A blinded, randomized and controlled multicenter field study investigating the safety and efficacy of long-term use of enflicoxib in the treatment of naturally occurring osteoarthritis in client-owned dogs
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SUBMITTER: Homedes J
PROVIDER: S-EPMC10995975 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Musculoskeletal disease (MSD) is common in ageing cats, resulting in chronic pain and mobility impairment, but diagnosis can be challenging. We hypothesised that there would be differences between cats with and without MSD in paw pressure and spatiotemporal and kinetic gait metrics. A cohort of 53 cats, aged between 7 and 10 years from the North West of the United Kingdom, underwent an orthopaedic examination and walked on a pressure sensitive walkway. Thirty-one of the cats (58%) were determined to be apparently-healthy, based on a normal orthopaedic examination and having no history of MSD, whilst the remaining 22 cats (42%) had findings consistent with MSD; 13/22 cats (59%) had multiple limb involvement, 7/22 (32%) had forelimb involvement and 2/22 (9%) had hindlimb involvement. Bodyweight (P = 0.048) and body condition score (BCS; P = 0.015) were both greater in cats with MSD (mean bodyweight 5.4 ± 1.35 kg; median BCS 6, IQR 6-7.75) compared with apparently-healthy cats (mean bodyweight 4.7 ± 0.94 kg; median BCS 5, IQR 4.5-6.5). There was a relatively large intra-cat variation in spatiotemporal and kinetic gait variables (coefficient of variation >3.0%), whilst a linear mixed-effects model suggested no significant difference in spatiotemporal or kinetic gait variables between apparently-healthy cats and those with MSD. Palmar and plantar pressure asymmetry was assessed by pedobarographic statistical parametric mapping (pSPM) within each individual cat, with no significant difference (P = 0.353) between the apparently heathy cats and those with MSD as to the presence or absence of asymmetry. Given the marked intra-cat variation and the 'multi-limb' nature of MSD in this cohort, it was not possible to differentiate healthy cats from those with MSD based on spatiotemporal and kinetic gait metrics or paw pressure asymmetry. Future work should examine gait in cats with defined musculoskeletal disorders (e.g. hip dysplasia) and also to track longitudinal changes within individual cats to better establish age-related trends.
| S-EPMC11654939 | biostudies-literature
Project description:AimThe point prevalence of ocular lesions due to leishmaniasis was evaluated in 127 dogs living in a municipal shelter placed in a highly endemic area (Sicily, Italy). Moreover, the period prevalence, the type, and prognosis of lesions due to leishmaniasis were evaluated in 132 dogs with ocular pathologies referred to a Veterinary Teaching Hospital (VTH) in the same endemic area over a 3-year period.Materials and methodsAll the dogs were submitted to ophthalmological examination. The diagnosis of leishmaniasis was made by cytological, serological (immune-fluorescent antibody test), and molecular (quantitative polymerase chain reaction) tests.ResultsThe point prevalence of ocular lesions in 45 shelter dogs with leishmaniasis was 71.11% (45/127 dogs). The most frequent ocular lesion was blepharitis (50%) while anterior uveitis was observed in only 9.37% of cases. The period prevalence of ocular lesions due to leishmaniasis in the VTH group was 36.36% (48/132 dogs). In both groups, most of the lesions were bilateral and involved the anterior segment. Anterior uveitis was the most frequent ophthalmic finding in client-owned dogs (37.50%), but it occurred in only 9.37% of the shelter dogs. Keratouveitis often occurred during or after antiprotozoal treatment (14.58%; 7/48). In this study, the healing of eye injury following systemic antiprotozoal treatment was recorded in about half of cases (48%; 12/25 dogs), in which follow-up was possible. In more than 1/3 of cases (36%; 9/25), there was an improvement, but it was necessary to associate a long-term topical treatment; most of them, as well as those who had not responded to systemic therapy (16%; 4/25), had anterior uveitis or keratoconjunctivitis sicca.ConclusionsOcular manifestations involve up to 2/3 of animals affected by canine leishmaniasis and lesions account for over 1/3 of ophthalmic pathologies observed at a referral clinic in an endemic area. The occurrence of anterior uveitis is more frequent in client-owned dogs than in shelter dogs. The onset of keratouveitis during or after antiprotozoal treatment could be attributed to the treatment or to a recurrence of the systemic form. The post-treatment uveal immune reaction, already observed in humans, could explain the difference in the frequency of keratouveitis between client-owned and shelter dogs, which have never been treated.
