East Anglian Region Research Articles

Pharmacogenomics and the Concept of Personalized Medicine for the Management of Hypertension

Pharmacogenomics and the Concept of Personalized Medicine for the Management of Hypertension

#6656 PATIENTS' PERSPECTIVES ON HAEMODIALYSIS ACCESS: A QUANTITATIVE STUDY

Abstract Background and Aims Vascular access is an essential requirement for haemodialysis (HD). There is strong evidence that an arteriovenous fistula (AVF) is preferable to access via a central venous catheter (CVC) for long term haemodialysis, yet many patients opt for access via a CVC. We performed a cross-sectional study to assess patient preferences regarding vascular access. The quantitative component of this work is presented here. Method Questionnaires were administered to patients attending dialysis at four sites in the East Anglia region of the UK (n = 380). Additional patient data was collected from medical records. Analysis was performed using the R software. Results 63% (n = 238) of patients completed the survey. The median age of respondents was 75 years (range 24-95 years), 64% were male (n = 153), the median length of time on dialysis was 23 months, and 64% (n = 152) were using an AVF. There was no significant association between age and form of access (p = 0.11). 65% of respondents believed that an AVF was the best access route for health, 10% believed a CVC was the best route, and 25% were unsure. This was not significantly affected by the participant's access route at the time of the study (p = 0.91) or self-reported pre-dialysis education (p = 0.09). Respondents who believed that the health professionals caring for them preferred AVFs were significantly more likely to believe that AVFs were best for their health (p < 0.0001 for both medical and nursing staff preference). However, overall, there was uncertainty about the preferred haemodialysis access of health professionals, with 40% and 47% of respondents unsure regarding the preference of medical and nursing staff, respectively. These patients were also more likely to respond as ‘unsure’ as to which access type was better for their health. We asked participants to rate 16 possible concerns they may have about access on a 1-9 scale (Figure 1). The most highly rated concerns were related to sleeping, pain, bleeding and access longevity, each receiving a rating of ≥2 in nearly 40% of participants. Notably, infection risk was rated as the lowest priority concern, only receiving a rating of ≥2 in 5% of participants. Concerns were similar regardless of the active form of access. 63% (n = 54) of respondents with a CVC would not consider changing to an AVF. The decision to switch from CVC to AVF was not significantly associated with age (p = 0.69), or the number of AVF operations a patient had undergone in the six years prior to the study year (p = 0.94). The decision was also not associated with respondent belief regarding the best access type for health (p = 0.84). Differences in access concerns could not significantly explain the decision to or not to switch from CVC to AVF. However, analysis of free-text responses identified peer experiences as a strong influence on the decision to switch. Conclusion Most HD patients are aware that an AVF is associated with better health outcomes than a CVC. Despite this, a large proportion of patients dialysing via a CVC do not wish to change their access, with many reporting concerns of bleeding, needling pain, and difficulty sleeping. Infection risk was not a consideration for most patients. Additionally, we found that patients reported significant uncertainty about doctor and nurse preference for haemodialysis access. These findings are mirrored by analysis of the free text responses to the questions in this study. In particular, peer experiences were a significant determinant of the decision to switch from a CVC to AVF. The findings suggest that when we discuss vascular access with patients, a broad scope of topics should be addressed, beyond health outcomes alone, to allow for effective shared decision making. They also suggest that there is room to improve the communication of our perspectives as healthcare workers, both from a nursing and medical perspective.

Molecular Epidemiology Questions Transmission Pathways Identified During the Year 2000 Outbreak of Classical Swine Fever in the UK.

