MRSA eradication of newly acquired lower respiratory tract infection in cystic fibrosis

UK cystic fibrosis (CF) guidelines recommend eradication of methicillin-resistant Staphylococcus aureus (MRSA) when cultured from respiratory samples. As there is no clear consensus as to which eradication regimen is most effective, we determined the efficacy of eradication regimens used in our CF centre and long-term clinical outcome. All new MRSA positive sputum cultures (n=37) that occurred between 2000 and 2014 were reviewed. Eradication regimen characteristics and clinical, microbiological and long-term outcome data were collected. Rifampicin plus fusidic acid was the most frequently used regimen (24 (65%) out of 37 patients), with an overall success rate of 79% (19 out of 24 patients). Eradication failure was more likely in patients with an additional MRSA-positive peripheral screening swab (p=0.03) and was associated with worse survival (p=0.04). Our results demonstrate the feasibility and clinical benefits of MRSA eradication. As peripheral colonisation was associated with lower eradication success, strategies combining systemic and topical treatments should be considered to optimise outcomes in CF patients

Wearable devices for remote vital signs monitoring in the outpatient setting: an overview of the field

Early detection of physiological deterioration has been shown to improve patient outcomes. Due to recent improvements in technology, comprehensive outpatient vital signs monitoring is now possible. This is the first review to collate information on all wearable devices on the market for outpatient physiological monitoring. A scoping review was undertaken. The monitors reviewed were limited to those that can function in the outpatient setting with minimal restrictions on the patient’s normal lifestyle, while measuring any or all of the vital signs: heart rate, ECG, oxygen saturation, respiration rate, blood pressure and temperature. A total of 270 papers were included in the review. Thirty wearable monitors were examined: 6 patches, 3 clothing-based monitors, 4 chest straps, 2 upper arm bands and 15 wristbands. The monitoring of vital signs in the outpatient setting is a developing field with differing levels of evidence for each monitor. The most common clinical application was heart rate monitoring. Blood pressure and oxygen saturation measurements were the least common applications. There is a need for clinical validation studies in the outpatient setting to prove the potential of many of the monitors identified. Research in this area is in its infancy. Future research should look at aggregating the results of validity and reliability and patient outcome studies for each monitor and between different devices. This would provide a more holistic overview of the potential for the clinical use of each device

The role of ABCG2 in modulating responses to anti-cancer photodynamic therapy

The ATP-binding cassette (ABC) superfamily G member 2 (ABCG2) transmembrane protein transporter is known for conferring resistance to treatment in cancers. Photodynamic therapy (PDT) is a promising anti-cancer method involving the use of light-activated photosensitisers to precisely induce oxidative stress and cell death in cancers. ABCG2 can efflux photosensitisers from out of cells, reducing the capacity of PDT and limiting the efficacy of treatment. Many studies have attempted to elucidate the relationship between the expression of ABCG2 in cancers, its effect on the cellular retention of photosensitisers and its impact on PDT. This review looks at the studies which investigate the effect of ABCG2 on a range of different photosensitisers in different pre-clinical models of cancer. This work also evaluates the approaches that are being investigated to address the role of ABCG2 in PDT with an outlook on potential clinical validation

Parameterized Edge Hamiltonicity

We study the parameterized complexity of the classical Edge Hamiltonian Path problem and give several fixed-parameter tractability results. First, we settle an open question of Demaine et al. by showing that Edge Hamiltonian Path is FPT parameterized by vertex cover, and that it also admits a cubic kernel. We then show fixed-parameter tractability even for a generalization of the problem to arbitrary hypergraphs, parameterized by the size of a (supplied) hitting set. We also consider the problem parameterized by treewidth or clique-width. Surprisingly, we show that the problem is FPT for both of these standard parameters, in contrast to its vertex version, which is W-hard for clique-width. Our technique, which may be of independent interest, relies on a structural characterization of clique-width in terms of treewidth and complete bipartite subgraphs due to Gurski and Wanke

Trial of remote continuous versus intermittent NEWS monitoring after major surgery (TRaCINg): a feasibility randomised controlled trial

