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    Vanya Gant

    This chapter discusses pathways for established prosthetic joint infection (PJI) and includes discussion on management of acute infection, surgical management of acute infection (including arthroscopic debridement and implant retention... more
    This chapter discusses pathways for established prosthetic joint infection (PJI) and includes discussion on management of acute infection, surgical management of acute infection (including arthroscopic debridement and implant retention strategies), formal revision surgery, and management of chronic low-grade infection (including management of low-grade infection, antibiotic suppression, and free flaps). The main emphasis of this chapter is to guide the team on what are safe and accepted treatments for patients with confirmed PJI. The most important decision is whether the underlying implant should be retained or replaced. The latter can be in a single or multiple stages.
    Additional file 4:. INHALE Micro Committee Terms of Reference v2.0 27JUN2021.
    Additional file 2:. INHALE WP3 Antibiotic Prescribing Guidance v2.0 8May2019 MASTER; Algorithm.
    Additional file 3: Table S1. Timeline for Trial Actions. *Later on day 1 and as soon as possible after decision to test for pneumonia. Further specimens from the same participant may be tested on the machine, within the 21-day trial... more
    Additional file 3: Table S1. Timeline for Trial Actions. *Later on day 1 and as soon as possible after decision to test for pneumonia. Further specimens from the same participant may be tested on the machine, within the 21-day trial period, only if clinically indicated and a sample has also been sent routinely to the microbiology laboratory. 1Every day until 14 days after randomisation or until clinical cure of pneumonia, whichever is first. Assessments only required on these days if in ICU/CCU and not cured of pneumonia. 2Which assessment is used depends on whether participant is a child or an adult. Clinical teams record these routinely and will know which should be used. 3Data collected may pre- and post-date the trial period, but will be collected from clinical records by hospital staff. 4Window for "day 21" phone call to occur is from days 20-24 post randomisation, discharged participants only. 5Record if relevant until 21 days after randomisation (even if pneumonia i...
    Background Hospital-acquired and ventilator-associated pneumonias (HAP and VAP) are common in critical care and can be life-threatening. Rapid microbiological diagnostics, linked to an algorithm to translate their results into antibiotic... more
    Background Hospital-acquired and ventilator-associated pneumonias (HAP and VAP) are common in critical care and can be life-threatening. Rapid microbiological diagnostics, linked to an algorithm to translate their results into antibiotic choices, could simultaneously improve patient outcomes and antimicrobial stewardship. Methods The INHALE Randomised Controlled Trial is a multi-centre, parallel study exploring the potential of the BioFire FilmArray molecular diagnostic to guide antibiotic treatment of HAP/VAP in intensive care units (ICU); it identifies pathogens and key antibiotic resistance in around 90 min. The comparator is standard care whereby the patient receives empirical antibiotics until microbiological culture results become available, typically after 48–72 h. Adult and paediatric ICU patients are eligible if they are about to receive antibiotics for a suspected lower respiratory infection (including HAP/VAP) for the first time or a change in antibiotic because of a dete...
    BackgroundAntibiotics are extensively prescribed in intensive care units (ICUs), yet little is known about how antibiotic-related decisions are made in this setting. We explored how beliefs, perceptions and contextual factors influenced... more
    BackgroundAntibiotics are extensively prescribed in intensive care units (ICUs), yet little is known about how antibiotic-related decisions are made in this setting. We explored how beliefs, perceptions and contextual factors influenced ICU clinicians’ antibiotic prescribing.MethodsWe conducted 4 focus groups and 34 semistructured interviews with clinicians involved in antibiotic prescribing in four English ICUs. Focus groups explored factors influencing prescribing, whereas interviews examined decision-making processes using two clinical vignettes. Data were analysed using thematic analysis, applying the Necessity Concerns Framework.ResultsClinicians’ antibiotic decisions were influenced by their judgement of the necessity for prescribing/not prescribing, relative to their concerns about potential adverse consequences. Antibiotic necessity perceptions were strongly influenced by beliefs that antibiotics would protect patients from deterioration and themselves from the ethical and l...