The last outbreak of classical swine fever (CSF) in the UK occurred in 2000. A total of 16 domestic pig holdings in the East Anglia region were confirmed as infected over a 3-month period. Obtaining viral genome sequences has since become easier and more cost-effective and has accordingly been applied to trace viral transmission events for a variety of viruses. The rate of genetic evolution varies for different viruses and is influenced by different transmission events, which will vary according to the epidemiology of an outbreak. To examine if genetic changes over the course of any future CSF outbreak would occur to supplement epidemiological investigations and help to track virus movements, the E2 gene and full genome of the virus present in archived tonsil samples from 14 of these infected premises were sequenced. Insufficient changes occurred in the full E2 gene to discriminate between the viruses from the different premises. In contrast, between 5 and 14 nucleotide changes were detected between the genome sequence of the virus from the presumed index case and the sequences from the other 13 infected premises. Phylogenetic analysis of these full CSFV genome sequences identified clusters of closely related viruses that allowed to corroborate some of the transmission pathways inferred by epidemiological investigations at the time. However, other sequences were more distinct and raised questions about the virus transmission routes previously implicated. We are thus confident that in future outbreaks, real-time monitoring of the outbreak via full genome sequencing will be beneficial.

Regional differences in presence of Shiga toxin-producing Escherichia coli virulence-associated genes in the environment in the North West and East Anglian regions of England.

Shiga toxin-producing Escherichia coli is carried in the intestine of ruminant animals, and outbreaks have occurred after contact with ruminant animals or their environment. The presence of STEC virulence genes in the environment was investigated along recreational walking paths in the North West and East Anglia regions of England. In all, 720 boot sock samples from walkers' shoes were collected between April 2013 and July 2014. Multiplex PCR was used to detect E. coli based on the amplification of the uidA gene and investigate STEC-associated virulence genes eaeA, stx1 and stx2. The eaeA virulence gene was detected in 45·5% of the samples, where stx1 and/or stx2 was detected in 12·4% of samples. There was a difference between the two regions sampled, with the North West exhibiting a higher proportion of positive boot socks for stx compared to East Anglia. In univariate analysis, ground conditions, river flow and temperature were associated with positive boot socks. The detection of stx genes in the soil samples suggests that STEC is present in the English countryside and individuals may be at risk for infection after outdoor activities even if there is no direct contact with animals. SIGNIFICANCE AND IMPACT OF THE STUDY: Several outbreaks within the UK have highlighted the danger of contracting Shiga toxin-producing Escherichia coli from contact with areas recently vacated by livestock. This is more likely to occur for STEC infections compared to other zoonotic bacteria given the low infectious dose required. While studies have determined the prevalence of STEC within farms and petting zoos, determining the risk to individuals enjoying recreational outdoor activities that occur near where livestock may be present is less researched. This study describes the prevalence with which stx genes, indicative of STEC bacteria, were found in the environment in the English countryside.

East Anglia’s Medieval Rood Screens: Conserving Sensitive Painted Artworks in Uncontrolled Church Environments

ABSTRACT England’s East Anglian region has c.550 late-medieval screens still in their original churches, one of Northern Europe’s most significant in situ collections of medieval panel painting. The churches are managed by non-specialist volunteers and are not museums. In many, congregations are shrinking and long-term sustainability will involve varying uses of the building. The buildings and their collections are at risk from, among other factors, weather, groundwater, fire, heat, moisture, light, pollutants and pests, as well as vandalism and theft. The same threats affect screens, causing flaking paint, microbiological growth, insect damage and photodegradation. A collaborative programme was forged between the Hamilton Kerr Institute, University of Cambridge, specialists in medieval panel painting conservation, and Tobit Curteis Associates, specialists in environmental deterioration in historic buildings, supported by the Church of England’s Cathedral and Church Buildings Division. This project aimed to bridge the gap between the conservation of sensitive artefacts and the conservation of the buildings in which they are situated. A methodology, utilising materials analysis, environmental monitoring and building and object surveys, was devised for the assessment of the deterioration of screens and their churches to produce holistic recommendations. Through a pilot study, solutions that are passive, cost effective, innovative and sustainable are being implemented.

Researching “British [Muslim] Values”: Vernacular Politics, Digital Storytelling, and Participant Researchers

This article reflects on methodological decisions, strategies, and challenges from a recent interdisciplinary project on the relationship between “British values” and Islam. The project employed digital storytelling to access “everyday” conceptions and constructions of this contentious relationship. The research was undertaken by participant researchers recruited from Muslim communities in the UK’s East Anglia region, working with academics from media studies and political science. In this article, we offer a detailed account of key moments relating especially to recruitment, retention, and the production of digital content. It offers two contributions. First, methodological guidance for researchers interested in combining participatory research with digital storytelling. And second, rationale for so doing given the methodology’s scope for producing rich visual content with capacity (i) to deepen and disrupt established knowledge and (ii) to change the views, ideas, and aspirations of those involved in the content’s creation.

