Veterinary Evidence

Thank you to our contributors: reflections on 2024

Peter Cockcroft — 2025-01-31

All submissions to Veterinary Evidence are handled by an Associate Editor specialising in the relevant topic area. We would like to thank these volunteer veterinary professionals for their expertise and time to support the journal. Associate Editors play a central role, assessing submitted papers, guiding the peer review process, and making decision recommendations based on peer review reports. We have welcomed six new Associate Editors to the journal in recent months, and we welcome new applications to join our editorial team. Our grateful thanks also extend to our peer reviewers, who are critical in ensuring we maintain the highest standards of excellence in our published articles.

In conjunction with our Editorial Board and publishing team, we have developed a new strategy for Veterinary Evidence, aiming to increase the visibility and findability of journal content and develop ways to measure real impact. We will aim to increase the volume and breadth of what we publish and expand the journal’s editorial capacity and capability to enable that. Quality remains central and we will continue to set strong standards for published content through our policies and processes, and to ensure we make the best use of the support from RCVS Knowledge, we will continually improve editorial processes and timelines to increase editorial efficiency and reduce publication timelines.

We are pleased to announce that Veterinary Evidence has recently been accepted for indexing in Scopus and has also been approved for inclusion in PubMed Central. The technical work for indexing to happen is underway, and we will continue to explore options to increase journal content visibility.

Knowledge Summaries guide readers through the evidence on a clinical question. To help with understanding the context of an included study, we have expanded the evidence summary sections to include the full title of the study, a link out to the original article, and a summary of the main aims. The journal continues to grow annually in terms of users and views, and in 2024 we saw a 13% increase in users and a 5% in page views. Submission to the journal also continue at a steady rate.

The process for updating published Knowledge Summaries has now been agreed. The journal runs an annual report of Knowledge Summaries that have search dates (the date that the search was carried out) that are 3 to 4 years old. For that set of papers, we review the usage metrics (views, downloads, citations) and consider whether the questions remain clinically relevant. On this basis, the Editor in Chief will select the top five papers of interest under each of the main three species categories (small animal, production animal, and equine), and we will aim to publish updates of these knowledge summaries.

Finally, we would like to encourage the continued submission of clinical queries and papers for consideration for publication so that the journal can continue to thrive and go from strength to strength.

Professor Peter Cockcroft
Editor in Chief, Veterinary Evidence

Veterinary Evidence: moving forward

Peter Cockcroft — 2024-09-18

Unrecognised and unknown information needs can significantly impact on the quality of decision making, advice, and patient care. In the practice of veterinary medicine, additional information may be required in one or more of epidemiology, diagnosis, treatment, prognosis, control (risk reduction), and prevention (risk avoidance), in order to optimise patient care.

Veterinary Evidence publishes Knowledge Summaries, which aim to answer a specific and focused clinical query by appraising the best available evidence published in peer-reviewed scientific journals. By presenting the evidence in a structured and easily digestible format, Knowledge Summaries enable veterinary professionals to stay informed and apply the best available evidence to their decision-making.

To assist in the identification of unrecognised deficits and the generation of clinical queries Veterinary Evidence has developed a list of common conditions for each species, alongside the different categories of information. The aim is to prompt and support the generation of new clinical queries in a more systematic format. This resource sits alongside our species-based lists of clinical queries that have already been suggested by practicing veterinarians, veterinary nurses, and other paraprofessionals (see veterinaryevidence.org/index.php/ve/clinical-queries). We hope readers and prospective authors will use these resources to generate new clinical queries or as a starting point for writing their own Knowledge Summaries.

Most of the papers published in Veterinary Evidence are Knowledge Summaries, but the journal has always accepted and will continue to accept and encourage other types of reviews and original research that provide evidence to inform clinical practice. For example, in this issue we have published a commentary paper by Professor Jonathan Elliott regarding the processes and evidence required for the registration of veterinary medicinal products which provides some important insights and debate into the publication of evidential information (Elliott, 2024).

A Knowledge Summary may not always be the best format to synthesise and summarise evidence on a multifaceted topic; scoping reviews, systematic reviews, or narrative reviews maybe more appropriate. Munn et al. (2018) provide a useful account of scoping reviews and how they differ from traditional literature and systematic reviews. In particular, we are keen to receive articles on artificial intelligence applications, sustainability, and quality improvement in clinical practice, as the impact and importance of these topics grows.

We are also making some changes to the presentation of Knowledge Summaries in Veterinary Evidence, to help readers more easily understand the details and context of the summarised evidence. In order to support everyone in appraising and understanding quantitative clinical studies, we will be publishing a glossary and guidance on basic statistical terms and tests on the journal website.

Methadone or buprenorphine: which is the better analgesic for feline ovariohysterectomy?

Isobel Lawrence — 2024-11-12

Question

In female cats undergoing routine ovariohysterectomy, is using methadone in the anaesthetic protocol associated with lower post-operative pain scores, compared to buprenorphine?

Clinical bottom line

The category of research question was:

Treatment.

The number and type of study designs that were critically appraised were:

Four assessor-blinded randomised controlled trials.

Critical appraisal of the selected papers meeting the inclusion criteria collectively provide zero/weak/moderate/strong evidence in terms of their experimental design and implementation:

Moderate.

