Factors affecting the successful implementation and sustainability of the Liverpool Care Pathway for dying patients – a realist evaluation

Objectives: The Liverpool Care Pathway for the dying patient (LCP) was designed to improve end-of-life care in generalist health care settings. Controversy has led to its withdrawal in some jurisdictions. The main objective of this research was to identify the influences that facilitated or hindered successful LCP implementation.

Method: An organisational case study using realist evaluation in one health and social care trust in Northern Ireland. Two rounds of semi-structured interviews were conducted with two policy makers and twenty two participants with experience and/or involvement in management of the LCP during 2011 and 2012.

Results: Key resource inputs included facilitation with a view to maintaining LCP ‘visibility’, reducing anxiety among nurses and increasing their confidence regarding the delivery of end-of-life care; and nurse and medical education designed to increase professional self-efficacy and reduce misuse and misunderstanding of the LCP. Key enabling contexts were consistent senior management support; ongoing education and training tailored to the needs of each professional group; and an organisational cultural change in the hospital setting that encompassed end-of-life care.

Conclusion: There is a need to appreciate the organizationally complex nature of intervening to improve end-of-life care. Successful implementation of evidence-based interventions for end-of-life care requires commitment to planning, training and ongoing review that takes account of different perspectives, institutional hierarchies and relationships and the educational needs of professional disciplines. There is a need also to recognise that medical consultants require particular support in their role as gatekeepers and as a lead communication channel with patients and their relatives.

Pertussis: A significant cause of prolonged acute cough in previously vaccinated school-aged children

No abstract available: Commentary on:
Wang KFry NKCampbell Het al. Whooping cough in school age children presenting with persistent cough in UK. BMJ 2014;348:g3668

Estimating the incidence, prevalence and true cost of asthma in the UK: Secondary analysis of national stand-alone and linked databases in England, Northern Ireland, Scotland and Wales-a study protocol

Introduction Asthma is now one of the most common long-term conditions in the UK. It is therefore important to develop a comprehensive appreciation of the healthcare and societal costs in order to inform decisions on care provision and planning. We plan to build on our earlier estimates of national prevalence and costs from asthma by filling the data gaps previously identified in relation to healthcare and broadening the field of enquiry to include societal costs. This work will provide the first UK-wide estimates of the costs of asthma. In the context of asthma for the UK and its member countries (ie, England, Northern Ireland, Scotland and Wales), we seek to: (1) produce a detailed overview of estimates of incidence, prevalence and healthcare utilisation; (2) estimate health and societal costs; (3) identify any remaining information gaps and explore the feasibility of filling these and (4) provide insights into future research that has the potential to inform changes in policy leading to the provision of more cost-effective care.

Methods and analysis Secondary analyses of data from national health surveys, primary care, prescribing, emergency care, hospital, mortality and administrative data sources will be undertaken to estimate prevalence, healthcare utilisation and outcomes from asthma. Data linkages and economic modelling will be undertaken in an attempt to populate data gaps and estimate costs. Separate prevalence and cost estimates will be calculated for each of the UK-member countries and these will then be aggregated to generate UK-wide estimates.

Ethics and dissemination Approvals have been obtained from the NHS Scotland Information Services Division's Privacy Advisory Committee, the Secure Anonymised Information Linkage Collaboration Review System, the NHS South-East Scotland Research Ethics Service and The University of Edinburgh's Centre for Population Health Sciences Research Ethics Committee. We will produce a report for Asthma-UK, submit papers to peer-reviewed journals and construct an interactive map.

Human mesenchymal stem cells reduce the severity of acute lung injury in a sheep model of bacterial pneumonia

Background Human bone marrow-derived mesenchymal stem (stromal) cells (hMSCs) improve survival in mouse models of acute respiratory distress syndrome (ARDS) and reduce pulmonary oedema in a perfused human lung preparation injured with Escherichia coli bacteria. We hypothesised that clinical grade hMSCs would reduce the severity of acute lung injury (ALI) and would be safe in a sheep model of ARDS.

