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BackgroundIncreased delivery of taurine-conjugated bile acids to the distal bowel can lead to dysbiosis resulting in colitis in mouse models of inflammatory bowel disease. A similar situation also could occur in cats with intestinal disease and might therefore result in decreased whole-body taurine concentration.Hypothesis/objectivesTo determine whether whole-blood taurine concentrations are decreased at the time of diagnosis in cats with intestinal disease and to correlate concentrations with clinical and laboratory variables.AnimalsTwenty-one cats with chronic inflammatory enteropathy and 7 cats with intestinal neoplasia from the University of Bristol.MethodsCats that had undergone a thorough investigation consisting of a CBC, serum biochemistry, serum cobalamin and folate concentrations, transabdominal ultrasound examination and histopathology of intestinal biopsy specimens, as well as additional testing if indicated, were included. Whole-blood from these cats collected at the time of histologic diagnosis and stored in ethylenediaminetetraacetic acid was retrospectively analyzed for taurine with an automated high-performance liquid chromatography amino acid analyzer.ResultsAlthough whole-blood taurine concentrations remained within the reference range, those cats with predominantly large intestinal clinical signs had significantly lower concentrations than did cats with small intestinal and mixed bowel clinical signs (P = 0.033) and this difference also was significant when assessed only in cats with chronic inflammatory enteropathy (P = 0.019).Conclusions and clinical importanceAdditional studies are needed to determine whether large intestinal signs in cats with chronic inflammatory enteropathy are caused by alterations in the microbiota arising as a consequence of increased delivery of taurine-conjugated bile acids.

Abdominal x rays expose patients to significant doses of radiation and have limited use in emergency medicine. This review explores the evidence supporting the use of abdominal x rays in the emergency department, with particular reference to recent guidelines published by the Royal College of Radiologists. The authors' recommendations for the use of abdominal x rays in the emergency department are given. [ABSTRACT FROM AUTHOR]

It is an honour and personal pleasure to give the inaugural Frank Ellis Lecture to celebrate his 100th birthday, and to acknowledge his enormous contributions to radiation oncology.Intensity-modulated radiotherapy (IMRT) allows dose to be concentrated in the tumour volume while sparing normal tissues. However, the downside to IMRT is the potential to increase the number of radiation-induced second cancers because more fields are used which involves a bigger volume of normal tissue exposed to lower doses.It has been estimated that IMRT may double the incidence of solid cancers in long-term survivors. This may be acceptable in older patients if balanced by an improvement in local tumour control and redced toxicity. On the other hand, the incidence of second cancers is higher in children, so that doubling it may not be acceptable. IMRT represents a special case for children. First, they are more sensitive to radiation-induced cancer than adults. Second, radiation scattered from the treatment volume is more important in the small body of the child. Third, there is the question of genetic susceptibility, as many childhood cancers involve a germline mutation.The levels of leakage radiation in current Linacs can be reduced, but the cost would be substantial. An alternative strategy is to replace X-rays with protons. This is an advantage only if the proton machine uses a pencil scanning beam, as passive modulation of a scattering foil produces neutrons, which results in an effective dose to the patient higher than that characteristic of IMRT. [ABSTRACT FROM AUTHOR]

Subcutaneous delivery of drugs using a syringe driver is common practice within specialist palliative care units. There is, however, little documented information regarding clinical practice. A survey performed in 1992 reported that at least 28 drugs were used in combination with others in a single syringe driver. The aim of the present study was to reassess practice in this field and to enquire more specifically about newer drugs. Postal questionnaires were sent to all adult specialist palliative care in-patient units in the UK and Eire (n = 208). One hundred and sixty-five units (79%) responded. The most common syringe driver in use was the Graseby 26 (61% of responding units). Most units delivered the contents of the syringe over 24 h, and water was usually used as the diluent in 90% of cases. The maximum number of drugs that respondents were prepared to mix in a single syringe was usually three (51%) or four (35%). In the UK, all units used diamorphine in doses from 2.5 mg/24 h upwards. All respondents also used haloperidol, in doses from 0.5 to 60 mg/24 h. A total of 28 different drugs were used in syringe drivers. The most common combinations were diamorphine and midazolam (37%), diamorphine and levomepromazine (35%), diamorphine and haloperidol (33%), and diamorphine and cyclizine (31%). In conclusion, there is much in common with regard to the way in which drugs are delivered in syringe drivers. However, a wide variety of drugs and drug combinations are still in use. [ABSTRACT FROM AUTHOR]

Diagnostic Radiology and Radiation Oncology represent beneficial uses of radiation. The possible price tag is that radiation can cause, as well as diagnose or cure, cancer. Cancer risks at high doses are well known from epidemiologic studies of the Japanese survivors. Risks at low doses must be extrapolated from the high-dose data. The standard-setting bodies recommend a linear no-threshold extrapolation, but this is controversial. A knowledge of mechanisms, while not replacing epidemiology as a source of radiation-induced cancer risks, may provide insights into the shape of the dose-response relationships, and therefore on the validity of the linear extrapolation. The spectrum of second malignancies in radiotherapy patients sheds some light on mechanisms. More useful are new experiments involving the single-particle microbeam; these have demonstrated a bystander effect, that is, biologic effects in cells that are not directly irradiated, as well as mutations in cells where the cytoplasm, but not the nucleus, has been traversed by an alpha-particle. [ABSTRACT FROM AUTHOR]

Patients undergoing cardiac surgery experience significant physiologic derangements that place them at risk for multiple shock phenotypes. Any combination of cardiogenic, obstructive, hemorrhagic, or vasoplegic shock occurs commonly in post-cardiotomy patients. The approach to the diagnosis and management of these shock states has many facets that are distinct compared to non-surgical cardiac intensive care unit patients. Additionally, the approach to and associated outcomes of cardiac arrest in the post-cardiotomy population are uniquely characterized by emergent bedside resternotomy if the circulation is not immediately restored. This review focuses on the unique aspects of the diagnosis and management of post-cardiotomy shock., Competing Interests: Disclosure: EJH is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number T32HL125247. CFB has received consulting fees from Zoll and Abiomed. All other authors have no conflicts of interest to declare., (Copyright © The Author(s), 2024. Published by Radcliffe Group Ltd.)