The outcomes reported are summarised as follows…

Two studies found methadone to be associated with significantly lower postoperative pain scores than buprenorphine; one showed significantly different pain scores over the entire 8-hour postoperative period and one only at 10 minutes postextubation. One study found buprenorphine to be associated with lower postoperative pain scores at some time points postsurgery. One study found no significant difference in pain scores between methadone and buprenorphine.

In view of the strength of evidence and the outcomes from the studies the following conclusion is made…

It can be concluded that using methadone in the anaesthetic protocol may provide better analgesia for cats undergoing ovariohysterectomy compared to buprenorphine. The two papers that used validated pain scoring both concluded that methadone was associated with lower pain scores at some points postoperatively. Although one of the studies concluded that buprenorphine is associated with lower postoperative pain scores, this paper provides only very weak evidence because an unvalidated pain scoring method was used. More evidence is needed to confidently recommend using one opioid over another.

Does conservative or arthroscopic management of canine medial coronoid disease lead to improved outcomes?

Anant Andy Banerjee — 2025-02-04

Question

In dogs diagnosed with medial coronoid disease, does arthroscopic surgical intervention, compared with conservative management, result in improved mobility and reduced pain?

Clinical bottom line

Category of research:

Treatment.

Number and type of study designs reviewed:

Three studies were identified directly addressing the PICO question. One paper was a retrospective cohort study, another study was a prospective randomised control trial, and the third was a non-randomised non-blinded observational study.

Strength of evidence:

Weak.

Outcomes reported:

The first study was a prospective non-randomised study that did not identify a difference in gait evaluation at the 52 week recheck in dogs treated conservatively compared to those treated arthroscopically, with lameness exacerbated in the arthroscopic treatment group until the 26 week recheck. The second study, a retrospective non-randomised cohort study, showed greater, but not statistically different, owner-reported clinical metrology scores in dogs treated arthroscopically compared to those treated conservatively. Liverpool Osteoarthritis in Dogs (LOAD) and Pain Severity Scores (PSS) were higher but not statistically significant, yet Pain Interference Scores (PIS) were statistically significantly higher at 52 weeks in arthroscopically treated dogs compared to conservatively treated dogs. Age at diagnosis and at time of questionnaire completion were statistically significant for LOAD, PSS, and PIS, with older dogs having higher scores. The third study performed a non-blinded observational study assessing canine patients with bilateral medial coronoid disease, with unilateral arthroscopic subtotal coronoidectomy performed on the most clinically affected limb. Radiographs and computed tomography (CT) imaging were performed at diagnosis, with radiographs taken at follow-up. At the time of follow-up, arthroscopically treated limbs had a higher radiographic score than those treated conservatively, although a significant improvement in lameness was seen at the walk in arthroscopically treated limbs. Conservatively managed dogs showed an unchanged (non-significant) gait. Radiographic changes did not appear to correlate to severity of clinical signs.

Conclusion:

The quality of the published evidence available to answer the PICO question is weak, due to the design of the three reviewed studies. Low patient populations in these three studies also hinder the statistical power of any recommendations made. None of the three studies assesses the complex nature of medial coronoid disease to clearly answer the question posed. The decision to recommend arthroscopy over conservative management therefore depends on the judgement and experience of the veterinary surgeon attending the case. Additionally, assessment of the imaging findings is important when discussing prospective treatment options.

Should joint lavage be performed in the treatment of juvenile canine spontaneous/haematogenous septic arthritis?

Philippa Wells — 2025-02-20

Question

In dogs less than 18 months old, with spontaneous/haematogenous bacterial septic arthritis, how effective is treatment with joint lavage and antimicrobial therapy compared to antimicrobial therapy alone?

Clinical bottom line

The category of research question was:

Treatment.

The number and type of study designs that were critically appraised were:

One case series of 5 dogs.

Critical appraisal of the selected papers meeting the inclusion criteria collectively provide zero/weak/moderate/strong evidence in terms of their experimental design and implementation:

Weak.

The outcomes reported are summarised as follows…

Successful clinical outcomes were reported in patients both with and without joint lavage.

In view of the strength of evidence and the outcomes from the studies the following conclusion is made…

No conclusions can be made regarding the impact of joint lavage on haematogenous septic arthritis in juvenile dogs as excellent outcomes were achieved in patients with and without lavage. However appropriate antibiosis continues to be pertinent with one case persistently infected when inappropriate antibiotics were selected.

Fasciola hepatica: can the coproantigen ELISA replace the faecal egg sedimentation test?

Jake Collyer — 2024-11-28

Question

In adult cattle, is the sensitivity of the coproantigen ELISA test equal or superior to the sensitivity of the faecal egg sedimentation test for the diagnosis of Fasciola hepatica?

Clinical bottom line

The category of research question was:

Diagnosis.

The number and type of study designs that were critically appraised were:

Three studies were appraised. This included two cross-sectional diagnostic accuracy studies and one case control diagnostic accuracy study.

Critical appraisal of the selected papers meeting the inclusion criteria collectively provide zero/weak/moderate/strong evidence in terms of their experimental design and implementation:

Moderate.

The outcomes reported are summarised as follows…

The first study reported the findings from 619 tested cattle over 3 sample periods comparing the sensitivity and specificity of the different tests. The sensitivity of the faecal egg sedimentation test varied greatly between the sample periods from 0.81 (95% beta coefficient (BCI) 0.72–0.90) to 0.58 (95% BCI 0.43–0.72) with the coproantigen ELISAs sensitivity remaining consistent at 0.77 (95% BCI 0.64–0.88) throughout.

