REDCap on FHIR: Clinical Data Interoperability Services.

BACKGROUND: Despite widespread use of electronic data capture (EDC) systems for research and electronic health records (EHR), most transfer of data between EHR and EDC systems is manual and error prone. Increased adoption of Health Level Seven Fast Healthcare Interoperability Resource (FHIR) application programming interfaces (APIs) in recent years by EHR systems has increased the availability of patient data for external applications such as REDCap. OBJECTIVE: Describe the development of the REDCap Clinical Data Interoperability Services (CDIS) module that provides seamless data exchange between the REDCap research EDC and any EHR system with a FHIR API. CDIS enables end users to independently set up their data collection projects, map EHR data to fields, and adjudicate data transfer without project-by-project involvement from Health Information Technology staff. METHODS: We identified two use cases for EHR data transfer into REDCap. Clinical Data Pull (CDP) automatically pulls EHR data into user-defined REDCap fields and replaces the workflow of having to transcribe or copy and paste data from the EHR. Clinical Data Mart (CDM) collects all specified data for a patient over a given time period and replaces the process of importing EHR data for registries from research databases. With an iterative process, we designed our access control, authentication, variable selection, and mapping interfaces in such a way that end users could easily set up and use CDIS. RESULTS: Since its release, the REDCap CDIS has been used to pull over 19.5 million data points for 82 projects at Vanderbilt University Medical Center. Software and documentation are available through the REDCap Consortium. CONCLUSIONS: The new REDCap Clinical Data and Interoperability Services (CDIS) module leverages the FHIR standard to enable real-time and direct data extraction from the EHR. Researchers can self-service the mapping and adjudication of EHR data into REDCap. The uptake of CDIS at VUMC and other REDCap consortium sites is improving the accuracy and efficiency of EHR data collection by reducing the need for manual transcription and flat file uploads.

Intra-operative techniques to reduce the risk of capsular contracture in patients undergoing aesthetic breast augmentation - A review.

BACKGROUND: Capsular contracture is a significant complication following aesthetic breast augmentation. Efforts to reduce this incidence have focused on the surgical approach, implant selection and IV antibiotics. Intra-operative methods to reduce the risk have had less investigation. This review focuses on these interventions and will document evidence to support pocket irrigation, nipple shields, drains and the use of an implant insertion funnel. METHODS: A comprehensive review of Pubmed, Scopus and Embase was performed to identify relevant papers published since 2000. These were reviewed and pertinent papers selected. Data regarding the intervention and its impact were recorded and compared. RESULTS: Ten relevant studies were identified. A total of 11,772 patients were included in the studies, with a pooled capsular contracture rate of 2.54%. Six papers reported the use of antibiotic irrigation, two papers reported the use of drains, two the use of an insertion funnel, two the use of povidone-iodine and one the use of nipple shields. Antibiotic irrigation was shown to reduce capsular contracture 10 fold in two papers, have no effect in one and increase it in a further paper. However these changes did not persist after multivariate analysis. CONCLUSIONS: There was limited evidence to support intra-operative techniques to reduce capsular contracture rate. Where available the literature tends to support the use of antibiotic and povidone-iodine irrigation, the use of insertion funnels and nipple shields and the avoidance of drains. However due to the poor quality of the evidence these findings should be treated cautiously.

The effect of tumour necrosis factor-α and insulin on equine digital blood vessel function in vitro.

OBJECTIVE AND DESIGN: Insulin and inflammatory cytokines may be involved in equine laminitis, which might be associated with digital vascular dysfunction. This study determined the effects of TNF-α and insulin on the endothelial-dependent relaxant responses of equine digital blood vessels and on equine digital vein endothelial cell (EDVEC) cGMP production. MATERIAL: Isolated rings of equine digital arteries (EDAs) and veins (EDVs) were obtained and EDVECs were cultured from horses euthanized at an abattoir. METHODS: The effect of incubation with TNF-α (10 ng/ml) and/or insulin (1,000 µIU/ml) for 1.5 h or overnight under hyperoxic and hypoxic conditions on carbachol (endothelium-dependent) induced relaxation was assessed. The time course and concentration dependency of the effect of TNF-α and the effect of insulin (1,000 µIU/ml) on EDVEC cGMP production was determined. RESULTS: Incubation of EDAs overnight with TNF-α under hypoxic conditions resulted in endothelial-dependent vascular dysfunction. EDVs produced a more variable response. TNF-α increased EDVEC cGMP formation in a time- and concentration-dependent manner. Insulin had no significant effects. CONCLUSIONS: There is a mismatch between the results obtained from isolated vessel rings and cultured endothelial cells suggesting TNF-α may reduce the biological effect of NO by reducing its bioavailability rather than its formation, leading to endothelial cell dysregulation.

