28 results on '"Dark PM"'
Search Results
2. Estimation of errors in determining intrathoracic blood volume using the single transpulmonary thermal dilution technique in hypovolemic shock.
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Nirmalan M, Willard TM, Edwards DJ, Little RA, Dark PM, Nirmalan, Mahesh, Willard, Terrance M, Edwards, Dennis J, Little, Rod A, and Dark, Paul M
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- 2005
3. Hemodynamic responses to fluid resuscitation after blunt trauma.
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Girolami A, Little RA, Foëx BA, Dark PM, Girolami, Anna, Little, Roderick A, Foëx, Bernard A, and Dark, Paul M
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- 2002
4. P129 Implementing target range oxygen in critical care (trocc); a baseline survey and pilot study
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O’Driscoll, BR, Fudge, T, Cardell, J, Millar, H, and Dark, PM
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Iatrogenic hyperoxaemia is common on Critical Care Units (CCUs) throughout the world and high blood oxygen levels have been associated with adverse outcomes including increased mortality. We have commenced a pilot quality implementation study to analyse the views of Critical Care staff regarding oxygen therapy and to change practice to ensure that all patients in the Critical Care Unit have a prescribed target oxygen saturation range. 33 CCU staff responded to an online questionnaire (16 doctors, 7 nurses, 9 physiotherapists, 1 ACCP). 76% thought that slightly too much oxygen was used on the unit but only 53% favoured a formal prescription for oxygen for all patients. For ventilated patients not at risk of hypercapnia, 83% would favour a target range of 94%–98% and 10% would opt for a target range of 90%–94%. For patients at risk of hypercapnia, all respondents favoured a target range of 88%–92%. A baseline audit of practice on the unit studied 54 patients (28 on ventilators) over one month prior to the implementation of a programme of change. 85% of audited patients (46 of 54) had a formal oxygen prescription with target range. Forty patients had target range 94%–98% and six patients had target range 88%–92%, all prescriptions were judged to be appropriate. The mean PaO2on blood gas samples was 13.1 kPa compared with 15.1 kPa in 2005 and 14.9 kPa in 2010. Mean PaCO2was 5.3 kPa. The mean SpO2(pulse oximetry) was 96.8% [median 97%, range 91%–100%]. 82% of SpO2values were within the target range but four of six patients with target range 88%–92% were at least 2% above this range. Attitudes and practice in our Critical Care Unit have changed in the past decade and hyperoxaemia is less common now. However, practice still lags behind the declared ambition of our Critical Care colleagues to maintain normoxaemia for most patients. We have instituted changes to CCU practice in May-June 2017. These changes will inform the design of a systematic randomised cluster implementation study using a step-wedge design to implement current best practice in a wide range of Critical Care units.
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- 2017
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5. On the retirement of Professor Rod Little: a key player in academic emergency medicine.
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Foëx BA, Dark PM, and Yates DW
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- 2003
6. Small volume fluid resuscitation and supplementation with 20% albumin versus buffered crystalloids in adults with septic shock: A protocol for a randomised feasibility trial.
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Bannard-Smith J, Bellomo R, Felton TW, McAuley DF, Kitchen GB, Fullwood C, Thompson A, and Dark PM
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Background: Fluid therapy is universally administered in the management of patients with sepsis, however excessive cumulative fluid balance has been shown to result in worse outcomes. Hyperoncotic albumin results in both lower fluid volumes and early cumulative fluid balance, and may reduce short-term mortality in patients with septic shock., Methods: In this single centre, open label, feasibility trial; patients with early septic shock will be randomly allocated either 20% albumin for resuscitation and daily supplementation, versus buffered crystalloids alone for all fluid therapy. The intervention period will last 7 days, with follow up points at ICU and hospital discharge, and 90 days after randomisation., Objectives: Primary outcome measures including recruitment rate, intervention adherence, data completeness and safety will constitute objective evidence of feasibility, according to pre-specified thresholds. Secondary outcomes will include mortality and healthcare utilisation at 90 days, alongside other physiological and patient centred outcomes to inform the design of a future effectiveness trial., Conclusion: This study will rigorously test the feasibility of conducting a future trial to test both the clinical and cost-effectiveness of hyperoncotic albumin in patients with early septic shock., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JBS has previously received an unrestricted research grant and free albumin from CSL Behring to support another trial.7 RB has received research funding from CSL Behring in support of the HAS Flair II trial.12, (© The Intensive Care Society 2024.)
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- 2024
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7. Adoption of CKD-EPI (2021) for Glomerular Filtration Rate Estimation: Implications for UK Practice.
