Gut microbiology of UK care home residents: a cross-sectional analysis from a randomised controlled trial.

OBJECTIVE: To describe the prevalence of potentially clinically relevant gut pathogens and associations with the carriage of resistant organisms in UK care home residents. METHODS: Stool samples were collected pre-randomisation from care home residents participating in a randomised placebo-controlled trial. Cultivable clinically relevant bacteria were analysed. Antimicrobial susceptibility testing was performed by agar dilution (amoxicillin, co-amoxiclav, gentamicin, trimethoprim, nitrofurantoin, and ciprofloxacin). We also aimed to detect resistance to third-generation cephalosporins, carbapenems, and vancomycin. RESULTS: Stool samples were available for 159/310 residents participating in the trial (51%) from 23 care homes between 2016 and 2018. In total, 402 bacterial isolates were cultured from 158 stool samples and 29 different species were cultured. The five most common species were Escherichia coli (155/158, 98%), Pseudomonas aeruginosa (40/158, 25%), Enterococcus faecalis (35/158, 22%), Enterococcus faecium (30/158, 19%), and Proteus mirabilis (25/158, 16%). Enterobacterales isolates were cultured from 157 samples (99%), and resistance to at least one of the tested antimicrobials was found in 119 of these (76%). There were high levels of variation in outcomes by care home. DISCUSSION: We demonstrated that care home residents harbour significant levels of antimicrobial-resistant organisms in their stool. This work emphasises the importance of both enhanced infection control practices and antimicrobial stewardship programmes to support the appropriate use of antimicrobials in this setting.

Nurse-led home-visitation programme for first-time mothers in reducing maltreatment and improving child health and development (BB:2-6): longer-term outcomes from a randomised cohort using data linkage.

OBJECTIVES: Measure effectiveness of family nurse partnership (FNP) home-visiting programme in reducing maltreatment and improving maternal health and child health, developmental and educational outcomes; explore effect moderators, mediators; describe costs. DESIGN: Follow-up of BB:0-2 trial cohort (ISRCTN:23019866) up to age 7 years in England using record linkage. PARTICIPANTS: 1618 mothers aged 19 years or younger and their firstborn child(ren) recruited to BB:0-2 trial at less than 25 weeks gestation and not mandatorily withdrawn from trial or opted out. Intervention families were offered up to a maximum of 64 home visits by specially trained nurses from pregnancy until firstborn child was 2 years old, plus usually provided health and social care support. Comparator was usual care alone. OUTCOME MEASURES: Primary outcome: state-verified child-in-need status recorded at any time during follow-up. SECONDARY OUTCOMES: referral to social services, child protection registration (plan), child-in-need categorisation, looked-after status, recorded injuries and ingestions any time during follow-up, early childcare and educational attendance, school readiness and attainment at key stage 1 (KS1), healthcare costs. RESULTS: Match rates for 1547 eligible children (1517 singletons, 15 sets of twins) were 98.3% (NHS Digital) and 97.4% (National Pupil Database). There was no difference between study arms in the proportion of children being registered as in need (adjusted OR 0.98, 95% CI 0.74 to 1.31), or for any other measure of maltreatment. Children in the FNP arm were more likely to achieve a good level of development at reception age (school readiness) (adjusted OR 1.24, 95% CI 1.01 to 1.52). After adjusting for birth month, children in FNP arm were more likely to reach the expected standard in reading at KS1 (adjusted OR 1.26, 95% CI 1.02 to 1.57). We found no trial arm differences for resource use and costs. CONCLUSIONS: FNP did not improve maltreatment or maternal outcomes. There was evidence of small advantages in school readiness and attainment at KS1. TRIAL REGISTRATION NUMBER: ISRCTN23019866.

Healthy eating and lifestyle in pregnancy (HELP): a cluster randomised trial to evaluate the effectiveness of a weight management intervention for pregnant women with obesity on weight at 12 months postpartum.

