Southampton NIHR Respiratory Biomedical Research Unit

Southampton, United Kingdom

Southampton NIHR Respiratory Biomedical Research Unit

Southampton, United Kingdom
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Jefferies J.M.C.,University of Southampton | Jefferies J.M.C.,Public Health England | Macdonald E.,University of Southampton | Faust S.N.,University of Southampton | And 3 more authors.
Human Vaccines | Year: 2011

The 13 valent pneumococcal conjugate vaccine (PCV13, Prevenar 13™) is the broader coverage successor to the highly effective seven valent vaccine (PCV7, Prevenar™) which has reduced rates of pneumococcal disease in many countries. Despite the success of PCV7, pneumococcal disease due to non-PCV7 serotypes remains a threat in many settings, in particular many developing countries with a high burden of pneumococcal disease where serotype 1 and 5 are among the most common serotypes. Disease due to certain non-PCV7 serotypes, in particular serotype 19A has also begun to increase in incidence in countries with widespread use of PCV7. PCV13 consists of 13 pneumococcal capsular polysaccharides individually conjugated to the diphtheria-derived protein carrier CRM197. In addition to serotypes 4, 6B, 9V, 14, 18C, 19F and 23F included in PCV7, PCV13 also includes serotypes 1, 3, 5, 6A, 7F and 19A. PCV13 was licensed on the basis of non-inferiority trials and has proved to be at least as safe and effective as PCV7. PCV13 replaced PCV7 in the childhood immunization schedules of the US and UK in 2010 and is being rolled out to an increasing number of developing countries during 2011. Here we review the current literature regarding this vaccine, describing safety, efficacy, global serotype coverage and use and future directions. © 2011 Landes Bioscience.

Siervo M.,Newcastle University | Riley H.L.,University of Warwick | Fernandez B.O.,University of Warwick | Fernandez B.O.,University of Southampton | And 15 more authors.
PLoS ONE | Year: 2014

Objectives: The mechanisms by which low oxygen availability are associated with the development of insulin resistance remain obscure. We thus investigated the relationship between such gluco-insular derangements in response to sustained (hypobaric) hypoxemia, and changes in biomarkers of oxidative stress, inflammation and counter-regulatory hormone responses. Methods: After baseline testing in London (75 m), 24 subjects ascended from Kathmandu (1,300 m) to Everest Base Camp (EBC;5,300 m) over 13 days. Of these, 14 ascended higher, with 8 reaching the summit (8,848 m). Assessments were conducted at baseline, during ascent to EBC, and 1, 6 and 8 week(s) thereafter. Changes in body weight and indices of gluco-insular control were measured (glucose, insulin, C-Peptide, homeostasis model assessment of insulin resistance [HOMA-IR]) along with biomarkers of oxidative stress (4-hydroxy-2-nonenal-HNE), inflammation (Interleukin-6 [IL-6]) and counter-regulatory hormones (glucagon, adrenalin, noradrenalin). In addition, peripheral oxygen saturation (SpO2) and venous blood lactate concentrations were determined. Results: SpO2 fell significantly from 98.0% at sea level to 82.0% on arrival at 5,300 m. Whilst glucose levels remained stable, insulin and C-Peptide concentrations increased by .200% during the last 2 weeks. Increases in fasting insulin, HOMA-IR and glucagon correlated with increases in markers of oxidative stress (4-HNE) and inflammation (IL-6). Lactate levels progressively increased during ascent and remained significantly elevated until week 8. Subjects lost on average 7.3 kg in body weight. Conclusions: Sustained hypoxemia is associated with insulin resistance, whose magnitude correlates with the degree of oxidative stress and inflammation. The role of 4-HNE and IL-6 as key players in modifying the association between sustained hypoxia and insulin resistance merits further investigation. © 2014 Siervo et al.

