Modified Exact Sample Size for Test Validation Studies Incorporating Adjustment for Clustered Data

ABSTRACT Design of epidemiologic studies for the validation of diagnostic tests necessitates accurate sample size calculations to allow for estimation of diagnostic sensitivity and specificity within a specified level of precision and with the desired level of confidence. The objective of this paper was to design and evaluate a computer algorithm for the calculation of sample sizes for diagnostic accuracy studies incorporating clustered sampling units using a beta-binomial model. A beta-binomial distribution can be used to model a proportion expected to vary across populations. The cluster-adjusted sample size is calculated as the product of the unadjusted sample size by the design effect, which is estimable after definition of the beta distribution. Design effect estimations varied depending upon the 90% limit inputs, hypothesized proportion, and evaluated number of clusters. Beta distributions representing larger variation (wider 90% probability intervals) resulted in larger design effects. Smaller number of clusters for sampling also caused larger design effects. Estimated design effects also tended to increase as the proportion approached 1. It is important to incorporate cluster adjustment to sample size calculations when designing epidemiologic studies for estimation of diagnostic accuracy in the situation of correlated data. Beta-binomial models can be used to account for clustering and design effects can be estimated by inducing beta distributions that encompass among herd variation

Influence of high-protein and high-carbohydrate diets on serum lipid and fructosamine concentrations in healthy cats

Objectives: The aim of this study was to determine whether high-protein and high-carbohydrate diets exert differential effects on serum cholesterol, triglyceride and fructosamine concentrations in healthy cats. Methods A randomised, crossover diet trial was performed in 35 healthy shelter cats. Following baseline health assessments, cats were randomised into groups receiving either a high-protein or high-carbohydrate diet for 4 weeks. The cats were then fed a washout diet for 4 weeks before being transitioned to whichever of the two studied diets they had not yet received. Fasting serum cholesterol, triglyceride and fructosamine concentrations were determined at the end of each 4-week diet period. Results Cats on the high-carbohydrate diet had significantly lower serum cholesterol ( P 5) had lower cholesterol ( P = 0.007) and triglyceride ( P = 0.032) concentrations on the high-protein diet than cats within other BCS groups. Conclusions and relevance Diets higher in protein and lower in carbohydrates appear beneficial for short-term glucose control in healthy cats. A high-protein diet was associated with significantly elevated cholesterol and triglyceride concentrations in healthy cats, even though the increase was significantly less pronounced in cats with a BCS >5. This finding suggests that overweight cats process high-protein diets, cholesterol and triglycerides differently than leaner cats

Chronic pancreatitis in dogs: A retrospective study of clinical, clinicopathological, and histopathological findings in 61 cases

The objective of the present study was to characterize the clinical, clinicopathologic, and histopathologic findings of dogs with chronic pancreatitis. The necropsy database at Texas A&M University was searched for reports of dogs with histologic evidence of chronic pancreatitis defined as irreversible histologic changes of the pancreas, i.e. fibrosis and atrophy. Medical records and necropsy reports were retrieved and reviewed. A reference necropsy population of 100 randomly selected dogs was used for signalment and concurrent disease comparisons. Cases were categorized as clinical or incidental chronic pancreatitis based on the presence of vomiting, decreased appetite, or both versus neither of these signs. All archived pancreata samples were evaluated histologically and scored using a published pancreatic scoring system. A total of 61 dogs with chronic pancreatitis were included in the study. The most frequent clinical signs were lethargy, decreased appetite, vomiting, and diarrhea. Compared to the reference necropsy population, chronic pancreatitis cases were more likely to be older, neutered, and of the non-sporting/toy breed group and to have concurrent endocrine, hepatobiliary, or neurologic diseases. Clinical chronic pancreatitis cases had significantly higher histological scores for pancreatic necrosis and peripancreatic fat necrosis. Clinical chronic pancreatitis cases were significantly more likely to have hepatobiliary or endocrine disease as well as increased liver enzyme activities, and cholesterol and bilirubin concentrations. In conclusion, clinical disease resulting from chronic pancreatitis might be related to the presence of pancreatic necrosis and pancreatic fat necrosis. The signalment, presentation, and concurrent diseases of dogs with chronic pancreatitis are similar to those previously reported for dogs with acute pancreatitis.http://www.elsevier.com/locate/tvjlam2013ab201

Comparison of a Flow Assay for Brucellosis Antibodies with the Reference cELISA Test in West African Bos indicus

Brucellosis is considered by the Food and Agricultural Organisation and the World Health Organisation as one of the most widespread zoonoses in the world. It is a major veterinary public health challenge as animals are almost exclusively the source of infection for people. It is often undiagnosed in both human patients and the animal sources and it is widely acknowledged that the epidemiology of brucellosis in humans and animals is poorly understood, particularly in sub-Saharan Africa. It is therefore important to develop better diagnostic tools in order to improve our understanding of the epidemiology and also for use in the field for disease control and eradication. As with any new diagnostic test, it is essential that it is validated in as many populations as possible in order to characterise its performance and improve the interpretation of its results. This paper describes a comparison between a new lateral flow assasy (LFA) for bovine brucellosis and the widely used cELISA in a no gold standard analysis to estimate test performance in this West African cattle population. A Bayesian formulation of the Hui-Walter latent class model incorporated previous studies' data on sensitivity and specificity of the cELISA. The results indicate that the new LFA is very sensitive (∼87%) and highly specific (∼97%). The analysis also suggests that the current cut-off of the cELSIA may not be optimal for this cattle population but alternative cut-offs did not significantly change the estimates of the LFA. This study demonstrates the potential usefulness of this simple to use test in field based surveillance and control which could be easily adopted for use in developing countries with only basic laboratory facilities

