Cardiovascular risk management in the peri-operative setting.

Peri-operative cardiovascular events occur in up to 3% of patients undergoing non-cardiac surgery. Accurate cardiovascular risk assessment is important in the peri-operative setting, as it allows informed and shared decisions regarding the appropriateness of proceeding with surgery, guides surgical and anaesthetic approaches, and may influence the use of preventive medications and post-operative cardiac monitoring. Quantitative risk assessment may also inform a reconsideration of choosing a more limited lower risk type of surgery, or conservative management. Pre-operative cardiovascular risk assessment starts with clinical assessment and should include an estimate of functional capacity. Specialised cardiac investigations are rarely indicated specifically to assess pre-operative cardiovascular risk. The decision regarding cardiac investigations is influenced by the nature, extent and urgency of surgery. The strategy of performing pre-operative revascularisation to improve post-operative outcomes is not evidence-based and recent international guidelines recommend against this.

Clinical utility of a rapid 'on-demand' laboratory-based SARS-CoV-2 diagnostic testing service in an acute hospital setting admitting COVID-19 patients.

BACKGROUND: With the onset of the COVID-19 pandemic in 2020, hospital clinical teams have realised that there is a need for a rapid, accurate testing facility that will allow them to move patients quickly into isolation rooms or specific COVID-19 cohort wards as soon as possible after admission. METHODS: Starting from July 2020, PCR-based test platforms, which could test 4-8 samples in parallel with turnaround (sample-to-result) times of 50-80 min, were placed in a satellite laboratory. This laboratory was on the same floor and within walking distance to the acute respiratory admissions ward. It was staffed by a team of three mid-Band 4 staff that split a 0700-2200 h-work day, 7 days a week, with 2 senior supervisors. Urgent sample testing was decided upon by the clinical teams and requested by phone. The test results were entered manually in real-time as they became available, and sent electronically to the requesting ward teams. RESULTS: The daily/monthly PCR positive test numbers approximately followed the local and national UK trend in COVID-19 case numbers, with the daily case numbers being reflective of the November and December 2020 surges. Test results were used to rapidly segregate positive patients into dedicated COVID-19 ward areas to minimise risk of potential nosocomial transmission in crowded waiting areas. Testing capacity was sufficient to include cases with uncertain diagnosis likely to require hospital admission. Following completion of other admission processes, based on these rapid test results, patients were allocated to dedicated COVID-19 positive or negative cohort wards. CONCLUSIONS: This rapid testing facility reduced unnecessary 'length-of-stay' in a busy acute respiratory ward. In the current absence of a treatment for mild-to-moderate COVID-19, on which patients could be discharged home to complete, the rapid test facility has become a successful aid to patient flow and reduced exposure and nosocomial transmission.

Feline allergic diseases: introduction and proposed nomenclature.

BACKGROUND: Feline allergic diseases present as challenging problems for clinicians, not least because of the number of reaction patterns of the feline skin, none of which are specific for allergy. Furthermore, there is some controversy over the nomenclature that should be used in their description. OBJECTIVES: To review the literature, assess the status of knowledge of the topic and the extent to which these diseases could be categorized as atopic in nature, and make recommendations concerning nomenclature. METHODS: Atopic diseases in humans and cats were researched. A comparison then was made of the essential features in the two species. RESULTS: There were sufficient similarities between human atopic diseases and the manifestations of feline diseases of presumed allergic aetiology to justify the use of "atopic" to describe some of the feline conditions affecting the skin, respiratory and gastrointestinal tract. However, none of the allergic skin diseases showed features consistent with atopic dermatitis as described in man and the dog. CONCLUSIONS AND CLINICAL IMPORTANCE: The term "Feline Atopic Syndrome" (FAS) is proposed to encompass allergic diseases of the skin, gastrointestinal tract and respiratory tract, and "Feline atopic skin syndrome" (FASS) proposed to describe allergic skin disease associated with environmental allergies. We are not aware of any adverse food reactions in cats that are attributable to causes other than immunological reactions against the food itself. We therefore propose an aetiological definition of "Food Allergy" (FA) to describe such cases.

Immunopathogenesis of the feline atopic syndrome.

