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Non-communicable diseases (NCDs) are a leading health and development challenge worldwide. Since 2015, WHO and the United Nations Development Programme have provided support to governments to develop national NCD investment cases to describe the socioeconomic dimensions of NCDs. To assess the impact of the investment cases, semistructured interviews and a structured process for gathering written feedback were conducted between July and October 2022 with key informants in 13 countries who had developed a national NCD investment case between 2015 and 2020. Investment cases describe: (1) the social and economic costs of NCDs, including their distribution and projections over time; (2) priority areas for scaled up action; (3) the cost and returns from investing in WHO-recommended measures to prevent and manage NCDs; and (4) the political dimensions of NCD responses. While no country had implemented all the recommendations set out in their investment case reports, actions and policy changes attributable to the investment cases were identified, across (1) governance; (2) financing; and (3) health service access and delivery. The pathways of these changes included: (1) stronger collaboration across government ministries and partners; (2) advocacy for NCD prevention and control; (3) grounding efforts in nationally owned data and evidence; (4) developing mutually embraced ‘language’ across health and finance; and (5) elevating the priority accorded to NCDs, by framing action as an investment rather than a cost. The assessment also identified barriers to progress on the investment case implementation, including the influence of some private sector entities on sectors other than health, the impact of the COVID-19 pandemic, and changes in senior political and technical government officials. The results suggest that national NCD investment cases can significantly contribute to catalysing the prevention and control of NCDs through strengthening governance, financing, and health service access and delivery.

Background Emollients are recommended for children with eczema (atopic eczema/dermatitis). A lack of head-to-head comparisons of the effectiveness and acceptability of the different types of emollients has resulted in a ‘trial and error’ approach to prescribing. Objective To compare the effectiveness and acceptability of four commonly used types of emollients for the treatment of childhood eczema. Design Four group, parallel, individually randomised, superiority randomised clinical trials with a nested qualitative study, completed in 2021. A purposeful sample of parents/children was interviewed at ≈ 4 and ≈ 16 weeks. Setting Primary care (78 general practitioner surgeries) in England. Participants Children aged between 6 months and 12 years with eczema, of at least mild severity, and with no known sensitivity to the study emollients or their constituents. Interventions Study emollients sharing the same characteristics in the four types of lotion, cream, gel or ointment, alongside usual care, and allocated using a web-based randomisation system. Participants were unmasked and the researcher assessing the Eczema Area Severity Index scores was masked. Main outcome measures The primary outcome was Patient-Oriented Eczema Measure scores over 16 weeks. The secondary outcomes were Patient-Oriented Eczema Measure scores over 52 weeks, Eczema Area Severity Index score at 16 weeks, quality of life (Atopic Dermatitis Quality of Life, Child Health Utility-9 Dimensions and EuroQol-5 Dimensions, five-level version, scores), Dermatitis Family Impact and satisfaction levels at 16 weeks. Results A total of 550 children were randomised to receive lotion (analysed for primary outcome 131/allocated 137), cream (137/140), gel (130/135) or ointment (126/138). At baseline, 86.0% of participants were white and 46.4% were female. The median (interquartile range) age was 4 (2–8) years and the median Patient-Oriented Eczema Measure score was 9.3 (SD 5.5). There was no evidence of a difference in mean Patient-Oriented Eczema Measure scores over the first 16 weeks between emollient types (global p = 0.765): adjusted Patient-Oriented Eczema Measure pairwise differences – cream–lotion 0.42 (95% confidence interval –0.48 to 1.32), gel–lotion 0.17 (95% confidence interval –0.75 to 1.09), ointment–lotion –0.01 (95% confidence interval –0.93 to 0.91), gel–cream –0.25 (95% confidence interval –1.15 to 0.65), ointment–cream –0.43 (95% confidence interval –1.34 to 0.48) and ointment–gel –0.18 (95% confidence interval –1.11 to 0.75). There was no effect modification by parent expectation, age, disease severity or the application of UK diagnostic criteria, and no differences between groups in any of the secondary outcomes. Median weekly use of allocated emollient, non-allocated emollient and topical corticosteroids was similar across groups. Overall satisfaction was highest for lotions and gels. There was no difference in the number of adverse reactions and there were no significant adverse events. In the nested qualitative study (n = 44 parents, n = 25 children), opinions about the acceptability of creams and ointments varied most, yet problems with all types were reported. Effectiveness may be favoured over acceptability. Parents preferred pumps and bottles over tubs and reported improved knowledge about, and use of, emollients as a result of taking part in the trial. Limitations Parents and clinicians were unmasked to allocation. The findings may not apply to non-study emollients of the same type or to children from more ethnically diverse backgrounds. Conclusions The four emollient types were equally effective. Satisfaction with the same emollient types varies, with different parents/children favouring different ones. Users need to be able to choose from a range of emollient types to find one that suits them. Future work Future work could focus on how best to support shared decision-making of different emollient types and evaluations of other paraffin-based, non-paraffin and ‘novel’ emollients. Trial registration This trial is registered as ISRCTN84540529 and EudraCT 2017-000688-34. