Feasibility trial of a film-based educational intervention for increasing boy's and girl's intentions to avoid teenage pregnancy: study protocol

The World Health Organisation, amongst others, recognises that adolescent men have a vital yet neglected role in reducing teenage pregnancies and that there is a pressing need for educational interventions designed especially for them. This study seeks to fill this gap by determining the feasibility of conducting an effectiveness trial of the If I Were Jack intervention in post-primary schools. This 4-week intervention aims to increase teenagers' intentions to avoid unintended pregnancy and addresses gender inequalities in sex education by explicitly focusing on young men. A cluster randomised feasibility trial with embedded process evaluation will determine: recruitment, participation and retention rates; quality of implementation; acceptability and feasibility of the intervention and trial procedures; and costs. (C) 2014 The Authors. Published by Elsevier Ltd.

Serum amyloid A-related inflammation is lowered by increased fruit and vegetable intake, while high-sensitive C-reactive protein, IL-6 and E-selectin remain unresponsive

The present study assessed whether increased fruit and vegetable (F&V) intake reduced the concentrations of the inflammatory marker serum amyloid A (SAA) in serum, HDL2 and HDL3 and whether the latter reduction influenced any of the functional properties of these HDL subfractions. The present study utilised samples from two previous studies: (1) the FAVRIT (Fruit and Vegetable Randomised Intervention Trial) study - hypertensive subjects (systolic blood pressure (BP) range 140-190 mmHg; diastolic BP range 90-110 mmHg) were randomised to receive a 1-, 3- or 6-portion F&V/d intervention for 8 weeks, and (2) the ADIT (Ageing and Dietary Intervention Trial) study - older subjects (65-85 years) were randomised to receive a 2- or 5-portion F&V/d intervention for 16 weeks. HDL2 and HDL3 were isolated by rapid ultracentrifugation. Measurements included the following: serum high-sensitive C-reactive protein (hsCRP) by an immunoturbidimetric assay; serum IL-6 and E-selectin and serum-, HDL2- and HDL3-SAA by ELISA procedures; serum-, HDL2- and HDL3-cholesterol ester transfer protein (CETP) activity by a fluorometric assay. Although the concentrations of hsCRP, IL-6 and E-selectin were unaffected by increasing F&V intake in both studies (P>0·05 for all comparisons), those of SAA in HDL3 decreased in the FAVRIT cohort (P= 0·049) and those in HDL2 and HDL3 decreased in the ADIT cohort (P= 0·035 and 0·032), which was accompanied by a decrease in the activity of CETP in HDL3 in the FAVRIT cohort (P= 0·010) and in HDL2 in the ADIT cohort (P= 0·030). These results indicate that SAA responds to increased F&V intake, while other inflammatory markers remain unresponsive, and this leads to changes in HDL2 and HDL3, which may influence their antiatherogenic potential. Overall, the present study provides tangible evidence of the effectiveness of increased F&V intake, which may be of use to health policy makers and the general public.

Scientific standards for human intervention trials evaluating health benefits of foods, and their application to infants, children and adolescents

Associations between the consumption of particular foods and health outcomes may be indicated by observational studies. However, intervention trials that evaluate the health benefits of foods provide the strongest evidence to support dietary recommendations for health. Thus, it is important that these trials are carried out safely, and to high scientific standards. Accepted standards for the reporting of the health benefits of pharmaceutical and other medical interventions have been provided by the Consolidated Standards of Reporting Trials (CONSORT) statement. However, there are no generally accepted standards for trials to evaluate the health benefits of foods. Trials with foods differ from medical trials in issues related to safety, ethics, research governance and practical implementation. Furthermore, these important issues can deter the conduct of both medical and nutrition trials in infants, children and adolescents. This paper provides standards for the planning, design, conduct, statistical analysis and interpretation of human intervention trials to evaluate the health benefits of foods that are based on the CONSORT guidelines, and outlines the key issues that need to be addressed in trials in participants in the paediatric age range.

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.