    This chapter discusses consideration of safe patient pathways. It includes discussion on skin necrosis, safe raising of fasciocutaneous flaps around the joints, tips and tricks to avoid iatrogenic skin necrosis, prosthetic joint infection... more
    This chapter discusses consideration of safe patient pathways. It includes discussion on skin necrosis, safe raising of fasciocutaneous flaps around the joints, tips and tricks to avoid iatrogenic skin necrosis, prosthetic joint infection negative-pressure dressings to reduce risk, and pathways for skin necrosis. The aim is to improve the safety and viability of the access incisions with the intention of enhancing primary healing of those incisions. This advice on tissue handling must be in addition to the holistic assessment of the patient as a ‘host’ for the arthroplasty implant.
    This chapter discusses thromboprophylaxis and haematomas within periprosthetic joint infection. The issue of venous thromboembolism is important for all surgical patients and, as such, those undergoing arthroplasty must undergo a careful... more
    This chapter discusses thromboprophylaxis and haematomas within periprosthetic joint infection. The issue of venous thromboembolism is important for all surgical patients and, as such, those undergoing arthroplasty must undergo a careful and accurate risk assessment. Prolonged surgery and delayed postoperative mobilization are risk factors and are common to most major joint arthroplasty. Use of prophylactic agents to prevent thrombosis must be balanced with the avoidance of haematoma formation as the latter contributes to a risk of prosthetic joint infection. Should deep vein thrombosis occur then swift methods of diagnosis and treatment must be in place.
    Samia N. Naccache, Karl S. Peggs, Frank M. Mattes, Rahul Phadke, Jeremy A. Garson, Paul Grant, Erik Samayoa, Scot Federman, Steve Miller, Michael P. Lunn, Vanya Gant, and Charles Y. Chiu Department of Laboratory Medicine, University of... more
    Samia N. Naccache, Karl S. Peggs, Frank M. Mattes, Rahul Phadke, Jeremy A. Garson, Paul Grant, Erik Samayoa, Scot Federman, Steve Miller, Michael P. Lunn, Vanya Gant, and Charles Y. Chiu Department of Laboratory Medicine, University of California, San Francisco, and UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, California; Departments of Clinical Hematology, Clinical Microbiology, Neuropathology, Neurology, University College London Hospitals NHS Foundation Trust, and Research Department of Infection, Division of Infection and Immunity, University College London, United Kingdom; and Department of Medicine, Division of Infectious Diseases, University of California, San Francisco
    Background Rapid molecular diagnostic tests to investigate the microbial aetiology of pneumonias may improve treatment and antimicrobial stewardship in intensive care units (ICUs). Clinicians’ endorsement and uptake of these tests is... more
    Background Rapid molecular diagnostic tests to investigate the microbial aetiology of pneumonias may improve treatment and antimicrobial stewardship in intensive care units (ICUs). Clinicians’ endorsement and uptake of these tests is crucial to maximise engagement; however, adoption may be impeded if users harbour unaddressed concerns or if device usage is incompatible with local practice. Accordingly, we strove to identify ICU clinicians’ beliefs about molecular diagnostic tests for pneumonias before implementation at the point-of-care. Methods We conducted semi-structured interviews with 35 critical care doctors working in four ICUs in the United Kingdom. A clinical vignette depicting a fictitious patient with signs of pneumonia was used to explore clinicians’ beliefs about the importance of molecular diagnostics and their concerns. Data were analysed thematically. Results Clinicians’ beliefs about molecular tests could be grouped into two categories: perceived potential of molecu...
    This book provides a concise overview of methods of assessing and managing prosthetic joint infection (PJI). It covers the classification of PJI sites, risk factors, and preoperative assessment, before considering safe patient pathways.... more
    This book provides a concise overview of methods of assessing and managing prosthetic joint infection (PJI). It covers the classification of PJI sites, risk factors, and preoperative assessment, before considering safe patient pathways. Drawn from the authors’ clinical experience and a review of the current literature, the book also explains surgical and drug management of acute infection, the management of chronic infection, and specific microbiology issues relating to PJI. Proposed models for revision arthroplasty networks are discussed and future aims are considered. The proposed pathways are backed by illustrated case histories.
