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.

The impact of living in a bio-secure bubble on mental health: An examination in elite cricket.

The COVID-19 pandemic has had a profound impact on many people's lives, including the use of bio-secure environments to facilitate the continuation of professional sport. Although it is well documented that the pandemic has negatively impacted mental health, the impact of bio-bubbles on mental health is yet to be investigated. In the present study we sought to identify the impact of bio-bubbles on the mental health of those residing within, and then to explore the underlying mechanism of any such impact. Individuals (n = 68) who resided in England and Wales Cricket Board (ECB) created bio-bubbles between March 2020 and April 2021 provided data, regarding their time inside and outside of bio-bubbles, on measures of mental health and basic psychological need satisfaction and frustration. Analysis revealed that bio-bubbles increased anxiety and depression and reduced wellbeing. Additionally, MEMORE mediation analyses revealed that autonomy frustration mediated the relationship between bubble status and all mental health markers. Furthermore, compared to men, women were more likely to experience elevated levels of anxiety and depression inside the bubble. The findings suggest that bio-bubbles negatively impact mental health and further suggest that satisfaction and frustration of basic psychological needs is a contributing factor. Findings suggest organizations tasked with creating bio-bubbles would do well to tailor their environment with an awareness of the importance of basic psychological needs and sex differences in relation to mental health. To the best of our knowledge, this research represents the first investigation of the impact of bio-bubbles on mental health.

Regulation of human trophoblast gene expression by endogenous retroviruses.

The placenta is a fast-evolving organ with large morphological and histological differences across eutherians, but the genetic changes driving placental evolution have not been fully elucidated. Transposable elements, through their capacity to quickly generate genetic variation and affect host gene regulation, may have helped to define species-specific trophoblast gene expression programs. Here we assess the contribution of transposable elements to human trophoblast gene expression as enhancers or promoters. Using epigenomic data from primary human trophoblast and trophoblast stem-cell lines, we identified multiple endogenous retrovirus families with regulatory potential that lie close to genes with preferential expression in trophoblast. These largely primate-specific elements are associated with inter-species gene expression differences and are bound by transcription factors with key roles in placental development. Using genetic editing, we demonstrate that several elements act as transcriptional enhancers of important placental genes, such as CSF1R and PSG5. We also identify an LTR10A element that regulates ENG expression, affecting secretion of soluble endoglin, with potential implications for preeclampsia. Our data show that transposons have made important contributions to human trophoblast gene regulation, and suggest that their activity may affect pregnancy outcomes.

Noncontact Injury Distribution and Relationship With Preseason Training Load and Nonmodifiable Risk Factors in Rugby Union Players Across Multiple Seasons.

ABSTRACT: Evans, SL, Whittaker, G, Elphinstone Davis, E, Jones, ES, Hardy, J, and Owen, JA. Noncontact injury distribution and relationship with preseason training load and non-modifiable risk factors in Rugby Union players across multiple seasons. J Strength Cond Res 37(7): 1456-1462, 2023-This study examined the distribution of noncontact injury during phases of the competitive season and the association between preseason training load (TL) and nonmodifiable risk factors on injury risk during these phases. Injury data were recorded from 1 senior academy team over 3 seasons (2017-2020) and analyzed across early-season, midseason, and late-season phases. A generalized estimating equation was used to model risk factors with noncontact injury for selected phases. The highest noncontact injury incidence occurred in the late-season phase (22.2 per 1,000 hours) compared with early (13.7 per 1,000 hours, p < 0.001) and midseason phases (15.5 per 1,000 hours, p = 0.001). Low preseason TL (8,949-12,589 arbitrary units; odds ratio [OR], 95% confidence interval [CI] = 4.7, 1.0-21.6; p = 0.04) and low preseason TL combined with high early-season TL and injury in the early-season phase (OR, 95% CI = 6.5, 1.1-35.5; p = 0.03) were associated with greater midseason noncontact injury risk. In addition, low preseason TL combined with previous injury was associated with increased risk of noncontact injury risk in the late season (OR, 95% CI = 12.2, 0.9-15.6, p = 0.05). Our results suggest players are at a greater injury risk during the late-season phase, with low preseason cumulative loads combined with a history of previous injury associated with increased in-season injury risk. Strength and conditioning coaches should therefore monitor cumulative preseason TL alongside screening for previous injury history to identify athletes at greater risk of noncontact injury risk during the competitive season.