BACKGROUND: Feline diseases of possible allergic origin with similar clinical phenotypes can have a varied underlying pathogenesis. Clinical phenotype, precise aetiology and underlying immunopathogenesis all need to be considered if advances in this neglected area of dermatology are to be made. OBJECTIVES: To document the status of research into the immunopathogenesis of the diseases that fall within the spectrum of the feline atopic syndrome (FAS ), to summarize the conclusions, identify the limitations and recommend future research directions. METHODS AND MATERIALS: A search of the literature was undertaken. The strengths and validity of the data and the contributions to our current understanding of the immunopathogenesis were analysed. Skin diseases of presumed allergic aetiology and asthma were assessed separately, as was the role of antibodies, cells and cytokines in each. RESULTS: The research varied in its quality and its impact often was limited by a failure to employ strict criteria in case selection. This reflected the difficulties of skin reaction patterns associated with a number of inciting causes. Research into feline asthma was handicapped by the difficulties of investigating clinical material, and much of the useful information was derived from experimental models. CONCLUSIONS AND CLINICAL IMPORTANCE: The evidence reviewed was supportive of a role for immunoglobulin (Ig)E in the pathogenesis of both feline atopic skin syndrome (FASS) and asthma, albeit not strongly so. The inflammation noted in both FASS and asthma is accompanied by eosinophils and lymphocytes, and these findings, together with the cytokine expression, are suggestive in some (not all) cats of T-helper type 2 immune dysregulation.

Co-reactivity between related and unrelated environmental allergens in equine allergen-specific IgE serology testing in the UK.

BACKGROUND: Identification of environmental allergens in horses with allergic disease facilitates allergen avoidance and targeted immunotherapy. HYPOTHESIS/OBJECTIVES: To evaluate allergenic co-reactivity between 44 environmental allergens. ANIMALS: Horses with suspected allergic disease (n = 344) whose sera were submitted for environmental allergen testing. METHODS AND MATERIALS: Allergen-specific IgE serological assays were performed using 44 allergens divided into six taxonomically related groups: house dust/storage mites, moulds, insects, grass, tree and weed pollens. Using pairwise comparisons, odds ratios (ORs) were calculated for each environmental pair to determine if there was increased or decreased likelihood of a positive result for one allergen, given a positive result to another. The OR significance was set (using Holm-Bonferroni correction) at P < 0.00006 for all horses (n = 344) and P < 0.00005 for horses with at least one positive reaction (n = 239). Using one-way ANOVA with Tukey's post hoc tests (significance at P < 0.05), differences in mean log e ORs between three groups, taxonomically related allergens with a statistically significant association (related-associated), related allergens lacking a significant association (related-nonassociated) and unrelated allergens were tested. RESULTS: Statistically significant associations were found between both related and unrelated allergen pairs, the former being more frequent. For all horses (n = 344) and horses with at least one positive reaction (n = 239), co-reactivity ranged from 100% (grasses) to 0% (moulds). The weeds group was exceptional in having more co-reactions with another group (grasses). CONCLUSIONS AND CLINICAL IMPORTANCE: Co-reactivity was shown within and between certain related allergen groups. Further studies are required to determine whether this is the result of antigenic cross-reactivity.

Co-sensitization and cross-reactivity between related and unrelated food allergens in dogs - a serological study.

BACKGROUND: Knowledge of cross-reactivity between foods is useful so that potentially cross-reactive allergens can be avoided in diet trials. HYPOTHESIS/OBJECTIVES: To evaluate allergenic cross-reactivity in related foods. ANIMALS: Sera from 469 dogs with suspected adverse food reactions. METHODS: An IgE-based serological assay using 19 food allergens was performed in 469 dogs. Pairwise comparisons were used to calculate the odds ratios (ORs) for each food pair, with significance at P < 0.0002 by Holm-Bonferroni correction, both in all 469 dogs and in the 261 of 469 dogs with at least one positive reaction. One-way ANOVA with Tukey's post hoc tests (significance at P < 0.05) were used to test for differences between mean logE ORs in different food groups. Inhibition enzyme-linked immunosorbent assays (ELISAs) were performed to assess allergenic cross-reactivity between beef, lamb and cow's milk. RESULTS: Significant associations were observed between both related and unrelated food pairs. Associations were, however, more frequent and stronger among related than unrelated foods. In all 469 dogs, 38 of 43 related food pairs were significantly associated [mean (SD) logE OR 3.4 (0.9)] compared with 79 of 128 unrelated pairs [2.7 (1.0)], P < 0.0002. In positive dogs, 32 of 43 related pairs were significantly associated [2.7 [1.0)] compared with 49 of 128 unrelated pairs [1.8 (1.0)], P < 0.0002. Inhibition ELISAs confirmed the presence of cross-reactive IgE-binding epitopes in beef, lamb and cow's milk. CONCLUSIONS AND CLINICAL IMPORTANCE: The results suggest that related and potentially cross-reactive foods should be avoided in elimination diets.

