Prehabilitation for frail patients undergoing colorectal surgery: lessons learnt from a randomised feasibility study

There is substantial interest by clinicians to improve the health outcomes of older and frail patients followingmajor surgery, with prehabilitation a potential and important component of future standard patient care. We studied the feasibility of a randomised controlled trial of pre-operative prehabilitation in frail patients scheduled for colorectal surgery in regional Australia. We conducted a single blind, parallel arm, randomised controlled trial in a regional referral centre where colorectal surgical patients aged over 50 were invited to participate and screened for frailty. Frail patients were randomised to undertake either a 4-week supervised exercise program with dietary advice, or usual care. The primary outcome was 6-min-walk-distance at baseline, pre-surgery (4 weeks later) and at follow-up (4–6 weeks post-operation). Secondary outcomes included physical activity level, health-related quality of life, and post-surgical complications. Feasibility outcomes were numbers of patients reaching each stage and barriers or reasons for withdrawal. Of 106 patients eligible for screening during the 2-year study period, only five were able to be randomised, of which one alone completed the entire study to follow-up. Fewer patients than expected met the frailty criteria (23.6%), and many (22.6%) were offered surgery in a shorter timeframe than the required 4 weeks. Physical and psychological aspects of frailty and logistical issues were key for patients declining study participation and/or not complying with the intervention and/or all outcome assessments. Feasibility for a large randomised controlled trial of prehabilitation for frail colorectal patients was poor (~5%) for our regional location. Addressing barriers, examination of a large, dense population base, and utilisation of a frailty-screening tool validated in surgical patients are necessary for future studies to identify the impact of prehabilitation for frail patients

Early high flow nasal cannula therapy in bronchiolitis, a prospective randomised control trial (protocol): A Paediatric Acute Respiratory Intervention Study (PARIS)

Background Bronchiolitis imposes the largest health care burden on non-elective paediatric hospital admissions worldwide, with up to 15 % of cases requiring admission to intensive care. A number of previous studies have failed to show benefit of pharmaceutical treatment in respect to length of stay, reduction in PICU admission rates or intubation frequency. The early use of non-invasive respiratory support devices in less intensive scenarios to facilitate earlier respiratory support may have an impact on outcome by avoiding progression of the disease process. High Flow Nasal Cannula (HFNC) therapy has emerged as a new method to provide humidified air flow to deliver a non-invasive form of positive pressure support with titratable oxygen fraction. There is a lack of high-grade evidence on use of HFNC therapy in bronchiolitis. Methods/Design Prospective multi-centre randomised trial comparing standard treatment (standard subnasal oxygen) and High Flow Nasal Cannula therapy in infants with bronchiolitis admitted to 17 hospitals emergency departments and wards in Australia and New Zealand, including 12 non-tertiary regional/metropolitan and 5 tertiary centres. The primary outcome is treatment failure; defined as meeting three out of four pre-specified failure criteria requiring escalation of treatment or higher level of care; i) heart rate remains unchanged or increased compared to admission/enrolment observations, ii) respiratory rate remains unchanged or increased compared to admission/enrolment observations, iii) oxygen requirement in HFNC therapy arm exceeds FiO2 ≥ 40 % to maintain SpO2 ≥ 92 % (or ≥94 %) or oxygen requirement in standard subnasal oxygen therapy arm exceeds >2L/min to maintain SpO2 ≥ 92 % (or ≥94 %), and iv) hospital internal Early Warning Tool calls for medical review and escalation of care. Secondary outcomes include transfer to tertiary institution, admission to intensive care, length of stay, length of oxygen treatment, need for non-invasive/invasive ventilation, intubation, adverse events, and cost. Discussion This large multicenter randomised trial will allow the definitive assessment of the efficacy of HFNC therapy as compared to standard subnasal oxygen in the treatment of bronchiolitis

ИЗУЧЕНИЕ РАЗНООБРАЗИЯ БАКТЕРИОФАГОВ ЛАКТОКОККОВ, ВЫДЕЛЕННЫХ ИЗ ФЕРМЕНТИРОВАННЫХ МОЛОЧНЫХ ПРОДУКТОВ, С ИСПОЛЬЗОВАНИЕМ МОЛЕКУЛЯРНО-ГЕНЕТИЧЕСКИХ МЕТОДОВ