Peden C.J.,Royal United Hospital NHS Trust | Peden C.J.,Health Services Research Center | Grocott M.P.W.,Health Services Research Center | Grocott M.P.W.,University of Southampton | Grocott M.P.W.,Southampton NIHR Respiratory Biomedical Research Unit
Anaesthesia | Year: 2014

Outcomes are essential measures of healthcare effectiveness and efficiency. Traditional measures of outcome, such as mortality and length of stay, are important and easy to measure but have significant limitations when evaluating the peri-operative care of elderly patients.alternative measures, including clinician-described (e.g. complication rates, functional status, frailty) and patient-reported outcome and experience measures, are important to provide a comprehensive description of peri-operative outcome in the older patient. However, few measurement tools have been developed or validated specifically for the elderly surgical patient. This paper describes the outcome measures currently in use, explores how they might be used to improve the quality of care provision, and indicates priority areas for perioperative outcomes research in the elderly surgical patients.©2013 The Association of Anaesthetists of Great Britain and Ireland.

Ozdemir B.A.,St George's, University of London | Sinha S.,St George's, University of London | Karthikesalingam A.,St George's, University of London | Poloniecki J.D.,St George's, University of London | And 6 more authors.
British Journal of Anaesthesia | Year: 2016

Background. Variations in patient outcomes between providers have been described for emergency admissions, including general surgery. The aim of this study was to investigate whether differences in modifiable hospital structures and processes were associated with variance in mortality, amongst patients admitted for emergency colorectal laparotomy, peptic ulcer surgery, appendicectomy, hernia repair and pancreatitis. Methods. Adult emergency admissions in the English NHS were extracted from the Hospital Episode Statistics between April 2005 and March 2010. The association between mortality and structure and process measures including medical and nursing staffing levels, critical care and operating theatre availability, radiology utilization, teaching hospital status and weekend admissions were investigated. Results. There were 294 602 emergency admissions to 156 NHS Trusts (hospital systems) with a 30-day mortality of 4.2%. Trust-level mortality rates for this cohort ranged from 1.6 to 8.0%. The lowest mortality rates were observed in Trusts with higher levels of medical and nursing staffing, and a greater number of operating theatres and critical care beds relative to provider size. Higher mortality rates were seen in patients admitted to hospital at weekends [OR 1.11 (95% CI 1.06-1.17) P<0.0001], in Trusts with fewer general surgical doctors [1.07 (1.01-1.13) P=0.019] and with lower nursing staff ratios [1.07 (1.01-1.13) P=0.024]. Conclusions. Significant differences between Trusts were identified in staffing and other infrastructure resources for patients admitted with an emergency general surgical diagnosis. Associations between these factors and mortality rates suggest that potentially modifiable factors exist that relate to patient outcomes, and warrant further investigation. © 2015 The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.

Edgecombe K.,University of Southampton | Latter S.,University of Southampton | Peters S.,St Marys Hospital | Roberts G.,University of Southampton | And 2 more authors.
Archives of Disease in Childhood | Year: 2010

Background and aims: Many adolescents with asthma experience continued symptoms and impaired quality of life despite modern therapy. This study sought to understand their experience and to use this understanding to improve their clinical management. Design and subjects: Qualitative study based on indepth semi-structured interviews conducted with adolescents with uncontrolled severe asthma. Results: 22 adolescents (11-18 years) with uncontrolled severe asthma were interviewed. Two of the overarching themes that emerged were: (A) medication and adherence; and (B) interaction with healthcare professionals and adherence with their advice. Despite frequent visits to clinic, some did not understand why they were using medications. Many felt that only some medications worked and were concerned about adverse effects. Factors related to intentional non-adherence were not being 'bothered' and conflicts with other activities. In particular, most were not using their spacer. Some though perceived a positive benefit to using their preventer treatment. Half the participants lived with a pet that they were sensitised to and two-thirds lived with a smoker. Adolescents felt involved in the clinic consultation and felt it was helpful but many did not take responsibility for interacting with health professionals. Parents were relied on to report symptoms, translate medical terms and remember the management plan. Conclusions: Adherence was often poor particularly with the use of spacers. Adolescents had a poor understanding of their medication and using it often conflicted with other activities. Adolescents are very reliant on their parents. Healthcare professionals need to work to empower them to gradually take on the responsibility for their asthma.

