Using postal questionnaires to evaluate physical activity and diet behaviour change: case study exploring implications of valid responder characteristics in interpreting intervention outcomes.

Background: Patient reported outcome measures (PROMs) are used to evaluate lifestyle interventions but littleis known about differences between patients returning valid and invalid responses, or of potential for bias inevaluations. We aimed to examine the characteristics of patients who returned valid responses to lifestylequestionnaires compared to those whose responses were invalid for evaluating lifestyle change. 
Methods: We conducted a secondary data analysis from the SPHERE Study, a trial of an intervention to improveoutcomes for patients with coronary heart disease in primary care. Postal questionnaires were used to assessphysical activity (Godin) and diet (DINE) among study participants at baseline and 18 month follow-up. Three binaryresponse variables were generated for analysis: (1) valid Godin score; (2) valid DINE Fibre score; and (3) validDINE Total Fat score. Multivariate analysis comprised generalised estimating equation regression to examine theassociation of patients’ characteristics with their return of valid responses at both timepoints. 
Results: Overall, 92.1% of participants (832/903) returned questionnaires at both baseline and 18 months. Relativelyfewer valid Godin scores were returned by those who left school aged <15 years (36.5%) than aged 18 and over(50.5%), manual workers (39.5%) than non-manual (49.5%) and those with an elevated cholesterol (>5 mmol)(34.7%) than those with a lower cholesterol (44.4%) but multivariate analysis identified that only school leaving age(p = 0.047) was of statistical significance.Relatively fewer valid DINE scores were returned by manual than non-manual workers (fibre: 80.8% v 86.8%;fat: 71.2% v 80.0%), smokers (fibre: 72.6% v 84.7%; fat: 67.5% v 76.9%), patients with diabetes (fibre: 75.9% v 82.9%;fat: 66.9% v 75.8%) and those with cholesterol >5 mmol (fat: 68.2% v 76.2%) but multivariate analysis showedstatistical significance only for smoking (fibre: p = 0.013; fat: p = 0.045), diabetes (fibre: p = 0.039; fat: p = 0.047), andcholesterol (fat: p = 0.039). 
Conclusions: Our findings illustrate the importance of detailed reporting of research methods, with clearinformation about response rates, respondents and valid outcome data. Outcome measures which are relevant to astudy population should be chosen carefully. The impact of methods of outcome measurement and valid responserates in evaluating healthcare requires further study.

Minimal intervention dentistry and older patients Part 1: Risk assessment and caries prevention

Ten million people in the UK today are aged over 65. The latest projections estimate that there will be 5 1/2 million more people aged 65 and older in the next 20 years. This projected pattern of population ageing will have profound consequences for dentistry. Minimal intervention dentistry (MID) is a modern evidence-based approach to caries management in dentate patients that uses the 'medical model' whereby disease is controlled by the 'oral physician'. This approach offers considerable benefits over conventional dentistry for older patients. It encourages patients to be responsible for their oral health through the provision of both knowledge and motivation. MID encompasses risk assessment for dental disease, early detection and control of disease processes, and minimally invasive treatment. 

Clinical Relevance: Risk assessment tools can aid the general dental practitioner and the patient to develop a suitable caries prevention programme for that individual and reduce the need for future operative intervention.

Stereotactic Body Radiotherapy for Oligometastatic Disease

Stereotactic body radiotherapy (SBRT) is now an established therapy in stage I lung cancer with comparable local control rates to surgical resection. Owing to the conformity of treatment dose delivery and with appropriate fractionation considerations, minimal side-effects to surrounding normal tissues are observed in most patients. SBRT is now being used in the treatment of oligometastatic disease, alone or alongside systemic therapy. At present there is a paucity of evidence available showing a clinical benefit, but several international studies are being set-up or have started recruitment. This overview considers the clinical entity of an oligometastatic state, discusses the role of SBRT in the management of oligometastatic disease and discusses potential novel therapy combinations with SBRT.

