19 results on '"Dean, Sarah"'
Search Results
2. Integration of HIV pre-exposure prophylaxis (PrEP) services for pregnant and breastfeeding women in eight primary care clinics: results of an implementation science study
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Nelson, Aurelie, Bheemraj, Kalisha, Dean, Sarah Schoetz, de Voux, Alex, Hlatshwayo, Lerato, Mvududu, Rufaro, Berkowitz, Natacha, Neumuller, Caroline, Jacobs, Shahida, Fourie, Stephanie, Coates, Thomas, Gail-Bekker, Linda, Myer, Landon, and Davey, Dvora Joseph
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- 2024
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3. “So that’s why I found PrEP to be safest way to protect yourself”: exploring IPV experiences and impact on HIV prevention among pregnant and postpartum women in Cape Town, South Africa
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Miller, Amanda P., Dean, Sarah Schoetz, Court, Lara, Mvududu, Rufaro, Mashele, Nyiko, Wara, Nafisa J., Myer, Landon, Shoptaw, Steven, and Davey, Dvora L. Joseph
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- 2024
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4. Understanding how therapeutic exercise prescription changes outcomes important to patients with persistent non-specific low back pain: a realist review protocol
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Wood, Lianne, Booth, Vicky, Dean, Sarah, Foster, Nadine E., Hayden, Jill A., and Booth, Andrew
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- 2024
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5. A group-based behavioural intervention for weight management (PROGROUP) versus usual care in adults with severe obesity: a feasibility randomised controlled trial protocol
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Swancutt, Dawn, Tarrant, Mark, Ingram, Wendy, Baldrey, Sarah, Burns, Lorna, Byng, Richard, Calitri, Raff, Creanor, Siobhan, Dean, Sarah, Evans, Lucy, Gill, Laura, Goodwin, Elizabeth, Hawkins, Lily, Hayward, Chris, Hind, Sarah, Hollands, Laura, Hosking, Joanne, Lloyd, Jenny, Moghadam, Shokraneh, Neilens, Helen, O’Kane, Mary, Perry, Steve, Sheaff, Rod, Spencer, Anne, Taylor, Adrian, Ward, Thomas, Watkins, Ross, Wilding, John, and Pinkney, Jonathan
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- 2022
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6. A process evaluation, with mediation analysis, of a web-based intervention to augment primary care exercise referral schemes: the e-coachER randomised controlled trial
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Lambert, Jeffrey, Taylor, Adrian, Streeter, Adam, Greaves, Colin, Ingram, Wendy M., Dean, Sarah, Jolly, Kate, Mutrie, Nanette, Taylor, Rod S., Yardley, Lucy, Price, Lisa, and Campbell, John
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- 2022
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7. Identifying policies and strategies for general practitioner retention in direct patient care in the United Kingdom: a RAND/UCLA appropriateness method panel study
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Chilvers, Rupa, Richards, Suzanne H., Fletcher, Emily, Aylward, Alex, Dean, Sarah, Salisbury, Chris, and Campbell, John
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- 2019
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8. Hope and despair: a qualitative exploration of the experiences and impact of trial processes in a rehabilitation trial
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Norris, Meriel, Poltawski, Leon, Calitri, Raff, Shepherd, Anthony I., Dean, Sarah G., and on behalf of the ReTrain Team
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- 2019
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9. Intervention fidelity in the definitive cluster randomised controlled trial of the Healthy Lifestyles Programme (HeLP) trial: findings from the process evaluation.
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Lloyd, Jenny, Dean, Sarah, Creanor, Siobhan, Abraham, Charles, Hillsdon, Melvyn, Ryan, Emma, and Wyatt, Katrina M.