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Roy R, Raman M, Dark PM, Kalra PA, and Green D
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Introduction: Recommendations to move to a race-free estimating equation for glomerular filtration rate (GFR) have gained increasing prominence since 2021. We wished to determine the impact of any future adoption upon the chronic kidney disease (CKD) patient population of a large teaching hospital, with a population breakdown largely similar to that of England as a whole., Methods: We compared four estimating equations (Modification of Diet in Renal Disease [MDRD], CKD-EPI [2009], CKD-EPI [2021], and European Kidney Function Consortium [EKFC]) using the Bland-Altman method. Bias and precision were calculated (in both figures and percentages) for all patients with CKD and specific subgroups determined by age, ethnic group, CKD stage, and sex. CKD stage was assessed using all four equations., Results: All equations studied had a positive bias in South Asian patients and a negative bias in black patients compared to CKD-EPI (2021). Similarly, there was a positive bias in white patients across all equations studied. Comparing CKD-EPI (2009) and EKFC, this positive bias increased as patients aged; the opposite was seen with MDRD. Between 10% and 28% of patients in our dataset changed their CKD staging depending upon the estimating equation used., Discussion: Our work confirms previous findings that the MDRD equation overestimates estimated GFR (eGFR) in South Asians and underestimates eGFR in blacks. The alternative equations also demonstrated similar bias. This may, in part, explain the health inequalities seen in ethnic minority patients in the UK. Applying our findings to the UK CKD population as a whole would result in anywhere from 260,000 to 730,000 patients having their CKD stage reclassified, which in turn will impact secondary care services., (© 2024 The Author(s). Published by S. Karger AG, Basel.)
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- 2024
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8. Analysis of exhaled breath to identify critically ill patients with ventilator-associated pneumonia.
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Felton TW, Ahmed W, White IR, van Oort P, Rattray NJW, Docherty C, Bannard-Smith J, Morton B, Welters I, McMullan R, Roberts SA, Goodacre R, Dark PM, and Fowler SJ
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- Humans, Biomarkers, Breath Tests methods, Critical Illness, Respiratory System chemistry, Pneumonia, Ventilator-Associated diagnosis, Pneumonia, Ventilator-Associated microbiology, Volatile Organic Compounds analysis
- Abstract
Ventilator-associated pneumonia commonly occurs in critically ill patients. Clinical suspicion results in overuse of antibiotics, which in turn promotes antimicrobial resistance. Detection of volatile organic compounds in the exhaled breath of critically ill patients might allow earlier detection of pneumonia and avoid unnecessary antibiotic prescription. We report a proof of concept study for non-invasive diagnosis of ventilator-associated pneumonia in intensive care (the BRAVo study). Mechanically ventilated critically ill patients commenced on antibiotics for clinical suspicion of ventilator-associated pneumonia were recruited within the first 24 h of treatment. Paired exhaled breath and respiratory tract samples were collected. Exhaled breath was captured on sorbent tubes and then analysed using thermal desorption gas chromatography-mass spectrometry to detect volatile organic compounds. Microbiological culture of a pathogenic bacteria in respiratory tract samples provided confirmation of ventilator-associated pneumonia. Univariable and multivariable analyses of volatile organic compounds were performed to identify potential biomarkers for a 'rule-out' test. Ninety-six participants were enrolled in the trial, with exhaled breath available from 92. Of all compounds tested, the four highest performing candidate biomarkers were benzene, cyclohexanone, pentanol and undecanal with area under the receiver operating characteristic curve ranging from 0.67 to 0.77 and negative predictive values from 85% to 88%. Identified volatile organic compounds in the exhaled breath of mechanically ventilated critically ill patients show promise as a useful non-invasive 'rule-out' test for ventilator-associated pneumonia., (© 2023 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)
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- 2023
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9. Current Perspectives and Concerns Facing Hospital Evacuation: The Results of a Pilot Study and Literature Review.
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Khorram-Manesh A, Phattharapornjaroen P, Mortelmans LJ, Goniewicz K, Verheul M, Sörensen JL, Pereira I, Ricklin ME, Faccincani R, Dark PM, Carlström E, Ahmadi Marzaleh M, Peyravi MR, Al Sultan M, Santamaria E, Comandante JD, and Burkle F
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- Humans, Netherlands, Pilot Projects, Disaster Planning, Hospitals
- Abstract
Objective: To analyze the evacuation preparedness of hospitals within the European Union (EU)., Method: This study consisted of 2 steps. In the first step, a systematic review of the subject matter, according to the PRISMA flow diagram, was performed. Using Scopus (Elsevier, Amsterdam, Netherlands), PubMed (National Library of Medicine, Bethesda, MD), and Gothenburg University´s search engine, 11 questions were extracted from the review and were sent to representatives from 15 European Union (EU)- and non-EU countries., Results: The findings indicate that there is neither a full preparedness nor a standard guideline for evacuation within the EU or other non-EU countries in this study. A major shortcoming revealed by this study is the lack of awareness of the untoward consequences of medical decision-making during an evacuation. Some countries did not respond to the questions due to the lack of relevant guidelines, instructions, or time., Conclusion: Hospitals are exposed to internal and external incidents and require an adequate evacuation plan. Despite many publications, reports, and conclusions on successful and unsuccessful evacuation, there is still no common guide for evacuation, and many hospitals lack the proper preparedness. There is a need for a multinational collaboration, specifically within the EU, to establish such an evacuation planning or guideline to be used mutually within the union and the international community.