The second study reported the findings of 200 tested cattle over 2 sampling periods comparing the sensitivity and specificity of the different tests. The mean sensitivity of the coproantigen ELISA was significantly higher than the 4 g/10 g preparations of the faecal egg sedimentation tests at 94% (95% CI 87%–98%) (P < 0.001).

The third study reported the findings of Coproantigen ELISA testing on 250 bovine faecal samples with 94 confirmed positive for liver fluke via faecal sedimentation testing. The sensitivity of the coproantigen ELISA was 80% and the specificity was 100% compared with 70% and 80% respectively for the faecal egg sedimentation test.

In view of the strength of evidence and the outcomes from the studies the following conclusion is made…

All three studies demonstrated either an increased or equivalent sensitivity of the coproantigen ELISA to the faecal sedimentation test, but only one study reported a statistically significant increase in test sensitivity. Whilst all three studies were diagnostic accuracy validity studies, the systematic sampling strategy of one study was superior to the convenience sampling method of one of the other studies and to the case control method of the other.

Several sources of bias also exist within the included studies. Sampling and selection bias is present in the two of studies due to the animals selected only being sampled over one year. The results of these studies are susceptible to changes in the fluke lifecycle of that year, and the sampled animals are more likely to be fit and well-conditioned as they are presenting for slaughter, and as such are less likely to carry significant/chronic fluke burdens. All three studies are susceptible to validity issues due to an absence of clinical information regarding flukicide treatment and concurrent parasitic diseases which, whilst not impacting the efficacy of diagnostic testing, may cause issues if the studies are to be repeated.

The coproantigen ELISA can be utilised as a suitable adjunctive test to aid in the diagnosis of Fasciola hepatica in adult cattle and has the scope to be used as an early diagnostic test, but whilst the results of the reported studies indicate that the coproantigen ELISA is an accurate and reliable test, it does not provide definitive evidence to warrant the discontinuation of the simple and affordable faecal egg sedimentation test. In order to come to a conclusion regarding the more sensitive test more literature is required that directly compares the coproantigen ELISA to the faecal egg sedimentation test in different clinical scenarios and exploring different diagnostic techniques.

Recurrence rates in dogs with GDV treated with gastric decompression versus dogs treated with gastric decompression and gastropexy

Costel Zagan — 2025-02-10

Question

In dogs diagnosed with gastric dilatation and volvulus (GDV), does gastric decompression and gastropexy reduce the risk of recurrence of dilatation compared to dogs undergoing gastric decompression alone?

Clinical bottom line

Category of research:

Treatment.

Number and type of study designs reviewed:

Four papers were critically reviewed. Two papers were retrospective studies, and two were prospective.

Strength of evidence:

Strong.

Outcomes reported:

In dogs with GDV, the risk of recurrence of this disease was much lower when gastropexy was performed.

Conclusion:

The studies comparing the recurrence rates in dogs with GDV treated either with gastric decompression (with or without gastric repositioning) or with gastric decompression and gastropexy indicate that gastropexy will significantly reduce the risk of recurrence.

Do cats receiving pre-appointment trazodone experience less stress during veterinary visits?

Stephanie Shone — 2025-02-17

Question

In cats does pre-appointment trazodone administration, compared to no trazodone, effectively reduce patients’ stress during veterinary visits?

Clinical bottom line

The category of research question was:

Treatment.

The number and type of study designs that were critically appraised were:

Two studies were identified and reviewed. One was a double blind, placebo controlled, randomised crossover study. The other was a blinded placebo controlled randomised crossover study.

Critical appraisal of the selected papers meeting the inclusion criteria collectively provide zero/weak/moderate/strong evidence in terms of their experimental design and implementation:

Weak.

The outcomes reported are summarised as follows…

In the first appraised paper 10 cats with ≥ 1 behavioural sign consistent with transport or veterinary examination associated anxiety were randomly assigned and orally administered a 50 mg trazodone tablet or a placebo (a sodium bicarbonate tablet identical in appearance to a trazodone tablet).

9/10 cats had anxiety-related signs during the veterinary visit when given the placebo, whereas 3/10 had them when given trazodone. Overall, behavioural scores assigned by the veterinarian were significantly (Wilcoxon signed rank test, P = 0.006) lower for cats after receiving trazodone versus the placebo. Trazodone administration resulted in significantly (Wilcoxon signed rank test, P = 0.01) more favourable tractability scores than with the placebo administration, with cats considered relaxed versus tense after receiving trazodone. For all components of the veterinary examination, trazodone administration resulted in significantly (McNemar test, P = 0.03 for each comparison) lower stress scores before, during and after veterinary examination. However, one cat was reported to become more fearful and vocal after trazodone administration.

The second paper assessed the sedative and anxiolytic effects of 50 mg, 75 mg, and 100 mg trazodone administration to 6 purpose-bred, male, neutered laboratory cats, prior to and during a veterinary examination to a placebo (food or treats with no tablet). Since the 50 mg and 75 mg doses were not randomised the author of this Knowledge Summary did not include them as part of the statistical analysis. This study found no statistically significant difference in scoring between the effects of the 100 mg trazodone and the placebo, after analysis of the total behavioural and mean overall stress scores. There was a statistically significant difference in enclosure activity with lower levels of activity in cats administered 100 mg trazodone compared to the placebo. However, this is likely more reflective of the sedative effects of trazodone rather than anxiolysis.

