What question are we trying to answer? Embracing causal inference.

This study summarizes a presentation at the symposium for the Calvin Schwabe Award for Lifetime Achievement in Veterinary Epidemiology and Preventive Medicine, which was awarded to the first author. As epidemiologists, we are taught that "correlation does not imply causation." While true, identifying causes is a key objective for much of the research that we conduct. There is empirical evidence that veterinary epidemiologists are conducting observational research with the intent to identify causes; many studies include control for confounding variables, and causal language is often used when interpreting study results. Frameworks for studying causes include the articulation of specific hypotheses to be tested, approaches for the selection of variables, methods for statistical estimation of the relationship between the exposure and the outcome, and interpretation of that relationship as causal. When comparing observational studies in veterinary populations to those conducted in human populations, the application of each of these steps differs substantially. The a priori identification of exposure-outcome pairs of interest are less common in observational studies in the veterinary literature compared to the human literature, and prior knowledge is used to select confounding variables in most observational studies in human populations, whereas data-driven approaches are the norm in veterinary populations. The consequences of not having a defined exposure-outcome hypotheses of interest and using data-driven analytical approaches include an increased probability of biased results and poor replicability of results. A discussion by the community of researchers on current approaches to studying causes in observational studies in veterinary populations is warranted.

How can we achieve more accurate reporting of average dog lifespan?

Despite major advances in our understanding of dogs as a biological system (including genetics/epigenetics, physiology, cognition, and behavior), the veterinary field lacks consensus around a critical piece of information: namely, the average lifespan/life expectancy of a domestic dog. This deficiency is due in part to unavailable and/or inconsistent collection of dog mortality data. In an effort to review historical and current reports of dog lifespan to determine whether the domestic dog's lifespan has changed over time, we found that incongruous data were prohibitive to conducting a formal meta-analysis of dog lifespan reports. However, in examining several different kinds of dog aging and mortality studies covering a span of about 40 years (1981 to 2023), it seems apparent that the median lifespan of domesticated dogs has not recently decreased, as has been reported in the popular press, but rather has increased steadily over that time frame. Still, assessing the validity of these numbers is a challenge, as methodology, cohort, and covariates (such as weight, breed, etc) vary from study to study. We therefore recommend the adoption of a comprehensive, standardized method for reporting and recording dog mortality so that a more accurate understanding of dogs' average lifespan can be obtained in the future.

Canine sentinels and our shared exposome.

Dogs are distinctly positioned to be indicators of human health and well-being.

Factors associated with behavioral euthanasia in pet dogs.

When pet dogs demonstrate certain serious problem behaviors, this may lead owners to choose behavioral euthanasia. However, research on behavioral euthanasia of pet dogs is sparse and previously published papers have not specifically sampled owners who made the decision to euthanize for behavior. The Behavioral Euthanasia in Pet Dogs Questionnaire was created to collect a wide range of information from dog owners who made behavioral euthanasia decisions. Using this survey, we explored the types of behaviors associated with behavioral euthanasia. Human-directed aggression, especially toward adults living in the household, was the most frequently reported reason for choosing behavioral euthanasia; followed by aggression toward other animals, especially other dogs living in the same household. The majority of dogs displaying human-directed or other animal-directed aggression were reported to have bitten and broken skin, and many of these had bitten in multiple or severe incidents. Most dogs had lived in their homes and displayed problem behaviors for over a year prior to behavioral euthanasia, and the euthanasia occurred at a variety of ages, from less than 1 year old to 18 years old. Additional research is required to understand environmental or nonbehavioral factors contributing to the behavioral euthanasia of companion animals, as well as the psychosocial and emotional impact of behavioral euthanasia on the human experience. Understanding the behavioral factors associated with behavioral euthanasia can direct resources toward problem behavior interventions, improve public education about animal behavior, and strengthen the human-animal bond.

Validation of the shortened version of the Canine Behavioral Assessment and Research Questionnaire (C-BARQ) using participants from the Dog Aging Project.

