Mild-moderate equine asthma: A scoping review of evidence supporting the consensus definition.

Current consensus defines mild-moderate equine asthma (mEA; previously inflammatory airway disease) by a hierarchy of indicators of lung pathology: cough, poor performance, increased tracheobronchial mucus, inflammatory bronchoalveolar lavage (BAL) cytology and pulmonary dysfunction. Exclusion criteria include fever, systemic disease, or increased resting respiratory effort. The aim of this review was to inform future research by identifying gaps, strengths and weaknesses in the current body of evidence supporting this consensus-proposed definition. Objectives were to critique evidence supporting the inclusion of each diagnostic indicator in the case definition, by summarising and evaluating evidence for its association with higher-level indicators of lung inflammation. Searches of three databases identified 2275 articles relating to mEA or its diagnostic indicators, from which 298 full-text articles were screened and 45 reviewed in full. Studies (n = 44) had been performed worldwide in clinics, hospitals, racetracks, yards or research herds, in 6092 horses. Studies were predominantly opportunistic observational (n = 13/44: 29.5%) or cross-sectional (n = 11/44; 25%). The median number of horses per study was 74. Where breed and use were reported most were Thoroughbreds (58.2%; 2730/4688) and racehorses (72.8%; n = 3960/5439). Domains rated as high risk of bias in almost 50% of articles were 'study power' and 'masking'. Heterogeneity in clinical and laboratory measures precluded meta-analysis. Evidence was more consistent for certain pairwise relationships (e.g., between cough and tracheobronchial mucus) than others (e.g., BAL cytology and lung function). Findings highlight the need for increased standardisation of diagnostic methods and reporting to facilitate future systematic review and meta-analysis.

Skin masses in dogs under one year of age.

OBJECTIVES: To utilise a large histopathology database to ascertain the incidence and nature of skin masses in young dogs from 0 to 12 months of age. MATERIALS AND METHODS: A total of 2554 submissions received for histopathology from dogs 0 to 12 months of age, clinically diagnosed with a skin mass between 2006 and 2013, were retrieved from the database of a large commercial diagnostic laboratory. The histological diagnosis and site of the lesion, together with age, breed and sex of the dog were recorded. RESULTS: The most common skin mass found in this study was histiocytoma (n=2212, 86.6%). The majority of all submissions were neoplastic (n=2408, 94.3%), and most of those were benign (n=2372, 98.5%). Almost all of the benign neoplastic lesions were of round cell origin (n=2229, 94.0%) whereas most of the non-neoplastic lesions were derived from the epithelium (n=136, 93.8%). The five most commonly diagnosed skin masses in young dogs were histiocytoma, papilloma, dermoid cyst, follicular cyst and mast cell tumour. A male predisposition was shown for histiocytoma (odds ratio 1.72) and mast cell tumour (odds ratio 2.18) with a strong site predilection for the limb region (30.8% and 27.8% respectively). Dermoid cysts and follicular cysts were most commonly found in the skin of the abdomen (64.7% and 52.3% respectively) with boxers being predisposed (25.9% of dermoid cyst and 25.0% of follicular cyst). CLINICAL SIGNIFICANCE: A large proportion of skin mass submissions in young dogs were neoplastic and benign. Also, the most common skin mass in young dogs was found to be histiocytoma. Tumours can occur in this age group and should be considered as a potential differential diagnosis also in young patients presenting with a skin mass.

Cost-effectiveness of health coaching and financial incentives to promote physical activity after total knee replacement.

