Efficacy of antimicrobial and nutraceutical treatment for canine acute diarrhoea: A systematic review and meta-analysis for European Network for Optimization of Antimicrobial Therapy (ENOVAT) guidelines.

Systemic antimicrobial treatments are commonly prescribed to dogs with acute diarrhoea, while nutraceuticals (prebiotics, probiotics, and synbiotics) are frequently administered as an alternative treatment. The aim of this systematic review and meta-analysis was to assess the effectiveness of antimicrobials and nutraceutical preparations for treatment of canine acute diarrhoea (CAD). The results of this study will be used to create evidence-based treatment guidelines. PICOs (population, intervention, comparator, and outcome) were generated by a multidisciplinary expert panel taking into account opinions from stakeholders (general practitioners and dog owners). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to evaluate the certainty of the evidence. The systematic search yielded six randomised controlled trials (RCT) for antimicrobial treatment and six RCTs for nutraceutical treatment meeting the eligibility criteria. Categories of disease severity (mild, moderate, and severe) were created based on the presence of systemic signs and response to fluid therapy. Outcomes included duration of diarrhoea, duration of hospitalization, progression of disease, mortality, and adverse effects. High certainty evidence showed that antimicrobial treatment did not have a clinically relevant effect on any outcome in dogs with mild or moderate disease. Certainty of evidence was low for dogs with severe disease. Nutraceutical products did not show a clinically significant effect in shortening the duration of diarrhoea (based on very low to moderate certainty evidence). No adverse effects were reported in any of the studies.

Exploration of body weight in 115 000 young adult dogs of 72 breeds.

High body weight (BW), due to large size or excess body fat, has been associated with developmental and metabolic alterations, and degenerative diseases in dogs. Study objectives were to determine mean BW in young adult dogs of different breeds, including changes over a 10-year period. Body weight data from the official Swedish hip dysplasia screening program were used, including data from dogs screened at 1-2.5 years of age, in breeds with ≥ 15 individual observations/year during 2007-2016. Mean BW per breed and sex was established from 114 568 dogs representing 72 breeds. Estimates of breed BW showed significant change in 33 (45%) breeds over the 10-year period. Body weight increased in five breeds (2-14% change) and decreased in 26 breeds (1-8% change). In two breeds, BW increased in male and decreased in female dogs. This observational study provides extensive breed BW data on young adult dogs. The change in breed BW, noted in almost half of the breeds, could be due to changes either in size or in body fat mass. In certain breeds, the change in BW over time might have an impact on overall health. Studies with simultaneous evaluation of BW and body condition over time are warranted.

Presence of nucleosomes in plasma and increased thrombin generation in dogs with acute and chronic gastroenteropathies.

Neutrophil extracellular traps (NETs) which contain nucleosomes protect the host by eliminating extracellular pathogens. However, any inflammatory stimuli can activate NETs and eventually lead to an immune overreaction leading to autoimmune diseases and thrombosis. Acute/chronic gastroenteropathies(aGE/cGE) are prevalent in dogs, and are associated with a strong inflammatory component. The aim of this study was to investigate if dogs with aGE and cGE have increased concentrations of nucleosomes indicative of NETs formation, and whether increased concentrations of nucleosomes are associated with hypercoagulability determined by increased thrombin generation. Twenty-six dogs were enrolled. The dogs were healthy (n = 11), or presented with aGE(n = 7) or cGE(n = 8). Minimum database including CRP, APTT, PT and fibrinogen, was obtained from all dogs. Citrated plasma was batched and used for subsequent analyses. Nucleosome concentration was analysed using a Cell-Death Detection ELISA-kit and thrombin generation by a calibrated automated thrombogram assay. No statistical differences in nucleosome concentrations were present between the groups. Although a numerically increased concentration of nucleosomes where seen in dogs with aGE(median;range) (0.019 AU;0.003-0.088) and cGE(0.023 AU;0.011-0.256) compared to controls(0.007 AU;0.003-0.042). One dog with GI-lymphoma demonstrated a markedly increased concentration of nucleosomes (0.256 AU). Dogs with aGE showed increased thrombin generation by increased peak (p = 0.03) and endogenous thrombin potential (p = 0.03); and increased CRP (p = 0.001), fibrinogen (p = 0.0002) and prolonged APTT (p = 0.03) compared to controls. This proof of concept study demonstrates that dogs with aGE and cGE have presence of nucleosomes with marked increase in one dog with GI-lymphoma. Nucleosomes might be linked to haemostatic alterations in dogs with inflammatory and neoplastic diseases.