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (HTA 15/130/07) and will be published in full in Health Technology Assessment; Vol. 27, No. 19. See the NIHR Journals Library website for further project information. Plain language summary One in five children in the UK have eczema, a long-term, itchy, dry skin condition. It can significantly affect both the child and their family. Most children are diagnosed and looked after by their family doctor (general practitioner) and are prescribed moisturisers (also called emollients) to relieve skin dryness and other creams (topical corticosteroids) to control flare-ups. However, there are many different types of emollients and, to our knowledge, limited research to show which is better. In the Best Emollients for Eczema clinical trial, we compared the four main types of moisturisers – lotions, creams, gels and ointments. These types vary in their consistency, from thin to thick. We recruited 550 children (most of whom were white and had moderate eczema) and randomly assigned them to use one of the four different types as their main moisturiser for 16 weeks. We found no difference in effectiveness. Parent-reported eczema symptoms, eczema severity and quality of life were the same for all the four types of moisturisers. However, overall satisfaction was highest for lotions and gels. Ointments may need to be used less and cause less stinging. We interviewed 44 parents and 25 children who took part. Opinions of all four types of moisturisers varied. What one family liked about a moisturiser was not necessarily the same for another and preferences were individual to each user. Sometimes there was a tension between how well a moisturiser worked (effectiveness) and how easy it was to use (acceptability). In these cases, effectiveness tended to decide whether or not parents kept using it. People found moisturisers in pumps and bottles easier to use than those in tubs. A number of participants valued the information they were given about how to use moisturisers. Our results suggest that the type of moisturiser matters less than finding one that suits the child and family. Scientific summary Background Eczema (also called atopic eczema/dermatitis) is a common condition that usually first appears in early childhood. It is characterised by dry, itchy skin. Emollients are recommended for all patients, used as a ‘leave-on’ treatment to add and help retain moisture in the skin. For all but the mildest disease, they are used in combination with topical anti-inflammatory (topical corticosteroids or calcineurin inhibitors) to treat and prevent eczema flare-ups. Despite the accepted importance of emollients in treating the dry skin of eczema, there is limited evidence to guide prescribers and users on what types to use. In previous research, parents/carers (hereafter, parents) of children with eczema have spoken of a ‘trial and error’ approach to finding an emollient that suits them and their child, with the attendant frustration, waste and costs to both users and the health service. Objectives We sought to: compare the effectiveness and acceptability of four commonly used types of emollients (lotion, cream, gel and ointment) in the treatment of childhood eczema explore carers’ and children’s experiences of study emollient use and their views about perceived effectiveness and/or acceptability of study emollients. Methods We recruited children with eczema via general practitioners’ (GPs’) surgeries based in three centres (West of England, Wessex and East Midlands). To be eligible, children had to be aged between 6 months and 12 years and to have at least a mild form of disease, and parents had to be willing to be randomly allocated to any of the types as their main emollient. Children with a known sensitivity to study emollients or their constituents were excluded. Participants were randomised to lotion, cream, gel or ointment groups in a 1 : 1 : 1 : 1 manner, stratified by centre and minimised by baseline eczema severity as determined by the Patient Orientated Eczema Measure (POEM) score [mild (3–7 points) vs. moderate/severe (≥ 8 points)] and participant age (< 2 years vs. ≥ 2 years). Participants received their allocated type of emollient via their GP, who prescribed products on their local formulary that were study approved. All study emollients were paraffin based and none contained antimicrobials or urea. Study lotions contained glycerol [Cetraben (Thornton & Ross Ltd, Huddersfield, UK), Diprobase (Bayer UK Ltd, Reading, UK), QV (QV Skincare, Melbourne, VIC, Australia)], study creams had no humectant or lanolin [AproDerm (Fontus Health, Walsall, UK), Aquamax (Intrapharm Laboratories, Maidenhead, UK), Diprobase, Epimax (Aspire Pharma, Petersfield, UK), Zerobase (Thornton & Ross Ltd, Huddersfield, UK)], gels did not contain povidine [AproDerm (Fontus Health, Walsall, UK), Doublebase (Diomed Developments, Hitchin, UK), Isomol (Aspire Pharma, Petersfield, UK), MyriBase (Penlan Healthcare,Weybridge, UK) and Zerodouble (Thornton & Ross Ltd, Huddersfield, UK)] and study ointments had no additives (Diprobase, Emulsifying, Paraffin White soft, Paraffin Yellow soft ointment, White soft/Liquid paraffin 50/50). Participants were asked to use their study emollient as their only leave-on treatment for the first 16 weeks; thereafter, they were free to change. However, if they had problems with or disliked their study emollient, they could stop it and seek an alternative from their GP. Participants’ skin was assessed using the Eczema Area Severity Index (EASI) at baseline and at 16 weeks by a researcher masked to treatment allocation. Other data were collected by self-completed questionnaires weekly (first 16 weeks) and then 4-weekly (until 52 weeks). The primary outcome was eczema symptoms measured using the POEM over 16 weeks. We sought to recruit 520 children to detect a difference of 3.0 points in POEM scores between any two groups with 90% power and a significance level of 0.05, allowing for 20% loss to follow-up and multiple comparison testing. We conducted semistructured interviews with parents and older children at around 4 weeks and 16 weeks after randomisation, sampling on the characteristics of the children. The interviews were conducted face to face and by telephone, informed by a topic guide that was revised during the course of the study. Interviews were audio-recorded and transcribed verbatim. Analysis was thematic and carried out alongside data collection, which stopped once saturation was reached. Ethics approval was granted by the NHS Research Ethics Committee (South West – Central Bristol Research Ethics Committee 17/SW/0089). Results Between January 2018 and October 2019, 78 GP surgeries sent 9437 invitations to potentially eligible children. Expressions of interest were received from 910 parents, and 550 children attended a baseline visit, were eligible and enrolled. At baseline, the characteristics of participants were balanced except for sex, as there were more girls in the cream group (55%) than in the gel group (40%). Most children were white (86.0%), with a median age of 4 years (interquartile range 2–8 years) and moderate severity eczema (mean POEM score 9.32 points; standard deviation 5.46 points). Creams (94.5%) were most likely to have been used before, followed by ointments (66%), lotions (63.0%) and gels (25.0%). Participants were randomised to receive lotion (n = 137), cream (n = 140), gel (n = 135) or ointment (n = 138), with prescriptions issued by their GP. The median number of days between randomisation and reported first use of emollient was 4 days (interquartile range 3–7 days), with 80% reporting first use within 7 days of randomisation. There were 29 withdrawals (24 in the first 16 weeks). A total of 95% of participants provided at least one post-baseline POEM score and, therefore, were included in the primary outcome analysis. The researcher undertaking the EASI assessment identified the correct allocation in seven participants. There was no difference in the primary outcome (repeated-measures analysis of weekly POEM scores over the first 16 weeks) between the different groups (global p = 0.765). The adjusted differences in mean POEM scores [95% confidence interval (CI)] for pairwise comparisons were as follows: lotion versus cream 0.42 (95% CI –0.48 to 1.32; p = 0.360); lotion versus gel 0.17 (95% CI –0.75 to 1.09; p = 0.718); lotion versus ointment –0.01 (95% CI –0.93 to 0.91; p = 0.983); cream versus gel –0.25 (95% CI –1.15 to 0.65; p = 0.586); cream versus ointment –0.43 (95% CI –1.34 to 0.48; p = 0.354); and gel versus ointment –0.18 (95% CI –1.11 to 0.75; p = 0.704). Adjusting for sex imbalance at baseline and imputing missing data using multiple imputation did not meaningfully alter these results. There was no evidence of a difference in mean POEM scores between treatment groups or in any of the pairwise comparisons in first 16 weeks in ‘per-protocol’ analysis (p = 0.238) or over the 52 weeks (p = 0.909). There was no evidence of effect modification in prespecified subgroup analyses by parent prior emollient expectation (p = 0.935), participant age (p = 0.343), participant eczema severity (p = 0.042), or UK diagnostic criteria for atopic dermatitis (p = 0.291). No differences between groups were seen in the following secondary outcomes at 16 weeks (or 52 weeks, if also collected): EASI scores, Atopic Dermatitis Quality of Life scores, Child Health Utility 9-Dimension scores, Dermatitis Family Impact scores and well-controlled weeks. During the first 16 weeks, median reported weekly use of the allocated emollient appeared to be higher in the lotion and cream groups (6 days per week) and lower in the gel (5 days) and ointment (3 days) groups, but this difference in usage was not statistically significant (p = 0.481). Similarly, there was no difference between groups in median reported daily use of non-allocated emollient or topical corticosteroids. Overall satisfaction was highest with lotions and gels (67.3% and 64.5% very or mostly satisfied, respectively) and dissatisfaction was highest with creams and ointments (34.2% and 40.4% dissatisfied or