Distinct methylation patterns in genes that affect mitochondrial function are associated with kidney disease in blood-derived DNA from individuals with Type 1 diabetes

AIMS: Epigenetic modifications, such as DNA methylation, can influence the risk of developing kidney disease. We studied methylation profiles in genes related to mitochondrial function to assess whether differences in these epigenetic features were associated with diabetic kidney disease in people with Type 1 diabetes.

METHODS: A case-control association study was undertaken (n = 196 individuals with diabetic kidney disease vs. n = 246 individuals without renal disease). Participants were White and diagnosed with Type 1 diabetes before 31 years of age. Genes that encode mitochondrial proteins (n = 780) were downloaded from mitoproteome. org. DNA methylation profiles from blood-derived DNA were generated using the Illumina Infinium HumanMethylation450 (262 samples) and Illumina Infinium HumanMethylation27 (192 samples) arrays. Beta values (β) were calculated and quality control was conducted, including evaluating blind duplicate DNA samples.

RESULTS: Fifty-four Cytosine-phosphate-Guanine probes across 51 unique genes were significantly associated (P ≤ 10(-8) ) with diabetic kidney disease across both the 450K and the 27K methylation arrays. A subanalysis, employing the 450K array, identified 755 Cytosine-phosphate-Guanine probes in 374 genes that were significantly associated (P ≤ 10(-8) ) with end-stage renal disease. Forty-six of the top-ranked variants for diabetic kidney disease were also identified as being differentially methylated in individuals with end-stage renal disease. The largest change in methylation (Δβ = 0.2) was observed for cg03169527 in the TAMM41 gene, chromosome 3p25.2. Three genes, PMPCB, TSFM and AUH, were observed with differential methylation at multiple Cytosine-phosphate-Guanine sites each (P < 10(-12) ).

CONCLUSIONS: Differential methylation in genes that influence mitochondrial function are associated with kidney disease in individuals with Type 1 diabetes. 

Deriving meteorological variables across Africa for the study and control of vector-borne disease:a comparison of remote sensing and spatial interpolation of climate

This paper presents the results of an investigation into the utility of remote sensing (RS) using meteorological satellites sensors and spatial interpolation (SI) of data from meteorological stations, for the prediction of spatial variation in monthly climate across continental Africa in 1990. Information from the Advanced Very High Resolution Radiometer (AVHRR) of the National Oceanic and Atmospheric Administration's (NOAA) polar-orbiting meteorological satellites was used to estimate land surface temperature (LST) and atmospheric moisture. Cold cloud duration (CCD) data derived from the High Resolution Radiometer (HRR) onboard the European Meteorological Satellite programme's (EUMETSAT) Meteosat satellite series were also used as a RS proxy measurement of rainfall. Temperature, atmospheric moisture and rainfall surfaces were independently derived from SI of measurements from the World Meteorological Organization (WMO) member stations of Africa. These meteorological station data were then used to test the accuracy of each methodology, so that the appropriateness of the two techniques for epidemiological research could be compared. SI was a more accurate predictor of temperature, whereas RS provided a better surrogate for rainfall; both were equally accurate at predicting atmospheric moisture. The implications of these results for mapping short and long-term climate change and hence their potential for the study anti control of disease vectors are considered. Taking into account logistic and analytical problems, there were no clear conclusions regarding the optimality of either technique, but there was considerable potential for synergy.

Did the Millennium Development Goals Change Trends in Child Mortality?

There has been little assessment of the role the MDGs have had in progressing international development. There has been a 41 per cent reduction in the under-5 mortality rate worldwide from 1990 to 2011 and an acceleration in the rate of reduction since 2000. This paper explores why this has occurred and results for all developing countries indicate that it is not due to more healthcare or public health interventions but is driven by a coincidental burst of economic growth. Although the MDGs are considered to have played an important part in securing progress against poverty, hunger and disease there is very little evidence to back this viewpoint up. A thorough analysis of the successes and failures of the MDGs is therefore necessary before embarking on a new round of global goals.