Multicentre study of physical abuse and limb fractures in young children in the East Anglia Region, UK

ObjectiveTo determine if the detection of physical abuse in young children with fractures is of uniform high standard in the East Anglia Region of the UK, and whether we can...

Adverse Tracheal Intubation-Associated Events in Pediatric Patients at Nonspecialist Centers: A Multicenter Prospective Observational Study.

In tertiary care PICUs, adverse tracheal intubation-associated events occur frequently (20%; severe tracheal intubation-associated events in 3-6.5%). However, pediatric patients often present to nonspecialist centers and require intubation by local teams. The rate of tracheal intubation-associated events is not well studied in this setting. We hypothesized that the rate of tracheal intubation-associated events would be higher in nonspecialist centers. Prospective observational study. We conducted a multicenter study covering 47 local hospitals in the North Thames and East Anglia region of the United Kingdom. All intubated children transported by the Children's Acute Transport Service from June 2016 to May 2018. None. Data were available in 1,051 of 1,237 eligible patients (85%). The overall rate of tracheal intubation-associated events was 22.7%, with severe tracheal intubation-associated events occurring in 13.8%. Younger, small-for-age patients and those with difficult airways had a higher rate of complications. Children with comorbidities and difficult airways were found to have increased severe tracheal intubation-associated events. The most common tracheal intubation-associated events were endobronchial intubation (6.2%), hypotension (5.4%), and bradycardia (4.2%). In multivariate analysis, independent predictors of tracheal intubation-associated events were number of intubation attempts (odds ratio for > 4 attempts compared with a single attempt 19.1; 95% CI, 5.9-61.4) and the specialty of the intubator (emergency medicine compared with anesthesiologists odds ratio 6.9; 95% CI, 1.1-41.4). Tracheal intubation-associated events are common in critically ill pediatric patients who present to nonspecialist centers. The rate of severe tracheal intubation-associated events is much higher in these centers as compared with the PICU setting. There should be a greater focus on improving the safety of intubations occurring in nonspecialist centers.

The detection of drugs of abuse and pharmaceuticals in drinking water using solid-phase extraction and liquid chromatography-mass spectrometry

Pharmaceuticals and drugs of abuse including novel psychoactive substances (NPS) are emerging as newer contaminants in the aquatic environment. The presence of such pollutants has implications on the environment as well as public health and therefore their identification is important when monitoring water quality. This research presents a new method for the simultaneous detection of 20 drugs of abuse and pharmaceuticals in drinking water, including 15 NPS, three traditional illicit drugs and two antidepressants. The developed method is based on the use of solid-phase extraction (SPE) followed by liquid chromatography-mass spectrometry (LC-MS). The SPE recoveries for the majority of target analytes ranged between 62 and 107%. The method detection and quantification limits ranged between 0.01 and 1.09 ng/L and 0.02–3.64 ng/L respectively. Both instrumental and method precisions resulted in relative standard deviations <15.04%, with an accuracy of < ±8.66%. The results show that LC-MS can be an alternative to the more popular technique of liquid chromatography-tandem mass spectrometry for the analysis of drugs of abuse and pharmaceuticals in drinking water. This newly developed simultaneous detection method has been applied to drinking water collected from the East Anglia region of the UK. Citalopram, cocaine, fluoxetine, ketamine, mephedrone, methamphetamine and methylone were detected at the range of 0.14 and 2.81 ng/L. This is the first time that the two NPS mephedrone and methylone, have been detected in UK drinking water.