OBJECTIVE: We evaluated the cost-effectiveness of Telephonic Health Coaching and Financial Incentives (THC + FI) to promote physical activity in total knee replacement recipients. DESIGN: We used the Osteoarthritis Policy Model, a computer simulation of knee osteoarthritis, to evaluate the cost-effectiveness of THC + FI compared to usual care. We derived transition probabilities, utilities, and costs from trial data. We conducted lifetime analyses from the healthcare perspective and discounted all cost-effectiveness outcomes by 3% annually. The primary outcome was the Incremental Cost-Effectiveness Ratio (ICER), defined as the ratio of the differences in costs and Quality-Adjusted Life Years (QALYs) between strategies. We considered ICERs <$100,000/QALY to be cost-effective. We conducted one-way sensitivity analyses that varied parameters across their 95% confidence intervals (CI) and limited the efficacy of THC + FI to 1 year or to 9 months. We also conducted a probabilistic sensitivity analysis (PSA), simultaneously varying cost, utilities, and transition probabilities. RESULTS: THC + FI had an ICER of $57,200/QALY in the base case and an ICER below $100,000/QALY in most deterministic sensitivity analyses. THC + FI cost-effectiveness depended on assumptions about long-term efficacy; when efficacy was limited to 1 year or to 9 months, the ICER was $93,300/QALY or $121,800/QALY, respectively. In the PSA, THC + FI had an ICER below $100,000/QALY in 70% of iterations. CONCLUSIONS: Based on currently available information, THC + FI might be a cost-effective alternative to usual care. However, the uncertainty surrounding this choice is considerable, and further research to reduce this uncertainty may be economically justified.

Combining online and in-person methods to evaluate the content validity of PROMIS fatigue short forms in rheumatoid arthritis.

PURPOSE: Fatigue is frequent and often severe and disabling in RA, and there is no consensus on how to measure it. We used online surveys and in-person interviews to evaluate PROMIS Fatigue 7a and 8a short forms (SFs) in people with RA. METHODS: We recruited people with RA from an online patient community (n = 200) and three academic medical centers (n = 84) in the US. Participants completed both SFs then rated the comprehensiveness and comprehensibility of the items to their fatigue experience. Cognitive debriefing of items was conducted in a subset of 32 clinic patients. Descriptive statistics were calculated, and associations were evaluated using Pearson and Spearman correlation coefficients. RESULTS: Mean SF scores were similar (p ≥ .61) among clinic patients reflecting mild fatigue (i.e., 54.5-55.9), but were significantly higher (p < .001) in online participants. SF Fatigue scores correlated highly (r ≥ 0.82; p < .000) and moderately with patient assessments of disease activity (r ≥ 0.62; p = .000). Most (70-92%) reported that the items "completely" or "mostly" reflected their experience. Almost all (≥ 94%) could distinguish general fatigue from RA fatigue. Most (≥ 85%) rated individual items questions as "somewhat" or "very relevant" to their fatigue experience, averaged their fatigue over the past 7 days (58%), and rated fatigue impact versus severity (72 vs. 19%). 99% rated fatigue as an important symptom they considered when deciding how well their current treatment was controlling their RA. CONCLUSIONS: Results suggest that items in the single-score PROMIS Fatigue SFs demonstrate content validity and can adequately capture the wide range of fatigue experiences of people with RA.

Cost-effectiveness of generic celecoxib in knee osteoarthritis for average-risk patients: a model-based evaluation.

OBJECTIVE: The cost-effectiveness of the recently-introduced generic celecoxib in knee OA has not been examined. METHOD: We used the Osteoarthritis Policy (OAPol) Model, a validated computer simulation of knee OA, to evaluate long-term clinical outcomes, costs, and cost-effectiveness of generic celecoxib in persons with knee OA. We examined eight treatment strategies consisting of generic celecoxib, over-the-counter (OTC) naproxen, or prescription naproxen, with or without prescription or OTC proton-pump-inhibitors (PPIs) to reduce gastrointestinal (GI) toxicity. In the base case, we assumed that annual cost was $130 for OTC naproxen, $360 for prescription naproxen, and $880 for generic celecoxib. We considered a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY) and discounted costs and benefits at 3% annually. In sensitivity analyses we varied celecoxib toxicity, discontinuation, cost, and pain level. RESULTS: In the base case analysis of the high pain cohort (WOMAC 50), celecoxib had an incremental cost-effectiveness ratio (ICER) of $284,630/QALY compared with OTC naproxen. Only under highly favorable cost, toxicity, and discontinuation assumptions (e.g., annual cost below $360, combined with a reduction in the cardiovascular (CV) event rates below baseline values) was celecoxib likely to be cost-effective. Celecoxib might also be cost-effective at an annual cost of $600 if CV toxicity were eliminated completely. In subjects with moderate pain (WOMAC 30), at the base case CV event rate of 0.2%, generic celecoxib was only cost-effective at the lowest plausible cost ($190). CONCLUSION: In knee OA patients with no comorbidities, generic celecoxib is not cost-effective at its current price.