The Canine Behavioral Assessment and Research Questionnaire (C-BARQ) is a 100-item owner-completed survey instrument used for assessing behavior and temperament of companion dogs. The shortened version of the C-BARQ (C-BARQ(S)) consists of 42 items of the long C-BARQ. We aimed to validate the shortened C-BARQ(S) by comparing it with the long questionnaire in the same human-dog pair. We examined data from a nationwide cohort of companion dogs enrolled in the large-scale longitudinal Dog Aging Project (DAP) study. Among 435 participating owners who completed both the long and shortened versions of the C-BARQ within 60 days of each other, agreement between individual questions of the long and shortened C-BARQ using an unweighted kappa statistic and percent agreement was examined. Associations between the two questionnaires for mean behavior and temperament domain scores and mean miscellaneous category scores were assessed using Pearson correlation coefficients. Of 435 dogs in the study, the mean (SD) age was 7.3 (4.3) years and 216 (50%) were female. Kappa values between the long and shortened C-BARQ for individual questions within the 14 behavior and temperament domains and a miscellaneous category ranged from fair to moderate (0.23 to 0.40 for 21 items and 0.41 to 0.58 for 26 items, respectively). Pearson correlation coefficients above 0.60 between both questionnaires for 12 of the 14 mean behavior and temperament domain scores and a category of miscellaneous items were observed. Kappa values for individual questions between the long and shortened C-BARQ ranged from fair to moderate and correlations between mean domain scores ranged from moderate to strong.

Analysis of 2,570 responses to Dog Aging Project End of Life Survey demonstrates that euthanasia is associated with cause of death but not age.

OBJECTIVE: The Dog Aging Project End of Life Survey was used to evaluate factors associated with manner of death (euthanasia vs unassisted death), including cause of death (CoD), reason for euthanasia (RFE) if performed, medical symptoms, old age characteristics, and perimortem quality of life (QoL). SAMPLE: Responses collected between the End of Life Survey launch (January 20, 2021) through December 31, 2021, from 2,570 participants whose dogs died. METHODS: Response frequencies were described. Associations between manner of death and medical symptoms or old age characteristics were evaluated using logistic regression. Factors associated with RFE were evaluated using multinomial regression. The effects of CoD, age at death, and QoL on the frequency of euthanasia as the manner of death were evaluated using multivariate logistic regression. RESULTS: 2,195 (85.4%) dogs were euthanized, and 375 (14.6%) experienced unassisted death. The most frequent owner-reported CoD was illness/disease (n = 1,495 [58.1%]). The most frequently reported RFE was pain/suffering (n = 1,080 [49.2% of those euthanized]). As age increased, RFE was more likely to be "poor QoL" than any other response. In a multivariate regression including CoD, chronologic age, and QoL, euthanasia as the manner of death was not significantly associated with age. CLINICAL RELEVANCE: Euthanasia was a common manner of death for dogs in the US. Compared with unassisted death, euthanasia was associated with CoD illness/disease, lower QoL scores, and the presence and number of medical symptoms and old age characteristics. Understanding factors associated with manner of death is important to veterinarians who care for dogs at the end of life.

"Sometimes I just forget them": capturing experiences of women about free menstrual products in a U.S. based public university campus.

BACKGROUND: Studies have proven that lack of access to menstruation products negatively affects school attendance, academic performance, and individual health. Implementing "period policies," or programs offering free menstruation products, are becoming popular in schools, businesses, and communities in high-income countries. U.S.-based Purdue University announced in February 2020 that free pads and tampons would be stocked in all women's and gender-neutral restrooms in campus buildings. This study aimed to capture the experiences of menstruators about free menstrual products and the impact of a university-wide free menstruation management product policy and program. A second purpose was to understand how access to menstrual management products is intertwined with broader socio-cultural experiences of a menstruator. METHODS: As part of a larger study, virtual focus group discussions (n = 32 across 5 focus groups) were conducted in February 2021. Eligible participants were student-menstruators attending Purdue University. We used thematic analysis techniques for data analysis, allowing for a constant comparative approach to data contextualization and theme identification. RESULTS: Focus group discussions revealed vivid menarche and menstruation experiences, shifting period culture, recollections of shame and stigma, and use of various technologies to manage menstruation. Recommendations for community-based programs offering free products included maintaining stock, making informed product choices, and broadly distributing program information to increase awareness of free product placements. CONCLUSIONS: Findings offer practical recommendations that will contribute to menstruation management and period poverty solutions for university communities.

A review of frailty instruments in human medicine and proposal of a frailty instrument for dogs.

