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1. Evaluating the Safety of Performing Flexible Cystoscopy When Urinalysis Suggests Presence of 'Infection': Results of a Prospective Clinical Study in 2350 patients

Author

Matthew Trail, Julia Cullen, Emma Fulton, Faye Clayton, Ewan McGregor, Faye McWilliam, Lachlan Dick, Pota Kalima, Roland Donat, and Paramananthan Mariappan

Subjects
Urinalysis, Urinary tract infection, Bladder cancer, Microbiology, Protocol, Safety, Diseases of the genitourinary system. Urology, RC870-923, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background: There is significant underutilisation of allocated health service resources when a scheduled flexible cystoscopy (FC) is cancelled because a pre-cystoscopy urinalysis (PCU) suggests “infection”, despite patients being asymptomatic for urinary tract infection (UTI). Objective: To evaluate the risk of UTI or urinary sepsis when FC is performed in asymptomatic patients with a PCU positive for leucocyte esterase and/or nitrites. Design, setting, and participants: A prospective cohort study was conducted in a high-volume UK centre recruiting all patients undergoing outpatient FC. Intervention: A protocol was developed to guide response to PCU performed prior to FC, which was performed regardless of the result, unless patients were symptomatic for UTI. All patients completed a questionnaire to identify risk factors and were followed up via a telephone survey and a review of electronic clinical records. Outcome measurements and statistical analysis: Post-FC UTI was defined as hospital admission with UTI/urinary sepsis or if patients were symptomatic for UTI with receipt of antibiotics or with positive urine culture and sensitivity. An analysis of the association was performed. Results and limitations: An initial pilot study confirmed the safety and feasibility of our protocol. Of 1996 patients, 136 (6.8%) developed a UTI by our definition, with 51 (2.6%) having a culture-proven infection. The risk was higher in patients with a positive PCU (odds ratio [OR] 1.61, 95% confidence interval [CI] = 1.07–2.40, p = 0.02), history of UTI (OR 1.72, 95% CI = 1.09–2.73, p = 0.02), or a bladder tumour on FC (OR 2.22, 95% CI = 1.27–3.90, p = 0.005). No patient with a positive PCU developed urinary sepsis. The main limitation of this study was the lack of pre-protocol control. Conclusions: We observed a clinically low and acceptable risk of UTI, with no incidence of sepsis, when FC was performed in asymptomatic patients with a PCU suggesting “infection”. Routine cancellation of these patients is unnecessary and may worsen the burden on health service resources. Patient summary: We evaluated the safety of performing flexible cystoscopy when the urine dipstick on the day suggested presence of an “infection” but the patient had no symptoms of urinary tract infection (UTI). Our study in over 2000 patients demonstrated a low incidence of UTI, and none of these patients developed sepsis. We therefore recommend that flexible cystoscopy should not be cancelled automatically on the basis of the dipstick result alone, as it might delay a time-sensitive crucial diagnosis.

Published
2021
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2. Establishing a Smartphone Ambulatory ECG Service for Patients Presenting to the Emergency Department with Pre-Syncope and Palpitations

Author

Matthew J. Reed, Alexandra Muir, Julia Cullen, Ross Murphy, Valery Pollard, Goran Zangana, Sean Krupej, Sylvia Askham, Patricia Holdsworth, and Lauren Davies

Subjects
emergency department, diagnosis, ECG monitoring, cardiac dysrhythmias, Medicine (General), R5-920
Abstract

Background and Objectives: The Investigation of Palpitations in the ED (IPED) study showed that a smartphone-based event recorder increased the number of patients in whom an electrocardiogram (ECG) was captured during symptoms over five-fold to more than 55% at 90 days compared to standard care and concluded that this safe, non-invasive and easy-to-use device should be considered part of on-going care to all patients presenting acutely with unexplained palpitations or pre-syncope. This study reports the process of establishing a smartphone palpitation and pre-syncope ambulatory care Clinic (SPACC) service. Materials and Methods: A clinical standard operating procedure (SOP) was devised, and funding was secured through a business case for the purchase of 40 AliveCor devices in the first instance. The clinic was launched on 22 July 2019. Results: Between 22 July 2019 and 31 October 2019, 68 patients seen in the emergency departments (EDs) with palpitations or pre-syncope were referred to SPACC. Of those, 30 were male and 38 were female, and the mean age was 45.8 years old (SD 15.1) with a range from 18 years old to 80 years old. A total of 50 (74%) patients underwent full investigation. On the first assessment, seven (10%) patients were deemed to have non-cardiac palpitations and were not fitted with the device. All patients who underwent full investigation achieved symptomatic rhythm correlation most with sinus rhythm, ventricular ectopics, or bigeminy. A symptomatic cardiac dysrhythmia was detected in six (8.8%) patients. Three patients had supraventricular tachycardia (4%), two had atrial fibrillation (3%), and one had atrial flutter (2%). Qualitative feedback from the SPACC team suggested several areas where improvement to the clinic could be made. Conclusion: We believe a smartphone palpitation service based on ambulatory care is simple to implement and is effective at detecting cardiac dysrhythmia in ED palpitation patients.

Published
2021
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3. Experience of a smartphone ambulatory ECG clinic for emergency department patients with palpitation: a single-centre cohort study

Author

Alexandra M. Muir, Goran Zangana, Matthew J. Reed, Sean Krupej, Sylvia Askham, Ross Murphy, Valery Pollard, Julia Cullen, Lauren Davies, and Patricia Holdsworth

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Cohort Studies, Electrocardiography, Young Adult, Ambulatory care, Atrial Fibrillation, medicine, Humans, Medical diagnosis, Atrial tachycardia, Aged, Aged, 80 and over, business.industry, Atrial fibrillation, Cardiac dysrhythmia, Emergency department, Middle Aged, medicine.disease, United States, Emergency medicine, Emergency Medicine, Supraventricular tachycardia, Smartphone, medicine.symptom, business, Emergency Service, Hospital, Cohort study
Abstract

Background and importance Palpitation is one of the commonest presenting complaints to the emergency department (ED). Diagnosis depends on capturing an ECG during the episode. Unlike syncope, patients retain consciousness and therefore their ability to activate an ECG event recorder. The Investigation of Palpitation in the ED study demonstrated Food and Drug Administration approved AliveCor/Kardia device that links to a smartphone app was safe and effective. A Smartphone Palpitation and Pre-syncope Ambulatory Care Clinic was therefore established. Objectives To review the first year of patients attending the service to determine the number and cost-effectiveness of cardiac dysrhythmias diagnoses. Design Single-center cohort study. Settings and participants Royal Infirmary of Edinburgh, UK. All patients (over 16 years) presenting consecutively to ED with palpitation or pre-syncope, whose ECG was normal, had a compatible device and where an underlying cardiac dysrhythmia was possible were enrolled. Intervention Ambulatory Care Clinic utilizing the AliveCor/Kardia device. Outcome measures and analysis Number diagnosed with cardiac dysrhythmia and mean cost per diagnosis. Main results Between 24 July 2019 and 23 July 2020, 290 consecutive patients were referred of age 16-80 years (mean 43.3, SD 15.0). One hundred twenty (41.4%) were male. Two hundred thirty-seven (81.7%) were fitted with the device and 220 (75.9%) underwent full investigation. Seventeen of 237 (7.2%) patients had a cardiac diagnosis (12 atrial fibrillation/flutter, 5 supraventricular tachycardia and 1 atrial tachycardia). Conclusions There were 17 cardiac diagnoses (7.2%). The cost per symptomatic rhythm diagnosis was 358 GBP (~415 Euro) and the cost per cardiac dysrhythmia diagnosis was 4570 GBP (~5298 Euro). A smartphone-based event recorder clinic should be considered for ED palpitation patients.