In view of the strength of evidence and the outcomes from the studies the following conclusion is made…

The first appraised paper found promising evidence that trazodone could be effective at reducing stress in cats during veterinary visits. However, despite the strong study design, many limitations were identified, most notably the small sample size and large number of uncontrolled variables. This undermined the statistically significant data produced. The second study did not produce statistically significant evidence that trazodone ameliorates stress during a veterinary visit.

A conclusion to the PICO question cannot be made due to lack of relevant studies and statistically significant data. Evidence found supporting the PICO question is weak and therefore more studies with larger sample sizes and less variability are needed to determine the efficacy of trazodone use to reduce stress in cats during veterinary visits.

Erratum to: Comparing the effectiveness of clomipramine and fluoxetine in dogs with anxiety-related behaviours

Olivia Williamson — 2024-06-14

The original article was published in Veterinary Evidence Vol 9, Issue 1 (2024): https://doi.org/10.18849/ve.v9i1.679

In the original version of the article the contributions of one of the authors, Christopher Minami, were listed as "Investigation, Writing – Original draft". This has now been corrected to accurately reflect Minami's contributions, with the agreement of all the authors:

Christopher Minami: Conceptualisation, Methodology, Investigation, Writing – Original draft.

This error was in both the HTML and PDF versions. This has now been updated in both the HTML and PDF versions, and can be found in the author contributions section.

Nonsteroidal anti-inflammatory drug administration to periparturient cows to reduce postpartum pain-related behaviours

Amelia Cannadine — 2024-10-18

Question

In periparturient cows does the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) aid in reducing pain-related behaviours after parturition when compared to cows not administered NSAIDs?

Clinical bottom line

The category of research question was:

Treatment.

The number and type of study designs that were critically appraised were:

Four randomised control trials.

Critical appraisal of the selected papers meeting the inclusion criteria collectively provide zero/weak/moderate/strong evidence in terms of their experimental design and implementation:

Moderate.

The outcomes reported are summarised as follows…

The evidence suggests that NSAIDs can reduce some pain-related behaviours and increase resting behaviours in postpartum cows, with the effect being most consistently observed when administered between 6 and 48 hours before calving or within 3 hours after calving. This effect was most consistently observed in individuals that had experienced uncomplicated calving events and primiparous animals. Primiparous animals administered meloxicam prior to natural calving displayed significantly more lying bouts on the day of calving when compared to primiparous control animals and primiparous animals administered meloxicam postpartum. A separate study reported that cows administered ketoprofen spent less time in lateral recumbency than cows in the placebo group, irrespective of whether calving was assisted. Additionally, when treatment cows were in sternal recumbency, they spent more time with their head in a rested position than the placebo group. There was no significant difference in feeding behaviours postpartum between treatment and placebo animals. There were conflicting results between papers assessing activity levels.

In view of the strength of evidence and the outcomes from the studies the following conclusion is made…

In some cows, in particular cows with an uncomplicated parturition, NSAIDs can reduce some pain-related behaviours and increase some resting behaviours postpartum. The NSAID should be administered between 6 and 48 hours before calving or within 3 hours after calving.

The therapeutic effectiveness of oral cannabidiol in addition to current treatment in cats with osteoarthritis

Oliver Wilkinson — 2024-10-23

Question

In cats with osteoarthritis (OA), does the oral supplementation of cannabidiol (CBD) oil, compared to conventional treatment alone, improve treatment outcomes of reducing pain and improving locomotion?

Clinical bottom line

The category of research question was:

Treatment.

The number and type of study designs that were critically appraised were:

No papers were found relevant to the PICO.

Critical appraisal of the selected papers meeting the inclusion criteria collectively provide zero/weak/moderate/strong evidence in terms of their experimental design and implementation:

Zero.

The outcomes reported are summarised as follows…

No studies relevant to the PICO were found (in English) on the use of CBD in cats with OA.

In view of the strength of evidence and the outcomes from the studies the following conclusion is made…

There is currently no evidence to recommend the use of CBD in cats for the treatment of OA and further studies on therapeutic use of CBD in cats with OA are required.

Does wearing facemasks during small animal surgery reduce the incidence of surgical site infections?

Alexander Bartlett — 2024-11-04

Question

In small animals undergoing theatre-based surgical procedures does having all theatre personnel masked, compared with not having all theatre personnel masked, result in a reduced incidence of surgical site infections?

Clinical bottom line

The category of research question was:

Incidence.

The number and type of study designs that were critically appraised were:

Zero. No records relevant to the PICO question were retrieved from the literature search.

Critical appraisal of the selected papers meeting the inclusion criteria collectively provide zero/weak/moderate/strong evidence in terms of their experimental design and implementation:

Zero.

The outcomes reported are summarised as follows…

There is no published evidence specific to small animals that assesses the effect of wearing facemasks during surgical procedures on the rate of postoperative surgical site infections.

In view of the strength of evidence and the outcomes from the studies the following conclusion is made…

In small animals undergoing theatre-based surgical procedures, there is no published evidence evaluating the effect of having all theatre personnel masked compared with not having all theatre personnel masked on the incidence of surgical site infections. However, this lack of evidence should not be interpreted as lack of efficacy.