Objective: To compare management of primary spontaneous pneumothorax (PSP) before and after the completion of multicentre study which showed non-inferiority of conservative compared to interventional treatment for PSP., Methods: This is a retrospective study of patients aged 14-50 years with a first diagnosis of medium to large PSP before and after March 2019 in a tertiary ED. Medical record and radiology database review were used to identify demographic, clinical and radiological data., Results: The proportion of patients receiving an intervention in the ED decreased from 31.3% (10/32) to 12.5% (3/24)., Conclusion: Intervention for management of PSP is less frequent, suggesting adoption and implementation of best evidence., (© 2024 The Authors. Emergency Medicine Australasia published by John Wiley & Sons Australia, Ltd on behalf of Australasian College for Emergency Medicine.)

Background: Dogs are exposed to increasing environmental risk for developing heat-related illness (HRI), with 2022 recorded as the hottest year to date in the UK and most of Europe., Methods: This study used VetCompass data to report the incidence risk, event fatality rate and canine risk factors for HRI in dogs presenting to Vets Now emergency care practices in the UK during 2022., Results: From the clinical records of 167,751 dogs under care at Vets Now emergency clinics in 2022, 384 HRI events were identified. The 2022 incidence risk of HRI within the Vets Now caseload was 0.23% (95% confidence interval [CI]: 0.21%‒0.25%), with an event fatality rate of 26.56% (95% CI: 21.66%-32.25%). Multivariable analysis identified breed, age and sex/neuter status as risk factors for HRI. Brachycephalic dogs had 4.21 times the odds of HRI compared to mesocephalic dogs (95% CI: 3.22‒5.49, p < 0.001)., Limitations: The clinical data used in this study were not primarily recorded for research and had some substantial levels of missing data (especially patient bodyweight)., Conclusion: In order to protect canine welfare, improved long-term mitigation strategies are urgently needed to minimise HRI risk and associated fatality in UK dogs., (© 2024 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Exercise is a common trigger of heat-related illness (HRI) events in dogs, accounting for 74% of canine HRI cases treated under primary veterinary care in the United Kingdom. However, few empirical studies have evaluated the effectiveness of differing cooling methods for dogs with exertional hyperthermia or HRI. This study aimed to prospectively evaluate effects of ambient conditions and post-exercise management practices (cooling methods and vehicular confinement) on the post-exercise temperature change of dogs participating in UK canicross events. Canine temperature was recorded at three intervals post-exercise: as close as possible to 0- (immediately post-exercise), 5-, and 15-min post-exercise. Ambient conditions and post-exercise management were recorded for 115 cooling profiles from 52 dogs. In 28/115 (24.4%) profiles, the dog's temperature increased during the first 5-min post-exercise. Overall, 68/115 (59.1%) profiles included passive cooling (stood or walked outside), 35 (30.4%) active cooling (cold-water immersion or application of a cooling coat), and 12 (10.4%) involved no cooling and were immediately housed in vehicles. No dogs developed hypothermia during the study and no adverse effects were observed from any cooling method. In hyperthermic dogs, overall post-exercise body temperature change was significantly negatively associated (i.e. the dogs cooled more) with 0-min post-exercise body temperature (β = -0.93, p < 0.001), and not being housed in a vehicle (β = -0.43, p = 0.013). This study provides evidence cold-water immersion (in water at 0.1-15.0 °C) can be used to effectively and safely cool dogs with exertional hyperthermia. Progressive temperature increases in many dogs - even after exercise has terminated - supports the message to "cool first, transport second" when managing dogs with HRI. When transporting dogs post-exercise or with HRI even after active cooling, care should be taken to cool the vehicle before entry and promote air movement around the dog during transport to facilitate ongoing cooling and prevent worsening of hyperthermia during travel., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dan O'Neill is a member of the “Dogs Die in Hot Cars” consortium. SB, SG and DB work for veterinary companies providing emergency veterinary care to dogs., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The COVID-19 pandemic has been associated with detrimental effects on mental health and psychological well-being. Although multiple studies have shown decreases in mental health-related Emergency Department (ED) presentations early in the COVID-19 pandemic, the medium-term effects on mental health-related ED presentations have remained less clear. This study aimed to evaluate the effect of the pandemic on mental health ED presentations by comparing observed presentation numbers to predictions from pre-pandemic data., Methods: This retrospective cohort study tallied weekly ED presentations associated with mental health disorders from a state-wide minimum dataset. Three time periods were identified: Pre-Pandemic (January 1, 2018-March 8, 2020), Statewide Lockdown (March 9, 2020-June 28, 2020), and Restrictions Easing (June 29, 2020-June 27, 2021). Time series analysis was used to generate weekly presentation forecasts using pre-pandemic data. Observed presentation numbers were compared to these forecasts., Results: Weekly presentation numbers were lower than predicted in 11 out of 16 weeks in the Statewide Lockdown period and 52 out of 52 weeks in the Restrictions Easing period. The largest decrease was seen for anxiety disorders (Statewide Lockdown: 76.8% of forecast; Restrictions Easing: 36.4% of forecast), while an increase was seen in presentations for eating disorders (Statewide Lockdown: 139.5% of forecast; Restrictions Easing: 194.4% of forecast)., Conclusions: Overall weekly mental health-related presentations across Queensland public EDs were lower than expected for the first 16 months of the COVID-19 pandemic. These findings underline the limitations of emergency department provision of mental health care and the importance of alternate care modalities in the pandemic context., (© 2024 The Authors. Asia-Pacific Psychiatry published by John Wiley & Sons Australia, Ltd.)

