The prospective testing of the accuracy of a prognosis prediction score in pleural infection

Lead Research Organisation: University of Oxford
Department Name: Clinical Medicine

Abstract

Pleural infection describes infected fluid collecting between the lung and chest wall. There are around 80,000 new cases each year (US+UK), of which 35% are either fatal or require chest surgery. Standard treatment involves antibiotics and drainage of infected fluid, achieved through a tube placed in the chest. If this fails, surgical drainage is required, but we currently do not have a reliable way of identifying which patients will need surgery. Prompt surgery may be life saving in needy cases, but it is also associated with major complications and results in a substantial amount of pain. Thus, targeting surgery to those who need it most is important. This study will test a prediction tool which may allow us to identify ?high risk? who may benefit most from surgery.
The proposed test is a risk prediction score calculated on admission to hospital. Previous data suggests it may be possible to predict patients who would die from their pleural infection from five test results which are routinely collected in clinical practice. While these predictors seem very powerful, they need to be tested in ?real world? use. In addition, other work suggests that the type of bacteria responsible for the infection may predict death, and these factors will also be explored as possible ?predictors?.
This study will collect information about 550 pleural infection patients, recruited from UK, Europe, USA and the Far East. All patients will receive the best available treatment, including antibiotics, chest drainage and surgery if needed. We will record which patients die or need surgery. At the end of the study, we will calculate whether the ?predictors? identify patients at high risk of death.
The team conducting this research have previously successfully completed many studies in this area. Together the research team holds #45m of clinical research funding. If the score tested here turns out to be a good way predict which patients will do badly, this can be immediately used to change how we treat patients with this disease.

Technical Summary

This proposal is to test a potentially powerful, novel, low-cost, and readily translatable prediction model that could be applied at presentation to all patients with pleural infection. If it is successful in prospective clinical testing, this model would allow clinicians to reliably identify subjects with pleural infection at high risk of death and poor outcome to receive targeted extra supportive care, surgery, and newer complex and expensive intrapleural interventions. Successful completion of this study would result in an immediately applicable score, which could be rapidly disseminated into care through specialist care guidelines.
The core of the prediction model is a combination score based on the blood urea, albumin, blood pressure, age, and the source of the infection. These factors have been identified using regression analysis from a previous large cohort of patients with pleural infection, and now require prospective testing. This clinical model will be combined with bacterial markers of prognosis recordable at baseline to create a novel multimodality score.
If it is successful in prospective clinical testing, it would allow clinicians to reliably identify subjects at high risk of death and poor outcome to receive targeted extra supportive care, surgery, and potentially the complex and expensive intrapleural interventions that have recently shown efficacy in clinical trials conducted by our unit.

Publications

10 25 50

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Asciak R (2018) Malignant Pleural Effusion: From Diagnostics to Therapeutics. in Clinics in chest medicine

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Bedawi EO (2021) Advances in pleural infection and malignancy. in European respiratory review : an official journal of the European Respiratory Society

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Bedawi EO (2018) The ongoing struggle with empyema management: is surgery really the answer? in Journal of thoracic disease

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Bhatnagar R (2016) Advanced medical interventions in pleural disease. in European respiratory review : an official journal of the European Respiratory Society

 
Description APPOINTED AS CO-CHAIR OF BTS PLEURAL GUIDELINES GROUP 2019
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guideline committee
 
Description Appointed as chair of BTS Pleural Specialist Advisory Committee
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
Impact Committee formed to increase quality and access to high quality pleural services through the BTS
 
Description BRITISH THORACIC SOCIETY - appointed as chair of Plerual Specialist Advisory Group
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
Impact Formation of a committee which looks critically at the provision of high quality pleural care across the UK, via the BTS
 
Description ERS RESPIRE2 fellowship scheme
Amount £120,000 (GBP)
Organisation European Respiratory Society (ERS) 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2015 
End 08/2017
 
Description ERS Short term fellowship
Amount € 25,000 (EUR)
Organisation European Respiratory Society (ERS) 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2019 
End 04/2019
 
Description MRC New Investigator Grant
Amount £415,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2011 
End 01/2014
 
Description NIHR RFPB
Amount £349,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 03/2015 
End 03/2017
 
Description Oxford Health Sciences Research Committee
Amount £3,000 (GBP)
Organisation Oxford University Hospitals NHS Foundation Trust 
Sector Academic/University
Country United Kingdom
Start 01/2013 
End 01/2014
 
Title OpenClinica experience 
Description Through these two studies (PILOT and RAMMP), we have gained experience and are using the OpenClinica research tool to gather data. This is now occurring highly successfully, and will be used for future funded studies. 
Type Of Material Improvements to research infrastructure 
Provided To Others? No  
Impact We will use electronic data capture and design for our future studies. 
 