Acute pain management: scientific evidence, fourth edition, 2015.

This guideline summary describes the fourth edition of Acute pain management: scientific evidence, which was published by the Australian and New Zealand College of Anaesthetists (ANZCA) and its Faculty of Pain Medicine (FPMANZCA) in December 2015. The fourth edition summarises the best available evidence on acute pain management, following methods established over the preceding three editions. It provides additional information by scoring the quality of and reporting further details on randomised controlled trials and meta-analyses. The information is condensed into key messages that provide: concise statements on each topic, showing the highest level of evidence; and clinical practice points based on clinical experience or expert opinion.

Canine generalized demodicosis treated with varying doses of a 2.5% moxidectin+10% imidacloprid spot-on and oral ivermectin: parasiticidal effects and long-term treatment outcomes.

Advocate(®) (2.5% moxidectin+10% imidacloprid) (Bayer HealthCare, Leverkusen, Germany) is a multiparasiticidal spot-on authorized for treating canine demodicosis in many countries. This blinded, randomized three-phase clinical trial compared its efficacy employing different dosing regimens with that of ivermectin. In the blinded first phase, 58 dogs suffering from generalized demodicosis were randomly assigned to one of four groups and treated with monthly, biweekly or weekly applications of Advocate(®), or with oral ivermectin (IVR) at 500 µg/kg daily. Dogs were evaluated clinically and multiple skin scrapings undertaken every 4 weeks until parasitological cure was achieved (defined as two consecutive series of deep skin scrapings at monthly intervals negative for all life forms). Forty dogs completed the 16-week initial blinded phase, with 5 cases achieving parasitological cure. Five dogs were deemed treatment failures and subsequently treated with ivermectin. The treatment protocol was then changed for the remaining 35 dogs and this cross-over phase (Phase 2) was maintained for a further 8 weeks with an additional 9 dogs achieving parasitological cure. Thereafter, all remaining animals were treated with IVR until cured (Phase 3). Overall, 26 dogs achieved parasitological cure during the clinical investigation. Of these, 23 remained disease-free for at least 12 months while two were lost to follow up and one died of unrelated causes. A total of 32 (55.2%) dogs were withdrawn at various stages of the investigation including the 5 dogs that were judged treatment failures. Other reasons for withdrawal included: non-compliance, lost to follow-up, ivermectin toxicity or reasons unrelated to the investigation. No adverse effects were attributable to the use of Advocate(®). Parasiticidal efficacy was assessed by changes in mite counts (live adult, juvenile and egg) and skin lesion extent & severity scores. Statistical significance was assessed using ANCOVA with initial mite counts or skin scores used as the covariate to account for variations in disease severity. Planned pairwise comparisons were used to identify differences between treatment groups. The efficacy of Advocate(®) increased with its rate of application across all measures of efficacy. Although ivermectin was shown to be more effective than Advocate(®) applied once weekly, both treatment protocols produced clinically satisfactory results. It was concluded that weekly application of Advocate(®) can be recommended as effective for the treatment of canine generalized demodicosis without the potential for toxicity associated with ivermectin.

Postoperative vascular complications in unrecognised Obstructive Sleep apnoea (POSA) study protocol: an observational cohort study in moderate-to-high risk patients undergoing non-cardiac surgery.

INTRODUCTION: Emerging epidemiological data suggest that obstructive sleep apnoea (OSA) is common in the general surgical population. Unfortunately, the majority of these patients are unrecognised and untreated at the time of surgery. There is substantial biological rationale to indicate that patients with unrecognised OSA are at a higher risk of postoperative vascular events. However, the extent of this morbidity is currently unknown. We have initated the postoperative vascular complications in the unrecognised obstructive sleep apnoea (POSA) study to determine the associations between OSA, nocturnal hypoxia and major postoperative vascular events in 1200 moderate-to-high risk patients undergoing major non-cardiac surgery. METHODS AND ANALYSIS: The POSA study is an international prospective observational cohort study. Using a type 3 portable sleep monitoring device and ambulatory oximetry, we will quantify the severity of OSA. The primary outcome is a composite of vascular death, myocardial infarction; non-fatal cardiac arrest; stroke; pulmonary embolism; congestive heart failure and new arrhythmia within 30 days of surgery. As of November 2013, we have recruited over 700 patients from nine centres in six countries. The mean age is 68 years, the mean body mass index is 27 kg/m(2) and 55% of patients are men. 27.9% of patients have known coronary artery disease, over 76% have diabetes. The majority of patients underwent orthopaedic surgery (28%) and colorectal resection (18.5%). ETHICS AND DISSEMINATION: The POSA study has received ethics approval from all study sites before patient recruitment. Informed consent will be obtained from all patients. The POSA study will determine the risk of unrecognised OSA in major non-cardiac surgery. We will publish these findings in peer-reviewed journals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01494181.