Neutering increases the risk of obesity in male dogs but not in bitches - A cross-sectional study of dog- and owner-related risk factors for obesity in Danish companion dogs.

Knowledge of risk factors for canine obesity is an important pre-requisite of effective preventative strategies. This study aimed to investigate risk factors for canine obesity in adult companion dogs across Zealand, Denmark. Client-owned dogs (>2 years of age and without chronic illness) were recruited and examined at eight companion animal veterinary practices in areas with varying socio-economic characteristics. The body condition score (BCS) of the dogs was examined by two investigators based on a 9-point scoring scheme. Dog owners answered a questionnaire that had prompts regarding: 1) dog characteristics, including neuter status, 2) owner characteristics, 3) feeding and exercise practices and 4) the owners' attachment to the dog. The effect of these factors on BCS and the risk of being heavy/obese (BCS scores 7-9) were analysed in two separate analyses. A total of 268 dogs were included in the analysis, of which 20.5% were found to be heavy/obese. The average BCS was 5.46. In terms of dog characteristics, neutering dramatically increased both BCS and the risk of being heavy/obese in male dogs but not in bitches. BCS and the risk of being heavy/obese increased in senior bitches and decreased in senior male dogs. The risk of being heavy/obese was higher in dogs with overweight and obese owners. Regarding feeding and exercise practices, providing only one meal per day increased BCS and risk of being heavy/obese. Treats during relaxation increased the risk of dogs being heavy/obese. It also increased the dogs' BCS, but only if the owners were overweight or obese. An increased duration of daily walking increased the risk of the dog being heavy/obese, but only if the owner was overweight or obese. Allowing the dog to run free in the garden/property decreased the risk of the dog being heavy/obese. The owners' attachment to the dog was not associated with the dogs' BCS or dogs' being heavy/obese. An important and novel finding was that neutering increased the risk of being overweight or obese for male dogs while bitches were at risk irrespective of neuter status. Furthermore, a complex interaction between owners' weight status, feeding practices and the risk of dogs being overweight or obese was found, which stresses the need to consider companion animal obesity from a One Health perspective in future prospective studies. Finally, this study was unable to confirm that canine obesity is a product of owners being too attached to their dogs.

Effects of Diagnostic Work-Up on Medical Decision-Making for Canine Urinary Tract Infection: An Observational Study in Danish Small Animal Practices.

BACKGROUND: Clinical signs of urinary tract disease in dogs often lead to prescription of antibiotics. Appropriate diagnostic work-up could optimize treatment and reduce the risk of inappropriate use of antibiotics. HYPOTHESIS/OBJECTIVES: To describe and evaluate the impact of diagnostic work-up on decision to treat (DTT) and choice of antibiotic treatment (COT) for dogs presenting with clinical signs of urinary tract disease. ANIMALS: One hundred and fifty-one dogs presenting to 52 Danish veterinary practices. METHODS: Prospective, observational study. Clinical signs, diagnostic work-up, and prescriptions were recorded. Urine samples were submitted to a reference laboratory for quantitative bacterial culture (QBC) and susceptibility testing. The laboratory results were used as reference for assessing the appropriateness of DTT and COT. RESULTS: In the majority of dogs, veterinarians performed dipstick (99%), microscopic examination of urine (80%) and bacterial culture (56%). Fifty-one percent of dogs had urinary tract infection (UTI) based on reference QBC. Appropriate DTT was made for 62% of the dogs, while 36% were over-prescribed and 2% under-prescribed. Inappropriate use of second-line agents was found in 57% of the UTI cases. Performing microscopy-but not culture-significantly impacted DTT (P = 0.039) while no difference was seen in COT (P = 0.67). The accuracy of in-house microscopy and culture were 64.5 and 77%, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Over-prescription of antibiotics was common among dogs with suspected UTI, regardless of the diagnostic work-up performed. Test inaccuracy under practice conditions and incoherence between diagnostic test results and decision-making both explained inappropriate and unnecessary use of antibiotics.