OBJECTIVE: To assess whether a weight management intervention for pregnant women with obesity was effective in reducing body mass index (BMI) 12 months after giving birth. METHODS: Pragmatic, cluster randomised controlled trial (RCT) with embedded cost-effectiveness analysis. 598 women with a BMI of ≥30 kg/m2 (between 12 and 20 weeks gestation) were recruited from 20 secondary care maternity units in England and Wales. BMI at 12 months postpartum was the primary outcome. A range of clinical and behavioural secondary outcomes were examined. INTERVENTIONS: Women attending maternity units randomised to intervention were invited to a weekly weight management group, which combined expertise from a commercial weight loss programme with clinical advice from midwives. Both intervention and control participants received usual care and leaflets on diet and physical activity in pregnancy. RESULTS: Mean (SD) BMI at 12 months postpartum was 36.0 kg/m2 (5.2) in the control group, and 37.5 kg/m2 (6.7) in the intervention group. After adjustment for baseline BMI, the intervention effect was -0.02 (95% CI -0.04 to 0.01). The intervention group had an improved healthy eating score (3.08, 95% CI 0.16 to 6.00, p < 0.04), improved fibre score (3.22, 1.07 to 5.37, p < 0.01) and lower levels of risky drinking at 12 months postpartum compared to the control group (OR 0.45, 0.27 to 0.74, p < 0.002). The net incremental monetary benefit was not statistically significantly different between arms, although the probability of the intervention being cost-effective was above 60%, at policy-relevant thresholds. CONCLUSIONS: There was no significant difference between groups on the primary outcome of BMI at 12 months. Analyses of secondary outcomes indicated improved healthy eating and lower levels of risky drinking. TRIAL REGISTRATION: Current Controlled Trials ISRCTN25260464.

Combination of the Probiotics Lacticaseibacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis, BB-12 Has Limited Effect on Biomarkers of Immunity and Inflammation in Older People Resident in Care Homes: Results From the Probiotics to Reduce Infections iN CarE home reSidentS Randomized, Controlled Trial.

Aging is associated with a decline in many components of the immune system (immunosenescence). Probiotics may improve the immune response in older people. The objective was to determine the effect of the combination of two probiotic organisms [Lacticaseibacillus (previously known as Lactobacillus) rhamnosus GG (LGG) and Bifidobacterium animalis subsp. lactis, BB-12 (BB-12)] on a range of immune biomarkers measured in the blood of older people resident in care homes in the UK. In a randomized controlled trial, older people [aged 67-97 (mean 86) years] resident in care homes received the combination of LGG+BB-12 (1.3-1.6 × 109 CFU per day) or placebo for up to 12 months. Full blood count, blood immune cell phenotypes, plasma immune mediator concentrations, phagocytosis, and blood culture responses to immune stimulation were all measured. Response to seasonal influenza vaccination was measured in a subset of participants. Paired samples (i.e., before and after intervention) were available for 30 participants per group. LGG and BB-12 were more likely to be present in feces in the probiotic group and were present at higher numbers. There was no significant effect of the probiotics on components of the full blood count, blood immune cell phenotypes, plasma immune mediator concentrations, phagocytosis by neutrophils and monocytes, and blood culture responses to immune stimulation. There was an indication that the probiotics improved the response to seasonal influenza vaccination with significantly (p = 0.04) higher seroconversion to the A/Michigan/2015 vaccine strain in the probiotic group than in the placebo group (47 vs. 15%).

Relationships Between Age, Frailty, Length of Care Home Residence and Biomarkers of Immunity and Inflammation in Older Care Home Residents in the United Kingdom.

Aging is associated with changes to the immune system, collectively termed immunosenescence and inflammageing. However, the relationships among age, frailty, and immune parameters in older people resident in care homes are not well described. We assessed immune and inflammatory parameters in 184 United Kingdom care home residents aged over 65 years and how they relate to age, frailty index, and length of care home residence. Linear regression was used to identify the independent contribution of age, frailty, and length of care home residence to the various immune parameters as dependent variables. Participants had a mean age (±SD) of 85.3 ± 7.5 years, had been residing in the care home for a mean (±SD) of 1.9 ± 2.2 years at the time of study commencement, and 40.7% were severely frail. Length of care home residence and frailty index were correlated but age and frailty index and age and length of care home residence were not significantly correlated. All components of the full blood count, apart from total lymphocytes, were within the reference range; 31% of participants had blood lymphocyte numbers below the lower value of the reference range. Among the components of the full blood count, platelet numbers were positively associated with frailty index. Amongst plasma inflammatory markers, C-reactive protein (CRP), interleukin-1 receptor antagonist (IL-1ra), soluble E-selectin and interferon gamma-induced protein 10 (IP-10) were positively associated with frailty. Plasma soluble vascular cell adhesion molecule 1 (sVCAM-1), IP-10 and tumor necrosis factor receptor II (TNFRII) were positively associated with age. Plasma monocyte chemoattractant protein 1 was positively associated with length of care home residence. Frailty was an independent predictor of platelet numbers, plasma CRP, IL-1ra, IP-10, and sE-selectin. Age was an independent predictor of activated monocytes and plasma IP-10, TNFRII and sVCAM-1. Length of care home residence was an independent predictor of plasma MCP-1. This study concludes that there are independent links between increased frailty and inflammation and between increased age and inflammation amongst older people resident in care homes in the United Kingdom. Since, inflammation is known to contribute to morbidity and mortality in older people, the causes and consequences of inflammation in this population should be further explored.