| S-EPMC4937056 | biostudies-literature
Project description:BackgroundAcupuncture has been used as a treatment for pain associated with osteoarthritis (OA) for thousands of years; however, there is a lack of definitive evidence for this indication in humans or animals. The aim of this study was to prospectively evaluate the efficacy of acupuncture on lameness and clinical function in dogs affected by naturally-occurring OA using objective outcome measures. A total of 32 client-owned dogs completed this prospective, randomized, placebo-controlled, blinded clinical trial, using a cross-over design. Participants were assigned to receive placebo or acupuncture treatment once weekly for 4 weeks in random order with a two-week wash-out period in between treatment phases. Outcome measures included ground reaction forces (GRF), subjective orthopedic scoring (SOS), activity counts (AC), and owner-completed clinical metrology instruments (CMI; Canine Brief Pain Inventory [CBPI] and Client Specific Outcome Measures [CSOM]). For statistical comparison, baseline GRF, SOS, and CMI data were compared to data obtained 1 week after each treatment phase. Similarly, total weekly AC of the final week of each treatment phase were compared to the baseline week.ResultsEvidence of differences between baseline versus acupuncture and placebo treatments was not identified for the following outcome measures: GRF, AC, or SOS. However, evidence of differences was identified for some of the CMI scores, including the CSOM questionnaire which showed evidence of improvement when comparing baseline versus acupuncture (p = 0.0002) as well as between placebo versus acupuncture treatments (p = 0.035) but not between baseline versus placebo treatments (p = 0.221).ConclusionsThe applied acupuncture protocol did not show improvement in function when using objective outcome measures for OA in dogs; however, certain CMI measurements recorded some degree of treatment response.
| S-EPMC7517673 | biostudies-literature
Project description:Osteoarthritis (OA) pain is associated with peripheral and central sensitization in humans and results in widespread increased sensitivity across the body. Sensitization contributes to the OA-associated pain (OAP) state. We recently identified increased levels of an endogenous neurotrophic factor, artemin (ARTN), in dogs with OAP compared to healthy pain-free controls. Circulating ARTN released from damaged tissues in OA, may play a central role in widespread sensitivity and pain. However, the relationship between ARTN and somatosensory sensitivity remains unknown. The study aimed to assess the relationship between serum ARTN concentrations and measures of sensitivity in dogs with OAP using quantitative sensory testing. We hypothesized that there would be a positive association between circulating ARTN and increased sensitivity to mechanical and thermal stimuli in dogs with OAP. We used linear and logistic regression models to assess the relationship between ARTN, sensitization, and pain within a cohort of 43 dogs with spontaneous OAP. Serum ARTN was not associated with the degree of sensitization within dogs with OAP. Further, across dogs with varying OAP severity, we did not find any association between ARTN, and clinical measures of joint pain and disability. Although a relationship between ARTN and joint pain was not ruled out.
| S-EPMC7988108 | biostudies-literature
Project description:BackgroundThere is an association between overweight status and life span in kenneled dogs, but a similar association has not been reported for pet dogs.ObjectivesTo examine the effects of being overweight in middle age on the life span of neutered client-owned dogs.AnimalsFifty-thousand seven-hundred eighty seven middle-aged neutered client-owned dogs attending a network of approximately 900 veterinary hospitals across North America.MethodsRetrospective case-control study. For each of 12 breeds, groups of dogs aged between 6.5 and 8.5 years were identified as being in "overweight" or "normal" body condition. Within each breed and sex, differences in life span between dogs in normal body condition and overweight body condition in the 2 groups were then analyzed by Cox proportional hazards models.ResultsFor all breeds, instantaneous risk of death for dogs in overweight body condition was greater than those in normal body condition throughout the age range studied, with hazard ratios ranging from 1.35 (99.79% confidence interval [CI] 1.05-1.73) for German Shepherd dog to 2.86 (99.79% CI 2.14-3.83) for Yorkshire Terrier. In all breeds, median life span was shorter in overweight compared with normal weight dogs, with the difference being greatest in Yorkshire Terriers (overweight: 13.7 years, 99.79% CI 13.3-14.2; normal: 16.2 years, 99.79% CI 15.7-16.5) and least in German Shepherd dogs (overweight: 12.1 years, 99.79% CI 11.8-12.4; normal: 12.5 years, 99.79% CI 12.2-12.9).Conclusions and clinical importanceVeterinary professionals should consider promoting healthy body condition for dogs, particularly from midlife onward.