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PREVENTION of childhood obesity , *CLINICAL trials , *FOOD labeling , *FOOD habits , *HEALTH promotion , *MARKETING , *RESEARCH methodology , *MEDICAL cooperation , *SCIENTIFIC observation , *RESEARCH , *STATISTICAL sampling , *SCHOOL environment , *STUDENT attitudes , *HOME environment , *THEMATIC analysis , *RANDOMIZED controlled trials , *HEALTH literacy , *COLLEGE teacher attitudes , *DESCRIPTIVE statistics , *CHILDREN - Abstract
Background: The Healthy Lifestyles Programme (HeLP) was a novel school-located intervention for 9-10 year olds, designed to prevent obesity by changing patterns of child behaviour through the creation of supportive school and home environments using dynamic and creative delivery methods. This paper reports on both the quantitative and qualitative data regarding the implementation of the HeLP intervention in the definitive cluster randomised controlled trial, which was part of the wider process evaluation. Methods: Mixed methods were used to collect data on intervention uptake, fidelity of delivery in terms of content and quality of delivery of the intervention, as well as school and child engagement with the programme. Data were collected using registers of attendance, observations and checklists, field notes, focus groups with children and semi-structured interviews with teachers. Qualitative data were analysed thematically and quantitative data were summarized using descriptive statistics. Results: All 16 intervention schools received a complete or near complete programme (94-100%), which was delivered in the spirit in which it had been designed. Of the 676 children in the intervention schools, over 90% of children participated in each phase of HeLP; 92% of children across the socio-economic spectrum were deemed to be engaged with HeLP and qualitative data revealed a high level of enjoyment by all children, particularly to the interactive drama workshops. Further evidence of child engagment with the programme was demonstrated by children's clear understanding of programme messages around marketing, moderation and food labelling. Thirteen of the intervention schools were deemed to be fully engaged with HeLP and qualitative data revealed a high level of teacher 'buy in', due to the programme's compatability with the National Curriculum, level of teacher support and use of innovative and creative delivery methods by external drama practitioners. Conclusion: Our trial shows that it is possible to successfully scale up complex school-based interventions, engage schools and children across the socio-economic spectrum and deliver an intervention as designed. As programme integrity was maintained throughout the HeLP trial, across all intervention schools, we can be confident that the trial findings are a true reflection of the effectiveness of the intervention, enabling policy recommendations to be made. Trial registration: ISRCTN15811706. [ABSTRACT FROM AUTHOR]
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- 2017
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10. The Fear Reduction Exercised Early (FREE) approach to low back pain: study protocol for a randomised controlled trial.
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Darlow, Ben, Stanley, James, Dean, Sarah, Abbott, J. Haxby, Garrett, Sue, Mathieson, Fiona, and Dowell, Anthony
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PAIN management ,LUMBAR pain ,GENERAL practitioners ,PSYCHOSOCIAL factors ,RANDOMIZED controlled trials ,COST effectiveness ,HEALTH ,COMPARATIVE studies ,CONVALESCENCE ,FUNCTIONAL assessment ,ECONOMIC aspects of diseases ,EXPERIMENTAL design ,EXERCISE therapy ,FAMILY medicine ,FEAR ,RESEARCH methodology ,MEDICAL care costs ,MEDICAL cooperation ,RESEARCH protocols ,PATIENT satisfaction ,PRIMARY health care ,QUALITY of life ,QUESTIONNAIRES ,RESEARCH ,TIME ,EVALUATION research ,PAIN measurement ,TREATMENT effectiveness ,ECONOMICS ,PSYCHOLOGY ,DIAGNOSIS - Abstract
Background: Low back pain (LBP) is a major health issue associated with considerable health loss and societal costs. General practitioners (GPs) play an important role in the management of LBP; however, GP care has not been shown to be the most cost-effective approach unless exercise and behavioural counselling are added to usual care. The Fear Reduction Exercised Early (FREE) approach to LBP has been developed to assist GPs to manage LBP by empowering exploration and management of psychosocial barriers to recovery and provision of evidence-based care and information. The aim of the Low Back Pain in General Practice (LBPinGP) trial is to explore whether patients with LBP who receive care from GPs trained in the FREE approach have better outcomes than those who receive usual care.Methods/design: This is a cluster randomised controlled superiority trial comparing the FREE approach with usual care for LBP management with investigator-blinded assessment of outcomes. GPs will be recruited and then cluster randomised (in practice groups) to the intervention or control arm. Intervention arm GPs will receive