Published
2021
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4. A recent history of opioid use in the US: Three decades of change

Author

Kelsey McCain, Jacob T. Painter, Howell R Foster, Julia Cullen, Lindsey Dayer, and Jarrod King

Subjects
medicine.medical_specialty, Health (social science), media_common.quotation_subject, Medicine (miscellaneous), History, 21st Century, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Pain Management, 030212 general & internal medicine, Practice Patterns, Physicians', Epidemics, skin and connective tissue diseases, Psychiatry, media_common, Opioid epidemic, business.industry, Opioid use, Addiction, Public Health, Environmental and Occupational Health, Opioid use disorder, History, 20th Century, Opioid-Related Disorders, medicine.disease, United States, Analgesics, Opioid, Substance abuse, Psychiatry and Mental health, Opioid, sense organs, Chronic Pain, Drug Overdose, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

The opioid epidemic in the United States is a problem that has developed over decades. While clinical, regulatory, and legislative changes have been implemented to combat this issue, changes will not be immediate. Moreover, the changes that have been carried out may have unintended negative consequences such as increased use of illicit opioids (e.g., heroin and synthetics) and challenges in effective and appropriate pain management.This review focuses on the last three decades and presents key changes the United States has seen in the use of opioids. Conclusions/Importance: There have been numerous policy changes and programs aimed at decreasing opioid use and abuse in the United States; however, it will take a major shift in the mindset of clinicians, the general public, and policy makers to alleviate this epidemic.

Published
2018
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5. Characteristics of effective parent-mediated interventions for parents of children with neurodevelopmental disorders in rural areas: a systematic review protocol

Author

Michael Curtin, Vagner Dos Santos, and Julia Cullenward

Subjects
Medicine
Abstract

Introduction Parent-mediated interventions are therapeutic approaches that use parent training to enable parents to provide primary support and intervention to their child through the development of necessary skills, knowledge, and resources.Parent-mediated interventions can be broadly divided into two stages: (1) Clinicians educating, training and coaching parents in the implementation of an intervention and relevant information regarding their child’s condition and (2) Parent(s) mediating and implementing the intervention based on the coaching and education received. These interventions can act as the primary intervention for children or supplement clinical interventions. This review will include both stages of the implementation process as well as both primary and supplementary interventions. Outcomes of parent-mediated interventions include long-term symptom reduction, improved prognosis for a wide range of behavioural and brain functions and enhanced parent–child dyadic social communication.Methods and analysis This systematic review aims to synthesise existing evidence and identify the characteristics of effective parent-mediated intervention for parents of children with neurodevelopmental disorders residing in rural areas. Systematic searches of CINAHL, PsycINFO, ProQuest allied health and nursing database, Ebscohost Psych and Behavioural database and SocINDEX were conducted twice with the latest completed on 5 March 2024 using preidentified search terms. Citations will be imported into EndNote V.20.6 (Clarivate Analytics, Pennsylvania, USA) to organise and de-duplicate and then Covidence to complete screening and extraction. The articles will be screened and reviewed following the Joanna Briggs Institute (JBI) guidelines for systematic reviews of Mixed methods. The JBI appraisal tools for systematic reviews will be used to assess the trustworthiness, relevance and results of qualitative, quantitative and mixed-methods studies. The scope of the literature analysed will include articles published between 2013 and 2024 in English. Literature was limited to the last 10 years to ensure the relevance of results as the intention is to report on current evidence. The start date of the study was March 2023 and the planned completion date is October 2024.Ethics and dissemination This study will neither involve human nor animal subjects and does not require ethics approval. Results will be disseminated to relevant groups in peer-reviewed journal(s) and at relevant children and parent health conferences or rural conferences. The key outcomes will also be shared on social media to support access for non-research audiences.

Published
2024
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6. Efficacy and Safety of the Early Addition of Vasopressin to Norepinephrine in Septic Shock

Author

Drayton A. Hammond, Oktawia A Clem, Amy L Brotherton, Divyan Chopra, Kelsey McCain, Nikhil Meena, Jacob T. Painter, and Julia Cullen

Subjects
Adult, Male, Vasopressin, Mean arterial pressure, Time Factors, Organ Dysfunction Scores, Vasopressins, Kaplan-Meier Estimate, Critical Care and Intensive Care Medicine, Early initiation, Drug Administration Schedule, Norepinephrine (medication), Norepinephrine, 03 medical and health sciences, 0302 clinical medicine, Intravenous fluid, Humans, Vasoconstrictor Agents, Medicine, Arterial Pressure, In patient, Aged, Retrospective Studies, business.industry, Septic shock, 030208 emergency & critical care medicine, Retrospective cohort study, Middle Aged, medicine.disease, Shock, Septic, Treatment Outcome, 030228 respiratory system, Anesthesia, Female, business, medicine.drug
Abstract

Background: Delays in achievement of target mean arterial pressure (MAP) have been associated with increased mortality in patients with septic shock. Vasopressin may be added to norepinephrine to raise MAP or decrease norepinephrine dosage. The purpose of this study was to determine whether early initiation of vasopressin to norepinephrine resulted in a reduced time to target MAP compared to norepinephrine monotherapy. Methods: This retrospective cohort study compared early addition of vasopressin within 4 hours of septic shock onset to norepinephrine versus initial norepinephrine monotherapy in medically, critically ill patients with septic shock admitted from May 2014 to October 2015. Time to goal MAP was compared using Student t test and examined with Kaplan-Meier curves. Changes in Sequential Organ Failure Assessment (SOFA) scores were evaluated with Wilcoxon rank sum test. Results: Each group contained 48 patients. Mean arterial pressure (61.5 vs 58.6 mm Hg) and intravenous fluid volume received at vasopressor initiation (14.3 vs 25.2 hours, P = .014) were similar. Patients started on early vasopressin achieved and maintained goal MAP sooner (6.2 vs 9.9 hours, P = .023), experienced greater reductions in SOFA scores at 72 hours (−4 vs −1, P = .012), and had shorter hospital durations (343 vs 604 hours, P = .014). Not initiating early vasopressin trended toward an association with increased time to goal MAP ( P = .067). Conclusion: Early initiation of vasopressin in patients with septic shock may achieve and maintain goal MAP sooner and resolve organ dysfunction at 72 hours more effectively than later or no initiation.