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- 2022
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10. SARS-CoV-2 environmental contamination from hospitalised patients with COVID-19 receiving aerosol-generating procedures.
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Winslow RL, Zhou J, Windle EF, Nur I, Lall R, Ji C, Millar JE, Dark PM, Naisbitt J, Simonds A, Dunning J, Barclay W, Baillie JK, Perkins GD, Semple MG, McAuley DF, and Green CA
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- Aerosols, Continuous Positive Airway Pressure methods, Humans, RNA, Viral, COVID-19, SARS-CoV-2
- Abstract
Background: Continuous positive airways pressure (CPAP) and high-flow nasal oxygen (HFNO) are considered 'aerosol-generating procedures' in the treatment of COVID-19., Objective: To measure air and surface environmental contamination with SARS-CoV-2 virus when CPAP and HFNO are used, compared with supplemental oxygen, to investigate the potential risks of viral transmission to healthcare workers and patients., Methods: 30 hospitalised patients with COVID-19 requiring supplemental oxygen, with a fraction of inspired oxygen ≥0.4 to maintain oxygen saturation ≥94%, were prospectively enrolled into an observational environmental sampling study. Participants received either supplemental oxygen, CPAP or HFNO (n=10 in each group). A nasopharyngeal swab, three air and three surface samples were collected from each participant and the clinical environment. Real-time quantitative polymerase chain reaction analyses were performed for viral and human RNA, and positive/suspected-positive samples were cultured for the presence of biologically viable virus., Results: Overall 21/30 (70%) participants tested positive for SARS-CoV-2 RNA in the nasopharynx. In contrast, only 4/90 (4%) and 6/90 (7%) of all air and surface samples tested positive (positive for E and ORF1a) for viral RNA respectively, although there were an additional 10 suspected-positive samples in both air and surfaces samples (positive for E or ORF1a). CPAP/HFNO use or coughing was not associated with significantly more environmental contamination than supplemental oxygen use. Only one nasopharyngeal sample was culture positive., Conclusions: The use of CPAP and HFNO to treat moderate/severe COVID-19 did not appear to be associated with substantially higher levels of air or surface viral contamination in the immediate care environment, compared with the use of supplemental oxygen., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)
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- 2022
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11. RAND appropriateness panel to determine the applicability of UK guidelines on the management of acute respiratory distress syndrome (ARDS) and other strategies in the context of the COVID-19 pandemic.
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Griffiths M, Meade S, Summers C, McAuley DF, Proudfoot A, Baladia MM, Dark PM, Diomede K, Finney SJ, Forni LG, Meadows C, Naldrett IA, Patel B, Perkins GD, Samaan MA, Sharifi L, Suntharalingam G, Tarmey NT, Young HF, Wise MP, and Irving PM
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- COVID-19 Testing, Humans, Pandemics, Research, Respiration, Artificial, SARS-CoV-2, United Kingdom epidemiology, COVID-19, Respiratory Distress Syndrome diagnosis, Respiratory Distress Syndrome epidemiology, Respiratory Distress Syndrome therapy
- Abstract
Background: COVID-19 has become the most common cause of acute respiratory distress syndrome (ARDS) worldwide. Features of the pathophysiology and clinical presentation partially distinguish it from 'classical' ARDS. A Research and Development (RAND) analysis gauged the opinion of an expert panel about the management of ARDS with and without COVID-19 as the precipitating cause, using recent UK guidelines as a template., Methods: An 11-person panel comprising intensive care practitioners rated the appropriateness of ARDS management options at different times during hospital admission, in the presence or absence of, or varying severity of SARS-CoV-2 infection on a scale of 1-9 (where 1-3 is inappropriate, 4-6 is uncertain and 7-9 is appropriate). A summary of the anonymised results was discussed at an online meeting moderated by an expert in RAND methodology. The modified online survey comprising 76 questions, subdivided into investigations (16), non-invasive respiratory support (18), basic intensive care unit management of ARDS (20), management of refractory hypoxaemia (8), pharmacotherapy (7) and anticoagulation (7), was completed again., Results: Disagreement between experts was significant only when addressing the appropriateness of diagnostic bronchoscopy in patients with confirmed or suspected COVID-19. Adherence to existing published guidelines for the management of ARDS for relevant evidence-based interventions was recommended. Responses of the experts to the final survey suggested that the supportive management of ARDS should be the same, regardless of a COVID-19 diagnosis. For patients with ARDS with COVID-19, the panel recommended routine treatment with corticosteroids and a lower threshold for full anticoagulation based on a high index of suspicion for venous thromboembolic disease., Conclusion: The expert panel found no reason to deviate from the evidence-based supportive strategies for managing ARDS outlined in recent guidelines., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2022
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12. Untargeted Molecular Analysis of Exhaled Breath as a Diagnostic Test for Ventilator-Associated Lower Respiratory Tract Infections (BreathDx).