Intranasal midazolam as an alternative to rectal diazepam for management of canine status epilepticus

Flora Foxx — 2024-12-10

Question

In canine patients in status epilepticus, is intranasal midazolam as effective as rectal diazepam for controlling seizures?

Clinical bottom line

The category of research question was:

Treatment.

The number and type of study designs that were critically appraised were:

One study was found—a multicentre randomised open-label clinical trial comparing intranasal midazolam and rectal diazepam in canine patients.

Critical appraisal of the selected papers meeting the inclusion criteria collectively provide zero/weak/moderate/strong evidence in terms of their experimental design and implementation:

Weak.

The outcomes reported are summarised as follows…

The study critically appraised in this summary indicated that intranasal midazolam is effective in achieving seizure control in canine patients, with tolerable safety margins. Mild adverse effects associated with benzodiazepine administration such as sedation and drowsiness were noted, but there were no reports of serious adverse events related to the use of intranasal midazolam.

In view of the strength of evidence and the outcomes from the studies the following conclusion is made…

Intranasal midazolam appears to be safe and effective for achieving seizure control in canine patients, both in terms of efficacy and speed of onset, and is a suitable first-line treatment option for status epilepticus, especially when intravenous access is not rapidly available. Patients should be monitored after drug administration for development of adverse effects, including sedation, sneezing, and nasal irritation. A nasal mucosal atomisation device may be used to enhance bioavailability of the drug, improving efficacy.

The use of adjuvant chemotherapy in cats with mammary carcinomas undergoing surgical removal

Gabriela Gonzalez-Ormerod — 2024-11-18

PICO Question

In cats with mammary carcinomas undergoing surgical removal, does the addition of adjuvant chemotherapy compared with surgical removal alone result in increased survival time?

Clinical bottom line

Category of research

Treatment.

Number and type of study designs reviewed

Five retrospective cohort studies were critically reviewed.

Strength of evidence

Weak.

Outcomes reported

In cats with mammary carcinomas undergoing surgical removal, the addition of adjuvant chemotherapy compared with surgical removal alone was significantly associated with an increase in disease-specific survival time in one of the studies. This statistical significance was not found in the other four papers.

Conclusion

All five studies reviewed presented weak evidence for the clinical question due to their retrospective nature and weak study design. It is, therefore, concluded that there is not enough evidence to suggest that cats with mammary carcinomas that have undergone surgical treatment will have a longer survival time if treated with adjuvant chemotherapy. More prospective, placebo-controlled, double-blinded studies are needed to understand the clinical significance of adjuvant chemotherapy in cats with mammary carcinomas.

Comparison of medical versus surgical management of liver lobe torsion in rabbits

Rachel Sibbald — 2024-07-19

PICO Question
Does medical management of liver lobe torsion in rabbits reduce mortality compared with surgical intervention?

Clinical bottom line

Category of research

Treatment.

Number and type of study designs reviewed

Six studies were appraised in total. This consisted of three retrospective cohort studies and three case series.

Strength of evidence

Weak.

Outcomes reported

Medical management carries a similar 7-day survival rate compared to surgical treatment; however, long-term morbidity and mortality is increased compared with surgery. Delayed diagnosis and severe anaemia negatively affect outcomes of both groups.

Conclusion

Medical management does not reduce mortality compared with surgical treatment and within the literature there appears to be a preference for surgery when treating rabbits with liver lobe torsion.

How to apply this evidence in practice

The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources.

Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

In adult dogs is supplementary tryptophan in the diet effective in reducing signs of anxiety?

Lesca Sofyan — 2024-10-24

Question

In adult dogs, is dietary supplementation with tryptophan compared with no dietary tryptophan supplement effective in reducing signs of anxiety?

Clinical bottom line

The category of research question was:

Treatment.

The number and type of study designs that were critically appraised were:

Two studies were found to be considered appropriate in the level of hierarchy of evidence pyramid. One study was a randomised double-blinded, placebo-controlled study and the other was a single-blind, placebo-controlled study.

Critical appraisal of the selected papers meeting the inclusion criteria collectively provide zero/weak/moderate/strong evidence in terms of their experimental design and implementation:

Moderate.

The outcomes reported are summarised as follows…

One study found no overall significant influence of tryptophan in the diet as an aid in reducing anxiety and fear-related behaviour in anxious dogs in household conditions. In contrast, the second study reported lower anxiety-related behaviour in dogs by owners but did not find significant differences in cortisol levels based on urine cortisol-to-creatinine ratio.

In view of the strength of evidence and the outcomes from the studies the following conclusion is made…

Current evidence reveals two studies that have evaluated the effectiveness of tryptophan as a supplement to the diets of anxious canines for pet owners. One study conducted did not find a significant effect or interaction in reducing anxiety-related behaviour whilst the second study reported lower anxiety-related behaviour in dogs by owners but did not find significant differences in cortisol levels based on urine cortisol-to-creatinine ratios. The use of tryptophan as a supplementary component in the diet is thus not enough as a sole treatment to assist in reducing anxiety in anxious adult dogs.