Effects of GnRH vaccination in wild and captive African Elephant bulls (Loxodonta africana) on reproductive organs and semen quality

OBJECTIVES: Although the African elephant (Loxodonta africana) is classified as endangered by the International Union for Conservation of Nature (IUCN), in some isolated habitats in southern Africa, contraception is of major interest due to local overpopulation. GnRH vaccination has been promoted as a non-invasive contraceptive measure for population management of overabundant wildlife. We tested the efficacy of this treatment for fertility control in elephant bulls. METHODS: In total, 17 male African elephants that were treated with a GnRH vaccine were examined in two groups. In the prospective study group 1 (n = 11 bulls, ages: 8±36 years), semen quality, the testes, seminal vesicles, ampullae and prostate, which were all measured by means of transrectal ultrasound, and faecal androgen metabolite concentrations were monitored over a three-year period. Each bull in the prospective study received 5 ml of Improvac® (1000 μg GnRH conjugate) intramuscularly after the first examination, followed by a booster six weeks later and thereafter every 5±7 months. In a retrospective study group (group 2, n = 6, ages: 19±33 years), one examination was performed on bulls which had been treated with GnRH vaccine for 5±11 years. RESULTS: In all bulls of group 1, testicular and accessory sex gland sizes decreased significantly after the third vaccination. In six males examined prior to vaccination and again after more than five vaccinations, the testis size was reduced by 57.5%. Mean testicular height and length decreased from 13.3 ± 2.6 cm x 15.2 ± 2.8 cm at the beginning to 7.6 ± 2.1 cm x 10.2 ± 1.8 cm at the end of the study. Post pubertal bulls (>9 years, n = 6) examined prior to vaccination produced ejaculates with viable spermatozoa (volume: 8±175 ml, sperm concentration: 410-4000x106/ml, total motility: 0±90%), while after 5±8 injections, only 50% of these bulls produced ejaculates with a small number of immotile spermatozoa. The ejaculates of group 2 bulls (vaccinated >8 times) were devoid of spermatozoa. Faecal androgen metabolite concentrations measured in captive males decreased significantly after the fourth vaccination. None of the males entered musth during the treatment period. CONCLUSIONS: Our results showed a marked decrease in semen quality, testicle and secondary sex gland sizes following repeated GnRH vaccinations. After 2±4 years of continuous treatment every 5±7 months, the effects were similar to surgical castration.ISIScopu

Minimally invasive approach to lumbosacral decompression in a cadaveric canine model

AIMS To determine efficacy of a minimally invasive (MI) surgical approach using a human MI lumbar retractor for canine lumbosacral dorsal laminectomy and partial discectomy and to compare this technique to the standard open surgical (OS) approach. METHODS Lumbosacral dorsal laminectomy and partial discectomy was performed on 16 large-breed canine cadavers using either a standard OS (n=8) or MI (n=8) approach. Skin and fascial incision length, procedure time, and intraoperative complications were recorded. Postoperatively specimens were evaluated for laminectomy and discectomy dimensions, and visible damage to the cauda equina and exiting nerve roots. RESULTS Median length of skin and fascial incisions in the OS group were longer than in the MI group (p<0.001). Median laminectomy length was similar between both approaches (p=0.234) but width was greater for the MI than OS approach (p=0.002). Both approaches achieved similar partial discectomy width (p=0.279). Overall surgical time was longer for MI approaches compared to OS, with a median of 18.5 (min 15.5, max 21.8) minutes for MI compared to 14.6 (min 13.1, max 16.9) minutes for OS (p=0.001). CONCLUSIONS The MI approach reduced incision lengths while retaining comparable laminectomy and discectomy dimensions. For this in vitro model the MI approach required more time to complete, but this difference may not be relevant in clinical cases. CLINICAL RELEVANCE Dogs undergoing lumbosacral dorsal laminectomy are commonly large-breed dogs. The traditional open approach requires a large skin incision and soft tissue dissection, especially in overweight animals. A MI approach accomplishing the same surgical result while minimising soft tissue trauma could reduce post-operative pain and recovery time, and may lower wound-related complications. Clinical studies are needed to confirm postoperative benefit and assess operating times in vivo

Anaesthetic, analgesic and cardiorespiratory effects of intramuscular medetomidine-ketamine combination alone or with morphine or tramadol for orchiectomy in cats