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van Oort PM, Nijsen TM, White IR, Knobel HH, Felton T, Rattray N, Lawal O, Bulut M, Ahmed W, Artigas A, Povoa PR, Martin-Loeches I, Weda H, Goodacre R, Schultz MJ, Dark PM, Fowler SJ, and Bos LD
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- Breath Tests, Diagnostic Tests, Routine, Exhalation, Humans, Ventilators, Mechanical, Pneumonia, Ventilator-Associated, Respiratory Tract Infections diagnosis
- Abstract
Patients suspected of ventilator-associated lower respiratory tract infections (VA-LRTIs) commonly receive broad-spectrum antimicrobial therapy unnecessarily. We tested whether exhaled breath analysis can discriminate between patients suspected of VA-LRTI with confirmed infection, from patients with negative cultures. Breath from 108 patients suspected of VA-LRTI was analysed by gas chromatography-mass spectrometry. The breath test had a sensitivity of 98% at a specificity of 49%, confirmed with a second analytical method. The breath test had a negative predictive value of 96% and excluded pneumonia in half of the patients with negative cultures. Trial registration number: UKCRN ID number 19086, registered May 2015., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)
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- 2022
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13. Ensuring that COVID-19 research is inclusive: guidance from the NIHR INCLUDE project.
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Witham MD, Anderson E, Carroll CB, Dark PM, Down K, Hall AS, Knee J, Maher ER, Maier RH, Mountain GA, Nestor G, O'Brien JT, Oliva L, Wason J, and Rochester L
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- Humans, Biomedical Research organization & administration, COVID-19 epidemiology, Minority Groups, SARS-CoV-2
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Objective: To provide guidance to researchers, funders, regulators and study delivery teams to ensure that research on COVID-19 is inclusive, particularly of groups disproportionately affected by COVID-19 and who may have been historically under-served by research., Summary of Key Points: Groups who are disproportionately affected by COVID-19 include (but are not limited to) older people, people with multiple long-term conditions, people with disabilities, people from Black, Asian and Ethnic minority groups, people living with obesity, people who are socioeconomically deprived and people living in care homes. All these groups are under-served by clinical research, and there is an urgent need to rectify this if COVID-19 research is to deliver relevant evidence for these groups who are most in need. We provide a framework and checklists for addressing key issues when designing and delivering inclusive COVID-19 research, based on the National Institute for Health Research INnovations in CLinical trial design and delivery for the UnDEr-served project roadmap. Strong community engagement, codevelopment and prioritisation of research questions and interventions are essential. Under-served groups should be represented on funding panels and ethics committees, who should insist on the removal of barriers to participation. Exclusion criteria should be kept to a minimum; intervention delivery and outcome measurement should be simple, flexible and tailored to the needs of different groups, and local advice on the best way to reach and engage with under-served communities should be taken by study delivery teams. Data on characteristics that allow identification of under-served groups must be collected, analyses should include these data to enable subgroup comparisons and results should be shared with under-served groups at an early stage., Conclusion: Inclusive COVID-19 research is a necessity, not a luxury, if research is to benefit all the communities it seeks to serve. It requires close engagement with under-served groups and attention to aspects of study topic, design, delivery, analysis and dissemination across the research life cycle., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)
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- 2020
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14. Developing a roadmap to improve trial delivery for under-served groups: results from a UK multi-stakeholder process.
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Witham MD, Anderson E, Carroll C, Dark PM, Down K, Hall AS, Knee J, Maier RH, Mountain GA, Nestor G, Oliva L, Prowse SR, Tortice A, Wason J, and Rochester L
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- Consensus, Cross-Sectional Studies, Humans, Surveys and Questionnaires, United Kingdom, Clinical Trials as Topic, Medically Underserved Area, Patient Participation, Research Design, Trust
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Background: Participants in clinical research studies often do not reflect the populations for which healthcare interventions are needed or will be used. Enhancing representation of under-served groups in clinical research is important to ensure that research findings are widely applicable. We describe a multicomponent workstream project to improve representation of under-served groups in clinical trials., Methods: The project comprised three main strands: (1) a targeted scoping review of literature to identify previous work characterising under-served groups and barriers to inclusion, (2) surveys of professional stakeholders and participant representative groups involved in research delivery to refine these initial findings and identify examples of innovation and good practice and (3) a series of workshops bringing together key stakeholders from funding, design, delivery and participant groups to reach consensus on definitions, barriers and a strategic roadmap for future work. The work was commissioned by the UK National Institute for Health Research Clinical Research Network. Output from these strands was integrated by a steering committee to generate a series of goals, workstream plans and a strategic roadmap for future development work in this area., Results: 'Under-served groups' was identified and agreed by the stakeholder group as the preferred term. Three-quarters of stakeholders felt that a clear definition of under-served groups did not currently exist; definition was challenging and context-specific, but exemplar groups (e.g. those with language barriers or mental illness) were identified as under-served. Barriers to successful inclusion of under-served groups could be clustered into communication between research teams and participant groups; how trials are designed and delivered, differing agendas of research teams and participant groups; and lack of trust in the research process. Four key goals for future work were identified: building long-term relationships with under-served groups, developing training resources to improve design and delivery of trials for under-served groups, developing infrastructure and systems to support this work and working with funders, regulators and other stakeholders to remove barriers to inclusion., Conclusions: The work of the INCLUDE group over the next 12 months will build on these findings by generating resources customised for different under-served groups to improve the representativeness of trial populations.