Prevention of needle stick injury in the clinical setting among new registered nurses

Background: Needle stick injury is one of the greatest work-related health hazard, that registered nurses encounter on an everyday basis for example the risk of being exposed to dangerous and deadly blood borne pathogens through contaminated needle sticks such as human immunodeficiency virus (HIV) and hepatitis viruses. New registered nurses' lacking knowledge and skills regarding standard precautions are exposed to needle stick injuries from unsafe practices such as recapping of needles, manipulating used needles such as bending, breaking or cutting hypodermic needles and passing needles from one nurse to another (American Nurses Association 2002). Methods: This was a quantitative descriptive study. The dependent variable was the needle stick injury and the independent variables consisted of factors which influenced the occurrence of needle stick injuries among new registered nurses. The factors are practice, knowledge, resources and attitudes. The population was new registered nurses with less than three years' experience at the San Fernando General Hospital. A total of 120 new registered nurses were employed during the period under review and the entire population was used as the sample. A 26 item instrument was used to collect data which were analyzed using SPSS version 20. Findings: Most of the respondents 59 (49.2%) were between the ages 20-<30 years and 88 (73.4%) were female. The most common years' experience was 53 (44.2%). Almost half 54 (45%) respondents had experienced a needle stick injury with the most common exposure being while in use (17.5%) and recapping needles (215%). A total of 49 (40.8%) respondents had at least one to less than 3 needle sticks since employment and this was most common among staff on the medical wards. There was a moderate correlation between respondents knowledge about institution's policies and need for training (r0.409, p0.01) and strong correlation between their perception of the need to be more vigilant and the quality of the sharps that they are provided with (r0.913, p0.01). Conclusion: Avoidable practices such as non-adherence to standard precautions while using hypodermic needles are contributing factors to needle stick injuries. Prevention of NSI's should be an integral part of occupational health programs in the work place. Therefore, mandatory training and evaluation of health care worker's, knowledge and attitude regarding safety practices and proper use of available resources should be enforced when carrying out their duties in the clinical area.

An outbreak of norovirus GI-6 infection following a wedding in North West England.

In August 2015 a gastroenteritis outbreak occurred following a wedding. An outbreak investigation was undertaken and a cohort study was conducted using an online survey. Of 140 guests, 134 received the survey and 113 responded (84·3% response rate). Seventy respondents met the case definition of vomiting and/or diarrhoea within 72 h of the wedding (61·9% attack rate). Fifteen exposures were associated with illness; on stratification, all were confounded by the ham hock starter. Multivariable analysis showed a significant association with exposure to ham hock (risk ratio 6·62, 95% confidence interval 2·19-20·03). Eight guests and two catering staff submitted stool samples. All tested positive for norovirus GI-6 infection, including a food handler who had vomiting less than 48 h before the wedding. A single genotype was detected among all samples, suggesting a single source of contamination. The transmission pattern suggested point-source exposure. The most plausible cause of the outbreak was transmission from an infected food handler via contaminated food. This highlights the importance of appropriate exclusions for symptomatic food handlers. Additionally, the food handler's stool sample was submitted 7 days after symptom resolution. The potential for extended viral excretion, and the extremely low infective dose of norovirus, may mean that current exclusion guidelines are not of sufficient duration.

Lipopolysaccharide and toll-like receptor 4 in dogs with congenital portosystemic shunts.