very dissatisfied, respectively) (p = 0.003). Overall, 37% of participants reported at least one adverse reaction, the most common being ‘application site reactions’ (e.g. worsening of eczema). There was no evidence that the proportion of children reporting adverse reactions in the first 16 weeks of follow-up differed by treatment group (p = 0.794). There were no significant adverse events. In the nested qualitative study, 44 parents were interviewed, 20 at both weeks 4 and 24 (including five repeat interviews at week 16). Children took part in 25 interviews. Participants judged the effectiveness of study emollients by comparing them with others they had used in the past (i.e. the perceived hydrating action of the emollient, skin feel after application, skin symptoms and appearance, the number of flare-ups, and the need for topical corticosteroid use). Other factors identified as affecting effectiveness were weather and the frequency and quantity of emollient application. Acceptability was usually considered alongside or as part of the effectiveness of an emollient. Characteristics of the emollients that participants considered were how it felt on the skin, ease of application and absorbency, with smell being less important. In terms of containers, participants favoured pumps and squeezer bottles for practical reasons, including older child being able to self-apply. Many participants in the lotion and gel groups reported ease of application but felt that these types of emollients had to be used more often, and there was a perception that they ‘maintained’ rather than improved the skin. Although participants using study creams and study ointment were more likely to report improvements, opinions about their acceptability were more divergent. Problems were reported with all types of emollients. At 16 weeks, there was no clear pattern or differentiation between the emollient types in terms of continued use over and above the factors listed above. Parents of children with very dry and/or rough skin tended to prefer an emollient with a thicker consistency, such as a cream or an ointment. Age was also reported to influence emollient use: application may be easier/more frequent in younger children, accompanying nappy changes, and more difficult in older children as they become more independent and attend school. Some participants thought that their child’s eczema and the effectiveness of their emollient was related to their ethnicity. Changes in behaviour and knowledge were reported as a result of taking part in the trial. For some, the regular study questionnaires had reminded them to apply their emollient regularly. Others reported persisting more with one treatment or that the emollient information sheet had improved their knowledge of eczema management. Conclusions No one type of emollient was found to be superior, although these findings may not apply to children from more ethnically diverse backgrounds. Parents and children should be made aware that application site reactions are common; persistence may be required to find an emollient that works for them; and preferences may change with time, season and body site. We have also demonstrated the need for choice and education around the use of emollients for the treatment of eczema in children. Without this, emollients may be applied incorrectly or not as frequently as prescribed. Most children with eczema will need, in addition to their emollient, a topical anti-inflammatory treatment (usually corticosteroids) appropriate to the site and severity of their eczema to get, and keep, control of their condition. Guidelines should advocate for, and formularies support, a range of emollients, with lotions, creams, gels and ointments all available. Prescribers and pharmacists have an important role in ensuring that families are aware of the different emollients available, to support them in selecting a type most likely to suit them and to advise on optimal use. Verbal advice could be accompanied by written or online information (including videos) on the role of emollients and how to use them, perhaps accompanied by a planned review at the end of an agreed trial period. Future research could evaluate a decision aid to support parents and clinicians in deciding which type of emollient to try first and the clinical effectiveness and cost-effectiveness of providing ‘tester pots’ of each type of emollient to try before selecting their preferred emollient. Further trials may be appropriate to compare emollients in more ethnically diverse populations and of different types not evaluated in this study, for example ointments with emulsifiers and humectant-containing, plant-based and ‘novel’ emollients, including those designed to alter the skin microbiome. Research in this field would benefit from an internationally agreed system of classifying different emollients and a common approach to measuring and reporting treatment use. Finally, further research is needed to determine how emollients best fit into an overall package of eczema care, which includes frequency of use, bathing, use of other topical treatments and avoidance of triggers. Trial registration This trial is registered as ISRCTN84540529 and EudraCT 2017-000688-34. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (HTA 15/130/07) and will be published in full in Health Technology Assessment; Vol. 27, No. 19. See the NIHR Journals Library website for further project information.

