The Gestational Obesity Weight Management: Implementation of National Guidelines (GLOWING) study: a pilot cluster randomised controlled trial.

BACKGROUND: Pregnancy weight management interventions can improve maternal diet, physical activity, gestational weight gain, and postnatal weight retention. UK guidelines were published in 2010 but health professionals report multiple complex barriers to practice. GLOWING used social cognitive theory to address evidence-based barriers to midwives' implementation of weight management guidelines into routine practice. This paper reports the pilot trial outcomes relating to feasibility and acceptability of intervention delivery and trial procedures. METHODS: GLOWING was a multi-centre parallel-group pilot cluster RCT comparing the delivery of a behaviour change intervention for midwives (delivered as training workshops) with usual practice. The clusters were four NHS Trusts in Northeast England, randomised to intervention or control arms. Blinding of allocation was not possible due to the nature of the intervention. We aimed to deliver the intervention to all eligible midwives in the intervention arm, in groups of 6 midwives per workshop, and to pilot questionnaire data collection for a future definitive trial. Intervention arm midwives' acceptability of GLOWING content and delivery was assessed using a mixed methods questionnaire, and pregnant women's acceptability of trial procedures by interviews. Quantitative data were analysed descriptively and qualitative data thematically. RESULTS: In intervention arm Trusts, 100% of eligible midwives (n = 67) were recruited to, and received, the intervention; however, not all workshops had the planned number of attendees (range 3-8). The consent rate amongst midwives randomised (n = 100) to complete questionnaires was 74% (n = 74) (95% CI 65%, 83%), and overall completion rate 89% (n = 66) (95% CI 82%, 96%). Follow-up response rate was 66% (n = 49) (95% CI 55%, 77%), with a marked difference between intervention (39%, n = 15) and control (94%, n = 34) groups potentially due to the volume of research activities. Overall, 64% (n = 47) (95% CI 53%, 75%) completed both baseline and follow-up questionnaires. Midwives viewed the intervention as acceptable and directly relevant to routine practice. The least popular components related to scripted role-plays. Pregnant women viewed the recruitment and trial processes to be acceptable. CONCLUSIONS: This rigorously conducted pilot study demonstrated feasibility intervention delivery and a high level of acceptability amongst participants. It has provided information required to refine the intervention and trial protocol, enhancing confidence that a definitive trial could be carried out. TRIAL REGISTRATION: ISRCTN46869894; retrospectively registered 25th May 2016, www.isrctn.com/ISRCTN46869894 .

Maternal Obesity and Patterns in Postnatal Diet, Physical Activity and Weight among a Highly Deprived Population in the UK: The GLOWING Pilot Trial.

Preconception obesity is associated with adverse pregnancy outcomes and deprivation. The postnatal period provides an opportunity for preconception intervention. There is a lack of published postnatal behaviour and weight data to inform intervention needs. Secondary analysis of the GLOWING study explored postnatal diet, physical activity (PA) and weight among women living with obesity in deprivation. Thirty-nine women completed food frequency and PA questionnaires and provided weight measurement(s) between 3-12 months postnatal. Women's diet and PA fell short of national guidelines, especially for fruit/vegetables (median 1.6-2.0 portions/day) and oily fish (0-4 g/day). PA was predominantly light intensity. Patterns in weight change across time points indicated postnatal weight loss compared with 1st (median -0.8 to -2.3 kg) and 3rd-trimester weights (-9.0 to -11.6 kg). Weight loss was higher among women without excessive gestational weight gain (GWG) (-2.7 to -9.7 kg) than those with excessive GWG (2.3 to -1.8 kg), resulting in postnatal weight measurements lower than their 1st trimester. These pilot data suggest preconception interventions should commence in pregnancy with a focus on GWG, and postnatal women need early support to achieve guideline-recommendations for diet and PA. Further research in a larger population could inform preconception intervention strategies to tackle inequalities in maternal obesity and subsequent pregnancy outcomes.

The Infant KIdney Dialysis and Utrafiltration (I-KID) Study: A Stepped-Wedge Cluster-Randomized Study in Infants, Comparing Peritoneal Dialysis, Continuous Venovenous Hemofiltration, and Newcastle Infant Dialysis Ultrafiltration System, a Novel Infant Hemodialysis Device.

OBJECTIVES: Renal replacement therapy (RRT) options are limited for small babies because of lack of available technology. We investigated the precision of ultrafiltration, biochemical clearances, clinical efficacy, outcomes, and safety profile for a novel non-Conformité Européenne-marked hemodialysis device for babies under 8 kg, the Newcastle Infant Dialysis Ultrafiltration System (NIDUS), compared with the current options of peritoneal dialysis (PD) or continuous venovenous hemofiltration (CVVH). DESIGN: Nonblinded cluster-randomized cross-sectional stepped-wedge design with four periods, three sequences, and two clusters per sequence. SETTING: Clusters were six U.K. PICUs. PATIENTS: Babies less than 8 kg requiring RRT for fluid overload or biochemical disturbance. INTERVENTIONS: In controls, RRT was delivered by PD or CVVH, and in interventions, NIDUS was used. The primary outcome was precision of ultrafiltration compared with prescription; secondary outcomes included biochemical clearances. MEASUREMENTS AND MAIN RESULTS: At closure, 97 participants were recruited from the six PICUs (62 control and 35 intervention). The primary outcome, obtained from 62 control and 21 intervention patients, showed that ultrafiltration with NIDUS was closer to that prescribed than with control: sd controls, 18.75, intervention, 2.95 (mL/hr); adjusted ratio, 0.13; 95% CI, 0.03-0.71; p = 0.018. Creatinine clearance was smallest and least variable for PD (mean, sd ) = (0.08, 0.03) mL/min/kg, larger for NIDUS (0.46, 0.30), and largest for CVVH (1.20, 0.72). Adverse events were reported in all groups. In this critically ill population with multiple organ failure, mortality was lowest for PD and highest for CVVH, with NIDUS in between. CONCLUSIONS: NIDUS delivers accurate, controllable fluid removal and adequate clearances, indicating that it has important potential alongside other modalities for infant RRT.