Contractile responses of isolated equine digital arteries under hypoxic or hyperoxic conditions in vitro: role of reactive oxygen species and Rho kinase.

The underlying pathophysiological triggers for equine acute laminitis are unknown, although digital vasoconstriction, ischaemia, hypoxia and reperfusion injury may be involved. The contractile responses of isolated equine digital arteries (EDAs), harvested from the hindlimbs of normal horses postmortem at an abattoir, were studied acutely (up to 3 h) under hyperoxic (95% oxygen, 5% CO2 ) and hypoxic (95% nitrogen, 5% CO2 ) conditions in organ baths. Phenylephrine (PHE; 10(-6) m), 5-hydroxytryptamine (5-HT; 10(-7) m) and high potassium (K(+) ; 118 mm) caused contraction in EDAs which was significantly (P<0.0001) enhanced under hypoxic conditions. In contrast, contraction stimulated by 9,11-dideoxy-9α,11α-epoxymethanoprostaglandin F2α (U44069; 3 × 10(-8) m) was not significantly enhanced by hypoxia (P=0.75). Hypoxia-enhanced contraction in response to K(+) was greater (P<0.03) in vessels with a functional endothelium than in vessels in which the endothelium was removed by rubbing. Fasudil (10(-6) to 10(-5) m), a Rho kinase inhibitor, and apocynin (10(-3) to 3 × 10(-3) m), an NADPH oxidase inhibitor, significantly (P ≤ 0.05) inhibited hypoxia-enhanced contraction in response to PHE and 5-HT. In conclusion, hypoxia-enhanced contraction occurred in EDAs. This appears to be partially mediated by reactive oxygen species produced by NAPDH oxidase, which activate Rho kinase to increase calcium sensitisation and enhance smooth muscle contraction.

Short Communication: Identification of equine corticotropin-like intermediate lobe peptide (CLIP) binding to an adrenocortipcotrophic hormone (ACTH) assay capture antibody.

A chemiluminescent immunoassay is commonly employed to measure adrenocorticotrophic hormone (ACTH) concentrations to assist pituitary pars intermedia dysfunction diagnosis. In a previous study, seasonally-dependent assay cross-reactivity to endogenous equine corticotropin-like intermediate lobe peptide (CLIP, ACTH 18-39) was suspected. The present study aimed to demonstrate binding of endogenous equine CLIP to the capture antibody of the ACTH chemiluminescent immunoassay. Liquid chromatography - mass spectrometry (LCMS) methods were optimised to identify selected ions from synthetic human ACTH, α-melanocyte stimulating hormone (α-MSH, ACTH 1-17) and CLIP. Synthetic ACTH and CLIP bound to the capture antibody of the chemiluminescent ACTH assay, but α-MSH did not. Equine endogenous CLIP was detected by LCMS in pony plasma taken in the autumn and could be eluted from the capture antibody of the ACTH chemiluminescent immunoassay. Further research is required to enable quantification of CLIP. Equine CLIP may alter measured ACTH concentrations in vivo.

Effect of Weight Change on Markers of Bone Turnover and Phosphorus Excretion.