| S-EPMC6335446 | biostudies-literature
Project description:Osteoarthritis (OA) is one of the major causes of chronic pain in dogs. However, the pathogenesis of OA has not been fully understood in dogs. The objective of this study was to comprehensively investigate the mRNA expression levels of proinflammatory cytokines, inflammatory mediators, nerve growth factor and its receptor, and matrix metalloproteinases in the synovium of dogs with spontaneous OA as well as to elucidate their relationships with the severity of synovitis. Dogs that were diagnosed with stifle OA on the basis of radiographic findings were included, and the degree of synovitis was observed using stifle arthroscopy. The dogs were assigned to two different groups depending on their synovitis scores: the low-grade group (score of 1 or 2; n = 8) and high-grade group (score of 3 to 5; n = 18). The dogs showing no evidence of orthopedic disease were included in the control group (n = 6). Synovial tissue samples were collected from the sites at which synovitis scores were assessed using arthroscopy. Total RNA was extracted from the collected synovial tissue, and cDNA was synthesized. Subsequently, RT-qPCR were performed using canine-specific primer sets for IL1B, IL6, CXCL8, TNF, TGFB1, PTGS2, PTGES, MMP3, MMP13, NGF, NTRK1, and PTGER4. Expression levels of IL1B, IL6, CXCL8, and MMP13 were significantly higher in the high-grade group than in the control group. In addition, expression levels of IL1B, CXCL8, TNF, and PTGS2 were significantly higher in the high-grade group than in the low-grade group. Expression levels of IL1B, IL6, CXCL8, TNF, PTGS2, and PTGER4 showed significant positive correlation with synovitis score. In conclusion, all mRNA expression levels in the synovial membrane varied according to the degree of synovitis in dogs with spontaneous OA. Thus, this study may partially elucidate the pathogenesis of synovitis in dogs with spontaneous OA.
| S-EPMC7842980 | biostudies-literature
Project description:BackgroundCiclosporin is approved for the treatment of atopic dermatitis (AD) in dogs and has been shown to be safe and effective. Placebo-controlled studies suggest that oclacitinib is a safe and effective alternative therapy.Hypothesis/objectivesTo evaluate the efficacy and safety of oclacitinib, in comparison to ciclosporin, for the control of AD in a blinded, randomized clinical trial, incorporating a noninferiority test at day 28.AnimalsA total of 226 client-owned dogs with a history of AD from eight sites were enrolled.MethodsEnrolled animals were randomized to receive oral oclacitinib (0.4-0.6 mg/kg twice daily for 14 days, then once daily) or oral ciclosporin (3.2-6.6 mg/kg once daily) for 12 weeks. Owners assessed pruritus using an enhanced visual analog scale (VAS), and veterinarians assessed dermatitis using the Canine Atopic Dermatitis Extent and Severity Index (CADESI)-02.ResultsOn days 1, 2, 7, 14, 28, 56 and 84, the percentage reduction from baseline for owner-assessed pruritus changed from 25.6 to 61.0% in the oclacitinib group compared with 6.5 to 61.5% in the ciclosporin group; differences were significant at all time points up to day 28. On day 56, ciclosporin-treated dogs showed a similar decrease in pruritus to oclacitinib-treated dogs. On day 14, the percentage reduction from baseline CADESI-02 was significantly greater in the oclacitinib group (58.7%) than in the ciclosporin group (43.0%). Three times as many adverse events attributed to gastrointestinal signs were reported in the ciclosporin group compared with the oclacitinib group.Conclusions and clinical importanceIn this study of treatment for canine AD, oclacitinib had a faster onset of action and a lower frequency of gastrointestinal side effects compared with ciclosporin.
| S-EPMC4365754 | biostudies-literature
Project description:Arthritis, including osteoarthritis (OA) and other musculoskeletal-associated pain, is a worldwide problem, however, effective drug options are limited. Several receptors, neurotransmitters, and endogenous mediators have been identified in rodent models, but the relevance of these molecules in disease-associated pain is not always clear. Artemin, a neurotrophic factor, and its receptor, glial-derived neurotrophic factor (GDNF) family receptor alpha-3 (GFR?3), have been identified as involved in pain in rodents. Their role in OA-associated pain is unknown. To explore a possible association, we analyzed tissue from naturally occurring OA in dogs to characterize the correlation with chronic pain. We used behavioral assessment, objective measures of limb use, and molecular tools to identify whether artemin and GFR?3 might be associated with OA pain. Our results using banked tissue from well-phenotyped dogs indicates that artemin/GFR?3 may play an important, and hitherto unrecognized, role in chronic OA-associated pain. Elevated serum levels of artemin from osteoarthritic humans compared to healthy individuals suggest translational relevance. Our data provide compelling evidence that the artemin/GFR?3 signaling pathway may be important in OA pain in both non-humans and humans and may ultimately lead to novel therapeutics.