Midwives' survey of their weight management practice before and after the GLOWING guideline implementation intervention: A pilot cluster randomised controlled trial.

BACKGROUND: Maternal weight management is a priority due to pregnancy risks for women and babies. Interventions significantly improve maternal diet, physical activity, weight, and pregnancy outcomes. There are complex barriers to midwives' implementation of guidelines; low self-efficacy is a core implementation barrier. The GLOWING intervention uses social cognitive theory (SCT) to address evidence-based barriers to practice. The intervention aimed to support midwives' implementation of guidelines. METHODS: An external rehearsal pilot cluster randomised controlled trial in four NHS Trusts (clusters) in England, UK. Clusters were randomised to intervention (where all eligible midwives received the intervention) or control (no intervention delivered) arms. A random sample of 100 midwives were invited to complete questionnaires pre- and post-intervention. UK guideline recommendations relating to midwives' practice were categorised into: 1) communication-related behaviours (including weight- and risk-communication), and 2) support/intervention-related behaviours (including diet/nutrition, physical activity, weight management, referrals/signposting). Questionnaires were developed using SCT constructs (self-efficacy, outcome expectancies, intentions, behaviours) and 7-point Likert scale, converted to a 0-100 scale. Higher scores were more positive. Descriptive statistics compared intervention and control arms, pre- and post-intervention. RESULTS: Seventy-four midwives consented and 68 returned questionnaires. Pre-intervention, self-efficacy for support/intervention-related behaviours scored lowest. In controls, there was limited difference between the pre- and post-intervention scores. Post-intervention, mean (SD) scores were consistently higher among intervention midwives than controls, particularly for support/intervention self-efficacy (71.4 (17.1) vs. 58.4 (20.1)). Mean (SD) self-efficacy was higher post-intervention than pre-intervention for all outcomes among intervention midwives, and consistently higher than controls. Mean differences pre- and post-intervention were greatest for support/intervention self-efficacy (17.92, 95% CI 7.78-28.07) and intentions (12.68, 95% CI 2.76-22.59). Self-efficacy was particularly increased for diet/nutrition and physical activity (MD 24.77, 95% CI 14.09-35.44) and weight management (18.88, 95% CI 7.88-29.88) behaviours, which showed the largest increase in scores. CONCLUSIONS: This study supports the theoretical models used to develop GLOWING, where low self-efficacy was a core implementation barrier. Results suggest that GLOWING successfully targets self-efficacy, potentially with a positive impact on guideline implementation. A definitive trial is required to determine effectiveness. TRIAL REGISTRATION: ISRCTN46869894, retrospectively registered 25/05/2016, http://isrctn.com/ISRCTN46869894.

Advancing cluster randomised trials in children's therapy: a survey of the acceptability of trial behaviours to therapists and parents.

BACKGROUND: Randomised controlled trials of non-pharmacological interventions in children's therapy are rare. This is, in part, due to the challenges of the acceptability of common trial designs to therapists and service users. This study investigated the acceptability of participation in cluster randomised controlled trials to therapists and service users. METHODS: A national electronic survey of UK occupational therapists, physiotherapists, speech and language therapists, service managers, and parents of children who use their services. Participants were recruited by NHS Trusts sharing a link to an online questionnaire with children's therapists in their Trust and with parents via Trust social media channels. National professional and parent networks also recruited to the survey. We aimed for a sample size of 325 therapists, 30 service managers, and 60 parents. Trial participation was operationalised as three behaviours undertaken by both therapists and parents: agreeing to take part in a trial, discussing a trial, and sharing information with a research team. Acceptability of the behaviours was measured using an online questionnaire based on the Theoretical Framework of Acceptability constructs: affective attitude, self-efficacy, and burden. The general acceptability of trials was measured using the acceptability constructs of intervention coherence and perceived effectiveness. Data were collected from June to September 2020. Numerical data were analysed using descriptive statistics and textual data by descriptive summary. RESULTS: A total of 345 survey responses were recorded. Following exclusions, 249 therapists and 40 parents provided data which was 69.6% (289/415) of the target sample size. It was not possible to track the number of people invited to take the survey nor those who viewed, but did not complete, the online questionnaire for calculation of response rates. A completion rate (participants who completed the last page of the survey divided by the participants who completed the first, mandatory, page of the survey) of 42.9% was achieved. Of the three specified trial behaviours, 140/249 (56.2%) therapists were least confident about agreeing to take part in a trial. Therapists (135/249, 52.6%) reported some confidence they could discuss a trial with a parent and child at an appointment. One hundred twenty of 249 (48.2%) therapists reported confidence in sharing information with a research team through questionnaires and interviews or sharing routine health data. Therapists (140/249, 56.2%) felt that taking part in the trial would take a lot of effort and resources. Support and resources, confidence with intervention allocation, and sense of control and professional autonomy over clinical practice were factors that positively affected the acceptability of trials. Of the 40 parents, twelve provided complete data. Most parents (18/40, 45%) agreed that it was clear how trials improve children's therapies and outcomes and that a cluster randomised trial made sense to them in their therapy situation (12/29, 30%). CONCLUSIONS: Using trials to evaluate therapy interventions is, in principle, acceptable to therapists, but their willingness to participate in trials is variable. The willingness to participate may be particularly influenced by their views related to the burden associated with trials, intervention allocation, and professional autonomy.