BackgroundNon-communicable diseases (NCDs) are increasingly recognized as a significant threat to health and development globally, and United Nations (UN) Member States adopted the Political Declaration of the Third High-level Meeting (HLM) on the prevention and control of NCDs in 2018. The negotiation process for the Declaration included consultations with Member States, intergovernmental organizations (IGOs), and non-state actors such as non-governmental organizations (NGOs) and the private sector. With NCD responses facing charges of inadequacy, it is important to scrutinize the governance process behind relevant high-level global decisions and commitments. MethodsThrough a review of 159 documents submitted by stakeholders during the negotiation process, we outline a typology of policy positions advocated by various stakeholders in the development of the Declaration. We document changes in text from the draft to the final version of the Declaration to analyse the extent to which various positions and their proponents were influential. ResultsNGOs and low- and middle-income countries (LMICs) generally pursued ‘stricter’ governance of NCD risk factors including stronger regulation of unhealthy products and improved management of conflicts of interest that arise when health-harming industries are involved in health policy-making. The private sector and high-income countries generally opposed greater restrictions on commercial factors. The pattern of changes between the draft and final Declaration indicate that advocated positions tended to be included in the Declaration if there was no clear opponent, whereas opposed positions were either not included or included with ambiguous language. ConclusionMany cost-effective policy options to address NCDs, such as taxation of health-harming products, were opposed by high-income countries and the private sector and not well-represented in the Declaration. To ensure robust political commitments and action on NCDs, multi-stakeholder governance for NCDs must consider imbalances in power and influence amongst constituents as well as biases and conflicts in positioning.

Abstract Background Addressing the social and other non-biological determinants of health largely depends on policies and programmes implemented outside the health sector. While there is growing evidence on the effectiveness of interventions that tackle these upstream determinants, the health sector does not typically prioritise them. From a health perspective, they may not be cost-effective because their non-health outcomes tend to be ignored. Non-health sectors may, in turn, undervalue interventions with important co-benefits for population health, given their focus on their own sectoral objectives. The societal value of win-win interventions with impacts on multiple development goals may, therefore, be under-valued and under-resourced, as a result of siloed resource allocation mechanisms. Pooling budgets across sectors could ensure the total multi-sectoral value of these interventions is captured, and sectors’ shared goals are achieved more efficiently. Under such a co-financing approach, the cost of interventions with multi-sectoral outcomes would be shared by benefiting sectors, stimulating mutually beneficial cross-sectoral investments. Leveraging funding in other sectors could off-set flat-lining global development assistance for health and optimise public spending. Although there have been experiments with such cross-sectoral co-financing in several settings, there has been limited analysis to examine these models, their performance and their institutional feasibility. Aim This study aimed to identify and characterise cross-sectoral co-financing models, their operational modalities, effectiveness, and institutional enablers and barriers. Methods We conducted a systematic review of peer-reviewed and grey literature, following PRISMA guidelines. Studies were included if data was provided on interventions funded across two or more sectors, or multiple budgets. Extracted data were categorised and qualitatively coded. Results Of 2751 publications screened, 81 cases of co-financing were identified. Most were from high-income countries (93%), but six innovative models were found in Uganda, Brazil, El Salvador, Mozambique, Zambia, and Kenya that also included non-public and international payers. The highest number of cases involved the health (93%), social care (64%) and education (22%) sectors. Co-financing models were most often implemented with the intention of integrating services across sectors for defined target populations, although models were also found aimed at health promotion activities outside the health sector and cross-sectoral financial rewards. Interventions were either implemented and governed by a single sector or delivered in an integrated manner with cross-sectoral accountability. Resource constraints and political relevance emerged as key enablers of co-financing, while lack of clarity around the roles of different sectoral players and the objectives of the pooling were found to be barriers to success. Although rigorous impact or economic evaluations were scarce, positive process measures were frequently reported with some evidence suggesting co-financing contributed to improved outcomes. Conclusion Co-financing remains in an exploratory phase, with diverse models having been implemented across sectors and settings. By incentivising intersectoral action on structural inequities and barriers to health interventions, such a novel financing mechanism could contribute to more effective engagement of non-health sectors; to efficiency gains in the financing of universal health coverage; and to simultaneously achieving health and other well-being related sustainable development goals.