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- 2020
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15. Biomarker-guided antibiotic cessation in sepsis: evidence and future challenges.
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Claxton AN and Dark PM
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- Anti-Bacterial Agents administration & dosage, Biomarkers blood, Evidence-Based Practice, Humans, Sepsis blood, Anti-Bacterial Agents therapeutic use, Sepsis drug therapy
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Sepsis is a medical emergency, which requires the initiation of broad-spectrum antimicrobial agents as early as possible. In the absence of positive microbiological cultures providing targeted antimicrobial advice, broad-spectrum antibiotics are commonly continued until there is clinical evidence of infection resolution. With an absence of robust evidence to inform when it is safe to stop antimicrobial agents in sepsis, the duration of antimicrobial courses may be longer than is required. Prolonged courses of potent broad-spectrum antimicrobials increase the risk of adverse drug events and contribute to the growing emergence of multidrug resistant pathogens, which is a global public health emergency. The protocolised use of protein biomarkers to guide clinical decision making can be used to help combat excessive durations of antimicrobials in patients with sepsis. This article reviews the current evidence for biomarker-guided antimicrobial discontinuation protocols in sepsis, identifies related evidence gaps and examines future innovation challenges in this field.
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- 2018
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16. Draft Genome Sequence of Erwinia billingiae OSU19-1, Isolated from a Pear Tree Canker.
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Klein JM, Bennett RW, MacFarland L, Abranches Da Silva ME, Meza-Turner BM, Dark PM, Frey ME, Wellappili DP, Beugli AD, Jue HJ, Mellander JM, Wei W, and Ream W
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Plant-associated Erwinia include pathogenic and nonpathogenic species. We report the 5.6-Mb genome sequence of Erwinia billingiae OSU19-1, isolated from a canker on a pear tree inoculated with Erwinia amylovora. OSU19-1 and a closely related European isolate, E. billingiae Eb661(T), share many similarities including 40 kb of plasmid sequence., (Copyright © 2015 Klein et al.)
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- 2015
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17. Removal of Contaminant DNA by Combined UV-EMA Treatment Allows Low Copy Number Detection of Clinically Relevant Bacteria Using Pan-Bacterial Real-Time PCR.
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Humphrey B, McLeod N, Turner C, Sutton JM, Dark PM, and Warhurst G
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- DNA Contamination, DNA Primers chemistry, DNA Primers genetics, Humans, Indicators and Reagents chemistry, Molecular Sequence Data, Propidium analogs & derivatives, Propidium chemistry, Sensitivity and Specificity, Ultraviolet Rays, Azides chemistry, DNA, Bacterial chemistry, DNA, Bacterial genetics, Decontamination methods, Gene Dosage genetics, Real-Time Polymerase Chain Reaction methods
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Background: More than two decades after its discovery, contaminant microbial DNA in PCR reagents continues to impact the sensitivity and integrity of broad-range PCR diagnostic techniques. This is particularly relevant to their use in the setting of human sepsis, where a successful diagnostic on blood samples needs to combine universal bacterial detection with sensitivity to 1-2 genome copies, because low levels of a broad range of bacteria are implicated., Results: We investigated the efficacy of ethidium monoazide (EMA) and propidium monoazide (PMA) treatment as emerging methods for the decontamination of PCR reagents. Both treatments were able to inactivate contaminating microbial DNA but only at concentrations that considerably affected assay sensitivity. Increasing amplicon length improved EMA/PMA decontamination efficiency but at the cost of assay sensitivity. The same was true for UV exposure as an alternative decontamination strategy, likely due to damage sustained by oligonucleotide primers which were a significant source of contamination. However, a simple combination strategy with UV-treated PCR reagents paired with EMA-treated primers produced an assay capable of two genome copy detection and a <5% contamination rate. This decontamination strategy could have important utility in developing improved pan-bacterial assays for rapid diagnosis of low pathogen burden conditions such as in the blood of patients with suspected blood stream infection.
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- 2015
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18. Surveillance for lower airway pathogens in mechanically ventilated patients by metabolomic analysis of exhaled breath: a case-control study.