There is little information about how weight change in horses impacts bone turnover and the metabolism of minerals associated with bone. This study evaluated weight change in mature horses as a factor that could alter bone turnover and fecal P output. Fifteen horses (555 ± 8 kg) were assigned to three treatments: weight loss (LO; n = 5), weight maintenance (MA; n = 5), and weight gain (GA; n = 5). Diets contained 75%, 100%, and 145% of maintenance digestible energy requirements for the three treatments, respectively, but contained similar amounts of protein and minerals. At the end of the weight change period (27 ± 6 d), blood samples were analyzed for bone biomarkers and a 5-day total fecal collection was conducted to measure fecal mineral output. Horses fed the MA diet had an average daily weight change that was not different from either the GA or LO treatments, while weight change was different between the GA group and the LO group (0.49 kg/d vs. -1.16 kg/d; P = .017). Weight change was negatively correlated with cross-linking C-terminal telopeptides of type-I collagen, a biomarker of bone resorption (r = -0.62; P = .014) and tended to be positively correlated with bone alkaline phosphatase, a biomarker of bone formation (r = 0.48; P = .068). Also, fecal P output tended to be lower in GA than in LO horses (P = .085), while MA was intermediate and not different, suggesting that weight loss was increasing bone resorption, resulting in a tendency for higher P loss from the body. Weight change in horses can influence bone metabolism as well as mineral excretion.

Could alkali production be considered an approach for caries control?

This study investigated the relationship of arginine deiminase (ADS) and urease activities with dental caries through a case-control study. ADS and urease activities were measured in dental smooth-surface supragingival plaque and whole saliva samples from 93 subjects, who were in three different groups: caries-free (n = 31), caries-active (n = 30), and caries-experienced (n = 32). ADS activity was measured by quantification of the ammonia generated from the incubation of plaque and saliva samples in a mixture containing 50 mM arginine-HCl and 50 mM Tris-maleate buffer, pH 6.0. ADS-specific activity was defined as nanomoles of ammonia generated per minute per milligram of protein. Urease activity was determined by quantification of ammonia produced from 50 mM urea. For bacterial identification and enumeration real-time qPCR analysis was used. Groups were compared using Kruskal-Wallis tests. Spearman correlations were used to analyze plaque metabolic activity and bacterial relationships. The results revealed significantly higher ammonia production from arginine in saliva (1.06 vs. 0.18; p < 0.0001) and plaque samples (1.74 vs. 0.58; p < 0.0001) from caries-free subjects compared to caries-active subjects. Urease levels were about 3-fold higher in the plaque of caries-free subjects (p < 0.0001). Although higher urease activity in saliva of caries-experienced and caries-free subjects was evident, no significant difference was found between the groups.

Effect of dietary restriction on body condition, composition and welfare of overweight and obese pony mares.

REASONS FOR PERFORMING STUDY: Increased prevalence of obesity among UK horses and ponies demands evidence-based advice to promote weight loss. HYPOTHESIS: Restriction of dry matter intake (DMI) to 1% of body mass (BM, 67% [corrected] of predicted maintenance digestible energy [DE] requirements) would promote weight loss without compromise to health. METHODS: Five mature (mean ± s.e. 10 ± 2 years), overweight/obese pony mares (BM, 257 ± 20 kg: body condition score [BCS] 6.8/9 ± 0.5) were studied over 12 weeks. Animals were individually housed. Daily provision of a chaff-based, complete diet (measured DE, 8.5 MJ/kg DM) was restricted to 1% of actual BM as DMI daily. BCS, girth measurements and ultrasound-derived measures of subcutaneous fat depth overlying the gluteal region and 12th intercostal space (rib-eye) were recorded weekly. Body fat content was estimated at the beginning and end of the study by deuterium oxide dilution methods. Clinical biochemistry was monitored weekly. Behaviour was observed (24 h, 3/5 ponies) on 3 occasions. RESULTS: BM decreased by 4.3 ± 1.1% during the first week and thereafter by 0.7 ± 0.1% of BM at end of Week 1 each week. BCS remained constant. Heart and belly girths, rump width and subcutaneous fat depth at rib-eye decreased significantly with time and BM. Fat comprised 45 ± 19% of BM loss. Fatter animals lost relatively more fat. With decreased feeding activity, time spent in 'play' and rest increased by 36 ± 11% and 438 ± 95%, respectively. CONCLUSIONS: This plane of nutrition resulted in an overall rate of weight loss of 1% of outset BM weekly. BCS was not a useful index of early weight loss but heart and belly girths and subcutaneous rib-eye fat were identified as alternative markers. POTENTIAL RELEVANCE: This study provides an evidence-base for the management of weight loss in obese animals, especially those for which exercise may be contra-indicated.

Current perceptions of 'Brazilian butt lift' (BBL) surgery in the UK: A BAAPS-led survey of BAAPS members.