Effect of Probiotic Use on Antibiotic Administration Among Care Home Residents: A Randomized Clinical Trial.

Importance: Probiotics are frequently used by residents in care homes (residential homes or nursing homes that provide residents with 24-hour support for personal care or nursing care), although the evidence on whether probiotics prevent infections and reduce antibiotic use in these settings is limited. Objective: To determine whether a daily oral probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 compared with placebo reduces antibiotic administration in care home residents. Design, Setting, and Participants: Placebo-controlled randomized clinical trial of 310 care home residents, aged 65 years and older, recruited from 23 care homes in the United Kingdom between December 2016 and May 2018, with last follow-up on October 31, 2018. Interventions: Study participants were randomized to receive a daily capsule containing a probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 (total cell count per capsule, 1.3 × 1010 to 1.6 × 1010) (n = 155), or daily matched placebo (n = 155), for up to 1 year. Main Outcomes and Measures: The primary outcome was cumulative antibiotic administration days for all-cause infections measured from randomization for up to 1 year. Results: Among 310 randomized care home residents (mean age, 85.3 years; 66.8% women), 195 (62.9%) remained alive and completed the trial. Participant diary data (daily data including study product use, antibiotic administration, and signs of infection) were available for 98.7% randomized to the probiotic group and 97.4% randomized to placebo. Care home residents randomized to the probiotic group had a mean of 12.9 cumulative systemic antibiotic administration days (95% CI, 0 to 18.05), and residents randomized to placebo had a mean of 12.0 days (95% CI, 0 to 16.95) (absolute difference, 0.9 days [95% CI, -3.25 to 5.05]; adjusted incidence rate ratio, 1.13 [95% CI, 0.79 to 1.63]; P = .50). A total of 120 care home residents experienced 283 adverse events (150 adverse events in the probiotic group and 133 in the placebo group). Hospitalizations accounted for 94 of the events in probiotic group and 78 events in the placebo group, and deaths accounted for 33 of the events in the probiotic group and 32 of the events in the placebo group. Conclusions and Relevance: Among care home residents in the United Kingdom, a daily dose of a probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 did not significantly reduce antibiotic administration for all-cause infections. These findings do not support the use of probiotics in this setting. Trial Registration: ISRCTN Identifier:16392920.

Protocol for a double-blind placebo-controlled trial to evaluate the efficacy of probiotics in reducing antibiotics for infection in care home residents: the Probiotics to Reduce Infections iN CarE home reSidentS (PRINCESS) trial.

