Towards a flexible and personalised development of veterinarians and veterinary nurses working in a companion animal referral care setting.

In the Netherlands, the demand for veterinarians and veterinary nurses (VNs) working within referral care is rapidly growing and currently exceeds the amount of available board-certified specialists. Simultaneously, a transparent structure to guide training and development and to assess quality of non-specialist veterinarians and VNs working in a referral setting is lacking. In response, we developed learning pathways guided by an entrustable professional activity (EPA) framework and programmatic assessment to support personalised development and competence of veterinarians and VNs working in referral settings. Between 4 and 35 EPAs varying per discipline (n = 11) were developed. To date, 20 trainees across five disciplines have been entrusted. Trainees from these learning pathways have proceeded to acquire new EPAs in addition to their already entrusted set of EPAs or progressed to specialist training during (n = 3) or after successfully completing (n = 1) the learning pathway. Due to their outcome-based approach, the learning pathways support flexible ways of development.

Approaching Training-Practice Gaps After the Transition: A Practice Proposal for Supervision After Training.

Transitions within medical, veterinarian, and other health professional training, from classroom to workplace, between undergraduate, postgraduate, fellowship phases, and to unsupervised clinical practice, are often stressful. Endeavors to alleviate inadequate connections between phases have typically focused on preparation of learners for a next phase. Yet, while some of these efforts show results, they cannot obliviate transitional gaps. If reformulated as 'not completely ready to assume the expected responsibilities in the next phase', transitions may reflect intrinsic problems in a training trajectory. Indeed, the nature of classroom teaching and even skills training for example, will never fully reflect the true context of clinical training. In various stages of clinical training, the supervision provided to trainees, particularly medical residents, has increased over the past decades. This addresses calls for enhanced patient safety, but may inadequately prepare trainees for unsupervised practice. Transitions often evolve around the question how much support or supervision incoming trainees or junior professionals require. We propose to consider receiving incoming trainees and new employees in clinical workplaces with a conversation about required supervision for discrete tasks, or entrustable professional activities (EPAs). EPAs lend themselves for the question: "At what level of supervision will you be able to carry out this task?". This question can be answered by both the trainee or junior employee and the supervisor or employer and can lead to agreement about specified supervision for a defined period of time. We expect that this "supported autonomy tool" could alleviate stress and enhance continued development after transitions.

Bridging the Gap between Undergraduate Veterinary Training and Veterinary Practice with Entrustable Professional Activities.

The transition from being a veterinary student to becoming a member of the veterinary profession is known to be challenging. Despite being licensed directly after graduation, many veterinarians do not feel fully equipped to practice unsupervised when they graduate. The increasing rate of attrition from veterinary practice, and a relatively high percentage of burnout during the first years in practice, has been suggested to be related to a lack of early career support. Over the past decade, medical education has adopted the concept of entrustable professional activities (EPAs). Recently, EPAs have been proposed to restructure veterinary education to help support the transition from veterinary student to practicing veterinarian. Implementing an EPA-based approach could help to bridge the gap between school and clinical practice, potentially preventing veterinary graduates from dropping out early on from what could have been a promising and exciting professional career.

Outcome of non-surgical dietary treatment with or without lactulose in dogs with congenital portosystemic shunts.

