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Background: Few adolescent girls engage in enough physical activity (PA) to meet recommendations and there is a need for new interventions to increase girls PA. We have previously published the results of the PLAN-A cluster randomised feasibility trial which was a peer-led school-based PA intervention, showing that the intervention was feasible and held promise to increase the PA of girls aged 12-13 years. In PLAN-A, pupils nominated by their peers as influential attend training to teach them how to influence, promote and normalise physical activity amongst their peer-group. This paper reports the results of the process evaluation of the PLAN-A feasibility study, specifically focussing on acceptability to key stakeholders, intervention fidelity, receipt/experiences and perceived effect and suggested intervention refinements before proceeding to a definitive RCT., Methods: A mixed-methods process evaluation triangulated data from qualitative focus groups and interviews with peer-supporter and non peer-supporter pupils (N = 52), parents (N = 12), teachers (N = 6) and intervention training deliverers (N = 5), quantitative questionnaires, and observations of intervention delivery. Quantitative data were analysed descriptively, and qualitative data were analysed with the Framework Method., Results: The duration, timings, content and delivery of the peer-supporter training were acceptable. There was good fidelity to the intervention manual and its underpinning theory including high fulfilment of session objectives and use of an autonomy-supportive motivational style. Peer-supporters engaged with and enjoyed the training and retained key peer-supporter messages (what counts as PA, encouragement, empathy and subtlety). Parents and teachers were supportive of the intervention and reported perceived effects including increased PA and awareness of it, improved peer relationships, and confidence. Suggested intervention refinements included increasing participatory learning, reducing technical jargon, and providing more support to overcome challenges to giving peer support., Conclusions: PLAN-A can be delivered as planned, is well-received, and appears to be effective in empowering adolescent girls to support their peer group to become more active. The refinements identified can be made within the original intervention structure, before proceeding to a definitive trial., Trial Registration: ISCTRN, ISRCTN12543546 , Registered on 28/7/2015.

Background: The nutrition and physical activity self-assessment for childcare (NAP SACC) intervention has demonstrated effectiveness in the USA. A feasibility randomised controlled trial was conducted in England to adapt the intervention to the UK context. An embedded process evaluation focused on three key questions. 1. Was it feasible and acceptable to implement the intervention as planned? 2. How did the intervention affect staff and parent mediators? 3. Were the trial design and methods acceptable?, Methods: Twelve nurseries in south-west England were recruited and randomised to intervention or control. The intervention comprised: NAP SACC UK Partner (Health Visitor) support to nurseries to review practice and policies against best practice, and then set goals to improve physical activity, nutrition and oral health; two staff training workshops; and a web-based parent support element. The process evaluation comprised: observations of Partner training (n = 1), Partner/manager meetings (n = 5) and staff workshops (n = 10); semi-structured interviews with Partners (n = 4), managers (n = 12), staff (n = 4) and parents (n = 20); analysis of self-assessment forms, goal setting forms and Partner logbooks; and assessment of staff and parent knowledge, motivation and self-efficacy mediators., Results: Overall, NAP SACC UK was feasible to implement and acceptable to nursery staff, managers, Partners and parents. The intervention was implemented as planned in five of the six intervention nurseries. Partners and managers appreciated the opportunity to review and improve nursery practices and valued the relationship forged between them. Staff rated the training workshops highly, despite attending outside of working hours. Most goals set by nurseries were achieved. However, Partners raised concerns about Health Visitors' capacity to deliver the intervention in any subsequent roll out. Mediator scores improved in all but two areas in intervention staff and parents, with decreases or minimal changes in the control group. The web-based parent element was not well used and should be removed from any subsequent trial. The trial methods were acceptable to managers, staff, Partners and parents., Conclusions: Implementing and evaluating a physical activity and nutrition intervention in nursery settings is feasible and acceptable. A full RCT of NAP SACC UK (with appropriate modifications) is warranted., Trial Registration: ISRCTN16287377 (10 Apr 2015).

Background: Many children do not meet the recommended level of daily physical activity, even with the widely acknowledged health benefits associated with being physically active. There is a need to establish factors related to physical activity in children so that public health interventions may be appropriately designed. We investigated the association between Pediatric Quality of Life Inventory (PedsQL), family expenditure on physical activity and objectively measured daily physical activity in 2-4-year-old children., Methods: Cross-sectional study with a sample of 81 UK preschool children taking part in the NAPSACC UK feasibility randomized controlled trial. Descriptive statistics are presented. We undertook Student t-tests to establish differences in physical activity by gender, age, parental education and nursery versus non-nursery days. Mixed effects linear regressions were used to model the association between minutes spent physically activity, minutes spent in moderate-to-vigorous (MVPA) physical activity and PedsQL scores (physical and psychosocial) and family expenditure on physical activity., Results: Most children (88.9%) did not engage in the recommended 180 min daily physical activity. There was mean (SD) of 141.9 (33.1) daily minutes of physically activity and 22.2 min per day (SD = 9.9) of MVPA. Boys and older children were more physically active. Children were more active on nursery days. There was no difference in physical activity by parental education. Half of the sample parents (50.6%) spent less than £9.00 weekly on their pre-schooler's physical activity. Children within the highest tertile of PedsQL physical functioning scores had higher levels of MVPA (3.6, 95% CI: - 1.3-8.4, p-value 0.15), although confidence intervals crossed the null in the adjusted model. We found no evidence of an association between positive PedsQL psychosocial scores, or higher parental expenditure on physical activity, with the physical activity variables., Conclusions: Children in this sample were not meeting the recommended 180 min of daily physical activity. The 2-4-year-olds were most active on nursery days. There is no evidence of an association between better PedsQL physical scores and higher levels of MVPA. There was no evidence of an association between expenditure on physical activity and time spent physically active. Further examination in larger representative datasets is needed.