Tocheva A.S.,University of Southampton | Jefferies J.M.C.,University of Southampton | Jefferies J.M.C.,Public Health England | Jefferies J.M.C.,Southampton NIHR Respiratory Biomedical Research Unit | And 10 more authors.
Vaccine | Year: 2011

Asymptomatic carriage of the opportunistic pathogen Streptococcus pneumoniae is known to precede the development of invasive disease. Young children are one of the major reservoirs for pneumococci and worldwide over 700,000 children under two years old die due to invasive pneumococcal disease each year. Heptavalent conjugate vaccine (PCV-7) was introduced into the UK childhood immunisation schedule in September 2006. Our objective was to assess the emergence of colonising serotypes in young children in the three years following PCV-7 implementation. Methods: Time-series prevalence survey set in the paediatric outpatients department of a large UK teaching hospital. Participants were children aged four years and under attending the outpatients department during PCV-7 introduction (October 2006-February 2007) and in the same months of the two subsequent years. The main outcome measure was prevalence of pneumococcal carriage by serotype. Results: The rate of pneumococcal nasopharyngeal carriage remained stable during the three year period. We observed a significant 69% (95% CI, -40% to -118%, p< 0.0001) decrease in carriage of PCV-7 serotypes during PCV-7 implementation and a concomitant increase in the proportion of non PCV-7 serotypes. The most prevalent emerging non-vaccine serotypes were 6C, 11A, 19A and 22F. By March 2009, PCV-13 was predicted to cover only 33.3% (95% CI, 24.2-42.5%) of strains carried in the study population. Conclusions: Although the overall pneumococcal carriage rate remained stable between 2006 and 2009, we observed a significant decrease in the serotype coverage of PCV-7 and PCV-13. PCV-7 was highly successful in reducing carriage of vaccine serotypes. However, the increase in the proportion of non-vaccine serotypes found both in our study and causing invasive disease currently in the UK, underlines the importance of continued surveillance of carriage and disease. © 2011 Elsevier Ltd.

Jauneikaite E.,University of Southampton | Jauneikaite E.,Genome Institute of Singapore | Jefferies J.M.,University of Southampton | Jefferies J.M.,Southampton NIHR Respiratory Biomedical Research Unit | And 5 more authors.
Vaccine | Year: 2012

Background: Streptococcus pneumoniae is a major cause of bacterial infections resulting in significant morbidity and mortality worldwide. Currently, up to 13 serotypes are included in pneumococcal conjugate vaccines (PCVs). However, the serotype formulation of these vaccines was initially designed to protect children against serotypes most commonly causing invasive disease in North America, and may not reflect the serotype distribution across the world. Data regarding pneumococcal epidemiology from the other parts of the world, in particular South East Asia, has not been reviewed. Methods: This systematic literature review analyses published serotype data regarding S. pneumoniae isolates from South East Asian countries (defined as countries belonging to the Association of South East Asian Nations, ASEAN): Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand and Vietnam up to 3rd of March 2012. Results: Analysis of data from six ASEAN countries, from which information on pneumococcal serotypes was available, showed that the most common disease causing serotypes (in rank order) were 19F, 23F, 14, 6B, 1, 19A and 3. Serotype distribution of pneumococcal isolates was similar across the ASEAN region. Serotype level data was more commonly reported for pneumococcal isolates causing invasive pneumococcal disease than for those from non-invasive disease. Studies from Malaysia, Thailand and Singapore contributed the largest proportion of pneumococcal isolates, and serotype data, when compared to other ASEAN countries. Conclusion: This review demonstrates that the majority of IPD causing serotypes in SE Asia are included in currently licensed PCVs. However, PCV's are included in the routine childhood immunisation schedule of only one of the ten countries included in this analysis. Our findings demonstrate the scarcity of information available on serotype prevalence and distribution of pneumococci in SE Asia. © 2012 Elsevier Ltd.

