Lessons for the UK on implementation and evaluation of breastfeeding support: evidence syntheses and stakeholder engagement

Background Breastfeeding impacts multiple health outcomes but less than 50% of UK women breastfeed at 8 weeks. Women with long-term conditions face additional challenges in breastfeeding. Objectives To synthesise global and UK evidence to co-create an implementation and evaluation toolkit for cost-effective breastfeeding support in the NHS. Design Evidence syntheses with stakeholder engagement. Review methods Systematic reviews examined effectiveness of breastfeeding support for i) healthy women, and ii) women with long-term conditions using Cochrane Pregnancy and Childbirth group methods. Mixed methods systematic reviews synthesised process evaluations of effective breastfeeding support interventions for healthy women, and experiences of receiving/providing support for breastfeeding women. Cross-study synthesis integrated qualitative and quantitative findings. Systematic reviews synthesised evidence on the incremental costs and cost-effectiveness of breastfeeding support following NICE guidance. All searches were conducted May 2021 to October 2022. Stakeholder engagement and toolkit development comprised online discussions, a modified Delphi study, focus groups and four workshops. Participants were: 23 stakeholders, 16 parents in the parents panels, 15 women in the focus groups, and 87 stakeholders attended the workshops. Results We found considerably more interventions that were designed for healthy women (Review 1) compared to those aimed at women with long-term conditions (Reviews 1 and 4, approximately half the studies were targeted at groups at higher risk of poor breastfeeding outcomes, and possibly the impact of support may be different in these populations. Despite this, studies from Review 2 found that women perceived the provision of support as positive, important and needed. Studies from Review 5 echoed a range of suggestions from participants regarding potential strategies to improve breastfeeding support, with the most widely reported being the need to acknowledge the role and influence of other sources of support (e.g., partners, family, friends, peers, external professionals, web-based resources) and involving them in the provision of breastfeeding support for women with long-term conditions. In Reviews 3 and 6, there was uncertainty in the cost-effectiveness of breastfeeding support interventions due to the limited number of studies and lack of good quality evidence. Limitations There is lack of evidence for effectiveness and cost-effectiveness of breastfeeding interventions in the UK. There was often insufficient information about intervention characteristics reported. Conclusions ‘Breastfeeding only’ support probably reduces the number of women stopping any or exclusive breastfeeding. The evidence for ‘breastfeeding plus’ interventions is less consistent but may reduce the number of women stopping exclusive breastfeeding at 4-6 weeks and 6 months. We found no evidence of differential intervention effects regarding mode of provision or provider. Cost-effectiveness is uncertain due to the lack of good quality evidence. Key enablers of successful implementation were responsiveness and tailoring of interventions to both women’s and supporters’ needs. Breastfeeding support as delivered in the included studies probably has little to no effect on breastfeeding outcomes for women with long-term conditions. The mixed-methods synthesis and stakeholder work identified that existing interventions may not address the complex needs of these women. The main study output is a co-produced toolkit to guide implementation and evaluation of breastfeeding support services in the UK. Future work Evaluation of breastfeeding support for all women, in particular those at risk of poor breastfeeding outcomes (e.g., long-term conditions, deprivation). This could involve tailoring the toolkit to local contexts via implementation and effectiveness studies or using quality improvement studies

VIKING II, a Worldwide Observational Cohort of Volunteers with Northern Isles Ancestry

