Long-term anaesthesia of broiler chickens

Objective To provide stable anaesthesia of long duration in broiler chickens in order to perform a terminal caecal ligated loop procedure. Study design Prospective experimental study. Animals Seven clinically healthy broiler chickens (Gallus domesticus) aged 27–36 days, weighing 884–2000 g. Methods Anaesthesia was induced and maintained with isoflurane in oxygen. All birds underwent intermittent positive pressure ventilation for the duration. End-tidal carbon dioxide, peripheral haemoglobin oxygen saturation, heart rate and oesophageal temperature were monitored continuously. All birds received intraosseous fluids. Butorphanol (2 mg kg–1) was administered intramuscularly at 2 hourly intervals. Euthanasia by parenteral pentobarbitone was performed at the end of procedure. Results Stable anaesthesia was maintained in four chickens for durations ranging from 435 to 510 minutes. One bird died and one was euthanized after 130 and 330 minutes, respectively, owing to surgical complications and another died from anaesthetic complication after 285 minutes. Conclusions and clinical relevance Long-term, stable anaesthesia is possible in clinically healthy chickens, provided complications such as hypothermia and hypoventilation are addressed and vital signs are carefully monitored. There are no known previous reports describing monitored, controlled anaesthesia of this duration in chickens

Prebiotic Driven Increases in IL-17A Do Not Prevent Campylobacter jejuni Colonization of Chickens

© Copyright © 2020 Flaujac Lafontaine, Richards, Connerton, O’Kane, Ghaffar, Cummings, Fish and Connerton. Worldwide Campylobacter jejuni is a leading cause of foodborne disease. Contamination of chicken meat with digesta from C. jejuni-positive birds during slaughter and processing is a key route of transmission to humans through the food chain. Colonization of chickens with C. jejuni elicits host innate immune responses that may be modulated by dietary additives to provide a reduction in the number of campylobacters colonizing the gastrointestinal tract and thereby reduce the likelihood of human exposure to an infectious dose. Here we report the effects of prebiotic galacto-oligosaccharide (GOS) on broiler chickens colonized with C. jejuni when challenged at either an early stage in development at 6 days of age or 20 days old when campylobacters are frequently detected in commercial flocks. GOS-fed birds had increased growth performance, but the levels of C. jejuni colonizing the cecal pouches were unchanged irrespective of the age of challenge. Dietary GOS modulated the immune response to C. jejuni by increasing cytokine IL-17A expression at colonization. Correspondingly, reduced diversity of the cecal microbiota was associated with Campylobacter colonization in GOS-fed birds. In birds challenged at 6 days-old the reduction in microbial diversity was accompanied by an increase in the relative abundance of Escherichia spp. Whilst immuno-modulation of the Th17 pro-inflammatory response did not prevent C. jejuni colonization of the intestinal tract of broiler chickens, the study highlights the potential for combinations of prebiotics, and specific competitors (synbiotics) to engage with the host innate immunity to reduce pathogen burdens

The PRECISE (PREgnancy Care Integrating translational Science, Everywhere) Network’s first protocol: deep phenotyping in three sub-Saharan African countries

