Comparative pharmacokinetics of phenylbutazone in healthy young-adult and geriatric horses.

OBJECTIVE: To evaluate the effects of aging on phenylbutazone (PBZ) disposition in older horses (≥ 25 years old) compared to young adults (4 to 10 years old) by characterizing the pharmacokinetic profile of PBZ and its active metabolite, oxyphenbutazone (OPBZ), following a 2.2-mg/kg dose, IV. We hypothesized that the disposition of PBZ will be affected by age. ANIMALS: 16 healthy horses (8 young adults aged 4 to 10 years and 8 geriatric horses ≥ 25 years old). METHODS: Horses were administered a single 2.2-mg/kg PBZ dose, IV. Plasma samples were collected at designated time points and frozen at -80 °C until assayed using liquid chromatography-tandem mass spectrometry. Pharmacokinetic analyses were performed using Phoenix WinNonlin, version 8.0 (Certara). Both clinical and pharmacokinetic data were compared between age groups using independent samples t tests, with P < .05 considered significant. RESULTS: Baseline characteristics did not differ between groups, with the exception of age, weight, and plasma total solids. Plasma concentrations of PBZ were best described by a two-compartment model. The maximum plasma concentration of OPBZ was reached at 5 hours for both age groups, and the metabolite-to-parent-drug area-under-the-curve ratios were approximately 20% for both groups. None of the pharmacokinetic parameters of PBZ or its metabolite, OPBZ, differed significantly between age groups. CLINICAL RELEVANCE: The hypothesis was rejected as there was no significant difference in PBZ disposition in young-adult horses compared to geriatric horses. Our data do not support the need for dose adjustments of PBZ in clinically healthy geriatric horses.

Comparative evaluation of clinical findings and prognostic outcome parameters in hospitalized, critically ill neonatal foals and crias.

OBJECTIVE: Species-related differences in the prevalence, manifestation, and outcome of neonatal illness may impact management practices of neonatal intensive care. The study aimed to elucidate similarities between disease manifestations and mortality risks of critically ill (CI) neonatal crias and foals admitted to the same referral center. DESIGN: A comparative, retrospective cohort evaluation of two species (camelid and equine). SETTING: The study was conducted in a University hospital. ANIMALS: Two hundred and forty-six CI neonatal crias (January 1999 to May 2016) and 356 neonatal foals (February 2001 to May 2016) under 4-week-old were admitted to a university hospital. INTERVENTION: All data are presented descriptively and compared between groups using univariate and multivariate analyses. MEASUREMENTS AND MAIN RESULTS: Female crias (142/246, 57.7%) were significantly overrepresented in comparison to fillies (132/352, 37.5%). Congenital defects and transfer failure of passive immunity were more often observed in neonatal crias, while colic, diarrhea, patent urachus, septic arthritis, and omphalitis were significantly more common in CI foals. Overall survival to discharge (excluding fatal congenital defects) was comparable between crias (174/224; 77.8%) and foals (287/347, 82.1%), while crias (26/48; 54.2%) were more likely than foals (21/60; 35%) to die naturally than undergo euthanasia. Lower respiratory disease and indications for oxygen or IV glucose support increased mortality in the multivariate outcome models of both species. Species-specific adaptations of pediatric diagnostic criteria for sepsis were significantly associated with mortality in the multivariate analysis of patients with complete hematological datasets. However, the diagnosis of systemic inflammatory response syndrome (SIRS) did not retain statistical significance as an independent outcome predictor. CONCLUSIONS: Lower respiratory disease and oxygen or glucose dysregulation increased mortality irrespective of species. However, despite species-specific differences in disease prevalence, the success of intensive care management was comparable.

Assessment of clinical and microbiota responses to fecal microbial transplantation in adult horses with diarrhea.

