The effects of acute wild blueberry supplementation on the cognition of 7-10 year old schoolchildren

Purpose: Previous evidence suggests consumption of flavonoids, a sub-class of polyphenols, is associated with improved cognitive function across the lifespan. In particular, acute intervention of a flavonoid-rich wild blueberry (WBB) drink has been shown to boost executive function (EF), short-term memory and mood 2-6 h post-consumption in 7-10 yr old children. However, confirmation of the aspects of EF and memory susceptible to WBB ingestion is required, particularly during childhood, a critical period of neurological development. In addition, the child literature on berry-flavonoid supplementation and cognition highlights the potential for such interventions to elicit positive benefits to real world educational scenarios, such as reading; a complex ability which relies upon aspects of cognition already known to improve following WBB. Methods: Here we examined which aspects of EF and memory are susceptible to acute WBB, as well as investigating whether acute WBB could further benefit reading ability. Fifty-four healthy children, aged 7-10 yrs, consumed a 200ml WBB drink (253mg anthocyanins) or a matched placebo according to a randomised, single-blind, parallel groups design. Verbal memory (Auditory Verbal Learning Task; AVLT), EF (Modified Attention Network Task; MANT), and reading efficiency (Test of Word Reading Efficiency-2; TOWRE-2) were assessed at baseline and 2 h post consumption. Results: For the MANT, significantly quicker RTs were observed for WBB participants when compared to placebo participants on 120 ms trials, without cost to accuracy. Furthermore, WBB participants showed enhanced verbal memory performance on the AVLT, recalling more words than placebo participants on short delay and memory acquisition measures post-consumption. Despite these significant improvements in cognitive performance, no significant effects were observed for reading measures. Conclusion: Consumption of WBB was found to significantly improve memory and attentional aspects of EF. This indicates that a flavonoid-rich blueberry product, equivalent to 240 g or 1½ cups of fresh blueberries can provide acute cognitive benefits in children. These findings support accumulating evidence that flavonoid-rich products are beneficial for healthy brain function, particularly during critical developmental periods. However, the lack of findings relating to reading ability suggested acute WBB may not be sufficient to elicit benefits to reading. Chronic supplementation and other more sensitive reading measures should be considered for examining the effects of WBB on such a complex skill in the future

Social marketing to encourage initiation and continuation of breastfeeding in Penhill and Pinehurst, Swindon

Executive Summary• NHS Swindon has targets to increase the initiation and duration of breastfeeding to 6-8 weeks and beyond. A number of interventions have been implemented to increase local breastfeeding prevalence, including the UNICEF Baby Friendly Initiative and the family nurse partnership. • Traditional health education approaches on their own do not appear to have much impact. Our own work and indicative results elsewhere position co-creation as a potentially highly effective strategy to use within deprived communities; its potential to embed behaviour change sustainably is clear. • Integrating programmes that address cultural perceptions of breastfeeding with targeted work aimed directly at vulnerable segments, which in turn are co-ordinated with strong ante and post-natal support, education programmes and peer supported group sessions will maximise the chances of increasing breastfeeding. • The UWE project team recruited women and some family members to individual interviews and women from four different categories (pregnant, did not breastfeed, tried breastfeeding but gave up and breastfed beyond 6-8 weeks) to focus groups. In total, 28 individuals took part in the project. Participants were asked a range of questions designed to elicit information about norms surrounding infant feeding, how decisions about feeding were reached, individual’s knowledge concerning the benefits of breastfeeding and social and private attitudes towards breastfeeding. • The norm in both Pinehurst and Penhill is to bottle feed babies. Mothers gained knowledge about breastfeeding for a range of sources, but the timing and volume of NHS leaflets could be problematic. The main reason given for breastfeeding was the associated health benefits for babies. The main reason given for bottle feeding were convenience and ease of feeding in public. • Following these interviews, six professionals involved in services for mothers and babies were interviewed. This cohort was selected to include managers and practitioners from the midwifery and health visiting services for Penhill and Pinehurst. • Lack of support for breastfeeding women is a problem. Contributing factors were thought to include lack of resources in the wider health and social care context, particularly with regard to home visits in the first month after birth. Provision of information appears to rely heavily on written literature, which women may not read. A coherent and integrated service was seen as the ideal to support and promote breastfeeding, but there was some concern expressed about how well the support workers and healthcare professionals worked together. • The general consensus is that there is very little community engagement in these areas and many women are unwilling to access locally based groups where they might learn about breastfeeding or observe other mothers breastfeeding. • Co-creation as an approach depends upon engaging and involving community members, and with levels of involvement and interaction in these communities so low, it was agreed to proceed with a continued focus on breastfeeding interventions, with Uscreates leading on designing and developing ideas, making and directing decisions and activity, and audience members contributing feedback and thoughts. The co-creation process was adapted to be delivered one to one with mobile researchers visiting mothers at home. • A design exercise facilitated mothers to build up a description of the ideal support service along a number of descriptors. This activity led to the plan to re-design and re-launch the Breastmates service. This existing breastfeeding support service satisfied most of the requirements for an ideal service that mothers had described. These characteristics guided the re-design of the Breastmates offering to include home visits, and to promote both online and telephone support for urgent needs. • Uscreates carried out a co-creation process with women in order to re-design the existing Breastmates brand and marketing materials. The marketing combined several support avenues and channels within one identity, presenting a more united front, and giving women a choice of how to access support. • The overall recommendation after the pilot phase is to continue to use the co-created Breastmates brand, and roll this out across Swindon. With face to face engagement and promotion having the biggest impact on uptake and attendance, continue with this as the primary focus for promotion activities. • The other attendant promotion components (Facebook, Breastmates site, Textmagic) should be tweaked as per the recommendations above, and continue as low cost methods to increase general awareness of Breastmates, and provide a professional and unified means of reinforcing messages delivered by the face to face activity