For production of fermented milk products in the territory of the Republic of Belarus, lactic acid bacteria related to p. Lactococcus are used more often. Continuous phage monitoring makes it possible to limit economic losses due to phagolysis at production of fermented milk products, as well as to reduce the risk of contamination of finished products with pathogenic microbiota. It is necessary to identify and determine the properties of bacteriophages for that circulating at enterprises, considering that at each individual enterprise there are no specific types (kinds) of phages, which is due to the assortment of products, types of ferments used and hygiene conditions. The article dwells on studies on isolation and characterization of lactococci bacteriophages. Of the 51 phagocontaining samples of products selected in the territory of the Republic of Belarus, 68 bacteriophages have been isolated. The spectrum of their lytic activity was determined. Based on the results of PCR with species specific primers, 39 bacteriophages are classified as C2 type. One bacteriophage was identified as P335 according to PCR results. 939 type bacteriophages were not detected among the isolated viruses. Differentiation of C2 type lactococcal phages was carried out. A selection of the restriction enzymes allowing to distinguish phages inside the C2 type is carried out. A scheme of intraspecific differentiation of lactococci bacteriophages was developed using RFLP analysis. RFLP-analysis allowed to divide 39 lactophages of type C2 into six groups. Acknowledgements. The work was carried out within the framework of research under task 9.5.50 “Study of species diversity of lactic acid bacteria obtained from natural sources, variability of lactococci phages obtained at milk processing plants, depending on season and region” of GPNI “Innovative technologies in agro-industrial complex”. В производстве ферментированных молочных продуктов на территории Республики Беларусь чаще других используют молочнокислые бактерии, относящиеся к р. Lactococcus. Непрерывный фаговый мониторинг позволяет ограничить экономические потери от фаголизиса при производстве кисломолочных продуктов, а также снизить риск контаминации готовой продукции патогенной микробиотой. Для этого необходимо выделять, идентифицировать, определять свойства бактериофагов, циркулирующих на предприятиях, принимая во внимание, что на каждом отдельном предприятии присутствуют определенные виды (типы) фагов, что обусловлено ассортиментом выпускаемой продукции, применяемыми видами заквасок и соблюдением санитарно-гигиенических условий. В статье представлены исследования по выделению и характеристике бактериофагов лактококков. Из 51 фагосодержа- щего образца продукции, отобранного на территории Республики Беларусь, выделено 68 бактериофагов. Определен спектр их литической активности. На основании результатов ПЦР с видоспецифичными праймерами 39 бактериофагов отнесены к виду С2. Один бактериофаг по результатам ПЦР идентифицирован как вид Р335. Бактериофагов вида 936 среди выделенных вирусов не выявлено. Проведена дифференциация лактококкофагов вида С2. Проведен подбор рестриктаз, позволяющих различать фаги внутри вида С2. Разработана схема внутривидовой дифференциации бактериофагов лактококков с помощью ПДРФ-анализа. Использование ПДРФ-анализа позволило разделить 39 лактофагов вида С2 на шесть групп. Благодарности. Работа выполнена в рамках исследований по заданию 9.5.50 «Изучение видового разнообразия молочнокислых бактерий, выделенных из природных источников, изменчивости фагов лактококков, выделенных на молокоперерабатывающих предприятиях, в зависимости от сезонности и региональности» ГПНИ «Инновационные технологии в АПК»

Epidemiology, prehospital care and outcomes of patients arriving by ambulance with dyspnoea: An observational study

Background: This study aimed to determine epidemiology and outcome for patients presenting to emergency departments (ED) with shortness of breath who were transported by ambulance. Methods: This was a planned sub-study of a prospective, interrupted time series cohort study conducted at three time points in 2014 and which included consecutive adult patients presenting to the ED with dyspnoea as a main symptom. For this sub-study, additional inclusion criteria were presentation to an ED in Australia or New Zealand and transport by ambulance. The primary outcomes of interest are the epidemiology and outcome of these patients. Analysis was by descriptive statistics and comparisons of proportions. Results: One thousand seven patients met inclusion criteria. Median age was 74 years (IQR 61-68) and 46.1 % were male. There was a high rate of co-morbidity and chronic medication use. The most common ED diagnoses were lower respiratory tract infection (including pneumonia, 22.7 %), cardiac failure (20.5%) and exacerbation of chronic obstructive pulmonary disease (19.7 %). ED disposition was hospital admission (including ICU) for 76.4 %, ICU admission for 5.6 % and death in ED in 0.9 %. Overall in-hospital mortality among admitted patients was 6.5 %. Discussion: Patients transported by ambulance with shortness of breath make up a significant proportion of ambulance caseload and have high comorbidity and high hospital admission rate. In this study, >60 % were accounted for by patients with heart failure, lower respiratory tract infection or COPD, but there were a wide range of diagnoses. This has implications for service planning, models of care and paramedic training. Conclusion: This study shows that patients transported to hospital by ambulance with shortness of breath are a complex and seriously ill group with a broad range of diagnoses. Understanding the characteristics of these patients, the range of diagnoses and their outcome can help inform training and planning of services