INTRODUCTION: Care home residents are at increased risk of infections and antibiotic prescription. Reduced antibiotic use from fewer infections would improve quality of life. The Probiotics to Reduce Infections iN CarE home reSidentS (PRINCESS) trial aims to determine the efficacy and investigate mechanisms of daily probiotics on antibiotic use and incidence of infections in care home residents. METHODS AND ANALYSIS: PRINCESS is a double-blind, individually randomised, placebo-controlled trial that will assess the effect of a daily oral probiotic combination of Lactobacillus rhamnosus, GG (LGG) and Bifidobacterium animalis subsp. lactis, BB-12 (BB-12) on cumulative antibiotic administration days (CAADs) (primary outcome) for infection in up to 330 care home residents aged ≥65 years over up to 12 months. Secondary outcomes include: Infection: Total number of days of antibiotic administration for each infection type (respiratory tract infection, urinary tract infection, gastrointestinal infection, unexplained fever and other); number, site, duration of infection; estimation of incidence and duration of diarrhoea and antibiotic-associated diarrhoea; Stool microbiology: Clostridium difficile infection; Gram-negative Enterobacteriaceae and vancomycin-resistant enterococci; LGG and BB-12. Oral microbiology: Candida spp. Health and well-being: Self and/or proxy health-related quality of life EQ5D (5 L); self-and/or proxy-reported ICEpop CAPability measure for older people. Hospitalisations: number and duration of all-cause hospital stays. Mortality: deaths. Mechanistic immunology outcomes: influenza vaccine efficacy (haemagglutination inhibition assay and antibody titres); full blood count and immune cell phenotypes, plasma cytokines and chemokines; cytokine and chemokine response in whole blood stimulated ex vivo by toll-like receptor 2 and 4 agonists; monocyte and neutrophil phagocytosis of Escherichia coli; serum vitamin D. ETHICS AND DISSEMINATION: Ethics approval is from the Wales Research Ethics Committee 3. Findings will be disseminated through peer-reviewed journals and conferences; results will be of interest to patient and policy stakeholders. TRIAL REGISTRATION NUMBER: ISRCTN16392920; Pre-results.

Assessing the medium-term impact of a home-visiting programme on child maltreatment in England: protocol for a routine data linkage study.

INTRODUCTION: Child maltreatment involves acts of omission (neglect) or commission (abuse) often by caregivers that results in potential or actual harm to a child. The Building Blocks trial (ISRCTN23019866) assessed the short-term impact of an intensive programme of antenatal and postnatal visiting by specially trained nurses to support young pregnant women in England. The Building Blocks: 2-6 Study will assess the medium-term impacts of the programme for mothers and children (n=1562), through the linkage of routinely collected data to the trial data, with a particular emphasis on the programme's impact on preventing child maltreatment. METHODS AND ANALYSIS: We have developed a bespoke model of data linkage whereby outcome data for the trial cohort will be retrieved by linked anonymous data abstraction from NHS Digital, Office for National Statistics and the Department for Education's National Pupil Database. Participants will be given reasonable opportunity to opt out of this study prior to data transfer. The information centres will match participants to the information held in their databases using standard identifiers and send extracts to a third-party safe haven. The study will have 80% power to detect a 4% difference (4%vs8%) for the binary primary outcome of child in need status (from birth to key stage 1) at a two-sided 5% alpha level by following up 602 children in each trial arm. Analysis will be by intention to treat using logistic multilevel modelling. A cost-and-consequences analysis will extend the time frame of the economic analysis from the original trial. ETHICS AND DISSEMINATION: The study protocol has been approved by the National Health Service Wales Research Ethics Committee and the Health Research Authority's Confidentiality Advisory Group. Methods of innovative study design and findings will be disseminated through peer-reviewed journals and conferences; results will be of interest to clinical and policy stakeholders in the UK. TRIAL REGISTRATION NUMBER: ISRCTN23019866.

The use of everolimus in the treatment of neurocognitive problems in tuberous sclerosis (TRON): study protocol for a randomised controlled trial.

BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disorder affecting about 1 in 6000 people and is characterised by the development of tumours in many organs, including the skin and kidneys, and by a range of neurological and neuropsychiatric manifestations. TSC-associated neuropsychiatric disorders (TAND) occur in the majority of those with TSC, and they have a significant impact on patients and their families, given the everyday impact of TAND on education, employment, family and social life. The potential benefits of better treatment for TAND therefore include reduction in health care demands and wider benefits for patients and their carers. METHODS/DESIGN: We have planned a single-centre, two-arm, individually randomised, phase II, double-blind, placebo-controlled trial of everolimus versus placebo in the treatment of neurocognitive problems in patients with tuberous sclerosis. Everolimus is a licensed medicine in this patient group, but for a different target of effect. The present trial is a proof-of-principle study developed to provide effect size estimates which may be used to inform the design of subsequent trials. Forty-eight patients aged 16-60 years with tuberous sclerosis who have an IQ >60 and a significant deficit (at least -2 SD) in one or more primary outcome measures will be randomly allocated in a ratio of 2:1 to receive everolimus or placebo, respectively. Participants will be assessed for eligibility and then be started on study medication 4 weeks later. They will then be randomised and receive placebo or everolimus for 24 weeks. Neurocognitive and safety assessments will be carried out at baseline and weeks 4, 12, 24 and 36. DISCUSSION: This study is designed to determine the effect sizes of treatment with everolimus or placebo for 6 months on specific neurocognitive functions-recall memory (verbal and non-verbal) and executive function-in people affected by TSC who have significant deficits in these functions. These data will provide new evidence to determine whether larger-scale trials are indicated and to explore suitable outcome measures and analytical methods for neurocognitive trial design. TRIAL REGISTRATION: ISRCTN09739757 . Registered on 28 Dec 2011.