Surgical attenuation of a congenital portosystemic shunt (CPSS) results in increased portal vein perfusion, liver growth and clinical improvement. Portal lipopolysaccharide (LPS) is implicated in liver regeneration via toll-like receptor (TLR) 4 mediated cytokine activation. The aim of this study was to investigate factors associated with LPS in dogs with CPSS. Plasma LPS concentrations were measured in the peripheral and portal blood using a limulus amoebocyte lysate (LAL) assay. LPS concentration was significantly greater in the portal blood compared to peripheral blood in dogs with CPSS (P = 0.046) and control dogs (P = 0.002). LPS concentrations in the peripheral (P = 0.012) and portal (P = 0.005) blood of dogs with CPSS were significantly greater than those of control dogs. The relative mRNA expression of cytokines and TLRs was measured in liver biopsies from dogs with CPSS using quantitative PCR. TLR4 expression significantly increased following partial CPSS attenuation (P = 0.020). TLR4 expression was significantly greater in dogs that tolerated complete CPSS attenuation (P = 0.011) and those with good portal blood flow on pre-attenuation (P = 0.004) and post-attenuation (P = 0.015) portovenography. Serum interleukin (IL)-6 concentration was measured using a canine specific ELISA and significantly increased 24 h following CPSS attenuation (P < 0.001). Portal LPS was increased in dogs with CPSS, consistent with decreased hepatic clearance. TLR4 mRNA expression was significantly associated with portal blood flow and increased following surgery. These findings support the concept that portal LPS delivery is important in the hepatic response to surgical attenuation. Serum IL-6 significantly increased following surgery, consistent with LPS stimulation via TLR4, although this increase might be non-specific.

Evaluation of Minichromosome Maintenance Protein 7 and c-KIT as Prognostic Markers in Feline Cutaneous Mast Cell Tumours.

Mast cell tumours (MCTs) are a common skin tumour in cats, but there is currently no histological grading system or reliable prognostic marker for this species (unlike the situation for dogs). This study utilized a set of 71 feline cutaneous MCTs with known clinical outcomes to assess the potential of various prognostic markers, including the cellular proliferation marker minichromosome maintenance protein (MCM)-7, mitotic index and various KIT labelling characteristics, including KIT positivity, KIT labelling pattern and KIT immunoreactivity score (IS). Of the factors studied, the mitotic index and the KIT labelling pattern were the only features associated significantly with survival times, while the proliferation marker MCM7 and the KIT IS were not. The study also highlights the variability of KIT labelling characteristics between tumours, which may prevent use of this marker as a diagnostic and prognostic tool.

Markers of angiogenesis associated with surgical attenuation of congenital portosystemic shunts in dogs.

BACKGROUND: Dogs with congenital portosystemic shunts (CPSS) have hypoplasia of the intrahepatic portal veins. Surgical CPSS attenuation results in the development of the intrahepatic portal vasculature, the precise mechanism for which is unknown, although new vessel formation by angiogenesis is suspected. HYPOTHESIS: That the degree of portal vascular development and the increase in portal vascularization after CPSS attenuation is significantly associated with hepatic vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) gene expression and serum VEGF concentration. ANIMALS: Client-owned dogs with CPSS undergoing surgical treatment. Forty-nine dogs were included in the gene expression data and 35 in the serum VEGF data. MATERIALS AND METHODS: Dogs surgically treated by partial or complete CPSS attenuation were prospectively recruited. Relative gene expression of VEGF and VEGFR2 was measured in liver biopsy samples taken at initial and follow-up surgery using quantitative polymerase chain reaction. Serum VEGF concentration was measured before and after CPSS attenuation using a canine specific ELISA. Statistical significance was set at the 5% level (P ≤ .05). RESULTS: There was a significant increase in the mRNA expression of VEGFR2 after partial attenuation (P = .006). Dogs that could tolerate complete attenuation had significantly greater VEGFR2 mRNA expression than those that only tolerated partial attenuation (P = .037). Serum VEGF concentration was significantly increased at 24 (P < .001) and 48 (P = .003) hours after attenuation. CONCLUSIONS AND CLINICAL IMPORTANCE: These findings suggest that intrahepatic angiogenesis is likely to occur after the surgical attenuation of CPSS in dogs, and contributes to the development of the intrahepatic vasculature postoperatively.