training in the FREE approach, and control arm GPs will continue to practice as usual. Patients presenting to their GP with a primary complaint of LBP will be allocated on the basis of allocation of the GP they consult. We aim to recruit 60 GPs and 275 patients (assuming patients are recruited from 75% of GPs and an average of 5 patients per GP complete the study, accounting for 20% patient participant dropout). Patient participants and the trial statistician will be blind to group allocation throughout the study. Analyses will be undertaken on an intention-to-treat basis. The primary outcome will be back-related functional impairment 6 months post-initial LBP consultation (interim data at 2 weeks, 6 weeks and 3 months), measured with the Roland-Morris Disability Questionnaire. Secondary patient outcomes include pain, satisfaction, quality of life, days off from work and costs of care. Secondary GP outcomes include beliefs about pain and impairment, GP confidence, and actual and reported clinical behaviour. Health economic and process evaluations will be conducted.Discussion: In the LBPinGP trial, we will investigate providing an intervention during the first interaction a person with back pain has with their GP. Because the FREE approach is used within a normal GP consultation, if effective, it may be a cost-effective means of improving LBP care.Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12616000888460 . Registered on 6 July 2016. [ABSTRACT FROM AUTHOR]- Published
- 2017
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11. Trial baseline characteristics of a cluster randomised controlled trial of a school-located obesity prevention programme; the Healthy Lifestyles Programme (HeLP) trial.
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Lloyd, Jenny, Creanor, Siobhan, Price, Lisa, Abraham, Charles, Dean, Sarah, Green, Colin, Hillsdon, Melvyn, Pearson, Virginia, Taylor, Rod S., Tomlinson, Richard, Logan, Stuart, Hurst, Alison, Ryan, Emma, Daurge, Wendy, and Wyatt, Katrina
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PREVENTION of obesity ,HEALTH of school children ,HEALTH programs ,SOCIAL status ,BODY mass index ,RANDOMIZED controlled trials ,PREVENTION of childhood obesity ,BODY weight ,COMPARATIVE studies ,DIET ,EXERCISE ,EXPERIMENTAL design ,FOOD habits ,HEALTH promotion ,RESEARCH methodology ,MEDICAL cooperation ,RESEARCH ,RESEARCH funding ,SCHOOL health services ,EVALUATION research ,WAIST circumference - Abstract
Background: We have developed a healthy lifestyles programme (HeLP) for primary school aged children (9-10 years), currently being evaluated in a definitive cluster randomised controlled trial. This paper descriptively presents the baseline characteristics of trial children (BMI, waist circumference, % body fat, diet and physical activity) by gender, cluster level socio-economic status, school size and time of recruitment into the trial.Methods: Schools were recruited from across the South West of England and allocated 1:1 to either intervention (HeLP) or control (usual practice) stratified by the proportion of children eligible for free school meals (FSM, <19%, ≥19%) and school size (one Year 5 class, >1 Year 5 class). The primary outcome is change in body mass index standard deviation score (BMI sds) at 24 months post-randomisation. Secondary outcomes are BMI sds at 18 months, waist circumference and percentage body fat sds at 18 and 24 months, proportion of children classified as underweight, overweight and obese at 18 and 24 months, physical activity (for a sub-sample) and food intake at 18 months.Results: At baseline 11.4% and 13.6% of children were categorised as overweight or obese respectively. A higher percentage of girls than boys (25.3% vs 24.8%) and children from schools in FSM category 2 (28.2% vs 23.2%) were overweight or obese. Children were consuming a mean (range) of 4.15 (0-13) energy dense snacks (EDS) and 3.23 (0-9) healthy snacks (HS) per day with children from schools in FSM category 2 consuming more EDS and negative food markers and less HS and positive food markers. Children spent an average 53.6 min per day (11.9 to 124.8) in MVPA and thirteen hours (779.3 min) per day (11 h to 15 h) doing less than 'light' intensity activity. Less than 5% of children achieved the Departments of Health's recommendation of 60 min of MVPA every day.Conclusion: We have excellent completeness of baseline data for all measures and have achieved compliance to accelerometry not seen before in other large scale studies. Our anthropometric baseline data is representative of local and national data for children this age and reflects the gender and socio-economic variations expected of children this age in relation to physical activity and weight status.Trial Registration: ISRCTN15811706 (1/05/2012). [ABSTRACT FROM AUTHOR]- Published
- 2017
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12. Opportunities, challenges and concerns for the implementation and uptake of pelvic floor muscle assessment and exercises during the childbearing years: protocol for a critical interpretive synthesis.