Increasing Fruit and Vegetable Intake Has No Dose-Response Effect on Conventional Cardiovascular Risk Factors in Overweight Adults at High Risk of Developing Cardiovascular Disease

BACKGROUND: Improving diet and lifestyle is important for prevention of cardiovascular disease (CVD). Observational evidence suggests that increasing fruit and vegetable (FV) consumption may lower CVD risk, largely through modulation of established risk factors, but intervention data are required to fully elucidate the mechanisms by which FVs exert benefits on vascular health.

OBJECTIVE: The aim of this study was to examine the dose-response effect of FV intake on cardiovascular risk factors in adults at high CVD risk.

METHODS: This was a randomized controlled parallel group study involving overweight adults (BMI: >27 and ≤35 kg/m(2)) with a habitually low FV intake (≤160 g/d) and a high total risk of developing CVD (estimated ≥20% over 10 y). After a 4-wk run-in period where FV intake was limited to <2 portions/d (<160 g/d), 92 eligible participants were randomly assigned to 1 of 3 groups: to consume either 2, 4, or 7 portions (equivalent to 160 g, 320 g, or 560 g, respectively) of FVs daily for 12 consecutive weeks. Fasting venous blood samples were collected at baseline (week 4) and post-intervention (week 16) for analysis of lipid fractions and high-sensitivity C-reactive protein (hsCRP) concentrations. Compliance with the FV intervention was determined with use of self-reported FV intake and biomarkers of micronutrient status. Ambulatory blood pressure and body composition were also measured pre- and post-intervention.

RESULTS: A total of 89 participants completed the study and body composition remained stable throughout the intervention period. Despite good compliance with the intervention, no significant difference was found between the FV groups for change in measures of ambulatory blood pressure, plasma lipids, or hsCRP concentrations.

CONCLUSIONS: There was no evidence of a dose-response effect of FV intake on conventional CVD risk factors measured in overweight adults at high CVD risk. This trial was registered at clinicaltrials.gov as NCT00874341.

Differential ecological impacts of an invader and a native under environmental change are revealed by comparative functional responses.

Predicting the ecological impacts of damaging invasive species under relevant environmental contexts is a major challenge, for which comparative functional responses (the relationship between resource availability and consumer uptake rate) have great potential. Here, the functional responses of Gammarus pulex, an ecologically damaging invader in freshwaters in Ireland and other islands, were compared with those of a native trophic equivalent Gammarus duebeni celticus. Experiments were conducted at two dissolved oxygen concentrations (80 and 50 % saturation), representative of anthropogenic water quality changes, using two larval prey, blackfly (Simuliidae spp.) and mayfly (Baetis rhodani). Overall, G. pulex had higher Type II functional responses and hence predatory impacts than G. d. celticus and the functional responses of both predators were reduced by lowered oxygen concentration. However, this reduction was of lower magnitude for the invader as compared to the native. Further, the invader functional response at low oxygen was comparable to that of the native at high oxygen. Attack rates of the two predators were similar, with low oxygen reducing these attack rates, but this effect occurred more strongly for blackfly than mayfly prey. Handling times were significantly lower for the invader compared with the native, and significantly higher at low oxygen, however, the effect of lowered oxygen on handling times was minimal for the invader and pronounced for the native. Maximum feeding rates were significantly greater for the invader compared with the native, and significantly reduced at low oxygen, with this effect again lesser for the invader as compared to the native. The greater functional responses of the invader corroborate with its impacts on recipient macroinvertebrate communities when it replaces the native. Further, our experiments predict that the impact of the invader will be less affected than the native under altered oxygen regimes driven by anthropogenic influences.