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Fowler SJ, Basanta-Sanchez M, Xu Y, Goodacre R, and Dark PM
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- Adult, Aged, Breath Tests methods, Bronchoalveolar Lavage Fluid microbiology, Case-Control Studies, Critical Care methods, Exhalation, Female, Humans, Intensive Care Units, Longitudinal Studies, Male, Middle Aged, Pneumonia, Ventilator-Associated microbiology, Population Surveillance methods, Metabolomics methods, Pneumonia, Ventilator-Associated diagnosis
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Background: Healthcare associated infections, including ventilator associated pneumonia, are difficult to diagnose and treat, and are associated with significant morbidity, mortality and cost. We aimed to demonstrate proof of concept that breath volatile profiles were associated with the presence of clinically relevant pathogens in the lower respiratory tract., Methods: Patients with sterile brain injury requiring intubation and ventilation on the intensive care unit were eligible for inclusion. Serial clinical and breath data were obtained three times a week, from admission up to a maximum of 10 days. Bronchial lavage for semiquantitative culture was collected immediately prior to breath sampling. Breath samples were collected in triplicate for off-line analysis by thermal-desorption/gas chromatography/time-of-flight mass spectrometry. Breath data were recorded as retention time/mass ion pairs, and analysed (pathogen present vs absent) by ANOVA-mean centre principal component analysis., Results: Samples were collected from 46 patients (mean (SD) age 49 (19) years; 27 male). The dominant factors affecting breath sample analysis were the individual breath profile and duration of intubation. When these were taken into account, clear separation was seen between breath profiles at each time point by the presence/absence of pathogens. Loadings plots identified consistent metabolite peaks contributing to this separation at each time point., Conclusions: Breath volatile analysis is able to classify breath profiles of patients with and without significant pathogen load in the lower respiratory tract. If validated in independent cohorts, these findings could lead to development of rapid non-invasive point-of-care surveillance systems and diagnostics for lower respiratory tract infection in the intensive care unit., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)
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- 2015
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19. Bench-to-bedside review: the promise of rapid infection diagnosis during sepsis using polymerase chain reaction-based pathogen detection.
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Dark PM, Dean P, and Warhurst G
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- Humans, Molecular Diagnostic Techniques methods, Time Factors, Early Diagnosis, Polymerase Chain Reaction, Sepsis diagnosis, Sepsis genetics
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Early infection diagnosis as the cause of a patient's systemic inflammatory syndrome is an important facet of sepsis care bundles aimed at saving lives. Microbiological culture provides the main route for infection diagnosis but by its nature cannot provide time-critical results that can impact on early management. Consequently, broad-spectrum and high-potency antibiotics are essential during the immediate management of suspected sepsis in critical care but are associated with the development of drug-resistant organisms and superinfections. Established molecular laboratory techniques based on polymerase chain reaction (PCR) technology can detect pathogen DNA rapidly and have been developed for translation into a clinical diagnostic setting. In the setting of sepsis in critical care, emerging commercial systems are now available for the analysis of whole blood within hours, with the presumed aim of adoption into the current care bundles. In this review, we consider the importance of early infection diagnosis in sepsis, how this is limited by culture approaches and how the emerging PCR methods are showing promise in early clinical observational studies. The strengths and weaknesses of culture and PCR pathogen detection in whole-blood samples will be highlighted and recommendations made for urgent appropriately powered diagnostic validation studies in advance of clinical effectiveness trials before these emerging PCR pathogen detection techniques can be considered for adoption in clinical practice.
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- 2009
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20. Organ-specific effects of oxygen and carbogen gas inhalation on tissue longitudinal relaxation times.
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O'Connor JP, Jackson A, Buonaccorsi GA, Buckley DL, Roberts C, Watson Y, Cheung S, McGrath DM, Naish JH, Rose CJ, Dark PM, Jayson GC, and Parker GJ
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- Administration, Inhalation, Adult, Arteries physiology, Fasting physiology, Female, Humans, Image Enhancement methods, Image Processing, Computer-Assisted methods, Imaging, Three-Dimensional methods, Kidney Cortex blood supply, Liver blood supply, Male, Muscle, Skeletal blood supply, Oxygen blood, Oxygen Consumption physiology, Regional Blood Flow physiology, Spleen blood supply, Subcutaneous Fat, Abdominal blood supply, Abdomen blood supply, Carbon Dioxide administration & dosage, Magnetic Resonance Imaging methods, Oxygen administration & dosage
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Molecular oxygen has been previously shown to shorten longitudinal relaxation time (T1) in the spleen and renal cortex, but not in the liver or fat. In this study, the magnitude and temporal evolution of this effect were investigated. Medical air, oxygen, and carbogen (95% oxygen/5% CO2) were administered sequentially in 16 healthy volunteers. T1 maps were acquired using spoiled gradient echo sequences (TR=3.5 ms, TE=0.9 ms, alpha=2 degrees/8 degrees/17 degrees) with six acquisitions on air, 12 on oxygen, 12 on carbogen, and six to 12 back on air. Mean T1 values and change in relaxation rate were compared between each phase of gas inhalation in the liver, spleen, skeletal muscle, renal cortex, and fat by one-way analysis of variance. Oxygen-induced T1-shortening occurred in the liver in fasted subjects (P<0.001) but not in non-fasted subjects (P=0.244). T1-shortening in spleen and renal cortex (both P<0.001) were greater than previously reported. Carbogen induced conflicting responses in different organs, suggesting a complex relationship with organ vasculature. Shortening of tissue T1 by oxygen is more pronounced and more complex than previously recognized. The effect may be useful as a biomarker of arterial flow and oxygen delivery to vascular beds., (Copyright (c) 2007 Wiley-Liss, Inc.)
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- 2007
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21. Differences between brain and rectal temperatures during routine critical care of patients with severe traumatic brain injury.