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Salmon, Victoria E., C. Hay-Smith, E. Jean, Jarvie, Rachel, Dean, Sarah, Oborn, Eivor, Bayliss, Susan E., Bick, Debra, Davenport, Clare, Ismail, Khaled M., MacArthur, Christine, and Pearson, Mark
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PELVIC floor physiology ,EXERCISE physiology ,PREGNANCY complications - Abstract
Background: Pregnancy and childbirth are important risk factors for urinary incontinence (UI) in women. Pelvic floor muscle exercises (PFME) are effective for prevention of UI. Guidelines for the management of UI recommend offering pelvic floor muscle training (PFMT) to women during their first pregnancy as a preventive strategy. The objective of this review is to understand the relationships between individual, professional, inter-professional and organisational opportunities, challenges and concerns that could be essential to maximise the impact of PFMT during childbearing years and to effect the required behaviour change. Methods: Following systematic searches to identify sources for inclusion, we shall use a critical interpretive synthesis (CIS) approach to produce a conceptual model, mapping the relationships between individual, professional, inter-professional and organisational factors and the implementation, acceptability and uptake of PFME education, assessment and training during the childbearing years. Purposive sampling will be used to identify potentially relevant material relating to topics or areas of interest which emerge as the review progresses. A wide range of empirical and non-empirical sources will be eligible for inclusion to encompass the breadth of relevant individual, professional, inter-professional and organisational issues relating to PFME during childbearing years. Data analysis and synthesis will identify key themes, concepts, connections and relationships between these themes. Findings will be interpreted in relation to existing frameworks of implementation, attitudes and beliefs of individuals and behaviour change. We will collate examples to illustrate relationships expressed in the conceptual model and identify potential links between the model and drivers for change. Discussion: The CIS review findings and resulting conceptual model will illustrate relationships between factors that might affect the implementation, acceptability and uptake of PFME education, assessment and training during the childbearing years. The model will inform the development and evaluation of a training package to support midwives with implementation and delivery of effective PFME during the antenatal period. The review forms part of the first phase of the United Kingdom National Institute for Health Research funded 'Antenatal Preventative Pelvic floor Exercises And Localisation (APPEAL)' programme (grant number: RP-PG-0514-20002) to prevent poor health linked to pregnancy and childbirth-related UI. [ABSTRACT FROM AUTHOR]
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- 2017
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13. Detailed statistical analysis plan for a cluster randomised controlled trial of the Healthy Lifestyles Programme (HeLP), a novel school-based intervention to prevent obesity in school children.
