Target trial emulation: Do antimicrobials or gastrointestinal nutraceuticals prescribed at first presentation for acute diarrhoea cause a better clinical outcome in dogs under primary veterinary care in the UK?

Target trial emulation applies design principles from randomised controlled trials to the analysis of observational data for causal inference and is increasingly used within human epidemiology. Veterinary electronic clinical records represent a potentially valuable source of information to estimate real-world causal effects for companion animal species. This study employed the target trial framework to evaluate the usefulness on veterinary observational data. Acute diarrhoea in dogs was used as a clinical exemplar. Inclusion required dogs aged ≥ 3 months and < 10 years, presenting for veterinary primary care with acute diarrhoea during 2019. Treatment strategies were: 1. antimicrobial prescription compared to no antimicrobial prescription and 2. gastrointestinal nutraceutical prescription compared to no gastrointestinal nutraceutical prescription. The primary outcome was clinical resolution (defined as no revisit with ongoing diarrhoea within 30 days from the date of first presentation). Informed from a directed acyclic graph, data on the following covariates were collected: age, breed, bodyweight, insurance status, comorbidities, vomiting, reduced appetite, haematochezia, pyrexia, duration, additional treatment prescription and veterinary group. Inverse probability of treatment weighting was used to balance covariates between the treatment groups for each of the two target trials. The risk difference (RD) of 0.4% (95% CI -4.5% to 5.3%) was non-significant for clinical resolution in dogs treated with antimicrobials compared with dogs not treated with antimicrobials. The risk difference (RD) of 0.3% (95% CI -4.5% to 5.0%) was non-significant for clinical resolution in dogs treated with gastrointestinal nutraceuticals compared with dogs not treated with gastrointestinal nutraceuticals. This study successfully applied the target trial framework to veterinary observational data. The findings show that antimicrobial or gastrointestinal prescription at first presentation of acute diarrhoea in dogs causes no difference in clinical resolution. The findings support the recommendation for veterinary professionals to limit antimicrobial use for acute diarrhoea in dogs.

Thirty-two cats with effusive or non-effusive feline infectious peritonitis treated with a combination of remdesivir and GS-441524.

BACKGROUND: GS-441524 has been successfully used to treat feline infectious peritonitis (FIP) in cats. However, the use of its prodrug, remdesivir, in combination with a PO GS-441524 containing product for the treatment of FIP has not yet been described. OBJECTIVES: Describe treatment protocols, response to treatment and outcomes in cats with FIP treated with a combination of PO GS-441524 and injectable remdesivir. ANIMALS: Thirty-two client-owned cats diagnosed with effusive or non-effusive FIP including those with ocular and neurological involvement. METHODS: Cats diagnosed with FIP at a single university hospital between August 2021 and July 2022 were included. Variables were recorded from time of diagnosis, and subsequent follow-up information was obtained from the records of referring veterinarians. All surviving cats were observed for the entire 12-week treatment period. RESULTS: Cats received treatment with different combinations of IV remdesivir, SC remdesivir, and PO GS-441524 at a median (range) dosage of 15 (10-20) mg/kg. Clinical response to treatment was observed in 28 of 32 cats (87.5%) in a median (range) of 2 (1-5) days. Twenty-six of 32 cats (81.3%) were alive and in clinical and biochemical remission at the end of the 12-week treatment period. Six of 32 cats (18.8%) died or were euthanized during treatment with 4 of the 6 cats (66%) dying within 3 days of starting treatment. CONCLUSIONS: We describe the effective use of injectable remdesivir and PO GS-441524 for the treatment of FIP in cats. Success occurred using different treatment protocols and with different presentations of FIP including cats with ocular and neurological involvement.

Investigation of single-nucleotide polymorphisms in the NR3C1a glucocorticoid receptor gene in Cocker Spaniels with primary immune thrombocytopenia.

BACKGROUND: In dogs, 6 single-nucleotide polymorphisms (SNPs) have been described in the glucocorticoid receptor gene NR3C1a, 2 of which were nonsynonymous SNPs in exons 2 and 8. The clinical importance of these SNPs is unknown. OBJECTIVES: To investigate whether SNPs in NR3C1a are associated with clinical outcome in Cocker Spaniels with primary immune thrombocytopenia (pITP). ANIMALS: Twenty-four Cocker Spaniels with pITP presented to a referral center. Dogs were classified as slow (n = 11) or fast responders (n = 12) based on time required after initiating glucocorticoid treatment to achieve a platelet count >70 000/µL. METHODS: Deoxyribonucleic acid was extracted from stored blood samples before amplification by PCR and sequencing of exons 2 and 8 of NR3C1a. Associations between genotype and clinical response variables were investigated. RESULTS: Neither previously identified nonsynonymous SNPs were identified. The synonymous SNP NR3C1a:c.798C>T in exon 2 was found at an increased prevalence compared to a previous report. No difference was found in prevalence of any genotype at NR3C1a:c.798C>T between fast and slow responders (P = .70). CONCLUSIONS AND CLINICAL IMPORTANCE: None of the previously reported nonsynonymous SNPs in exons 2 and 8 of the NR3C1a gene were detected in our cohort of Cocker Spaniels with pITP. The synonymous SNP NR3C1a:c.798C>T in exon 2 was reported at a higher frequency than previously, but was not associated with outcome measures that estimated responsiveness to glucocorticoids.