Published
2017
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7. Discontinuation of Vasopressin Before Norepinephrine in the Recovery Phase of Septic Shock

Author

Kelsey McCain, Nikhil Meena, Jacob T. Painter, Oktawia A Clem, Drayton A. Hammond, Julia Cullen, Divyan Chopra, and Amy L Brotherton

Subjects
Male, Vasopressin, Critical Care, Organ Dysfunction Scores, Vasopressins, Critical Care and Intensive Care Medicine, Drug Administration Schedule, Norepinephrine (medication), Norepinephrine, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Vasoconstrictor Agents, Aged, Retrospective Studies, Septic shock, business.industry, 030208 emergency & critical care medicine, Middle Aged, medicine.disease, Shock, Septic, Discontinuation, Intensive Care Units, Treatment Outcome, 030228 respiratory system, Anesthesia, Female, business, Recovery phase, medicine.drug
Abstract

Background: Guidance for the discontinuation of vasopressors in the recovery phase of septic shock is limited. Norepinephrine is more easily titrated; however, septic shock is a vasopressin deficient state, which exogenous vasopressin endeavors to resolve. Discontinuation of vasopressin before norepinephrine may result in clinically significant hypotension. Methods: This retrospective, cohort study compared discontinuation of norepinephrine and vasopressin in medically, critically ill patients in the recovery phase of septic shock from May 2014 to June 2016. Difference in clinically significant hypotension after norepinephrine or vasopressin discontinuation was evaluated with χ2 test. Linear regression was performed, examining the effect of agent discontinuation on clinically significant hypotension. Baseline variables were examined for a bivariate relationship with clinically significant hypotension; those with P < .2 were included in the model. Results: Vasopressin was discontinued first or last in 62 and 92 patients, respectively. Sequential Organ Failure Assessment scores at 72 hours (7.9 vs 7.6, P = .679) were similar. In unadjusted analysis, when vasopressin was discontinued first, more clinically significant hypotension developed (10.9% vs 67.8%, P < .001). There was no difference in intensive care unit (174 vs 216 hours, P = .178) or hospital duration (470 vs 473 hours, P = .977). In adjusted analyses, discontinuing vasopressin first was associated with increased clinically significant hypotension (odds ratio [OR]: 13.837, 95% confidence interval [CI]: 3.403-56.250, P < .001) but not in-hospital (OR: 0.659, 95% CI: 0.204-2.137, P = .488) or 28-day mortality (OR: 0.215, 95% CI: 0.037-1.246, P = .086). Conclusion: Adult patients receiving norepinephrine and vasopressin in the resolving phase of septic shock may be less likely to develop clinically significant hypotension if vasopressin is the final vasopressor discontinued.

Published
2017
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8. Prospective Open-label Trial of Early Concomitant Vasopressin and Norepinephrine Therapy versus Initial Norepinephrine Monotherapy in Septic Shock

Author

Krishna Kakkera, Amy L Brotherton, Kelsey McCain, Oktawia A. Ficek, Jacob T. Painter, Julia Cullen, Drayton A. Hammond, Divyan Chopra, and Nikhil Meena

Subjects
Male, Mean arterial pressure, Vasopressin, Time Factors, Vasopressins, 030204 cardiovascular system & hematology, Norepinephrine (medication), 03 medical and health sciences, Norepinephrine, 0302 clinical medicine, Interquartile range, medicine, Humans, Vasoconstrictor Agents, Pharmacology (medical), Arterial Pressure, Prospective Studies, Vasopressin deficiency, Aged, Academic Medical Centers, Septic shock, business.industry, 030208 emergency & critical care medicine, Middle Aged, medicine.disease, Shock, Septic, Clinical trial, Intensive Care Units, Treatment Outcome, Concomitant, Anesthesia, Drug Therapy, Combination, Female, business, medicine.drug
Abstract

Purpose Delays in achieving target mean arterial pressure (MAP) are associated with increased morbidity and mortality in patients with septic shock. This trial was conducted to test the hypothesis that early concomitant treatment with vasopressin and norepinephrine reduces the time to achieve and maintain target MAP compared with initial norepinephrine monotherapy. Methods A single-center prospective open-label trial was conducted in patients with septic shock between November 2015 and June 2016 at a medical intensive care unit in an academic medical center. Initial norepinephrine monotherapy was initiated between November 2015 and February 2016. Between March and June 2016, vasopressin was initiated within 4 hours of norepinephrine. The primary outcome was time to achieving and maintaining MAP of 65 mm Hg for at least 4 hours that was compared between groups using the Student t test and examined using the Kaplan-Meier curve (Clinical Trials registration: NCT02454348). Results Eighty-two patients were included (41 in each group). Patients treated with early concomitant vasopressin and norepinephrine more frequently had a positive culture (59% vs 37%, p=0.05) and grew nonlactose fermenting gram-negative bacilli (34% vs 10%, p=0.01) compared with patients treated with norepinephrine monotherapy, respectively. The median time to achieve and maintain MAP occurred faster in the early concomitant vasopressin and norepinephrine group, at 5.7 hours (interquartile range [IQR] 1.7-10.3 hrs), compared with 7.6 hours (IQR 3.6-16.7 hrs, p=0.058) in the norepinephrine group. Durations of therapy for norepinephrine or vasopressin, amount of norepinephrine received in the first 24 hours, norepinephrine dosage when MAP was achieved and maintained, maximum norepinephrine dosage, and mortality were similar between groups. Conclusion Patients treated with early concomitant vasopressin and norepinephrine achieved and maintained MAP of 65 mm Hg faster than those receiving initial norepinephrine monotherapy, suggesting that overcoming vasopressin deficiency sooner may reduce the time patients spend in the early phase of septic shock.