BACKGROUND: The BAAPS advice against Brazilian butt lift (BBL) surgery in the UK was set in October 2018. A Delphi study conducted by BAAPS highlighted the importance of defining current practice and perceptions amongst UK surgeons, as this is currently unknown. OBJECTIVES: To evaluate BAAPS members' current practice and perceptions around BBL surgery to ensure patient safety and propose better recommendations. METHODS: A BAAPS-commissioned survey was emailed to all BAAPS members through an on-line link. The survey collected quantitative and qualitative information in several domains. RESULTS: This survey received a 44% response rate. Of 102 respondents, 32 surgeons undertook BBL surgery before the BAAPS advice to halt it. There was a wide variation in actual fat volumes injected, and in perceptions of what constituted a small or large volume. Virtually all respondents (96.9%) performed only subcutaneous fat injections. There were differences in fat harvest techniques. The majority (66.7%) felt that BAAPS should maintain its recommendation against undertaking BBL surgery until further data became available. Nearly a quarter of 102 respondents (20.6%) had been treated for BBL complications, the majority as a result of surgical tourism. CONCLUSIONS: The survey provides member-reported perception and experience with regard to BBL surgery in the UK. The demand for BBL surgery and its provision should be reassessed in the UK. This information will be analysed with further national and international data to better define and shape the scope of the safety of BBL surgery in the UK. BAAPS will use such data towards the production of future guidance and support for surgeons and patients.

Circannual variation in plasma adrenocorticotropic hormone concentrations and dexamethasone suppression test results in Standardbred horses, Andalusian horses and mixed-breed ponies.

OBJECTIVE: To compare circannual plasma concentrations of adrenocorticotropic hormone (ACTH) and seasonal dexamethasone suppression test (DST) results between three different equine breed groups. METHODS: Six Standardbred horses, six Andalusian horses and six mixed-breed ponies were followed over a 1-year period, during which time groups were managed identically. Blood samples were collected monthly (around the autumn equinox) or in every second month (other times of the year) for the determination of plasma ACTH concentrations using a chemiluminescent immunoassay. Overnight DSTs were performed quarterly, with suppression of plasma cortisol to below 27 nmol/L at 19 h considered a normal result. RESULTS: Seasonal variation in plasma ACTH concentrations was present among all breed groups with, as expected, higher levels detected around the autumn equinox, from February to April (P < 0.001). Plasma ACTH concentrations were different between breed groups in March, with higher levels in Andalusians compared with Standardbreds (P = 0.048) and in ponies compared with Standardbreds (P = 0.010). Suppression of cortisol during the DST was normal for all animals in winter, spring and summer, but five Andalusians and three ponies returned abnormally high results in autumn, compared with zero Standardbreds. CONCLUSION: Higher plasma ACTH concentrations and more false-positive DST results were obtained during autumn in ponies and Andalusian horses when compared with Standardbred horses. Potential differences between breeds should be considered when interpreting test results for horses and ponies that are evaluated for pituitary pars intermedia dysfunction. Further work is recommended to establish population-based reference intervals and clinical cut-off values for ACTH in different equine breeds.

Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors.

Most traditional cytotoxic anticancer agents ablate the rapidly dividing epithelium of the hair follicle and induce alopecia (hair loss). Inhibition of cyclin-dependent kinase 2 (CDK2), a positive regulator of eukaryotic cell cycle progression, may represent a therapeutic strategy for prevention of chemotherapy-induced alopecia (CIA) by arresting the cell cycle and reducing the sensitivity of the epithelium to many cell cycle-active antitumor agents. Potent small-molecule inhibitors of CDK2 were developed using structure-based methods. Topical application of these compounds in a neonatal rat model of CIA reduced hair loss at the site of application in 33 to 50% of the animals. Thus, inhibition of CDK2 represents a potentially useful approach for the prevention of CIA in cancer patients.

Prediction of incipient pasture-associated laminitis from hyperinsulinaemia, hyperleptinaemia and generalised and localised obesity in a cohort of ponies.