Over the last few decades, frailty has become a pillar of research and clinical assessment in human gerontology. This complex syndrome, characterized by loss of physiologic reserves leading to decreased resilience to stressors, is of critical importance because it predicts higher risks of poor health outcomes, including mortality. Thus, identifying frailty among the elderly human population has become a key focus of gerontology. This narrative review presents current scientific literature on frailty in both humans and animals. The authors discuss the need for an accessible frailty instrument for companion dogs suitable for general use in veterinary medicine and the advances that would be facilitated by this instrument. A phenotypic frailty instrument for companion dogs, utilizing components that are easily collected by owners, or in the general practice setting, is proposed. The authors elaborate on the domains (physical condition, physical activity, mobility, strength, cognitive task performance, and social behavior), factors that will be included, and the data from the Dog Aging Project that inform each domain.

Social determinants of health and disease in companion dogs: a cohort study from the Dog Aging Project.

Exposure to social environmental adversity is associated with health and survival across many social species, including humans. However, little is known about how these health and mortality effects vary across the lifespan and may be differentially impacted by various components of the environment. Here, we leveraged a relatively new and powerful model for human aging, the companion dog, to investigate which components of the social environment are associated with dog health and how these associations vary across the lifespan. We drew on comprehensive survey data collected on 21,410 dogs from the Dog Aging Project and identified five factors that together explained 33.7% of the variation in a dog's social environment. Factors capturing financial and household adversity were associated with poorer health and lower physical mobility in companion dogs, while factors that captured social support, such as living with other dogs, were associated with better health when controlling for dog age and weight. Notably, the effects of each environmental component were not equal: the effect of social support was 5× stronger than financial factors. The strength of these associations depended on the age of the dog, including a stronger relationship between the owner's age and the dog's health in younger as compared to older dogs. Taken together, these findings suggest the importance of income, stability and owner's age on owner-reported health outcomes in companion dogs and point to potential behavioral and/or environmental modifiers that can be used to promote healthy aging across species.

Approaches Used to Construct Antibiograms for Dogs in a Veterinary Teaching Hospital in the United States.

Non-judicious antimicrobial use (AMU) is a major driver of antimicrobial resistance (AMR). In human hospitals, cumulative antibiograms are often used by clinicians to evaluate local susceptibility rates and to select the most appropriate empiric therapy with the aim of minimizing inappropriate AMU. However, the use of cumulative antibiograms to guide empiric antimicrobial therapy in veterinary hospitals in the United States is limited, and there are no specific guidelines or standardized methods available for the construction of antibiograms in veterinary clinical settings. The objective of this methods article is to describe the approaches that were used to construct antibiograms from clinical samples collected from dogs seen at a veterinary teaching hospital. Laboratory data for 563 dogs for the period from 1 January 2015 to 31 December 2015 was utilized. We used the Clinical and Laboratory Standards Institute (CLSI) guidelines for use in the construction of the antibiograms in human healthcare settings as the basis for the veterinary antibiograms. One general antibiogram and antibiograms stratified by hospital section, the anatomic region of sample collection/by sample type, were created and the challenges encountered in preparing these antibiograms were highlighted. The approaches described could be useful in guiding veterinary antibiogram development for empiric therapy.

Predicting health outcomes in dogs using insurance claims data.

In this paper we propose a machine learning-based approach to predict a multitude of insurance claim categories related to canine diseases. We introduce several machine learning approaches that are evaluated on a pet insurance dataset consisting of 785,565 dogs from the US and Canada whose insurance claims have been recorded over 17 years. 270,203 dogs with a long insurance tenure were used to train a model while the inference is applicable to all dogs in the dataset. Through this analysis we demonstrate that with this richness of data, supported by the right feature engineering, and machine learning approaches, 45 disease categories can be predicted with high accuracy.

Age at gonadectomy, sex, and breed size affect risk of canine overweight and obese outcomes: a retrospective cohort study using data from United States primary care veterinary clinics.