Physical activity (PA) patterns track from childhood through to adulthood. The study aimed to determine the levels and correlates of sedentary time (ST), total PA (TPA), and moderate-to-vigorous PA (MVPA) in preschool-aged children. We conducted cross-sectional analyses of 1052 children aged three-to-four-years-old from six studies included in the International Children's Accelerometry Database. Multilevel linear regression models adjusting for age, gender, season, minutes of wear time, and study clustering effects were used to estimate associations between age, gender, country, season, ethnicity, parental education, day of the week, time of sunrise, time of sunset, and hours of daylight and the daily minutes spent in ST, TPA, and MVPA. Across the UK, Switzerland, Belgium, and the USA, children in our analysis sample spent 490 min in ST per day and 30.0% and 21.2% of children did not engage in recommended daily TPA (≥180 min) and MVPA (≥60 min) guidelines. There was evidence for an association between all 10 potential correlates analyzed and at least one of the outcome variables; average daily minutes spent in ST, TPA and/or MVPA. These correlates can inform the design of public health interventions internationally to decrease ST and increase PA in preschoolers.

Objective: To determine the acceptability, internal consistency and test-retest reliability of self-efficacy, motivation and knowledge scales relating to pre-school children's nutrition, oral health and physical activity., Design: An online questionnaire was completed twice with an interval of 7-11d., Setting: Online questionnaires were sent to participants via email from nursery managers. The parent questionnaire was also available on the parenting website www.netmums.com.ParticipantsEighty-two parents and sixty-nine nursery staff from Bristol, UK who had and worked with 2-4-year-olds, respectively., Results: Response rates were 86·3 and 86·0 % and missing data 15·9 and 14·5 % for the second administration of the parent and nursery staff questionnaires, respectively. Weighted κ coefficients for individual items mostly fell under the 'moderate' agreement category for the parental (75·0 %) and nursery staff (55·8 %) items. All self-efficacy and motivation scales had acceptable levels of internal consistency (Cronbach's α coefficients>0·7). The intraclass correlation coefficients for the self-efficacy, motivation and knowledge scales ranged between 0·48 and 0·82. Paired t tests found an increase between test and retest knowledge scores for the Nutrition Motivation (t=-2·91, df=81, P=0·00) and Knowledge (t=-3·22, df=81, P=0·00) scales in the parent questionnaire., Conclusions: Our findings demonstrate that the items and scales show good acceptability, internal consistency and test-retest reliability.

Mentoring programmes are commonplace, yet little is known about the circumstances in which they operate. This study aimed to gain insight into the context surrounding youth mentoring programmes by asking programme managers and experts in the United Kingdom about their experiences. Telephone interviews with twenty-three programme managers and five experts were undertaken. Interviews were recorded, transcribed verbatim and analysed iteratively using thematic analysis. Contextual influences at the individual-, interpersonal-, organisational-, community-, policy-, and societal-level were identified to impact on programme's development, delivery and maintenance and were summarised in a model. This study further found that youth mentoring programmes operate within a complex context. This context provides challenges and opportunities that impact on programme's sustainability; resulting in many externally-funded programmes to 'hang by a thread'. It is important for service providers, commissioners and academics to recognise the complexity surrounding mentoring programmes to ensure that programmes are delivered as intended and evaluated appropriately.

Background: Childhood obesity tracks into adulthood with detrimental effects on health. We aimed to examine the relationships of diet in childcare settings and daily physical activity (PA) of preschoolers with body mass index z-score (z-BMI)., Methods: We conducted a cross-sectional study of 150 children aged 2-4-years participating in the Nutrition and Physical Activity Self-Assessment for Child Care (NAP SACC) UK study to examine the associations of their diet in childcare settings and daily PA with z-BMI. Dietary intake was observed and recorded by fieldworkers using a validated tick-list food questionnaire and diet quality was assessed based on adherence to Children's Food Trust (CFT) guidelines. PA was measured using accelerometers. We derived z-BMI scores using the UK 1990 and International Obesity Taskforce growth reference charts. Multilevel regression models were used to estimate associations between diet and PA with z-BMI separately, adjusted for age, gender, ethnicity, parental education level and clustering., Results: Among children who consumed one main meal or snack at childcare, 34.4% and 74.3% met the standards on fruits and vegetables and high sugar or fat snacks, respectively. Adherence to CFT guidelines was not associated with zBMI. Only 11.4% of children met recommended UK guidelines of three hours per day of physical activity. Minutes spent in light PA (β = 0.08, 95% CI = 0.01, 0.15) and active time (β = 0.07, 95% CI = 0.01, 0.12) were positively associated with UK 1990 zBMI scores., Conclusions: The low proportion of children meeting the standards on fruits and vegetables and high sugar or fat snacks and recommended physical activity levels highlight the need for more work to support nurseries and parents to improve preschool children's diet and activity. In our exploratory analyses, we found children with higher zBMI were more physically active which could be attributed to fat-free mass or chance finding and so requires replication in a larger study., Trial Registration: ISRCTN16287377 . Registered 12 June 2014.