Holocene landscape intervention and plant food production strategies in island and mainland Southeast Asia

In the areas adjacent to the drowned Pleistocene continent of Sunda – present-day Mainland and Island SE Asia – the Austronesian Hypothesis of a diaspora of rice cultivators from Taiwan ∼4200 years ago has often been linked with the start of farming. Mounting evidence suggests that these developments should not be conflated and that alternative explanations should be considered, including indigenous inception of complex patterns of plant food production and early exchange of plants, animals, technology and genes. We review evidence for widespread forest disturbance in the Early Holocene which may accompany the beginnings of complex food-production. Although often insubstantial, evidence for incipient and developing management of rainforest vegetation and of developing complex relationships with plants is present, and early enough to suggest that during the Early to mid-Holocene this vast region was marked by different approaches to plant food production. The trajectory of the increasingly complex relationships between people and their food organisms was strongly locally contingent and in many cases did not result in the development of agricultural systems that were recognisable as such at the time of early European encounters. Diverse resource management economies in the Sunda and neighbouring regions appear to have accompanied rather than replaced a reliance on hunting and gathering. This, together with evidence for Early Holocene interaction between these neighbours, gives cause for us to question some authors continued adherence to a singular narrative of the Austronesian Hypothesis and the ‘Neolithisation’ of this part of the world. It also leads us to suggest that the forests of this vast region are, to an extent, a cultural artefact.

SWAT-1: The effectiveness of a 'site visit' intervention on recruitment rates in a multi-centre randomised trial

Background: Recruitment rates in multi-centre randomised trials often fall below target recruitment rates, causing problems for study outcomes. The Studies Within A Trial (SWAT) Programme, established by the All-Ireland Hub for Trials Methodology Research in collaboration with the Medical Research Council Network of Hubs in the United Kingdom and others, is developing methods for evaluating aspects of trial methodology through the conduct of research within research. A recently published design for a SWAT-1 provides a protocol for evaluating the effect of a site visit by the principal investigator on recruitment in multi-centre trials.

Methods: Using the SWAT-1 design, the effect of a site visit, with the sole purpose of discussing trial recruitment, on recruitment rates in a large multicentre trial in the Republic of Ireland was evaluated. A controlled before and after intervention comparison was used, where the date of the site visit provides the time point for the intervention, and for the comparison to control sites. Site A received the intervention. Site B and Site C acted as the controls. Z-scores for proportions were calculated to determine within site recruitment differences. Odds ratios and 95% confidence intervals were calculated to determine between site recruitment differences.

Results: Recruitment rates were increased in Site A post-intervention (17% and 14% percentage point increases at 1 and 3 months, respectively). No differences in recruitment occurred in Site B or in Site C. Comparing between site differences, at 3 months post-intervention, a statistically significant difference was detected in favour of higher recruitment in Site A (34% versus 25%; odds ratio 1.57, 95% confidence interval 1.09 to 2.26).

Conclusions: This is the first reported example of a study in the SWAT programme.. It provides evidence that a site visit, combined with a scheduled meeting, increases recruitment in a clinical trial. Using this example, other researchers might be encouraged to consider conducting a similar study, allowing the findings of future SWAT-1s to be compared and combined, so that higher level evidence on the effect of a site visit by the principal investigator can be obtained.

Combining vitamin C and carotenoid biomarkers better predicts fruit and vegetable intake than individual biomarkers in dietary intervention studies

PURPOSE: The aim of this study was to determine whether combining potential biomarkers of fruit and vegetables is better at predicting FV intake within FV intervention studies than single biomarkers.

DESIGN: Data from a tightly controlled randomised FV intervention study (BIOFAV; all food provided and two meals/day on weekdays consumed under supervision) were used. A total of 30 participants were randomised to either 2, 5 or 8 portions FV/day for 4 weeks, and blood samples were collected at baseline and 4 weeks for plasma vitamin C and serum carotenoid analysis. The combined biomarker approach was also tested in three further FV intervention studies conducted by the same research team, with less strict dietary control (FV provided and no supervised meals).

RESULTS: The combined model containing all carotenoids and vitamin C was a better fit than either the vitamin C only (P < 0.001) model or the lutein only (P = 0.006) model in the BIOFAV study. The C-statistic was slightly lower in the lutein only model (0.85) and in the model based upon factor analysis (0.88), and much lower in the vitamin C model (0.68) compared with the full model (0.95). Results for the other studies were similar, although the differences between the models were less marked.