Background Despite medical advances, major surgery remains high risk with up to 44% of patients experiencing postoperative complications. Early recognition of postoperative complications is crucial in reducing morbidity and preventing long-term disability. The current standard of care is intermittent manual vital signs monitoring, but new wearable remote monitors offer the benefits of continuous vital signs monitoring without limiting the patient’s mobility. The aim of this study was to evaluate the feasibility, acceptability and clinical outcomes of continuous remote monitoring after major surgery. Methods The study was a randomised, controlled, unblinded, parallel group, feasibility trial. Adult patients undergoing elective major surgery were randomly assigned to receive continuous remote monitoring and normal National Early Warning Score (NEWS) monitoring (intervention group) or normal NEWS monitoring alone (control group). Continuous remote monitoring was achieved using the SensiumVitals® wireless patch which is worn on the patient’s chest and monitors heart rate, respiratory rate and temperature continuously, and alerts the nurse when there is deviation from pre-set physiological norms. Feasibility was assessed by evaluating recruitment rate, adherence to protocol and randomisation and the amount of missing data. Clinical outcomes included time to antibiotics in cases of sepsis, length of hospital stay, number of critical care admissions and rate of hospital readmission within 30 days of discharge. Results One hundred and thirty-six patients were randomised between October 2018 and April 2019: 67 to the control group and 69 to the intervention group. Recruitment was completed prior to the 12 month target with a high rate of eligibility and consent. Missing data was limited only to questionnaire responses; no participants were lost to follow-up and only one participant was withdrawn due to loss of capacity. The number of patients classed as ‘drop-out’ due to design (8.1%) were less than anticipated, and there were no participants who crossed over into the alternative trial allocation group. Seventeen participants in the intervention group (28%) did not adhere to the monitoring protocol. No formal comparisons between arms was undertaken; however, participants had fewer unplanned critical care admissions (1 versus 5) and had a shorter average length of hospital stay (11.6 days (95% confidence interval 9.5–13.7 days) versus 16.2 days (95% confidence interval 11.3–21.2 days)) in the continuous vital signs monitoring group. The time taken to receive antibiotics in cases of sepsis was similar in both arms. A cost-utility analysis indicated that the remote monitoring system was cost-saving when compared to standard NEWS monitoring alone. Conclusions It is feasible to perform a large-scale randomised controlled trial of continuous remote monitoring after major surgery. Progression to a definitive multicentre randomised controlled trial would be appropriate, taking consideration of factors, such as patient adherence, that might mask the potential benefit of additional monitoring. Trial registration ISRCTN registry with study ID ISRCTN16601772. Registered 30 August 2017

Crossing Paths with Hans Bodlaender:A Personal View on Cross-Composition for Sparsification Lower Bounds

On the occasion of Hans Bodlaender’s 60th birthday, I give a personal account of our history and work together on the technique of cross-composition for kernelization lower bounds. I present several simple new proofs for polynomial kernelization lower bounds using cross-composition, interlaced with personal anecdotes about my time as Hans’ PhD student at Utrecht University. Concretely, I will prove that Vertex Cover, Feedback Vertex Set, and the H-Factor problem for every graph H that has a connected component of at least three vertices, do not admit kernels of (formula presented) bits when parameterized by the number of vertices n for any (formula presented), unless (formula presented). These lower bounds are obtained by elementary gadget constructions, in particular avoiding the use of the Packing Lemma by Dell and van Melkebeek.</p

T helper cell subsets specific for pseudomonas aeruginosa in healthy individuals and patients with cystic fibrosis

Background: We set out to determine the magnitude of antigen-specific memory T helper cell responses to Pseudomonas aeruginosa in healthy humans and patients with cystic fibrosis. Methods: Peripheral blood human memory CD4+ T cells were co-cultured with dendritic cells that had been infected with different strains of Pseudomonas aeruginosa. The T helper response was determined by measuring proliferation, immunoassay of cytokine output, and immunostaining of intracellular cytokines. Results: Healthy individuals and patients with cystic fibrosis had robust antigen-specific memory CD4+ T cell responses to Pseudomonas aeruginosa that not only contained a Th1 and Th17 component but also Th22 cells. In contrast to previous descriptions of human Th22 cells, these Pseudomonal-specific Th22 cells lacked the skin homing markers CCR4 or CCR10, although were CCR6+. Healthy individuals and patients with cystic fibrosis had similar levels of Th22 cells, but the patient group had significantly fewer Th17 cells in peripheral blood. Conclusions: Th22 cells specific to Pseudomonas aeruginosa are induced in both healthy individuals and patients with cystic fibrosis. Along with Th17 cells, they may play an important role in the pulmonary response to this microbe in patients with cystic fibrosis and other conditions

Inspiratory muscle training reduces blood lactate concentration during volitional hyperpnoea

Although reduced blood lactate concentrations ([lac−]B) have been observed during whole-body exercise following inspiratory muscle training (IMT), it remains unknown whether the inspiratory muscles are the source of at least part of this reduction. To investigate this, we tested the hypothesis that IMT would attenuate the increase in [lac−]B caused by mimicking, at rest, the breathing pattern observed during high-intensity exercise. Twenty-two physically active males were matched for 85% maximal exercise minute ventilation (V˙Emax) and divided equally into an IMT or a control group. Prior to and following a 6 week intervention, participants performed 10 min of volitional hyperpnoea at the breathing pattern commensurate with 85% V˙Emax