A collaborative approach to develop an intervention to strengthen health visitors' role in prevention of excess weight gain in children.

BACKGROUND: The high prevalence of childhood obesity is a concern for public health policy and practitioners, leading to a focus on early prevention. UK health visitors (HVs) are well-positioned to prevent excessive weight gain trends in pre-school children but experience barriers to implementing guideline recommended practices. This research engaged with HVs to design an intervention to strengthen their role in prevention of early childhood obesity. METHODS: We describe the processes we used to develop a behaviour change intervention and measures to test its feasibility. We conducted a systematic review to identify factors associated with implementation of practices recommended for prevention of early childhood obesity. We carried out interactive workshops with HVs who deliver health visiting services in County Durham, England. Workshop format was informed by the behaviour change wheel framework for developing theory-based interventions and incorporated systematic review evidence. As intended recipients of the intervention, HVs provided their views of what is important and acceptable in the local context. The findings of the workshops were combined in an iterative process to inform the four steps of the Implementation Intervention development framework that was adapted as a practical guide for the development process. RESULTS: Theoretical analysis of the workshop findings revealed HVs' capabilities, opportunities and motivations related to prevention of excess weight in 0-2 year olds. Intervention strategies deemed most likely to support implementation (enablement, education, training, modelling, persuasion) were combined to design an interactive training intervention. Measures to test acceptability, feasibility, and fidelity of delivery of the proposed intervention were identified. CONCLUSIONS: An interactive training intervention has been designed, informed by theory, evidence, and expert knowledge of HVs, in an area of health promotion that is currently evolving. This research addresses an important evidence-practice gap in prevention of childhood obesity. The use of a systematic approach to the development process, identification of intervention contents and their hypothesised mechanisms of action provides an opportunity for this research to contribute to the body of literature on designing of implementation interventions using a collaborative approach. Future research should be directed to evaluate the acceptability and feasibility of the intervention.

Developing the FEEDS toolkit of parent-delivered interventions for eating, drinking and swallowing difficulties in young children with neurodisability: findings from a Delphi survey and stakeholder consultation workshops.

BACKGROUND: Young children with neurodisability commonly experience eating, drinking and swallowing difficulties (EDSD). Little is documented about which interventions and outcomes are most appropriate for such children. We aimed to seek consensus between parents of children with neurodisability and health professionals on the appropriate interventions and outcomes to inform future clinical developments and research studies. METHODS: Two populations were sampled: parents of children aged up to 12 years with neurodisability who experienced EDSD; health professionals working with children and young people (aged 0-18 years) with neurodisability with experience of EDSD. Participants had taken part in a previous national survey and were invited to take part in a Delphi survey and/or consultation workshops. Two rounds of this Delphi survey sought agreement on the appropriate interventions and outcomes for use with children with neurodisability and EDSD. Two stakeholder consultation workshops were iterative, with the findings of the first discussed at the second, and conclusions reached. RESULTS: A total of 105 parents and 105 health professionals took part. Parents and health professionals viewed 19 interventions and 10 outcomes as essential. Interventions related to improvement in the physical aspects of a child's EDSD, behavioural changes of the child or parent, and changes in the child or family's well-being. Both parents and health professionals supported a 'toolkit' of interventions that they could use together in shared decision making to prioritise and implement timely interventions appropriate to the child. CONCLUSIONS: This study identified interventions viewed as essential to consider for improving EDSD in children with neurodisability. It also identified several key outcomes that are valued by parents and health professionals. The Focus on Early Eating, Drinking and Swallowing (FEEDS) Toolkit of interventions to improve EDSD in children with neurodisability has been developed and now requires evaluation regarding its use and effectiveness.

Emesis in pregnancy - a qualitative study on trial recruitment failure from the EMPOWER internal pilot.