Immunometabolic parameters in overweight dogs during weight loss with or without an exercise program.

The influence of physical activity on metabolic health in overweight dogs is unknown. This study was conducted to evaluate biomarkers of immunometabolic health in relation to changes in physical activity and adiposity. Client-owned overweight dogs participated in a 12-wk intervention based on caloric restriction combined with a training program (fitness and diet [FD] group, n = 8), or caloric restriction alone (diet-only [DO] group, n = 8). Physical activity was monitored by accelerometry. All dogs were fed the same diet and achieved similar weight loss. Fasting blood samples were collected before and after 6- and 12-wk intervention. Insulin resistance was evaluated from plasma insulin and C-peptide as well as homeostasis model assessment. Inflammation and dyslipidemia were evaluated from circulating leptin, adiponectin, C-reactive protein (CRP), monocyte chemoattractant factor-1 (MCP-1), interleukin-8 (IL-8), and cholesterol. Accelerometer counts in both groups were high compared with previous reports of physical activity in overweight dogs. No difference in blood parameters was evident between groups, evaluated by linear mixed-effects model (P > 0.05). Within the groups, the following changes were significant by t-test (P < 0.05): leptin decreased in both groups. Within the FD group, IL-8, MCP-1, and CRP decreased at 6 wk and IL-8 and cholesterol at 12 wk. Within the DO group, C-peptide and HOMA decreased at 6 wk and C-peptide at 12 wk. We conclude that, for both groups, weight loss resulted in minor indications of improved immunometabolic health, whereas this level of physical activity did not add further benefits.

Evaluation of different sampling methods and criteria for diagnosing canine urinary tract infection by quantitative bacterial culture.

The use of voided urine specimens for bacteriological culture in dogs is discouraged because contamination from external genitalia could lead to misinterpretation of laboratory results. Quantitative culturing and defining significant bacteriuria could increase the usefulness of voided specimens. However, limited evidence exists for the cut-offs currently recommended. The aim of this study was to evaluate the accuracy of current veterinary cut-off values for significant bacteriuria in voided canine urine. A secondary aim was to investigate if accuracy improved when applying qualitative criteria used in humans. Paired urine specimens were collected by both cystocentesis and voiding, and quantitative bacteriological cultures were performed within the same day. Cystocentesis was used as the reference standard with a cut-off for significant bacteriuria of ≥1000 colony forming units (CFU)/mL. Voided specimens were compared to cystocentesis using: (1) the veterinary cut-off of ≥100,000 CFU/mL; and (2) various cut-offs depending on qualitative criteria (sex, clinical signs and complicating factors), adapted from human guidelines. Ninety-four dogs with suspected urinary tract infection (UTI) were included for analysis. The veterinary cut-off yielded an accuracy of 94% with a sensitivity and specificity of 94% (95% confidence intervals [CI] 0.81, 0.99) and 94% (95% CI 0.86, 0.98), respectively. Applying the human guidelines did not improve overall accuracy (89%), and yielded a sensitivity and specificity of 97% (95% CI 0.86, 1.00) and 86% (95% CI 0.77, 0.92), respectively. The veterinary cut-off value of ≥100,000 CFU/mL for voided urine is appropriate for determining significant bacteriuria in the majority of dogs with suspected UTI if specimens are refrigerated and cultured on the day of collection.