Health effects of space radiation are a serious concern for astronauts on long-duration missions. The lens of the eye is one of the most radiosensitive tissues in the body and, therefore, ocular health risks for astronauts is a significant concern. Studies in humans and animals indicate that ionizing radiation exposure to the eye produces characteristic lens changes, termed "radiation cataract," that can affect visual function. Animal models of radiation cataractogenesis have previously utilized inbred mouse or rat strains. These studies were essential for determining morphological changes and dose-response relationships between radiation exposure and cataract. However, the relevance of these studies to human radiosensitivity is limited by the narrow phenotypic range of genetically homogeneous animal models. To model radiation cataract in genetically diverse populations, longitudinal cataract phenotyping was nested within a lifetime carcinogenesis study in male and female heterogeneous stock (HS/Npt) mice exposed to 0.4 Gy HZE ions (n = 609) or 3.0 Gy γ-rays (n = 602) and in unirradiated controls (n = 603). Cataractous change was quantified in each eye for up to 2 years using Merriam-Focht grading criteria by dilated slit lamp examination. Virtual Optomotry™ measurement of visual acuity and contrast sensitivity was utilized to assess visual function in a subgroup of mice. Prevalence and severity of posterior lens opacifications were 2.6-fold higher in HZE ion and 2.3-fold higher in γ-ray irradiated mice compared to unirradiated controls. Male mice were at greater risk for spontaneous and radiation associated cataracts. Risk for cataractogenesis was associated with family structure, demonstrating that HS/Npt mice are well-suited to evaluate genetic determinants of ocular radiosensitivity. Last, mice were extensively evaluated for cataract and tumor formation, which revealed an overlap between individual susceptibility to both cancer and cataract., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Norman J Kleiman reports financial support and administrative support were provided by Columbia University., (Copyright © 2023 The Committee on Space Research (COSPAR). Published by Elsevier B.V. All rights reserved.)

Objectives: The objectives of this study were to report the complications in radial and ulnar diaphyseal fractures in cats and to compare the differences in outcome between single and dual bone internal fixation., Methods: Medical records between 2004 and 2022 were searched retrospectively for cats with antebrachial diaphyseal fractures treated with internal bone-plate fixation. In total, 49 cases were included from six referral hospitals, including one teaching hospital. Patient information was collated, including fracture configuration, location, repair method and clinical outcome as assessed by veterinary physical examination, radiography and owner questionnaire., Results: A total of 47 cats (mean age 4.2 years) were included. Fractures were located distally (24/49, 49%), proximally (13/49, 26.5%) and mid-diaphyseally (12/49, 24.5%). Dual bone fixation was used in 13/49 (26.5%) cases, with only 1/13 (7.7%) having major complications. By comparison, 4/36 (11.1%) of single plated fractures had major complications. Single bone fixation was 14.25 times more likely (95% confidence interval [CI] 2.07-97.99) to have a successful outcome (veterinarian-assigned score of 0) compared with dual bone fixation ( P  = 0.007). When evaluating owner-assessed outcomes, single bone fixation was 9.4 times more likely (95% CI 1.4-61.96) to have a successful outcome (owner score of 0) compared with dual bone fixation ( P  = 0.019)., Conclusions and Relevance: Fractures that were repaired with single bone fixation had a greater chance of a better outcome. Although the difference was not significant, there was a higher major complication rate and a lower minor complication rate for cases treated with single bone fixation compared with dual bone fixation. The majority of fractures were located in the distal diaphysis. Comminution of the fracture and concurrent orthopaedic issues did not significantly affect the outcome. Further prospective studies with standardised follow-up, radiographic assessment, surgeon and implants are required to truly assess the difference between dual and single bone fixation., Competing Interests: Conflict of interestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Chronic venous disease is a circulatory system dysfunction that has the potential to lead to venous leg ulceration. Although research on the influence of specific gene variants on chronic venous disease has been limited, a few studies have reported an association between hemochromatosis and chronic venous disease. However, no studies have looked at the prevalence of lower-limb venous disease and leg ulcers in people with hemochromatosis. This study aimed to review the existing literature for any association between venous disease and hemochromatosis and investigate the prevalence of venous disease and leg ulcers in people with hemochromatosis., Methods: Scoping systematic literature review and cross-sectional study surveying people with hemochromatosis., Results: This scoping systematic literature review included nine articles and indicated a link between hemochromatosis and venous disease/leg ulcers, although further studies are needed to support this link. Analysis of survey results from people with hemochromatosis found a 9.2% prevalence of leg ulcers in those with self-reported hemochromatosis, considerably higher than the 1% to 3% expected, suggesting that hemochromatosis gene variants may be associated with the pathogenesis of chronic venous disease and leg ulcers., Conclusions: This is the first known study to complete a review of the literature regarding hemochromatosis and venous leg ulcers and document the association between hemochromatosis and venous disease/leg ulcers. There is a lack of research in this area and hence limited evidence to guide practice., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Hydrolyzed protein diets are extensively used to treat chronic enteropathy (CE) in cats. However, the biochemical effects of such a diet on feline CE have not been characterized. In this study an untargeted 1 H nuclear magnetic resonance spectroscopy-based metabolomic approach was used to compare the urinary, plasma, and fecal metabolic phenotypes of cats with CE to control cats with no gastrointestinal signs recruited at the Royal Veterinary College (RVC). In addition, the biomolecular consequences of a hydrolyzed protein diet in cats with CE was also separately determined in cats recruited from the RVC (n = 16) and the University of Bristol (n = 24) and whether these responses differed between dietary responders and non-responders. Here, plasma metabolites related to energy and amino acid metabolism significantly varied between CE and control cats in the RVC cohort. The hydrolyzed protein diet modulated the urinary metabolome of cats with CE (p = 0.005) in both the RVC and Bristol cohort. In the RVC cohort, the urinary excretion of phenylacetylglutamine, p-cresyl-sulfate, creatinine and taurine at diagnosis was predictive of dietary response (p = 0.025) although this was not observed in the Bristol cohort. Conversely, in the Bristol cohort plasma betaine, glycerol, glutamine and alanine at diagnosis was predictive of outcome (p = 0.001), but these same results were not observed in the RVC cohort. The biochemical signature of feline CE in the RVC cohort was consistent with that identified in human and animal models of inflammatory bowel disease. The hydrolyzed protein diet had the same effect on the urinary metabolome of cats with CE at both sites. However, biomarkers that were predictive of dietary response at diagnosis differed between the 2 sites. This may be due to differences in disease severity, disease heterogeneity, factors unrelated to the disease or small sample size at both sites. As such, further studies utilizing larger number of cats are needed to corroborate these findings., (© 2023. The Author(s).)