Methods Adult sheep (30–40 kg) were surgically prepared. After 5 days of recovery, ALI was induced with cotton smoke insufflation, followed by instillation of live Pseudomonas aeruginosa (2.5×10¹¹ CFU) into both lungs under isoflurane anaesthesia. Following the injury, sheep were ventilated, resuscitated with lactated Ringer's solution and studied for 24 h. The sheep were randomly allocated to receive one of the following treatments intravenously over 1 h in one of the following groups: (1) control, PlasmaLyte A, n=8; (2) lower dose hMSCs, 5×10⁶ hMSCs/kg, n=7; and (3) higher-dose hMSCs, 10×10⁶ hMSCs/kg, n=4.

Results By 24 h, the PaO₂/FiO₂ ratio was significantly improved in both hMSC treatment groups compared with the control group (control group: PaO₂/FiO₂ of 97±15 mm Hg; lower dose: 288±55 mm Hg (p=0.003); higher dose: 327±2 mm Hg (p=0.003)). The median lung water content was lower in the higher-dose hMSC-treated group compared with the control group (higher dose: 5.0 g wet/g dry [IQR 4.9–5.8] vs control: 6.7 g wet/g dry [IQR 6.4–7.5] (p=0.01)). The hMSCs had no adverse effects.

Conclusions Human MSCs were well tolerated and improved oxygenation and decreased pulmonary oedema in a sheep model of severe ARDS.

In women, increased dietary antioxidants are associated with reduced risk of developing heart failure

Commentary on

Rautiainen S, Levitan EB, Mittleman MA, et al. Total antioxidant capacity of diet and risk of heart failure: a population-based prospective cohort of women. Am J Med 2013;126:494–500.

A realist literature review of transition to adult services by young people with life-limiting conditions in ireland.

Background As a result of improvements in care and treatment more young people with life-limiting conditions are now living beyond childhood, meaning they must make the transition from children's to adult services. The loss of long-standing relationships with providers of children's services combines with poor co-ordination of services to make this a daunting prospect for young people and their families. However, there is little evidence on transition services for young people with life limiting conditions, with few models of good practice in the literature.


Aims The purpose of this review was to determine the factors that promote or hinder the transition to adult services for young adults with life limiting conditions, and identify gaps to be addressed.


Methods A comprehensive search of the literature was undertaken using key terms, of the following databases; MEDLINE and the Cochrane Database of Systematic Reviews. 314 articles were sourced and inclusion and exclusion criteria were applied to highlight the most relevant literature.


Results Studies were reviewed using a realist review approach and three themes emerged from the literature. Barriers and facilitators to the transition process were identified associated with: 1. The patient 2. Parents/carers 3. The organisation.


Conclusion It is unclear from the literature what the specific factors are that promote or hinder the transition process for young adults with life limiting conditions who go through the transition from children's to adult services, therefore, research is required to identify the factors that promote and hinder the transition process in Ireland. This research is currently being carried out by the author as part of Doctoral studies. The three year full time Doctoral study commenced in January 2013 and is funded by the All Ireland Institute of Hospice and Palliative Care.

Viability of Pseudomonas aeruginosa in cough aerosols generated by persons with cystic fibrosis

Background Person-to-person transmission of respiratory pathogens, including Pseudomonas aeruginosa, is a challenge facing many cystic fibrosis (CF) centres. Viable P aeruginosa are contained in aerosols produced during coughing, raising the possibility of airborne transmission.

Methods Using purpose-built equipment, we measured viable P aeruginosa in cough aerosols at 1, 2 and 4 m from the subject (distance) and after allowing aerosols to age for 5, 15 and 45 min in a slowly rotating drum to minimise gravitational settling and inertial impaction (duration). Aerosol particles were captured and sized employing an Anderson Impactor and cultured using conventional microbiology. Sputum was also cultured and lung function and respiratory muscle strength measured.

Results Nineteen patients with CF, mean age 25.8 (SD 9.2) years, chronically infected with P aeruginosa, and 10 healthy controls, 26.5 (8.7) years, participated. Viable P aeruginosa were detected in cough aerosols from all patients with CF, but not from controls; travelling 4 m in 17/18 (94%) and persisting for 45 min in 14/18 (78%) of the CF group. Marked inter-subject heterogeneity of P aeruginosa aerosol colony counts was seen and correlated strongly (r=0.73-0.90) with sputum bacterial loads. Modelling decay of viable P aeruginosa in a clinic room suggested that at the recommended ventilation rate of two air changes per hour almost 50 min were required for 90% to be removed after an infected patient left the room.

Conclusions: Viable P aeruginosa in cough aerosols travel further and last longer than recognised previously, providing additional evidence of airborne transmission between patients with CF.

Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative bacteria from patients with cystic fibrosis

BACKGROUND: Pseudomonas aeruginosa is the most common bacterial pathogen in patients with cystic fibrosis (CF). Current infection control guidelines aim to prevent transmission via contact and respiratory droplet routes and do not consider the possibility of airborne transmission. It was hypothesised that subjects with CF produce viable respirable bacterial aerosols with coughing.

METHODS: A cross-sectional study was undertaken of 15 children and 13 adults with CF, 26 chronically infected with P aeruginosa. A cough aerosol sampling system enabled fractioning of respiratory particles of different sizes and culture of viable Gram-negative non-fermentative bacteria. Cough aerosols were collected during 5 min of voluntary coughing and during a sputum induction procedure when tolerated. Standardised quantitative culture and genotyping techniques were used.

RESULTS: P aeruginosa was isolated in cough aerosols of 25 subjects (89%), 22 of whom produced sputum samples. P aeruginosa from sputum and paired cough aerosols were indistinguishable by molecular typing. In four cases the same genotype was isolated from ambient room air. Approximately 70% of viable aerosols collected during voluntary coughing were of particles <or=3.3 microm aerodynamic diameter. P aeruginosa, Burkholderia cenocepacia, Stenotrophomonas maltophilia and Achromobacter xylosoxidans were cultivated from respiratory particles in this size range. Positive room air samples were associated with high total counts in cough aerosols (p = 0.003). The magnitude of cough aerosols was associated with higher forced expiratory volume in 1 s (r = 0.45, p = 0.02) and higher quantitative sputum culture results (r = 0.58, p = 0.008).

CONCLUSION: During coughing, patients with CF produce viable aerosols of P aeruginosa and other Gram-negative bacteria of respirable size range, suggesting the potential for airborne transmission.

S21 Culture Independent Identification Of Bacterial Communities In The Respiratory Tract Of Patients With Copd, Healthy Non-smokers And Healthy Smokers

Introduction and aims: The role bacteria play in the development and progression of Chronic Obstructive Pulmonary Disease (COPD) is unclear. We used culture-independent methods to describe differences and/or similarities in microbial communities in the lower airways of patients with COPD, healthy non-smokers and smokers.

Methods: Bronchial wash samples were collected from patients with COPD (GOLD 1–3; n = 18), healthy non-smokers (HV; n = 11) and healthy smokers (HS; n = 8). Samples were processed using the Illumina MiSeq platform. The Shannon-Wiener Index (SW) of diversity, lung obstruction (FEV1/FVC ratio) and ordination by Non-Metric Multidimensional Scaling (NMDS) on Bray-Curtis dissimilarity indices were analysed to evaluate how samples were related. Principal component analysis (PCA) was performed to assess the effect specific taxa had within each cohort. Characteristics of each cohort are shown in Table 1.

Results: There was no difference in taxa richness between cohorts (range: 69–71; p = 0.954). Diversity (SW Index) was significantly lower in COPD samples compared to samples from HV and HS (p = 0.009 and p = 0.033, respectively). There was no significant difference between HV and HS (p = 0.186). The FEV1/FVC ratio was significantly lower for COPD compared to HV (p = 9*10–8) and HS (p = 2*10–6), respectively. NMDS analysis showed that communities belonging to either of the healthy groups were more similar to each other than they were to samples belonging to the COPD group. PCA analysis showed that members of Streptococcus sp. and Haemophilus sp. had the largest effect on the variance explained in COPD. In HS, Haemophilus sp., Fusobaterium sp., Actinomyces sp., Prevotella sp. and Veillonella sp. had the largest effect on the variance explained, while in HV Neisseria sp., Porphyromonas sp., Actinomyces sp., Atopobium sp., Prevotella and Veillonella sp. had the largest effect on the variance explained.