Cross-sectional study of approaches to diagnosis and management of dogs with immune-mediated haemolytic anaemia in primary care and referral veterinary practices in the United Kingdom.

OBJECTIVES: To determine whether veterinarians in primary care practices (PCPs) and board-certified clinicians (BCCs) approach treatment of dogs with immune-mediated haemolytic anaemia (IMHA) similarly, and whether practitioners with more experience treat similarly to those with less experience. We hypothesised those in PCPs would show more variation in their approach to similar cases than BCCs. METHODS: A cross-sectional study was conducted by distributing a questionnaire to BCCs and veterinarians in PCPs. The questionnaire included direct questions and a number of clinical scenarios intended to capture approaches to common treatment problems. RESULTS: Questionnaire responses were received from 241 veterinarians, including 216 in PCPs and 25 BCCs. Veterinarians in both settings used similar tests for diagnosis of IMHA, but BCCs performed more tests to exclude underlying causes of 'associative' disease. All veterinarians reported use of similar initial dosages of glucocorticoids (median 2 mg/kg per day in both groups, p = 0.92) but those used by more experienced practitioners were higher than those with less experience. Most veterinarians made allowances for the weight of dogs, using lower prednisolone dosages in a clinical scenario involving a 40 kg dog compared to a 9 kg dog (p = 0.025 for PCP, p = 0.002 for BCC). BCCs reported greater use of combinations of immunosuppressive drugs (p<0.0001) and of antithrombotic drugs (p<0.0001); use of antithrombotic drugs was also less common among more experienced practitioners compared to less experienced. CONCLUSIONS: Approaches to treatment of dogs with IMHA differ between BCCs and those in PCP. These differences may affect design and implementation of future research studies and clinical guidelines.

Gastroesophageal intussusception and extreme esophageal dilatation secondary to bilateral laryngeal paralysis in a cat.

Gastroesophageal intussusception, extreme esophageal dilatation, and laryngeal paralysis are individually rare clinical entities in cats and the simultaneous occurrence in a single animal has not been described. We describe these 3 conditions occurring concurrently in a geriatric cat, and resolution of the cat's clinical signs after treatment with unilateral arytenoid lateralization. This finding supports the need for thorough history taking and examination in cats with extreme esophageal dilatation to determine if upper respiratory tract abnormalities are present, as appropriate treatment might resolve the esophageal dilatation.

Blood taurine concentrations in dogs with exocrine pancreatic insufficiency.

OBJECTIVE: To determine whether blood taurine concentrations in dogs with exocrine pancreatic insufficiency (EPI) were lower than the reference interval (200 to 350 nmol/mL) or the cutoff used to indicate taurine deficiency (< 150 nmol/mL). ANIMALS: 18 dogs with clinical or presumptive subclinical EPI with residual blood samples available for taurine concentration analysis. PROCEDURES: Dogs were classified as having clinical EPI if they had a serum trypsin-like immunoreactivity concentration of < 2.0 µg/L and presumptive subclinical EPI if they had a concentration of 2.0 to 5.0 µg/L. Archived, frozen blood samples stored in EDTA were submitted for measurement of taurine concentration with an automated high-performance liquid chromatography amino acid analyzer. Medical record data were examined for associations with blood taurine concentration. RESULTS: None of the 18 dogs had a blood taurine concentration < 150 nmol/mL. Two dogs had a concentration < 200 nmol/mL. No clinical signs, physical examination findings, or serum biochemical abnormalities were associated with blood taurine concentration. Eleven of the 17 dogs for which diet histories were available were not receiving a diet that met recommendations of the World Small Animal Veterinary Association Global Nutrition Committee. CONCLUSIONS AND CLINICAL RELEVANCE: A low blood taurine concentration was noted in a small subset of dogs with EPI. Additional research is needed to determine whether EPI was the primary cause of this low concentration. Findings suggested the importance of obtaining complete diet histories and ensuring dietary requirements are sufficiently met in dogs with EPI. (Am J Vet Res 2020;81:958-963).