Published
2018

9. Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe

Author

Walid Habre, Nicola Disma, Katalin Virag, Karin Becke, Tom G Hansen, Martin Jöhr, Brigitte Leva, Neil S Morton, Petronella M Vermeulen, Marzena Zielinska, Krisztina Boda, Francis Veyckemans, Walter Klimscha, Regina Konecny, Robert Luntzer, Ulrike Morawk-Wintersperger, Franz Neiger, Lydia Rustemeyer, Christian Breschan, Denise Frey, Manuela Platzer, Reinhard Germann, Joachim Oeding, Birgit Stoegermüller, Bernhard Ziegler, Philipp Brotatsch, Anton Gutmann, Gerlinde Mausser, Brigitte Messerer, Wolfgang Toller, Maria Vittinghoff, Gregor Zangl, Natascha Seidel-Ahyai, Christoph Hochhold, Ruth Kroess, Peter Paal, Steven Cnudde, Patricia Coucke, Birgit Loveniers, John Mitchell, David Kahn, Thierry Pirotte, Caroline Pregardien, Marc Coppens, Stefan De Hert, Björn Heyse, Martine Neckebroek, Aliaksandra Parashchanka, Jurgen Van Limmen, Nancy Van Den Eynde, Caroline Vanpeteghem, Piet Wyffels, Michaël Lalot, Jean-Paul Lechat, France Stevens, Sari Casaer, Françoise De Groote, Françoise De Pooter, Andrée De Villé, Marc Gerin, Natalia Magasich, Cristel Sanchez Torres, Denise Van Deenen, Johan Berghmans, Dirk Himpe, Eva Roofthooft, Ellen Joukes, Carine Smitz, Veronique Van Reeth, Christel Huygens, Julie Lauweryns, Karen De Smet, Nadia Najafi, Jan Poelaert, Anne Van de Velde, Veerle Van Mossevelde, Ivan Bekavac, Diana Butkovic, Dubravka Heli Litvic, Ivana Kerovec Soric, Hrvoje Maretic, Djurdjica Moscatello, Ljiljana Popovic, Slobodan Micici, Ivana Stuck Tus, Lada Kalagac Fabris, Tatjana Simurina, Nina Sulen, Gordana Kesic-Valpotic, Dajana Djapic, Jirí Žurek, Lucie Jureckova, Iveta Mackova, Monika Skacel, Stanislava Weinlichova, Jan Divák, Michal Frelich, René Urbanec, Vera Biskupova, Vladimir Mixa, Jana Pavlickova, Arash Afshari, Morten Bøttger, Marguerite B. Ellekvist, Mathias Johansen, Birgitte Ingeborg Madsen, Jens Christian Nilsson, Birgitte MB Schousboe, Nicola G. Clausen, Tom G. Hansen, Nick Phaff Steen, Mari-Liis Ilmoja, Virge Tonise, Juri Karjagin, Reet Kikas, Mika Isohanni, Anniina Lyly, Annika Takala, Johanna Happo, Kai Kiviluoma, Kati Martikainen, Riku Aantaa, Tuula Manner, Sanna Vilo, Catherine Amory, Hugues Ludot, Patricia Lambotte, René Busche, Olivier Jacqmarcq, Corinne Lejus, Julien Corouge, Christian Erb, Delphine Garrigue, Patricia Gillet, Anne Laffargue, Veronique Lambelin, Hélène Le Freche, Daliana Peresbota, Pierre Richart, Jerome Berton, Catherine Chapotte, Laurent Colbus, Thierry Lehousse, Jean Monrigal, Catherine Baujard, Philippe Roulleau, Giuseppe Staiti, Hélène Batoz, Maryline Bordes, Anne Didier, Yann Hamonic, Sylvaine Lagarde, Karine Nouette-Gaulain, François Semjen, Brigitte Zaghet, Jacky Dekens, Axelle Delcuze, Hervé Dupont, Aurélien Legrand, Celine Raffoflandreur, Noémie Audren, Blandine Camus, Marielle Cartal, Chantal Chazelet, Isabelle Davin, Marion Guillier, Luc Desjeux, Claire Larcher, Elodie Grein, Mickeal Leclercq, Roxana Levitchi, Lilica Rosu, Dominique Simon, Aurélien Zang, Anne Migeon, Anne-Charlotte Gagey, Nathalie Bourdaud, Anne-Charlotte Carre, Frédéric Duflo, Jean-Claude Riche, Philippe Robert, Emilie Druot, Olivier Maupain, Gilles Orliaguet, Lucie Sabau, Hanna Taright, Lynn Uhrig, Juliette Verchere-Montmayeur, Lise Debrabant, Clotaire Pilla, Alexandre Podvin, Benjamin Roth, Souhayl Dahmani, Florence Julien-Marsollier, Nada Sabourdin, Bogdan Alexandri, Gilles Brezac, Francois de la Brière, Catherine Hayem, Elizabeth Lhubat, Jean Paul Mission, Charlotte Rémond, Christophe Dadure, Maud Maniora, Anais Marie, Philippe Pirat, Anne-Charlotte Saour, Chrystelle Sola, Claude Ecoffey, Eric Wodey, Christian Adam, Thomas Standl, Ehrenfried Schindler, Tomohiro Yamamoto, Michael Brackhahn, Christoph Bernhard Eich, Holger Guericke, Petra Kindermann, Michael Laschat, Cornel Schink, Frank Wappler, Claudia Hoehne, Natalia Skordou, Johanna Ulrici, Martin Jetzek-Zader, Peter Kienbaum, Tanja Meyer-Treschan, Olaf Picker, Maximilian S. Schaefer, Golo Mielke, Sabine Baethge, Axel Ramminger, Martin Bauer, Matthias Bollinger, José Hinz, Michael Quintel, Sebastian G. Russo, Michael Bauer, Dfominik Geil, Andreas Kortgen, Niels-Peter Preussler, Ulrich Hofmann, Manfred Raber, Doris Reindl, Karin Oppenrieder, Bettina Schierlinger, Jens Roth, Wolfgang Funk, Thomas Fischer, Christian Gernoth, Christina Wiefelspütz, Hauke Volger, Nicole Zederer, Anja Diers, Matthias Huber, Clemens Schorer, Andreas Weyland, Konrad Schwarzkopf, Catharina Grau, Winfried Roth, Rolf Holy, Thomas Mader, Laura Peter, Hauke Supthut, Thomas Kuehhirt, Alexander Milde, Fritz Fiedler, Carsten Isselhorst, Ulrich Grundmann, Alexander Pattar, Jennifer Reinert, Birgit Ehm, Katrin Fritzsche, Ralf Gaebler, Patrick Meybohm, Maximilian Hein, Ines Guzman, Johanna Jokinen, Peter Kranke, Ulrich Goebel, Sarah Harris, Christoph Eisner, Miriam Ochsenreiter, Michael Schoeler, Elke Thil, Richard Ellerkmann, Andreas Hoeft, Claudia Neumann, Stefan Weber, Julia Keilhauer, Jan Kloessing, Michael Schramm, Uwe Trieschmann, Kristina Knauss, Barbara Sinner, Johannes Steinmann, Herbert Koessler, Evagelia Kalliardou, Anna Malisiova, Adelais Tsiotou, Pelagia Chloropoulou, Mpratzou Chrysi, Despoina Iordanidou, Merkourios Ntavlis, Krisztina B Boda, Christilynn Guerin, Janice Irwin, Claire Magner, Solmaz Nakhjavani, Brendan O'Hare, Deborah Galvin, Yosry Jamil, Carlos Lesmes, Yuri Barak, Haran Fisher, Ludmyla Kachko, Jacob Katz, Dmitry Kirilov, Michael Levinzon, Yair Manevich, Konstantin Nekrasov, Elia Peled, Elena Sanko, Dmitri Schmain, Olga Sheinkin, Eliahu Simhi, Alex Tarabikin, Evelina Trabkin, Irena Yagudaev, Yelena Zeitlin, Igor Zunser, Elisabetta Cerutti, Maria Maddalena Schellino, Silvia Valzan, Rosa Lucia Pinciroli, Luciano Bortone, Giorgia Cerati, Fabiana Salici, Leonardo Bussolin, Giuliana Rizzo, Francesca Rossetti, Laura Marchesini, Simonetta Tesoro, Brita De Lorenzo, Fabio Guarracino, Beate Kuppers, Marinella Astuto, Sofia Pitino, Rita Scalisi, Lucia Scordo, Sandra D'Alessandro, Luigi Dei Giudici, Ivano Farinelli, Giuseppe Lofino, Giuliano Marchetti, Sergio Giuseppe Picardo, Simone Reali, Alessandro Vittori, Francesco Antonio Idone, Maria Sammartino, Fabio Sbaraglia, Cinzia Barbera, Michela Bevilacqua, Valeria Cento, Svetlana Kotzeva, Leila Mameli, Giovanni Montobbio, Leandro Passariello, Cinzia Punzo, Rosanna Sileo, Rosanna Viacava, Claudia Volpe, Clelia Zanaboni, Edoardo Calderini, Daniele Genco, Simona Neri, Davide