Conclusions: The study demonstrates that microbial communities in the lower airways of patients with COPD are significantly different from that seen in healthy comparison groups. Patients with COPD had lower microbial diversity than either of the healthy comparison groups, higher relative abundance of members of Streptococcus sp. and lower relative abundance of a number of key anaerobes.Characteristics

CULTURE AND CULTURE INDEPENDANT IDENTIFICATION OF BACTERIAL COMMUNITIES IN THE CYSTIC FIBROSIS RESPIRATORY TRACT

Introduction and Aims: The identification of complex chronic polymicrobial infections, such as those observed in the cystic fibrosis (CF) airways, are often a diagnostic challenge. Few studies have compared culture-dependent methods with molecular identification making it hard to describe bacterial communities in a comprehensive manner. The aim of the study is to compare four different methods with respect to their similarities and differences in detection of bacteria. Methods: We compared41 sputum samples fromroutine clinical-culture, extended-culture (aerobic and anaerobic), and molecular identification such as Roche 454-FLX Titanium and T-RFLP to assess concurrence between methodologies in detecting bacteria. The agreement between methodologies in detecting either absence or presence of bacterial taxa was assessed by Kappa (κ) statistics. Results: The majority of bacterial taxa identified by culture were also identified with molecular analysis. In total 2, 60, 25, and 179 different bacterial taxa were identified with clinical-culture, extended-culture, T-RFLP and 454-FLX respectively. Clinical-culture, extended-culture and T-RFLP were poor predictors of species richness when compared to 454-FLX (p < 0.0001). Agreement between methods for detecting Pseudomonas sp. and Burkholderia sp. was good with κ ≥ 0.7 [p < 0.0001] and κ ≥ 0.9 [p < 0.0001] respectively. Detection of anaerobic bacteria, such as Prevotella sp. and Veillonella sp., was moderate between extended-culture and 454-FLX with κ = 0.461 [p < 0.0001] and κ = 0.311 [p = 0.032] respectively, and good between T-RFLP and 454-FLX with κ = 0.577 [p < 0.0001] and κ = 0.808 [p < 0.0001] respectively. Agreement between methods for other main bacterial taxa, such as Staphylcoccus sp. and Streptococcus sp., was poor with only a moderate agreement for detection of Streptococcus sp. observed between T-RFLP and 454-FLX (κ = 0.221 [p = 0.024]). Conclusions: This study demonstrates the increased sensitivity culture-independent microbial identification such as the 454-FLX have over clinical-culture, extended-culture and T-RFLP methodologies. The extended-culture detected majority of the most prevalent bacterial taxa associated with chronic colonisation of the CF airways which were also detected by culture-independent methodologies. However, agreement between methods in detecting number of potentially relevant bacteria is largely lacking.

MICROBIAL COMMUNITY COMPOSITION IN THE LUNGS OF PATIENTS WITH CYSTIC FIBROSIS AND NON-CF BRONCHIECTASIS

Introduction and Aims: Persistent bacterial infection is a major cause of morbidity and mortality in patients with both Cystic Fibrosis (CF) and non-CF Bronchiectasis (non-CFBX). Numerous studies have shown that CF and non-CFBX airways are colonised by a complex microbiota. However, many bacteria are difficult, if not impossible, to culture by conventional laboratory techniques. Therefore, molecular detection techniques offer a more comprehensive view of bacterial diversity within clinical specimens. The objective of this study was to characterise and compare bacterial diversity and relative abundance in patients with CF and non-CFBX during exacerbation and when clinically stable.

Methods: Sputum samples were collected from CF (n=50 samples) and non-CFBX (n=52 samples) patients at the start and end of treatment for an infective exacerbation and when clinically stable. Pyrosequencing was used to assess the microbial diversity and relative genera (or the closest possibly taxonomic order) abundance within the samples. Each sequence read was defined based on 3% difference.

Results: High-throughput pyrosequencing allowed a sensitive and detailed examination of microbial community composition. Rich microbial communities were apparent within both CF (171 species-level phylotypes per genus) and non-CFBX airways (144 species-level phylotypes per genus). Relative species distribution within those two environments was considerably different; however, relatively few genera formed a core of microorganisms, representing approximately 90% of all sequences, which dominated both environments. Relative abundance based on observed operational taxonomic units demonstrated that the most abundant bacteria in CF were Pseudomonas (28%), Burkholderia (22%), Streptococcus (13%), family Pseudomonadaceae (8%) and Prevotella (6%). In contrast, the most commonly detected operational taxonomic units in non-CFBX were Haemophilus (22%), Streptococcus (14%), other (unassigned taxa) (11%), Pseudomonas (10%), Veillonella (7%) and Prevotella (6%).

