat as a means to effectively convey this information to bovine practitioners.

Type II error and statistical power in reports of small animal clinical trials.

OBJECTIVE: To describe reporting of key methodological elements associated with type II error in published reports of small animal randomized controlled trials (RCTs) and to determine the statistical power in a subset of RCTs with negative results. DESIGN: Descriptive literature survey. SAMPLE: Reports of parallel-group clinical RCTs published in 11 English-language veterinary journals from 2005 to 2012. PROCEDURES: Predefined criteria were used to identify trial primary outcomes and classify results as negative or positive. Details of sample size determination and use of confidence intervals in results reporting were recorded. For each 2-group RCT with negative results, the statistical power to detect 25% and 50% relative differences in outcome was calculated. RESULTS: Of 238 RCTs, 42 (18%) stated a primary outcome, 52 (22%) reported a sample size calculation, and 18 (9%) included a confidence interval around the observed treatment effect. Reports of only 2 (0.8%) RCTs included all 3 elements. Among 103 two-group RCTs with negative results, only 14 (14%) and 40 (39%) were sufficiently powered (ß < 0.20) to detect 25% and 50% relative differences in outcome between treatments, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The present survey found that small animal RCTs with negative results were often underpowered to detect moderate-to-large effect sizes between study groups. Information needed for critical appraisal was missing from most reports. The potential for clinicians to base treatment decisions on inappropriate interpretations of RCTs was worrisome. Design and reporting of small animal RCTs must be improved.

An introduction to systematic reviews in animal health, animal welfare, and food safety.

In this paper, we provide an introduction to systematic reviews and discuss the process for conducting systematic reviews in animal health, animal welfare, and food safety. The research synthesis need that can be addressed by a systematic review is discussed. The use of systematic reviews to address questions about intervention effects, etiology, diagnostic tests evaluation and disease burden are discussed. The steps included in a systematic review are described.

Pain management in the neonatal piglet during routine management procedures. Part 1: a systematic review of randomized and non-randomized intervention studies.

Routine procedures carried out on piglets (i.e. castration, tail docking, teeth clipping, and ear notching) are considered painful. Unfortunately the efficacy of current pain mitigation modalities is poorly understood. The aim of this systematic review was to synthesize the existing primary scientific literature regarding the effectiveness of pain management interventions used for routine procedures on piglets. The review question was, 'In piglets under twenty-eight days old, undergoing castration, tail docking, teeth clipping, and/or methods of identification that involve cutting of the ear tissue, what is the effect of pain mitigation compared with no pain mitigation on behavioral and non-behavioral outcomes that indicate procedural pain and post-procedural pain?' A review protocol was designed a priori. Data sources used were Agricola (EBSCO), CAB Abstracts (Thomson Reuters), PubMed, Web of Science (Thomson Reuters), BIOSIS Previews (Thomson Reuters), and ProQuest Dissertations & Theses Full Text. No restrictions on year of publication or language were placed on the search. Eligible studies assessed an intervention designed to mitigate the pain of the procedures of interest and included a comparison group that did not receive an intervention. Eligible non-English studies were translated using a translation service. Two reviewers independently screened titles and abstracts for relevance using pre-defined questions. Data were extracted from relevant articles onto pre-defined forms. From the 2203 retrieved citations forty publications, containing 52 studies met the eligibility criteria. In 40 studies, piglets underwent castration only. In seven studies, piglets underwent tail docking only. In one study, piglets underwent teeth clipping only, and in one study piglets underwent ear notching only. Three studies used multiple procedures. Thirty-two trial arms assessed general anesthesia protocols, 30 trial arms assessed local anesthetic protocols, and 28 trial arms assessed non-steroidal anti-inflammatory drugs (NSAIDs) protocols. Forty-one trial arms were controls where piglets received either placebo or no treatment. Forty-five outcomes were extracted from the studies, however only the results from studies that assessed cortisol (six studies), ß-endorphins (one study), vocalisations (nine studies), and pain-related behaviors (nine studies) are reported. Other outcomes were reported in only one or two studies. Confident decision making will likely be difficult based on this body of work because lack of comprehensive reporting precludes calculation of the magnitude of pain mitigation for most outcomes.