Ottolina, Anna Camporesi, Francesca Izzo, Ida Salvo, Andrea Wolfler, Andrea Sanna, Angela Sciascia, Paolo Stoia, Annamaria Guddo, Maria Lapi, Giorgio Ivani, Annalisa Longobardo, Valeria Mossetti, Dino Pedrotti, Maurizia Grazzini, Luisa Meneghini, Salvatore Metrangolo, Stefania Michelon, Carmelo Minardi, Costanza Tognon, Nicola Zadra, Ilaria Busi, Magda Khotcholava, Bruno Guido Locatelli, Valter Sonzogni, Giusi Starita, Nicole Almenrader, Caterina Aurilio, Pasquale Sansone, Raffaella Albarello, Paolo Bracci, Mariateresa Cecini, Maria Cristina Mondardini, Lorena Pasini, Milo Vason, Gianluca Zani, Roberto Zoppellari, Laura Pistidda, Andrea Cortegiani, Santi Maurizio Raineri, Antigona Hasani, Medita Hashimi, Agris Ancupans, Arta Barzdina, Zane Straume, Anda Zundane, Mikhail Chlopin, Dalia Gestautaite, Laura Lukosiene, Evelina Paliokaite, Ilona Razlevice, Inesa Armoniene, Aurelija Bernotiene, Vidunas Daugelavicius, Ilona Dockiene, Lina Gaidelyte, Nijole Saviciene, Jolita Krikstaponiene, Dominika Sidlovskaite-Baltake, Vladyslav Stasevski, Agne Vaitoskaite, David Gatt, Stephanie Mifsud, Simone Zammit, Celia Allison, Hamid Aslami, Susanne Eberl, Mireille F M van Stijn, Markus F Stevens, Kees Punt, Rob van Osch, Arthur Bauwman, Harm Scholten, Vesna Svircevic, Veronique Adriaens, Maaike Dirckx, Jaap Dogger, Ilse Dons-Sinke, Andreas Machotta, Xavier Moors, Mandana Rad, Lonneke Staals, Anouk van der Knijff - van Dortmont, Caroline van der Marel, Anne Sieben, Tim van der Zwan, Marianne Veldhuizen, David Alders, Wolfgang Buhre, Nicole Engel, Carine Vossen, Ravin Mahadewsing, Patrick Meijer, Volker Gerling, Roelof van der Schatte Olivier, Thea van Doorn, Kristy Vons Mark Hendriks, Sandra Lako, Gert jan Scheffer, Luc Tielens, Marieke Voet, Anthony Absalom, Margot Bergsma, Vera Spanjer, Rob Spanjersberg, Yvette van de Riet, Martin Volkers, Jurgen C. de Graaff, Geranne A.J. Hopman, Teus H. Kappen, J. Hannie, A.M. Megens, Sandra C. Numan, Anton N.J. Schouten, Nigel M. Turner, Désirée B.M. Van Der Werff, Renee T.M. 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M, Stevens, Markus F, Punt, Kee, van Osch, Rob, Bauwman, Arthur, Scholten, Harm, Svircevic, Vesna, Adriaens, Veronique, Dirckx, Maaike, Dogger, Jaap, Dons Sinke, Ilse, Machotta, Andrea, Moors, Xavier, Rad, Mandana, Staals, Lonneke, Van, der Knijff, van der Marel, Caroline, Sieben, Anne, van der Zwan, Tim, Veldhuizen, Marianne, Alders, David, Buhre, Wolfgang, Engel, Nicole, Vossen, Carine, Mahadewsing, Ravin, Meijer, Patrick, Gerling, Volker, van der Schatte Olivier, Roelof, van Doorn, Thea, Vons Mark Hendriks, Kristy, Lako, Sandra, jan Scheffer, Gert, Tielens, Luc, Voet, Marieke, Absalom, Anthony, Bergsma, Margot, Spanjer, Vera, Spanjersberg, Rob, van de Riet, Yvette, Volkers, Martin, de Graaff, Jurgen C., Hopman, Geranne A. J., Kappen, Teus H., Hannie, J., Megens, A. M., Numan, Sandra C., Schouten, Anton N. J., Turner, Nigel M., Van Der Werff, Désirée B. M., Wensing, Renee T. M., Ephraim, Erik, Nolte, Claire, Reikvam, Tore, Fredrik Lund, Ole, Skaaden, Lene, Marthe Ballovarre, Kari, Bakken Boerke, Wenche, Grindheim, Guro, Lindenskov, Pal H. H, Beate Solas, Anne, Sponheim, Sjur, Ullensvang, Kyrre, Viken, Oddbjorn, Marie Drage, Inger, Gymoese Berthelsen, Kasper, Anders Kroken, Bjørn, Bergland, Unni, Pryzmont, Miroslaw, Talalaj, Mariola, Wasiluk, Malgorzata, Zalewska, Dorota, Damps, Maria, Siemek Mitela, Jadzia, Wieczorek, Pawel, Juzwa, Magdalena, Rosada Kurasinska, Jowita, Bartkowska Sniatkowska, Alicja, Cettler, Maciej, Kopycinska, Renata, Rudewicz, Iwona, Sobczyk, Jaek, Wojciechowski, Dariusz, Baranowski, Artur, Basiewicz, Ewa, Mierzewska Schmidt, Magdalena, Retka, Wlodzimierz, Sawicki, Piotr, Checinska, Magdalena, Zurawska, Magdalena, Leal, Teresa, Mascarenhas, Catia, Pedro Pina, António, Joao Susano, Maria, Moniz, Antonio, Teresa Rocha, Maria, Calvao Santos, Carolina, Domingas Patuleia, M., Pereira, Ricardo, Roxo, Helena, Amaral, Rosa, Guedes, Isabel, Gomes, Cristina, Gonçalves, Marta, Salgado, Helena, Santos, Maria, Rodrigues, Sara, Sa, Angela, Machado, Elvira, Pé d'Arca, Sandra, Seabra, Manuel, Mihaela Gheorghe, Ligia, Ivascu, Constantin, Moraru Draghici, Lucia, Suvejan, Mirela, Babici, Remu, Eniko, Kovac, Hogea, Cristiana, Mihaela, Dubau, Nicoleta, Daraban, Barbunc, Danut, Maria Nistor, Alina, Stefan, Violeta, Catalina Ionescu, Gabriela, Davidescu, Irina, Teodora Nastase, Alina, Dumitru Rusu, Florin, Badarau, Victoria, Cindea, Iulia, Moscaliuc, Melania, Olteanu, Dana, Petrescu, Luxita, Ceuca, Daniela, Galinescu, Irena, Badeti, Rodica, Capusan, Alin, Cucui Cozma, Cosmina, Popescu, Barbura, Cimpeanu, Luminita, Birliba, Mihaela Petronela, Miulescu, Magdalena, Balamat, Stefania, Gurita, Adriana, Ilie, Luminita, Mocioiu, Gabriel, Pick, Darina, Sirghie, Rodica, Tabacaru, Radu, Trante, Irinel, Horhota, Lucian, Bandrabur, Daniela, Ciobanu, Tudor, Cuciuc, Veaceslav, Munteanu, Valentin, Olaru, Valentin, Paiu, Corneliu, Savu, Anca, Trifan, Oana, Elena Malos, Anca, Glazunov, Anton, Ivanov, Alexander, Poduskov, Evgeny, Popov, Alexander, Guskov, Igor, Lugovoy, Alexander, Nechaev, Vladislav, Ovezov, Alexey, Basov, Mikhail, Kochkin, Vladimir, Lazarev, Vladimir, Chizhov, Dmitri, Ostreikov, Ivan, Tolasov, Konstantin, Budic, Ivana, Marjanovic, Vesna, Draskovic, Biljana, Pandurov, Marina, Simin, Jovana, Dolinaj, Vladimir, Janjevic, Dusanka, Mandras, Ana, Mircetic, Maja, Petrovic, Sladjana, Rebac, Vlatka, Slavkovic, Bojana, Stevanovic, Vesna, Velcev, Ana, Knezevic, Mirjana, Milojevic, Irina, Puric, Selena, Simic, Irena, Stevic, Marija, Stranjanac, Vladimir, Simic, Dusica, Cabanova, Barbora, Hanula, Miloslav, Grynyuk, Andry, Berger, Jelena, Cerne, Uro, Nastran, Andraz, Pirc, Dejan, Popic, Rok, Stupnik, Spela, Rubio, Paloma, del Río, Cristina, Benito, Pilar, Pino, Gema, Gutierrez, Ignacio, Gutierrez Valcarcel, Andrea, León Carsi, Irene, Perez Garcia, Anibal, López Galera, Sílvia, Marco Valls, Joan, Ricol Lainez, Laura, Vallejo Tarrat, Andrea, Artes, David, Banus, Ester, Chirichiello, Luca, De Abreu, Leidy, De Josemaria, Belen, Helena Gaitan, M., Garces, Antonio, Lazaro, Juan J, Manen Berga, Ferran, Molies, Dolor, Monclus, Enric, Navaro, Montserrat, Pamies, Carmen, Perelló, Marina, Prat, Mar, Ribo, Laura, Angeles Sanz, M., Serrano, Silvia, Sola Ruiz, Eva, Anuncia Escontrela Rodríguez, Blanca, Maria Gago Martinez, Andrea, Martínez Ruiz, Alberto, De La Cruz Benito, Fausto, Gabilondo Garcia, Gustavo, Martinez Maldonado, Ever, Noriega, Bryant, Oller