Background: Nucleoside analog GS-441524 is effective in treating cats with feline infectious peritonitis (FIP). Investigation into the use of parent nucleotide analog remdesivir (GS-5734) is needed., Objectives: To assess efficacy and tolerability of remdesivir with or without transition to GS-441524 in cats with FIP and document clinical and clinicopathologic progression over 6 months., Animals: Twenty-eight client-owned cats with FIP., Methods: Cats were prospectively recruited between May 2021 and May 2022. An induction dosage of remdesivir 10 to 15 mg/kg intravenously or subcutaneously q24h was utilized for 4 doses, with a maintenance dosage of remdesivir (6-15 mg/kg SC) or GS-441524 (10-15 mg/kg per os) every 24 hours continued for at least 84 days. Laboratory testing, veterinary, and owner assessments were recorded., Results: Twenty-four cats survived to 6 months (86%). Three cats died within 48 hours. Excluding these, survival from 48 hours to 6 months was 96% (24/25). Remission was achieved by day 84 in 56% (14/25). Three cats required secondary treatment for re-emergent FIP. Remission was achieved in all 3 after higher dosing (15-20 mg/kg). Adverse reactions were occasional site discomfort and skin irritation with remdesivir injection. Markers of treatment success included resolution of pyrexia, effusions, and presenting signs of FIP in the first half of treatment and normalization of globulin concentration, and continued body weight gains in the latter half of the treatment period., Conclusions and Clinical Importance: Parenteral administration of remdesivir and oral administration of GS-441524 are effective and well-tolerated treatments for FIP. Early emphasis on clinical, and later emphasis on clinicopathologic response, appears prudent when monitoring treatment efficacy., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

The management of heat-related illness (HRI) in dogs has received limited attention in the veterinary literature, especially regarding effective cooling methods. Guidelines published in 2016 for prehospital management of dogs with HRI advised "cool first, transport second", and recommended using cold-water immersion and evaporative cooling (water application with air movement) as the optimal approaches to reduce the patient's temperature. The current retrospective cross-sectional observation study analysed electronic patient records from the VetCompass programme to describe the cooling methods used in dogs with HRI presented to primary care veterinary practices during 2016-2018. Of 623 HRI events identified, 341 (54.74%, 95% CI 50.81-58.60%) included information on cooling in their clinical record. Of these, 74/341 (21.70%, 95% CI 17.65-26.38%) were cooled prior to transport for veterinary care. Overall, 23.97% (95% CI 19.24-29.44%) were cooled using one of the two recommended cooling methods, whilst the most common cooling method recorded was the application of wet towels (51.31%, 95% CI 45.34-57.24%). Canine cooling guidance and messaging in both the public and veterinary sectors requires urgent review to ensure that the most effective cooling methods are promoted because delays to canine temperature reduction worsen patient outcomes.

Background: The COVID-19 pandemic has evolved through multiple phases characterized by new viral variants, vaccine development, and changes in therapies. It is unknown whether rates of cardiovascular disease (CVD) risk factor profiles and complications have changed over time., Methods: We analyzed the American Heart Association COVID-19 CVD registry, a national multicenter registry of hospitalized adults with active COVID-19 infection. The time period from April 2020 to December 2021 was divided into 3-month epochs, with March 2020 analyzed separately as a potential outlier. Participating centers varied over the study period. Trends in all-cause in-hospital mortality, CVD risk factors, and in-hospital CVD outcomes, including a composite primary outcome of cardiovascular death, cardiogenic shock, new heart failure, stroke, and myocardial infarction, were evaluated across time epochs. Risk-adjusted analyses were performed using generalized linear mixed-effects models., Results: A total of 46 007 patient admissions from 134 hospitals were included (mean patient age 61.8 years, 53% male, 22% Black race). Patients admitted later in the pandemic were younger, more likely obese, and less likely to have existing CVD ( P trend ≤0.001 for each). The incidence of the primary outcome increased from 7.0% in March 2020 to 9.8% in October to December 2021 (risk-adjusted P trend =0.006). This was driven by an increase in the diagnosis of myocardial infarction and stroke ( P trend <0.0001 for each). The overall rate of in-hospital mortality was 14.2%, which declined over time (20.8% in March 2020 versus 10.8% in the last epoch; adjusted P trend <0.0001). When the analysis was restricted to July 2020 to December 2021, no temporal change in all-cause mortality was seen (adjusted P trend =0.63)., Conclusions: Despite a shifting risk factor profile toward a younger population with lower rates of established CVD, the incidence of diagnosed cardiovascular complications of COVID increased from the onset of the pandemic through December 2021. All-cause mortality decreased during the initial months of the pandemic and thereafter remained consistently high through December 2021., Competing Interests: Disclosures Dr Elkind reports serving as an unpaid Officer of the American Heart Association. Dr Hall, C. Rutan, J. Walchok, J.H. Williams, Dr Stevens, and P. Mallya are employees of the American Heart Association. Dr Wang reports receiving research grants to the Duke Clinical Research Institute from Abbott, AstraZeneca, Bristol Myers Squibb, Boston Scientific, Cryolife, Chiesi, Merck, Portola, and Regeneron, as well as consulting honoraria from AstraZeneca, Bristol Myers Squibb, Cryolife, and Novartis. All other authors have no relationships to report.