Background: The PRECISE (PREgnancy Care Integrating translational Science, Everywhere) Network is a new and broadly-based group of research scientists and health advocates based in the UK, Africa and North America. Methods: This paper describes the protocol that underpins the clinical research activity of the Network, so that the investigators, and broader global health community, can have access to ‘deep phenotyping’ (social determinants of health, demographic and clinical parameters, placental biology and agnostic discovery biology) of women as they advance through pregnancy to the end of the puerperium, whether those pregnancies have normal outcomes or are complicated by one/more of the placental disorders of pregnancy (pregnancy hypertension, fetal growth restriction and stillbirth). Our clinical sites are in The Gambia (Farafenni), Kenya (Kilifi County), and Mozambique (Maputo Province). In each country, 50 non-pregnant women of reproductive age will be recruited each month for 1 year, to provide a final national sample size of 600; these women will provide culturally-, ethnically-, seasonallyand spatially-relevant control data with which to compare women with normal and complicated pregnancies. Between the three countries we will recruit ≈10,000 unselected pregnant women over 2 years. An estimated 1500 women will experience one/more placental complications over the same epoch. Importantly, as we will have accurate gestational age dating using the TraCer device, we will be able to discriminate between fetal growth restriction and preterm birth. Recruitment and follow-up will be primarily facility-based and will include women booking for antenatal care, subsequent visits in the third trimester, at time-of-disease, when relevant, during/ immediately after birth and 6 weeks after birth. Conclusions: To accelerate progress towards the women’s and children’s health-relevant Sustainable Development Goals, we need to understand how a variety of social, chronic disease, biomarker and pregnancy-specific determinants health interact to result in either a resilient or a compromised pregnancy for either mother or fetus/ newborn, or both. This protocol has been designed to create such a depth of understanding. We are seeking funding to maintain the cohort to better understand the implications of pregnancy complications for both maternal and child health

Consequences Matter : Compassion in Conservation Means Caring for Individuals, Populations and Species

Funding This research received no external funding. Acknowledgments The manuscript benefitted from significant input from Dan Brockington, J.B. Callicott, Peter Coals, Tim Hodgetts, David Macdonald and Jeremy Wilson. Conflicts of Interest The authors declare no conflict of interest.Peer reviewedPublisher PD

The challenges of a randomised placebo-controlled trial of CTO PCI vs. placebo with optimal medical therapy: The ORBITA-CTO pilot study design and protocol

BackgroundPercutaneous coronary intervention (PCI) for coronary chronic total occlusion (CTO) has been performed for the improvement of symptoms and quality of life in patients with stable angina. The ORBITA study demonstrated the role of the placebo effect in contemporary PCI in non-CTO chronic coronary syndromes. However, the benefit of CTO PCI beyond that of a placebo has not been demonstrated.AimsThe ORBITA-CTO pilot study will be a double-blind, placebo-controlled study of CTO PCI randomising patients who have: (1) been accepted by a CTO operator for PCI; (2) experienced symptoms due to a CTO; (3) evidence of ischaemia; (4) evidence of viability within the CTO territory; and (5) a J-CTO score ≤3.MethodsPatients will undergo medication optimisation that will ensure they are on at least a minimum amount of anti-anginals and complete questionnaires. Patients will record their symptoms on an app daily throughout the study. Patients will undergo randomisation procedures, including an overnight stay, and be discharged the following day. All anti-anginals will be stopped after randomisation and re-initiated on a patient-led basis during the 6-month follow-up period. At follow-up, patients will undergo repeat questionnaires and unblinding, with a further 2-week unblinded follow-up.ResultsThe co-primary outcomes are feasibility (blinding) in this cohort and angina symptom score using an ordinal clinical outcome scale for angina. Secondary outcomes include changes in quality-of-life measures, Seattle Angina Questionnaire (SAQ), peak VO2, and anaerobic threshold on the cardiopulmonary exercise test.ConclusionThe feasibility of a placebo-controlled CTO PCI study will lead to future studies assessing efficacy. The impact of CTO PCI on angina measured using a novel daily symptom app may provide improved fidelity in assessing symptoms in patients with CTO's

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Variation in postoperative outcomes of patients with intracranial tumors: insights from a prospective international cohort study during the COVID-19 pandemic