Background: Engagement in multiple risk behaviours can have adverse consequences for health during childhood, during adolescence, and later in life, yet little is known about the impact of different types of interventions that target multiple risk behaviours in children and young people, or the differential impact of universal versus targeted approaches. Findings from systematic reviews have been mixed, and effects of these interventions have not been quantitatively estimated., Objectives: To examine the effects of interventions implemented up to 18 years of age for the primary or secondary prevention of multiple risk behaviours among young people., Search Methods: We searched 11 databases (Australian Education Index; British Education Index; Campbell Library; Cumulative Index to Nursing and Allied Health Literature (CINAHL); Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; Embase; Education Resource Information Center (ERIC); International Bibliography of the Social Sciences; MEDLINE; PsycINFO; and Sociological Abstracts) on three occasions (2012, 2015, and 14 November 2016)). We conducted handsearches of reference lists, contacted experts in the field, conducted citation searches, and searched websites of relevant organisations., Selection Criteria: We included randomised controlled trials (RCTs), including cluster RCTs, which aimed to address at least two risk behaviours. Participants were children and young people up to 18 years of age and/or parents, guardians, or carers, as long as the intervention aimed to address involvement in multiple risk behaviours among children and young people up to 18 years of age. However, studies could include outcome data on children > 18 years of age at the time of follow-up. Specifically,we included studies with outcomes collected from those eight to 25 years of age. Further, we included only studies with a combined intervention and follow-up period of six months or longer. We excluded interventions aimed at individuals with clinically diagnosed disorders along with clinical interventions. We categorised interventions according to whether they were conducted at the individual level; the family level; or the school level., Data Collection and Analysis: We identified a total of 34,680 titles, screened 27,691 articles and assessed 424 full-text articles for eligibility. Two or more review authors independently assessed studies for inclusion in the review, extracted data, and assessed risk of bias.We pooled data in meta-analyses using a random-effects (DerSimonian and Laird) model in RevMan 5.3. For each outcome, we included subgroups related to study type (individual, family, or school level, and universal or targeted approach) and examined effectiveness at up to 12 months' follow-up and over the longer term (> 12 months). We assessed the quality and certainty of evidence using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach., Main Results: We included in the review a total of 70 eligible studies, of which a substantial proportion were universal school-based studies (n = 28; 40%). Most studies were conducted in the USA (n = 55; 79%). On average, studies aimed to prevent four of the primary behaviours. Behaviours that were most frequently addressed included alcohol use (n = 55), drug use (n = 53), and/or antisocial behaviour (n = 53), followed by tobacco use (n = 42). No studies aimed to prevent self-harm or gambling alongside other behaviours.Evidence suggests that for multiple risk behaviours, universal school-based interventions were beneficial in relation to tobacco use (odds ratio (OR) 0.77, 95% confidence interval (CI) 0.60 to 0.97; n = 9 studies; 15,354 participants) and alcohol use (OR 0.72, 95% CI 0.56 to 0.92; n = 8 studies; 8751 participants; both moderate-quality evidence) compared to a comparator, and that such interventions may be effective in preventing illicit drug use (OR 0.74, 95% CI 0.55 to 1.00; n = 5 studies; 11,058 participants; low-quality evidence) and engagement in any antisocial behaviour (OR 0.81, 95% CI 0.66 to 0.98; n = 13 studies; 20,756 participants; very low-quality evidence) at up to 12 months' follow-up, although there was evidence of moderate to substantial heterogeneity (I² = 49% to 69%). Moderate-quality evidence also showed that multiple risk behaviour universal school-based interventions improved the odds of physical activity (OR 1.32, 95% CI 1.16 to 1.50; I² = 0%; n = 4 studies; 6441 participants). We considered observed effects to be of public health importance when applied at the population level. Evidence was less certain for the effects of such multiple risk behaviour interventions for cannabis use (OR 0.79, 95% CI 0.62 to 1.01; P = 0.06; n = 5 studies; 4140 participants; I² = 0%; moderate-quality evidence), sexual risk behaviours (OR 0.83, 95% CI 0.61 to 1.12; P = 0.22; n = 6 studies; 12,633 participants; I² = 77%; low-quality evidence), and unhealthy diet (OR 0.82, 95% CI 0.64 to 1.06; P = 0.13; n = 3 studies; 6441 participants; I² = 49%; moderate-quality evidence). It is important to note that some evidence supported the positive effects of universal school-level interventions on three or more risk behaviours.For most outcomes of individual- and family-level targeted and universal interventions, moderate- or low-quality evidence suggests little or no effect, although caution is warranted in interpretation because few of these studies were available for comparison (n ≤ 4 studies for each outcome).Seven studies reported adverse effects, which involved evidence suggestive of increased involvement in a risk behaviour among participants receiving the intervention compared to participants given control interventions.We judged the quality of evidence to be moderate or low for most outcomes, primarily owing to concerns around selection, performance, and detection bias and heterogeneity between studies., Authors' Conclusions: Available evidence is strongest for universal school-based interventions that target multiple- risk behaviours, demonstrating that they may be effective in preventing engagement in tobacco use, alcohol use, illicit drug use, and antisocial behaviour, and in improving physical activity among young people, but not in preventing other risk behaviours. Results of this review do not provide strong evidence of benefit for family- or individual-level interventions across the risk behaviours studied. However, poor reporting and concerns around the quality of evidence highlight the need for high-quality multiple- risk behaviour intervention studies to further strengthen the evidence base in this field.