Duque, Lara, Olmos Mendez, Alberto, Perez Ferrer, Antonio, Reinoso Barbero, Francisco, Acevedo Bambaren, Ismael, Domínguez, Fernando, Franco, Teresa, Jiménez, Anabel, Melero, Alicia, Feliu, Montserrat, García, Irene, Montferrer, Núria, Munar, Francisca, Muro, Cristina, Nuño, Rosario, Perera, Remel, Schmucker, Erika, Börjesson, Glenda, Gillberg, Lar, Castellheim, Albert, Sandström, Kerstin, Bauer, Annette, Roos, Torbjörn, Hedlund, Lar, Boegli, Yann, Dolci, Mirko, Marcucci, Carine, Spahr Schopfer, Isabelle, Pellegrini, Michel, Book, Malte, Errass, Loreen, Riggenbach, Christine, Casutt, Mattia, Hölzle, Martin, Hurni, Thoma, Mauch, Jacqueline, Anselmi, Luciano, Anselmi, Irene, Jacomet, Alfred, Oberhauser, Marku, Wossner, Stephanie, Zettl, Angelika, Erb, Thoma, Mackiewicz, Tomasz, Simitzes, Helena, Ozer, Yetkin, Takil, Arzu, Alanoglu, Zekeriyya, Bermede, Onat, Cakar Turhan, K. Sanem, Alkis, Neslihan, Yildirim Guclu, Cigdem, Ceyda Meco, Basak, Hatipoglu, Zehra, Ozcengiz, Dilek, Begec, Zekine, Ilksen Toprak, Huseyin, Kendigelen, Pinar, Cigdem Tütüncü, Ayse, Karadeniz, Meltem Savran, Seyhan Ozkan, Tulay, Sivrikoz, Nuket, Kemal Arslantas, Mustafa, Hizal, Ayse, Tore Altun, Gülbin, Umuroglu, Tumay, Baris, Sibel, Kazak Bengisun, Zuleyha, Goncharenko, Galyna, Khrapak, Maksym, Klymenko, Tetyana, Pavlenko, Vitaliy, Prysiazhniuk, Dmytro, Rudio, Olga, Varyvoda, Mykhailo, Vodianytskyi, Sergii, Boryshkevych, Ivanna, Kyselova, Iryna, Trikash, Nikolay, Albokrinov, Andrew, Perova Sharonova, Valentina, Sklyar, Vitaliy, Surkov, Deni, Abdelaal, Amr, Barber, Nicola, Checuti, Sarah, Godsiff, Leisha, Johanne, Lynch, Simpson, Joanna, Underhill, Helen, Diwan, Rishi, Kelgeri, Nivedita, Masip, Nuria, Ravi, Radha, Roberts, Steve, Cillis, Annagrazia, Marcus, Ritchie, Merella, Federica, Love, David, Baraggia, Paolo, Bird, Victoria, Hussey, Joseph, Alderson, Peter, Bartholomew, Karen, Moncreiff, Michael, Davidson, Sarah, Hare, Alison, Kotecha, Ami, Lee, Corina, Liyanage, Ganga, Patel, Shivali, Samani, Amee, Abou Samra, Mark, Boyd, Matthew, Hullatt, Laurence, Levy, David, Pauling, Mark, Sharman, Sarah Jane, Smith, Natalie, Rutherford, John, Cavalier, Alison, Locke, Christie, Sage, Frederic, Bapat, Smita, Hammerschlag, Jacinda, Ioannou, Ioanni, King, Stephanie, Pegg, Rachel, Salota, Vishal, Sketcher, Jonathan, Thadsad, Muthu, Zeitlin, Deborah, Jack, Ewan, Lang, Colin, Ahmed, Samira, Ayyash, Reema, Bari, Francoise, Bell, Sarah J, Elizabeth Biercamp, Claire, Briggs, Sandra, Gabriella Elena Clement, Maria, Dalton, Mark, Ali Eissa Eid, Mohamed, Gandhi, Monica, Harmen Herrema, Idse, Khaffaf, Ranj, Jeng Min Law, Savio, Mcclintock, Joanna, Ireland, Nichola, Majid Saleem, Mohammed, Smith, Fiona, Cohen, Marc, Lee, Clover Ann, O'Donahue, Lizanne, Powell, Alex, Rawlinson, Ellen, Snoek, Aarjan, Weiss, Katja, Wellesley, Hugo, Crawford, Michael, Abdel Hafiz, Mostafa, Day, Alexandra, Rajamani, Balaji, Saha, Rita, Wright, Dave, Chee, Lew Chin, Bew, Stephanie, Homer, Rachel, Malarkkan, Nalini, Wolfe Barry, Juliet, Angadi, Pradeep, Cagney, Brid, De Melo, Eric, Dekker, Elsa, Helm, Emma, Jones, Gareth, Peiris, Kawshala, Russell, William, Slater, Patricia, Sodhi, Puja, Browning, Mike, Phillips, Trudie, Van Hecke, Rachel, Muir, Vimty, Singh, Piyush, Soskova, Tereza, Cumming, Craig, Farquharson, Pamela, Pearson, Karen, Shaw, Neil, Whiteside, Jonathan, Whyte, Emma, Byers, Gordon, Davies, Kay, Engelhardt, Thoma, Faliszewski, Isabella, Johnston, Graham, Kaufmann, Nil, Kusnirikova, Zuzana, Wilson, Graham, Carachi, Peter, Makin, Andrew, Foster, Brian, Lipczynski, Dariusz, Mawer, Rebecca, Rutherford, William, Rogerson, David, Rushman, Sarah, Taylor, Christopher, Tomlinson, William, Dix, Philippa, Woodward, Tom, Bell, Graham, Boyle, David, Cloherty, Marianne, Cullen, Julia, Cullen, Pauline, Fairgrieve, Ro, Ghent, Robert, Glasgow, Russell, Gordeeva, Elena, Harden, Alison, Hivey, Sarah, Jerome, Kevin, Mckee, Lesley, Morton, Neil, Pribul, Vicky, Sinclair, John, Steiner, Maria, Steward, Heather, Sweeney, Lorraine, Thomson, Wendy, Whiteside, Jeanette, Dalton, Andrew, Ross, Mark, Smith, Carolyn, Allen, Claire, Anders, Nicola, Barlow, Victoria, Bassett, Mike, Darwin, Leanne, Davison, Rachel, Diacono, Jacque, Hobbs, Amy, Hutchinson, Adel, Lomas, Bernadette, Lonsdale, Hannah, Nasser, Leila, Oshan, Vimmi, Patel, Pradip, Raistrick, Christopher, Scott Warren, Victoria, Talbot, Laura, Wai, Carolynn, Childs, Sophie, Dickinson, Matthew, Bloomfield, Tom, Garrioch, Sweyn, Watson, Karen, Gaynor, Jame, Harrison, Richard, Lee, Juliette, Blythe, Elizabeth, Dorman, Teresa, Eissa, Ayman, Ellwood, Jame, Gooch, Ingrid, Hearn, Robert, Hodgetts, Vanessa, John, Robert, Kirton, Christine, Ladak, Nadia, Morgan, Judith, Plant, Nina, Shepherd, Elizabeth, Short, Judith, Stack, Charle, Steel, Simon, Taylor, Matthew, Thomas, Deborah, Wilson, Catharine, Wilson Smith, Elaine, Bradbury, Carol L., Hussain, Nageena, Mayell, Antonia, Mesbah, Ahmed, Qureshi, Arif, Vaidyanath, Chandra, Geary, Tim, Hawksworth, Chri, Parasuraman, Tamaraichelvi, Perry, Nicole, Banerjee, Indrani, Barr, Katharine, Butler, Patrick, Davies, Jack, Flewin, Lisa, Gande, Richard, Montague, Jame, Plumb, Jame, Pratt, Thoma, Sutherland, Paul, Vail, Hannah, Wilkins, Andrew, Hunter, Catherine, Russell, Susan, Thomas, Alun, Mifsud, Mark, Strachan, Dominic, Plichon, Benoit, Harlet, Pierre, Child and Adolescent Psychiatry / Psychology, Morawk-Wintersperger, Ulrike, Seidel-Ahyai, Natascha, Lechat, Jean-Paul, Kesic-Valpotic, Gordana, Ilmoja, Mari-Lii, Nouette-Gaulain, Karine, Gagey, Anne-Charlotte, Carre, Anne-Charlotte, Riche, Jean-Claude, Verchere-Montmayeur, Juliette, Julien-Marsollier, Florence, Saour, Anne-Charlotte, Jetzek-Zader, Martin, Meyer-Treschan, Tanja, Preussler, Niels-Peter, Sidlovskaite-Baltake, Dominika, van Stijn, Mireille F M, Dons-Sinke, Ilse, van der Knijff - van Dortmont, Anouk, Hopman, Geranne A.J., Megens, A.M., Schouten, Anton N.J., Van Der Werff, Désirée B.M., Wensing, Renee T.M., Lindenskov, Pal H H, Siemek-Mitela, Jadzia, Rosada-Kurasinska, Jowita, Bartkowska-Sniatkowska, Alicja, Mierzewska-Schmidt, Magdalena, Moraru-Draghici, Lucia, Cucui-Cozma, Cosmina, Birliba, Mihaela-Petronela, Perez- Ferrer, Antonio, Spahr-Schopfer, Isabelle, Cakar Turhan, K.Sanem, Perova-Sharonova, Valentina, Abou-Samra, Mark, Sharman, Sarah-Jane, McClintock, Joanna, Lee, Clover-Ann, Abdel-Hafiz, Mostafa, Chee, Lew-Chin, McKee, Lesley, Scott-Warren, Victoria, and Wilson-Smith, Elaine