Background: Congenital portosystemic shunts (CPSS) are vascular anomalies, allowing portal blood to bypass the hepatic parenchyma, thereby accumulating toxic substances such as ammonia in the systemic circulation resulting in hepatic encephalopathy.Aim: To evaluate the outcome of non-surgically treated dogs with a CPSS.Methods: Case records of 78 dogs with a single congenital CPSS confirmed by ultrasound and/or computed tomography between September 2003 and February 2015 were reviewed. Median age at diagnosis of CPSS in dogs was 10.8 months (range 2-133 months). Non-surgical treatment was started as an adjusted diet (a diet restricted in protein) with or without lactulose. Owners were contacted by telephone to determine survival time and presumed cause of death, if applicable. In addition, a questionnaire was used to retrospectively assess quality of life (QoL) and CPSS scores in 37 dogs before and during non-surgical treatment. Differences between Kaplan-Meier curves were tested by a Log rank test.Results: Overall estimated median survival time (EMST) was 38.5 months (range 1 day - 91 months; 78 dogs). No significant differences between EMSTs were found between dogs with extra- (n = 48) or intrahepatic (n = 29) shunts, nor between treatment with only an adjusted diet, or an adjusted diet combined with lactulose. During non-surgical treatment, significant improvement in perceived QoL and CPSS scores were found (P < 0.01).Conclusion: Our study demonstrated that an overall median EMST of 3.2 years was reached and that owners retrospectively perceived that non-surgical treatment resulted in an improved QoL and clinical performance, irrespective of intrahepatic or extrahepatic CPSS location.

Identifying entrustable professional activities for surgical skills training in companion animal health.

BACKGROUND: Veterinary medical education is increasingly moving towards outcome-based training based on competency frameworks. A source of concern is the translation of competencies into the practice of clinical teaching, for example, surgical skills training. It is suggested that the use of entrustable professional activities (EPAs) might bridge this gap. The purpose of this study, therefore, was to identify EPAs related to surgical skills for companion animal health to enhance competency-based education. METHODS: Draft versions of EPAs related to surgical skills were established by an iterative consensus-based approach through 45-min interview sessions. These draft versions were used to explore the opinion of companion animal veterinarians, both veterinarians (specialists, residents and interns) involved in undergraduate teaching and veterinarians working in private practice involved in extramural clinical teaching, on the relevance and level of entrustment of the EPAs through a modified Delphi procedure. Mean (relevance) and median (level of entrustment) scores were calculated and textual comments were analysed to create a final framework of EPAs related to surgical skills. RESULTS AND CONCLUSION: The Delphi panel reached consensus in three rounds. Thirty-four per cent of those invited to participate in the study completed the final survey. Finally, a list of 13 EPAs related to companion animal surgical skills a student should be entrusted to perform at time of graduation was established.

Gene expressions of de novo hepatic lipogenesis in feline hepatic lipidosis.

OBJECTIVES: The aim of this study was to evaluate if de novo hepatic lipid synthesis contributes to fatty acid overload in the liver of cats with feline hepatic lipidosis (FHL). METHODS: Lipogenic gene expression of peroxisome proliferator-activated receptor-alpha (PPAR-α), peroxisome proliferator-activated receptor-gamma (PPAR-γ), fatty acid synthase (FASN) and sterol regulatory element-binding factor (SREBF1) were evaluated using quantitative RT-PCR in liver tissue of six cats with FHL and compared with the liver tissue of eight healthy cats. RESULTS: In liver tissue, PPAR-α, PPAR-γ and FASN mRNA expression levels were not significantly different (P >0.12, P >0.89 and P >0.5, respectively) in the FHL group compared with the control group. SREBF1 gene expression was downregulated around 10-fold in the FHL group vs the control group (P = 0.039). CONCLUSIONS AND RELEVANCE: The downregulation of SREBF1 in the liver tissue of cats with FHL does not support the hypothesis that de novo lipogenesis in the liver is an important pathway of fatty acid accumulation in FHL.

Efficacy of orally administered sodium benzoate and sodium phenylbutyrate in dogs with congenital portosystemic shunts.