A multicentre randomised controlled trial of levetiracetam versus phenytoin for convulsive status epilepticus in children (protocol): Convulsive Status Epilepticus Paediatric Trial (ConSEPT) - a PREDICT study

Background: Convulsive status epilepticus (CSE) is the most common life-threatening childhood neurological emergency. Despite this, there is a lack of high quality evidence supporting medication use after first line benzodiazepines, with current treatment protocols based solely on non-experimental evidence and expert opinion. The current standard of care, phenytoin, is only 60% effective, and associated with considerable adverse effects. A newer anti-convulsant, levetiracetam, can be given faster, is potentially more efficacious, with a more tolerable side effect profile. The primary aim of the study presented in this protocol is to determine whether intravenous (IV) levetiracetam or IV phenytoin is the better second line treatment for the emergency management of CSE in children. Methods/Design: 200 children aged between 3 months and 16 years presenting to 13 emergency departments in Australia and New Zealand with CSE, that has failed to stop with first line benzodiazepines, will be enrolled into this multicentre open randomised controlled trial. Participants will be randomised to 40 mg/kg IV levetiracetam infusion over 5 min or 20 mg/kg IV phenytoin infusion over 20 min. The primary outcome for the study is clinical cessation of seizure activity five minutes following the completion of the infusion of the study medication. Blinded confirmation of the primary outcome will occur with the primary outcome assessment being video recorded and assessed by a primary outcome assessment team blinded to treatment allocation. Secondary outcomes include: Clinical cessation of seizure activity at two hours; Time to clinical seizure cessation; Need for rapid sequence induction; Intensive care unit (ICU) admission; Serious adverse events; Length of Hospital/ICU stay; Health care costs; Seizure status/death at one-month post discharge. Discussion: This paper presents the background, rationale, and design for a randomised controlled trial comparing levetiracetam to phenytoin in children presenting with CSE in whom benzodiazepines have failed. This study will provide the first high quality evidence for management of paediatric CSE post first-line benzodiazepines. Trial registration: Prospectively registered with the Australian and New Zealand Clinical Trial Registry (ANZCTR): ACTRN12615000129583(11/2/2015). UTN U1111-1144-5272. ConSEPT protocol version 4 (12/12/2014).The study is funded by grants from the Health Research Council of New Zealand (HRC 12/525), Auckland, New Zealand; A+ Trust (Auckland District Health Board), Auckland, New Zealand; Queensland Emergency Medicine Research Foundation, Milton, Queensland, Australia (EMPJ-105R21–2014- FURYK); Private Practice Research and Education Trust Fund, The Townsville Hospital and Health Service, Douglas, Queensland, Australia; Eric Ormond Baker Charitable Fund, Equity Trustees, Clayton, Victoria, Australia; and Princess Margaret Hospital Foundation, Perth, Western Australia, Australia. The PREDICT network is supported as a Centre of Research Excellence for Paediatric Emergency Medicine by the National Health and Medical Research Council, Canberra, Australian Capital Territory, Australia (NHMRC GNT1058560). The Victorian sites were supported by the Victorian Government’s Infrastructure Support Program, Melbourne, Victoria, Australia. FEB’s time was part funded by a grant from the Murdoch Childrens Research Institute and the Royal Children’s Hospital Foundation, Melbourne, Victoria, Australia. SRD’s time was part funded by the Health Research Council of New Zealand (HRC13/556). The study sponsor is Starship Children’s Health, Private Bag 92,024, Auckland 1142, New Zealan