REASONS FOR PERFORMING STUDY: The ability to predict ponies at increased risk of laminitic episodes, when exposed to nutrient dense pasture, would facilitate management to avoid disease. OBJECTIVES: To identify variables and clinically useful cut-off values with reproducible diagnostic accuracy for the prediction of ponies that subsequently developed laminitis when exposed to nutrient dense pasture. METHODS: A cohort of predominantly Welsh and Dartmoor ponies from a closed herd was evaluated in March 2006 (n = 74) and March 2007 (n = 57). Ponies were categorised as never laminitic or previously laminitic according to reported laminitic history and as clinically laminitic (CL) if laminitis was observed within 3 months following evaluation. Body condition score (BCS), cresty neck score (CNS), girth and neck circumferences (NC), withers height, blood pressure and hoof surface temperature, and plasma insulin, glucose, triglyceride, leptin, cortisol, ACTH, uric acid and TNF-alpha concentrations were measured. Analysis of sensitivity, specificity and receiver operating characteristic curves was used to evaluate the diagnostic accuracy for a variable to predict CL ponies. RESULTS: Variables with diagnostic accuracy for the prediction of CL ponies included insulin, leptin, BCS, CNS, and NC:height ratio. Specific cut-off values of insulin (>32 mu/l), leptin (>73 ng/ml), BCS (> or = 7), CNS (> or = 4) and NC:height ratio (>0.71) had reproducible diagnostic accuracy for the prediction of laminitis. Combining tests did not result in higher diagnostic accuracy than individual tests of insulin or leptin during either evaluation. CONCLUSIONS: Tests of insulin and leptin concentrations and measures of generalised (BCS) and localised (CNS or NC:height ratio) obesity were beneficial in the prediction of laminitic episodes. POTENTIAL RELEVANCE: These results highlight the importance of monitoring and reducing insulin concentration, and generalised and regional obesity in ponies to reduce risk of laminitis.

Characterization of insulin and IGF-1 receptor binding in equine liver and lamellar tissue: implications for endocrinopathic laminitis.

Although it is well established that equine laminitis can be triggered by extreme hyperinsulinemia, the mechanism of insulin action is not known. High concentrations of insulin lead to separation of the weight-bearing apparatus from the hoof wall and are associated with an increased cycle of cell death and proliferation in the lamellae. Gene expression and immunohistochemistry studies have indicated that the lamellae are sparsely populated with insulin receptors, whereas IGF-1 receptors (IGF-1R) are abundant, suggesting that the action of insulin may be mediated by insulin binding to the IGF-1R. To investigate this possibility, cell membrane fragments containing IGF-1R were extracted from the livers of 6 horses and the lamellae of >50 horses euthanized for nonresearch purposes at an abattoir. Radioligand-binding studies using 125I-IGF-1 and 125I-insulin confirmed an abundance of high-affinity IGF-1R in the liver (KD 0.11 nM, Bmax 223 fmol/mg protein) and lamellae (KD 0.16 nM, Bmax 243 fmol/mg protein). However, the affinity of insulin for binding to the lamellar IGF-1R (Ki 934 nM) was >5,800 fold less than that of IGF-1, suggesting that insulin is unlikely to bind to equine IGF-1R at physiological concentrations. Although insulin receptors could be detected in the liver (KD 0.48 nM, Bmax 123 fmol/mg protein), they were barely detectable in lamellae (estimated Bmax 14 fmol/mg protein). There was no evidence to support the presence of insulin/IGF-1 hybrid receptors in either tissue. These findings suggest that insulin does not act directly through IGF-1 receptors and that an alternative theory is required to explain the mechanism of insulin action in laminitis.

Effects of a commercial dose of L-tryptophan on plasma tryptophan concentrations and behaviour in horses.

REASON FOR PERFORMING STUDY: L-tryptophan is a common ingredient in equine calmative products, but its effectiveness has not been demonstrated in horses. HYPOTHESIS: To determine whether a commercial dose of L-tryptophan increases plasma tryptophan and alters behaviour in horses fed a roughage or concentrate meal. METHODS: L-tryptophan (6.3 g) or placebo (water) was administered per os in a cross-over design, to 12 Thoroughbred horses (503 +/- 12.1 kg bwt), just before a meal of lucerne hay or oats. Plasma tryptophan was measured by gas chromatography. Horse behaviour was observed in an empty enclosure, then in the presence of an unfamiliar person and a novel object. RESULTS: Total plasma tryptophan increased 3-fold in both studies, peaking 1.5-2 h after dosing. After the peak, tryptophan remained high for several hours if the horses had been fed hay, but fell sharply if fed oats, consistent with the glycaemic responses to these meals. However, the ratio of tryptophan to 4 large neutral amino acids (phenylalanine, tyrosine, leucine and isoleucine) increased in the tryptophan-treated horses to a similar extent and for a similar duration, with both diets. The presence of a stranger or novel object increased heart rate (P<0.05), but caused no behavioural effects that were altered by tryptophan, regardless of the diet. CONCLUSIONS: Plasma tryptophan increases when tryptophan is administered at a dose used in some commercial products, but this is not reflected by marked behavioural changes in the horse. POTENTIAL RELEVANCE: Further work is required to refine behavioural tests and identify an effective dose of L-tryptophan in the horse.