Objectives: To explore the association between adolescent multiple risk behaviours (MRBs) and educational attainment., Design: Prospective population-based UK birth cohort study., Setting: Avon Longitudinal Study of Parents and Children (ALSPAC), a UK birth cohort of children born in 1991-1992., Participants: Data on some or all MRB measures were available for 5401 ALSPAC participants who attended a clinic at age 15 years and/or completed a detailed questionnaire at age 16 years. Multiple imputation was used to account for missing data., Primary Outcome Measures: Capped General Certificate of Secondary Education (GCSE) score and odds of attaining five or more GCSE examinations at grades A*-C. Both outcome measures come from the National Pupil Database and were linked to the ALSPAC data., Results: Engagement in MRB was strongly associated with poorer educational attainment. Each additional risk equated to -6.31 (95% CI -7.03 to -5.58, p<0.001) in capped GCSE score, equivalent to a one grade reduction or reduced odds of attaining five or more A*-C grades of 23% (OR 0.77, 95% CI 0.74 to 0.81, p<0.001). The average cohort member engaged in 3.24 MRB and therefore have an associated reduction in GCSE score equivalent to three and a half grades in one examination, or reduced odds of attaining five or more A*-C grades of 75%., Conclusion: Engagement in adolescent MRB is strongly associated with poorer educational attainment at 16 years. Preventing MRB could improve educational attainment and thereby directly and indirectly improve longer-term health., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.)

Background: Most adolescent girls in the UK do not meet government physical activity recommendations and effective interventions are needed. This study reports the results of a feasibility trial of PLAN-A, a novel school-based peer-led physical activity intervention for adolescent girls., Methods: A two-arm cluster randomised controlled feasibility study was conducted in six English secondary schools (4 intervention & 2 control). Year 8 (age 12-13) girls were eligible and randomisation was at school-level. The intervention involved training Year 8 girls (out of school for two consecutive days, plus one top-up day 5 weeks later), who were identified by their peers as influential, to provide informal support to their friends to increase their physical activity. Feasibility of the intervention and the research was examined, including: recruitment, training attendance and data provision rates, evidence of promise of the intervention to affect weekday moderate-to-vigorous physical activity (MVPA), intervention cost and estimation of the sample size for a definitive trial. Accelerometer and questionnaire data were collected at the beginning of Year 8 (Time 0), the end of Year 8 (10-weeks after peer-supporter training) and the beginning of Year 9 (Time 2)., Results: Four hundred twenty-seven girls were recruited (95% recruitment rate). 55 girls consented to be a peer-supporter and 53 peer-supporters were trained (97% of those invited). Accelerometer return rates exceeded 85% at each time point and wear time criteria was met by 83%, 71% and 62% participants at Time 0, 1 and 2 respectively. Questionnaire data were provided by >91% of participants at each time point. Complete-case adjusted linear regression analysis showed evidence of a 6.09 minute (95% CI = 1.43, 10.76) between-arms difference in weekday MVPA at Time 2 in favour of the intervention arm. On average PLAN-A cost £2685 per school to deliver (£37 per Year 8 girl). There were no adverse events. A trial involving 20 schools would be adequately powered to detect a between-arms difference in weekday MVPA of at least six minutes., Conclusions: The PLAN-A intervention adopts a novel peer-led approach, is feasible, and shows evidence of promise to positively affect girls' physical activity levels. A definitive trial is warranted., Trial Registration: ISCTRN, ISRCTN12543546, Registered on 28/7/2015, URL of registry record: http://www.isrctn.com/ISRCTN12543546.

Mentoring programmes are commonplace and delivered in a range of different ways in the United Kingdom and North America. To better understand the type of programmes available and to inform future evaluations, we developed a typology of formal mentoring programmes for young people in secondary schools in the United Kingdom. Telephone interviews with 23 programme managers from purposively sampled mentoring organisations were conducted and analysed using thematic and framework analysis. The typology was consulted on with five experts in mentoring. The final typology differentiates mentoring programmes by three overarching categories: type of mentor (older student, school staff, adult volunteer, paid adult), programme setting (school, community, online) and programme aim. The findings suggest that although mentoring programmes are heterogeneous, it is possible to group programmes into 'personal and developmental' and 'academic and employability' mentoring programmes and to differentiate between 12 overall mentoring models. The typology helps understand what is being delivered and how, which is a necessary precursor to any evaluation of health, educational, relational and social outcomes.