Genetically Determined Height and Coronary Artery Disease

Background: The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear. 
Methods: We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes. 
Results: We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; P<0.001) in the risk of CAD per 1-SD decrease in genetically determined height. There was a graded relationship between the presence of an increased number of height-raising variants and a reduced risk of CAD (odds ratio for height quartile 4 versus quartile 1, 0.74; 95% CI, 0.68 to 0.84; P<0.001). Of the 12 risk factors that we studied, we observed significant associations only with levels of low-density lipoprotein cholesterol and triglycerides (accounting for approximately 30% of the association). We identified several overlapping pathways involving genes associated with both development and atherosclerosis. 
Conclusions: There is a primary association between a genetically determined shorter height and an increased risk of CAD, a link that is partly explained by the association between shorter height and an adverse lipid profile. Shared biologic processes that determine achieved height and the development of atherosclerosis may explain some of the association. (Funded by the British Heart Foundation and others.)

Six-year follow-up of the SPHERE RCT: secondary prevention of heart disease in general practice.

Objective: To determine the long-term effectiveness of a complex intervention in primary care aimed at improving outcomes for patients with coronary heart disease.

Design: A 6-year follow-up of a cluster randomised controlled trial, which found after 18 months that both total and cardiovascular hospital admissions were significantly reduced in intervention practices (8% absolute reduction).

Setting: 48 general practices in the Republic of Ireland and Northern Ireland.

Participants: 903 patients with established coronary heart disease at baseline in the original trial.

Intervention: The original intervention consisted of tailored practice and patient plans; training sessions for practitioners in medication prescribing and behavioural change; and regular patient recall system. Control practices provided usual care. Following the intervention period, all supports from the research team to intervention practices ceased.

Outcome measures: Primary outcome: hospital admissions, all cause and cardiovascular; secondary outcomes: mortality; blood pressure and cholesterol control.

Results: At 6-year follow-up, data were collected from practice records of 696 patients (77%). For those who had died, we censored their data at the point of death and cause of death was established. There were no significant differences between the intervention and control practices in either total (OR 0.83 (95% CI 0.54 to 1.28)) or cardiovascular hospital admissions (OR 0.91 (95% CI 0.49 to 1.65)). We confirmed mortality status of 886 of the original 903 patients (98%). There were no significant differences in mortality (15% in intervention and 16% in control) or in the proportions of patients above target control for systolic blood pressure or total cholesterol.

Conclusions: Initial significant differences in the numbers of total and cardiovascular hospital admissions were not maintained at 6 years and no differences were found in mortality or blood pressure and cholesterol control. Policymakers need to continue to assess the effectiveness of previously efficacious programmes.

Trial registration number: Current Controlled Trials ISRCTN24081411.

Alzheimer's disease-like pathology has transient effects on the brain and blood metabolome

The pathogenesis of Alzheimer's disease (AD) is complex involving multiple contributing factors. The extent to which AD pathology impacts upon the metabolome is still not understood, nor is it known how disturbances change as the disease progresses. For the first time we have profiled longitudinally (6, 8, 10, 12 and 18 months) both the brain and plasma metabolome of APP/PS1 double transgenic and wild type (WT) mice. A total of 187 metabolites were quantified using a targeted metabolomics methodology. Multivariate statistical analysis produced models that distinguished APP/PS1 from WT mice at 8, 10 and 12 months.Metabolic pathway analysis found perturbed polyamine metabolism in both brain and blood plasma. There were other disturbances in essential amino acids,branched chain amino acids and also in the neurotransmitter serotonin.Pronounced imbalances in phospholipid and acylcarnitine homeostasis was evident in two age groups. AD-like pathology therefore impacts greatly on both the brain and blood metabolomes, although there appears to be a clear temporal sequence whereby changes to brain metabolites precede those in blood.

A monster that lives in our lives - experiences of caregivers of people with motor neuron disease and identifying avenues for support.

Background A developing body of evidence has provided valuable insight into the experiences of caregivers of people with motor neuron disease; however, understandings of how best to support caregivers remain limited.