Accounting for rainfall and the length of growing season in technical efficiency analysis

The physical environment of farming systems is rarely considered when conducting farm level efficiency analysis, which is likely to lead to bias of performance measurements based on benchmarking methods such as Data Envelopment Analysis (DEA). We incorporate variations of the physical environment (rainfall and length of growing season) through the specifications of the linear programming in DEA to investigate performance measurement bias. The derived technical efficiency estimates are obtained using a sub-vector DEA which ensures farms are compared in a homogenous environment (i.e. accounting for differences in rainfall levels amongst distinct farm units). We use the Farm Business Survey to analyse a representative sample of 245 cereal farms in the East Anglia region between 2009 and 2010. Efficiency rankings obtained from a standard DEA model and a non-discretionary DEA model that incorporates the variations in the physical environment. We show that incorporating rainfall and the length of the growing season as non-discretionary inputs into the production function had significantly altered the farm efficiency ranking between the two models. Hence, to improve extension services to farmers and to reduce biased estimates of farm technical efficiency, variations in environmental conditions need to be integral to the analysis of efficiency.

Emergence of Klebsiella pneumoniae subspecies pneumoniae as a cause of septicaemia in pigs in England.

Between 2011 and 2014 outbreaks of septicaemia due to Klebsiella pneumoniae subspecies pneumoniae (Kpp) were diagnosed on thirteen English pig farms. The most consistent features were rapid deaths of pigs from ten-days-old to weaning, seasonal occurrence (May to September), affected farms being outdoor breeding herds and the location of all but one of the outbreaks in the East Anglia region in Eastern England. Molecular characterisation of the outbreak Kpp isolates showed that by multilocus sequencing all were sequence type 25 (ST25) of K2 capsular type with a combination of a 4.3kb plasmid (pKPMC25), three phage sequences and the rmpA virulence gene. No archived Kpp isolates of porcine origin pre-dating 2011 were identified as ST25. In 2013 there was the first detection of an outbreak Kpp isolate showing antimicrobial resistance to six antibiotics. Human infection with Kpp ST25 has not been reported in the UK.

BLUE FUTURES, Blue Opportunities from the future: knowledge and tools to inform sustainable growth for an integrated terrestrial, coastal and marine zone economy

BLUE FUTURES, Blue Opportunities from the future: knowledge and tools to inform sustainable growth for an integrated terrestrial, coastal and marine zone economy

Historic Global Commodity Networks: the Research Potential of Rubbish Dumps for the Study of Rural Household Market Access during the late Nineteenth and Early Twentieth Centuries

AbstractThis article discusses the research potential of rubbish dumps for the study of rural household market access during the late nineteenth and early twentieth centuries. By investigating the global commodity networks associated with four rubbish dumps excavated by the authors in the East Anglian region, at Hempstead (Norfolk), Kirton and Falkenham (Suffolk) and Holme Hale (Norfolk), the article will show how these archives can be used to locate individual rural households within the international capitalist system. This article also discusses the potential challenges faced when analysing the historic rubbish dump archives.

Public engagement with marine climate change issues: (Re)framings, understandings and responses

Climate change impacts on marine environments have been somewhat neglected in climate change research, particularly with regard to their social dimensions and implications. This paper contributes to addressing this gap through presenting a UK focused mixed-method study of how publics frame, understand and respond to marine climate change-related issues. It draws on data from a large national survey of UK publics (N=1,001), undertaken in January 2011 as part of a wider European survey, in conjunction with in-depth qualitative insights from a citizens’ panel with participants from the East Anglia region, UK. This reveals that discrete marine climate change impacts, as often framed in technical or institutional terms, were not the most immediate or significant issues for most respondents. Study participants tended to view these climate impacts ‘in context’, in situated ways, and as entangled with other issues relating to marine environments and their everyday lives. Whilst making connections with scientific knowledge on the subject, public understandings of marine climate impacts were mainly shaped by personal experience, the visibility and proximity of impacts, sense of personal risk and moral or equity-based arguments. In terms of responses, study participants prioritised climate change mitigation measures over adaptation, even in high-risk areas. We consider the implications of these insights for research and practices of public engagement on marine climate impacts specifically, and climate change more generally.