BACKGROUND: As part of the internal pilot of the EMPOWER trial investigating the second-line antiemetic therapies in severe emesis in pregnancy ( https://www.isrctn.com/ISRCTN16924692 ), a qualitative study of women's views was carried out, to improve our understanding of why women did, or did not, consent to participation in the trial. Interviews were also conducted with site research staff, to broaden our analysis and explore other factors affecting recruitment. METHODS: The sample comprised women who accepted or declined trial participation (n=21) and site research staff (n=22). A structured topic guide was used, in four email interviews and 17 telephone interviews with women, and semi-structured telephone interviews were carried out with staff. Of the women interviewed, seven had declined trial participation, and of the staff interviewed, 16 were research midwives/research nurses and six were principal investigators. All transcripts were checked for accuracy, anonymised and entered into NVIVO12 for indexing and retrieval. Data was analysed using a reflexive thematic analytic approach. In total, 72 codes were generated from the thematic analysis, and 36 from each sample group. RESULTS: Three key themes based on all the interviews were (a) the diversity of recruitment pathways and boundaries of care, (b) the impact of trial complexity on recruitment and staff morale and (c) the ethics of caring for a patient with emesis. Ethical issues discussed included the use of double dummy and time to treat, particularly those suffering severely from the effects of nausea and vomiting. To illustrate these themes, staff perspectives are given more prominence. CONCLUSIONS: The main reason the trial was stopped related to the high proportion of women ineligible for recruitment due to prior treatment with study drug(s) because of unanticipated changes in clinical practice. The qualitative results also demonstrate the impact of the trial on women and staff and highlight how the diversity of referral pathways, boundaries of care and the complexity of the trial and protocol resulted in additional barriers to successful trial recruitment. Qualitative work in pilot and feasibility studies of a clinical trial is recommended, to evaluate whether recruitment strategies remain viable in unanticipated contexts. TRIAL REGISTRATION: Trial registration number ISRCTN16924692 . Date: 08/01/2018.

Effect of Different Corticosteroid Dosing Regimens on Clinical Outcomes in Boys With Duchenne Muscular Dystrophy: A Randomized Clinical Trial.

Importance: Corticosteroids improve strength and function in boys with Duchenne muscular dystrophy. However, there is uncertainty regarding the optimum regimen and dosage. Objective: To compare efficacy and adverse effects of the 3 most frequently prescribed corticosteroid regimens in boys with Duchenne muscular dystrophy. Design, Setting, and Participants: Double-blind, parallel-group randomized clinical trial including 196 boys aged 4 to 7 years with Duchenne muscular dystrophy who had not previously been treated with corticosteroids; enrollment occurred between January 30, 2013, and September 17, 2016, at 32 clinic sites in 5 countries. The boys were assessed for 3 years (last participant visit on October 16, 2019). Interventions: Participants were randomized to daily prednisone (0.75 mg/kg) (n = 65), daily deflazacort (0.90 mg/kg) (n = 65), or intermittent prednisone (0.75 mg/kg for 10 days on and then 10 days off) (n = 66). Main Outcomes and Measures: The global primary outcome comprised 3 end points: rise from the floor velocity (in rise/seconds), forced vital capacity (in liters), and participant or parent global satisfaction with treatment measured by the Treatment Satisfaction Questionnaire for Medication (TSQM; score range, 0 to 100), each averaged across all study visits after baseline. Pairwise group comparisons used a Bonferroni-adjusted significance level of .017. Results: Among the 196 boys randomized (mean age, 5.8 years [SD, 1.0 years]), 164 (84%) completed the trial. Both daily prednisone and daily deflazacort were more effective than intermittent prednisone for the primary outcome (P < .001 for daily prednisone vs intermittent prednisone using a global test; P = .017 for daily deflazacort vs intermittent prednisone using a global test) and the daily regimens did not differ significantly (P = .38 for daily prednisone vs daily deflazacort using a global test). The between-group differences were principally attributable to rise from the floor velocity (0.06 rise/s [98.3% CI, 0.03 to 0.08 rise/s] for daily prednisone vs intermittent prednisone [P = .003]; 0.06 rise/s [98.3% CI, 0.03 to 0.09 rise/s] for daily deflazacort vs intermittent prednisone [P = .017]; and -0.004 rise/s [98.3% CI, -0.03 to 0.02 rise/s] for daily prednisone vs daily deflazacort [P = .75]). The pairwise comparisons for forced vital capacity and TSQM global satisfaction subscale score were not statistically significant. The most common adverse events were abnormal behavior (22 [34%] in the daily prednisone group, 25 [38%] in the daily deflazacort group, and 24 [36%] in the intermittent prednisone group), upper respiratory tract infection (24 [37%], 19 [29%], and 24 [36%], respectively), and vomiting (19 [29%], 17 [26%], and 15 [23%]). Conclusions and Relevance: Among patients with Duchenne muscular dystrophy, treatment with daily prednisone or daily deflazacort, compared with intermittent prednisone alternating 10 days on and 10 days off, resulted in significant improvement over 3 years in a composite outcome comprising measures of motor function, pulmonary function, and satisfaction with treatment; there was no significant difference between the 2 daily corticosteroid regimens. The findings support the use of a daily corticosteroid regimen over the intermittent prednisone regimen tested in this study as initial treatment for boys with Duchenne muscular dystrophy. Trial Registration: ClinicalTrials.gov Identifier: NCT01603407.

Barriers and facilitators of childhood flu vaccination: the views of parents in North East England.

Aim: The aim of this study was to complete a descriptive qualitative investigation of parents' perceptions of the barriers and facilitators to flu vaccination for pre-school children. Subject and method: Participants were recruited through various communication channels to maximize sample variation. Invitations to participate in the study were sent to members of the Newcastle University Parent Network and to parents who had participated in previous research conducted at Newcastle University. Twelve participants (six with vaccinated children, six whose children were not vaccinated) took part in a semi-structured interview via Zoom. Transcripts were coded using Nvivo 12 and data were thematically analyzed using the COM-B model of health behavior change. Results: Participants whose children were not vaccinated against flu nonetheless generally held favourable views of vaccination and reported low concern about side-effects. Barriers involved a combination of internal and external factors, mainly a lack of convenient access to vaccination opportunities and flu vaccination being a low priority for busy parents. Conclusion: Our findings suggest that socioeconomic status, which is known to influence other vaccination behaviors, may influence uptake of the flu vaccine in this population. Inconvenient vaccination opportunities and a lack of awareness of the need to vaccinate are major barriers to uptake for some parents. The finding that belief that flu vaccination is a civic responsibility is a new contribution to the literature. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-022-01695-2.