Background: Primary care guidelines for managing adult overweight/obesity recommend routine measurement of body mass index (BMI) and the offer of weight management interventions. Many studies state that this is rarely done, but the extent to which overweight/obesity is recognised, considered, and documented in routine care has not been determined., Aim: To identify the epidemiology of adult overweight documentation and management by UK GPs., Design and Setting: A systematic review of studies since 2006 from eight electronic databases and grey literature., Method: Included studies measured the proportion of adult patients with documented BMI or weight loss intervention offers in routine primary care in the UK. A narrative synthesis reports the prevalence and pattern of the outcomes., Results: In total, 2845 articles were identified, and seven were included; four with UK-wide data and three with regional-level data. The proportion of patients with a documented BMI was 58-79% (28-37% within a year). For overweight/obese patients alone, 43-52% had a recent BMI record, and 15-42% had a documented intervention offer. BMI documentation was positively associated with older age, female sex, higher BMI, coexistent chronic disease, and higher deprivation., Conclusion: BMI is under-recorded and weight loss interventions are under-referred for primary care adult patients in the UK despite the obesity register in the Quality and Outcomes Framework (QOF). The review identified likely underserved groups such as younger males and otherwise healthy overweight/obese individuals to whom attention should now be directed. The proposed amendment to the obesity register QOF could prompt improvements but has not been adopted for 2017., (© British Journal of General Practice 2017.)

Background: Excessive use of antibiotics accelerates the acquisition/spread of antimicrobial resistance. A systematic review was conducted to identify the components of successful communication interventions targeted at the general public to improve antibiotic use., Methods: The databases MEDLINE, EMBASE, CINAHL, Web of Science and Cochrane Library were searched. Search terms were related to the population (public, community), intervention (campaign, mass media) and outcomes (antibiotic, antimicrobial resistance). References were screened for inclusion by one author with a random subset of 10% screened by a second author. No date restrictions were applied and only articles in the English language were considered. Studies had to have a control group or be an interrupted time-series. Outcomes had to measure change in antibiotic-related prescribing/consumption and/or the public's knowledge, attitudes or behaviour. Two reviewers assessed the quality of studies. Narrative synthesis was performed., Results: Fourteen studies were included with an estimated 74-75 million participants. Most studies were conducted in the United States or Europe and targeted both the general public and clinicians. Twelve of the studies measured changes in antibiotic prescribing. There was quite strong ( P  < 0·05 to ≥ 0·01) to very strong ( P  < 0·001) evidence that interventions that targeted prescribing for RTIs were associated with decreases in antibiotic prescribing; the majority of these studies reported reductions of greater than -14% with the largest effect size reaching -30%., Conclusion: Multi-faceted communication interventions that target both the general public and clinicians can reduce antibiotic prescribing in high-income countries but the sustainability of reductions in antibiotic prescribing is unclear., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Previous analyses of adolescent suicides in England and Wales have focused on short time periods., Aims: To investigate trends in suicide and accidental deaths in adolescents between 1972 and 2011., Method: Time trend analysis of rates of suicides and deaths from accidental poisoning and hanging in 10- to 19-year-olds by age, gender and deprivation. Rate ratios were estimated for 1982-1991, 1992-2001 and 2002-2011 with 1972-1981 as comparator., Results: Suicide rates have remained stable in 10- to 14-year-olds, with strong evidence for a reduction in accidental deaths. In males aged 15-19, suicide rates peaked in 2001 before declining. Suicide by hanging is the most common method of suicide. Rates were higher in males and in 15- to 19-year-olds living in more deprived areas., Conclusions: Suicide rates in adolescents are at their lowest since the early 1970s with no clear evidence that changes in coroners' practices underlie this trend., Competing Interests: Declaration of interest D.G. is a member of the National Suicide Prevention Strategy Advisory Group (England)., (© The Royal College of Psychiatrists 2016.)