Effect of varying the dose of corn syrup on the insulin and glucose response to the oral sugar test.

BACKGROUND: The oral sugar test (OST) is used to identify equine insulin dysregulation (ID); however only a dose of 0.15 mL/kg bwt corn syrup has been evaluated. OBJECTIVES: To determine the effect of varying the dose of corn syrup on insulin and glucose response to the OST and the test's ability to distinguish between ponies with a history of laminitis (PL) and without laminitis (NL). STUDY DESIGN: Randomised crossover experiment. METHODS: After an overnight fast, in a three-way randomised crossover study with a 7-day washout, 0.15, 0.3 or 0.45 mL/kg bwt corn syrup was administered orally to eight ponies (5 PL and 3 NL) and blood obtained between 0 and 120 min. Serum [insulin] and [glucose] were measured using previously validated radioimmunoassay and colorimetric assays respectively. The repeatability of and the effect of continued pasture access on the dose that best distinguished PL and NL ponies were then assessed. The effect of dose, laminitis history and fasting on serum [insulin] and [glucose] responses were assessed using mixed-effects models. RESULTS: The serum [insulin] following 0.15 mL/kg bwt were not significantly different from 0.3 mL/kg bwt at any time point, while serum [insulin] following 0.45 mL/kg bwt significantly (P<0.01) differed from 0.15 and 0.3 mL/kg bwt at all time points apart from 0 min. The serum [insulin] concentration significantly (P<0.01) differed between NL (mean 86 [95% CI 59, 113] µiu/mL) and PL (146 [95% CI 124, 167] µiu/mL) only following 0.45 mL/kg bwt at 60 min. Repeatability of serum [insulin] at 60 min following 0.45 mL/kg bwt dose under fasted conditions was 0.51. Using AUC insulin improved repeatability to 0.83. There was no significant difference between the fasted and at pasture results. MAIN LIMITATIONS: The OST was performed in small numbers of ponies on limited occasions. CONCLUSIONS: A dose of 0.45 mL/kg bwt corn syrup may be preferable to differentiate PL and NL ponies.

Effect of age and dietary carbohydrate profiles on glucose and insulin dynamics in horses.

BACKGROUND: Glucose and insulin dynamics may be different in adult and aged horses. OBJECTIVES: To determine the effects of age and dietary carbohydrates on glucose and insulin dynamics in healthy horses. STUDY DESIGN: Balanced Latin square with four isocaloric diets: CONTROL (hay plus restricted-starch-and-sugar fortified pellets), STARCH (control plus kibbled corn), FIBER (control plus unmolassed sugar beet pulp/soybean hull pellets) and SUGAR (control plus dextrose powder). METHODS: A total of 16 healthy Thoroughbreds and Standardbreds divided into two age groups: ADULT (8.8 ± 2.9 years; n = 8) and AGED (20.6 ± 2.1 years; n = 8). Following dietary adaptation, horses underwent an insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT), modified oral sugar test (OST) and dietary meal challenge. Outcome variables included: insulin sensitivity (SI), disposition index (DI), glucose effectiveness (Sg) and acute insulin response to glucose (AIRg) from the FSIGTT; peak glucose, peak insulin, time to peak, area under the curve for glucose (AUCg) and insulin (AUCi) from the OST and dietary meal challenge. Data were analyzed using multivariable linear mixed regression modelling. RESULTS: AIRg was higher in AGED (mean [95% confidence interval]; 582.0 [455.0-709.0]) vs. ADULT (358.0 [224.0-491.0]; P = 0.03). ADULT and AGED horses had a higher SI on STARCH (adult: 3.3 [2.3-4.2]; aged: 2.8 [1.9-3.7]) and SUGAR (adult: 3.4 [2.5-4.3]; aged: 4.0 [3.1-4.9]) diets compared with CONTROL (adult: 2.0 [1.1-2.9], P = 0.029 (starch), P = 0.009 (sugar); aged: 1.4 [0.5-2.2], P = 0.009 (starch), P < 0.001 (sugar)). Feeding a STARCH (adult: 21581.0 [15029.0-28133.0]; aged: 35205.0 [29194.0-41216.0]) or SUGAR (adult: 26050.0 [19885.0-32215.0]; aged: 25720.0 [19770.0-31670.0]) meal resulted in postprandial hyperinsulinaemia (AUCi). MAIN LIMITATIONS: Study cohort contained two insulin-sensitive breeds and no insulin-resistant breeds. CONCLUSIONS: Age and diet should be considered when evaluating glucose and insulin dynamics.