OBJECTIVE: To examine the risk of developing an overweight or obese (O/O) body condition score (BCS) in gonadectomized versus intact dogs and, separately, the impact of age at gonadectomy on O/O outcomes among sterilized dogs. ANIMALS: Dogs were patients of Banfield Pet Hospital in the US from 2013 to 2019. After exclusion criteria were applied, the final sample consisted of 155,199 dogs. PROCEDURES: In this retrospective cohort study, Cox proportional hazards models evaluated associations between O/O and gonadectomy status, sex, age at gonadectomy, and breed size. Models were used to estimate the risk of becoming O/O in gonadectomized versus intact dogs and, separately, to estimate risk of O/O BCS according to age at surgery among gonadectomized dogs. RESULTS: Gonadectomy increased O/O risk for most dogs compared to intact dogs. Unlike most prior findings, O/O hazard ratios among gonadectomized versus intact dogs were larger for males than females. O/O risk varied according to breed size but not linearly. Sterilizing at 1 year old tended to yield a lower O/O risk compared to doing so later. Comparative O/O risk among dogs gonadectomized at 6 months versus 1 year varied by breed size. Overall patterns for obesity related to size were similar to patterns in the O/O analysis. CLINICAL RELEVANCE: Veterinarians are uniquely positioned to help prevent O/O in their patients. Results extend understanding of risk factors for O/O development in dogs. In combination with information about other benefits and risks associated with gonadectomy, these data can help tailor recommendations regarding gonadectomy in individual dogs.

Development and validation of a novel instrument to capture companion dog mortality data: the Dog Aging Project End of Life Survey.

OBJECTIVE: The researchers and clinicians within the Dog Aging Project (DAP), a longitudinal cohort study of aging in companion dogs, created and validated a novel survey instrument titled the End of Life Survey (EOLS) to gather owner-reported mortality data about companion dogs. SAMPLE: Bereaved dog owners who participated in the refinement, face validity assessment, or reliability assessment of the EOLS (n = 42) and/or completed the entire survey between January 20 and March 24, 2021 (646). PROCEDURES: The EOLS was created and modified by veterinary health professionals and human gerontology experts using published literature, clinical veterinary experience, previously created DAP surveys, and feedback from a pilot study conducted with bereaved dog owners. The EOLS was subjected to qualitative validation methods and post hoc free-text analysis to evaluate its ability to thoroughly capture scientifically relevant aspects of companion dogs' deaths. RESULTS: The EOLS was well received with excellent face validity as assessed by dog owners and experts. The EOLS had fair to substantial reliability for the 3 validation themes-cause of death (κ = 0.73; 95% CI, 0.5 to 0.95), perimortem quality of life (κ = 0.49; 95% CI, 0.26 to 0.73), and reason for euthanasia (κ = 0.3; 95% CI, 0.08 to 0.52)-and had no need for any substantial content alterations based on free-text analysis. CLINICAL RELEVANCE: The EOLS has proven to be a well-accepted, comprehensive, and valid instrument for capturing owner-reported companion dog mortality data and has the potential to enhance veterinarians' ability to care for the aging dog population by illuminating their understanding of companion dogs' end-of-life experiences.

The standards of reporting randomized trials in pets (PetSORT): Methods and development processes.

Background: Reporting of clinical trials conducted in client- and shelter-owned dog and cat populations is not optimal, which inhibits the ability to assess the reliability and validity of trial findings and precludes the ability to include some trials in evidence synthesis. Objective: To develop a reporting guideline for parallel group and crossover trials that addresses the unique features and reporting requirements for trials conducted in client- and shelter-owned dog and cat populations. Design: Consensus statement. Setting: Virtual. Participants: Fifty-six experts from North America, the United Kingdom, Europe, and Australia working in academia, government (research and regulatory agencies), industry, and clinical veterinary practice. Methods: A steering committee created a draft checklist for reporting criteria based upon the CONSORT statement and the CONSORT extensions for reporting of abstracts and crossover trials. Each item was presented to the expert participants and was modified and presented again until >85% of participants were in agreement about the inclusion and wording of each item in the checklist. Results: The final PetSORT checklist consists of 25 main items with several sub-items. Most items were modifications of items contained in the CONSORT 2010 checklist or the CONSORT extension for crossover trials, but 1 sub-item pertaining to euthanasia was created de novo. Conclusion: The methods and processes used to develop this guideline represent a novel departure from those used to create other reporting guidelines, by using a virtual format. The use of the PetSORT statement should improve reporting of trials conducted in client- and shelter-owned dogs and cats and published in the veterinary research literature.

The standards of reporting trials in pets (PetSORT): Explanation and elaboration.