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Creanor, Siobhan, Lloyd, Jenny, Hillsdon, Melvyn, Dean, Sarah, Green, Colin, Taylor, Rod S., Ryan, Emma, and Wyatt, Katrina
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LIFESTYLES & health ,HEALTH programs ,HEALTH care intervention (Social services) ,CHILDHOOD obesity ,SCHOOL children ,RANDOMIZED controlled trials ,JUVENILE diseases - Abstract
Background: The Healthy Lifestyles Programme (HeLP) trial is being conducted to determine whether a novel school-based intervention is effective and cost-effective in preventing obesity in 9-10 year-old children. This article describes the detailed statistical analysis plan for the HeLP trial, including an amendment (and rationale for amendment) made to originally planned sensitivity analyses. Methods and design: The HeLP trial is a definitive, pragmatic, superiority, cluster randomised controlled trial with two parallel groups and blinded outcome assessment. This update article describes in detail (1) the primary and secondary outcomes, (2) the statistical analysis principles (including which children will be included in each analysis, how the clustered nature of the study design will be accounted for, which covariates will be included in each analysis, how the results will be presented), (3) planned sensitivity analyses, planned subgroup analyses and planned adherence-adjusted analyses for the primary outcome, (4) planned analyses for the secondary outcomes and (e) planned longitudinal analyses. [ABSTRACT FROM AUTHOR]
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- 2016
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14. Synthesising practice guidelines for the development of community-based exercise programmes after stroke.
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Poltawski, Leon, Abraham, Charles, Forster, Anne, Goodwin, Victoria A., Kilbride, Cherry, Taylor, Rod S., and Dean, Sarah
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EXERCISE ,EVALUATION of medical care ,CLINICAL medicine ,HEALTH outcome assessment ,PUBLIC health ,PHYSICAL fitness - Abstract
Background: Multiple guidelines are often available to inform practice in complex interventions. Guidance implementation may be facilitated if it is tailored to particular clinical issues and contexts. It should also aim to specify all elements of interventions that may mediate and modify effectiveness, including both their content and delivery. We conducted a focused synthesis of recommendations from stroke practice guidelines to produce a structured and comprehensive account to facilitate the development of community-based exercise programmes after stroke. Methods: Published stroke clinical practice guidelines were searched for recommendations relevant to the content and delivery of community-based exercise interventions after stroke. These were synthesised using a framework based on target intervention outcomes, personal and programme proximal objectives, and recommended strategies. Results: Nineteen guidelines were included in the synthesis (STRIDES; STroke Rehabilitation Intervention- Development Evidence Synthesis). Eight target outcomes, 14 proximal objectives, and 94 recommended strategies were identified. The synthesis was structured to present best practice recommendations in a format that could be used by intervention programme developers. It addresses both programme content and context, including personal factors, service standards and delivery issues. Some recommendations relating to content, and many relating to delivery and other contextual issues, were based on low level evidence or expert opinion. Where opinion varied, the synthesis indicates the range of best practice options suggested in guidelines. Conclusions: The synthesis may assist implementation of best practice by providing a structured intervention description that focuses on a particular clinical application, addresses practical issues involved in programme development and provision, and illustrates the range of best-practice options available to users where robust evidence is lacking. The synthesis approach could be applied to other areas of stroke rehabilitation or to other complex interventions. [ABSTRACT FROM AUTHOR]
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- 2013
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15. Informing the design of a randomised controlled trial of an exercise-based programme for long term stroke survivors: lessons from a before-and-after case series study.