Subjects
Male, Pediatrics, Health Status, OPERATING-ROOM, Respiratory Tract Diseases, CHILDREN, 0302 clinical medicine, REGIONAL ANESTHESIA, Postoperative Complications, 030202 anesthesiology, CARDIAC-ARREST, Medicine, General anaesthesia, Prospective Studies, Prospective cohort study, Child, Intraoperative Complications, COMPLICATIONS, ddc:617, Incidence (epidemiology), Mortality rate, musculoskeletal, neural, and ocular physiology, Incidence, Age Factors, Hospitals, Europe, Cardiovascular Diseases, Child, Preschool, RESPIRATORY ADVERSE EVENTS, Female, Clinical Competence, Cohort study, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Adolescent, macromolecular substances, Anesthesia, General, Drug Hypersensitivity, 03 medical and health sciences, MORBIDITY, Journal Article, Humans, business.industry, Infant, Newborn, Infant, 030208 emergency & critical care medicine, Perioperative, nervous system, PROSPECTIVE COHORT, Relative risk, RISK-FACTORS, Observational study, Human medicine, Nervous System Diseases, business, SYSTEM
Abstract

Background Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. Methods The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered with ClinicalTrials.gov, number NCT01878760. Findings Between April 1, 2014, and Jan 31, 2015, 31 127 anaesthetic procedures in 30 874 children with a mean age of 6·35 years (SD 4·50) were included. The incidence of perioperative severe critical events was 5·2% (95% CI 5·0–5·5) with an incidence of respiratory critical events of 3·1% (2·9–3·3). Cardiovascular instability occurred in 1·9% (1·7–2·1), with an immediate poor outcome in 5·4% (3·7–7·5) of these cases. The all-cause 30-day in-hospital mortality rate was 10 in 10 000. This was independent of type of anaesthesia. Age (relative risk 0·88, 95% CI 0·86–0·90; p

Published
2017
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10. 1432: DISCONTINUATION OF VASOPRESSIN BEFORE NOREPINEPHRINE IN RECOVERY PHASE OF SEPTIC SHOCK: COHORT STUDY

Author

Jacob T. Painter, Nikhil Meena, Amy L Brotherton, Kelsey McCain, Divyan Chopra, Oktawia A Clem, Julia Cullen, and Drayton A. Hammond

Subjects
Norepinephrine (medication), Vasopressin, business.industry, Septic shock, Anesthesia, Medicine, Critical Care and Intensive Care Medicine, business, medicine.disease, medicine.drug, Recovery phase, Discontinuation, Cohort study
Published
2016
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11. 1350: NOREPINEPHRINE AND VASOPRESSIN VS NOREPINEPHRINE ALONE FOR SEPTIC SHOCK: RANDOMIZED CONTROLLED TRIAL

Author

Jacob T. Painter, Oktawia A Clem, Drayton A. Hammond, Julia Cullen, Nikhil Meena, Krishna Kakkera, and Kelsey McCain

Subjects
medicine.medical_specialty, Vasopressin, business.industry, Septic shock, 030208 emergency & critical care medicine, Critical Care and Intensive Care Medicine, medicine.disease, Norepinephrine (medication), 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, medicine, 030212 general & internal medicine, business, medicine.drug
Published
2016
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12. 1451: NOREPINEPHRINE AND VASOPRESSIN VS NOREPINEPHRINE ALONE FOR SEPTIC SHOCK: RETROSPECTIVE, COHORT STUDY

Author

Drayton A. Hammond, Jacob T. Painter, Nikhil Meena, Julia Cullen, Divyan Chopra, Kelsey McCain, Amy L Brotherton, and Oktawia A Clem

Subjects
Norepinephrine (medication), medicine.medical_specialty, Vasopressin, Endocrinology, business.industry, Septic shock, Internal medicine, medicine, Critical Care and Intensive Care Medicine, business, medicine.disease, medicine.drug
Published
2016
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14. Evidence for Renal Control of Urinary Excretion of Bile Acids and Bile Acid Sulphates in the Cholestatic Syndrome