Background: There is modest evidence that exercise referral schemes increase physical activity in inactive individuals with chronic health conditions. There is a need to identify additional ways to improve the effects of exercise referral schemes on long-term physical activity. Objectives: To determine if adding the e-coachER intervention to exercise referral schemes is more clinically effective and cost-effective in increasing physical activity after 1 year than usual exercise referral schemes. Design: A pragmatic, multicentre, two-arm randomised controlled trial, with a mixed-methods process evaluation and health economic analysis. Participants were allocated in a 1 : 1 ratio to either exercise referral schemes plus e-coachER (intervention) or exercise referral schemes alone (control). Setting: Patients were referred to exercise referral schemes in Plymouth, Birmingham and Glasgow. Participants: There were 450 participants aged 16–74 years, with a body mass index of 30–40 kg/m2, with hypertension, prediabetes, type 2 diabetes, lower limb osteoarthritis or a current/recent history of treatment for depression, who were also inactive, contactable via e-mail and internet users. Intervention: e-coachER was designed to augment exercise referral schemes. Participants received a pedometer and fridge magnet with physical activity recording sheets, and a user guide to access the web-based support in the form of seven ‘steps to health’. e-coachER aimed to build the use of behavioural skills (e.g. self-monitoring) while strengthening favourable beliefs in the importance of physical activity, competence, autonomy in physical activity choices and relatedness. All participants were referred to a standard exercise referral scheme. Primary outcome measure: Minutes of moderate and vigorous physical activity in ≥ 10-minute bouts measured by an accelerometer over 1 week at 12 months, worn ≥ 16 hours per day for ≥ 4 days including ≥ 1 weekend day. Secondary outcomes: Other accelerometer-derived physical activity measures, self-reported physical activity, exercise referral scheme attendance and EuroQol-5 Dimensions, five-level version, and Hospital Anxiety and Depression Scale scores were collected at 4 and 12 months post randomisation. Results: Participants had a mean body mass index of 32.6 (standard deviation) 4.4 kg/m2, were referred primarily for weight loss and were mostly confident self-rated information technology users. Primary outcome analysis involving those with usable data showed a weak indicative effect in favour of the intervention group (n = 108) compared with the control group (n = 124); 11.8 weekly minutes of moderate and vigorous physical activity (95% confidence interval –2.1 to 26.0 minutes; p = 0.10). Sixty-four per cent of intervention participants logged on at least once; they gave generally positive feedback on the web-based support. The intervention had no effect on other physical activity outcomes, exercise referral scheme attendance (78% in the control group vs. 75% in the intervention group) or EuroQol-5 Dimensions, five-level version, or Hospital Anxiety and Depression Scale scores, but did enhance a number of process outcomes (i.e. confidence, importance and competence) compared with the control group at 4 months, but not at 12 months. At 12 months, the intervention group incurred an additional mean cost of £439 (95% confidence interval –£182 to £1060) compared with the control group, but generated more quality-adjusted life-years (mean 0.026, 95% confidence interval 0.013 to 0.040), with an incremental cost-effectiveness ratio of an additional £16,885 per quality-adjusted life-year. Limitations: A significant proportion (46%) of participants were not included in the primary analysis because of study withdrawal and insufficient device wear-time, so the results must be interpreted with caution. The regression model fit for the primary outcome was poor because of the considerable proportion of participants [142/243 (58%)] who recorded no instances of ≥ 10-minute bouts of moderate and vigorous physical activity at 12 months post randomisation. Future work: The design and rigorous evaluation of cost-effective and scalable ways to increase exercise referral scheme uptake and maintenance of moderate and vigorous physical activity are needed among patients with chronic conditions. Conclusions: Adding e-coachER to usual exercise referral schemes had only a weak indicative effect on long-term rigorously defined, objectively assessed moderate and vigorous physical activity. The provision of the e-coachER support package led to an additional cost and has a 63% probability of being cost-effective based on the UK threshold of £30,000 per quality-adjusted life-year. The intervention did improve some process outcomes as specified in our logic model. Trial registration: Current Controlled Trials ISRCTN15644451. 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. 24, No. 63. See the NIHR Journals Library website for further project information.