Recombinant canine IgE Fc and an IgE Fc-TRAIL fusion protein bind to neoplastic canine mast cells.

Screening for expression of the high affinity receptor for IgE by reverse transcriptase PCR, revealed that almost all canine mast cell tumors expressed FcɛRIα mRNA, supporting the rationale for developing anti-neoplastic treatments based on molecules that could target this receptor. Use of cytotoxic cytokines to trigger an apoptotic signal is one strategy for inducing cell death in malignant mast cells. The coding sequences for canine IgE and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were identified through genome analyses. Selected regions of the coding sequences for these genes were cloned and compared to the predicted genome sequences. The Fc region of canine IgE, death domain of canine TRAIL and an IgE Fc: TRAIL fusion construct were generated and epitope-tagged proteins expressed, using a eukaryotic expression system. Specific binding of recombinant canine IgE Fc-containing proteins to recombinant human FcɛRIα and to a canine mast cell tumor line expressing FcɛRIα (C2), but not one failing to express FcɛRIα (MCLA), was demonstrated. Specific binding of the IgE: TRAIL fusion protein was not abrogated by the TRAIL moiety. These results are proof of principle that canine IgE targeting to FcɛRIα can be used as a platform for selective delivery of therapies to FcɛRIα-expressing cells, potentially enhancing their therapeutic index and efficacy.

Infectious risk factors and clinical indicators for tracheal mucus in British National Hunt racehorses.

REASONS FOR PERFORMING STUDY: Many studies of respiratory disease in racehorses have focused on a combination of increased tracheal mucus and airway neutrophilia. Examination of each component separately should provide further insight into this condition. OBJECTIVES: To identify infectious risk factors for endoscopically visible tracheal mucus in National Hunt racehorses. STUDY DESIGN: A 2 year prospective longitudinal study. METHODS: Monthly quantitative bacteriological examinations of tracheal wash samples and viral serological examinations were conducted. Risk factors for 'small amounts of mucus' (mucus score = 1/3) and 'increased mucus' (score ≥2/3) were identified. RESULTS: There were increased odds of small amounts of mucus when both Streptococcus zooepidemicus and nonhaemolytic streptococci (NHS) were isolated (odds ratio [OR] 2.6; 95% confidence interval [CI] 1.5-4.6; P<0.001) but not when either species was isolated in the absence of the other. Increased odds of increased mucus were associated with the isolation of either S. zooepidemicus (OR 5.6; 95% CI 1.2-25.9; P = 0.03) or NHS (OR 3.7; 95% CI 1.2-11.6; P = 0.02), with an increased effect when both were isolated together (OR 12.5; 95% CI 3.7-41.6; P<0.001). Approximately 6-fold increased odds of small amounts of mucus were associated with the first 3 months in training (OR 6.3; 95% CI 2.0-19.4; P<0.001) and 3-fold increased odds of increased mucus associated with the first 6 months in training (OR 2.9; 95% CI 1.3-6.4; P = 0.01). Coughing at exercise and increased serous nasal discharge were specific but insensitive indicators of increased mucus. CONCLUSIONS: Associations with S. zooepidemicus corroborate previous research, but an independent effect of NHS has not previously been reported. The possibility that there are individual pathogenic species within this group should be considered. Further work is required to identify S. zooepidemicus subtypes and NHS species associated with disease. Closer monitoring of the respiratory health of horses entering training for the first time is likely to be valuable.

A cross-sectional study of mental health in UK veterinary undergraduates.

Wellbeing (positive mental health) and mental ill-health of veterinary students from a single UK school were quantified using validated psychological scales. Attitudes towards mental ill-health and suicide were also assessed. Results were compared with published data from the UK general population and veterinary profession. Of the total student population (N=1068), 509 (48 per cent) completed a questionnaire. Just over half (54 per cent) of the respondents had ever experienced mental ill-health, with the majority reporting a first occurrence before veterinary school. Student wellbeing was significantly poorer (p<0.0001) than general population estimates, but not significantly different (p=0.2) from veterinary profession estimates. Degree of mental distress in students was significantly higher than in the general population (p<0.0001). Despite the majority (94 per cent) agreeing that 'Anyone can suffer from mental health problems', students were significantly more likely than members of the general population to agree that 'If I were suffering from mental health problems, I wouldn't want people knowing about it' (p<0.0001). Students were more likely to have thought about suicide, but less likely to have made an attempt (p<0.001; p=0.005), than members of the general population. The possibility of non-response bias must be considered when interpreting findings. However, strong similarities between results from this study population and the UK veterinary profession, as well as other veterinary student populations internationally, suggest no substantial school-level bias.