Jefferies J.M.C.,University of Southampton | Jefferies J.M.C.,Public Health England | Jefferies J.M.C.,Southampton NIHR Respiratory Biomedical Research Unit | Clarke S.C.,University of Southampton | And 5 more authors.
Trends in Microbiology | Year: 2011

Pathogens increasingly evade current vaccines, and new strategies to control them are needed. There is mounting evidence that replacement of vaccine serotypes of Streptococcus pneumoniae with non-vaccine serotypes has taken place following widespread use of limited-serotype conjugate vaccines. New strategies to control vaccine evasion are needed and understanding evolutionary theory is important for the development of such approaches. Hosts are under selection pressure to evolve resistance against pathogens whereas pathogens are under selection pressure to evolve counter-resistance against the resistance mechanism of their host. Evolutionary changes in both host and pathogen lead to a continuous turnover of host and pathogen genotypes; this is known as Red Queen dynamics. We argue that integrating evolutionary thinking into pneumococcal vaccine design will lead to the avoidance of Red Queen dynamics and improved interventions against pneumococci. © 2011 Elsevier Ltd.

Schuhmann M.,University of Southampton | Brims F.J.H.,Portsmouth Hospitals NHS Trust | O'Reilly K.M.A.,University of Southampton | O'Reilly K.M.A.,Southampton NIHR Respiratory Biomedical Research Unit
Clinical Pulmonary Medicine | Year: 2011

In this work, we describe both benign and malignant asbestos-related diseases and provide an updated review of recent advances in the field. It has long been appreciated that the inhalation of asbestos fibers causes several well-described respiratory diseases including pleural plaques, diffuse pleural thickening, asbestosis, lung cancer, and malignant pleural mesothelioma (MPM). However, despite this knowledge and stricter industrial controls, the incidence of these diseases continues to increase in many parts of the world. In fact, despite the introduction of strict limits early in the 20th century, the mortality rate due to MPM is still increasing in industrialized countries such as the United Kingdom and Australia. In this update we provide an overview of each disease entity while concentrating on the role that newer imaging techniques, including high-resolution computed tomography, magnetic resonance imaging, and positron emission tomography /computed tomography, play in the diagnosis of asbestos-related pleural and parenchymal diseases. As the incidence of MPM continues to increase in many parts of the world, this review also focuses on new approaches to the diagnosis and treatment of this devastating condition. A description of the potential use and limitations of biomarkers in the diagnosis and monitoring of the disease is included along with recent trial data examining novel vaccine-based biological therapies. © 2011 by Lippincott Williams & Wilkins.

Walker W.T.,University of Southampton | Faust S.N.,University of Southampton | Faust S.N.,Southampton NIHR Respiratory Biomedical Research Unit
Expert Review of Vaccines | Year: 2010

The first cases of pandemic influenza A (H1N1) 2009 infection were seen in Mexico in March 2009. Since then, it is thought to have been responsible for at least 18,337 deaths globally. Owing to the young age of fatalities, there have been an estimated 2 million years of life lost, which is comparable to the previous pandemics of 1957 and 1968. In this article, we consider the available data on a monovalent inactivated split-virion AS03-adjuvanted pandemic influenza A (H1N1) vaccine, Pandemrix™ (GlaxoSmithKline, Rixensart, Belgium). At present, Pandemrix appears to be highly immunogenic in all age groups, including children and infants under 3 years of age, with an acceptable safety profile in the context of an influenza pandemic. However, owing to the novel adjuvant, further studies on the safety, immunogenicity and vaccine effectiveness of Pandemrix together with robust post-marketing surveillance are required. © 2010 Expert Reviews Ltd.

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