Objectives: To assess emergency department (ED) presentation numbers in Queensland during the coronavirus disease 2019 (COVID-19) pandemic to mid-2021, a period of relatively low COVID-19 case numbers., Design: Interrupted time series analysis., Setting: All 105 Queensland public hospital EDs., Main Outcome Measures: Numbers of ED presentations during the COVID-19 lockdown period (11 March 2020 - 30 June 2020) and the period of easing restrictions (1 July 2020 - 30 June 2021), compared with pre-pandemic period (1 January 2018 - 10 March 2020), overall (daily numbers) and by Australasian Triage Scale (ATS; daily numbers) and selected diagnostic categories (cardiac, respiratory, mental health, injury-related conditions) and conditions (stroke, sepsis) (weekly numbers)., Results: During the lockdown period, the mean number of ED presentations was 19.4% lower (95% confidence interval, -20.9% to -17.9%) than during the pre-pandemic period (predicted mean number: 5935; actual number: 4786 presentations). The magnitudes of the decline and the time to return to predicted levels varied by ATS category and diagnostic group; changes in presentation numbers were least marked for ATS 1 and 2 (most urgent) presentations, and for presentations with cardiac conditions or stroke. Numbers remained below predicted levels during the 12-month post-lockdown period for ATS 5 (least urgent) presentations and presentations with mental health problems, respiratory conditions, or sepsis., Conclusions: The COVID-19 pandemic and related public restrictions were associated with profound changes in health care use. Pandemic plans should include advice about continuing to seek care for serious health conditions and health emergencies, and support alternative sources of care for less urgent health care needs., (© 2022 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

This clinical image vignette describes the inadvertent placement of a balloon pump in the vena cava during a "code blue" scenario, and the lessons to be learned from that experience. The hemodynamic benefits of intra-aortic balloon pump during experimental cardiac arrest include shorter circulation time and increases in end-tidal CO2 and coronary perfusion pressure. However, the hemodynamic effects of venous diastolic augmentation during experimental cardiogenic shock vary, being detrimental in cases of low preload, and possibly beneficial in a high preload state. When performed emergently at the bedside, inadvertent intra-caval placement of a balloon pump can occur due to elevated venous pressures, in the presence of severe tricuspid regurgitation, or through an arteriovenous fistula. A similar radiographic appearance can also be seen in the presence of a right-sided aortic arch. Clues to improper position include an abnormal pressure waveform and the absence of hemodynamic changes or blood pressure augmentation.