| S-EPMC7031206 | biostudies-literature
Project description:In periodontitis patients, dysbiosis of the oral microbiota is not only found at clinically diseased periodontal sites but also at clinically healthy periodontal sites, buccal mucosae, tongue, and saliva. The present study evaluated the safety and efficacy of an oral microbiota transplant (OMT) for the treatment of periodontitis in dogs. Eighteen systemically healthy beagle dogs with naturally occurring periodontitis were enrolled in the study and randomly assigned to a test or control group. A 4-y-old, periodontally healthy female beagle dog served as a universal OMT donor. To reduce periodontal inflammation, all dogs received full-mouth mechanical debridement of teeth and mucosae 2 wk before baseline. At baseline, full-mouth mechanical debridement was repeated and followed by adjunctive subgingival and oral irrigation with 0.1% NaOCl. Subsequently, test dogs were inoculated with an OMT from the healthy donor. No daily oral hygiene was performed after OMT transplantation. Adverse events were assessed throughout the observation period. Clinical examinations were performed and whole-mouth oral microbiota samples were collected at week 2, baseline, week 2, and week 12. The composition of oral microbiota samples was analyzed using high-throughput 16S ribosomal RNA gene amplicon sequencing followed by taxonomic assignment and downstream bioinformatic and statistical analyses. Results demonstrated that the intergroup difference in the primary outcome measure, probing pocket depth at week 12, was statistically insignificant. However, the single adjunctive OMT had an additional effect on the oral microbiota composition compared to the full-mouth mechanical and antimicrobial debridement alone. The OMT resulted in an "ecological shift" toward the composition of the donor microbiota, but this was transient in nature and was not observed at week 12. No local or systemic adverse events were observed throughout the study period. The results indicate that OMT may modulate the microbiota composition in dogs with naturally occurring periodontitis and can be applied safely.
| S-EPMC8217902 | biostudies-literature
Project description:RationaleBarriers to developing treatments for human status epilepticus include the inadequacy of experimental animal models. In contrast, naturally occurring canine epilepsy is similar to the human condition and can serve as a platform to translate research from rodents to humans. The objectives of this study were to characterize the pharmacokinetics of an intravenous (IV) dose of topiramate (TPM) in dogs with epilepsy and evaluate its effect on intracranial electroencephalographic (iEEG) features.MethodsFive dogs with naturally occurring epilepsy were used for this study. Three were getting at least one antiseizure drug as maintenance therapy including phenobarbital (PB). Four (ID 1-4) were used for the 10 mg/kg IV TPM + PO TPM study, and three (ID 3-5) were used for the 20 mg/kg IV TPM study. IV TPM was infused over 5 min at both doses. The animals were observed for vomiting, diarrhea, ataxia, and lethargy. Blood samples were collected at scheduled pre- and post-dose times. Plasma concentrations were measured using a validated high-performance liquid chromatography-mass spectrometry method. Non-compartmental and population compartmental modeling were performed (Phoenix WinNonLin and NLME) using plasma concentrations from all dogs in the study. iEEG was acquired in one dog. The difference between averaged iEEG energy levels at 15 min pre- and post-dose was assessed using a Kruskal-Wallis test.ResultsNo adverse events were noted. TPM concentration-time profiles were best fit by a two compartment model. PB co-administration was associated with a 5.6-fold greater clearance and a ~4-fold shorter elimination half-life. iEEG data showed that TPM produced a significant energy increase at frequencies >4 Hz across all 16 electrodes within 15 min of dosing. Simulations suggested that dogs on an enzyme inducer would require 25 mg/kg, while dogs on non-inducing drugs would need 20 mg/kg to attain the target concentration (20-30 μg/mL) at 30 min post-dose.ConclusionThis study shows that IV TPM has a relatively rapid onset of action, loading doses appear safe, and the presence of PB necessitates a higher dose to attain targeted concentrations. Consequently, it is a good candidate for further evaluation for treatment of seizure emergencies in dogs and people.
| S-EPMC5136567 | biostudies-literature