CONCLUSIONS: Although there was some variation between studies, which may relate to the level of dietary control or participant characteristics, a combined biomarker approach to assess overall FV consumption may more accurately predict FV intake within intervention studies than the use of a single biomarker. The generalisability of these findings to other populations and study designs remains to be tested. 

Developing the clinical components of a complex intervention for a glaucoma screening trial:a mixed methods study

BACKGROUND: Glaucoma is a leading cause of avoidable blindness worldwide. Open angle glaucoma is the most common type of glaucoma. No randomised controlled trials have been conducted evaluating the effectiveness of glaucoma screening for reducing sight loss. It is unclear what the most appropriate intervention to be evaluated in any glaucoma screening trial would be. The purpose of this study was to develop the clinical components of an intervention for evaluation in a glaucoma (open angle) screening trial that would be feasible and acceptable in a UK eye-care service.

METHODS: A mixed-methods study, based on the Medical Research Council (MRC) framework for complex interventions, integrating qualitative (semi-structured interviews with 46 UK eye-care providers, policy makers and health service commissioners), and quantitative (economic modelling) methods. Interview data were synthesised and used to revise the screening interventions compared within an existing economic model.

RESULTS: The qualitative data indicated broad based support for a glaucoma screening trial to take place in primary care, using ophthalmic trained technical assistants supported by optometry input. The precise location should be tailored to local circumstances. There was variability in opinion around the choice of screening test and target population. Integrating the interview findings with cost-effectiveness criteria reduced 189 potential components to a two test intervention including either optic nerve photography or screening mode perimetry (a measure of visual field sensitivity) with or without tonometry (a measure of intraocular pressure). It would be more cost-effective, and thus acceptable in a policy context, to target screening for open angle glaucoma to those at highest risk but for both practicality and equity arguments the optimal strategy was screening a general population cohort beginning at age forty.

CONCLUSIONS: Interventions for screening for open angle glaucoma that would be feasible from a service delivery perspective were identified. Integration within an economic modelling framework explicitly highlighted the trade-off between cost-effectiveness, feasibility and equity. This study exemplifies the MRC recommendation to integrate qualitative and quantitative methods in developing complex interventions. The next step in the development pathway should encompass the views of service users.

Defining the content and delivery of an intervention to Change AdhereNce to treatment in BonchiEctasis (CAN-BE): a qualitative approach incorporating the Theoretical Domains Framework, behavioural change techniques and stakeholder expert panels

Background
Low patient adherence to treatment is associated with poorer health outcomes in bronchiectasis. We sought to use the Theoretical Domains Framework (TDF) (a framework derived from 33 psychological theories) and behavioural change techniques (BCTs) to define the content of an intervention to change patients’ adherence in bronchiectasis (Stage 1 and 2) and stakeholder expert panels to define its delivery (Stage 3).

Methods
We conducted semi-structured interviews with patients with bronchiectasis about barriers and motivators to adherence to treatment and focus groups or interviews with bronchiectasis healthcare professionals (HCPs) about their ability to change patients’ adherence to treatment. We coded these data to the 12 domain TDF to identify relevant domains for patients and HCPs (Stage 1). Three researchers independently mapped relevant domains for patients and HCPs to a list of 35 BCTs to identify two lists (patient and HCP) of potential BCTs for inclusion (Stage 2). We presented these lists to three expert panels (two with patients and one with HCPs/academics from across the UK). We asked panels who the intervention should target, who should deliver it, at what intensity, in what format and setting, and using which outcome measures (Stage 3).

Results
Eight TDF domains were perceived to influence patients’ and HCPs’ behaviours: Knowledge, Skills, Beliefs about capability, Beliefs about consequences, Motivation, Social influences, Behavioural regulation and Nature of behaviours (Stage 1). Twelve BCTs common to patients and HCPs were included in the intervention: Monitoring, Self-monitoring, Feedback, Action planning, Problem solving, Persuasive communication, Goal/target specified:behaviour/outcome, Information regarding behaviour/outcome, Role play, Social support and Cognitive restructuring (Stage 2). Participants thought that an individualised combination of these BCTs should be delivered to all patients, by a member of staff, over several one-to-one and/or group visits in secondary care. Efficacy should be measured using pulmonary exacerbations, hospital admissions and quality of life (Stage 3).