Title Pleural disease biobank 
Description The TIME1 study and several other prospective pleural trials (PILOT) led to the establishment of several projects in malignant / infectious pleural disease which collected biological samples (biopsies and pleural fluid) in conjunction with accurate clinical data. These represent a valuable resource to begin exploring genetic and physiological mechanisms of maligant pleural disease genesis, treatment and models of risk 
Type Of Material Biological samples 
Year Produced 2012 
Provided To Others? Yes  
Impact Assesssment of potential novel genetic virulence factors in malignant mesothelioma (work in progress). Use of soluble mesothelin to diagnose malignant mesothelioma in pleural fluid (Pubmed reference number : 19299498). Ongoing work with infection samples in collaboration. 
URL http://europepmc.org/abstract/MED/19299498
 
Title ORTU research patient database 
Description We have constructed an ethically approved and consented list of patients who are willing to be contacted for research with respirator disease 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? No  
Impact Increased recruitment to industry and other studies, place to conduct PPI work for future applications 
 
Title Pleural infection database 
Description Collated a group of patients who have survived pleural infection and willing to be contacted for participation in patient group, TSC and DMC 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? No  
Impact Allowed the patient focus group to be conducted and planned on twice yearly basis. Informed outcomes for the MIST3 study and conduct of the study 
 
Description American Pleural Network 
Organisation Banner MD Anderson Cancer Center
Country United States 
Sector Hospitals 
PI Contribution I have put together a US collaboration of expert centres who will deliver future trials in pleural infection
Collaborator Contribution Willingness to contribute to studies in the future, and comment on trial design and deliverability
Impact Nil as yet - awaiting an NIH funded study, we hope in q4 2019
Start Year 2018
 
Description American Pleural Network 
Organisation Johns Hopkins Medicine
Country United States 
Sector Hospitals 
PI Contribution I have put together a US collaboration of expert centres who will deliver future trials in pleural infection
Collaborator Contribution Willingness to contribute to studies in the future, and comment on trial design and deliverability
Impact Nil as yet - awaiting an NIH funded study, we hope in q4 2019
Start Year 2018
 
Description American Pleural Network 
Organisation Texas Medical Center
Country United States 
Sector Hospitals 
PI Contribution I have put together a US collaboration of expert centres who will deliver future trials in pleural infection
Collaborator Contribution Willingness to contribute to studies in the future, and comment on trial design and deliverability
Impact Nil as yet - awaiting an NIH funded study, we hope in q4 2019
Start Year 2018
 
Description American Pleural Network 
Organisation Vanderbilt University
Department Vanderbilt Medical Center
Country United States 
Sector Academic/University 
PI Contribution I have put together a US collaboration of expert centres who will deliver future trials in pleural infection
Collaborator Contribution Willingness to contribute to studies in the future, and comment on trial design and deliverability
Impact Nil as yet - awaiting an NIH funded study, we hope in q4 2019
Start Year 2018
 
Description INTERNATIONAL RESEARCH PARTNERSHIP 
Organisation University of Stellenbosch
Country South Africa 
Sector Academic/University 
PI Contribution Through the MRC grant to conduct the PILOT study, we have established an international recruitment base for pleural trials which includes centres in Australia, the USA and South Africa. These are now actively recruiting patients to the trial and will be used in future for large scale pleural trials.
Collaborator Contribution Recruitment to trials, input on to trial committees
Impact Recruitment to current study, discussion around potential recruitment to future studies
Start Year 2015
 
Description INTERNATIONAL RESEARCH PARTNERSHIP 
Organisation University of Western Australia
Country Australia 
Sector Academic/University 
PI Contribution Through the MRC grant to conduct the PILOT study, we have established an international recruitment base for pleural trials which includes centres in Australia, the USA and South Africa. These are now actively recruiting patients to the trial and will be used in future for large scale pleural trials.
Collaborator Contribution Recruitment to trials, input on to trial committees
Impact Recruitment to current study, discussion around potential recruitment to future studies
Start Year 2015
 