    A key question in COVID-19 infection is why some previously healthy patients develop severe pulmonary failure and some ultimately die. Initial pulmonary failure does not exhibit classical features of ARDS; hypercoagulability is a common... more
    A key question in COVID-19 infection is why some previously healthy patients develop severe pulmonary failure and some ultimately die. Initial pulmonary failure does not exhibit classical features of ARDS; hypercoagulability is a common laboratory feature, and pulmonary thrombotic microangiopathy has been reported post mortem1,2,3. Biomarkers cannot robustly identify such patients pre-emptively and no specific interventions exist to mitigate clinical deterioration. Mononuclear phagocytic cells are key immune cells and bind fibrinogen through the CD11b/CD18 dimer CR3, whose activated form can initiate microthrombus formation. Accordingly, we profiled circulating monocyte CD11b/CD18 cell surface density from COVID-19 infected adults who were (i) symptomatic but breathless, (ii) requiring ventilatory support, and (iii) recovering following ICU care for hypoxia.
    CAP18 is a cationic antimicrobial protein originally isolated from rabbit neutrophils, of which a 32-mer sequence from its C-terminal and (CAP18(106-137)) has been found to be the most active. The bactericidal action of this peptide has... more
    CAP18 is a cationic antimicrobial protein originally isolated from rabbit neutrophils, of which a 32-mer sequence from its C-terminal and (CAP18(106-137)) has been found to be the most active. The bactericidal action of this peptide has been characterized by conventional culture techniques and flow cytometry. Cultures of Escherichia coli NCTC10418 were exposed to the MBC (12 microM) of the peptide for up to 60 min and stained with a fluorochrome sensitive to changes in either membrane potential (bis-(1,3-dibutylbarbituric acid)trimethine oxonol [DiBAC4(3)), or membrane integrity (propidium iodide [PI]) before flow cytometric analysis. Addition of CAP18(106-137) to E. coli in broth culture resulted in immediate collapse of membrane potential [as determined by uptake of DiBAC4(3)] and loss of membrane integrity (as indicated by uptake of PI), with a corresponding 6- to 8-log decrease in viable counts as determined by colony formation on solid media. In identical experiments, the prese...
    The treatment of tuberculosis is based on combinations of drugs that directly target Mycobacterium tuberculosis. A new global initiative is now focusing on a complementary approach of developing adjunct host-directed therapies.
    Ninety-eight percent of the cells in a population of Escherichia coli in log-phase growth lost colony-forming ability after being exposed for 3 h to the quinolone antibiotic ciprofloxacin at four times the MIC in nutrient broth, a... more
    Ninety-eight percent of the cells in a population of Escherichia coli in log-phase growth lost colony-forming ability after being exposed for 3 h to the quinolone antibiotic ciprofloxacin at four times the MIC in nutrient broth, a concentration easily reached in vivo. Flow cytometric analysis, however, demonstrated that only 68% of this bacterial population had lost membrane potential, as judged by the membrane potential-sensitive dye bis-(1,3-dibutylbarbituric acid) trimethine oxonol [DiBAC 4 (3)], and only 30% could no longer exclude the nucleic acid-binding dye propidium iodide (PI), reflecting lost membrane integrity, efflux mechanisms, or both. Subsequent removal of ciprofloxacin and resuspension in nutrient broth resulted in renewed cell division after 2 h, with a calculated postantibiotic effect (PAE) time of 57 min. The proportion of DiBAC- and PI-fluorescent cells in this recovering population remained stable for more than 4 h after antibiotic removal. Eighty percent of cel...
    ABSTRACTBiofilm‐associated implant‐related bone and joint infections are clinically important due to the extensive morbidity, cost of care and socioeconomic burden that they cause. Research in the field of biofilms has expanded in the... more
    ABSTRACTBiofilm‐associated implant‐related bone and joint infections are clinically important due to the extensive morbidity, cost of care and socioeconomic burden that they cause. Research in the field of biofilms has expanded in the past two decades, however, there is still an immense knowledge gap related to many clinical challenges of these biofilm‐associated infections. This subject was assigned to the Biofilm Workgroup during the second International Consensus Meeting on Musculoskeletal Infection held in Philadelphia USA (ICM 2018) (https://icmphilly.com). The main objective of the Biofilm Workgroup was to prepare a consensus document based on a review of the literature, prepared responses, discussion, and vote on thirteen biofilm related questions. The Workgroup commenced discussing and refining responses prepared before the meeting on day one using Delphi methodology, followed by a tally of responses using an anonymized voting system on the second day of ICM 2018. The Workin...