Thank you to our reviewers 2023

Kit Sturgess — 2024-03-28

2024 has started with a bang or perhaps more accurately floods, snow and ice. The world remains an uncertain place with the conflict in Ukraine and Gaza as well as tension around the Korean peninsula, Sea of Japan and Taiwan. Economically 2023 was a very hard year with inflation exceeding wage increases making it hard for animal carers, with food banks in the UK seeing an increasing demand for pet food. Thankfully inflation is falling and the economic outlook, although not rosy, is perhaps not as gloomy as originally forecast. The big stories in publishing for 2023 were the explosion of large language models (LLM) like ChatGPT and their impact on publishing (we now have a policy on the use of artificial intelligence (AI) in papers submitted to Veterinary Evidence) and the burgeoning challenge of paper mills (organisations that produce and sell authorship of fabricated or manipulated manuscripts which resemble genuine legitimate research) that has led to some journals losing their citation.

Veterinary Evidence continues to grow and flourish with increased visits to our website and a regular stream of articles being published. Good governance and ethical publication remain a key focus of the Board that has been strengthened by a number of new members, bringing a broader range of expertise and experience. Our Student Awards continue to be a success and I would like to thank the whole team of staff and reviewers for turning round these submissions so quickly. I had the pleasure of talking to the prize-winning authors and it was great to hear their enthusiasm, but also how much they have valued the help and support from the journal.

Our new submission system, Editorial Manager, has been installed and is working well providing better insight into how the publishing process is working for us. It has been a learning experience for all and like any new system there are a few areas where we can further improve the author and reviewer experience. Thanks to the hard work of staff, reviewers and Associate Editors, there are now no papers left in the old OJS system. The journal has strived to make the reviewing process as straightforward as possible with a prereview checklist to ensure papers are ready for review. A mentoring system is up and running for new reviewers open to all who may be interested in contributing to the publication of veterinary literature. Veterinary Evidence has been working hard on our next review date policy and processes so some of our early Knowledge Summaries can be updated as new literature becomes available. We are also preparing to make an application for citation in PubMed Central to increase the visibility of Veterinary Evidence’s content.

None of this would be possible without the input from our volunteers and I would like to take this opportunity to say a huge thank you to all our reviewers, Associate Editors and everyone who has served on the Board this year for their tireless efforts on behalf of Veterinary Evidence without your support the journal could not exist. This year the Board has again had three online meetings, which have been essential in helping develop the strategy for Veterinary Evidence; such as our response to LLM, graphic content and further work on which types of evidence can be included in our Knowledge Summaries. On a personal note, my time as Editor-in-Chief is drawing to a close. It has been a great 3 years plus and I have had incredible support from everyone at Veterinary Evidence which has made my role so much easier and more enjoyable.

Once again, a massive thank you to everyone who works for and supports Veterinary Evidence, wishing you all a safe and productive 2024.

Kit Sturgess

Editor-in-Chief

In dogs with thoracolumbar disc extrusion does the use of acupuncture improve clinical recovery?

Justin Ng — 2024-05-22

PICO Question
In dogs with thoracolumbar intervertebral disc extrusion does the use of acupuncture with medical management compared with medical management alone improve clinical recovery?

Clinical bottom line

Category of research

Treatment.

Number and type of study designs reviewed

Three papers were critically appraised: one randomised controlled trial, one non-randomised controlled trial, and one cohort study.

Strength of evidence

Moderate.

Outcomes reported

Acupuncture, and more specifically the combination of electroacupuncture and manual stimulation of acupuncture points when used as an adjunct to medical management, is more likely to result in both the recovery of ambulation and a quicker recovery of ambulation in dogs presenting with nonambulatory paraparesis or paralysis with deep pain perception due to thoracolumbar intervertebral disc extrusion, compared with medical management alone. It is less likely to make a difference in dogs that present with paralysis and no pain sensation.

There is less robust evidence supporting the use of bee venom injections in acupoints, however; it too may have a beneficial effect when used as an adjunct treatment in dogs with nonambulatory paraparesis or paralysis with deep pain perception due to thoracolumbar intervertebral disc extrusion, compared with medical management alone.

Conclusion

There is moderate evidence supporting the conclusion that there is a mild benefit in the use of acupuncture with medical management to improve the clinical recovery of dogs with thoracolumbar intervertebral disc extrusion.

How to apply this evidence in practice

The peri / postoperative analgesic effect of intravenous paracetamol in dogs

Laura Mckay — 2024-04-04

PICO Question

In healthy dogs undergoing a surgical procedure, is there improved pain control in dogs receiving intravenous paracetamol in the peri / postoperative period compared to dogs not receiving intravenous paracetamol?

Clinical bottom line

Category of research

Treatment.

Number and type of study designs reviewed

Three randomised, controlled, and blinded studies. Two studies directly address the PICO question whereby postoperative pain assessment was clinically evaluated following intravenous (IV) paracetamol. The third study addressed the question to a lesser extent, whereby the impact on the sevoflurane minimum alveolar concentration (MAC) reduction in response to noxious stimuli was assessed following the administration of IV paracetamol.

Strength of evidence

Weak.

Outcomes reported

The findings of the first two studies presented appear to directly contradict each other. The first study demonstrated a reduction in pain in all groups and found no differences in analgesia between IV paracetamol and other non-steroidal anti-inflammatories drugs (NSAIDs), while the second study reported no analgesia effects from IV paracetamol and was terminated prematurely because a high number of dogs required rescue analgesia. The first study reported sufficient analgesic effects of IV paracetamol and the second study reported no analgesia effects of IV paracetamol. Both were blinded, randomised, controlled studies and directly addressed the PICO question in relation to the peri / postoperative analgesic effects of IV paracetamol. However, their methods and sample sizes were very different. The third study did not demonstrate a clinically relevant sevoflurane MAC reduction after IV paracetamol in dogs.