BACKGROUND: Hyperammonemia can result in hepatic encephalopathy, which in severe cases eventually can lead to coma and death. In dogs, congenital portosystemic shunts (CPSS) are the most common cause for hyperammonemia. Conservative treatment consists of a protein modified diet, nonabsorbable disaccharides, antibiotics, or some combinations of these. Sodium benzoate (SB) and sodium phenylbutyrate (SPB) both are used in the acute and long-term treatment of humans with hyperammonemia caused by urea cycle enzyme deficiencies. Both treatments are believed to lower blood ammonia concentrations by promoting excretion of excess nitrogen via alternative pathways. OBJECTIVES: To evaluate the efficacy and safety of PO treatment with SB and SPB on hyperammonemia and clinical signs in CPSS dogs. METHODS: Randomized, double-blind, placebo-controlled crossover trial. Concentrations of blood ammonia and bile acids were measured in CPSS dogs before and after a 5-day treatment with SB, SPB, and placebo. A wash-out period of 3 days was used between treatments. A standard questionnaire was developed and distributed to owners to evaluate clinical signs before and after each treatment. RESULTS: Blood ammonia concentrations were not influenced by any of the treatments and were comparable to those observed during placebo treatment. In addition, SB and SPB treatment did not result in improvement of clinical signs. Adverse effects during treatment included anorexia, vomiting, and lethargy. CONCLUSIONS AND CLINICAL IMPORTANCE: Based on our results, we conclude that SB or SPB are not useful in the conservative treatment of hyperammonemia in dogs with CPSS.

Inter-Rater Reliability of Grading Undergraduate Portfolios in Veterinary Medical Education.

The reliability of high-stakes assessment of portfolios containing an aggregation of quantitative and qualitative data based on programmatic assessment is under debate, especially when multiple assessors are involved. In this study carried out at the Faculty of Veterinary Medicine, Utrecht University, the Netherlands, two independent assessors graded the portfolios of students in their second year of the 3-year clinical phase. The similarity of grades (i.e., equal grades) and the level of the grades were studied to estimate inter-rater reliability, taking into account the potential effects of the assessor's background (i.e., originating from a clinical or non-clinical department) and student's cohort group, gender, and chosen master track (Companion Animal Health, Equine Health, or Farm Animal/Public Health). Whereas the similarity between the two grades increased from 58% in the first year the grading system was introduced to around 80% afterwards, the grade level was lower over the next 3 years. The assessor's background had a minor effect on the proportion of similar grades, as well as on grading level. The assessor intraclass correlation was low (i.e., all assessors scored with a similar grading pattern [same range of grades]). The grades awarded to female students were higher but more often dissimilar. We conclude that the grading system was well implemented and has a high inter-rater reliability.

Immunohistochemical characterisation of the hepatic stem cell niche in feline hepatic lipidosis: a preliminary morphological study.

OBJECTIVES: The aim of this study was to describe the cellular and stromal components of the hepatic progenitor cell niche in feline hepatic lipidosis (FHL). METHODS: Immunohistochemical staining for the progenitor/bile duct marker (K19), activated Kupffer cells (MAC387), myofibroblasts (alpha-smooth muscle actin [α-SMA]) and the extracellular matrix component laminin were used on seven liver biopsies of cats with FHL and three healthy cats. Double immunofluorescence stainings were performed to investigate co-localisation of different cell types in the hepatic progenitor cell (HPC) niche. RESULTS: HPCs, Kupffer cells, myofibroblasts and laminin deposition were observed in the liver samples of FHL, although with variability in the expression and positivity of the different immunostainings between different samples. When compared with the unaffected cats where K19 positivity and minimal α-SMA and laminin positivity were seen mainly in the portal area, in the majority of FHL samples K19 and α-SMA-positive cells and laminin positivity were seen also in the periportal and parenchymatous area. MAC387-positive cells were present throughout the parenchyma. CONCLUSIONS AND RELEVANCE: This is a preliminary morphological study to describe the activation and co-localisation of components of the HPC niche in FHL. Although the HPC niche in FHL resembles that described in hepatopathies in dogs and in feline lymphocytic cholangitis, the expression of K19, α-SMA, MAC387 and lamin is more variable in FHL, and a common pattern of activation could not be established. Nevertheless, when HPCs were activated, a spatial association between HPCs and their niche could be demonstrated.

Immunohistochemical evaluation of the activation of hepatic progenitor cells and their niche in feline lymphocytic cholangitis.