Introduction The purpose of VIKING II is to create an observational cohort of volunteers with ancestry from the Northern Isles of Scotland, primarily for identifying genetic variants influencing disease. The new online protocol is separate to, but follows on from, earlier genetic epidemiological clinic-based studies in the isolated populations of Orkney and Shetland. These populations are favourable for the study of rarer genetic variants due to genetic drift, the large number of relatives, and availability of pedigree information. They are known to be genetically distinct from mainland British populations. Methods and Analysis Online methods are being used to recruit ~4,000 people who have Northern Isles ancestry, living anywhere in the world. The option for participants to have actionable genetic results returned is offered. Consent will be taken electronically. Data will be collected at baseline through an online questionnaire and longitudinally through linkage to NHS data in the electronic health record. The questionnaire collects a variety of phenotypes including personal and family health. DNA will be extracted from saliva samples then genome-wide genotyped and exome sequenced. VIKING II aims to capitalise on the special features of the Northern Isles populations to create a research cohort that will facilitate the analysis of genetic variants associated with a broad range of traits and disease endpoints, including otherwise rare variants that have drifted to high frequency in these populations. Ethics and Dissemination The South East Scotland Research Ethics Committee gave the study a favourable opinion. VIKING II is sponsored by the University of Edinburgh and NHS Lothian. Summary research findings will be disseminated to participants and funding bodies, presented at conferences and reported in peer-reviewed publications. Article Summary Strengths and limitations of this study • Detailed data and biological sample collection of research volunteers with unique ancestry. • Consent for access to routinely collected clinical EHR data and for future re-contact, providing a longitudinal component. • Optional consent for return of actionable genetic results. • ~4,000 participants is a relatively small number for certain types of genetic analyses, so the cohort is underpowered on its own, in some study designs. • Resources to maintain the cohort, and to store data and DNA samples, are significant, with sustainability dependent on infrastructure support and funding

Newsprint coverage of smoking in cars carrying children : a case study of public and scientific opinion driving the policy debate

Acknowledgements Date of Acceptance:17/10/2014 Acknowledgements: This project was funded by Cancer Research UK (MC_U130085862) and the Scottish School of Public Health Research. Cancer Research UK and the Scottish School of Public Health Research was not involved in the collection, analysis, and interpretation of data, writing of the manuscript or the decision to submit the manuscript for publication. Shona Hilton, Karen Wood, Josh Bain and Chris Patterson are funded by the UK Medical Research Council as part of the Understandings and Uses of Public Health Research programme (MC_UU_12017/6) at the MRC/CSO Social and Public Health Sciences Unit, University of Glasgow. We thank Alan Pollock who provided assistance with coding.Peer reviewedPublisher PD

Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial

Background Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus.Methods This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894.Findings Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91–1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]). Interpretation Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus

Health, education, and social care provision after diagnosis of childhood visual disability

Aim: To investigate the health, education, and social care provision for children newly diagnosed with visual disability.Method: This was a national prospective study, the British Childhood Visual Impairment and Blindness Study 2 (BCVIS2), ascertaining new diagnoses of visual impairment or severe visual impairment and blindness (SVIBL), or equivalent vi-sion. Data collection was performed by managing clinicians up to 1-year follow-up, and included health and developmental needs, and health, education, and social care provision.Results: BCVIS2 identified 784 children newly diagnosed with visual impairment/SVIBL (313 with visual impairment, 471 with SVIBL). Most children had associated systemic disorders (559 [71%], 167 [54%] with visual impairment, and 392 [84%] with SVIBL). Care from multidisciplinary teams was provided for 549 children (70%). Two-thirds (515) had not received an Education, Health, and Care Plan (EHCP). Fewer children with visual impairment had seen a specialist teacher (SVIBL 35%, visual impairment 28%, χ2p < 0.001), or had an EHCP (11% vs 7%, χ2p < 0 . 01).Interpretation: Families need additional support from managing clinicians to access recommended complex interventions such as the use of multidisciplinary teams and educational support. This need is pressing, as the population of children with visual impairment/SVIBL is expected to grow in size and complexity.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Factors affecting the implementation of effective interventions to support women to breastfeed: a systematic review and mixed methods synthesis