Effectiveness of a nurse-led intensive home-visitation programme for first-time teenage mothers (Building Blocks): a pragmatic randomised controlled trial.

BACKGROUND: Many countries now offer support to teenage mothers to help them to achieve long-term socioeconomic stability and to give a successful start to their children. The Family Nurse Partnership (FNP) is a licensed intensive home-visiting intervention developed in the USA and introduced into practice in England that involves up to 64 structured home visits from early pregnancy until the child's second birthday by specially recruited and trained family nurses. We aimed to assess the effectiveness of giving the programme to teenage first-time mothers on infant and maternal outcomes up to 24 months after birth. METHODS: We did a pragmatic, non-blinded, randomised controlled, parallel-group trial in community midwifery settings at 18 partnerships between local authorities and primary and secondary care organisations in England. Eligible participants were nulliparous and aged 19 years or younger, and were recruited at less than 25 weeks' gestation. Field-based researchers randomly allocated mothers (1:1) via remote randomisation (telephone and web) to FNP plus usual care (publicly funded health and social care) or to usual care alone. Allocation was stratified by site and minimised by gestation (<16 weeks vs ≥16 weeks), smoking status (yes vs no), and preferred language of data collection (English vs non-English). Mothers and assessors (local researchers at baseline and 24 months' follow-up) were not masked to group allocation, but telephone interviewers were blinded. Primary endpoints were biomarker-calibrated self-reported tobacco use by the mother at late pregnancy, birthweight of the baby, the proportion of women with a second pregnancy within 24 months post-partum, and emergency attendances and hospital admissions for the child within 24 months post-partum. Analyses were by intention to treat. This trial is registered with ISRCTN, number ISRCTN23019866. FINDINGS: Between June 16, 2009, and July 28, 2010, we screened 3251 women. After enrolment, 823 women were randomly assigned to receive FNP and 822 to usual care. All follow-up data were retrieved by April 25, 2014. 304 (56%) of 547 women assigned to FNP and 306 (56%) of 545 assigned to usual care smoked at late pregnancy (adjusted odds ratio [AOR] 0·90, 97·5% CI 0·64-1·28). Mean birthweight of 742 babies with mothers assigned to FNP was 3217·4 g (SD 618·0), whereas birthweight of 768 babies assigned to usual care was 3197·5 g (SD 581·5; adjusted mean difference 20·75 g, 97·5% CI -47·73 to 89·23. 587 (81%) of 725 assessed children with mothers assigned to FNP and 577 (77%) of 753 assessed children assigned to usual care attended an emergency department or were admitted to hospital at least once before their second birthday (AOR 1·32, 97·5% CI 0·99-1·76). 426 (66%) of 643 assessed women assigned to FNP and 427 (66%) 646 assigned to usual care had a second pregnancy within 2 years (AOR 1·01, 0·77-1·33). At least one serious adverse event (mainly clinical events associated with pregnancy and infancy period) was reported for 310 (38%) of 808 participants (mother-child) in the usual care group and 357 (44%) of 810 in the FNP group, none of which were considered related to the intervention. INTERPRETATION: Adding FNP to the usually provided health and social care provided no additional short-term benefit to our primary outcomes. Programme continuation is not justified on the basis of available evidence, but could be reconsidered should supportive longer-term evidence emerge. FUNDING: Department of Health Policy Research Programme.

A feasibility randomised controlled trial of a motivational interviewing-based intervention for weight loss maintenance in adults.