Solution-processed soldering of carbon nanotubes for flexible electronics.

We report a simple lithography-free, solution-based method of soldering of carbon nanotubes with Ohmic contacts, by taking specific examples of multi-walled carbon nanotubes (MWNTs). This is achieved by self-assembling a monolayer of soldering precursor, Pd(2+) anchored to 1,10 decanedithiol, onto which MWNTs could be aligned across the gap electrodes via solvent evaporation. The nanosoldering was realized by thermal/electrical activation or by both in sequence. Electrical activation and the following step of washing ensure selective retention of MWNTs spanning across the gap electrodes. The soldered joints were robust enough to sustain strain caused during the bending of flexible substrates as well as during ultrasonication. The estimated temperature generated at the MWNT-Au interface using an electro-thermal model is ∼150 °C, suggesting Joule heating as the primary mechanism of electrical activation. Further, the specific contact resistance is estimated from the transmission line model.

Histopathological findings in the livers of cats with a congenital portosystemic shunt before and after surgical attenuation.

Histopathological changes are reported in the livers of cats with congenital portosystemic shunts (CPSS) before and after surgical attenuation. Medical records, portovenograms and liver biopsies from cats treated surgically for CPSS were reviewed. Biopsies were graded for histopathological features characteristic of CPSS. Of 40 cats with CPSS included in the study, all had portal vein hypoplasia and arteriolar hyperplasia at initial surgery, 20 (50 per cent) had hepatocyte swelling with microvesicular vacuolar change, 17 (42.5 per cent) had fibrosis, 12 (30 per cent) had hepatocyte swelling with macrovesicular vacuolar change, 8 (20 per cent) had biliary hyperplasia and 2 (5 per cent) had haemosiderin within Küpffer cells. Cats with macrovesicular vacuolar change were significantly older than cats without (P = 0.001), with median ages of 18.5 months and 8.5 months, respectively. Twenty-five cats had partial attenuation of the CPSS at initial surgery, and 16 of these had follow-up biopsy samples. There were no significant differences in the histopathological features of biopsies before and after partial attenuation. From first to second surgery, there was a significant improvement in intrahepatic vasculature on portovenography both before (P = 0.001) and after (P = 0.039) temporary complete attenuation. Following partial CPSS attenuation, there was no significant change in histopathological features despite an improvement in intrahepatic vasculature on portovenography.

The first report of otarine herpesvirus-1-associated urogenital carcinoma in a South American fur seal (Arctocephalus australis).

Otarine herpesvirus (OtHV)-1-associated urogenital carcinoma has been well documented in the California sea lion (Zalophus californianus, CSL), but this is the first report of this tumour in a captive South American fur seal (Arctocephalus australis, SAFS). The gross and microscopical morphology of the tumour in the SAFS was identical to that described previously in CSLs and the tumour in the present case had metastasized within the urogenital tract and draining lymph nodes and to the lungs and one kidney. Immunohistochemistry revealed intra- and extracytoplasmic labelling of herpesvirus antigen in the cells of the tumour tissue and transitional epithelium of the urethra. OtHV-1 nucleic acids were detected within tumour tissue and from a urogenital swab by polymerase chain reaction. The ranges of these two species of pinniped do not overlap normally in the wild, suggesting that transmission of OtHV-1 probably occurred in captivity. This confirmed susceptibility of the SAFS to the development of OtHV-1-associated urogenital carcinoma suggests that all species of Otariidae should be screened for OtHV-1 infection prior to movement within and between zoological collections.