BackgroundExisting evidence suggests that when standalone breastfeeding support interventions are offered to women who choose to breastfeed, the duration and exclusivity of breastfeeding are likely to be increased (Gavine et al., 2022). However, many women in the UK and elsewhere continue to report that lack of adequate breastfeeding support results in them stopping breastfeeding earlier than planned. Therefore, one key research question is now to identify how known effective interventions can successfully be implemented in practice.As part of the of the Action4Breastfeeding study, this review aimed to synthesise existing evidence on factors affecting the implementation of effective interventions identified in the updated Cochrane review on breastfeeding support for healthy women with healthy term babies (Gavine et al., 2022).MethodsWe systematically searched six bibliographic databases. Citation and reference searches of outcome papers from known effective interventions were also undertaken. No restrictions were applied on publication date and language. Articles reporting relevant qualitative and/or quantitative research were included. Quality appraisal was undertaken following study selection. Qualitative data were synthesised thematically (Thomas &amp; Harden, 2008), and quantitative data narratively (Popay et al., 2006). A cross-study synthesis (Kavanagh et al., 2012) integrated qualitative and quantitative findings.Results/findingsSixteen articles were included in the final synthesis. A range of eighteen factors affecting the implementation of effective interventions were identified and grouped around five broad types of implementation factors. The types of factors with a more widespread evidence base were related to the implementation process (particularly those relating to the ability to monitor and collect quantitative and qualitative feedback about the progress and quality of implementation) followed by those relating to the external context of the implementing organisation (particularly in terms of the organisation’s knowledge of their women’s/families’ breastfeeding support needs).ConclusionAvailable evidence on the range of factors known to have impacted implementation of effective breastfeeding support interventions can inform guidance for organisations to develop robust implementation strategies which may be more likely to ensure successful implementation of evidence into practice

Identifying effective breastfeeding support for healthy women and those with long-term conditions

Background: Many women stop breastfeeding before they intended and report a lack of support from healthcare providers (Fox, McMullen, &amp; Newburn, 2015). Moreover, women with multiple long‐term conditions may have additional difficulties breastfeeding(Scime, Patten, Tough &amp; Chaput, 2022). The aim of this work is to identify effective interventions to support all women to breastfeed.Methods: This presentation is comprised of two linked work packages of the Action4breastfeeding study. The first is an update of the Cochrane Review on Breastfeeding Support for healthy women with healthy term babies (Gavine et al., 2022). As this Cochrane review excludes women with long‐term conditions, an additional Systematic Review to identify effective interventions for women with long‐term conditions is currently underway. Results: The updated Cochrane review identified 116 randomised controlled trials which involved 98,816 women and their babies. Interventions were grouped into ‘breastfeeding only’ interventions and ‘breastfeeding plus’ interventions which contain other aspects of maternal and newborn care. We found moderate certainty evidence that ‘breastfeeding only’ support helped reduce the number of women stopping any at exclusive breastfeeding at 4‐6 weeks, 3‐4months and 6 months. For ‘breastfeeding plus’ the evidence is less certain but there was some evidence of a beneficial effect on exclusive breastfeeding. Meta‐regression identified that a schedule of 4‐8 contacts may help with exclusive breastfeeding. However, there were no differences in terms of who provides the support (i.e. peer or professional) or the mode of deliver (e.g. face‐to‐face, telephone, digital). The Systematic Review on breastfeeding support for women with long‐term conditions has identified 20 studies meeting the inclusion criteria. Analysis is currently underway, and results will be presented. Conclusion: For healthy women, organized support can help increase the duration and exclusivity of breastfeeding. Given the increase in prevalence of maternal long‐term conditions (NHS England, 2016), we need to better understand if support can also be effective for women with long‐term conditions. Further linked work is also on‐going to better understand how the effective interventions identified in these work packages can be implemented in an NHS setting. <br/

Viking II Data Dictionary

VIKING II was made possible thanks to Medical Research Council (MRC) funding. We aim to better understand what might cause diseases such as heart disease, eye disease, stroke, diabetes and others by inviting 4,000 people with 2 or more grandparents from Orkney and Shetland to complete a questionnaire and provide a saliva sample. This data dictionary outlines what volunteers were asked and indicates the data you can access. To access the data, please e-mail [email protected], Jim Flett; Buchanan, David; Kerr, Shona M; Edwards, Rachel. (2021). Viking II Data Dictionary, [dataset]. University of Edinburgh. Institute of Genetics and Cancer. MRC Human Genetics Unit. https://doi.org/10.7488/ds/3145