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Poltawski, Leon, Briggs, Jacqueline, Forster, Anne, Goodwin, Victoria A., James, Martin, Taylor, Rod S., and Dean, Sarah
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STROKE ,PHYSICAL activity ,FEASIBILITY studies ,COMMUNITY-based clinical trials ,QUALITY of life - Abstract
Background: To inform the design of a randomised controlled trial (RCT) of an exercise-based programme for long term stroke survivors, we conducted a mixed methods before-and-after case series with assessment at three time points. We evaluated Action for Rehabilitation from Neurological Injury (ARNI), a personalised, functionally-focussed programme. It was delivered through 24 hours of one-to-one training by an Exercise Professional (EP), plus at least 2 hours weekly unsupervised exercise, over 12- 14 weeks. Assessment was by patient-rated questionnaires addressing function, physical activity, confidence, fatigue and health-related quality of life; objective assessment of gait quality and speed; qualitative individual interviews conducted with participants. Data were collected at baseline, 3 months and 6 months. Fidelity and acceptability was assessed by participant interviews, audit of participant and EP records, and observation of training. Findings: Four of six enrolled participants completed the exercise programme. Quantitative data demonstrated little change across the sample, but marked changes on some measures for some individuals. Qualitative interviews suggested that small benefits in physical outcomes could be of great psychological significance to participants. Participant-reported fatigue levels commonly increased, and non-completers said they found the programme too demanding. Most key components of the intervention were delivered, but there were several potentially important departures from intervention fidelity. Discussion: The study provided data and experience that are helping to inform the design of an RCT of this intervention. It suggested the need for a broader recruitment strategy; indicated areas that could be explored in more depth in the qualitative component of the trial; and highlighted issues that should be addressed to enhance and evaluate fidelity, particularly in the preparation and monitoring of intervention providers. The experience illustrates the value of even small sample before-and-after studies in the development of trials of complex interventions [ABSTRACT FROM AUTHOR]
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- 2013
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16. The Healthy Lifestyles Programme (HeLP), a novel school-based intervention to prevent obesity in school children: study protocol for a randomised controlled trial.
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Wyatt, Katrina M., Lloyd, Jennifer J., Abraham, Charles, Creanor, Siobhan, Dean, Sarah, Densham, Emma, Daurge, Wendy, Green, Colin, Hillsdon, Melvyn, Pearson, Virginia, Taylor, Rod S., Tomlinson, Richard, and Logan, Stuart
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PREVENTION of obesity ,SCHOOL children ,HEALTH behavior ,CLINICAL trials ,CLINICAL medicine ,JUVENILE diseases - Abstract
Background: Over the last three decades there has been a substantial increase in the proportion of children who are overweight or obese. The Healthy Lifestyles Programme (HeLP) is a novel school-based intervention, using highly interactive and creative delivery methods to prevent obesity in children. Methods/Design: We describe a cluster randomised controlled trial to evaluate the effectiveness and cost effectiveness of HeLP. The intervention has been developed using intervention mapping (involving extensive stakeholder involvement) and has been guided by the Information, Motivation, Behavioural Skills model. HeLP includes creating a receptive environment, drama activities, goal setting and reinforcement activities and runs over three school terms. Piloting showed that 9 to 10 year olds were the most receptive and participative. This study aims to recruit 1,300 children from 32 schools (over half of which will have ⩾19% of pupils eligible for free school meals) from the southwest of England. Participating schools will be randomised to intervention or control groups with baseline measures taken prior to randomisation. The primary outcome is change in body mass index standard deviation score (BMI SDS) at 24 months post baseline. Secondary outcomes include, waist circumference and percent body fat SDS and proportion of children classified as overweight or obese at 18 and 24 months and objectively measured physical activity and food intake at 18 months. Between-group comparisons will be made using random effects regression analysis taking into account the hierarchical nature of the study design. An economic evaluation will estimate the incremental cost-effectiveness of HeLP, compared to control, from the perspective of the National Health Service (NHS)/third party payer. An in-depth process evaluation will provide insight into how HeLP works, and whether there is any differential uptake or engagement with the programme. Discussion: The results of the trial will provide evidence on the effectiveness and cost effectiveness of the Healthy Lifestyles Programme in affecting the weight status of children. [ABSTRACT FROM AUTHOR]
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- 2013
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17. An indigenous approach to explore health-related experiences among Māori parents: the Pukapuka Hauora asthma study.