Psychosocial and Physiological Factors Affecting Selection to Regional Age-Grade Rugby Union Squads: A Machine Learning Approach.

Talent selection programmes choose athletes for talent development pathways. Currently, the set of psychosocial variables that determine talent selection in youth Rugby Union are unknown, with the literature almost exclusively focusing on physiological variables. The purpose of this study was to use a novel machine learning approach to identify the physiological and psychosocial models that predict selection to a regional age-grade rugby union team. Age-grade club rugby players (n = 104; age, 15.47 ± 0.80; U16, n = 62; U18, n = 42) were assessed for physiological and psychosocial factors during regional talent selection days. Predictive models (selected vs. non-selected) were created for forwards, backs, and across all players using Bayesian machine learning. The generated physiological models correctly classified 67.55% of all players, 70.09% of forwards, and 62.50% of backs. Greater hand-grip strength, faster 10 m and 40 m sprint, and power were common features for selection. The generated psychosocial models correctly classified 62.26% of all players, 73.66% of forwards, and 60.42% of backs. Reduced burnout, reduced emotional exhaustion, and lower reduced sense of accomplishment, were common features for selection. Selection appears to be predominantly based on greater strength, speed, and power, as well as lower athlete burnout.

Match and training injury risk in semi-professional rugby union: A four-year study.

OBJECTIVES: Describe medical-attention and time-loss injuries during matches and training in a Welsh Premiership Rugby Union team. DESIGN: Prospective cohort observational study. METHODS: Injury incidence, severity, burden, location, type, and cause were determined in sixty-nine players from one semi-professional Rugby Union team. RESULTS: Medical-attention and time-loss injury incidence was greater for matches (incidence, 95% confidence interval = 122.8, 108.9-138.4 and 99.8, 87.3-114.0) than training (incidence, 95% confidence interval = 2.2, 1.8-2.6 and 1.7, 1.4-2.1) per 1000 player-hours. Injury severity was similar for matches (time-loss ± standard deviation = 24.9 ± 30.8 days) and training (time-loss ± SD = 22.4 ± 29.1 days), with injury burden greater for matches (burden, 95% confidence interval = 3148.8, 3019.8-6479.2) than training (burden, 95% confidence interval = 49.7, 36.7-129.6). Lower-limb time-loss injuries were most common during matches (incidence, 95% confidence interval = 46.0, 37.9-55.9) and training (incidence, 95% confidence interval = 1.3, 1.0-1.7) per 1000 player-hours, whilst upper-limb injuries were most severe in matches (time-loss, 95% confidence interval = 38.8, 28.3-44.4 days) and training (time-loss, 95% confidence interval = 45.9, 17.5-52.7 days). The prevalent cause of contact-injury was tackling (31%) with running (11%) the common cause of non-contact injury. CONCLUSIONS: Time-loss match-injury incidence, severity, and burden were similar to data reported in the professional tier, with similar patterns of injuries for location, type, and inciting event. These figures are greater than previously reported for semi-professional Rugby Union, warranting further investigation at this level of play.

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.

3D model of harlequin ichthyosis reveals inflammatory therapeutic targets.

The biology of harlequin ichthyosis (HI), a devastating skin disorder caused by loss-of-function mutations in the gene ABCA12, is poorly understood, and to date, no satisfactory treatment has been developed. We sought to investigate pathomechanisms of HI that could lead to the identification of new treatments for improving patients' quality of life. In this study, RNA-Seq and functional assays were performed to define the effects of loss of ABCA12 using HI patient skin samples and an engineered CRISPR/Cas9 ABCA12 KO cell line. The HI living skin equivalent (3D model) recapitulated the HI skin phenotype. The cytokines IL-36α and IL-36γ were upregulated in HI skin, whereas the innate immune inhibitor IL-37 was strongly downregulated. We also identified STAT1 and its downstream target inducible nitric oxide synthase (NOS2) as being upregulated in the in vitro HI 3D model and HI patient skin samples. Inhibition of NOS2 using the inhibitor 1400W or the JAK inhibitor tofacitinib dramatically improved the in vitro HI phenotype by restoring the lipid barrier in the HI 3D model. Our study has identified dysregulated pathways in HI skin that are feasible therapeutic targets.