BACKGROUND AND AIMS: Fecal microbial transplantation (FMT) is empirically implemented in horses with colitis to facilitate resolution of diarrhea. The purpose of this study was to assess FMT as a clinical treatment and modulator of fecal microbiota in hospitalized horses with colitis. METHODS: A total of 22 horses with moderate to severe diarrhea, consistent with a diagnosis of colitis, were enrolled at two referral hospitals (L1: n = 12; L2: n = 10). FMT was performed in all 12 patients on 3 consecutive days at L1, while treatment at L2 consisted of standard care without FMT. Manure was collected once daily for 4 days from the rectum in all colitis horses, prior to FMT for horses at L1, and from each manure sample used for FMT. Fecal samples from 10 clinically healthy control horses housed at L2, and 30 healthy horses located at 5 barns in regional proximity to L1 were also obtained to characterize the regional healthy equine microbiome. All fecal microbiota were analyzed using 16S amplicon sequencing. RESULTS AND CONCLUSIONS: As expected, healthy horses at both locations showed a greater α-diversity and lower ß-diversity compared to horses with colitis. The fecal microbiome of healthy horses clustered by location, with L1 horses showing a higher prevalence of Kiritimatiellaeota. Improved manure consistency (lower diarrhea score) was associated with a greater α-diversity in horses with colitis at both locations (L1: r = -0.385, P = 0.006; L2: r = -0.479, P = 0.002). Fecal transplant recipients demonstrated a greater overall reduction in diarrhea score (median: 4±3 grades), compared to untreated horses (median: 1.5±3 grades, P = 0.021), with a higher incidence in day-over-day improvement in diarrhea (22/36 (61%) vs. 10/28 (36%) instances, P = 0.011). When comparing microbiota of diseased horses at study conclusion to that of healthy controls, FMT-treated horses showed a lower mean UniFrac distance (0.53±0.27) than untreated horses (0.62±0.26, P<0.001), indicating greater normalization of the microbiome in FMT-treated patients.

Assessment of the impact of age and of blood-derived inflammatory markers in horses with colitis.

OBJECTIVES: To determine the impact of age on survival in horses with colitis and to elucidate whether a lower type-1/type-2 cytokine ratio or an exaggerated inflammatory state contribute to reduced survival in aged horses. DESIGN: Part 1: Retrospective cohort analysis. Part 2: Analytic observational study. ANIMALS: Part 1: One hundred twenty-four adult horses with colitis. Part 2: Twenty-nine adult horses with new diarrhea onset while hospitalized. MEASUREMENTS AND MAIN RESULTS: Part 1: Patient signalment, select clinicopathological data, diagnoses, treatment, hospitalization length, and invoice were compared between survivors (n = 101) and nonsurvivors (n = 23). Only age and plasma transfusion retained statistical significance in the final multivariate outcome model, with 8.5 times lower odds of survival in transfused horses (95% confidence interval [CI], 2.6-27.2%). Additionally, the likelihood of nonsurvival increased by 11.8% (95% CI, 4-20.2%) for every year the horse aged (P = 0.002). Similarly, geriatric horses (≥20 years) were 15.2 times more likely to die than young-adults (2-12 years, P = 0.03), independent of financial investment, documented comorbidities, and duration of hospitalization. Part 2: Select cytokine analyses were performed on serum collected from hospitalized horses within 1 hour of diarrhea onset (T0) and 6 hours later. At T0, all recorded clinicopathological variables were comparable between geriatric and young-adult horses, suggesting a similar degree of systemic illness. The median concentration of type-2 cytokines interleukin-4 and interleukin-10, and type-1 cytokine interferon-γ did not differ between age groups. Inflammatory cytokines interleukin-6 and tumor necrosis factor-α were significantly higher in geriatric compared to young-adult horses at both sampling time points. CONCLUSIONS: Outcome of colitis was less favorable in aging horses and patients receiving a plasma transfusion. Although an exaggerated inflammatory state, based on increased interleukin-6 and tumor necrosis factor-α concentrations, in geriatric horses may contribute to reduced survival, a lower type-1/type-2 cytokines ratio was not identified in our geriatric population.

The fecal microbiota of healthy donor horses and geriatric recipients undergoing fecal microbial transplantation for the treatment of diarrhea.

BACKGROUND AND AIMS: Fecal microbial transplantation (FMT), a treatment for certain gastrointestinal conditions associated with dysbiosis in people, is also empirically employed in horses with colitis. This study used microbiota high-throughput sequencing to compare the fecal microbial profile of healthy horses to that of geriatric microbial transplant recipients experiencing diarrhea and tested whether FMT restores microbiota diversity. METHODS: To evaluate the effect of environment and donor characteristics on the intestinal microbiota, fecal samples were collected per rectum from 15 healthy young-adult (2-12 years) and 15 geriatric (≥20 years) horses. Additionally, FMT was performed for 3 consecutive days in 5 geriatric horses with diarrhea using feces from the same healthy donor. Fecal samples were collected from both donor and recipient prior to each FMT and from recipients 24 hours following the last FMT. The profile of the fecal bacterial microbiota was compared using 16S amplicon sequencing. RESULTS AND CONCLUSIONS: In contrast to diet and farm location, age did not significantly affect the healthy equine fecal microbiota, indicating that both healthy geriatric and young-adult horses may serve as FMT donors. The fecal microbiota of horses with diarrhea was significantly more variable in terms of ß-diversity than that of healthy horses. An inverse correlation between diarrhea score and relative abundance of Verrucomicrobia was identified in surviving FMT recipients. At study completion, the fecal microbiota of horses which responded to FMT had a higher α-diversity than prior to treatment and was phylogenetically more similar to that of the donor.