Barriers and facilitators to implementing practices for prevention of childhood obesity in primary care: A mixed methods systematic review.

Primary care providers (PCPs) have an important role in prevention of excess weight gain in pre-school children. Guidelines exist to support PCPs' practices. This systematic review of PCPs' practice behaviors and their perceptions of barriers to and facilitators of implementation of guidelines was the first step toward the development of an intervention aimed at supporting PCPs. Five databases were searched to identify qualitative, quantitative, and mixed methods studies which examined PCPs' practice patterns and factors influencing implementation of recommended practices. The convergent integrated approach of the Joanna Briggs Institute (JBI) methodology for mixed methods reviews was used for data synthesis. Following analyses, the resultant factors were mapped onto the Capability, Opportunity, and Motivation model of Behaviour (COM-B). Fifty studies met the eligibility criteria. PCPs inconsistently implement recommended practices. Barriers and facilitators were identified at the provider (e.g., lack of knowledge), parent (e.g., lack motivation), and organization level (e.g., inadequate training). Factors were mapped to all three components of the COM-B model: psychological capability (e.g., lack of skills), reflective motivation (e.g., beliefs about guidelines), automatic motivation (e.g., discomfort), physical opportunity (e.g., time constraints), and social opportunity (e.g., stigma). These findings reflect the complexity of implementation of childhood obesity prevention practices.

Clinical and Genetic Characteristics in Young, Glucocorticoid-Naive Boys With Duchenne Muscular Dystrophy.

BACKGROUND AND OBJECTIVES: Duchenne muscular dystrophy (DMD) is a paediatric neuromuscular disorder caused by mutations in the dystrophin gene. Geneotype-phenotype associations have been examined in glucocorticoid treated boys, but there are few data on the young glucocorticoid-naïve DMD population. A sample of young glucocorticoid-naïve DMD boys is described and genotype-phenotype associations are investigated. METHODS: Screening and baseline data were collected for all the participants in the Finding the Optimum Corticosteroid Regime for Duchenne Muscular Dystrophy (FOR-DMD)study, an international, multi-centre, randomized, double-blind, clinical trial comparing three glucocorticoid regimens in glucocorticoid-naïve, genetically confirmed boys with DMD between 4 and <8 years of age. RESULTS: One hundred and ninety-six boys were recruited. The meanage at randomization (+ standard deviation) was 5.8+ 1.0 years. The predominant mutation type was out of frame deletions 67.4%, (130/193) of which 68.5% (89/130) were amenable to exon skipping. The most frequent mutations were deletions amenable to exon 51 skipping 13.0% (25/193). Stop codon mutations accounted for 10.4% (20/193).The mean age at first parental concerns was 29.8 + 18.7 months, the mean age at genetic diagnosis was 53.9 + 21.9 months and the mean diagnostic delay was 25.9 + 18.2 months. The mean diagnostic delay for boys diagnosed following an incidental finding of isolated hyperCKemia (n=19) was 6.4 + 7.4 months. The mean ages at independent walking and talking in sentences were 17.1 + 4.2 and 29.0 + 10.7 months, respectively. Median height percentiles were below the 25th percentile regardless of age group. No genotype-phenotype associations were identified expect for boys with an exon 8 skippable deletions who had better performance on time to walk/run 10 meters (p=0.02)compared to boys with deletions not amenable to skipping. DISCUSSION: This study describes clinical and genetic characteristics of a sample of young glucocorticoid-naïve boys with DMD. A low threshold for CK testing can lead to an earlier diagnosis. Motor and speech delay were common presenting symptoms.The effects of low, pre-treatment height on growth and adults height requires further study. These findings may promote earlier recognition of DMD and inform study design for future clinical trials.

Ondansetron and metoclopramide as second-line antiemetics in women with nausea and vomiting in pregnancy: the EMPOWER pilot factorial RCT.