Description INTERNATIONAL RESEARCH PARTNERSHIP 
Organisation Vanderbilt University
Department Vanderbilt Medical Center
Country United States 
Sector Academic/University 
PI Contribution Through the MRC grant to conduct the PILOT study, we have established an international recruitment base for pleural trials which includes centres in Australia, the USA and South Africa. These are now actively recruiting patients to the trial and will be used in future for large scale pleural trials.
Collaborator Contribution Recruitment to trials, input on to trial committees
Impact Recruitment to current study, discussion around potential recruitment to future studies
Start Year 2015
 
Description LUNG THERAPEUTICS COLLABORATION 
Organisation University of Texas
Country United States 
Sector Academic/University 
PI Contribution Provided methodology advice to LTI on an IMP trial to be conducted in the USA / UK, and negotiated with our established pleural network.
Collaborator Contribution Funding and provision of IMP
Impact IMP study due to begin in 2020
Start Year 2019
 
Description Microbiology collaboration 
Organisation University of Oxford
Department Medical Sciences Division
Country United Kingdom 
Sector Academic/University 
PI Contribution Prospectively collected samples will be used to assess the microbiological profile of pleural infection, and tested using novel DNA based techniques.
Collaborator Contribution Advice has been received from collaborators in microbiology on optimal sample collection and storage for this future collaboration
Impact Nil thus far
Start Year 2012
 
Description Pleural infection surgery trial collaboration 
Organisation Blackpool Teaching Hospitals NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution A collaboration of centres able to recruit to the MIST3 protocol has been established with two meetings held
Collaborator Contribution Contributed to protocol design, trial design and delivery
Impact Nil as yet - awaited ethical approval for recruitment
Start Year 2018
 
Description Pleural infection surgery trial collaboration 
Organisation Plymouth Hospitals NHS Trust
Country United Kingdom 
Sector Public 
PI Contribution A collaboration of centres able to recruit to the MIST3 protocol has been established with two meetings held
Collaborator Contribution Contributed to protocol design, trial design and delivery
Impact Nil as yet - awaited ethical approval for recruitment
Start Year 2018
 
Description Pleural infection surgery trial collaboration 
Organisation Southmead Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution A collaboration of centres able to recruit to the MIST3 protocol has been established with two meetings held
Collaborator Contribution Contributed to protocol design, trial design and delivery
Impact Nil as yet - awaited ethical approval for recruitment
Start Year 2018
 
Description Pleural infection surgery trial collaboration 
Organisation Taunton and Somerset NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution A collaboration of centres able to recruit to the MIST3 protocol has been established with two meetings held
Collaborator Contribution Contributed to protocol design, trial design and delivery
Impact Nil as yet - awaited ethical approval for recruitment
Start Year 2018
 
Description Pleural infection surgery trial collaboration 
Organisation Western Infirmary, Glasgow
Country United Kingdom 
Sector Hospitals 
PI Contribution A collaboration of centres able to recruit to the MIST3 protocol has been established with two meetings held
Collaborator Contribution Contributed to protocol design, trial design and delivery
Impact Nil as yet - awaited ethical approval for recruitment
Start Year 2018
 
Description Western Australia 
Organisation Sir Charles Gairdner Hospital
Department Lung Institute of Western Australia (LIWA)
Country Australia 
Sector Academic/University 
PI Contribution Contribution of clinical samples and clinical data
Collaborator Contribution Analysis of genetic markers of mesothelioma; investigation of the biology of pleurodesis permitting translation of novel molecules to the clinical setting
Impact The genetic profiling of malignant pleural disease, and specifically malignant mesothelioma, is a collaborative project formed between our unit and our collaborators. Our collaborators have an interest in the biology and physiological mechanisms behind malignant pleural disease and pleurodesis. The TIME1 trial has permitted the set up of a biobank of pleural fluid samples with associated clinical information, allowing meaningful translational work to be conducted.
Start Year 2007
 
Description ATS 2012 and 2013 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Health professionals
Results and Impact Postgraduate courses and symposium on up to date pleural management in the light of evidence published by our group.