Dietary supplementation with flaxseed mucilage alone or in combination with calcium in dogs: effects on apparent digestibility of fat and energy and fecal characteristics.

BACKGROUND: In humans, dietary supplementation with flaxseed mucilage and calcium decrease apparent digestibility of fat and energy. These supplements could prove useful for weight management in dogs. OBJECTIVE: To examine dry matter, energy and fat apparent digestibility, and fecal characteristics following dietary flaxseed mucilage supplementation alone or in combination with calcium. METHODS: A single-blinded crossover feeding trial was conducted on 11 privately owned dogs. During three consecutive 14-day periods, dogs where fed commercial dog food supplemented with potato starch (control diet), flaxseed mucilage or flaxseed mucilage and calcium. Feces from the past 2 days of each period were collected for analysis. Owners recorded fecal score (1-7: 1=very hard/dry feces, 2-3=ideal and 7=diarrhea). RESULTS: Apparent digestibility of fat was lower in both flaxseed mucilage diet (94.5±0.8%), and flaxseed mucilage and calcium diet (92.9±0.9%) compared with control diet (96.9±0.2%, P<0.0001) with fat digestibility in flaxseed mucilage and calcium diet being significantly lower than the diet supplemented with only flaxseed mucilage. Dry matter and energy digestibility was not significantly affected by diet. Fecal wet weight, dry weight and dry matter percentage was not affected by diet despite a higher fecal score for test diets (3.7±0.3) compared with control (2.8±0.2, P<0.007). CONCLUSION: In dogs, flaxseed mucilage decreased fat apparent digestibility and this effect was enhanced when combined with calcium. Dry matter and energy apparent digestibility was not affected. Decreased fecal quality may limit the acceptable level of supplementation. Further studies on incorporating flaxseed mucilage in pet food products for weight management are needed.

Overweight and the feline gut microbiome - a pilot study.

Compared with lean humans, the gut microbiota is altered in the obese. Whether these changes are due to an obesogenic diet, and whether the microbiota contributes to adiposity is currently discussed. In the cat population, where obesity is also prevalent, gut microbiome changes associated with obesity have not been studied. Consequently, the aim of this study was to compare the gut microbiota of lean cats, with that of overweight and obese cats. Seventy-seven rescue-shelter cats housed for ≥3 consecutive days were included in the study. Faecal samples were obtained by rectal swab and, when available, by a paired litter box sample. Body condition was assessed using a 9-point scoring system. DNA was extracted, and the 16S rRNA gene was amplified with a high-throughput quantitative real-time PCR chip. Overweight and obese cats had a significantly different gut microbiota compared to lean cats (p < 0.05), but this finding could not be linked to differences in specific bacterial groups. The rectal samples obtained higher DNA concentration than litter box samples (p < 0.0001). In conclusion, overweight and obese cats seem to have an altered gut microbiome as compared to lean cats.

Effect of antibiotic treatment in canine and feline urinary tract infections: a systematic review.

Urinary tract infection (UTI) is a major reason for antibiotic prescription in small animal practice. Optimal antibiotic treatment strategies have not been established for veterinary species, especially when considering duration of treatment, which is often considerably longer than for human patients with UTI. The aims of this study were (1) to identify and assess evidence related to the efficacy of antibiotic treatment in canine and feline UTIs; and (2) to compare the efficacy of short (<5 days) and standard (≥7 days) duration of antibiotic treatment for canine uncomplicated UTI. An electronic literature search was conducted for publications to 1 May 2014. Fourteen peer-reviewed prospective and controlled studies were retrieved, 10 of which evaluated antibiotic treatment in dogs and four in cats. Of the 14 studies, seven were clinical trials and five of those were randomised controlled trials. Most (12/14) studies were not considered to contribute sufficient evidence to evaluate treatment strategies. There were no clinical studies examining the effect of duration of the same drug. Of the short duration regimens evaluated, the efficacy of 3 day antibiotic therapy with trimethoprim-sulphonamide (females only) or high-dose enrofloxacin in dogs with uncomplicated UTIs was supported by fair evidence, as these treatment strategies were non-inferior to medium duration (10-14 days) therapy with ß-lactam antimicrobials. In conclusion, there is little published evidence relating to antibiotic treatment of UTIs in dogs and cats. Well-designed clinical trials focusing on the duration of treatment are warranted to create evidence-based treatment protocols.