Conclusions
Twelve BCTs form the intervention content. An individualised selection from these 12 BCTs will be delivered to all patients over several face-to-face visits in secondary care. Future research should focus on developing physical materials to aid delivery of the intervention prior to feasibility and pilot testing. If effective, this intervention may improve adherence and health outcomes for those with bronchiectasis in the future.

Modulation of human corticospinal excitability by paired associative stimulation

Paired Associative Stimulation (PAS) has come to prominence as a potential therapeutic intervention for the treatment of brain injury/disease, and as an experimental method with which to investigate Hebbian principles of neural plasticity in humans. Prototypically, a single electrical stimulus is directed to a peripheral nerve in advance of transcranial magnetic stimulation (TMS) delivered to the contralateral primary motor cortex (M1). Repeated pairing of the stimuli (i.e., association) over an extended period may increase or decrease the excitability of corticospinal projections from M1, in manner that depends on the interstimulus interval (ISI). It has been suggested that these effects represent a form of associative long-term potentiation (LTP) and depression (LTD) that bears resemblance to spike-timing dependent plasticity (STDP) as it has been elaborated in animal models. With a large body of empirical evidence having emerged since the cardinal features of PAS were first described, and in light of the variations from the original protocols that have been implemented, it is opportune to consider whether the phenomenology of PAS remains consistent with the characteristic features that were initially disclosed. This assessment necessarily has bearing upon interpretation of the effects of PAS in relation to the specific cellular pathways that are putatively engaged, including those that adhere to the rules of STDP. The balance of evidence suggests that the mechanisms that contribute to the LTP- and LTD-type responses to PAS differ depending on the precise nature of the induction protocol that is used. In addition to emphasizing the requirement for additional explanatory models, in the present analysis we highlight the key features of the PAS phenomenology that require interpretation.

Low alanine aminotransferase levels and higher number of cardiovascular events in people with Type 2 diabetes: analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

AIMS: To determine whether alanine aminotransferase or gamma-glutamyltransferase levels, as markers of liver health and non-alcoholic fatty liver disease, might predict cardiovascular events in people with Type 2 diabetes.

METHODS: Data from the Fenofibrate Intervention and Event Lowering in Diabetes study were analysed to examine the relationship between liver enzymes and incident cardiovascular events (non-fatal myocardial infarction, stroke, coronary and other cardiovascular death, coronary or carotid revascularization) over 5 years.

RESULTS: Alanine aminotransferase level had a linear inverse relationship with the first cardiovascular event occurring in participants during the study period. After adjustment, for every 1 sd higher baseline alanine aminotransferase value (13.2 U/l), the risk of a cardiovascular event was 7% lower (95% CI 4-13; P=0.02). Participants with alanine aminotransferase levels below and above the reference range 8-41 U/l for women and 9-59 U/l for men, had hazard ratios for a cardiovascular event of 1.86 (95% CI 1.12-3.09) and 0.65 (95% CI 0.49-0.87), respectively (P=0.001). No relationship was found for gamma-glutamyltransferase.

CONCLUSIONS: The data may indicate that in people with Type 2 diabetes, which is associated with higher alanine aminotransferase levels because of prevalent non-alcoholic fatty liver disease, a low alanine aminotransferase level is a marker of hepatic or systemic frailty rather than health. This article is protected by copyright. All rights reserved.

DNA microarray profiling of genes differentially regulated by the histone deacetylase inhibitors vorinostat and LBH589 in colon cancer cell lines

BACKGROUND: Despite the significant progress made in colon cancer chemotherapy, advanced disease remains largely incurable and novel efficacious chemotherapies are urgently needed. Histone deacetylase inhibitors (HDACi) represent a novel class of agents which have demonstrated promising preclinical activity and are undergoing clinical evaluation in colon cancer. The goal of this study was to identify genes in colon cancer cells that are differentially regulated by two clinically advanced hydroxamic acid HDACi, vorinostat and LBH589 to provide rationale for novel drug combination partners and identify a core set of HDACi-regulated genes.

METHODS: HCT116 and HT29 colon cancer cells were treated with LBH589 or vorinostat and growth inhibition, acetylation status and apoptosis were analyzed in response to treatment using MTS, Western blotting and flow cytometric analyses. In addition, gene expression was analyzed using the Illumina Human-6 V2 BeadChip array and Ingenuity Pathway Analysis.