Conclusion

At present, there is limited and weak evidence to suggest that IV paracetamol provides peri / postoperative analgesia in dogs. However, further studies are required to better assess its efficacy, its duration of action, and the appropriate doses that are necessary to reach therapeutic plasma levels. The reduced incidence of side effects at the currently recommended doses could support its peri / postoperative use, where NSAIDs use is contraindicated.

How to apply this evidence in practice

Publication of registration studies for veterinary medicine in peer-reviewed academic journals

Jonathan Elliott — 2024-09-18

Much clinically applied research undertaken by research and development departments of pharmaceutical companies is used to support the registration of veterinary medicinal products but is only made publicly available in summary form by the authorisation bodies (e.g. European Medicines Agency or U.S. Food and Drug Administration Center for Veterinary Medicine). Many veterinary practitioners do not read these summaries and are not fully aware of what is required to gain a product authorisation. When pivotal registration trials are published in peer-reviewed academic journals some might think this is all the research that underpins the authorisation of the product.

This could not be further than the truth. In order to gain a marketing authorisation for a veterinary medicinal product, the company needs to have demonstrated that the product:

can be manufactured to highly reproducible standards (quality of product);
has a favourable risk-benefit analysis which supports its proposed clinical use such that if used as per the datasheet indications, the patients treated (and owners administering the treatment) should not be harmed by its administration. Any patient groups at higher risk of suffering adverse effects will be identified by the datasheet warnings and so excluded from receiving treatment. Furthermore, they need to show the environment is not harmed by the use of the product (safety of the product);
is efficacious and the evidence supporting the indications claimed on the datasheet is robust (efficacy of the product).

Registration dossiers containing the evidence for the quality, safety and efficacy of new veterinary medicinal products are substantial, usually contain multiple studies undertaken over several years, and each part is evaluated by trained assessors who can have access to all the raw data from all the studies companies have conducted. All pivotal studies are expected to have been undertaken to a quality standard that is agreed internationally to be to Good Manufacturing Practice (GMP), Good Laboratory Practice (GLP), or Good Clinical Practice (GCP) standards. Published VICH^[1] guidelines explain what is expected in each of these international standards. Principles of GCP and GLP relevant to all pivotal preclinical and clinical studies under-pinning the safety and efficacy of a product include producing an agreed study protocol ahead of commencing the study. The protocol should be clear and strictly adhered to with any protocol violations or amendments that occur during the study clearly documented and explained in the final study report. This protocol will define and justify the study’s primary efficacy end-points, explaining their relevance to the general patient population, how they will be measured, and how the test and control treatments will be compared. It is standard practice to also provide a plan for statistical analysis alongside the study protocol which justifies the number of patients to be included in each group and identifies the statistical methods to be used.

Because assessors can have access to the raw data, they can check that the inclusion and exclusion criteria were adhered to, and the protocol has been correctly followed for each patient. Indeed, quality audits undertaken by the companies should have identified any anomalies prior to submission and corrected these if they are found. In addition, measurement methods (e.g. drug plasma concentration assays, hormone evaluation assays) used in these studies are expected to be fully validated and evidence of validation and the quality assurance assessments carried out and will need to be presented as part of the data package submitted within the dossier.

Furthermore, for EU submissions, companies are required to include detailed and critical assessments of the studies submitted (‘expert report’) which are written by suitably qualified individuals who are independent of the study investigator and are often not an employee of the company, albeit they are engaged by the company on a consultancy basis. Expert reports are required for each part of the dossier. This provides the company with an independent review of their data ahead of submission of the dossier for registration purposes and identifies where any scientific weaknesses lie. This critical evaluation may lead to further studies being undertaken or datasheet claims, contraindications, or warnings being changed.

When registration studies are presented to peer-reviewed academic journals for publication, the data included needs to conform to the journal’s requirements in terms of word length of the manuscript (often 4000 to 5000 words). In many cases this limits the amount of data and level of description that can be included in the manuscript such that many details have to be omitted.

Thus, any published manuscript will be much less detailed than the dossier required for registration purposes and will generally not include the ancillary (non-pivotal) studies that informed the design of the pivotal field safety and efficacy (FSE) study or the quality assurance data that underpinned the measurement methodology used. These ancillary studies would normally include research that determines and justifies the dose to be used in the pivotal FSE study. This may involve an experimental model of the disease to be treated in the field combined with pharmacokinetic (absorption, distribution, metabolism and elimination (ADME) studies), pharmacodynamic, and toxicology studies, and preliminary margin of safety studies in the target species.

Some journals do allow submission of supplementary data which does not count in terms of the final word count of the manuscript, but this would not usually extend to experiments that might constitute another full manuscript as would be the case for dose determination studies. Most do not require submission of the raw data from individual animals that were included in the study or the quality assurance data to be made available to the reviewers. Reviewers of academic papers are not paid for the time they spend undertaking the review process nor do they have access to the raw data to undertake a complete evaluation of the study, hence the review process relies on accurate and faithful recording, inclusion, and interpretation of data by the authors of the paper. Peer review relies on the time and diligence of the reviewer who can only assess the data and the inferences made by the authors of the paper by benchmarking them against previous publications and the reviewers’ subject knowledge. This is very different from the processes undertaken by regulatory authorities with access to all the data, which undergoes a much greater degree of scrutiny and validation.