Developing a core outcome set for periodontal trials

Acknowledgments The authors wish to thank all patients and professionals who took part in the Delphi process and face-to-face consensus meeting. We wish to thank Jillian Sutherland, Shirley Bell, Margaret Mooney and Lorna Barnsley for helping to organise the face-to-face consensus meeting. Patient participant recruitment to this study was facilitated by SHARE–the Scottish Health Research Register. SHARE is supported by NHS Research Scotland and the Chief Scientists Office Funding: TL received research funding for the core outcome set development for the prevention and management of periodontal diseases which was provided by the Tattershall fund, Dundee Dental School. This grant provided funds for the e-Delphi software, SHARE services and the face-to-face consensus meeting travel and catering costs. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptPeer reviewedPublisher PD

Selective Caries Removal in Permanent Teeth (SCRiPT) for the treatment of deep carious lesions:a randomised controlled clinical trial in primary care

Background Dental caries is one of the most prevalent non-communicable disease globally and can have serious health sequelae impacting negatively on quality of life. In the UK most adults experience dental caries during their lifetime and the 2009 Adult Dental Health Survey reported that 85% of adults have at least one dental restoration. Conservative removal of tooth tissue for both primary and secondary caries reduces the risk of failure due to tooth-restoration, complex fracture as well as remaining tooth surfaces being less vulnerable to further caries. However, despite its prevalence there is no consensus on how much caries to remove prior to placing a restoration to achieve optimal outcomes. Evidence for selective compared to complete or near-complete caries removal suggests there may be benefits for selective removal in sustaining tooth vitality, therefore avoiding abscess formation and pain, so eliminating the need for more complex and costly treatment or eventual tooth loss. However, the evidence is of low scientific quality and mainly gleaned from studies in primary teeth. Method This is a pragmatic, multi-centre, two-arm patient randomised controlled clinical trial including an internal pilot set in primary dental care in Scotland and England. Dental health professionals will recruit 623 participants over 12-years of age with deep carious lesions in their permanent posterior teeth. Participants will have a single tooth randomised to either the selective caries removal or complete caries removal treatment arm. Baseline measures and outcome data (during the 3-year follow-up period) will be assessed through clinical examination, patient questionnaires and NHS databases. A mixed-method process evaluation will complement the clinical and economic outcome evaluation and examine implementation, mechanisms of impact and context. The primary outcome at three years is sustained tooth vitality. The primary economic outcome is net benefit modelled over a lifetime horizon. Clinical secondary outcomes include pulp exposure, progession of caries, restoration failure; as well as patient-centred and economic outcomes. Discussion SCRiPT will provide evidence for the most clinically effective and cost-beneficial approach to managing deep carious lesions in permanent posterior teeth in primary care. This will support general dental practitioners, patients and policy makers in decision making. Trial Registration Trial registry: ISRCTN. Trial registration number: ISRCTN76503940. Date of Registration: 30.10.2019

Articulating the effect of food systems innovation on the Sustainable Development Goals

