First steps: study protocol for a randomized controlled trial of the effectiveness of the Group Family Nurse Partnership (gFNP) program compared to routine care in improving outcomes for high-risk mothers and their children and preventing abuse

Background: Evidence from the USA suggests that the home-based Family Nurse Partnership program (FNP), extending from early pregnancy until infants are 24 months, can reduce the risk of child abuse and neglect throughout childhood. FNP is now widely available in the UK. A new variant, Group Family Nurse Partnership (gFNP) offers similar content but in a group context and for a shorter time, until infants are 12 months old. Each group comprises 8 to 12 women with similar expected delivery dates and their partners. Its implementation has been established but there is no evidence of its effectiveness.

Methods/Design: The study comprises a multi-site randomized controlled trial designed to identify the benefits of gFNP compared to standard care. Participants (not eligible for FNP) must be either aged <20 years at their last menstrual period (LMP) with one or more previous live births, or aged 20 to 24 at LMP with low educational qualifications and no previous live births. 'Low educational qualifications' is defined as not having both Maths and English Language GCSE at grade C or higher or, if they have both, no more than four in total at grade C or higher. Exclusions are: under 20 years and previously received home-based FNP and, in either age group, severe psychotic mental illness or not able to communicate in English. Consenting women are randomly allocated (minimized by site and maternal age group) when between 10 and 16 weeks pregnant to either to the 44 session gFNP program or to standard care after the collection of baseline information. Researchers are blind to group assignment. The primary outcomes at 12 months are child abuse potential based on the revised Adult-Adolescent Parenting Inventory and parent/infant interaction coded using the CARE Index based on a video-taped interaction. Secondary outcomes are maternal depression, parenting stress, health related quality of life, social support, and use of services.

Discussion: This is the first study of the effectiveness of gFNP in the UK. Results should inform decision-making about its delivery alongside universal services, potentially enabling a wider range of families to benefit from the FNP curriculum and approach to supporting parenting.

The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial.:the results of the LRF AML14 trial

The acute myeloid leukaemia (AML)14 trial addressed four therapeutic questions in patients predominantly aged over 60 years with AML and High Risk Myelodysplastic Syndrome: (i) Daunorubicin 50 mg/m(2) vs. 35 mg/m(2); (ii) Cytarabine 200 mg/m(2) vs. 400 mg/m(2) in two courses of DA induction; (iii) for part of the trial, patients allocated Daunorubicin 35 mg/m(2) were also randomized to receive, or not, the multidrug resistance modulator PSC-833 in a 1:1:1 randomization; and (iv) a total of three versus four courses of treatment. A total of 1273 patients were recruited. The response rate was 62% (complete remission 54%, complete remission without platelet/neutrophil recovery 8%); 5-year survival was 12%. No benefits were observed in either dose escalation randomization, or from a fourth course of treatment. There was a trend for inferior response in the PSC-833 arm due to deaths in induction. Multivariable analysis identified cytogenetics, presenting white blood count, age and secondary disease as the main predictors of outcome. Although patients with high Pgp expression and function had worse response and survival, this was not an independent prognostic factor, and was not modified by PSC-833. In conclusion, these four interventions have not improved outcomes in older patients. New agents need to be explored and novel trial designs are required to maximise prospects of achieving timely progress.

The effect of radiation technique and bladder filling on the acute toxicity of pelvic radiotherapy for localized high risk prostate cancer

Purpose: The goal of this project was to see if using IMRT to deliver elective pelvic nodal irradiation (EPNI) for prostate cancer reduced acute treatment toxicity.

Methods: Two hundred and thirty patients were enrolled into prospective trials delivering EPNI with a concomitant hypofractionated IMRT boost to the prostate. During accrual, the method of EPNI delivery changed as new literature emerged. Three methods were used (1) 4FB, (2) IMRT with 2 cm CTV margins around the pelvic vessels as suggested by Shih et al. (2005) [7] (IMRT-Shih), and (3) IMRT with nodal volumes suggested by the RTOG (IMRT-RTOG). Initially patients were treated with an empty bladder, with the remainder treated with bladder full.