Safety of any registered veterinary medicinal product is of paramount importance, yet it is difficult to prove a medicine is without adverse effects before it is authorised. This is why the assessment of risk-benefit is made, taking account of all the data available for the particular product at the time. The pivotal target animal species (TAS) safety study is just one piece of evidence presented in the registration dossier and sometimes these studies will also be submitted to peer-reviewed academic journals for publication. Usually, these studies are neither exciting nor innovative science, but nevertheless they are an important part of the risk-benefit analysis. Unlike the pivotal FSE study, these studies are undertaken in fit healthy, usually young experimental animals of the target species. Their design depends on the dose and duration of treatment that is to be used in the FSE study. Usually these studies examine 1x, 3x and 5x the recommended therapeutic dose administered for at least the maximum recommended duration of treatment or, if the treatment is intended to be chronic, for up to 6 months. A placebo group is included to give the background level of spontaneous adverse events or pathological lesions found in animals of this age.

It is important to recognise that the TAS safety study is not powered to demonstrate statistical significant effects against a placebo. The minimum number of animals is used to reduce the sacrifice of healthy experimental dogs or cats for this purpose in alignment with the principles of the 3Rs (Replacement, Reduction, Refinement). International guidelines on the design and conduct of TAS safety studies have been published. Group sizes are typically four males and four females per dose group and the pattern of effects on particular organ structure or function will be assessed over time by undertaking comprehensive haematology and serum biochemistry testing at regular intervals over the dosing period and assessing organ pathology at the end of the study (both gross and histopathology). If product-related effects are evident, they are usually dose and / or exposure time-related. Idiosyncratic reactions are very unlikely to be identified in registration studies. Toxicokinetic studies are increasingly being used to identify drugs which accumulate within the body and will be complemented by the basic pharmacokinetic studies undertaken in the target species. Such dose and time-dependent signals from the TAS will be taken seriously, particularly if they are seen in the majority of the animals tested and are deemed likely to be clinically significant (regardless of whether statistically significant changes are seen). These signals will inform the monitoring, interpretation and analysis of safety data (suspected adverse drug effects) from the FSE study and feed into the risk-benefit analysis.

Many of the veterinary medicinal products that are being developed will have been widely screened in pre-clinical development to understand selectivity of receptor binding, what metabolites are formed, whether they have mutagenic potential, and so on. They will also have been tested for toxicity in laboratory animals and, when the same class of active ingredient is in use in humans, information on adverse effects seen will also be used in designing and interpreting the TAS study. If, for example, the active ingredient has effects on the electrocardiogram (ECG) in people, ECG analysis will be part of the TAS study or a specific study assessing cardiac effects will be conducted. Thus, if TAS studies are submitted to peer-reviewed academic journals for publication, it should be recognised that they are just part of the information which is used to inform the risk-benefit analysis of a specific veterinary product.

Assessment of safety (and efficacy) of a particular Veterinary Medicinal Product does not end with the product authorisation based on the pivotal TAS and FSE studies. Pharmacovigilance is an important aspect of the assessment of the safety of authorised products. This is dependent on veterinary professionals reporting suspected adverse events (including lack of efficacy) when they encounter them in individual animals they treat with the medicinal product. These are reportable to the market authorisation holder and to the body issuing the product authorisation (in the UK that would be the Veterinary Medicines Directorate). Providing as much information as possible about the case will facilitate the pharmacovigilance team’s ability to recognise important patterns in the data they receive from the field. Companies are required to share any reports they receive, and Medicines Agencies monitor these data continuously and may require investigation as and when patterns of adverse effects or reports of lack of efficacy emerge.

In conclusion, it is desirable for companies to publish pivotal clinical trial data on new products in peer-reviewed academic journals so that veterinary practitioners can read part of the evidence underpinning the claims of efficacy and that is used in the risk-benefit analysis that was undertaken prior to granting a product authorisation. When reading these publications, practitioners should recognise that the FES and TAS studies, whilst pivotal to the authorisation, are supported by many other studies that underpin their design and interpretation and provide assurance of the quality of the data. Most of these supporting studies will not be presented alongside the pivotal studies in peer-reviewed academic journals but were very much an important part of the registration dossier submitted when applying for a marketing authorisation.

[1] International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH)

Further reading

European Medicines Agency. Good laboratory practice compliance, [online]. Available at: https://www.ema.europa.eu/en/human-regulatory/research-development/compliance/good-laboratory-practice-compliance [Accessed 20 Aug 2024].

The European Agency for the Evaluation of Medicinal Products. (2000). VICH Topic GL9 (GCP). Veterinary Medicines and Information Technology Unit, [online]. Available at: https://www.ema.europa.eu/en/documents/scientific-guideline/vich-gl9-good-clinical-practices-step-7_en.pdf

European Medicines Agency. (2008). VICH Topic GL43. Guideline on target animal safety for veterinary pharmaceutical products. Veterinary Medicines and Inspections, [online]. Available at: https://www.ema.europa.eu/en/documents/scientific-guideline/vich-gl43-target-animal-safety-veterinary-pharmaceutical-products-step-7_en.pdf