Tumour gastrin expression and serum gastrin concentrations in dogs with gastric carcinoma are poor diagnostic indicators.

Hypergastrinaemia is observed commonly in human patients with gastric carcinoma and is associated with atrophic gastritis and Helicobacter pylori infection, both of which predispose to development of gastric tumours. Increased expression of gastrin is also described as a prognostic indicator for gastric carcinoma in man. Gastric carcinoma is rare in dogs and generally carries a grave prognosis. In this study, the expression of gastrin was investigated immunohistochemically in gastric biopsy samples from 64 dogs with gastric carcinoma. Serum gastrin concentrations were measured in 15 of these dogs and compared with those of seven healthy control dogs. Tumour tissue expressed gastrin in 8% (5/64) of the dogs with gastric carcinoma. There was no significant difference in serum gastrin concentrations between dogs with gastric carcinoma and healthy controls (P = 0.08). Expression of gastrin in gastric carcinomas is less common in dogs than in man and may therefore not be relied on as a prognostic marker in this species. Serum gastrin concentration alone is also not a useful biomarker for gastric carcinoma in dogs.

Obesity and sex influence insulin resistance and total and multimer adiponectin levels in adult neutered domestic shorthair client-owned cats.

In this study, we estimated insulin sensitivity and determined plasma concentrations of total-, low-molecular-weight (LMW), and high-molecular-weight (HMW) adiponectin and leptin in 72 domestic shorthair, neutered, client-owned cats. Glucose tolerance was assessed with an intravenous glucose tolerance test and body fat percentage (BF%) was measured with dual-energy x-ray absorptiometry. Total adiponectin was measured with 2 different ELISAs. Low-molecular-weight and HMW adiponectin plasma concentrations were determined by Western blot analysis after sucrose-gradient velocity centrifugation, and the adiponectin multimer ratio [SA = HMW/(HMW + LMW)] was calculated. Differences in glucose tolerance, leptin, total adiponectin, and multimer ratio among lean (BF% <35; n = 26), overweight (35 45; n = 18) cats as well as between male (n = 34) and female (n = 38) neutered cats were evaluated by linear regression and 2-way ANOVA. Sex and age were included as covariates for analysis of BF%, whereas BF%, fat mass, and lean body mass were covariates for analysis of sex differences. Increased BF% was negatively correlated with multimer ratio (SA, r = -45; P < 0.002), whereas no differences were found in total adiponectin concentrations among BF% groups (P > 0.01). Male cats had indices of decreased insulin tolerance and significantly lower total adiponectin concentrations than did female cats (mean ± SEM, 3.7 ± 0.4 vs 5.4 ± 0.5 µg/mL; P < 0.02). Altered SAs could contribute to an obesity-associated decreasing glucose tolerance in cats, and low total adiponectin concentrations may relate to increased risk of diabetes mellitus in neutered male cats.

Obesity increases initial rate of fibrin formation during blood coagulation in domestic shorthaired cats.