Survey of human-horse relationships and veterinary care for geriatric horses.

OBJECTIVE To assess relationships between horse owners (or lessees) and geriatric or nongeriatric horses and to investigate factors influencing veterinary care decision-making. DESIGN Descriptive, cross-sectional, survey-based study. SAMPLE 2,879 people who owned or leased ≥ 1 horse. PROCEDURES Participants were recruited through social media and online horse forums to participate in an online survey about their horses, including measures of attachment, veterinary care decision-making, and experiences surrounding the death of a horse. Data were collected for primary horses (those respondents interacted with most) and secondary horses. Horses were further categorized as geriatric (≥ 20 years of age) and nongeriatric. RESULTS Geriatric primary horses were considered companion animals, retired, or used as part of a business significantly more frequently, and described as competition horses significantly less frequently, than nongeriatric horses. Geriatric horses were owned or leased significantly longer than nongeriatric horses, but the degree of respondents' attachment did not differ for geriatric versus nongeriatric horses. When respondents reported the death of a horse in the previous year, euthanasia was associated with higher levels of bereavement than death by other means. Death of geriatric horses most commonly followed a chronic illness and was associated with significantly higher levels of bereavement than death of nongeriatric horses. Among factors influencing decisions regarding expensive or long-term medical care, the horse's ability to lead a comfortable life was ranked highest. Respondents with geriatric horses made numerous accommodations for their care. CONCLUSIONS AND CLINICAL RELEVANCE Results provided important initial information about the relationships people have with geriatric horses. Understanding how individuals perceive their horses and how they make decisions regarding complex veterinary care is critical in informing effective client communication.

Use of a multivariable model to estimate the probability of discharge in hospitalized foals that are 7 days of age or less.

OBJECTIVE: To create a mathematical model to assist in early prediction of the probability of discharge in hospitalized foals < or= 7 days old. STUDY DESIGN: Prospective study. ANIMALS: 1,073 foals. PROCEDURES: Medical records from 910 hospitalized foals < or = 7 days old for which outcome was recorded as died or discharged alive were reviewed. Thirty-four variables including historical information, physical examination findings, and laboratory results were examined for association with survival. Variables associated with being discharged alive were entered into a multivariable logistic regression model. Accuracy of the model was validated prospectively on data from 163 foals. RESULTS: Factors in the final model included age group, ability to stand, presence of a suckle reflex, WBC count, serum creatinine concentration, and anion gap. Sensitivity and specificity of the model to predict live discharge were 92% and 74%, respectively, in the retrospective population and 90% and 46%, respectively, in the prospective population. Accuracy of an equine clinician's initial prediction of the foal being discharged alive was 83%, and accuracy of the model's prediction was 81%. Combining the clinician's prediction of probability of live discharge with that of the model significantly increased (median increase, 12%) the accuracy of the prediction for foals that were discharged and nonsignificantly decreased (median decrease, 9%) the accuracy of the predication for nonsurvivors. CONCLUSIONS AND CLINICAL RELEVANCE: Combining the clinician's initial predication of the probability of a foal being discharged alive with that of the model appeared to provide a more precise early estimate of the probability of live discharge for hospitalized foals.

Demographic and clinical characteristics of geriatric horses: 467 cases (1989-1999).

OBJECTIVE: To describe the demographic and clinical characteristics of a population of geriatric horses. DESIGN: Retrospective study. ANIMALS: 467 horses that were > or = 20 years of age. PROCEDURE: Medical records of 539 geriatric horses that were evaluated at a university large animal hospital between 1989 and 1999 were reviewed. Data collected included signalment, reason for evaluation, specific diagnoses, surgical procedures, inpatient or outpatient care, duration of hospitalization, and outcome. RESULTS: 467 horses met the criteria for inclusion in the study. Horses that were > or = 20 years of age comprised 2.2 and 12.5% of horses evaluated during 1989 and 1999, respectively. Pony breeds were significantly overrepresented in the > or = 30-years-of-age group. Gastrointestinal tract, musculoskeletal, and respiratory tract problems were most frequently reported. Colic was the most common clinical sign, followed by lameness. Diagnoses made most frequently included pituitary dysfunction, strangulating lipoma of the small intestine, laminitis, heaves, large colon impaction, and gastric ulcers. Pituitary dysfunction was significantly more prevalent in horses that were > 30 years of age. Laminitis was significantly associated with the presence of pituitary dysfunction. CONCLUSIONS AND CLINICAL RELEVANCE: It was difficult to assess association of age with illnesses identified in these horses. Demographic data and information regarding common diseases of horses that are > or = 20 years of age are limited but will become increasingly important as this geriatric population increases.