RESULTS: Treatment with either vorinostat or LBH589 rapidly induced histone acetylation, cell cycle arrest and inhibited the growth of both HCT116 and HT29 cells. Bioinformatic analysis of the microarray profiling revealed significant similarity in the genes altered in expression following treatment with the two HDACi tested within each cell line. However, analysis of genes that were altered in expression in the HCT116 and HT29 cells revealed cell-line-specific responses to HDACi treatment. In addition a core cassette of 11 genes modulated by both vorinostat and LBH589 were identified in both colon cancer cell lines analyzed.

CONCLUSION: This study identified HDACi-induced alterations in critical genes involved in nucleotide metabolism, angiogenesis, mitosis and cell survival which may represent potential intervention points for novel therapeutic combinations in colon cancer. This information will assist in the identification of novel pathways and targets that are modulated by HDACi, providing much-needed information on HDACi mechanism of action and providing rationale for novel drug combination partners. We identified a core signature of 11 genes which were modulated by both vorinostat and LBH589 in a similar manner in both cell lines. These core genes will assist in the development and validation of a common gene set which may represent a molecular signature of HDAC inhibition in colon cancer.

Improving appropriate polypharmacy for older people in primary care: selecting components of an evidence-based intervention to target prescribing and dispensing.

Background
The use of multiple medicines (polypharmacy) is increasingly common in older people. Ensuring that patients receive the most appropriate combinations of medications (appropriate polypharmacy) is a significant challenge. The quality of evidence to support the effectiveness of interventions to improve appropriate polypharmacy is low. Systematic identification of mediators of behaviour change, using the Theoretical Domains Framework (TDF), provides a theoretically robust evidence base to inform intervention design. This study aimed to (1) identify key theoretical domains that were perceived to influence the prescribing and dispensing of appropriate polypharmacy to older patients by general practitioners (GPs) and community pharmacists, and (2) map domains to associated behaviour change techniques (BCTs) to include as components of an intervention to improve appropriate polypharmacy in older people in primary care.

Methods
Semi-structured interviews were conducted with members of each healthcare professional (HCP) group using tailored topic guides based on TDF version 1 (12 domains). Questions covering each domain explored HCPs’ perceptions of barriers and facilitators to ensuring the prescribing and dispensing of appropriate polypharmacy to older people. Interviews were audio-recorded and transcribed verbatim. Data analysis involved the framework method and content analysis. Key domains were identified and mapped to BCTs based on established methods and discussion within the research team.

Results
Thirty HCPs were interviewed (15 GPs, 15 pharmacists). Eight key domains were identified, perceived to influence prescribing and dispensing of appropriate polypharmacy: ‘Skills’, ‘Beliefs about capabilities’, ‘Beliefs about consequences’, ‘Environmental context and resources’, ‘Memory, attention and decision processes’, ‘Social/professional role and identity’, ‘Social influences’ and ‘Behavioural regulation’. Following mapping, four BCTs were selected for inclusion in an intervention for GPs or pharmacists: ‘Action planning’, ‘Prompts/cues’, ‘Modelling or demonstrating of behaviour’ and ‘Salience of consequences’. An additional BCT (‘Social support or encouragement’) was selected for inclusion in a community pharmacy-based intervention in order to address barriers relating to interprofessional working that were encountered by pharmacists.

Conclusions
Selected BCTs will be operationalised in a theory-based intervention to improve appropriate polypharmacy for older people, to be delivered in GP practice and community pharmacy settings. Future research will involve development and feasibility testing of this intervention.

Exploring inequities in child welfare and child protection services: Explaining the ‘inverse intervention law’

Attempts to record, understand and respond to variations in child welfare and protection reporting, service patterns and outcomes are international, numerous and longstanding. Reframing such variations as an issue of inequity between children and between families opens the way to a new approach to explaining the profound difference in intervention rates between and within countries and administrative districts. Recent accounts of variation have frequently been based on the idea that there is a binary division between bias and risk (or need). Here we propose seeing supply (bias) and demand (risk) factors as two aspects of a single system, both framed, in part, by social structures. A recent finding from a study of intervention rates in England, the 'inverse intervention law', is used to illustrate the complex ways in which a range of factors interact to produce intervention rates. In turn, this analysis raises profound moral, policy, practice and research questions about current child welfare and child protection services.