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Childs C, Vail A, Protheroe R, King AT, and Dark PM
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- Abbreviated Injury Scale, Adult, Aged, Brain Injuries therapy, Female, Humans, Male, Middle Aged, Monitoring, Physiologic methods, Prospective Studies, Body Temperature, Brain physiopathology, Brain Injuries physiopathology, Critical Care methods, Rectum physiopathology
- Abstract
Theoretical models suggest that small differences only exist between brain and body temperature in health. Once the brain is injured, brain temperature is generally regarded to rise above body temperature. However, since reports of the magnitude of the temperature gradient between brain and body vary, it is still not clear whether conventional body temperature monitoring accurately predicts brain temperature at all times. In this prospective, descriptive study, 20 adults with severe primary brain trauma were studied during their stay in the neurointensive care unit. Brain temperature ranged from 33.4 to 39.9 degrees C. Comparisons between paired brain and rectal temperature measurements revealed no evidence of a systematic difference [mean difference -0.04 degrees C (range -0.13 to 0.05 degrees C, 95% CI), p = 0.39]. Contrary to popular belief, brain temperature did not exceed systemic temperature in this relatively homogeneous patient series. The mean values masked inconsistent and unpredictable individual brain-rectal temperature differences (range 1.8 to -2.9 degrees C) and reversal of the brain-body temperature gradient occurred in some patients. Brain temperature could not be predicted from body temperature at all times.
- Published
- 2005
- Full Text
- View/download PDF
22. The validity of trans-esophageal Doppler ultrasonography as a measure of cardiac output in critically ill adults.
- Author
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Dark PM and Singer M
- Subjects
- Adult, Humans, Reproducibility of Results, Thermodilution, Cardiac Output, Critical Illness, Echocardiography, Doppler, Echocardiography, Transesophageal
- Abstract
Objective: To determine the validity of the esophageal Doppler monitor (EDM) and echo-esophageal Doppler (Echo-ED) in measuring cardiac output in the critically ill., Design: Systematic search of relevant international literature and data synthesis., Search Strategy: Literature search (1989-2003) using Ovid interface to Medline, Embase and Cochrane databases aimed at finding studies comparing EDM or Echo-ED cardiac output with that derived from simultaneous pulmonary artery thermodilution (PAC(TD)) with Bland Altman measures of validity., Patients: Critically ill adults in operating departments or intensive care units., Data Synthesis: Summary validity measures synthesized from Bland Altman analyses included pooled median bias and the median percentage of clinical agreement (PCA) derived from the limits of agreement., Main Results: Eleven validation papers for EDM (21 studies) involving 314 patients and 2,400 paired measurements. The pooled median bias for PAC(TD) versus EDM was 0.19 l/min (range -0.69 to 2.00 l/min) for cardiac output (16 studies), and 0.6% (range 0-2.3%) for changes in cardiac output (5 studies). The pooled median percentage of clinical agreement for PAC(TD) versus EDM was 52% (interquartile range 42-69%) for cardiac output and 86% (interquartile range 55-93%) for changes in cardiac output. These differences in PCA were significant ( p=0.03 Mann-Whitney) for bolus PAC(TD) as the clinical "gold standard". We found an insufficient number of studies (2 papers) to assess the validity of Echo-ED., Conclusions: The esophageal Doppler monitor has high validity (no bias and high clinical agreement with pulmonary artery thermodilution) for monitoring changes in cardiac output.
- Published
- 2004
- Full Text
- View/download PDF
23. Estimation of errors in determining intrathoracic blood volume using thermal dilution in pigs with acute lung injury and haemorrhage.
- Author
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Nirmalan M, Niranjan M, Willard T, Edwards JD, Little RA, and Dark PM
- Subjects
- Animals, Dye Dilution Technique, Female, Hemodynamics, Hypertension, Pulmonary physiopathology, Lung Compliance, Reproducibility of Results, Swine, Thermodilution methods, Blood Volume, Hemorrhage physiopathology, Respiratory Distress Syndrome physiopathology
- Abstract
Background: Global end diastolic volume (GEDV) has a constant and predictable relationship to intrathoracic blood volume (ITBV). The present study assesses the difference between ITBV derived from GEDV and ITBV measured directly in pigs with acute lung injury (ALI) and mild haemorrhage., Methods: We caused ALI in 12 anaesthetized pigs by i.v. injection of oleic acid and removed 10% of estimated blood volume. EVLW, GEDV, ITBV (COLD; Pulsion Medical Systems), Pa(o(2))/Fi(o(2)), lung compliance and haemodynamic variables were measured at baseline (time 0) and at 30 and 120 min. All animals were volume-resuscitated, followed by measurements at 180 min. A linear equation estimated from the 44 pairs of ITBV and GEDV values in 11 animals was applied iteratively to the four GEDV measurements in the 12th animal, enabling 48 comparisons between measured (ITBVm) and derived ITBV (ITBVd) to be made., Results: Increase in extravascular lung water index (EVLWi) was associated with significant pulmonary hypertension, worsening of oxygenation and compliance (repeated measures ANOVA; P<0.05). There was good within-subject correlation and agreement between ITBV(m) and ITBV(d) (r=0.72, mean bias 0.8 ml; sd 32 ml). Mean error in deriving ITBV from GEDV was 4.5%. (sd 4.2%; range 0.05-19%). There were no significant differences in errors in the presence of small (up to 10%) deficits in blood volume (F=1.0; P=0.41)., Conclusions: ITBV estimated by thermodilution alone is comparable to measurements made by the thermo-dye dilution technique in the presence of pulmonary hypertension and mild deficits in total blood volume.