Network Analysis of Competitive State Anxiety.

Competitive state anxiety is an integral feature of sports performance but despite its pervasiveness, there is still much debate concerning the measurement of the construct. Adopting a network approach that conceptualizes symptoms of a construct as paired associations, we proposed re-examining competitive state anxiety as a system of interacting components in a dataset of 485 competitive athletes from the United Kingdom. Following a process of data reduction, we estimated a network structure for 15 items from the modified Three Factor Anxiety Inventory using the graphical LASSO algorithm. We then examined network connectivity using node predictability. Exploratory graph analysis was used to detect communities in the network and bridge expected influence calculated to estimate the influence of items from one community to items in other communities. The resultant network produced a range of node predictability values. Community detection analysis derived three communities that corresponded with previous research and several nodes were identified that bridged these communities. We conclude that network analysis is a useful tool to explore the competitive state anxiety response and we discuss how the results of our analysis might inform the assessment of the construct and how this assessment might inform interventions.

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.

Interventions to provide culturally-appropriate maternity care services: factors affecting implementation.

BACKGROUND: The World Health Organization recently made a recommendation supporting 'culturally-appropriate' maternity care services to improve maternal and newborn health. This recommendation results, in part, from a systematic review we conducted, which showed that interventions to provide culturally-appropriate maternity care have largely improved women's use of skilled maternity care. Factors relating to the implementation of these interventions can have implications for their success. This paper examines stakeholders' perspectives and experiences of these interventions, and facilitators and barriers to implementation; and concludes with how they relate to the effects of the interventions on care-seeking outcomes. METHODS: We based our analysis on 15 papers included in the systematic review. To extract, collate and organise data on the context and conditions from each paper, we adapted the SURE (Supporting the Use of Research Evidence) framework that lists categories of factors that could influence implementation. We considered information from the background and discussion sections of papers included in the systematic review, as well as cost data and qualitative data when included. RESULTS: Women's and other stakeholders' perspectives on the interventions were generally positive. Four key themes emerged in our analysis of facilitators and barriers to implementation. Firstly, interventions must consider broader economic, geographical and social factors that affect ethnic minority groups' access to services, alongside providing culturally-appropriate care. Secondly, community participation is important in understanding problems with existing services and potential solutions from the community perspective, and in the development and implementation of interventions. Thirdly, respectful, person-centred care should be at the core of these interventions. Finally, cohesiveness is essential between the culturally-appropriate service and other health care providers encountered by women and their families along the continuum of care through pregnancy until after birth. CONCLUSION: Several important factors should be considered and addressed when implementing interventions to provide culturally-appropriate care. These factors reflect more general goals on the international agenda of improving access to skilled maternity care; providing high-quality, respectful care; and community participation.

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 interventions to provide culturally appropriate maternity care in increasing uptake of skilled maternity care: a systematic review.

Addressing cultural factors that affect uptake of skilled maternity care is recognized as an important step in improving maternal and newborn health. This article describes a systematic review to examine the evidence available on the effects of interventions to provide culturally appropriate maternity care on the use of skilled maternity care during pregnancy, for birth or in the postpartum period. Items published in English, French and/or Spanish between 1 January 1990 and 31 March 2014 were considered. Fifteen studies describing a range of interventions met the inclusion criteria. Data were extracted on population and intervention characteristics; study design; definitions and data for relevant outcomes; and the contexts and conditions in which interventions occurred. Because most of the included studies focus on antenatal care outcomes, evidence of impact is particularly limited for care seeking for birth and after birth. Evidence in this review is clustered within a small number of countries, and evidence from low- and middle-income countries is notably lacking. Interventions largely had positive effects on uptake of skilled maternity care. Cultural factors are often not the sole factor affecting populations' use of maternity care services. Broader social, economic, geographical and political factors interacted with cultural factors to affect targeted populations' access to services in included studies. Programmes and policies should seek to establish an enabling environment and support respectful dialogue with communities to improve use of skilled maternity care. Whilst issues of culture are being recognized by programmes and researchers as being important, interventions that explicitly incorporate issues of culture are rarely evaluated.

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.