Author

Barbara H. Billing, J. A. Summerfield, Stephen Barnes, and Julia Cullen

Subjects
Adult, Male, medicine.medical_specialty, Lithocholic acid, medicine.drug_class, Urine, Kidney, digestive system, Gastroenterology, Bile Acids and Salts, chemistry.chemical_compound, Cholestasis, Chenodeoxycholic acid, Internal medicine, medicine, Bile, Humans, Bile acid, Deoxycholic acid, Cholic acid, General Medicine, Middle Aged, Sulfuric Acids, medicine.disease, medicine.anatomical_structure, Endocrinology, chemistry, Female
Abstract

1. The bile acids and bile acid sulphates in the urine, serum and bile of eight cholestatic patients were studied quantitatively by gas-liquid chromatography and gas-liquid chromatography/mass spectrometry. 2. The primary bile acids (cholic acid and chenodeoxycholic acid) comprised on average 94% of the total bile acids in bile, 70% in the serum and 64% in urine. 3. The percentage composition of bile acids in bile was relatively constant and was not influenced by the degree of cholestasis. In contrast, in the serum only the primary bile acids were increased, the concentrations of the secondary bile acids (deoxycholic acid and lithocholic acid) and the minor bile acids remaining constant. 4. The data do not support the hypothesis that monohydroxy bile acids accumulate in cholestasis and are related to the pathogenesis of this syndrome. 5. The pattern of bile acid urinary excretion was similar to that in the serum. But in one patient, 3α,7β,12α-trihydroxy-5β-cholan-24-oic acid was a principal urinary bile acid, although very low concentrations of the compound were found in that patient's serum, suggesting that some of the minor bile acids in urine may originate by epimerization in the kidney. 6. In bile only a small proportion of the bile acids was sulphated (range 2·1–4·6%) and in serum the degree of sulphation was very variable (9–50%). However, in urine, sulphate esters accounted for a large proportion of the total bile acids (33–72%). 7. The output of bile acid sulphate in the urine was related to the urine total bile acid output but the serum concentration of bile acid sulphate remained relatively constant. Consequently, in contrast to the non-sulphated bile acids, whose renal clearance was relatively constant, the renal clearance of sulphated bile acids was directly related to the urine total bile acid output. This finding is inconsistent with the earlier hypothesis that their predominance in urine was due to a high renal clearance. It may indicate renal synthesis of some of the bile acid sulphates in the urine and/or inhibition of active renal tubular reabsorption of sulphated bile acids by non-sulphated bile acids.

Published
1977
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15. An extracellular lipopolysaccharide-phospholipid-protein complex produced by Escherichia coli grown under lysine-limiting conditions

Author

Elizabeth Work, K. W. Knox, and Julia Cullen

Subjects
Lipopolysaccharides, General Mathematics, Lysine, Size-exclusion chromatography, Cystine, Phospholipid, medicine.disease_cause, Cell wall, chemistry.chemical_compound, Bacterial Proteins, Cell Wall, Escherichia coli, Extracellular, medicine, Phospholipids, Phosphatidylethanolamine, Chromatography, Applied Mathematics, Polysaccharides, Bacterial, Articles, Lipids, Microscopy, Electron, Biochemistry, chemistry, Dialysis, Ultracentrifugation
Abstract

Lysine limitation during growth of the lysine-requiring mutant of Escherichia coli 12408 resulted in the excretion of a complex containing 60% of lipopolysaccharide, 26% of extractable phospholipid and 11% of protein. The complex was obtained from the culture filtrate in yields of about 0·5g./l. by precipitation with chloroform or gel filtration; some purification steps are described. The greater part of the phospholipid consisted of phosphatidylethanolamine, which contained four main fatty acids; two monoenoic acids and a cyclopropane acid were esterified mainly in the β-position, and a saturated acid was located mainly in the γ-position. The protein component was relatively insoluble and contained an excess of acidic over basic amino acids and little cystine. The lipopolysaccharide resembled in composition the intracellular lipopolysaccharides from rough strains of E. coli. Both protein and lipopolysaccharide constituents of the complex were serologically active; the complex was less toxic than the purified lipopolysaccharide. In the electron microscope the complex showed a mixture of particles of various sizes and shapes. Rods and hollow spheroids (diameter 12–200mμ) were most common and resembled the particles previously found surrounding cells actively excreting the complex. The chloroform-precipitated material showed a tubular lamellar structure. Soluble lipopolysaccharide prepared from the complex also consisted of hollow spheres and rods.

Published
1967
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16. Fatty acid synthesis in Escherichia coli

Author

V. A. Knivett and Julia Cullen

Subjects
Cyclopropanes, Glycerol, Chromatography, Gas, Octadecenoic Acid, General Mathematics, Oleic Acids, Palmitic Acids, Biology, medicine.disease_cause, Phosphates, chemistry.chemical_compound, Exponential growth, Escherichia coli, medicine, Magnesium, Fatty acid synthesis, chemistry.chemical_classification, Bacteriological Techniques, Chromatography, Strain (chemistry), Sulfates, Applied Mathematics, Fatty Acids, Fatty acid, Articles, Lipids, Culture Media, Quaternary Ammonium Compounds, Hexadecenoic Acid, chemistry
Abstract

1. Fatty acid formation by cells of a strain of Escherichia coli has been studied in the exponential, post-exponential and stationary phases of growth. 2. During the exponential phase of growth, the metabolic quotient (mmumoles of fatty acid synthesized/mg. dry wt. of cells/hr.) for each fatty acid in the extractable lipid was constant. 3. The newly synthesized fatty acid mixtures produced during this phase contained hexadecanoic acid (41%), hexadecenoic acid (31%), octadecenoic acid (21%) and the C(17)-cyclopropane acid, methylenehexadecanoic acid (4%). 4. As the proportion of newly synthesized material increased, changes in the fatty acid composition of the cells during this period were towards this constant composition. 5. Abrupt changes in fatty acid synthesis occurred when exponential growth ceased. 6. In media in which glycerol, or SO(4) (2-) or Mg(2+), was growth-limiting there was a small accumulation of C(17)-cyclopropane acid in cells growing in the post-exponential phase of growth. 7. Where either NH(4) (+) or PO(4) (3-) was growth-limiting and there were adequate supplies of glycerol, Mg(2+) and SO(4) (2-), there was a marked accumulation of C(17)-cyclopropane acid and C(19)-cyclopropane acid appeared. 8. Under appropriate conditions the metabolic quotient for C(17)-cyclopropane acid increased up to sevenfold at the end of exponential growth. Simultaneously the metabolic quotients of the other acids fell. 9. A mixture of glycerol, Mg(2+) and SO(4) (2-) stimulated cyclopropane acid formation in resting cells.

Published
1967
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17. Odd-Numbered Fatty Acids in Micrococcus radiodurans

Author

M. J. Jackson, V. A. Knivett, and Julia Cullen

Subjects
chemistry.chemical_classification, biology, Biochemical Phenomena, Research, Applied Mathematics, General Mathematics, Fatty Acids, Micrococcus, Micrococcus radiodurans, Ornithine, biology.organism_classification, Biochemistry, Fats, Unsaturated, Microbiology, Amino acid, chemistry.chemical_compound, chemistry, Radiosensitivity, Bacteria
Published
1965
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