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Jones, Bernadette, Ingham, Tristram R., Cram, Fiona, Dean, Sarah, and Davies, Cheryl
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ASTHMA in children ,DISEASES in teenagers ,DISEASE prevalence ,SYMPTOMS ,HOSPITAL care - Abstract
Background: The prevalence of asthma for Indigenous New Zealand Māori is amongst the highest in the world. Recent evidence shows ethnic differences in asthma symptom prevalence in New Zealand have widened, with asthma symptoms and hospitalisation rates consistently higher for Māori across all age-groups, especially children and adolescents. This paper: outlines our qualitative, longitudinal research exploring the practical issues Māori children and their families face trying to achieve optimum asthma outcomes; details the research methods used within this study; and discusses the process evaluation findings of the features that made this approach successful in engaging and retaining participants in the study. Methods: Thirty-two Māori families were recruited using a Kaupapa Māori (Māori way) Research approach. Each participated in a series of four in-depth interviews that were carried out at seasonal intervals over the course of one year. Families also took part in an interviewer-administered questionnaire and participated in a Photovoice exercise. All interviews were digitally recorded, transcribed verbatim and independently coded by two researchers. The research team then conducted the analysis and theme development. The questionnaires were analysed separately, with explanations for findings explored within the qualitative data. Results: The methodology produced a 100 percent retention rate of the participating families over the course of the follow-up. This was attributed to the research collaboration, the respectful research relationships established with families, and the families' judgement that the methods used enabled them to tell their stories. The acceptability of the methodology will add to the validity and trustworthiness of the findings. Conclusion: Given the extent and persistence of ethnic disparities in childhood asthma management, it is imperative that an indigenous approach be taken to understanding the core issues facing Māori families. By conducting community-partnership research underpinned by an indigenous methodology, and employing a range of appropriate methods, we have successfully recruited and retained a cohort of Māori families with experiences of childhood asthma. We aim to make their voices heard in order to develop a series of culturally relevant interventions aimed at remediating these disparities. [ABSTRACT FROM AUTHOR]
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- 2013
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18. Triple-negative breast cancer and PTEN (phosphatase and tensin homologue)loss are predictors of BRCA1 germline mutations in women with early-onset and familial breast cancer, but not in women with isolated late-onset breast cancer.
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Sze-Yee Phuah, Lai-Meng Looi, Norhashimah Hassan, Rhodes, Anthony, Dean, Sarah, Aishah Mohd Taib, Nur, Cheng-Har Yip, and Soo-Hwang Teo
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BREAST cancer patients ,PHOSPHATASES ,GERM cells ,GENETIC mutation ,GENE amplification ,LOGISTIC regression analysis ,ESTROGEN receptors - Abstract
Introduction: Given that breast cancers in germline BRCA1 carriers are predominantly estrogen-negative and triple-negative, it has been suggested that women diagnosed with triple-negative breast cancer (TNBC) younger than 50 years should be offered BRCA1 testing, regardless of family cancer characteristics. However, the predictive value of triple-negative breast cancer, when taken in the context of personal and family cancer characteristics, is unknown. The aim of this study was to determine whether TNBC is a predictor of germline BRCA1 mutations, in the context of multiple predictive factors. Methods: Germline mutations in BRCA1 and BRCA2 were analyzed by Sanger sequencing and multiple ligation-dependent probe amplification (MLPA) analysis in 431 women from the Malaysian Breast Cancer Genetic Study, including 110 women with TNBC. Logistic regression was used to identify and to estimate the predictive strength of major determinants. Estrogen receptor (ER) and phosphatase and tensin homologue (PTEN) status were assessed and included in a modified Manchester scoring method. Results: Our study in an Asian series of TNBC patients demonstrated that 27 (24.5%) of 110 patients have germline mutations in BRCA1 (23 of 110) and BRCA2 (four of 110). We found that among women diagnosed with breast cancer aged 36 to 50 years but with no family history of breast or ovarian cancer, the prevalence of BRCA1 and BRCA2 mutations was similar in TNBC (8.5%) and non-TNBC patients (6.7%). By contrast, in women diagnosed with breast cancer, younger than 35 years, with no family history of these cancers, and in women with a family history of breast cancer, the prevalence of mutations was higher in TNBC compared with non-TNBC (28.0% and 9.9%; P = 0.045; and 42.1% and 14.2%; P < 0.0001, respectively]. Finally, we found that incorporation of estrogen-receptor and TNBC status improves the sensitivity of the Manchester Scoring method (42.9% to 64.3%), and furthermore, incorporation of PTEN status further improves sensitivity (42.9% to 85.7%). Conclusions: We found that TNBC is an important criterion for highlighting women who may benefit from genetic testing, but that this may be most useful for women with early-onset breast cancer (35 years or younger) or with a family history of cancers. Furthermore, addition of TNBC and PTEN status improves the sensitivity of the Manchester scoring method and may be particularly important in the Asian context, where risk-assessment models underestimate the number of mutation carriers. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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19. Triple-negative breast cancer and PTEN (phosphatase and tensin homologue) loss are predictors of BRCA1 germline mutations in women with early-onset and familial breast cancer, but not in women with isolated late-onset breast cancer.
- Author
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Phuah, Sze-Yee, Looi, Lai-Meng, Hassan, Norhashimah, Rhodes, Anthony, Dean, Sarah, Taib, Nur, Yip, Cheng-Har, Teo, Soo-Hwang, and Taib, Nur Aishah Mohd
- Abstract
Introduction: Given that breast cancers in germline BRCA1 carriers are predominantly estrogen-negative and triple-negative, it has been suggested that women diagnosed with triple-negative breast cancer (TNBC) younger than 50 years should be offered BRCA1 testing, regardless of family cancer characteristics. However, the predictive value of triple-negative breast cancer, when taken in the context of personal and family cancer characteristics, is unknown. The aim of this study was to determine whether TNBC is a predictor of germline BRCA1 mutations, in the context of multiple predictive factors.Methods: Germline mutations in BRCA1 and BRCA2 were analyzed by Sanger sequencing and multiple ligation-dependent probe amplification (MLPA) analysis in 431 women from the Malaysian Breast Cancer Genetic Study, including 110 women with TNBC. Logistic regression was used to identify and to estimate the predictive strength of major determinants. Estrogen receptor (ER) and phosphatase and tensin homologue (PTEN) status were assessed and included in a modified Manchester scoring method.Results: Our study in an Asian series of TNBC patients demonstrated that 27 (24.5%) of 110 patients have germline mutations in BRCA1 (23 of 110) and BRCA2 (four of 110). We found that among women diagnosed with breast cancer aged 36 to 50 years but with no family history of breast or ovarian cancer, the prevalence of BRCA1 and BRCA2 mutations was similar in TNBC (8.5%) and non-TNBC patients (6.7%). By contrast, in women diagnosed with breast cancer, younger than 35 years, with no family history of these cancers, and in women with a family history of breast cancer, the prevalence of mutations was higher in TNBC compared with non-TNBC (28.0% and 9.9%; P = 0.045; and 42.1% and 14.2%; P < 0.0001, respectively]. Finally, we found that incorporation of estrogen-receptor and TNBC status improves the sensitivity of the Manchester Scoring method (42.9% to 64.3%), and furthermore, incorporation of PTEN status further improves sensitivity (42.9% to 85.7%).Conclusions: We found that TNBC is an important criterion for highlighting women who may benefit from genetic testing, but that this may be most useful for women with early-onset breast cancer (35 years or younger) or with a family history of cancers. Furthermore, addition of TNBC and PTEN status improves the sensitivity of the Manchester scoring method and may be particularly important in the Asian context, where risk-assessment models underestimate the number of mutation carriers. [ABSTRACT FROM AUTHOR]- Published
- 2012
- Full Text
- View/download PDF
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