BACKGROUND: Around one-third of pregnant women suffer from moderate to severe nausea and vomiting, causing physical and emotional distress and reducing their quality of life. There is no cure for nausea and vomiting in pregnancy. Management focuses on relieving symptoms and preventing morbidity, and often requires antiemetic therapy. National guidelines make recommendations about first-, second- and third-line antiemetic therapies, although care varies in different hospitals and women report feeling unsupported, dissatisfied and depressed. OBJECTIVES: To determine whether or not, in addition to intravenous rehydration, ondansetron compared with no ondansetron and metoclopramide compared with no metoclopramide reduced the rate of treatment failure up to 10 days after drug initiation; improved symptom severity at 2, 5 and 10 days after drug initiation; improved quality of life at 10 days after drug initiation; and had an acceptable side effect and safety profile. To estimate the incremental cost per treatment failure avoided and the net monetary benefits from the perspectives of the NHS and women. DESIGN: This was a multicentre, double-dummy, randomised, double-blinded, dummy-controlled 2 × 2 factorial trial (with an internal pilot phase), with qualitative and health economic evaluations. PARTICIPANTS: Thirty-three patients (who were < 17 weeks pregnant and who attended hospital with nausea and vomiting after little or no improvement with first-line antiemetic medication) who attended 12 secondary care NHS trusts in England, 22 health-care professionals and 21 women participated in the qualitative evaluation. INTERVENTIONS: Participants were randomly allocated to one of four treatment groups (1 : 1 : 1: 1 ratio): (1) metoclopramide and dummy ondansetron; (2) ondansetron and dummy metoclopramide; (3) metoclopramide and ondansetron; or (4) double dummy. Trial medication was initially given intravenously and then continued orally once women were able to tolerate oral fluids for a maximum of 10 days of treatment. MAIN OUTCOME MEASURES: The primary end point was the number of participants who experienced treatment failure, which was defined as the need for further treatment because symptoms had worsened between 12 hours and 10 days post treatment. The main economic outcomes were incremental cost per additional successful treatment and incremental net benefit. RESULTS: Of the 592 patients screened, 122 were considered eligible and 33 were recruited into the internal pilot (metoclopramide and dummy ondansetron, n = 8; ondansetron and dummy metoclopramide, n = 8; metoclopramide and ondansetron, n = 8; double dummy, n = 9). Owing to slow recruitment, the trial did not progress beyond the pilot. Fifteen out of 30 evaluable participants experienced treatment failure. No statistical analyses were performed. The main reason for ineligibility was prior treatment with trial drugs, reflecting an unpredicted change in prescribing practice at several points along the care pathway. The qualitative evaluation identified the requirements of the study protocol, in relation to guidelines on anti-sickness drugs, and the diversity of pathways to care as key hurdles to recruitment while the role of research staff was a key enabler. No important adverse events or side effects were reported. LIMITATIONS: The pilot trial failed to achieve the recruitment target owing to unforeseen changes in the provision of care. CONCLUSIONS: The trial was unable to provide evidence to support clinician decisions about the best choice of second-line antiemetic for nausea and vomiting in pregnancy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16924692 and EudraCT 2017-001651-31. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 63. See the NIHR Journals Library website for further project information.

Nausea and vomiting in pregnancy cause physical and emotional distress, and up to 30% of affected women require medical treatment. Guidelines on the use of anti-sickness drugs exist, but evidence is limited about which drugs work the best. The EMPOWER (EMesis in Pregnancy ­ Ondansetron With mEtoClopRamide) trial aimed to compare the clinical effectiveness and cost-effectiveness of two anti-sickness drugs [metoclopramide (metoclopramide hydrochloride, Actavis UK Ltd, Barnstable, UK; IV Ratiopharm GmbH, Ulm, Germany) and ondansetron (ondansetron hydrochloride dehydrate, Wockhardt UK Ltd, Wrexham, UK; IV Hameln Pharma plus GmbH, Hameln)] for the treatment of nausea and vomiting in pregnancy. Women who were < 17 weeks pregnant with severe nausea and vomiting who attended hospital because their first anti-sickness drug had failed to improve their symptoms were asked to take part in the trial. Participants received fluids and, with consent, were randomly allocated to one of four groups: (1) metoclopramide and dummy ondansetron, (2) ondansetron and dummy metoclopramide, (3) metoclopramide and ondansetron or (4) double dummy. Trial drugs were administered into a vein and then by tablet for 10 days. On advice from sufferers, the trial focused on treatment failure, but other outcomes, including drug side effects, costs and pregnancy outcome, were collected. The trial was unable to recruit enough women and, therefore, did not progress. Nearly 600 women at 11 hospitals were screened, of whom 122 (21%) were eligible and 33 were recruited. The main reason for ineligibility (68%) was prior use of trial drug (mostly ondansetron). Overall, 15 out of 30 evaluable women experienced treatment failure. Interviews with 21 women who were approached about the trial and 22 research staff identified complex hurdles to and enablers of recruitment. The main hurdles were the requirements of the study protocol in relation to guidelines on anti-sickness drugs and the diversity of pathways to care. The role of research staff was a key enabler. The trial was too small to draw useful conclusions and it highlights the challenges of conducting complex studies on sick pregnant women. Subsequent concerns about the safety of ondansetron highlight the need for further studies to help inform women and the NHS about the best care for nausea and vomiting in pregnancy.

Preventing Cardiomyopathy in DMD: A Randomized Placebo-Controlled Drug Trial.

OBJECTIVE: To determine whether a combination of 2 heart medications would be tolerated and could prevent/delay the onset of cardiomyopathy in boys with Duchenne muscular dystrophy (DMD) compared with placebo. METHODS: This multicenter, parallel group, 1:1 patient randomized, placebo-controlled study of prophylactic perindopril and bisoprolol recruited boys with DMD aged 5-13 years, with normal ventricular function. Repeat assessments of left ventricular (LV) function, electrocardiogram, and adverse event reporting were performed 6 monthly. The primary outcome was change in ejection fraction between arms after 36 months. The study was approved by the National Research Ethics Service Committee East Midlands-Derby. RESULTS: Eighty-five boys were recruited (76% on steroid therapy) and randomized to combination heart drugs or matched placebo. Group change in left ventricular ejection fraction (LVEF%) at 36 months from baseline was -2.2% ± 6.0% and -2.9% ± 6.1% in active and placebo arms (adjusted mean difference: -2.1, 95% CI -5.2 to 1.1). There was no difference between treatment arms over repeated assessments (analysis of variance) up to 36 months (trial arms p = 0.53); arm-over-time (p = 0.44). Four participants on placebo but none on active therapy were withdrawn due to deteriorations in LV function. Secondary outcomes did not differ between arms either. Thirty-six serious adverse events occurred none due to cardiac events or trial medication. CONCLUSIONS: Combination therapy was well tolerated. Consistent with the previous prophylactic perindopril heart study, there was no evidence of group benefit after 36-month treatment. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that combination perindopril-bisoprolol therapy was well tolerated but did not change decline in LVEF significantly in boys with DMD.