Experiences and insights from the collection of a novel multimedia EEG dataset

There is a growing interest in utilising novel signal sources such as EEG (Electroencephalography) in multimedia research. When using such signals, subtle limitations are often not readily apparent without significant domain expertise. Multimedia research outputs incorporating EEG signals can fail to be replicated when only minor modifications have been made to an experiment or seemingly unimportant (or unstated) details are changed. This can lead to overoptimistic or overpessimistic viewpoints on the potential real-world utility of these signals in multimedia research activities. This paper describes an EEG/MM dataset and presents a summary of distilled experiences and knowledge gained during the preparation (and utilisiation) of the dataset that supported a collaborative neural-image labelling benchmarking task. The goal of this task was to collaboratively identify machine learning approaches that would support the use of EEG signals in areas such as image labelling and multimedia modeling or retrieval. The contributions of this paper can be listed thus; a template experimental paradigm is proposed (along with datasets and a baseline system) upon which researchers can explore multimedia image labelling using a brain-computer interface, learnings regarding commonly encountered issues (and useful signals) when conducting research that utilises EEG in multimedia contexts are provided, and finally insights are shared on how an EEG dataset was used to support a collaborative neural-image labelling benchmarking task and the valuable experiences gained

Treatment patterns and frequency of key outcomes in acute severe asthma in children: A Paediatric Research in Emergency Departments International Collaborative (PREDICT) multicentre cohort study

Rationale: Severe acute paediatric asthma may require treatment escalation beyond systemic corticosteroids, inhaled bronchodilators and lowflow oxygen. Current large asthma datasets report parenteral therapy only. Objectives To identify the use and type of escalation of treatment in children presenting to hospital with acute severe asthma. Methods: Retrospective cohort study of children with an emergency department diagnosis of asthma or wheeze at 18 Australian and New Zealand hospitals. The main outcomes were use and type of escalation treatment (defined as any of intensive care unit admission, nebulised magnesium, respiratory support or parenteral bronchodilator treatment) and hospital length of stay (LOS). Measurements and main results: Of 14 029 children (median age 3 (IQR 1–3) years; 62.9% male), 1020 (7.3%, 95% CI 6.9% to 7.7%) had treatment escalation. Children with treatment escalation had a longer LOS (44.2 hours, IQR 27.3–63.2 hours) than children without escalation 6.7 hours, IQR 3.5–16.3 hours; p<0.001). The most common treatment escalations were respiratory support alone (400; 2.9%, 95% CI 2.6% to 3.1%), parenteral bronchodilator treatment alone (380; 2.7%, 95% CI 2.5% to 3.0%) and both respiratory support and parenteral bronchodilator treatment (209; 1.5%, 95% CI 1.3% to 1.7%). Respiratory support was predominantly nasal high-flow therapy (99.0%). The most common intravenous medication regimens were: magnesium alone (50.4%), magnesium and aminophylline (24.6%) and magnesium and salbutamol (10.0%).Simon Craig ... Charmaine Gray ... Amit Kochar ... et. a

Bell's Palsy in Children (BellPIC): protocol for a multicentre, placebo-controlled randomized trial