Results: Patients in the 4FB group had higher rates of grade 2 acute GI toxicities compared to the IMRT-Shih and IMRT-RTOG groups (31.9% vs 20.8% vs 7.2%, p = 0.0009). Patients in the 4FB group had higher rates of grade 3 urinary frequency compared to the two IMRT groups (8.5% vs 0% vs 0%, p = 0.027). However, multivariate analysis suggested the factor that most influenced toxicity was bladder filling followed by IMRT.

Conclusions: Bladder filling appeared to be the dominant factor which predicted for acute toxicity, followed by the use of IMRT.

The Prenatal Distress Questionnaire:An investigation of factor structure in a high risk population

Background: The Prenatal Distress Questionnaire (PDQ) is a short measure designed to assess specific worries and concerns related to pregnancy. The aim of this study was to confirm the factor structure of the PDQ in a group of pregnant women with a small for gestational age infant (< 10th centile). Methods: The first PDQ assessment for each of 337 pregnant women participating in the Prospective Observational Trial to Optimise paediatric health (PORTO) study was analysed. All women enrolled in the study were identified as having a small for gestational age foetus (< 10th centile), thus representing an 'elevated risk' group. Data were analysed using confirmatory factor analysis (CFA). Three models of the PDQ were evaluated and compared in the current study: a theoretical uni-dimensional measurement model, a bi-dimensional model, and a three-factor model solution. Results: The three-factor model offered the best fit to the data while maintaining sound theoretical grounds(χ² (51df) = 128.52; CFI = 0.97; TLI = 0.96; RMSEA = 0.07). Factor 1 contained items reflecting concerns about birth and the baby, factor 2 concerns about physical symptoms and body image and factor 3 concerns about emotions and relationships. Conclusions: CFA confirmed that the three-factor model provided the best fit, with the items in each factor reflecting the findings of an earlier exploratory data analysis. © 2013 Society for Reproductive and Infant Psychology.

Increasing Fruit and Vegetable Intake Has No Dose-Response Effect on Conventional Cardiovascular Risk Factors in Overweight Adults at High Risk of Developing Cardiovascular Disease

BACKGROUND: Improving diet and lifestyle is important for prevention of cardiovascular disease (CVD). Observational evidence suggests that increasing fruit and vegetable (FV) consumption may lower CVD risk, largely through modulation of established risk factors, but intervention data are required to fully elucidate the mechanisms by which FVs exert benefits on vascular health.

OBJECTIVE: The aim of this study was to examine the dose-response effect of FV intake on cardiovascular risk factors in adults at high CVD risk.

METHODS: This was a randomized controlled parallel group study involving overweight adults (BMI: >27 and ≤35 kg/m(2)) with a habitually low FV intake (≤160 g/d) and a high total risk of developing CVD (estimated ≥20% over 10 y). After a 4-wk run-in period where FV intake was limited to <2 portions/d (<160 g/d), 92 eligible participants were randomly assigned to 1 of 3 groups: to consume either 2, 4, or 7 portions (equivalent to 160 g, 320 g, or 560 g, respectively) of FVs daily for 12 consecutive weeks. Fasting venous blood samples were collected at baseline (week 4) and post-intervention (week 16) for analysis of lipid fractions and high-sensitivity C-reactive protein (hsCRP) concentrations. Compliance with the FV intervention was determined with use of self-reported FV intake and biomarkers of micronutrient status. Ambulatory blood pressure and body composition were also measured pre- and post-intervention.

RESULTS: A total of 89 participants completed the study and body composition remained stable throughout the intervention period. Despite good compliance with the intervention, no significant difference was found between the FV groups for change in measures of ambulatory blood pressure, plasma lipids, or hsCRP concentrations.

CONCLUSIONS: There was no evidence of a dose-response effect of FV intake on conventional CVD risk factors measured in overweight adults at high CVD risk. This trial was registered at clinicaltrials.gov as NCT00874341.