Aim This study sought to understand concepts related to the motor neuron disease caregiver experience which could inform the development of supportive interventions.

Design A qualitative thematic analysis of a one-off semistructured interview with caregivers was undertaken.

Setting/participants Caregivers of people with motor neuron disease were recruited from a progressive neurological diseases clinic in Melbourne, Australia.

Results 15 caregivers participated. Three key themes were identified: (1) The Thief: the experience of loss and grief across varied facets of life; (2) The Labyrinth: finding ways to address ever changing challenges as the disease progressed; (3) Defying fate: being resilient and hopeful as caregivers tried to make the most of the time remaining.

Conclusions Caregivers are in need of more guidance and support to cope with experiences of loss and to adapt to changeable care giving duties associated with disease progression. Therapeutic interventions which target these experiences of loss and change are worth investigation.

Chapter Six – The Increase of Exotic Zoonotic Helminth Infections: The Impact of Urbanization, Climate Change and Globalization

Zoonotic parasitic diseases are increasingly impacting human populations due to the effects of globalization, urbanization and climate change. Here we review the recent literature on the most important helminth zoonoses, including reports of incidence and prevalence. We discuss those helminth diseases which are increasing in endemic areas and consider their geographical spread into new regions within the framework of globalization, urbanization and climate change to determine the effect these variables are having on disease incidence, transmission and the associated challenges presented for public health initiatives, including control and elimination.

Behaviour change techniques in home-based cardiac rehabilitation: a systematic review

BACKGROUND: Cardiac rehabilitation (CR) programmes offering secondary prevention for cardiovascular disease (CVD) advise healthy lifestyle behaviours, with the behaviour change techniques (BCTs) of goals and planning, feedback and monitoring, and social support recommended. More information is needed about BCT use in home-based CR to support these programmes in practice.

AIM: To identify and describe the use of BCTs in home-based CR programmes.

DESIGN AND SETTING: Randomised controlled trials of home-based CR between 2005 and 2015 were identified by searching MEDLINE(®), Embase, PsycINFO, Web of Science, and Cochrane Database.

METHOD: Reviewers independently screened titles and abstracts for eligibility. Relevant data, including BCTs, were extracted from included studies. A meta-analysis studied risk factor change in home-based and comparator programmes.

RESULTS: From 2448 studies identified, 11 of good methodological quality (10 on post-myocardial infarction, one on heart failure, 1907 patients) were included. These reported the use of 20 different BCTs. Social support (unspecified) was used in all studies and goal setting (behaviour) in 10. Of the 11 studies, 10 reported effectiveness in reducing CVD risk factors, but one study showed no improvement compared to usual care. This study differed from effective programmes in that it didn't include BCTs that had instructions on how to perform the behaviour and monitoring, or a credible source.

CONCLUSION: Social support and goal setting were frequently used BCTs in home-based CR programmes, with the BCTs related to monitoring, instruction on how to perform the behaviour, and credible source being included in effective programmes. Further robust trials are needed to determine the relative value of different BCTs within CR programmes.

The Great Transition:Climate, disease and society in the late-medieval world

In the fourteenth century the Old World witnessed a series of profound and abrupt changes in the trajectory of long-established historical trends. Trans-continental networks of exchange fractured and an era of economic contraction and demographic decline dawned from which Latin Christendom would not begin to emerge until its voyages of discovery at the end of the fifteenth century. In a major new study of this 'Great Transition', assessment is made of the contributions of commercial recession, war, climate change,and eruption of the Black Death to a far-reaching reversal of fortunes which spared no part of Eurasia. A wealth of new historical, palaeoecological and biological evidence are synthesised, including estimates of national income, reconstructions of past climates. and genetic analysis of DNA extracted from the teeth of plague victims, to provide a fresh account of the creation, collapse and realignment of western Europe's late-medieval commercial economy.