Bioprosthetic heart valves (BHV) fabricated from heterograft tissue, such as glutaraldehyde pretreated bovine pericardium (BP), are the most frequently used heart valve replacements. BHV durability is limited by structural valve degeneration (SVD), mechanistically associated with calcification, advanced glycation end products (AGE), and serum protein infiltration. We investigated the hypothesis that anti-AGE agents, Aminoguanidine, Pyridoxamine [PYR], and N-Acetylcysteine could mitigate AGE-serum protein SVD mechanisms in vitro and in vivo, and that these agents could mitigate calcification or demonstrate anti-calcification interactions with BP pretreatment with ethanol. In vitro, each of these agents significantly inhibited AGE-serum protein infiltration in BP. However, in 28-day rat subdermal BP implants only orally administered PYR demonstrated significant inhibition of AGE and serum protein uptake. Furthermore, BP PYR preincubation of BP mitigated AGE-serum protein SVD mechanisms in vitro, and demonstrated mitigation of both AGE-serum protein uptake and reduced calcification in vivo in 28-day rat subdermal BP explants. Inhibition of BP calcification as well as inhibition of AGE-serum protein infiltration was observed in 28-day rat subdermal BP explants pretreated with ethanol followed by PYR preincubation. In conclusion, AGE-serum protein and calcification SVD pathophysiology are significantly mitigated by both PYR oral therapy and PYR and ethanol pretreatment of BP., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Robert J. Levy reports financial support was provided by National Institutes of Health. Robert J. Levy reports a relationship with National Institutes of Health that includes: funding grants., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Venoarterial extracorporeal life support (VA-ECLS) is a powerful tool that can provide complete cardiopulmonary support for patients with refractory cardiogenic shock. However, VA-ECLS increases left ventricular (LV) afterload, resulting in greater myocardial oxygen demand, which can impair myocardial recovery and worsen pulmonary edema. These complications can be ameliorated by various LV venting strategies to unload the LV. Evidence suggests that LV venting improves outcomes in VA-ECLS, but there is a paucity of randomized trials to help guide optimal strategy and the timing of venting. In this review, we discuss the available evidence regarding LV venting in VA-ECLS, explain important hemodynamic principles involved, and propose a practical approach to LV venting in VA-ECLS., Competing Interests: Conflict of interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: The cardiac natriuretic peptides [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] are important regulators of cardiovascular physiology, with reduced natriuretic peptide (NP) activity linked to multiple human cardiovascular diseases. We hypothesized that deficiency of either ANP or BNP would lead to similar changes in left ventricular structure and function given their shared receptor affinities., Methods and Results: We directly compared murine models deficient of ANP or BNP in the same genetic backgrounds (C57BL6/J) and environments. We evaluated control, ANP-deficient (Nppa-/-) or BNP-deficient (Nppb-/-) mice under unstressed conditions and multiple forms of pathological myocardial stress. Survival, myocardial structure, function and electrophysiology, tissue histology, and biochemical analyses were evaluated in the groups. In vitro validation of our findings was performed using human-derived induced pluripotent stem cell cardiomyocytes (iPS-CMs). In the unstressed state, both ANP- and BNP-deficient mice displayed mild ventricular hypertrophy which did not increase up to 1 year of life. NP-deficient mice exposed to acute myocardial stress secondary to thoracic aortic constriction (TAC) had similar pathological myocardial remodelling but a significant increase in sudden death. We discovered that the NP-deficient mice are more susceptible to stress-induced ventricular arrhythmias using both in vivo and ex vivo models. Mechanistically, deficiency of either ANP or BNP led to reduced myocardial cGMP levels and reduced phosphorylation of the cAMP response element-binding protein (CREBS133) transcriptional regulator. Selective CREB inhibition sensitized wild-type hearts to stress-induced ventricular arrhythmias. ANP and BNP regulate cardiomyocyte CREBS133 phosphorylation through a cGMP-dependent protein kinase 1 (PKG1) and p38 mitogen-activated protein kinase (p38 MAPK) signalling cascade., Conclusions: Our data show that ANP and BNP act in a non-redundant fashion to maintain myocardial cGMP levels to regulate cardiomyocyte p38 MAPK and CREB activity. Cardiac natriuretic peptide deficiency leads to a reduction in CREB signalling which sensitizes the heart to stress-induced ventricular arrhythmias., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Objective structured clinical examinations (OSCEs) are used to assess students' skills on a variety of tasks using live animals, models, cadaver tissue, and simulated clients. OSCEs can be used to provide formative feedback, or they can be summative, impacting progression decisions. OSCEs can also drive student motivation to engage with clinical skill development and mastery in preparation for clinical placements and rotations. This teaching tip discusses top tips for running an OSCE for veterinary and veterinary nursing/technician students as written by an international group of authors experienced with running OSCEs at a diverse set of institutions. These tips include tasks to perform prior to the OSCE, on the day of the examination, and after the examination and provide a comprehensive review of the requirements that OSCEs place on faculty, staff, students, facilities, and animals. These tips are meant to assist those who are already running OSCEs and wish to reassess their existing OSCE processes or intend to increase the number of OSCEs used across the curriculum, and for those who are planning to start using OSCEs at their institution. Incorporating OSCEs into a curriculum involves a significant commitment of resources, and this teaching tip aims to assist those responsible for delivering these assessments with improving their implementation and delivery.

Heat-related illness (HRI) is predicted to increase in dogs due to rising global temperatures. This study evaluated retrospective VetCompass veterinary clinical records to explore geographical variability and ambient conditions associated with HRI events in UK dogs, and report the intrinsic (canine) and extrinsic (location, trigger, ambient weather) risk factors for severe disease and fatal outcome in dogs affected by HRI. Dogs living in London had the greatest odds for developing HRI compared with dogs living in the North West (OR 1.9, 95% CI 1.31-2.74). The median ambient temperature on days of HRI events was 16.9 °C. For dogs with HRI, age, bodyweight and trigger were risk factors associated with severe disease. Age, skull shape and clinical grade of HRI presentation were associated with a fatal outcome. Whilst the majority of HRI events overall were triggered by exertion, the risk of severe disease was greater in situations where dogs could not escape the heat source (vehicular confinement), and the risk of death in HRI cases was greater for those dogs with reduced capacity to thermoregulate (older and brachycephalic dogs). These results highlight the need for better owner awareness of the factors that increase the risk of severe and fatal HRI, as a first stage in protecting canine welfare in the face of rising global temperatures.

Aims: GSK3358699 is a mononuclear myeloid-targeted bromodomain and extra-terminal domain (BET) family inhibitor which demonstrates immunomodulatory effects in vitro. This phase 1, randomized, first-in-human study evaluated the safety, pharmacokinetics, and pharmacodynamics of GSK3358699 in healthy male participants (NCT03426995)., Methods: Part A (N = 23) included three dose-escalating periods of 1-40 mg of GSK3358699 or placebo in two cohorts in a single ascending-dose crossover design. Part C (N = 25) was planned as an initial dose of 10 mg of GSK3358699 or placebo daily for 14 days followed by selected doses in four sequential cohorts., Results: In part A, exposure to GSK3358699 and its metabolite GSK3206944 generally increased with increasing doses. The median initial half-life ranged from 0.7 to 1.1 (GSK3358699) and 2.1 to 2.9 (GSK3206944) hours after a single dose of 1-40 mg. GSK3206944 concentrations in monocytes were quantifiable at 1-hour post-dose following 10 mg of GSK3358699 and 1 and 4 hours post-dose following 20-40 mg. Mean predicted percentage inhibition of ex vivo lipopolysaccharide-induced monocyte chemoattractant protein (MCP)-1 reached 75% with 40 mg of GSK3358699. GSK3358699 did not inhibit interleukin (IL)-6 and tumour necrosis factor (TNF). The most common adverse event (AE) was headache. Four AEs of nonsustained ventricular tachycardia were observed across parts A and C. One serious AE of atrial fibrillation (part C) required hospitalization., Conclusions: Single doses of GSK3358699 are generally well tolerated with significant metabolite concentrations detected in target cells. A complete assessment of pharmacodynamics was limited by assay variability. A causal relationship could not be excluded for cardiac-related AEs, resulting in an inability to identify a suitable repeat-dose regimen and study termination., (© 2021 GlaxoSmithKline. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