Animal-Assisted Interventions for the Improvement of Mental Health Outcomes in Higher Education Students: A Systematic Review of Randomised Controlled Trials.

BACKGROUND: The aim of this systematic review was to evaluate the effectiveness of Animal-Assisted Interventions (AAIs), particularly Animal-Assisted Therapy (AAT) and Animal-Assisted Activity (AAA), in improving mental health outcomes for students in higher education. The number of students in higher education reporting mental health problems and seeking support from universities' student support services has risen over recent years. Therefore, providing engaging interventions, such as AAIs, that are accessible to large groups of students are attractive. METHODS: MEDLINE, PsycINFO, Embase and Cochrane Library were searched from relative inception to end of April 2020. Additionally, a grey literature search was undertaken. Independent screening, data extraction and risk of bias assessment were completed, with varying percentages, by two reviewers. RESULTS: After de-duplication, 6248 articles were identified of which 11 studies were included in the narrative synthesis. The evidence from randomised controlled trials suggests that AAIs could provide short-term beneficial results for anxiety in students attending higher education but with limited evidence for stress, and inconclusive evidence for depression, well-being and mood. For the non-statistically significant results, the studies either did not include a power calculation or were under-powered. CONCLUSIONS: Potential emerging evidence for the short-term benefits of AAI for anxiety, and possibly stress, for students in higher education was found.

Health related quality of life in young, steroid-naïve boys with Duchenne muscular dystrophy.

Knowledge of health related quality of life (HRQOL) in the immediate phase following DMD diagnosis has not been well-characterized. It is important to understand HRQOL early in disease for both clinical care and studies of treatment. The relationship between parent-proxy and child self-report HRQOL and their associations with medical, psycho-social and behavioral symptoms deserve study. In this study HRQOL was measured using the PedsQL inventory in parent/caregiver and corticosteroid-naïve boys (ages 4 to 7 years) participating in the FOR-DMD study. Agreement between the parent-proxy report and the boys' self-report HRQOL was measured using intraclass correlation coefficients (ICCs). Factors associated with HRQOL, including standardized psychosocial and behavioral measures in this cross-sectional sample, were explored using correlations. The results showed that the level of agreement between 70 dyads of child self-report and parent-proxy ratings of HRQOL was poor for the generic PedsQL total score (ICC=0.48, 95% CI (0.23, 0.66)) and its subscale scores, and was similarly low for the neuromuscular disease module (ICC=0.24, 95% CI (0.00, 0.45)). Parents rated their child's HRQOL as poorer than the children rated themselves in all scales. Psychosocial outcome measures were more highly associated with HRQOL measures than disease severity or patient demographic variables. In the early phases of DMD, child and parent-proxy HRQOL ratings were discordant. In early DMD, psychosocial and behavioral aspects appear to be more relevant to HRQOL than disease severity factors.

Diet, Physical Activity and Gestational Weight Gain Patterns among Pregnant Women Living with Obesity in the North East of England: The GLOWING Pilot Trial.

Maternal diet, physical activity (PA) behaviours, and gestational weight gain (GWG) are important for optimum health of women and their babies. This secondary analysis of the GLOWING pilot cluster trial explored these among women living with obesity in high deprivation. Pregnant women completed food frequency, PA and psychosocial questionnaires. Weights were retrieved from medical records and measured during routine appointments with midwives. Descriptive and regression analyses were stratified by obesity class. A total of 163 women were recruited; 54.0% had class 1 obesity, 25.8% class 2, 20.2% class 3, and 76.1% lived in the two most deprived quintiles. Women had suboptimal dietary intake, particularly for oily fish, fruit and vegetables. PA was predominantly light intensity, from household, care and occupational activities. Most women gained weight outside of Institute of Medicine (IOM) guideline recommendations (87.8%); women in class 3 obesity were most likely to have inadequate GWG below IOM recommendations (58.3%, p < 0.01) and reduced odds of excessive GWG compared with class 1 (AOR 0.13, 95% 0.04-0.45). Deprived women with obesity have a double inequality as both increase pregnancy risks. This population requires support to meet guideline recommendations for diet, PA and GWG. Further research exploring obesity classes would inform policies and care to achieve the best pregnancy outcomes.

Implementation Factors for the Delivery of Alcohol and Drug Interventions to Children in Care: Qualitative Findings from the SOLID Feasibility Trial.