Assessment of clinical characteristics, management practices, and activities of geriatric horses.

OBJECTIVE: To describe the demographic and clinical characteristics, management practices, and owner perception of a population of geriatric horses, and to compare these data with findings in a group of younger horses. DESIGN: Original study. ANIMALS: 218 horses. PROCEDURE: Data were collected via a survey tool from owners of 165 horses that were > or = 20 years of age and 53 horses that were < 20 years of age. RESULTS: Compared with young horses, the geriatric group included a significantly greater number of ponies; geriatric horses were also more likely to have a history of colic, dental disease, tumors, lameness, and pituitary disease, but not laminitis, diarrhea, allergies, respiratory tract disease, thyroid disease, or fractures. Horses that had participated in Western equestrian disciplines were more likely to have a history of lameness. Among old horses, those with pituitary dysfunction were more likely to have a history of laminitis than those without pituitary dysfunction. Geriatric horses were more likely to have long hair and shedding abnormalities than were younger horses. Owners perceived their horses as old at approximately 22 years of age. In horses older than 16.5 years of age, age was a negative factor in the purchase of horses. CONCLUSIONS AND CLINICAL RELEVANCE: Geriatric and young horses share some similar health problems, but old horses have distinct health problems and veterinary medical requirements. The management and athletic history of horses may influence health as they age.

Bacterial meningitis and brain abscesses secondary to infectious disease processes involving the head in horses: seven cases (1980-2001).

OBJECTIVE: To determine clinical features of horses with bacterial meningitis or brain abscesses secondary to infectious disease processes involving the head. DESIGN: Retrospective study. ANIMALS: 7 adult horses. PROCEDURE: Medical records of Tufts University, the University of Pennsylvania, and the Livestock Disease Diagnostic Center (Lexington, Ky) were reviewed to identify adult (> 12 months old) horses in which a postmortem diagnosis of bacterial meningitis or brain abscess had been made. Horses were included in the study if an intracranial infection was confirmed, the horse had a primary infectious disease process involving the head, and there were no signs of systemic infection. RESULTS: 23 adult horses with bacterial meningitis or a brain abscess were examined during the study period, but only 7 met the criteria for inclusion in the study. Primary sites of infection included the paranasal sinuses, nasal cavity, periocular tissues, and submandibular lymph nodes. Three horses died suddenly prior to hospitalization, and 1 horse was hospitalized but died 7 days after the onset of neurologic abnormalities. The remaining 3 horses were euthanatized because of a rapid deterioration in clinical status. CONCLUSIONS AND CLINICAL RELEVANCE: Although rare, fatal intracranial complications can develop in horses with infectious diseases involving the head.

Acute recumbency associated with Anaplasma phagocytophilum infection in a horse.

An 11-year-old Hanoverian-cross gelding was evaluated because of acute onset of ataxia, recumbency, and fever. At the stable, this and other horses had recently been infested with ticks. Results of analysis of a sample of CSF were within reference limits, but hematologic abnormalities included lymphopenia, thrombocytopenia, mild anemia, and intracytoplasmic inclusion bodies in neutrophils that were consistent with Anaplasma phagocytophilum (previously Ehrlichia equi). Results of serum biochemical analyses were characteristic of infection and included high, unconjugated bilirubin concentration. Other common causes of recumbency in horses, such as equine protozoal myeloencephalitis, infection with eastern or western equine encephalitis viruses and equine herpesvirus-1, West Nile viral encephalitis, trauma, and metabolic disease, were ruled out. The horse responded quickly to i.v. administration of oxytetracycline and recovered fully within 6 days.

Demographics of health and disease in the geriatric horse.

Owners of older horses have generally owned them for a long time. They have developed a bond that is similar to that seen with companion animals. Their desire to have their animal(s) age gracefully with comfort and mobility has stirred research in the field of equine geriatric medicine. Equine geriatric medicine is to the first decade of the twenty-first century as neonatal medicine was to the 1980s. Hopefully, the demographics discussed in this article highlight area where research can be most helpful.