The effect of a hydrolyzed protein diet on the fecal microbiota has not been studied in feline chronic enteropathy (CE). Our study aimed to (1) compare the fecal microbiota of cats with CE to control cats with no gastrointestinal signs and (2) determine the effect of a hydrolyzed protein diet on the fecal microbiota of cats with CE and whether this differs between dietary responders and non-responders. The fecal microbiome of cats with CE (n = 36) showed decreased α-diversity in terms of genus richness (P = 0.04) and increased β-diversity in terms of Bray-Curtis Dissimilarity (P < 0.001) compared to control cats (n = 14). Clostridium was the only genera significantly over-represented in cats with CE compared to control cats (adjusted P < 0.1). After 6-weeks of feeding the diet, fifteen cats were classified as responders and 18 as non-responders, based on clinical signs. At the genus level, α-diversity was increased in non-responders versus responders at diagnosis, but decreased after dietary intervention in both groups (P < 0.05). At the family level, non-responders became increasingly dissimilar after dietary intervention (P = 0.012). In general, the abundance of bacteria decreased with feeding a hydrolyzed diet, with the genera most significantly affected being more frequently observed in non-responders. Bifidobacterium was the only genus that increased significantly in abundance post-diet and this effect was observed in both responders and non-responders. Both Oscillibacter and Desulfovibrionaceae&#95;unclassified were most abundant in non-responders at diagnosis but were rarely observed post diet in neither responders nor non-responders. Cats with CE had similar microbiota changes to those described in human inflammatory bowel disease. Whether the presence of Oscillibacter and Desulfovibrionaceae&#95;unclassified are indicators of non-response to the diet at diagnosis requires further investigation. Despite the hydrolyzed diet reducing α-diversity in all cats with CE, this did not resolve gastrointestinal signs in some cats. However, responders metabolized the diet in a similar manner, reflected by sustained β-diversity, while the microbiome of non-responders became increasingly dissimilar compared to diagnosis at the family level. Therefore, the microbiome may not be as tightly regulated in cats with CE that are non-responders and therefore, these cats would require additional therapy for remission of clinical signs., (© 2022. The Author(s).)

Background: Heat-related illness (HRI) can affect all companion animals and is likely to become more common as global temperatures rise. The misconception that HRI is primarily a result of dogs being trapped in hot cars, highlights a lack of awareness of HRI risk factors within the UK companion animal population., Aim: This project aimed to review all species of small animal presentations of HRI to UK veterinary practices participating in the Small Animal Veterinary Surveillance Network (SAVSNET), describe the inciting triggers and seasonality of HRI events, and review the clinical grade of canine patients presenting with HRI., Methods: Electronic consultation records were submitted by volunteer veterinary practices across the UK to SAVSNET. Cases were defined as animals presented for consultation with strong evidence of current, or recent heat induced illness during the study period (2013-2018)., Results: The HRI cases included 146 dogs, 16 cats, 8 guinea pigs, 3 rabbits and 1 ferret. Of the 118 HRI cases with a recorded trigger, exercise was the primary trigger for dogs presenting (73.5%); 7 (6.9%) canine HRI events followed vehicular confinement. Environmental HRI was recorded as a trigger for the remaining dogs (19.6%), and for all cats, guinea pigs, rabbits and the ferret. Brachycephalic breeds comprised 21.2% of canine HRI cases, and all rabbits were brachycephalic breeds. Dogs with HRI were presented between April and October, with 42.5% during July, typically the UK's hottest month of the year. Cats with HRI were presented between May and September, with 75.0% during June and July. The smaller companion species-ferrets, rabbits and guinea pigs-were presented during the UK's summer months June to August., Conclusion: This study highlights the risk of HRI to all pet animals during the UK's warmer summer months (June to August). The findings support previous claims that exercise is the most common trigger of HRI in dogs, while environmental HRI (a hot ambient temperature) accounted for all HRI events in cats, rabbits, guinea pigs, and ferrets. Both brachycephalic dogs and rabbits were overrepresented, adding further evidence that owners of these animals should be particularly vigilant for HRI during hot weather., Competing Interests: The authors declare that there is no conflict of interest.

Climate change is leading to more instances of seasonal weather variation. Studies have explored the impact of adverse winter weather on dog walking, but the impact on the dog's overall activity levels have not been previously considered. This study explored dog owner perceptions of the effects of both summer and winter weather on their dog's activity levels. An international online survey recruited 3153 respondents between May and December 2018, to explore the impact of summer and winter weather conditions on baseline activity levels. Owners reported their dogs were more impacted by cold (48.2% less likely to exercise their dog in the cold) and ice (64.0% less likely), than rain (25.3% were less likely). In hot weather, over 80% of owners reported reduced exercise duration and vigour for their dogs. Carrying water or walking near water to facilitate activity in the summer was the most popular mitigation strategy (90.8%). Participation in dog sports appeared to reduce the impact of winter weather on canine activity and increase owner awareness of cooling strategies to facilitate summer activity. Strategies to promote safe activity participation are needed to maintain canine activity levels amidst rising global temperatures, including better understanding of cooling strategies for exercising dogs.