Objectives The aim of the study was to compare the hepatic progenitor cell niche in healthy feline livers and the liver tissue of cats with lymphocytic cholangitis. Methods Immunohistochemical stainings for vimentin, laminin, beta (ß)-catenin and Notch1 intracellular domain (NICD) were used on formalin-fixed liver biopsies from affected (n = 12) and unaffected cats (n = 2). Results All immunohistochemical markers used were expressed in more cells, or more intensely, in the liver tissue of cats with lymphocytic cholangitis than in the liver tissue of unaffected cats. Conclusions and relevance Enhanced expression of vimentin, laminin, cytoplasmic/nuclear ß-catenin and NICD in liver biopsies from cats with lymphocytic cholangitis indicates that the hepatic progenitor cell (HPC) niche is remodelled and activated. HPCs might provide insights into new regenerative treatment options for lymphocytic cholangitis in cats in the future.

Sex specific differences in hepatic and plasma lipid profiles in healthy cats pre and post spaying and neutering: relationship with feline hepatic lipidosis.

BACKGROUND: A link between lipid metabolism and disease has been recognized in cats. Since hepatic lipidosis is a frequent disorder in cats, the aim of the current study was to evaluate liver and plasma lipid dimorphism in healthy cats and the effects of gonadectomy on lipid profiling. From six female and six male cats plasma and liver lipid profiles before and after spaying/neutering were assessed and compared to five cats (three neutered male and two spayed female) diagnosed with hepatic lipidosis. RESULTS: Intact female cats had a significantly lower level of plasma triacylglycerides (TAG) and a higher liver level of the long chain polyunsaturated fatty acid arachidonic acid (AA) compared to their neutered state. Both male and female cats with lipidosis had a higher liver, but not plasma TAG level and an increased level of plasma and liver sphingomyelin compared to the healthy cats. CONCLUSION: Although lipid dimorphism in healthy cats resembles that of other species, intact female cats show differences in metabolic configuration that could predispose them to develop hepatic lipidosis. The increased sphingomyelin levels in cats with lipidosis could suggest a potential role in the pathogenesis of hepatic lipidosis in cats.

Students' motivation toward feedback-seeking in the clinical workplace.

In medical education, students are increasingly regarded as active seekers of feedback rather than passive recipients. Previous research showed that in the intentions of students to seek feedback, a learning and performance goal can be distinguished. In this study, we investigated the intentions (defined as level and orientation of motivation) of different performing students (low, average, and high performing students) to seek feedback in the clinical workplace using Self-Determination Theory. We conducted a quantitative study with students in their clinical clerkships and grouped them based on their performance. The level of motivation was measured by the number of Mini-CEXs each student collected. The orientation of motivation was measured by conducting the Academic Self-Regulation Questionnaire. We found that high performing students were more motivated and demonstrated higher self-determination compared to low performing students.

Applicability of Progress Testing in Veterinary Medical Education.

A substantial part of graduate education in veterinary medicine is spent in clinical practice. During the clinical experiential phase, it is difficult to monitor students' actual knowledge development: they build individual records of experiences based on the cases they have to deal with, while mainly focusing on knowledge that is of direct, clinical relevance to them. As a result, students' knowledge bases may differ to such a degree that a single test alone may not be able to provide an adequate reflection of progress made. In these circumstances, progress testing, which is a method of longitudinal assessment independent of the curricular structure, may offer a viable solution. The purpose of this study, therefore, was to determine the extent to which progress tests (PT) can be used to monitor progress in knowledge development at a graduate level in veterinary medical education. With a 6-month interval, we administered two tests to students based on the Maastricht Progress Test format that covered a large variety of veterinary topics. Consequently, we analyzed students' progress in knowledge development. Based on a substantive appraisal of the questions and analysis of the test results, we concluded that the tests met the measurement criteria. They appeared sensitive enough to gauge the progress made and were appreciated by the students. Hence, in spite of the differences within the whole graduate group, the PT format can be used to monitor students' knowledge development.

Feline Hepatic Lipidosis.