BACKGROUND: Obesity has significant health and NHS cost implications. Relatively small reductions in weight have clinically important benefits, but long-term weight loss maintenance (WLM) is challenging. Behaviour change interventions have been identified as key for WLM. Motivation is crucial to supporting behaviour change, and motivational interviewing (MI) has been identified as a successful approach to changing health behaviours. The study was designed as an adequately powered, pragmatic randomised controlled trial (RCT); however, owing to recruitment issues, the study became a feasibility trial. OBJECTIVES: To assess recruitment, retention, feasibility, acceptability, compliance and delivery of a 12-month intervention to support WLM. Secondary objectives were to assess the impact of the intervention on body mass index (BMI) and other secondary outcomes. DESIGN: Three-arm individually randomised controlled trial comprising an intensive arm, a less intensive arm and a control arm. SETTING: Community setting in South Wales and the East Midlands. PARTICIPANTS: Individuals aged 18-70 years with a current or previous BMI of ≥ 30 kg/m(2) who could provide evidence of at least 5% weight loss during the previous 12 months. INTERVENTION: Participants received individually tailored MI, which included planning and self-monitoring. The intensive arm received six face-to-face sessions followed by nine telephone sessions. The less intensive arm received two face-to-face sessions followed by two telephone sessions. The control arm received a leaflet advising them on healthy lifestyle. MAIN OUTCOME MEASURES: Feasibility outcomes included numbers recruited, retention and adherence. The primary effectiveness outcome was BMI at 12 months post randomisation. Secondary outcomes included waist circumference, waist-to-hip ratio, physical activity, proportion maintaining weight loss, diet, quality of life, health service resource usage, binge eating and well-being. A process evaluation assessed intervention delivery, adherence, and participants' and practitioners' views. Economic analysis aimed to assess cost-effectiveness in terms of quality-adjusted life-years (QALYs). RESULTS: A total of 170 participants were randomised. Retention was good (84%) and adherence was excellent (intensive, 83%; less intensive, 91%). The between-group difference in mean BMI indicated the intensive arm had BMIs 1.0 kg/m(2) lower than the controls [95% confidence interval (CI) -2.2 kg/m(2) to 0.2 kg/m(2)]. Similarly, a potential difference was found in weight (average difference of 2.8 kg, 95% CI -6.1 kg to 0.5 kg). The intensive arm had odds of maintaining on average 43% [odds ratio(OR) 1.4, 95% CI 0.6 to 3.5] higher than controls. None of these findings were statistically significant. Further analyses controlling for level of adherence indicated that average BMI was 1.2 kg/m(2) lower in the intensive arm than the control arm (95% CI -2.5 kg/m(2) to 0.0 kg/m(2)). The intensive intervention led to a statistically significant difference in weight (mean -3.7 kg, 95% CI -7.1 kg to -0.3 kg). The other secondary outcomes showed limited evidence of differences between groups. The intervention was delivered as planned, and both practitioners and participants were positive about the intervention and its impact. Although not powered to assess cost-effectiveness, results of this feasibility study suggest that neither intervention as currently delivered is likely to be cost-effective in routine practice. CONCLUSION: This is the first trial of an intervention for WLM in the UK, the intervention is feasible and acceptable, and retention and adherence were high. The main effectiveness outcome showed a promising mean difference in the intensive arm. Owing to the small sample size, we are limited in the conclusions we can draw. However, findings suggest that the intensive intervention may facilitate long-term weight maintenance and, therefore, further testing in an effectiveness trial may be indicated. Research examining WLM is in its infancy, further research is needed to develop our understanding of WLM and to expand theory to inform the development of interventions to be tested in rigorously designed RCTs with cost-effectiveness assessed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN35774128. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 50. See the NIHR Journals Library website for further project information.

Healthy eating and lifestyle in pregnancy (HELP): a protocol for a cluster randomised trial to evaluate the effectiveness of a weight management intervention in pregnancy.