Rationale: Respiratory support (noninvasive ventilation or high-flow nasal cannula) applied at the time of extubation has been reported to reduce reintubation rates, but concerns regarding effectiveness have limited uptake into practice. Objectives: To determine if providing postextubation respiratory support to all patients undergoing extubation in a medical ICU would decrease the incidence of reintubation. Methods: We conducted a pragmatic, two-armed, cluster-crossover trial of adults undergoing extubation from invasive mechanical ventilation between October 1, 2017, and March 31, 2019, in the medical ICU of an academic medical center. Patients were assigned to either protocolized postextubation respiratory support (a respiratory therapist-driven protocol in which patients with suspected hypercapnia received noninvasive ventilation and patients without suspected hypercapnia received high-flow nasal cannula) or usual care (postextubation management at the discretion of treating clinicians). The primary outcome was reintubation within 96 hours of extubation. Measurements and Main Results: A total of 751 patients were enrolled. Of the 359 patients assigned to protocolized support, 331 (92.2%) received postextubation respiratory support compared with 66 of 392 patients (16.8%) assigned to usual care, a difference driven by differential use of high-flow nasal cannula (74.7% vs. 2.8%). A total of 57 patients (15.9%) in the protocolized support group experienced reintubation compared with 52 patients (13.3%) in the usual care group (odds ratio, 1.23; 95% confidence interval, 0.82 to 1.84; P  = 0.32). Conclusions: Among a broad population of critically ill adults undergoing extubation from invasive mechanical ventilation at an academic medical center, protocolized postextubation respiratory support, primarily characterized by an increase in the use of high-flow nasal cannula, did not prevent reintubation compared with usual care.Clinical trial registered with www.clinicaltrials.gov (NCT0328831).

Identifying reforms that minimize US healthcare costs is imperative. This commentary explores one intervention with potential cost-saving implications that has received comparably minimal consideration: spiritual care provision. It highlights the staff and patient costing benefits of spiritual care in addressing spiritual distress and urges practical policy and research initiatives to maximize its impact.

Heat-related illness is a potentially fatal condition in dogs. Rapid and accurate recognition of the severity can improve clinical management in affected dogs and lead to better outcomes. This study explored retrospective VetCompass veterinary clinical records to investigate the clinical signs recorded for dogs presenting with heat-related illness to primary-care veterinary practice from 2016 to 2018. The relative risk of death associated with these clinical signs was reported and used to develop a novel clinical grading tool. From the clinical records of 856 heat-related illness events, the most frequently recorded clinical signs were respiratory changes (68.73%) and lethargy (47.79%). The clinical signs with the highest relative risk of death were neurological dysfunction, gastrointestinal haemorrhage and bleeding disorders. The novel VetCompass Clinical Grading Tool for Heat-Related Illness in dogs defines three grades: mild (altered respiration, lethargy), moderate (gastrointestinal signs, a single seizure, episodic collapse) and severe (neurological dysfunction, gastrointestinal haemorrhage, bleeding disorders). This novel grading tool offers a simple, evidence-based device to improve recognition of heat-related illness in dogs and promote improved decision-making for earlier interventions such as cooling and hospitalisation. This could improve outcomes and protect the welfare of dogs in the face of rising global temperatures.

Background: Dogs with protein-losing enteropathy (PLE) are at risk of developing a hypercoagulable state, but the prevalence of hypercoagulability in dogs with chronic enteropathies (CE) and normal serum albumin concentration is unknown., Hypothesis: Dogs with CE are predisposed to a hypercoagulable state as assessed by thromboelastography (TEG) independent of serum albumin concentration., Methods: Dogs with chronic gastrointestinal signs from suspected inflammatory CE between 2017 and 2019 were included. Thirty-eight were evaluated; every dog had a CBC, serum biochemistry panel, and abdominal imaging performed. The Canine Inflammatory Bowel Disease Activity Index (CIBDAI) was calculated. Thromboelastography was performed at presentation, and reaction time (R), kinetic time (K), α-angle, maximal amplitude (MA), and global clot strength (G) were recorded. Dogs were considered hypercoagulable if the G value was ≥25% above the reference interval., Results: Seventeen of 38 (44.7%; 95% confidence interval [CI], 28.6-61.7%) dogs with CE were hypercoagulable. The G value did not differ between the 19 dogs with normal (≥28 g/L) serum albumin concentrations (9.05 kdyn/cm 2 ; 95% CI, 7.26-10.84; SD 3.71) and 19 dogs with hypoalbuminemia (11.3 kdyn/cm 2 ; 95% CI, 9.04-13.6, SD; 4.7; P = .11). The G value was negatively correlated with hematocrit, serum albumin concentration, and duration of signs and positively correlated with age., Conclusions and Clinical Importance: Dogs with CE and normal serum albumin concentration can be hypercoagulable as measured by TEG., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

Elective health checks form an important part of the preventative healthcare of many zoo-housed animals. These procedures are not without risk or financial expenditure, meaning careful cost-benefit analysis is required when determining the frequency and intensity with which they are implemented. This study evaluated the value of elective health checks ( n = 74) carried out on 33 gibbons at a single UK zoological collection from 2011 to 2018. Data were categorised by health check type, animal age, clinical findings and outcome. Univariable binary logistic regression and multivariable modelling were used to identify factors associated with the likelihood of actionable (clinically significant) outcomes. In total, 51.35% of all elective health checks resulted in an actionable outcome. Elderly heath checks had 13.64 times greater odds of an actionable outcome and 34 times greater odds of a significant radiographic finding, when compared to routine (non-elderly) health checks. Our findings suggest that 75% wild longevity is a suitable threshold for identifying elderly captive gibbons and increasing health check frequency. Whilst further work is needed to ascertain whether these findings can be extrapolated to other collections and/or species, this study demonstrates how the analysis of clinical data can aid in the implementation of an effective and evidence-based preventative healthcare plan.