Feline hepatic lipidosis (FHL) is a common and potentially fatal liver disorder. Although the pathophysiologic mechanisms of FHL remain elusive, there is an imbalance between the influx of fatty acids from peripheral fat stores into the liver, de novo liposynthesis, and the rate of hepatic oxidation and dispersal of hepatic TAG via excretion of very-low density lipoproteins. The diagnosis of FHL is based on anamnestic, clinical, and clinicopathologic findings, associated with diagnostic imaging of the liver, and cytology, or histological examination of liver biopsies. Fluid therapy, electrolyte correction and adequate early nutrition are essential components of the therapy for FHL.

CCC- and WASH-mediated endosomal sorting of LDLR is required for normal clearance of circulating LDL.

The low-density lipoprotein receptor (LDLR) plays a pivotal role in clearing atherogenic circulating low-density lipoprotein (LDL) cholesterol. Here we show that the COMMD/CCDC22/CCDC93 (CCC) and the Wiskott-Aldrich syndrome protein and SCAR homologue (WASH) complexes are both crucial for endosomal sorting of LDLR and for its function. We find that patients with X-linked intellectual disability caused by mutations in CCDC22 are hypercholesterolaemic, and that COMMD1-deficient dogs and liver-specific Commd1 knockout mice have elevated plasma LDL cholesterol levels. Furthermore, Commd1 depletion results in mislocalization of LDLR, accompanied by decreased LDL uptake. Increased total plasma cholesterol levels are also seen in hepatic COMMD9-deficient mice. Inactivation of the CCC-associated WASH complex causes LDLR mislocalization, increased lysosomal degradation of LDLR and impaired LDL uptake. Furthermore, a mutation in the WASH component KIAA0196 (strumpellin) is associated with hypercholesterolaemia in humans. Altogether, this study provides valuable insights into the mechanisms regulating cholesterol homeostasis and LDLR trafficking.

No up-regulation of the phosphatidylethanolamine N-methyltransferase pathway and choline production by sex hormones in cats.

BACKGROUND: Feline hepatic lipidosis (FHL) is a common cholestatic disease affecting cats of any breed, age and sex. Both choline deficiency and low hepatic phosphatidylethanolamine N-methyltransferase (PEMT) activity are associated with hepatic lipidosis (HL) in humans, mice and rats. The PEMT expression is known to be upregulated by oestrogens, protecting the females in these species from the development of HL when exposed to choline deficient diets. The aim of the present study was to evaluate the influence of sex hormones on choline synthesis via the PEMT pathway in healthy male and female cats before and after spaying/neutering, when fed a diet with recommended dietary choline content. RESULTS: From six female and six male cats PEMT activity was assayed directly in liver biopsies taken before and after spaying/neutering, and assessed indirectly by analyses of PEMT-specific hepatic phosphatidylcholine (PC) species and plasma choline levels. Hepatic PEMT activity did not differ between intact female and male cats and no changes upon spaying/neutering were observed. Likewise, no significant differences in liver PC content and PEMT-specific polyunsaturated PC species were found between the sexes and before or after spaying/neutering. CONCLUSION: These results suggest that choline synthesis in cats differs from what is observed in humans, mice and rats. The lack of evident influence of sex hormones on the PEMT pathway makes it unlikely that spaying/neutering predisposes cats for HL by causing PC deficiency as suggested in other species.

Aberrant expression of copper associated genes after copper accumulation in COMMD1-deficient dogs.