Canine atopic dermatitis - what have we learned?

Canine atopic dermatitis is a complex multifactorial disease. Here, Tim Nuttall, Maarja Uri and Richard Halliwell, representing three generations of veterinary dermatologists, describe the research underpinning our understanding of the condition and highlight its relevance to clinical practice.

Serum anti-Staphylococcus pseudintermedius IgE and IgG antibodies in dogs with atopic dermatitis and nonatopic dogs.

BACKGROUND: Dogs and humans with atopic dermatitis (AD) are predisposed to colonization and recurrent infection with Staphylococcus spp. Studies in humans suggest that staphylococcus-specific immunoglobulin E (IgE) plays a key role in disease pathogenesis. Few such studies have been undertaken in dogs. HYPOTHESIS/OBJECTIVES: The aim of this study was to compare levels of staphylococcus-specific IgE and immunoglobulin G (IgG) in dogs with AD, nonatopic dogs with staphylococcal pyoderma, and nonatopic and noninfected control dogs. ANIMALS: Sera were collected from 108 dogs with AD, 39 nonatopic dogs with staphylococcal pyoderma secondary to different underlying conditions, 67 age-matched nonatopic control dogs, and nine control dogs reared in minimal disease conditions. METHODS: Serum Staphylococcus pseudintermedius-specific IgE and IgG antibodies were measured by enzyme-linked immunosorbent assay. RESULTS: Dogs with AD had significantly higher levels of anti-staphylococcal IgE than nonatopic dogs with staphylococcal pyoderma and the two groups of control dogs. Levels of anti-staphylococcal IgG were significantly higher in atopic dogs and nonatopic dogs with pyoderma compared with nonatopic control dogs and control dogs reared in minimal disease conditions, but there was no significant difference in levels of anti-staphylococcal IgG between dogs with AD and nonatopic dogs with pyoderma. CONCLUSIONS AND CLINICAL IMPORTANCE: A significantly increased IgE response to S. pseudintermedius antigens in atopic dogs suggests an immunopathogenic role for anti-staphylococcal IgE. The finding of elevated IgE and IgG in atopic dogs is also important as a prelude to studies on antigenic specificity and possible correlations with disease phenotype.

Food allergen-specific serum IgG and IgE before and after elimination diets in allergic dogs.

Serum food allergen-specific antibody testing is widely offered to identify suitable ingredients for diets to diagnose adverse food reaction (AFR) in dogs with allergic skin disease. Antibody concentrations in blood samples obtained during an unsuccessful diet to help in the choice of diet changes may be influenced by the previous diet. The objective of this paper was to measure food antigen-specific IgE and IgG for the most commonly used 16 food antigens before and after an elimination diet. Levels of food-specific serum IgE and IgG antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Dogs had detectable IgE antibodies to beef, pork, lamb and cows' milk; and detectable IgG antibodies to beef, pork, lamb, cows' milk, chicken and turkey. Of 19 dogs with complete data sets, 14 dogs showed clear improvement during diet and in 7 dogs AFR could be diagnosed by deterioration on rechallenge and subsequent improvement on refeeding the diet. Serum was obtained before and 6-8 weeks after beginning such a diet. There was no significant difference in pre- and post-diet levels for any of the individual allergens nor for the total IgE and IgG concentrations of all antigens (P=0.55 and P=0.53 respectively). In these 19 dogs in which an elimination diet was used for the diagnosis of food allergy and in which 14 were probably food allergic and 7 were proven food allergic there were no significant differences in food-specific antibodies before and after an elimination diet of 6-8 weeks.

Clinical and immunological heterogeneity of canine subepidermal blistering dermatoses with anti-laminin-332 (laminin-5) auto-antibodies.