Opportunities for collaboration.
Recruited an ERS funded research fellow after discussion
Year(s) Of Engagement Activity 2012,2013
 
Description Ancona Interventional Course 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited to give seminars at Italian conference on pleura intervention
Year(s) Of Engagement Activity 2019
 
Description British Thoracic Society Winter Meeting 2019 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited to chair sessions at the national Winter BTS conference on pleural malignancy, pneumothorax and infection.
Year(s) Of Engagement Activity 2019
 
Description Difficult Respiratory Disease Conference Sheffield 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited to give presentation on pleural infection at national meeting
Year(s) Of Engagement Activity 2019
 
Description Duke Pleural Course 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited to give presentations and case based teaching at the Duke pleural course
Year(s) Of Engagement Activity 2019
 
Description EABIP Meeting Dubrovnik 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited to give talks at the EABIP international lung conference on all aspects of pleural disease
Year(s) Of Engagement Activity 2019
 
Description ERS 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Asked to present data from malignant and infective pleural trials conducted by my group at the European Respiratory Society Conference, Vienna 2012

Several requests to host fellows in my research department, increased potential european collaborators
Year(s) Of Engagement Activity 2012
 
Description ERS Pleural Skills Course 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Organised and delivered (at request of the ERS) a pleural skills course, attracting delegates from around the world, and providing procedural and evidence base update to ensure high quality practice
Year(s) Of Engagement Activity 2018
 
Description ERS Video 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Video conducted with ERS to explain developments in pleural disease including in malignant and infectious effusion
Year(s) Of Engagement Activity 2018
 
Description ERS Video interview 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Conducted interview at ERS for the media outlets on plerual disease at the conference, new directions and impact for patients. Available online
Year(s) Of Engagement Activity 2019
 
Description European Respiratory Society 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited to give talks at the ERS international conference and chair sessions
Year(s) Of Engagement Activity 2019
 
Description Israel Pulmonary Course 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited to give talks at the Israel course on pleural disease and discussed research aspects with local lab scientists
Year(s) Of Engagement Activity 2019
 
Description Johns Hopkins Grand and Pulmonary Rounds 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited to give grand rounds at Johns Hopkins University on pleural trials and pleural infection
Year(s) Of Engagement Activity 2020
 
Description Mexico Pleural Course 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited to give talks at the Mexico national lung conference on all aspects of pleural disease
Year(s) Of Engagement Activity 2019
 
Description Midland thoracic society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Invited to speak on pleural infection
Year(s) Of Engagement Activity 2019
 
Description NDM PODCAST 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Podcast conducted for the University of Oxford, explaining the importance of clinical trials research in respiratory medicine.

Nil as yet
Year(s) Of Engagement Activity 2013
URL http://www.ndm.ox.ac.uk/najib-rahman-respiratory-medicine
 
Description NLHC Conference, Turkey 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited to be keynote speaker at national Turkish Lung Conference - on all aspects of pleural disease
Year(s) Of Engagement Activity 2019
 
Description Pleural Research Day 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Yearly Pleural Research Day organised and conducted in Oxford 22nd June 2018 with over 120 delegates, discussing latest developments in pleural diseaes
Year(s) Of Engagement Activity 2018
 
Description RCP Edinburgh update in medicine 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited to give a talk by the Royal College of Physicians on Pleural Diseases
Year(s) Of Engagement Activity 2019
 
Description Stoke Pleural Course 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Pleural specific disease course for 50 delegates - described advanced ultrasound (SIMPLE) and pleural infection (MIST3)
Year(s) Of Engagement Activity 2019
 
Description UK Pleural Diseases course 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited to give talks at the UK Pleural Diseases course on pleural infection and chair sessions on imaging and intervention
Year(s) Of Engagement Activity 2019
 
Description UK Pleural Research Day 2015 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact We hosted a national pleural research day attended by 100 delegates who were respiratory research teams from around the UK and with international speakers. This discussed a number of pleural trials including PILOT and RAMMP, generating significant interest.
Year(s) Of Engagement Activity 2015
 
Description UK Pleural Research Day 2017 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The UK pleural research day 2017 involved presentations from around the UK of ongoing work - include an update on the SIMPLE trial and its excellent ongoing recruitment, and factors which had led to this success. This success has been used as an exemplar to other studies to try to improve their recruitment.
Year(s) Of Engagement Activity 2017
 
Description USA (ATS and ACCP) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Requested to give keynote talks on pleural malignancy and infection at the American College of Chest Physicians (Atlanta, 2012), the American Thoracic Society (San Francisco, 2012)

Several requests to host international fellows in my research group, increased potential international collaborators for future projects
Year(s) Of Engagement Activity 2012
 
Description University College Access medicine event 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact Gave a lecture on Respiratory Disease and how this impacts on patients, and how we approach it, to school students interested in applying for medicine.
Year(s) Of Engagement Activity 2018