Effect of dietary carbohydrates and time of year on ACTH and cortisol concentrations in adult and aged horses.

Diagnosis of equine pituitary pars intermedia dysfunction (PPID) remains a challenge as multiple factors (stress, exercise, and time of year) influence ACTH and cortisol concentrations. To assess endocrine status in a study designed to evaluate the effects of age and diet on glucose and insulin dynamics, we performed thyrotropin-releasing hormone (TRH) stimulation tests and overnight dexamethasone suppression tests in March, May, August, and October on 16 healthy Thoroughbred and Standardbred mares and geldings. Horses were grouped by age: adult (mean ± SD; 8.8 ± 2.9 yr; n = 8) and aged (20.6 ± 2.1 yr; n = 8). None of the horses showed clinical signs (hypertrichosis, regional adiposity, skeletal muscle atrophy, lethargy) of pituitary pars intermedia dysfunction. Horses were randomly assigned to groups of 4, blocked for age, and fed grass hay plus 4 isocaloric concentrate diets (control, starch-rich, fiber-rich, and sugar-rich) using a balanced Latin square design. Data were analyzed using a multivariable linear mixed regression model. Baseline ACTH was significantly higher in aged horses (mean ± standard error of the mean; 60.0 ± 10.7 pg/mL) adapted to the starch-rich diet compared to adult horses (15.7 ± 12.0 pg/mL) on the same diet (P = 0.017). After controlling for age and diet, baseline ACTH concentrations were significantly increased in October (57.7 ± 7.1 pg/mL) compared to March (13.2 ± 7.1 pg/mL; P < 0.001), May (12.4 ± 7.1 pg/mL; P < 0.001), and August (24.2 ± 7.1 pg/mL; P < 0.001), whereas post-TRH ACTH was higher in August (376.6 ± 57.6 pg/mL) and October (370.9 ± 57.5 pg/mL) compared to March (101.9 ± 57.3 pg/mL; P < 0.001) and May (74.5 ± 57.1 pg/mL; P < 0.001). Aged horses had significantly higher post-dexamethasone cortisol on the starch-rich diet (0.6 ± 0.1 µg/dL) compared to the sugar-rich diet (0.2 ± 0.1 µg/dL; P = 0.021). Post-dexamethasone cortisol was significantly higher in October (0.6 ± 0.1 µg/dL) compared to March (0.3 ± 0.1 µg/dL; P = 0.005), May (0.2 ± 0.1 µg/dL; P < 0.001), and August (0.3 ± 0.1 µg/dL; P = 0.004). Breed did not influence ACTH or cortisol measurements. In conclusion, in addition to age and time of year, diet is a potential confounder as animals on a starch-rich diet may be incorrectly diagnosed with pituitary pars intermedia dysfunction.

Cell specific microvesicles vary with season and disease predisposition in healthy and previously laminitic ponies.

Microvesicles are small (up to 1 µm) vesicles found in plasma and other bodily fluids. They are recognised as part of the normal system of inter-cellular communication but altered numbers are also used as biomarkers of disease. Microvesicles have not been studied in detail in the horse but may be relevant to diseases such as laminitis. Identification of equine cell specific microvesicles was performed by developing a panel of cross reactive antibodies to use in flow cytometry to detect microvesicles of platelet, leucocyte and endothelial origin in plasma from healthy ponies and those predisposed to laminitis. The total number and proportion of microvesicles from the different cell types varied with season and there were more annexin V positive endothelial MV in non laminitic ponies compared to previously laminitic ponies. Development of this antibody panel and the technique for measuring microvesicles in the horse opens a new field for further investigation of these important structures in equine health and disease.