BACKGROUND: Approximately 1 in 5 pregnant women in the United Kingdom are obese. In addition to being associated generally with poor health, obesity is known to be a contributing factor to pregnancy and birth complications and the retention of gestational weight can lead to long term obesity.This paper describes the protocol for a cluster randomised trial to evaluate whether a weight management intervention for obese pregnant women is effective in reducing women's Body Mass Index at 12 months following birth. METHODS/DESIGN: The study is a cluster randomised controlled trial involving 20 maternity units across England and Wales. The units will be randomised, 10 to the intervention group and 10 to the control group. 570 pregnant women aged 18 years or over, with a Body Mass Index of +/=30 (kg/m2) and between 12 and 20 weeks gestation will be recruited. Women allocated to the control group will receive usual care and two leaflets giving advice on diet and physical activity. In addition to their usual care and the leaflets, women allocated to the intervention group will be offered to attend a weekly 1.5 hour weight management group, which combines expertise from Slimming World with clinical advice and supervision from National Health Service midwives, until 6 weeks postpartum.Participants will be followed up at 36 weeks gestation and at 6 weeks, 6 months and 12 months postpartum. Body Mass Index at 12 months postpartum is the primary outcome. Secondary outcomes include pregnancy weight gain, quality of life, mental health, waist-hip ratio, child weight centile, admission to neonatal unit, diet, physical activity levels, pregnancy and birth complications, social support, self-regulation and self-efficacy. A cost effectiveness analysis and process evaluation will also be conducted. DISCUSSION: This study will evaluate the effectiveness of a theory-based intervention developed for obese pregnant women. If successful the intervention will equip women with the necessary knowledge and skills to enable them to make healthier choices for themselves and their unborn child. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN25260464 Date of registration: 16th April 2010.

The effectiveness and cost-effectiveness of the Family Nurse Partnership home visiting programme for first time teenage mothers in England: a protocol for the Building Blocks randomised controlled trial.

BACKGROUND: The Nurse Family Partnership programme was developed in the USA where it is made available to pregnant young mothers in some socially deprived geographic areas. The related Family Nurse Partnership programme was introduced in England by the Department of Health in 2006 with the aim of improving outcomes for the health, wellbeing and social circumstances of young first-time mothers and their children. METHODS / DESIGN: This multi-centre individually randomised controlled trial will recruit 1600 participants from 18 Primary Care Trusts in England, United Kingdom. The trial will evaluate the effectiveness of Family Nurse Partnership programme and usual care versus usual care for nulliparous pregnant women aged 19 or under, recruited by 24 weeks gestation and followed until the child's second birthday. Data will be collected from participants at baseline, 34-36 weeks gestation, 6, 12, 18 and 24 months following birth. Routine clinical data will be collected from maternity, primary care and hospital episodes statistics. Four primary outcomes are to be reported from the trial: birth weight; prenatal tobacco use; child emergency attendances and/or admissions within two years of birth; second pregnancy within two years of first birth. DISCUSSION: This trial will evaluate the effectiveness and cost effectiveness of the Family Nurse Partnership in England. The findings will provide evidence on pregnancy and early childhood programme outcomes for policy makers, health professionals and potential recipients in three domains (pregnancy and birth, child health and development, and parental life course and self-sufficiency) up to the child's second birthday. TRIAL REGISTRATION: Trial registration number: ISRCTN23019866.

Evaluating the family nurse partnership in England: the Building Blocks trial.

The Family Nurse Partnership (FNP) Programme is a structured intensive home visiting programme delivered by trained family nurses to nulliparous teenagers throughout pregnancy and until their child is two years old. Currently FNP is provided in over 60 primary healthcare sites in England with a planned capacity increase to 13,000 concurrent clients by 2015. Researchers from the South East Wales Trials Unit at Cardiff University are testing the effectiveness of FNP in England in the Building Blocks study--a randomised controlled trial funded by the Department of Health (DH). The trial team includes collaborators from the Universities of York, Bristol and Glamorgan.

Delays in response and triage times reduce patient satisfaction and enablement after using out-of-hours services.

BACKGROUND: several different models of out-of-hours primary care now exist in the UK. Important outcomes of care include users' satisfaction and enablement to manage their illness or condition, but the determinants of these outcomes in the unscheduled care domain are poorly understood. Aim. To identify predictors of user satisfaction and enablement across unscheduled care or GP out-of-hours service providers in Wales. The design of the study is a cross-sectional survey. The setting of the study is nine GP out-of-hours services, three Accident and Emergency units and an all Wales telephone advice service in Wales. METHODS: postal survey using the Out-of-hours Patient Questionnaire. Logistic regression was used to fit both satisfaction and enablement models, based on demographic variables, service provider and treatment received and perceptions or ratings of the care process. RESULTS: eight hundred and fifty-five of 3250 users responded (26% response rate, range across providers 14-41%, no evidence of non-response bias for age or gender). Treatment centre consultations were significantly associated with decreased patient satisfaction and decreased enablement compared with telephone advice. Delays in call answering or callback for triage and shorter consultations were significantly associated with lower satisfaction. Waiting more than a minute for initial call answering was associated with lower enablement. CONCLUSIONS: giving users more time to discuss their illness in consultations may enhance satisfaction and enablement but this may be resource intensive. More simple interventions to improve access by quicker response and triage, and keeping users informed of waiting times, could also serve to increase satisfaction and ultimately impact on their enablement.