- Published
- 2004
- Full Text
- View/download PDF
24. Editorial IV: physical and pharmacological restraint of critically ill patients: clinical facts and ethical considerations.
- Author
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Nirmalan M, Dark PM, Nightingale P, and Harris J
- Subjects
- Ethics, Clinical, Humans, Psychomotor Agitation etiology, Psychomotor Agitation therapy, United Kingdom, Behavior Control ethics, Critical Care ethics, Critical Illness therapy
- Published
- 2004
- Full Text
- View/download PDF
25. Duration of breast feeding and adult arterial distensibility. Statistical analysis was unclear.
- Author
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Dark PM and Rölli MJ
- Subjects
- Data Interpretation, Statistical, Elasticity, Humans, Infant, Infant, Newborn, Regression Analysis, Vasodilation physiology, Breast Feeding adverse effects, Cardiovascular Diseases etiology
- Published
- 2001
26. Monitoring the circulatory responses of shocked patients during fluid resuscitation in the emergency department.
- Author
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Dark PM, Delooz HH, Hillier V, Hanson J, and Little RA
- Subjects
- Adult, Aged, Aged, 80 and over, Blood Flow Velocity, Chi-Square Distribution, Critical Illness, Female, Hemodynamics, Humans, Male, Middle Aged, Prospective Studies, Shock diagnosis, Shock, Septic diagnosis, Shock, Septic physiopathology, Shock, Septic therapy, Statistics, Nonparametric, Survival Analysis, Ultrasonography, Doppler instrumentation, Emergency Service, Hospital, Fluid Therapy, Shock physiopathology, Shock therapy, Stroke Volume, Ventricular Dysfunction, Left diagnostic imaging, Ventricular Dysfunction, Left physiopathology
- Abstract
Objectives: To assess the feasibility of constructing left ventricular response curves non-invasively during the fluid resuscitation of critically ill patients in the emergency department (ED) using a portable suprasternal Doppler ultrasound (PSSDU) device., Design: Prospective case series., Setting: Emergency department, Catholic University of Leuven, Belgium., Patients: Shocked patients in the ED were diagnosed by predefined criteria. Only those thought to require standardised intravenous colloid challenges were observed i. e., sequential boluses of 3.5 ml/kg/10 min titrated against changes in stroke distance (Doppler surrogate for left ventricular stroke volume)., Results: A total of 50 shocked patients were studied. Stroke distance was measurable in 45 patients. 35 patients were fluid responders in terms of stroke distance. Group mean stroke distance increased during resuscitation (8.6 +/- 4.1 cm to 19.5 +/- 4.6 cm, P < 0.001) and then reached a plateau value (19.6 +/- 4.6 cm, P = 0.488). No response to fluid was seen in nine patients of which eight had severe sepsis. Alternative therapeutic approaches increased stroke distance for all of these patients. Evidence for right ventricular dysfunction was found as a cause for fluid non-response in the majority of patients with sepsis., Conclusions: Previous experimental work has shown that changes in central blood flow can be derived using the PSSDU device. This clinical feasibility study suggests that the PSSDU can help tailor haemodynamic therapy for an individual patient and give an early indication of treatment failure in the ED.
- Published
- 2000
- Full Text
- View/download PDF
27. Hypothermia in trauma patients.
- Author
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Van Camp LA and Dark PM
- Subjects
- Humans, Hypothermia etiology, Injury Severity Score, Multiple Trauma complications, Research Design
- Published
- 1996
- Full Text
- View/download PDF
28. An objective analysis of an accident flying squad.
- Author
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Dark PM, Little K, Steedman DJ, Gordon MW, and Robertson CE
- Subjects
- Heart Arrest therapy, Humans, Prognosis, Scotland, Severity of Illness Index, Wounds and Injuries therapy, Emergency Medical Services, Transportation of Patients statistics & numerical data
- Abstract
An objective evaluation of an accident flying squad, in relation to trauma call-outs during a six month period, was performed using the Injury Severity Score and the recently described Revised TRISS methodology. We have demonstrated improvement in patient survival for those trauma cases treated at the scene. This has not been previously documented. Objective evaluation of these squads in relation to medical emergencies is even more difficult. The profile of these call-outs is described. (11.1%) of those treated at the scene for cardiac arrest survived to leave hospital. Ventricular fibrillation was the primary arrhythmia recorded in this group of survivors. This supports the vogue for extended ambulance personnel training.
- Published
- 1990
- Full Text
- View/download PDF
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