Food system innovations will be instrumental to achieving multiple Sustainable Development Goals (SDGs). However, major innovation breakthroughs can trigger profound and disruptive changes, leading to simultaneous and interlinked reconfigurations of multiple parts of the global food system. The emergence of new technologies or social solutions, therefore, have very different impact profiles, with favourable consequences for some SDGs and unintended adverse side-effects for others. Stand-alone innovations seldom achieve positive outcomes over multiple sustainability dimensions. Instead, they should be embedded as part of systemic changes that facilitate the implementation of the SDGs. Emerging trade-offs need to be intentionally addressed to achieve true sustainability, particularly those involving social aspects like inequality in its many forms, social justice, and strong institutions, which remain challenging. Trade-offs with undesirable consequences are manageable through the development of well planned transition pathways, careful monitoring of key indicators, and through the implementation of transparent science targets at the local level

Articulating the effect of food systems innovation on the Sustainable Development Goals

Acknowledgments MH, DM-D, JP, JRB, AH, GDB, CMG, CLM, and KR acknowledge funding from the Commonwealth Scientific and Industrial Research Organisation. PKT, BMC, AJ, and AML acknowledge funding from the CGIAR Research Program on Climate Change, Agriculture and Food Security, which is supported by the CGIAR Trust Fund and through bilateral funding agreements. PP acknowledges funding from the German Federal Ministry of Education and Research for the BIOCLIMAPATHS project.Peer reviewedPublisher PD

Correction to: Pulpotomy for the Management of Irreversible Pulpitis in Mature Teeth (PIP): a feasibility study

Background Progression of dental caries can result in irreversible pulpal damage. Partial irreversible pulpitis is the initial stage of this damage, confined to the coronal pulp whilst the radicular pulp shows little or no sign of infection. Preserving the pulp with sustained vitality and developing minimally invasive biologically based therapies are key themes within contemporary clinical practice. However, root canal treatment involving complete removal of the pulp is often the only option (other than extraction) given to patients with irreversible pulpitis, with substantial NHS and patient incurred costs. The European Society of Endodontology’s (ESE 2019) recent consensus statement recommends full pulpotomy, where the inflamed coronal pulp is removed with the goal of keeping the radicular pulp vital, as a more minimally invasive technique, potentially avoiding complex root canal treatment. Although this technique may be provided in secondary care, it has not been routinely implemented or evaluated in UK General Dental Practice. Method This feasibility study aims to identify and assess in a primary care setting the training needs of general dental practitioners and clinical fidelity of the full pulpotomy intervention, estimate likely eligible patient pool and develop recruitment materials ahead of the main randomised controlled trial comparing the clinical and cost-effectiveness of full pulpotomy compared to root canal treatment in pre/molar teeth of adults 16 years and older showing signs indicative of irreversible pulpitis. The feasibility study will recruit and train 10 primary care dentists in the full pulpotomy technique. Dentists will recruit and provide full pulpotomy to 40 participants (four per practice) with indications of partial irreversible pulpitis. Discussion The Pulpotomy for the Management of Irreversible Pulpitis in Mature Teeth (PIP) study will address the lack of high-quality evidence in the treatment of irreversible pulpitis, to aid dental practitioners, patients and policymakers in their decision-making. The PIP feasibility study will inform the main study on the practicality of providing both training and provision of the full pulpotomy technique in general dental practice. Trial registration ISRCTN Registry, ISRCTN17973604. Registered on 28 January 2021. Protocol version Protocol version: 1; date: 03.02.202

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The Remote distractor effect in manual responses

The remote distracter effect (RDE) has previously only been studied in relation to the saccadic system. Given the hypothesis of the premotor theory (Rizzolatti et al, 1987) that a covert shift of attention is a programmed overt attentional shift (i.e. a saccade) where the actual saccade has been inhibited, it can therefore be assumed that influences affecting shifts of overt attention should also influence covert attentional shifts. This study investigated whether RDE occurs in a non-saccadic paradigm by presenting participants with a manual response task requiring a covert shift of attention as well as a saccadic and a simple manual response task. Although there was no significant effect of task on the influence of remote distracters on reaction times (including saccades), the trends in the means of effect of distracter showed a tendency to agree with the experimental hypothesis. It is concluded that although this experiment does not supply premotor theory with any cast-iron support, trends in the data imply that further research, and specifically further power, is required to ascertain the true influence of remote distracters on manual reaction times