The minimal invasive anterolateral Yale 2-incision approach for total hip arthroplasty aims minimizing damage to the muscles for faster recovery of function. Therefore the hypothesis was investigated, that during the rehabilitation process the Yale approach shows a faster return to natural gait than a conventional lateral approach. Nineteen patients had the Yale, 16 the conventional Bauer approach. Instrumented gait analysis was performed 3 days, 3 and 12 month post operatively. Velocity, cadence, step length, weight bearing, thorax lean, Trendelenburg limp, hip abduction moments, and hip muscle activation times were evaluated. Three days post-surgery a significantly greater loading of the treated limb and increased hip abduction moment were observed in the Yale group. In addition, the Yale group showed its greatest improvement in walking speed and step length between at 3 days and 3 months, whereas the conventional group showed an additional significant gain between 3 and 12 month to reach a similar walking speed as the Yale group. For all hip muscles investigated, only muscle tensor fasciae latae in the conventional group showed a significant increase in activation time between 3 days and 3 months. This study showed significantly faster return to natural gait in the Yale compared to the conventional approach, which could be biomechanically related to less impairment of abductor muscles in the Yale approach., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Physical activity levels are low amongst adolescent girls, and this population faces specific barriers to being active. Peer influences on health behaviours are important in adolescence and peer-led interventions might hold promise to change behaviour. This paper describes the protocol for a feasibility cluster randomised controlled trial of Peer-Led physical Activity iNtervention for Adolescent girls (PLAN-A), a peer-led intervention aimed at increasing adolescent girls' physical activity levels., Methods/design: A two-arm cluster randomised feasibility trial will be conducted in six secondary schools (intervention n  = 4; control n  = 2) with year 8 (12-13 years old) girls. The intervention will operate at a year group level and consist of year 8 girls nominating influential peers within their year group to become peer-supporters. Approximately 15 % of the cohort will receive 3 days of training about physical activity and interpersonal communication skills. Peer-supporters will then informally diffuse messages about physical activity amongst their friends for 10 weeks. Data will be collected at baseline (time 0 (T0)), immediately after the intervention (time 1 (T1)) and 12 months after baseline measures (time 2 (T2)). In this feasibility trial, the primary interest is in the recruitment of schools and participants (both year 8 girls and peer-supporters), delivery and receipt of the intervention, data provision rates and identifying the cost categories for future economic analysis. Physical activity will be assessed using 7-day accelerometry, with the likely primary outcome in a fully-powered trial being daily minutes of moderate-to-vigorous physical activity. Participants will also complete psychosocial questionnaires at each time point: assessing motivation, self-esteem and peer physical activity norms. Data analysis will be largely descriptive and focus on recruitment, attendance and data provision rates. The findings will inform the sample size required for a definitive trial. A detailed process evaluation using qualitative and quantitative methods will be conducted with a variety of stakeholders (i.e. pupils, parents, teachers and peer-supporter trainers) to identify areas of success and necessary improvements prior to proceeding to a definitive trial., Discussion: This paper describes the protocol for the PLAN-A feasibility cluster randomised controlled trial which will provide the information necessary to design a fully-powered trial should PLAN-A demonstrate evidence of promise., Trial Registration: ISRCTN12543546.

TriplatinNC is a highly positively charged, substitution-inert derivative of the phase II clinical anticancer drug, BBR3464. Such substitution-inert complexes form a distinct subset of polynuclear platinum complexes (PPCs) interacting with DNA and other biomolecules through noncovalent interactions. Rapid cellular entry is facilitated via interaction with cell surface glycosoaminoglycans and is a mechanism unique to PPCs. Nanoscale secondary ion mass spectrometry (nanoSIMS) showed rapid distribution within cytoplasmic and nucleolar compartments, but not the nucleus. In this article, the downstream effects of nucleolar localization are described. In human colon carcinoma cells, HCT116, the production rate of 47S rRNA precursor transcripts was dramatically reduced as an early event after drug treatment. Transcriptional inhibition of rRNA was followed by a robust G1 arrest, and activation of apoptotic proteins caspase-8, -9, and -3 and PARP-1 in a p53-independent manner. Using cell synchronization and flow cytometry, it was determined that cells treated while in G1 arrest immediately, but cells treated in S or G2 successfully complete mitosis. Twenty-four hours after treatment, the majority of cells finally arrest in G1, but nearly one-third contained highly compacted DNA; a distinct biological feature that cannot be associated with mitosis, senescence, or apoptosis. This unique effect mirrored the efficient condensation of tRNA and DNA in cell-free systems. The combination of DNA compaction and apoptosis by TriplatinNC treatment conferred striking activity in platinum-resistant and/or p53 mutant or null cell lines. Taken together, our results support that the biological activity of TriplatinNC reflects reduced metabolic deactivation (substitution-inert compound not reactive to sulfur nucleophiles), high cellular accumulation, and novel consequences of high-affinity noncovalent DNA binding, producing a new profile and a further shift in the structure-activity paradigms for antitumor complexes.