Effect of a Web-Based Behavior Change Program on Weight Loss and Cardiovascular Risk Factors in Overweight and Obese Adults at High Risk of Developing Cardiovascular Disease:Randomized Controlled Trial

BACKGROUND: Web-based programs are a potential medium for supporting weight loss because of their accessibility and wide reach. Research is warranted to determine the shorter- and longer-term effects of these programs in relation to weight loss and other health outcomes.

OBJECTIVE: The aim was to evaluate the effects of a Web-based component of a weight loss service (Imperative Health) in an overweight/obese population at risk of cardiovascular disease (CVD) using a randomized controlled design and a true control group.

METHODS: A total of 65 overweight/obese adults at high risk of CVD were randomly allocated to 1 of 2 groups. Group 1 (n=32) was provided with the Web-based program, which supported positive dietary and physical activity changes and assisted in managing weight. Group 2 continued with their usual self-care (n=33). Assessments were conducted face-to-face. The primary outcome was between-group change in weight at 3 months. Secondary outcomes included between-group change in anthropometric measurements, blood pressure, lipid measurements, physical activity, and energy intake at 3, 6, and 12 months. Interviews were conducted to explore participants' views of the Web-based program.

RESULTS: Retention rates for the intervention and control groups at 3 months were 78% (25/32) vs 97% (32/33), at 6 months were 66% (21/32) vs 94% (31/33), and at 12 months were 53% (17/32) vs 88% (29/33). Intention-to-treat analysis, using baseline observation carried forward imputation method, revealed that the intervention group lost more weight relative to the control group at 3 months (mean -3.41, 95% CI -4.70 to -2.13 kg vs mean -0.52, 95% CI -1.55 to 0.52 kg, P<.001), at 6 months (mean -3.47, 95% CI -4.95 to -1.98 kg vs mean -0.81, 95% CI -2.23 to 0.61 kg, P=.02), but not at 12 months (mean -2.38, 95% CI -3.48 to -0.97 kg vs mean -1.80, 95% CI -3.15 to -0.44 kg, P=.77). More intervention group participants lost ≥5% of their baseline body weight at 3 months (34%, 11/32 vs 3%, 1/33, P<.001) and 6 months (41%, 13/32 vs 18%, 6/33, P=.047), but not at 12 months (22%, 7/32 vs 21%, 7/33, P=.95) versus control group. The intervention group showed improvements in total cholesterol, triglycerides, and adopted more positive dietary and physical activity behaviors for up to 3 months verus control; however, these improvements were not sustained.

CONCLUSIONS: Although the intervention group had high attrition levels, this study provides evidence that this Web-based program can be used to initiate clinically relevant weight loss and lower CVD risk up to 3-6 months based on the proportion of intervention group participants losing ≥5% of their body weight versus control group. It also highlights a need for augmenting Web-based programs with further interventions, such as in-person support to enhance engagement and maintain these changes.

Identification and validation of the dopamine agonist bromocriptine as a novel therapy for high-risk myelodysplastic syndromes and secondary acute myeloid leukemia

Myelodysplastic syndromes (MDS) represent a broad spectrum of diseases characterized by their clinical manifestation as one or more cytopenias, or a reduction in circulating blood cells. MDS is predominantly a disease of the elderly, with a median age in the UK of around 75. Approximately one third of MDS patients will develop secondary acute myeloid leukemia (sAML) that has a very poor prognosis. Unfortunately, most standard cytotoxic agents are often too toxic for older patients. This means there is a pressing unmet need for novel therapies that have fewer side effects to assist this vulnerable group. This challenge was tackled using bioinformatic analysis of available transcriptomic data to establish a gene-based signature of the development and progression of MDS. This signature was then used to identify novel therapeutic compounds via statistically-significant connectivity mapping. This approach suggested re-purposing an existing and widely-prescribed drug, bromocriptine as a novel potential therapy in these disease settings. This drug has shown selectivity for leukemic cells as well as synergy with current therapies.