Well-designed randomized controlled trials (RCTs) provide the best evidence of the primary research designs for evaluating the effectiveness of interventions. However, if RCTs are incompletely reported, the methodological rigor with which they were conducted cannot be reliably evaluated and it may not be possible to replicate the intervention. Missing information also may limit the reader's ability to evaluate the external validity of a trial. Reporting guidelines are available for clinical trials in human healthcare (CONSORT), livestock populations (REFLECT), and preclinical experimental research involving animals (ARRIVE 2.0). The PetSORT guidelines complement these existing guidelines, providing recommendations for reporting controlled trials in pet dogs and cats. The rationale and scientific background are explained for each of the 25 items in the PetSORT reporting recommendations checklist, with examples from well-reported trials.

Development and Validation of a Novel Instrument to Capture Companion Dog Mortality Data: The Dog Aging Project End of Life Survey.

Objective: The researchers and clinicians within the Dog Aging Project (DAP), a longitudinal cohort study of aging in companion dogs, created and validated a novel survey instrument titled the End of Life Survey (EOLS) to gather owner-reported mortality data about companion dogs. Sample: Bereaved dog owners who participated in the refinement, face validity assessment, or reliability assessment of the EOLS (n=42) and/or completed the entire survey between January 20 and March 24, 2021 (n=646). Procedures: The EOLS was created and modified by veterinary health professionals and human gerontology experts using published literature, clinical veterinary experience, previously created DAP surveys, and feedback from a pilot study conducted with bereaved dog owners. The EOLS was subjected to qualitative validation methods and post-hoc free-text analysis to evaluate its ability to thoroughly capture scientifically relevant aspects of companion dogs' death. Results: The EOLS was well-received with excellent face validity as assessed by dog owners and experts. The EOLS had fair to substantial reliability for the three validation themes: cause of death (kappa = 0.73; 95% CI [0.5-0.95]), perimortem quality of life (kappa = 0.49; 95% CI [0.26-0.73]), and reason for euthanasia (kappa = 0.3; 95% CI [0.08-0.52]) and had no need for any substantial content alterations based on free-text analysis. Clinical Relevance: The EOLS has proven to be a well-accepted, comprehensive, and valid instrument for capturing owner-reported companion dog mortality data and has the potential to enhance veterinarians' ability to care for the aging dog population by illuminating their understanding of companion dogs' end-of-life experiences.

Antimicrobial Susceptibility of Bacteria Isolated from Freshwater Mussels in the Wildcat Creek Watershed, Indiana, United States.

Antimicrobial resistance (AMR) is a global health crisis that threatens the health of humans and animals. The spread of resistance among species may occur through our shared environment. Prevention of AMR requires integrated monitoring systems, and these systems must account for the presence of AMR in the environment in order to be effective. The purpose of this study was to establish and pilot a set of procedures for utilizing freshwater mussels as a means of surveillance for microbes with AMR in Indiana waterways. One hundred and eighty freshwater mussels were sampled from three sites along the Wildcat Creek watershed in north-central Indiana. Specimens were evaluated for the presence of ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species), Escherichia coli, Campylobacter, and Salmonella species, and the isolates were tested for antimicrobial resistance. A total of 24 bacterial isolates were obtained from tissue homogenates of freshwater mussels collected at a site directly downstream from Kokomo, Indiana. Of these, 17 were Enterobacter spp., five were Escherichia coli, one was Pseudomonas aeruginosa, and one was Klebsiella pneumoniae. All isolates were resistant to three or more antimicrobial drug classes. Further work is necessary to determine the source of the bacterial species found in the mussels.

Serum thymidine kinase 1 activity as a prognostic biomarker in dogs with chemotherapy-treated diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is frequently treated with chemotherapy incorporating cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP), which induces remission in 80% to 95% of cases. However, not all dogs derive meaningful benefit from CHOP, and prognostic factors for dogs with DLBCL are poorly defined. Serum thymidine kinase 1 (TK1) activity, a marker of tumour cell proliferation, has shown promising initial results as a prognostic biomarker in dogs with multicentric lymphomas. The purpose of this study was to determine if baseline serum TK1 activity is associated with clinical outcome in dogs with CHOP-treated DLBCL. Baseline serum TK1 activity was measured in banked sera from 98 dogs with CHOP-treated DLBCL using a commercially available ELISA kit. Data on other potential prognostic factors were abstracted retrospectively from electronic medical records. Multivariable statistical methods were used to identify associations between TK1 and other potential prognostic factors with progression-free survival (PFS) and attainment of complete remission. TK1 activity at baseline was not associated with PFS (p = .299) or attainment of complete remission (p = .910) following CHOP chemotherapy. Of the other prognostic factors analysed, only purebred (vs. mixed breed) status (HR 8.81, 95% CI 1.68-46.30, p = .010), attainment of complete (vs. partial) remission (HR 0.09, 95% CI 0.02-0.49, p = .006), and baseline serum C-reactive protein concentration (HR 1.19, 95% CI 1.07-1.32, p = .001) were independently associated with PFS. Based on these findings, baseline serum TK1 activity does not appear to be a useful prognostic biomarker in dogs with CHOP-treated DLBCL.