Obesity predisposes to a prothrombotic state in humans, but whether a similar state occurs in obese animals is unknown. The objective of the current study was to examine the effect of body fat percentage (BF) on haemostatic parameters including thromboelastography with tissue factor as activator (TF-TEG) in client owned indoor-confined physically inactive cats. Seventy-two cats were included following an initial thorough health examination, and a complete blood count, biochemistry panel, conventional coagulation panel and a TF-TEG analysis were performed with tissue factor (1:50,000) as activator. The cats were anaesthetized, and BF was measured using Dual-energy X-ray absorptiometry. Significant difference between lean (BF < 35%, n = 26), overweight (35% < BF < 45%, n = 28) and obese (BF > 45%, n = 18) cats was identified using ANOVA. The correlation between BF, serum leptin and total adiponectin, respectively, with individual TEG and conventional coagulation parameters was evaluated. Obese cats showed a faster rate of fibrin formation (TF-TEG(R), p < 0.05), and TF-TEG(R) was positively correlated with plasma leptin levels. Increasing BF did not affect other conventional coagulation or TF-TEG parameters. In conclusion, this study indicates a connection between body fat content and altered haemostasis, also in cats. Whether feline obesity causes a hypercoagulable state of clinical relevance should be further investigated.

The intestinal trophic response to enteral food is reduced in parenterally fed preterm pigs and is associated with more nitrergic neurons.

In term neonates, total parenteral nutrition (TPN) induces mucosal atrophy, whereas the first intake of milk is followed by intestinal growth. This may be explained in part by an NO-mediated increased blood flow. We hypothesized that the immature gut has an altered response to TPN and enteral nutrition. In Expt. 1, preterm caesarean-delivered pigs were administered elemental nutrients for 3 d, infused parenterally (TPN, n = 7) or enterally (TENT, n = 7). In Expt. 2, preterm pigs were fed sow's colostrum, cow's colostrum, or infant formula for 2 d after a 3-d TPN period (TPN-SOW, TPN-COW, TPN-FORM, n = 8-11). Intestinal morphology and the number of enteric neurons containing nitric oxide synthase-1 (NOS-1) were quantified. Both the TPN and TENT groups had increases in intestinal mass, circumference, and mucosal mass, volume, and surface density, relative to values at birth (+30-50%, P < 0.05). In Expt. 2, the magnitudes of the intestinal trophic responses to feeding were similar to those in Expt. 1, but were also associated with an increased number of nitrergic myenteric neurons and some mucosal damage, most frequently observed for the formula group. We conclude that 1) a short period of TPN does not induce mucosal atrophy in preterm pigs, whereas elemental nutrients infused luminally do not mimic the trophic response seen with milk diets, 2) enteral feeding of preterm pigs after a short period of TPN is associated with a modest, diet-dependent trophic response that may be related in part to the actions of an increased population of enteric NOS-1 neurons.

Short-term fasting induces intra-hepatic lipid accumulation and decreases intestinal mass without reduced brush-border enzyme activity in mink (Mustela vison) small intestine.

For many mammalian species short-term fasting is associated with intestinal atrophy and decreased digestive capacity. Under natural conditions, strictly carnivorous animals often experience prey scarcity during winter, and they may therefore be particularly well adapted to short-term food deprivation. To examine how the carnivorous gastrointestinal tract is affected by fasting, small-intestinal structure, brush-border enzyme activities and hepatic structure and function were examined in fed mink (controls) and mink that had been fasted for 1-10 days. During the first 1-2 days of fasting, intestinal mass decreased more rapidly than total body mass and villus heights were reduced 25-40%. In contrast, tissue-specific activity of the brush-border enzymes sucrase, maltase, lactase, aminopeptidase A and dipeptidylpeptidase IV increased 0.5- to 1.5-fold at this time, but returned to prefasting levels after 6 days of fasting. After 6-10 days of fasting there was a marked increase in the activity of hepatic enzymes and accumulation of intra-hepatic lipid vacuoles. Thus, mink may be a useful model for studying fasting-induced intestinal atrophy and adaptation as well as mechanisms involved in accumulation of intra-hepatic lipids following food deprivation in strictly carnivorous domestic mammals, such as cats and ferrets.