Young people in care have a four-fold increased risk of drug and alcohol use compared to their peers. The SOLID study aimed to deliver two behaviour change interventions to reduce risky substance use (illicit drugs and alcohol) and improve mental health in young people in care. The study was carried out in 6 local authorities in the North East of England. Young people in care aged 12-20 years, who self-reported substance use within the previous 12 months were randomised to Motivational Enhancement Therapy, Social Behaviour and Network Therapy or control. In-depth 1:1 interviews and focus groups were used with young people in care, foster carers, residential workers, social workers and drug and alcohol practitioners to explore the key lessons from implementing the interventions. The Consolidated Framework of Implementation Research framed the analysis. Findings illustrated that the everyday interaction between individuals, service level dynamics and external policy related factors influenced the implementation of these new interventions at scale. We concluded that unless interventions are delivered in a way that can accommodate the often-complex lives of young people in care and align with the drug and alcohol practitioners' and social workers priorities, it is unlikely to be successfully implemented and become part of routine practice.

Parent-delivered interventions used at home to improve eating, drinking and swallowing in children with neurodisability: the FEEDS mixed-methods study.

BACKGROUND: Eating, drinking and swallowing difficulties are common in young children with neurodisability. These difficulties may lead to inadequate calorie intake, which affects a child's nutrition, growth and general physical health. OBJECTIVE: To examine which interventions are available that can be delivered at home by parents to improve eating, drinking and swallowing in young children with neurodisability and are suitable for investigation in pragmatic trials. DESIGN: This was a mixed-methods study that included focus groups, surveys, an update of published systematic reviews of interventions, a systematic review of measurement properties of existing tools, evidence mapping, evidence synthesis, a Delphi survey and stakeholder workshops. SETTING: The study was carried out in NHS hospitals, community services, family homes and schools. PARTICIPANTS: Parents of children who had neurodisability and eating, drinking and swallowing difficulties. Professionals from health and education. Young people with eating, drinking and swallowing difficulties or young people who had previously experienced eating, drinking and swallowing difficulties. DATA SOURCES: Literature reviews; national surveys of parents and professionals; focus groups with parents, young people and professionals; and stakeholder consultation workshops. REVIEW METHODS: An update of published systematic reviews of interventions (searched July-August 2017), a mapping review (searched October 2017) and a systematic review of measurement properties using COnsensus-based Standards for the Selection of health status Measurement INstruments (COSMIN) methodology (searched May 2018). RESULTS: Significant limitations of the available research evidence regarding interventions and tools to measure outcomes were identified. A total of 947 people participated: 400 parents, 475 health professionals, 62 education professionals and 10 young people. The survey showed the wide range of interventions recommended by NHS health professionals, with parents and professionals reporting variability in the provision of these interventions. Parents and professionals considered 19 interventions as relevant because they modified eating, drinking and swallowing difficulties. Parents and professionals considered 10 outcomes as important to measure (including Nutrition, Growth and Health/safety); young people agreed that these were important outcomes. Stakeholder consultation workshops identified that project conclusions and recommendations made sense, were meaningful and were valued by parents and professionals. Parents and health professionals were positive about a proposed Focus on Early Eating, Drinking and Swallowing (FEEDS) toolkit of interventions that, through shared decision-making, could be recommended by health professionals and delivered by families. LIMITATIONS: The national surveys included large numbers of parents and professionals but, as expected, these were not representative of the UK population of parents of children with eating, drinking and swallowing difficulties. Owing to the limitations of research evidence, pragmatic decisions were made about interventions that might be included in future research and outcomes that might be measured. For instance, the reviews of research found only weak or poor evidence to support the effectiveness of interventions. The review of outcome measures found only limited low-level evidence about their psychometric properties. CONCLUSIONS: Opportunities and challenges for conducting clinical trials of the effectiveness of the FEEDS toolkit of interventions are described. Parents and professionals thought that implementation of the toolkit as part of usual NHS practice was appropriate. However, this would first require the toolkit to be operationalised through development as a complex intervention, taking account of constituent interventions, delivery strategies, implementation and manualisation. Subsequently, an evaluation of its clinical effectiveness and cost-effectiveness could be undertaken using appropriate research methods. FUTURE WORK: Initial steps include FEEDS toolkit development and evaluation of its use in clinical practice, and identification of the most robust methods to measure valued outcomes, such as Nutrition and Growth. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10454425. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 22. See the NIHR Journals Library website for further project information.

Some young children with disabilities, such as those with cerebral palsy and autism spectrum disorder, have difficulties with eating, drinking and swallowing. Many strategies are employed to help with these difficulties (e.g. 'Positioning'), but we need to know more about which ones work best. We wanted to find out about the strategies parents use at home to help their children with eating, drinking and swallowing difficulties. We wanted to understand what is already known about the strategies that are available now and if children are getting the right help. We wanted to find out if doing more research would tell us which interventions work. We looked at what has been written about the ways in which parents help their child to eat, drink and swallow. We discussed this information with parents and health professionals. We developed a survey to ask what parent-delivered strategies are recommended by NHS professionals, which strategies parents use and how we would know if things had improved. We discussed the findings with parents and professionals. We then used a different type of survey. Parents and professionals were asked which strategies were most important and what they would most like to improve. We then held workshops to hear parents' and professionals' views on what we had found and to agree on how we would organise future research. We discussed some of the findings with young people. Research about these strategies and how to measure improvements in eating and drinking is of poor quality. A wide variety of strategies are used: 19 strategies were thought to be the most useful by parents and professionals. Parents and professionals agreed on 10 areas that they would most like to improve. Both groups thought that it was a good idea to have a 'toolkit' of strategies so that they could choose the right strategy at the right time.