    Background Hospital-acquired and ventilator-associated pneumonias (HAP and VAP) are common in critical care and can be life-threatening. Rapid microbiological diagnostics, linked to an algorithm to translate their results into antibiotic... more
    Background Hospital-acquired and ventilator-associated pneumonias (HAP and VAP) are common in critical care and can be life-threatening. Rapid microbiological diagnostics, linked to an algorithm to translate their results into antibiotic choices, could simultaneously improve patient outcomes and antimicrobial stewardship. Methods The INHALE Randomised Controlled Trial is a multi-centre, parallel study exploring the potential of the BioFire FilmArray molecular diagnostic to guide antibiotic treatment of HAP/VAP in intensive care units (ICU); it identifies pathogens and key antibiotic resistance in around 90 min. The comparator is standard care whereby the patient receives empirical antibiotics until microbiological culture results become available, typically after 48–72 h. Adult and paediatric ICU patients are eligible if they are about to receive antibiotics for a suspected lower respiratory infection (including HAP/VAP) for the first time or a change in antibiotic because of a dete...
    ABSTRACTIntroductionSeveral viral respiratory infections - notably influenza - are associated with secondary bacterial infection and additional pathology. The extent to which this applies for COVID-19 is unknown. Accordingly, we aimed to... more
    ABSTRACTIntroductionSeveral viral respiratory infections - notably influenza - are associated with secondary bacterial infection and additional pathology. The extent to which this applies for COVID-19 is unknown. Accordingly, we aimed to define the bacteria causing secondary pneumonias in COVID-19 ICU patients using the FilmArray Pneumonia Panel, and to determine this test’s potential in COVID-19 management.MethodsCOVID-19 ICU patients with clinically-suspected secondary infection at 5 UK hospitals were tested with the FilmArray at point of care. We collected patient demographic data and compared FilmArray results with routine culture.ResultsWe report results of 110 FilmArray tests on 94 patients (16 had 2 tests): 69 patients (73%) were male, the median age was 59 yrs; 92 were ventilated. Median hospital stay before testing was 14 days (range 1-38). Fifty-nine (54%) tests were positive, with 141 bacteria detected. Most were Enterobacterales (n=55, including Klebsiella spp. [n= 35]) ...
    SummaryBackgroundICU patients with hospital-acquired or ventilator-associated pneumonia (HAP or VAP) have high mortality, so broad-spectrum antibiotics are initiated at clinical diagnosis, then refined after 2-3 days, once microbiology... more
    SummaryBackgroundICU patients with hospital-acquired or ventilator-associated pneumonia (HAP or VAP) have high mortality, so broad-spectrum antibiotics are initiated at clinical diagnosis, then refined after 2-3 days, once microbiology results become available. Unfortunately, culture-based microbiological investigation is also insensitive, with aetiological agents remaining unidentified in many cases. This leads to extended over-treatment of patients with susceptible pathogens, whilst those with highly-resistant pathogens are treated inadequately for prolonged periods. Using PCR to seek pathogens and their resistance genes directly from clinical samples may improve therapy and stewardship. The INHALE study compared two PCR platforms for HAP/VAP diagnosis against routine microbiology (RM), identifying one to progress into a Randomised Controlled Trial (RCT).MethodsSurplus routine sputa, endotracheal tube exudates and bronchoalveolar lavages were collected from ICU patients about to r...