Variation in colorectal cancer treatment and survival: a cohort study covering the East Anglia region

National guidelines for colorectal cancer management aim to optimize cancer outcomes irrespective of postcode. However, in order to ensure equal performance of cancer services, variation in outcome must be monitored and intelligently assessed. In this study, detailed regional cancer registry data were used to quantify and explore the reasons for variation in colorectal cancer outcomes at nine hospitals in East Anglia. We analysed data on colorectal cancers registered by the Eastern Cancer Registry and Information Centre (ECRIC) between 1999 and 2005. Tumours were grouped by site, in keeping with surgical resection. Multivariable Cox regression models were used to identify the effects of patient, disease and treatment variables on an individual's risk of death. After adjusting for demographic, disease and treatment variables there were significant differences in survival among hospitals in emergency admissions with cancer of the right colon, in elective admissions with cancer of the left, sigmoid or recto-sigmoid colon and in emergency admissions with cancer of the rectum. There were also differences among hospitals in terms of perioperative death, nonsurgical management and numbers of nodes examined. For rectal cancers, rates of anterior resection compared with abdominoperineal excision differed, as well as the use of neoadjuvant radiotherapy. Detailed analysis of demographic, disease and treatment factors are required when comparing the survival of individuals with colorectal cancer across hospitals. The results imply that cancer management was not consistent across East Anglia in 1999-2005 but the reasons for this are uncertain. Nevertheless, 5-year age-standardized survival with colon cancer in the Anglia Cancer Network region is currently among the best in the UK.

Predictors of health behaviours among people with recently diagnosed Type 2 diabetes

Background: Behavioural interventions shown to be an effective strategy (in terms of changing behaviour among those at risk) for targeting multiple high risk behaviours in relation Type 2 diabetes. Physical activity plays an important role in the management of Type 2 diabetes. Aims & Objective: The overall aim of study was to identify demographic and psychosocial predictors of change in selfreported physical activity and to identify targets for future interventions. Material and Methods: Participants (N = 478) of this study were all randomized into the ADDITION Plus trial and were recruited from 36 practices in East Anglia region, in U.K. Participants were people recently diagnosed with diabetes (screen detected and clinically diagnosed within the preceding 3 years were individually randomized) and were between the age group of 40-69 years, (mean age 59.2 years). The present study is an observational cohort study. For the current study self-reported data regarding physical activity measured at baseline and one year were used and all demographic (age, sex, ethnic group, age finished full time education, current working status, socioeconomic status) and psychosocial (perceived behaviour control, intention) predictors were assessed at baseline. Linear univariate and multivariable linear regression analysis was used to quantify the associations between demographic and psychosocial correlates. Results: Adjusting for baseline physical activity, only ‘current working status’ and ‘physical activity at baseline’ independently predicted physical activity at one year. No significant associations were found for any other correlates. Conclusion: Present study found very few predictors of physical activity over the year. It is critical to further investigate the change in physical activity by including other correlates related to demography, psycho-social, environmental influences such as family support, physical environment etc. Present findings outline that being employed predicted physical activity over 12 months, accordingly it may be suggested that future interventions should be planned for retired, not working and employed people.

Winter daily precipitation variability over the East Anglian region of Great Britain and its relationship with river flow

This paper investigates winter (DJF) precipitation variability over East Anglia at the daily and 2 d timescales using rain gauge data from 134 sites. The first three principal components (PCs) explain 80.2% (82.0%) of the variance in daily (2 d totals). Precipitation displays higher spatial coherence in winter, with the first three PCs of summer daily totals (Neal and Phillips, 2009, International Journal of Climatology 29: 1661–1679) explaining only 72.3% of the variance. The winter PCs for both 24- and 48-h timescales display precipitation maxima in South Essex (PC 1), NE Norfolk (PC 2), and NW Cambridgeshire (PC 3). The rainfall maximum over South Essex is more important in winter than in summer. Lamb Weather Types and synoptic charts are used to explain the causes of the PCs. A precipitation regionalization is also produced. Discharge for 11 rivers is then modelled as a linear function of the rainfall patterns (as represented by the PC scores). With the exception of the River Babingley, whose discharge is not significantly related to the PCs, these models explain on average 26.5% of the variance. For most rivers, there are significant relationships between discharge and precipitation that fell up to 4 d ago on average. In general, East Anglian river flows show persistence over 6–8 d.