Conclusions: These results suggest that distinctive microbial communities are associated with infection and/or colonisation in patients with both CF and non-CFBX. Although relatively high species richness was observed within the two environments, each was dominated by different core taxa. This suggests that differences in the lung environment of these two diseases may affect adaptability of the relevant bacterial taxa.

THE CULTURE MICROBIOME IN THE LUNGS OF PATIENTS WITH COPD

Introduction and Aims: Previous studies have shown that the lungs of Cystic Fibrosis (CF) and bronchiectasis (BE, not caused by CF) patients are colonised by a range of aerobic and anaerobic bacteria. As bacteria are also implicated in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD), this study aimed to determine the culture microbiome of the COPD airways.

Methods: Samples were collected from 13 stable COPD patients during routine bronchoscopy. Bronchial washings were taken at a single location in the right middle lobe by flushing and removing 30 ml of sterile saline. Samples were cultured under strict anaerobic conditions with bacteria detected by plating on both selective and non-selective agar media and quantified by total viable count (TVC). Identification of the cultured bacteria was performed by amplification and subsequent sequencing of the 16sRNA gene.

Results: Mean FEV1 was 1.36 (range 0.84–2.26, mean per cent predicted FEV1, 54%), and the mean ratio (FEV1/FVC) was 51%. Bacteria were detected in 12/13 samples (92%) with bacteria from the genera Streptococcus [12/13 samples, 92%; mean (range) TVC 9.62×105 cfu/ml (1.50×103–1.42×107)] and Haemophilus [4/13 samples, 31%; mean (range) 6.40×104 cfu/ml (2.20×103–1.60×105)] most frequently detected. Anaerobic bacteria primarily from the genera Prevotella [8/13 samples, 62%; mean (range) TVC 1.12×104 cfu/ml (1.30×103–4.20×104)] and Veillonella [5/13 samples, 38%; mean (range) TVC 1.29×105 cfu/ml (4.20×103–3.60×105)] were also detected. Pseudomonas and Moraxella were not detected in any samples.

Conclusions: Our results show that bacteria from the genera Streptococcus, Haemophilus, Prevotella and Veillonella are frequently present the airways of patients suffering from COPD. Taking account of the dilutional effect of the bronchial wash procedure and extrapolating to allow comparison with sputum data in our laboratory for CF and BE, the relative load of bacteria from the genera Streptococcus, Prevotella and Veillonella is similar in these three airway diseases. The potential role of these bacteria in the progression and pathogenesis of COPD requires further investigation.

Stress in parents of children born very preterm is predicted by child externalising behaviour and parent coping at age 7 years

Objective: To examine factors which predict parenting stress in a longitudinal cohort of children born very preterm seen at age seven years.
Methods: We recruited 100 very preterm (< 32 weeks GA) child-parent dyads and a control group of 50 term-born dyads born between 2001 and 2004 with follow-up at seven years. Parents completed the Parenting Stress Index, Ways of Coping Questionnaire, Child Behavior Check List, Beck Depression Inventory and the State Trait Anxiety Inventory questionnaires. Child IQ was assessed using the Wechsler Intelligence Scale-IV.
Results: After controlling for maternal education, parents of preterm children (95% CI, 111.1 to 121.4) scored higher (p = .027) on the Parenting Stress Index than term born controls (95% CI, 97.8 to 113.2). Regression analyses showed that child externalising behaviour, sex and parent escape/avoidance coping style, predicted higher parenting stress in the preterm group. Parents of preterm girls expressed higher levels of stress than those of boys. 
Conclusions: Maladaptive coping strategies contribute to greater stress in parents of very preterm children. Our findings suggest that these parents need support for many years after birth of a very preterm infant.

RAS testing of colorectal carcinoma—a guidance document from the Association of Clinical Pathologists Molecular Pathology and Diagnostics Group

Analysis of colorectal carcinoma (CRC) tissue for KRAS codon 12 or 13 mutations to guide use of anti-epidermal growth factor receptor (EGFR) therapy is now considered mandatory in the UK. The scope of this practice has been recently extended because of data indicating that NRAS mutations and additional KRAS mutations also predict for poor response to anti-EGFR therapy. The following document provides guidance on RAS (i.e., KRAS and NRAS) testing of CRC tissue in the setting of personalised medicine within the UK and particularly within the NHS. This guidance covers issues related to case selection, preanalytical aspects, analysis and interpretation of such RAS testing.