Several chlorido and amino Pt(2+) complexes of 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinone Mannich bases HL exhibiting moderate to high cytotoxicity against cancer cell lines were studied in order to investigate their modes of DNA binding, in vitro DNA strand breaks, mechanism of topoisomerase (Topo I) inhibition and cellular accumulation. DNA model base studies have shown that complex 1a [Pt(HL1)Cl(2)] was capable of binding covalently to 9-ethylguanine (9-EtG) and 5'-GMP. (1)H NMR and mass spectrometry studies have shown that both chlorides were substituted by 9-EtG ligands, whereas 5'-GMP was able to replace only one chlorido ligand, due to steric hindrance. The chlorido Pt(2+) complexes [Pt(HL)Cl(2)] highly accumulate in prostate (PC-3) and melanoma (MDA-MB-435) cell lines, being able to induce DNA strand breaks in vitro and inhibit Topo I by a catalytic mode. On the other hand, the free 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinones HL and the amino Pt(2+) complexes [Pt(L(-))(NH(3))(2)]NO(3) neither cause DNA strand breakage nor exhibit strong DNA interaction, nevertheless the latter were also found to be catalytic inhibitors of Topo I at 100μM. Thus, coordination of the Mannich bases HL to the "PtCl(2)" fragment substantially affects the chemical and biophysical properties of the pro-ligands, leading to an improvement of their DNA binding properties and generating compounds that cleave DNA and catalytically inhibit Topo I. Finally, the high cytotoxicity exhibited by the free (uncomplexed) 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinones might be associated with their decomposition in solution, which is not observed for the Pt(2+) complexes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Little is known about the effectiveness of parent involvement in school-based obesity prevention interventions., Methods: A qualitative study with parents of children aged 9-10 years was conducted to identify possible methods to involve them in a school-based obesity prevention intervention, followed by a process evaluation of homework and school newsletters to involve parents., Results: Qualitative study: parents supported the use of homework and school newsletters to involve them and overcome the main barriers of their work and time. Process evaluation: Ten homeworks and inserts for the school newsletter about the obesity prevention intervention were developed and delivered. The majority of homeworks were given out (73%), completed by children (84%) and recalled by parents (60-68%). The majority of homeworks were enjoyed by parents and children. All the schools put information about the project in the newsletter and this was recalled by parents. Most parents felt the homeworks were a practical way of involving them., Conclusions: Homeworks are routinely given to children and provide a means of engaging potentially all parents if parental support is required. Homeworks which are novel, fun and involve activities and social contact are enjoyed by parents and children and may increase awareness of healthy diet and physical activity.

The overall efficacy of platinum based drugs is limited by metabolic deactivation through covalent drug-protein binding. In this study the factors affecting cytotoxicity in the presence of glutathione, human serum albumin (HSA) and whole serum binding with cisplatin, BBR3464, and TriplatinNC, a "noncovalent" derivative of BBR3464, were investigated. Upon treatment with buthionine sulfoximine (BSO), to reduce cellular glutathione levels, cisplatin and BBR3464-induced apoptosis was augmented whereas TriplatinNC-induced cytotoxicity was unaltered. Treatment of A2780 ovarian carcinoma cells with HSA-bound cisplatin (cisplatin/HSA) and cisplatin preincubated with whole serum showed dramatic decreases in cytotoxicity, cellular accumulation, and DNA adduct formation compared to treatment with cisplatin alone. Similar effects are seen with BBR3464. In contrast, TriplatinNC, the HSA-bound derivative (TriplatinNC/HSA), and TriplatinNC pretreated with whole serum retained identical cytotoxic profiles and equal levels of cellular accumulation at all time points. Confocal microscopy of both TriplatinNC-NBD, a fluorescent derivative of TriplatinNC, and TriplatinNC-NBD/HSA showed nuclear/nucleolar localization patterns, distinctly different from the lysosomal localization pattern seen with HSA. Cisplatin-NBD, a fluorescent derivative of cisplatin, was shown to accumulate in the nucleus and throughout the cytoplasm while the localization of cisplatin-NBD/HSA was limited to lysosomal regions of the cytoplasm. The results suggest that TriplatinNC can avoid high levels of metabolic deactivation currently seen with clinical platinum chemotherapeutics, and therefore retain a unique cytotoxic profile after cellular administration.

The 1.7 Å X-ray crystal structure of the B-DNA dodecamer, [d(CGCGAATTCGCG)]₂ (DDD)-bound non-covalently to a platinum(II) complex, [{Pt(NH₃)₃}₂-µ-{trans-Pt(NH₃)₂(NH₂(CH₂)₆NH₂)₂}](NO₃)₆ (1, TriplatinNC-A,) shows the trinuclear cation extended along the phosphate backbone and bridging the minor groove. The square planar tetra-am(m)ine Pt(II) units form bidentate N-O-N complexes with OP atoms, in a Phosphate Clamp motif. The geometry is conserved and the interaction prefers O2P over O1P atoms (frequency of interaction is O2P > O1P, base and sugar oxygens > N). The binding mode is very similar to that reported for the DDD and [{trans-Pt(NH₃)₂(NH₂(CH₂)₆(NH₃(+))}₂-µ-{trans-Pt(NH₃)₂(NH₂(CH₂)₆NH₂)₂}](NO₃)₈ (3, TriplatinNC), which exhibits in vivo anti-tumour activity. In the present case, only three sets of Phosphate Clamps were found because one of the three Pt(II) coordination spheres was not clearly observed and was characterized as a bare Pt²(+) ion. Based on the electron density, the relative occupancy of DDD and the sum of three Pt(II) atoms in the DDD-1 complex was 1:1.69, whereas the ratio for DDD-2 was 1:2.85, almost the mixing ratio in the crystallization drop. The high repetition and geometric regularity of the motif suggests that it can be developed as a modular nucleic acid binding device with general utility.