Background: Bell's palsy or acute idiopathic lower motor neurone facial paralysis is characterized by sudden onset paralysis or weakness of the muscles to one side of the face controlled by the facial nerve. While there is high level evidence in adults demonstrating an improvement in the rate of complete recovery of facial nerve function when treated with steroids compared with placebo, similar high level studies on the use of steroids in Bell's palsy in children are not available. The aim of this study is to assess the utility of steroids in Bell's palsy in children in a randomised placebo-controlled trial. Methods/Design: We are conducting a randomised, triple-blinded, placebo controlled trial of the use of prednisolone to improve recovery from Bell's palsy at 1 month. Study sites are 10 hospitals within the Australian and New Zealand PREDICT (Paediatric Research in Emergency Departments International Collaborative) research network. 540 participants will be enrolled. To be eligible patients need to be aged 6 months to < 18 years and present within 72 hours of onset of clinician diagnosed Bell's palsy to one of the participating hospital emergency departments. Patients will be excluded in case of current use of or contraindications to steroids or if there is an alternative diagnosis. Participants will receive either prednisolone 1 mg/kg/day to a maximum of 50 mg/day or taste matched placebo for 10 days. The primary outcome is complete recovery by House-Brackmann scale at 1 month. Secondary outcomes include assessment of recovery using the Sunnybrook scale, the emotional and functional wellbeing of the participants using the Pediatric Quality of Life Inventory and Child Health Utility 9D Scale, pain using Faces Pain Scale Revised or visual analogue scales, synkinesis using a synkinesis assessment questionnaire and health utilisation costs at 1, 3 and 6 months. Participants will be tracked to 12 months if not recovered earlier. Data analysis will be by intention to treat with primary outcome presented as differences in proportions and an odds ratio adjusted for site and age. Discussion: This large multicenter randomised trial will allow the definitive assessment of the efficacy of prednisolone compared with placebo in the treatment of Bell's palsy in children.Franz E. Babl, Mark T. Mackay, Meredith L. Borland, David W. Herd, Amit Kochar, Jason Hort, Arjun Rao, John A. Cheek, Jeremy Furyk, Lisa Barrow, Shane George, Michael Zhang, Kaya Gardiner, Katherine J. Lee, Andrew Davidson, Robert Berkowitz, Frank Sullivan, Emily Porrello, Kim Marie Dalziel, Vicki Anderson, Ed Oakley, Sandy Hopper, Fiona Williams, Catherine Wilson, Amanda Williams, Stuart R Dalziel, and for the PREDICT, Paediatric Research In Emergency Departments International Collaborative, research networ

Protocol for take-home naloxone In multicentre emergency (TIME) settings: Feasibility study

Background: Opioids, such as heroin, kill more people worldwide by overdose than any other type of drug, and death rates associated with opioid poisoning in the UK are at record levels (World Drug Report 2018 [Internet]. [cited 2019 Nov 19]. Available from: http://www.unodc.org/wdr2018/; Deaths related to drug poisoning in England and Wales - Office for National Statistics [Internet]. [cited 2019 Nov 19]. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/bulletins/deathsrelatedtodrugpoisoninginenglandandwales/2018registrations). Naloxone is an opioid antagonist which can be distributed in 'kits' for administration by witnesses in an overdose emergency. This intervention is known as take-home naloxone (THN). We know that THN can save lives on an individual level, but there is currently limited evidence about the effectiveness of THN distribution on an aggregate level, in specialist drug service settings or in emergency service settings. Notably, we do not know whether THN kits reduce deaths from opioid overdose in at-risk populations, if there are unforeseen harms associated with THN distribution or if THN is cost-effective. In order to address this research gap, we aim to determine the feasibility of a fully powered cluster randomised controlled trial (RCT) of THN distribution in emergency settings. Methods: We will carry out a feasibility study for a RCT of THN distributed in emergency settings at four sites, clustered by Emergency Department (ED) and catchment area within its associated ambulance service. THN is a peer-administered intervention. At two intervention sites, emergency ambulance paramedics and ED clinical staff will distribute THN to adult patients who are at risk of opioid overdose. At two control sites, practice will carry on as usual. We will develop a method of identifying a population to include in an evaluation, comprising people at risk of fatal opioid overdose, who may potentially receive naloxone included in a THN kit. We will gather anonymised outcomes up to 1 year following a 12-month 'live' trial period for patients at risk of death from opioid poisoning. We expect approximately 100 patients at risk of opioid overdose to be in contact with each service during the 1-year recruitment period. Our outcomes will include deaths, emergency admissions, intensive care admissions, and ED attendances. We will collect numbers of eligible patients attended by participating in emergency ambulance paramedics and attending ED, THN kits issued, and NHS resource usage. We will determine whether to progress to a fully powered trial based on pre-specified progression criteria: sign-up of sites (n = 4), staff trained (≥ 50%), eligible participants identified (≥ 50%), THN provided to eligible participants (≥ 50%), people at risk of death from opioid overdose identified for inclusion in follow-up (≥ 75% of overdose deaths), outcomes retrieved for high-risk individuals (≥ 75%), and adverse event rate (< 10% difference between study arms). Discussion: This feasibility study is the first randomised, methodologically robust investigation of THN distribution in emergency settings. The study addresses an evidence gap related to the effectiveness of THN distribution in emergency settings. As this study is being carried out in emergency settings, obtaining informed consent on behalf of participants is not feasible. We therefore employ novel methods for identifying participants and capturing follow-up data, with effectiveness dependent on the quality of the available routine data