    BACKGROUNDThe objective of this study was to evaluate the performance characteristics of early commercial SARS-CoV-2 antibody assays in mild and asymptomatic subjects to enable the selection of suitable serological assays for routine... more
    BACKGROUNDThe objective of this study was to evaluate the performance characteristics of early commercial SARS-CoV-2 antibody assays in mild and asymptomatic subjects to enable the selection of suitable serological assays for routine diagnostic use within HCA Healthcare UK.METHODSWe used serum samples from a pre-Covid era patient cohort (n=50, pre-December 2019), designated SARS-CoV-2 negative, and serum samples from a SARS-CoV-2 RT-PCR-positive cohort (n=90) taken > 14 days post symptom onset (April-May 2020). We evaluated 6 ELISA assays including one confirmation assay to investigate antibody specificity. We also evaluated one point-of-care lateral flow device and one high throughput electrochemiluminescence immunoassay.RESULTSThe ELISA specificities ranged from 84-100%, with sensitivities ranging from 75.3-90.0%. The LFIA showed 100% specificity and 80% sensitivity using smaller sample numbers. The Roche CLIA immunoassay showed 100% specificity and 90.7% sensitivity. When used...
    SUMMARY Clinical microbiology is experiencing revolutionary advances in the deployment of molecular, genome sequencing-based, and mass spectrometry-driven detection, identification, and characterization assays. Laboratory automation and... more
    SUMMARY Clinical microbiology is experiencing revolutionary advances in the deployment of molecular, genome sequencing-based, and mass spectrometry-driven detection, identification, and characterization assays. Laboratory automation and the linkage of information systems for big(ger) data management, including artificial intelligence (AI) approaches, also are being introduced. The initial optimism associated with these developments has now entered a more reality-driven phase of reflection on the significant challenges, complexities, and health care benefits posed by these innovations. With this in mind, the ongoing process of clinical laboratory consolidation, covering large geographical regions, represents an opportunity for the efficient and cost-effective introduction of new laboratory technologies and improvements in translational research and development. This will further define and generate the mandatory infrastructure used in validation and implementation of newer high-throu...
    We compared the performance of an ultramicrofibre (UMF)-based system with or without a novel copper-based biocide (CuWB50) with standard cleaning using Actichlor Plus in four hospital wards in a crossover study design, and analysed our... more
    We compared the performance of an ultramicrofibre (UMF)-based system with or without a novel copper-based biocide (CuWB50) with standard cleaning using Actichlor Plus in four hospital wards in a crossover study design, and analysed our results using univariate and multivariate statistics. We measured total viable counts (TVCs) and ATP levels in 10 near-patient sites three times weekly, one hour before and after cleaning. Standard cleaning reduced TVCs further than UMF cleaning with water, but UMF cleaning with CuWB50 produced equivalent TVC reduction. Furthermore we identified a ‘residual effect’ with UMF + CuWB50, conferring TVC suppression for up to a week after application. ATP results did not correlate with TVCs. We conclude that UMF-based cleaning with CuWB50 results in TVC reductions equivalent to hypochlorite-based standard cleaning, with the added advantages of a residual effect that keeps TVCs lower between cleaning rounds.
    ... Mayfield Road Edinburgh EH9 3JL UK Robert F. Harrison Dept of Automatic Control and ... The structure of the brain as a complex network of multiply connected cells (neural networks ... training sets should be used for underrepresented... more
    ... Mayfield Road Edinburgh EH9 3JL UK Robert F. Harrison Dept of Automatic Control and ... The structure of the brain as a complex network of multiply connected cells (neural networks ... training sets should be used for underrepresented classes (or novelty detection used when ...