Objective: Implantation of a total hip endoprosthesis with minimal trauma to the soft tissue. The need for visual aids (e.g., navigation or X-rays) during the procedure is frequently avoided., Indications: All kinds of coxarthrosis for every age group, for every variation of bone construction, and even in obese patients., Contraindications: Extremely dysplastic hip joints involving the development of a secondary socket and the necessity of reconstruction of the acetabular socket (e.g., in the Harris method)., Surgical Technique: Using a fixed lateral position, a small entry incision is made between the tensor fasciae latae and the sartorius muscles and the prosthesis socket is put into place. Via a second dorsal incision, after stripping the exterior rotators, the prosthesis stem and ball are implanted and the two parts of the prosthesis are attached., Postoperative Management: Full weight bearing allowed immediately. A luxation prophylaxis, in the form of a self-developed hip bodice (the so-called Yale bandage), is used until the end of the 4th postoperative week. Discharge from hospital is possible after just a few days. Upon discharge, the patient is sent to a rehabilitation facility, either as a resident or as an outpatient, for approximately 3 weeks. Return to the workplace, with only light physical activity, is possible once the wound has healed completely; this could be as soon as 14 days after the operation. Checkups are made after 4 weeks, 6 months, 1 year and then every year; these checkups include a full examination, X-rays and laboratory tests. Full exposure to sport or heavy manual labor is usually approved after the 6-month checkup., Results: Between October 2004 and April 2006, a total of 221 patients underwent surgery using this new technique (of these 15 patients underwent two-stage bilateral hip joint replacements). Patients were followed up for a minimum of 12 months and a maximum of 30 months. The Harris Hip Score improved from an average of 45.25 preoperatively to 96.4 postoperatively.

Ciguatera toxin causes a range of gastrointestinal, cardiovascular and neurological symptoms that occur within 1-6 h of ingesting fish with the toxin and can last for days, months or years. It is a well-recognized problem in the tropics. Avon Health Protection Team investigated food poisoning on a ship at Avonmouth, which was thought by the crew to be related to a white snapper fish from the Caribbean. The symptoms were initially thought to be scombroid fish poisoning but were consistent with ciguatera fish poisoning. Cases of fish poisoning from fish imported from the Caribbean and Pacific or travellers returning from tropical countries may be ciguatera fish poisoning, but mistakenly diagnosed as scombroid fish poisoning.

Problem: NHS patients requiring elective surgery usually have to wait before being treated and are usually told when a date becomes available., Design: 18 month pilot programme to enable day case patients to book date of hospital admission at time of decision to operate., Background and Setting: 24 pilot sites in England with relatively short waiting times and some experience of booking appointments., Key Measures for Improvement: Proportion of patients with booked or "to come in" date during and after pilot programme, proportion not attending for admission, and proportion waiting > or = 6 months. Comparison of pilot sites with non-pilot sites., Strategies for Change: National Patients' Access Team established to help pilot sites enable patients to book admission dates. Provision of 9.9m pounds sterling to pilot sites to employ project managers, purchase equipment, buy extra time from clinical and other staff, and invest in information and communications technology., Effects of Change: Proportion of patients with booked or "to come in" date increased from 51.1% to 72.7% between end of March 1999 and end of March 2000, and then fell to 66.2% by end of March 2001. Over the same periods, the proportion of patients waiting > or = 6 months fell from 10.9% to 10.5% and then increased to 11.9%. The proportion of patients failing to attend fell from 5.7% to 3.1% between the first quarter of 1999 and the first quarter of 2000, and then increased to 4.0% in the first quarter of 2001. Pilot sites varied widely in performance during and after the pilot phase. Pilot sites had higher proportions of patients with booked or "to come in" date than non-pilot sites at end of each period., Lessons Learnt: Increasing the proportion of patients who book their date of hospital admission is possible, but there are difficulties in sustaining this. Several factors facilitated or hindered the implementation of booking, and the roll out of the programme across the NHS is seeking to incorporate these factors.

The proportion of patients with booked appointments for hospital admissions and day-case treatment will have to more than double by 2005 to meet the NHS plan targets. Most patients with a booked appointment liked the system. Implementing a booking system requires considerable commitment from health professionals. The booking targets of the NHS plan will not be achieved without an increase in capacity.

Pilot schemes for direct booking of hospital appointments have won support from the consultants involved. Skilled leadership has been crucial to managing changes that enable direct booking to be put into practice. The nursing role is central to the system, particularly in pre-operative assessment clinics. For direct booking to become widespread, management of all acute hospital resources will have to be reviewed.

New Zealand is attempting to replace waiting lists with a booking system for elective surgery such as hip replacements, cataract removal and heart bypass operations, and medical procedures. The propose system would only accept for treatment those patients assessed as likely to gain the greatest benefit. Purchasers were originally instructed to implement the system by this month. This has now been postponed until July 1999. The proposals are being opposed by clinicians on the basis that, in some cases, they would rule out 30 per cent of patients from treatment.

Aim: To compare two priority access criteria scoring methods for elective cholecystectomy, with a score based on clinical judgement obtained using a linear analogue scale., Methods: Patients placed on the waiting list for elective laparoscopic cholecystectomy between June and October 1997 were prioritised using the three methods., Results: Data were obtained for 22 patients. The distributions of scores were different but there was a significant correlation between them. However, limits of agreement analysis demonstrated little agreement between them with a difference of +/- 30 points (out of a 100) between scores obtained with each method., Conclusion: The proposed methods for establishing priority access to elective cholecystectomy are poor tools, require validation and bear little relation to expert clinical judgement.