BACKGROUND: COMMD1-deficient dogs progressively develop copper-induced chronic hepatitis. Since high copper leads to oxidative damage, we measured copper metabolism and oxidative stress related gene products during development of the disease. METHODS: Five COMMD1-deficient dogs were studied from 6 months of age over a period of five years. Every 6 months blood was analysed and liver biopsies were taken for routine histological evaluation (grading of hepatitis), rubeanic acid copper staining and quantitative copper analysis. Expression of genes involved in copper metabolism (COX17, CCS, ATOX1, MT1A, CP, ATP7A, ATP7B, ) and oxidative stress (SOD1, catalase, GPX1 ) was measured by qPCR. Due to a sudden death of two animals, the remaining three dogs were treated with d-penicillamine from 43 months of age till the end of the study. Presented data for time points 48, 54, and 60 months was descriptive only. RESULTS: A progressive trend from slight to marked hepatitis was observed at histology, which was clearly preceded by an increase in semi-quantitative copper levels starting at 12 months until 42 months of age. During the progression of hepatitis most gene products measured were transiently increased. Most prominent was the rapid increase in the copper binding gene product MT1A mRNA levels. This was followed by a transient increase in ATP7A and ATP7B mRNA levels. CONCLUSIONS: In the sequence of events, copper accumulation induced progressive hepatitis followed by a transient increase in gene products associated with intracellular copper trafficking and temporal activation of anti-oxidative stress mechanisms.

Aberrant expression and distribution of enzymes of the urea cycle and other ammonia metabolizing pathways in dogs with congenital portosystemic shunts.

The detoxification of ammonia occurs mainly through conversion of ammonia to urea in the liver via the urea cycle and glutamine synthesis. Congenital portosystemic shunts (CPSS) in dogs cause hyperammonemia eventually leading to hepatic encephalopathy. In this study, the gene expression of urea cycle enzymes (carbamoylphosphate synthetase (CPS1), ornithine carbamoyltransferase (OTC), argininosuccinate synthetase (ASS1), argininosuccinate lyase (ASL), and arginase (ARG1)), N-acetylglutamate synthase (NAGS), Glutamate dehydrogenase (GLUD1), and glutamate-ammonia ligase (GLUL) was evaluated in dogs with CPSS before and after surgical closure of the shunt. Additionally, immunohistochemistry was performed on urea cycle enzymes and GLUL on liver samples of healthy dogs and dogs with CPSS to investigate a possible zonal distribution of these enzymes within the liver lobule and to investigate possible differences in distribution in dogs with CPSS compared to healthy dogs. Furthermore, the effect of increasing ammonia concentrations on the expression of the urea cycle enzymes was investigated in primary hepatocytes in vitro. Gene-expression of CPS1, OTC, ASL, GLUD1 and NAGS was down regulated in dogs with CPSS and did not normalize after surgical closure of the shunt. In all dogs GLUL distribution was localized pericentrally. CPS1, OTC and ASS1 were localized periportally in healthy dogs, whereas in CPSS dogs, these enzymes lacked a clear zonal distribution. In primary hepatocytes higher ammonia concentrations induced mRNA levels of CPS1. We hypothesize that the reduction in expression of urea cycle enzymes, NAGS and GLUD1 as well as the alterations in zonal distribution in dogs with CPSS may be caused by a developmental arrest of these enzymes during the embryonic or early postnatal phase.

A morphological and immunohistochemical study of the effects of prednisolone or ursodeoxycholic acid on liver histology in feline lymphocytic cholangitis.

Feline lymphocytic cholangitis (LC) has been commonly treated with prednisolone, and more recently with ursodeoxycholic acid (UDCA). Previously, we found that prednisolone treatment resulted in a statistically longer survival time than treatment with UDCA. In order to explain this difference, we compared the effects of prednisolone and UDCA treatment on hepatic tissue by evaluating consecutive liver biopsies. Archival serial biopsy materials from cats with LC treated with prednisolone (n = 5) or UDCA (n = 4) were evaluated. We employed haematoxylin and eosin staining to evaluate inflammation, and reticulin staining for fibrosis. Immunohistochemical stainings for Ki-67, K19 (Cytokeratin 19) and α-smooth muscle actin were used to evaluate cell type-specific proliferation and activation of hepatic stellate cells. Inflammation decreased more in the group treated with prednisolone, while the number of cholangiocytes, progenitor cells and fibroblasts did not differ between the treatment groups. Additionally, no difference was found for the amount of fibrosis in both treatment groups.