Evaluation of Surgical Gown Cuff Contamination During Orthopaedic Surgery in a Veterinary Teaching Hospital.

OBJECTIVE: The objective of this study was to determine the frequency of positive cultures of the surgical gown cuffs among scrubbed personnel prior to and immediately after orthopaedic surgical procedures performed on client-owned dogs. STUDY DESIGN: In this cross-sectional study, the left and right surgical gown cuffs of three scrubbed persons in 10 orthopaedic surgical procedures were individually sampled using a sterile wipe prior to and immediately after surgery in order to determine the frequency of and risk factors associated with positive bacterial cultures. RESULTS: Fifty of 120 (41.6%) cultures were positive with an even distribution before and after surgery. The three most common genera were Staphylococcus, Corynebacterium and Streptococcus. Using multivariable logistic regression models, humidity in the operating room (odds ratio: 1.04, 95% confidence interval: 1.00-1.08; p = 0.038) and the number of individuals scrubbed into surgery (odds ratio: 0.59, 95% confidence interval: 0.39-0.91; p = 0.016) had a significant effect on the likelihood of positive culture after surgery. Of the nine patients available for follow-up, one dog developed osteomyelitis. CONCLUSIONS: Maintaining the humidity in the operating room to the lowest comfortable level may reduce contamination of the surgical gown cuffs. Confirmation of bacterial contamination of surgical gown cuffs warrants adherence to operative guidelines to minimize the risk of surgical gown cuffs' contact with sterile attire, equipment and the surgical field during surgical procedures.

Identification of a naturally-occurring canine model for early detection and intervention research in high grade urothelial carcinoma.

Background: Early detection and intervention research is expected to improve the outcomes for patients with high grade muscle invasive urothelial carcinoma (InvUC). With limited patients in suitable high-risk study cohorts, relevant animal model research is critical. Experimental animal models often fail to adequately represent human cancer. The purpose of this study was to determine the suitability of dogs with high breed-associated risk for naturally-occurring InvUC to serve as relevant models for early detection and intervention research. The feasibility of screening and early intervention, and similarities and differences between canine and human tumors, and early and later canine tumors were determined. Methods: STs (n=120) ≥ 6 years old with no outward evidence of urinary disease were screened at 6-month intervals for 3 years with physical exam, ultrasonography, and urinalysis with sediment exam. Cystoscopic biopsy was performed in dogs with positive screening tests. The pathological, clinical, and molecular characteristics of the "early" cancer detected by screening were determined. Transcriptomic signatures were compared between the early tumors and published findings in human InvUC, and to more advanced "later" canine tumors from STs who had the typical presentation of hematuria and urinary dysfunction. An early intervention trial of an oral cyclooxygenase inhibitor, deracoxib, was conducted in dogs with cancer detected through screening. Results: Biopsy-confirmed bladder cancer was detected in 32 (27%) of 120 STs including InvUC (n=29, three starting as dysplasia), grade 1 noninvasive cancer (n=2), and carcinoma in situ (n=1). Transcriptomic signatures including druggable targets such as EGFR and the PI3K-AKT-mTOR pathway, were very similar between canine and human InvUC, especially within luminal and basal molecular subtypes. Marked transcriptomic differences were noted between early and later canine tumors, particularly within luminal subtype tumors. The deracoxib remission rate (42% CR+PR) compared very favorably to that with single-agent cyclooxygenase inhibitors in more advanced canine InvUC (17-25%), supporting the value of early intervention. Conclusions: The study defined a novel naturally-occurring animal model to complement experimental models for early detection and intervention research in InvUC. Research incorporating the canine model is expected to lead to improved outcomes for humans, as well as pet dogs, facing bladder cancer.