The need to improve the interface between in-hours and out-of-hours GP care, and between out-of-hours care and self-care.

BACKGROUND: considerable changes have occurred over the last 5 years in the organization of out-of-hours care in the UK. Users' experiences of their care are an important part of 'quality of care' and are valuable for identifying areas for improvement. AIM: to identify strengths and weaknesses of out-of hours service provision in Wales. The design of the study is a cross-sectional survey. The setting of the study is nine GP services, three Accident and Emergency units and NHS Direct in Wales. METHOD: survey using the validated Out-of-Hours questionnaire. We identified the four most and least favourably rated items regarding users' experience of care. These were analysed by type of care provided, telephone advice, treatment centre and home visit groups. RESULTS: eight hundred and fifty-five of 3250 users responded (26% response rate). Across providers and types of care, consistent strengths were the 'manner of treatment by call operator' and the 'explanation of the next step by call operator'. Consistent weaknesses were the 'speed of call back by the clinician', the 'information provided by the GP', 'getting medication after the consultation' and 'when to contact the (in-hours) GP'. CONCLUSIONS: users of out-of-hours care identify clear and consistent strengths and weaknesses of service provision across Wales. Specific areas for improvement concern the interface between in-hours care and out-of-hours care and between out-of-hours care and self-care. GP surgeries need to give better information on how to access the out-of-hours services. Out-of-hours providers should improve their advice on how and when to access in-hours surgeries and also improve the availability of medicines after out-of-hours consultations.

Intrinsic patterns of behavior of epithelial stem cells.

The early concepts concerning hematopoietic and epithelial stem cells that were derived from kinetic studies have been greatly enhanced by new information about a range of other properties of somatic and embryonic stem cells. Firstly, the stem and amplifying pattern characteristically established by epithelial lineages has been found to represent an intrinsic pattern that is generated by somatic epithelial stem cells without the need for additional environmental information. Secondly, it is now apparent that somatic epithelial stem cells are plastic and can be directed into a range of new pathways of differentiation by heterotypic interactions. The mechanisms of this plasticity need to be reconciled with the normally stable commitment of these cells to production only of progeny entering a tightly restricted range of phenotypic pathways. The present review discusses the intrinsic properties of epithelial stem cells and how they may be acted upon by connective tissues to generate a wide range of phenotypically different epithelial structures.

Increased circulating normal and BCR-ABL+Ve progenitor numbers in Philadelphia chromosome-positive acute myeloid leukaemia.

We recorded elevated numbers of circulating myeloid and erythroid colony-forming cells in 15 adult patients with acute myeloid leukaemia (AML) who presented with high blood white cell counts. Since leukaemic blasts from three of these patients were Philadelphia chromosome-positive (Ph+), we were able to determine if blood progenitors from these particular patients arose from the leukaemic clone or from residual normal progenitors. Blasts and colonies were intensively investigated using a combination of cell surface marker analysis by flow cytometry, RT-PCR and interphase fluorescence in situ hybridization (FISH). FISH detected rearrangements within the major breakpoint BCR (M-BCR) region in blasts and in some myeloid and erythroid colonies from patients 1 and 2. The minor breakpoint (m-BCR) region was detected in blasts and in some myeloid and erythroid colonies from patient 3. RT-PCR detected long b2a2 BCR-ABL transcripts in blasts from patients 1 and 2, although misspliced short e1a2 transcripts were also seen in patient 1. Only e1a2 transcripts were found in blasts from patient 3. Flow sorting demonstrated the B-cell marker CD19 on blasts and on a proportion of myeloid and erythroid progenitors from patients 1 and 3. RT-PCR also detected IgH rearrangements, further evidence of B-cell differentiation, in blasts from these two patients. We conclude that both normal and clonal circulating progenitor numbers can be raised in both M-BCR and m-BCR Ph+ AML. The underlying cause, perhaps efflux from a congested marrow, may be common to AML patients with a high blood white cell count.