Laminin-332 (laminin-5) is a basement membrane heterotrimeric protein composed of alpha-3, beta-3 and gamma-2 laminin chains. Laminin-332 polypeptides are targeted by auto-antibodies in human patients with mucous membrane (cicatricial) pemphigoid or, more rarely, subepidermal vesicular diseases that resemble epidermolysis bullosa acquisita (EBA) or bullous pemphigoid (BP). The objectives of this report were to characterize the clinical, histopathological and immunological characteristics of nine dogs with auto-antibodies targeting laminin-332. Immunological investigations consisted of direct immunofluorescence (IF), indirect IF with intact and salt-split canine gingival, and salt-split normal or laminin-332-deficient human skin, immunoblotting with purified human laminin-332 and immunoblotting with recombinant NC1 domain of human collagen VII. All dogs exhibited varying degrees of skin blistering and ulceration associated with microscopic subepidermal vesiculation with or without inflammatory cells. Indirect IF established that circulating IgG auto-antibodies bound the dermal side of salt-split canine lip and human skin. In five dogs, IgG variably recognized the basement membrane of laminin-332-deficient human skin (three dogs negative, two dogs positive). In all nine dogs, IgG auto-antibodies detected purified human laminin-332 by immunoblotting. In two dogs, additional targeting of collagen VII-NC1 was present. These observations establish laminin-332 as a novel basement membrane antigen in dogs with autoimmune blistering diseases with variable clinical phenotypes. The names 'acquired junctional epidermolysis bullosa', 'anti-laminin-332 mucous membrane pemphigoid (MMP)' and 'mixed auto-immune subepidermal blistering dermatosis' are proposed for dogs with clinical signs reminiscent of EBA, MMP or BP respectively.

Treatment of canine-generalized demodicosis: a blind, randomized clinical trial comparing the efficacy of Advocate(Bayer Animal Health) with ivermectin.

Advocate (moxidectin 2.5% + imidacloprid 10%) is a multiparasiticidal agent authorized for treating canine demodicosis in many countries. This blind, randomized clinical trial assessed the efficacy of Advocate at varying treatment intervals and compared it with that of oral ivermectin. Fifty dogs with generalized demodicosis were randomly assigned to one of four treatment groups: oral ivermectin (500 microg/kg once daily), Advocate applied at the authorized dose monthly (ADV1), every 2 weeks (ADV2) or weekly (ADV4). Each dog was evaluated every 4 weeks for 4 months or until negative scrapings at all sites resulted on two successive evaluations (parasitological cure). Miticidal efficacy was determined through deep skin scrapings taken from the same three sites on each occasion. Total numbers of live and dead adult mites, juveniles and eggs were determined. Thirty-five dogs completed the 4-month trial. Parasiticidal efficacy was assessed using several parameters including reduction in live adult mite counts. ancova analysis for this parameter confirmed that there were differences in efficacy among the treatment groups (P < 0.002). Tukey-Kramer all pairwise multiple comparison tests revealed that ADV4 was more effective than ADV1 (P = 0.016). Ivermectin was more effective than ADV1 (P = 0.003). Both ivermectin and ADV4 showed clinically substantial reductions in adult mite counts (89% for ADV4 and 98% for ivermectin). In conclusion, the efficacy of Advocate increased with the rate of application and weekly application may represent a new approach to the treatment of caninegeneralized demodicosis.

Levels of house dust mite-specific serum immunoglobulin E (IgE) in different cat populations using a monoclonal based anti-IgE enzyme-linked immunosorbent assay.

Levels of serum immunoglobulin E (IgE) specific for the house dust mites (HDMs) Dermatophagoides farinae (DF) and Dermatophagoides pteronyssinus (DP) in 58 cats with clinical signs suggestive of atopic dermatitis (allergic dermatitis cats), 52 cats with no history of allergic or immunological disease (nonallergic cats) and 26 specific pathogen-free (SPF) cats were measured using a monoclonal anti-IgE enzyme-linked immunosorbent assay. Reactivity to both native and reduced HDM allergens was compared. SPF cats had significantly lower levels of HDM-specific serum IgE than cats with allergic dermatitis and nonallergic cats. The difference in levels of HDM-specific IgE in the serum of cats with allergic dermatitis and nonallergic cats was significant for native DF allergen, but not for native DP allergen or reduced HDM allergens. The results suggest that DF in its native form may be a significant allergen in cats with allergic dermatitis. The clinical relevance of these reactions, however, remains to be proven.