Between Aspiration and Achievement: Structure and Agency in Young Migrant Lives

This article puts forward the argument that young migrants considering Higher and Further Education require robust structural support that attends to their psycho-social, communal, and material needs. Despite evidence of young migrants having high aspirations to achieve in this country, policy in the United Kingdom increasingly presents them with structural barriers rather than structures of support. This argument is based on findings from a recent research project which was conducted in the East Anglian region of the UK with children originally from central and eastern Europe. The children were all aged between 13–15 years and living in designated deprived areas. The article situates the project's findings in the context of the wider literature on aspirations in relation to education and employment, and examines the implications of recent UK government policy changes on the structures impacting on migrant youth's agency to achieve through Higher and Further Education. The authors suggest that migrant students are uncomfortably suspended in the gulf between desires and outcomes, with government policies failing to match the vibrancy of their agency to achieve.

Protocol for the ADDITION-Plus study: a randomised controlled trial of an individually-tailored behaviour change intervention among people with recently diagnosed type 2 diabetes under intensive UK general practice care.

BackgroundThe increasing prevalence of type 2 diabetes poses both clinical and public health challenges. Cost-effective approaches to prevent progression of the disease in primary care are needed. Evidence suggests that intensive multifactorial interventions including medication and behaviour change can significantly reduce cardiovascular morbidity and mortality among patients with established type 2 diabetes, and that patient education in self-management can improve short-term outcomes. However, existing studies cannot isolate the effects of behavioural interventions promoting self-care from other aspects of intensive primary care management. The ADDITION-Plus trial was designed to address these issues among recently diagnosed patients in primary care over one year.Methods/DesignADDITION-Plus is an explanatory randomised controlled trial of a facilitator-led, theory-based behaviour change intervention tailored to individuals with recently diagnosed type 2 diabetes. 34 practices in the East Anglia region participated. 478 patients with diabetes were individually randomised to receive (i) intensive treatment alone (n = 239), or (ii) intensive treatment plus the facilitator-led individual behaviour change intervention (n = 239). Facilitators taught patients key skills to facilitate change and maintenance of key behaviours (physical activity, dietary change, medication adherence and smoking), including goal setting, action planning, self-monitoring and building habits. The intervention was delivered over one year at the participant's surgery and included a one-hour introductory meeting followed by six 30-minute meetings and four brief telephone calls. Primary endpoints are physical activity energy expenditure (assessed by individually calibrated heart rate monitoring and movement sensing), change in objectively measured dietary intake (plasma vitamin C), medication adherence (plasma drug levels), and smoking status (plasma cotinine levels) at one year. We will undertake an intention-to-treat analysis of the effect of the intervention on these measures, an assessment of cost-effectiveness, and analyse predictors of behaviour change in the cohort.DiscussionThe ADDITION-Plus trial will establish the medium-term effectiveness and cost-effectiveness of adding an externally facilitated intervention tailored to support change in multiple behaviours among intensively-treated individuals with recently diagnosed type 2 diabetes in primary care. Results will inform policy recommendations concerning the management of patients early in the course of diabetes. Findings will also improve understanding of the factors influencing change in multiple behaviours, and their association with health outcomes.Trial registrationISRCTN: ISRCTN99175498

Ethnolinguistic vitality and language use amongst Eastern European migrants in East Anglia

This paper discusses language usage patterns amongst Eastern European migrants living in the East Anglia region of Great Britain. It examines the relationship between individual speakers' language use and societal factors, with an emphasis of respondents' perceptions of ethnic, cultural and linguistic vitality. A linguistic vitality and language usage questionnaire adapted from Yagmur, and Yagmur and Akinci, capturing domain-specific language use as well as respondents' perception of their own and other ethnolinguistic groups, was completed by 58 migrants from new European Union member states. Data analysis uncovers three themes: first, language use is domain-specific, with preferences for the L1 in the home/family domain only, and L2 English being the language of choice elsewhere; second, there are low perceptions of ethnolinguistic vitality of the L1 group across the sample; and third, there is initial evidence for a potential longitudinal shift in language use as a result of an integrative attitude to migration by the respondents and long-term plans to reside in the UK from the outset.