    ABSTRACT Lipoxins are biologically active trihydroxytetraene containing products derived from arachidonic acid that are formed by interactions between lipoxygenases. Although the lipoxins have been generated from mixed cell suspensions in... more
    ABSTRACT Lipoxins are biologically active trihydroxytetraene containing products derived from arachidonic acid that are formed by interactions between lipoxygenases. Although the lipoxins have been generated from mixed cell suspensions in vitro, it has not been established whether these products are synthesized in vivo. We have performed bronchoalveolar lavage (BAL) in 12 patients with lung disease (sarcoid, six; pneumonia, two; asthma, two; carcinoma, one; alveolitis of unknown cause, one) and in six normal control subjects. The BAL fluid was analyzed for lipoxin A4 (LXA4) using gas chromatography mass spectrometry with selective ion monitoring, and the levels of the sulfidopeptide leukotrienes were determined using reverse-phase high-performance liquid chromatography and radioimmunoassay. LXA4 was detected in BAL fluid from nine of the 12 patients studied. The levels of LXA4 ranged from 0.4 to 2.8 ng/ml. LXA4 was not detected in any of the six normal subjects. Sulfidopeptide leukotrienes were detected in all the BAL samples, ranging from 0.04 to 0.7 ng/ml, and there was no significant difference between the patients and the normal subjects. In patients with detectable LXA4 in BAL fluid, the ratio of the concentrations of LXA4 to those of the sulfidopeptide leukotrienes ranged from 1.9 to 62 (mean, 19.0). This is the first demonstration of the presence of LXA4 in disease.
    Haemophilus influenzaeis a significant causative agent of respiratory tract infections (RTI) worldwide. The development of a rapidH. influenzaediagnostic assay that would allow for the implementation of infection control measures and also... more
    Haemophilus influenzaeis a significant causative agent of respiratory tract infections (RTI) worldwide. The development of a rapidH. influenzaediagnostic assay that would allow for the implementation of infection control measures and also improve antimicrobial stewardship for patients is required. A number of nucleic acid diagnostics approaches that detectH. influenzaein RTIs have been described in the literature; however, there are reported specificity and sensitivity limitations for these assays. In this study, a novel real-time PCR diagnostic assay targeting thesmpBgene was designed to detect all serogroups ofH. influenzae. The assay was validated using a panel of well-characterizedHaemophilusspp. Subsequently, 44Haemophilusclinical isolates were collected, and 36 isolates were identified asH. influenzaeusing a gold standard methodology that combined the results of matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) and afucKdiagnostic assa...
    The capacity of peripheral blood monocytes and alveolar macrophages (AM) obtained by bronchoalveolar lavage (BAL) to present recall antigens, namely, tuberculin purified protein derivative (PPD) or streptokinase-streptodornase (SKSD), to... more
    The capacity of peripheral blood monocytes and alveolar macrophages (AM) obtained by bronchoalveolar lavage (BAL) to present recall antigens, namely, tuberculin purified protein derivative (PPD) or streptokinase-streptodornase (SKSD), to highly purified autologous T-cells has been studied in 11 asthmatic and 11 healthy, nonatopic normal subjects. In the asthmatic group, AM accessory cell function was variable, and most subjects were unable to present either recall antigen as effectively as blood monocytes, although one asthmatic subject demonstrated larger proliferative responses than blood monocytes for both antigens. AM accessory cell activity was not antigen-specific, and there was a correlation between accessory cell efficacy for the two antigens (r = 0.92; confidence interval, 0.53 to 0.98). Furthermore, a correlation existed between the percentage lymphocyte count in the BAL fluid and the ratio of macrophage to monocyte antigen-presenting capability for both PPD (r = 0.92; 95%...
    Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) continue to present very significant diagnostic and management challenges. The development, introduction and use of a wider range of immunosuppressive therapies... more
    Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) continue to present very significant diagnostic and management challenges. The development, introduction and use of a wider range of immunosuppressive therapies are leading to a broader spectrum of microorganisms causing HAP and VAP. The persistent clinical dilemma regarding their cause is that detection of a microorganism from a respiratory tract sample does not necessarily signify it is the causative agent of the pneumonia. The ever-increasing antibiotic resistance problem means that HAP and VAP are becoming progressively more difficult to treat. In this article, we review the cause, antimicrobial resistance, diagnosis and treatment of HAP and VAP and encapsulate recent developments and concepts in this rapidly moving field. Although the microbial causes of HAP and VAP remain at present similar to those identified in previous studies, there are marked geographical differences. Resistance rates among Gram-n...