Background: This study assessed the international variation in surgical neuro-oncology practice and 30-day outcomes of patients who had surgery for an intracranial tumor during the COVID-19 pandemic. Methods: We prospectively included adults aged ≥18 years who underwent surgery for a malignant or benign intracranial tumor across 55 international hospitals from 26 countries. Each participating hospital recorded cases for 3 consecutive months from the start of the pandemic. We categorized patients’ location by World Bank income groups (high [HIC], upper-middle [UMIC], and low- and lower-middle [LLMIC]). Main outcomes were a change from routine management, SARS-CoV-2 infection, and 30-day mortality. We used a Bayesian multilevel logistic regression stratified by hospitals and adjusted for key confounders to estimate the association between income groups and mortality. Results: Among 1016 patients, the number of patients in each income group was 765 (75.3%) in HIC, 142 (14.0%) in UMIC, and 109 (10.7%) in LLMIC. The management of 200 (19.8%) patients changed from usual care, most commonly delayed surgery. Within 30 days after surgery, 14 (1.4%) patients had a COVID-19 diagnosis and 39 (3.8%) patients died. In the multivariable model, LLMIC was associated with increased mortality (odds ratio 2.83, 95% credible interval 1.37–5.74) compared to HIC. Conclusions: The first wave of the pandemic had a significant impact on surgical decision-making. While the incidence of SARS-CoV-2 infection within 30 days after surgery was low, there was a disparity in mortality between countries and this warrants further examination to identify any modifiable factors

Sudden Cardiac Death in Ischaemic Cardiomyopathy and the Primary Prevention ICD: Time for a More a Personalised Approach?

Guidelines recommend primary prevention implantable cardioverter defibrillator (PPICD) for left ventricular ejection fraction (LVEF) <35% only after 3 months of optimal medical therapy (OMT) or 6 weeks after acute MI with persistent LVEF dysfunction. A 73-year-old woman presented with decompensated heart failure secondary to ischaemic cardiomyopathy. Severe coronary disease with sufficient dysfunctional myocardial segments on cardiac MRI suggested potential benefit from revascularisation. Following discussion with the heart team, she underwent percutaneous coronary intervention (PCI). PPICD implantation was deferred as per guideline recommendations. However, 20 days post-PCI, the patient died from malignant ventricular arrhythmia captured on a Holter monitor. This case demonstrates that some high-risk patients may not receive a potentially life-saving PPICD if guidelines are stringently adhered to. We highlight evidence that LVEF alone is of limited value in a risk assessment of arrhythmogenic death, and postulate that a more personalised ICD prescription should be considered using scar characteristics on cardiac MRI to prompt upstream ICD implantation in high-risk patients

Acceptability, usability, and credibility of a mindfulness-based digital therapeutic for pediatric concussion: A mixed-method study

Background The ability to cope with concussion symptoms and manage stress is an important determinant of risk for prolonged symptoms. Objective This open-label mixed-methods pilot study assessed the acceptability and credibility of a mindfulness-based intervention delivered through a digital therapeutic (DTx; therapeutic smartphone app) for pediatric concussion. Methods Participants aged 12 to 18 years were recruited from an emergency department within 48 hours of a concussion (acute cohort) or from a tertiary care clinic at least 1-month post-concussion (persisting symptoms cohort). Participants completed a novel 4-week mindfulness-based intervention, for 10 to 15 minutes/day, at a minimum of 4 days/week. At 2 weeks, participants completed a credibility and expectancy questionnaire. At 4 weeks, participants completed questionnaires assessing satisfaction, usability and working alliance, as well as a semi-structured phone interview. Results Ten participants completed the study outcomes (7 acute; 3 persisting symptoms). The intervention was perceived as credible (median/max possible = 6.50/9.00 [6.83,8.75]) and DTx was usable (median/max possible = 70.00/100.00 [55.00,82.50]). Participants rated their satisfaction with the DTx (median/max possible = 27.00/32.00 [24.50,29.50]) and the working alliance with the digital mindfulness guides (median/max possible = 3.92/5.00 [3.38–4.33]) as high. Four themes were identified from the qualitative data: (a) positive attributes; (b) negative attributes; (c) ideas for modifications; and (d) technical issues. Conclusion Results show modifications to the DTx, instructions and mindfulness intervention, and potential ways to increase adherence by leveraging positive attributes. A randomized control trial will assess the effectiveness of the DTx MBI to decrease the risk of persisting symptoms and reduce the symptom burden following pediatric concussion