Objectives: To compare the anaesthetic, analgesic and cardiorespiratory effects of intramuscular (IM) medetomidine and ketamine administered alone or combined with morphine or tramadol, for orchiectomy in cats. Study design: Randomised, blinded, prospective clinical study. Animals: Thirty client-owned cats. Materials and methods: Cats (n = 10 in each group) received a combination of medetomidine (60 μgkg−1) and ketamine (10 mg kg−1) alone (MedK); combined with morphine (0.2 mg kg−1) (MedKM), or combined with tramadol (2 mg kg−1) (MedKT) IM. Time of induction, surgical and recovery events were recorded, and physiological parameters measured and recorded. Analgesia was evaluated with a visual analogue scale, a composite scoring system and the von Frey mechanical threshold device, every hour from three to eight hours post-drug administration injection. Data were analyzed with a linear mixed model, Kruskal–Wallis or Chi-square tests (p < 0.05). Results: Median (IQR) induction and recovery times (minutes) were not significantly (p = 0.125) different between groups: 5.6 (2.7–8.0), 7.4 (5.1–9.6) and 8.0 (5.8–14.9) for induction and 128.5 (95.1–142.8), 166.4 (123.1–210.0) and 142.9 (123.4–180.2) for recovery, with MedK, MedKT and MedKM, respectively. Two cats (MedKM) required alfaxalone for endotracheal intubation. In all groups, three or four cats required additional isoflurane for surgery. Arterial oxygen tension overall (mean ± SD: 66 ± 2 mmHg) was low. Surgery resulted in increased systolic arterial blood pressure (p < 0.001), haemoglobin saturation (p < 0.001), respiratory (p = 0.003) and heart rates (p = 0.002). Pain scores did not differ significantly between groups. Von Frey responses decreased over time; changes over time varied by treatment (p < 0.001), MedK returning to baseline values more rapidly than MedKM and MedKT. No cat required rescue analgesics. Conclusion and clinical relevance: All three protocols can provide adequate anaesthesia and analgesia for orchiectomy in cats. However, rescue intervention to maintain surgical anaesthesia may be required in some cats. Oxygen supplementation is advised

Magnetic resonance imaging susceptibility artifacts in the cervical vertebrae and spinal cord related to monocortical screw-polymethylmethacrylate implants in canine cadavers.

OBJECTIVE To characterize and compare MRI susceptibility artifacts related to titanium and stainless steel monocortical screws in the cervical vertebrae and spinal cord of canine cadavers. SAMPLE 12 canine cadavers. PROCEDURES Cervical vertebrae (C4 and C5) were surgically stabilized with titanium or stainless steel monocortical screws and polymethylmethacrylate. Routine T1-weighted, T2-weighted, and short tau inversion recovery sequences were performed at 3.0 T. Magnetic susceptibility artifacts in 20 regions of interest (ROIs) across 4 contiguous vertebrae (C3 through C6) were scored by use of an established scoring system. RESULTS Artifact scores for stainless steel screws were significantly greater than scores for titanium screws at 18 of 20 ROIs. Artifact scores for titanium screws were significantly higher for spinal cord ROIs within the implanted vertebrae. Artifact scores for stainless steel screws at C3 were significantly less than at the other 3 cervical vertebrae. CONCLUSIONS AND CLINICAL RELEVANCE Evaluation of routine MRI sequences obtained at 3.0 T revealed that susceptibility artifacts related to titanium monocortical screws were considered mild and should not hinder the overall clinical assessment of the cervical vertebrae and spinal cord. However, mild focal artifacts may obscure small portions of the spinal cord or intervertebral discs immediately adjacent to titanium screws. Severe artifacts related to stainless steel screws were more likely to result in routine MRI sequences being nondiagnostic; however, artifacts may be mitigated by implant positioning

Influence of an Exercise Program, Muscle Strength, Proprioception, and Arm Length on Veterinary Students' Bovine Pregnancy Diagnosis Accuracy

Bovine pregnancy diagnosis (PD) by transrectal palpation (TRP) is an important skill for veterinary graduates. Factors influencing students' PD accuracy were investigated to optimize bovine PD by TRP training without increasing live animal exposure. The objective was to determine whether arm length and strength, proprioception, and exposure to a 6-week exercise training program were significantly associated with students' PD accuracy. Veterinary students (n = 128) who had previously received formal theoretical and practical training in bovine TRP and PD (live cows and TRP simulators) were assessed for PD accuracy on live cows. Prior to assessment, arm muscle strength measurement, an exercise program, and additional TRP sessions on Breed'n Betsy¯ simulators and live cows were offered to the students. Seventy-eight students volunteered to participate in the arm length measurement, muscle strength, and proprioception testing. Of these, 35 randomly allocated students completed a 6-week exercise program, after which muscle strength was reassessed. Each student performed PDs on six cows of which the pregnancy status, ranging from 6 weeks to 9 months pregnant or not pregnant, was predetermined by an experienced veterinarian. PD accuracy was measured as sensitivity and specificity, being defined as the proportion of pregnant or nonpregnant cows, respectively, correctly identified by the student. It is concluded that hand grip strength and participation in an exercise program are significant predictors of veterinary students' PD accuracy. Implementation of an exercise program aimed at improving grip strength in the veterinary curriculum is a novel approach to improve bovine TRP and PD training