Effects of age and diet on glucose and insulin dynamics in the horse.

BACKGROUND: Age and diet may affect insulin sensitivity (SI) but these factors have received limited investigation in horses. OBJECTIVES: To measure minimal model parameters during an insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT) after adaptation to a forage only diet (HAY) or forage supplemented with either starch/sugar-rich (SS) or oil/fibre-rich (FF) concentrate feeds; and to assess glucose and insulin responses to a standardised meal challenge (SMC, 4 g/kg BW of SS) after diet adaptation in adult and aged mares. STUDY DESIGN: Latin square design with eight adult (5-12 years) and nine aged (>19 years) healthy mares. METHODS: Diets were fed for 6 weeks, and the FSIGTT and SMC were performed after 31-32 and 41 days on each diet respectively. Data were analysed by a mixed ANOVA for repeated measures. RESULTS: Acute insulin response to glucose (AIRg) was greater and SI was lower in aged horses, compared with adults, regardless of diet. Both AIRg and SI were greater in aged mares after adaptation to SS, as compared with HAY. Similar trends, although not statistically significant, were observed after adaptation to SS in adult mares. Peak insulin concentration and area under the insulin vs. time curve during the SMC were greater in aged than adult mares with all diets. Furthermore, area under the glucose vs. time curve was lower after adaptation to SS, when compared with other diets, in both groups. MAIN LIMITATIONS: Transient weight loss occurred at the beginning of the study and only one sex was included. Incomplete ingestion of the SMC by four mares was another limitation. CONCLUSIONS: Insulin responses to i.v. and enteral nonstructural carbohydrate challenge increase with age in healthy horses, regardless of diet fed.

Plasma adrenocorticotropic hormone (ACTH) concentrations in ponies measured by two different assays suggests seasonal cross-reactivity or interference.

BACKGROUND: Analysis of plasma adrenocorticotropic hormone concentration [ACTH] aids diagnosis of pituitary pars intermedia dysfunction (PPID). Comparisons of the validated chemiluminescent-immunoassay (CI) and immunofluorescent (IF) assays are limited. OBJECTIVES: To compare the results of [ACTH] analysis by CI and IF methods of samples collected in autumn and spring and assess cross-reactivity. STUDY DESIGN: Method comparison. METHODS: Plasma from nonlaminitic ponies was analysed concurrently using the IF and CI methods in autumn and the following spring. Diagnostic thresholds for the IF method were derived using ROC curves and Youden indices to correspond with CI thresholds. Assay specificity was assessed using commercially available ACTH fragments and degradation products of endogenous ACTH. RESULTS: CI and IF methods yielded different results (P<0.001); mean differences (CI-IF), (95% confidence intervals): Autumn (n=99) 38.6 (30.6-46.5) pg/ml, Spring (n=88) 5.1 (3.9-6.3) pg/ml. The association between CI and IF results differed in autumn and spring, consistent with seasonally dependent cross-reactivity or interference. Good (κ=0.66-0.74) agreement was obtained for binary interpretation in spring between IF and CI using thresholds of >24 and >29 pg/ml respectively and in autumn between IF and CI using thresholds of >27 and >47 pg/ml respectively or >33 and >77 pg/ml respectively. Of 88 ponies with both spring and autumn samples, 56 (64%) exceeded a published autumn CI threshold (>47 pg/ml), of which 39 (70%) were below the equivalent threshold (<29 pg/ml) the following spring without treatment. The CI assay showed apparent increases in [ACTH] following addition of CLIP (ACTH 18-39). Degradation of ACTH during storage affected the assays differently. MAIN LIMITATIONS: Limited numbers of PPID cases were included. Immunoreactivity of commercially available peptides may differ from their endogenous equivalents. CONCLUSIONS: The methods yielded different absolute values but the agreement for binary classification was good. An altered pituitary secretome in autumn that affects apparent [ACTH] values is likely. The Summary is available in Spanish - see Supporting information.