    Fourteen NHS hospital ward cleaning staff were interviewed about their background, job satisfaction and motivation as part of the evaluation of a new cleaning system. Four (28%) staff had attended university, five (35%) had no... more
    Fourteen NHS hospital ward cleaning staff were interviewed about their background, job satisfaction and motivation as part of the evaluation of a new cleaning system. Four (28%) staff had attended university, five (35%) had no qualifications and the remainder had a range of educational attainments. Nine (64%) did the job to earn money, three (22%) because they liked it and two (14%) because there were no other opportunities. Repetitive tasks were undertaken routinely with tight control of method and order of working. The work was tiring and ad hoc requests increased the burden. Although all staff knew what was expected of them in their job, nine (62%) reported they “knew themselves” if they had done a good job as feedback was frequently absent or belated. Opportunities including access to the internet were limited and long hours doing extra work reduced free time. This pilot study highlights the potential of these healthcare cleaning professionals to contribute and develop given the...
    The development of the systemic inflammatory response syndrome (SIRS) is associated with increased morbidity and mortality. Numerous anticytokine trials have failed to demonstrate any outcome benefit and there has been little evidence of... more
    The development of the systemic inflammatory response syndrome (SIRS) is associated with increased morbidity and mortality. Numerous anticytokine trials have failed to demonstrate any outcome benefit and there has been little evidence of improvement in the prognosis of this condition over the past 20 years. This study examines the effect of using a white cell filter designed to remove polymorphonuclear cells (PMNs) in patients who developed SIRS 36 h after cardiopulmonary bypass (CPB). Twenty-four patients were randomized to receive either leucofiltration (LF) or control therapy (CT). The two groups were well matched at study entry in terms of age, severity of illness and length of time on CPB. LF patients received 60 min filtration periods using a venovenous extracorporeal circuit at a flow rate of 200 ml/min with the cycle repeated every 12 h while SIRS and other entry criteria were met. CT patients received standard therapy. LF patients received an average of 4.2 cycles (range 1-8) and, after 15 min filtration, the total leucocyte count had fallen from 16.2 +/- 5.3 to 10.4 +/- 3.3 x 10(9)/l and PMN from 14.4 +/- 5.2 to 8.3 +/- 4.2 x 10(9)/l. The mean platelet count changed from 127 +/- 87 to 117 +/- 82 x 10(9)/l. No adverse effects related to leucodepletion were observed. There was no difference between the groups in either mortality or length of stay at the intensive care unit or at hospital discharge. Organ function was assessed regularly during the study period and significant changes occurred only in respiratory and renal function. In the LF patients, respiratory function assessed by change in hypoxaemia index from baseline and renal function assessed by serum creatinine showed significant treatment effects compared to CT patients (p < 0.01, < 0.01 respectively); three CT patients, but no LF patients, received haemofiltration during the study period. Leucofiltration safely and effectively removes circulating PMNs from patients with SIRS following CPB. This may result in improved pulmonary and renal function in these patients. Further studies are required of the kinetics and phenotypic characteristics of PMN removal by leucofiltration and a larger multicentre study will be necessary to determine whether this novel therapy has a significant outcome benefit in critically ill patients with SIRS.
    Respiratory tract infections rank second as causes of adult and paediatric morbidity and mortality worldwide. Respiratory tract infections are caused by many different bacteria (including mycobacteria) and viruses, and rapid detection of... more
    Respiratory tract infections rank second as causes of adult and paediatric morbidity and mortality worldwide. Respiratory tract infections are caused by many different bacteria (including mycobacteria) and viruses, and rapid detection of pathogens in individual cases is crucial in achieving the best clinical management, public health surveillance, and control outcomes. Further challenges in improving management outcomes for respiratory tract infections exist: rapid identification of drug resistant pathogens; more widespread surveillance of infections, locally and internationally; and global responses to infections with pandemic potential. Developments in genome amplification have led to the discovery of several new respiratory pathogens, and sensitive PCR methods for the diagnostic work-up of these are available. Advances in technology have allowed for development of single and multiplexed PCR techniques that provide rapid detection of respiratory viruses in clinical specimens. Microarray-based multiplexing and nucleic-acid-based deep-sequencing methods allow simultaneous detection of pathogen nucleic acid and multiple antibiotic resistance, providing further hope in revolutionising rapid point of care respiratory tract infection diagnostics.

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