[This corrects the article DOI: 10.1371/journal.pone.0223412.].

Introduction Parkinson’s disease (PD) is a progressive neurodegenerative condition affecting approximately 185,000 people in the UK. No drug has been proven to slow disease progression. Epidemiological and pre-clinical data support simvastatin, a widely used cholesterol-lowering drug with a well-established safety profile, having neuroprotective properties. The aim of this study (Simvastatin as a neuroprotective treatment for PD (PD STAT)) is to determine whether simvastatin has the potential to slow PD progression. The study is part of the International Linked Clinical Trials initiative coordinated by The Cure Parkinson’s Trust. This paper describes the protocol for the PD STAT study.Methods and analysis PD STAT is a double-blind, randomised, placebo-controlled, multi-centre, parallel group, futility trial in patients with PD of mild–moderate severity. 235 participants have been recruited and randomly allocated in a 1:1 ratio to receive either oral simvastatin or matched placebo. Treatment involves a 1-month low-dose phase (40 mg daily), followed by a 23-month high-dose phase (80 mg daily) and ends with a 2-month washout period. Participants are reviewed at clinic visits at 1 month, 6, 12, 18, 24 and 26 months post-baseline, with interim telephone follow-up to monitor for adverse events.The primary outcome is the change in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale part III motor subscale score in the practically defined OFF medication state (OFF state) between baseline and 24 months. Primary analysis will be on a modified intention to treat basis and will include only those participants who progress to the high-dose phase of the study.Ethics and dissemination The protocol has been approved by the North East–Newcastle and North Tyneside 2 Research Ethics Committee. The results will be disseminated via research articles in peer-reviewed journals and presentations at local, national and international scientific meetings, as well as disseminated via patient groups, websites and networks. A summary of the study findings will be posted to participants at the end of the study.Trial Registration ISRCTN16108482 (prospectively registered); EudraCT 2015-000148-40; ClinicalTrials.gov NCT02787590; Pre-results.

Noncommunicable diseases (NCDs) are a broad challenge for decision-makers. NCDs account for seven out of every 10 deaths globally, with 42 percent occurring prematurely in individuals under age 70. Despite their heavy toll, NCDs are underfunded, with only around two percent of global funding dedicated to the disease set. Country governments are responsible for funding targeted actions to reduce the NCD burden, but among other priorities, many have yet to invest in the health-system interventions and policy measures that can reduce the burden. This article examines "investment cases" as a potential mechanism for catalyzing attention to-and funding for-NCDs. In Jamaica, using the UN inter-agency OneHealth Tool, we conducted an economic analysis to estimate the return-on-investment from scaling up strategic clinical interventions, and from implementing or intensifying policy measures that target NCD risk factors. In addition, we conducted an institutional and context (ICA) analysis, interviewing stakeholders across sectors to take stock of promising policy pathways (e.g., areas of general consensus, political appetite and opportunity) as well as challenges to implementation. The economic analysis found that scaling up clinical interventions that target CVD, diabetes, and mental health disorders, and policy measures that target tobacco and alcohol use, would save over 6,600 lives between 2017-2032, and avert JMD 81.3 billion (USD 640 million) in direct and indirect economic costs that result from mortality and morbidity linked to NCDs. The ICA uncovered government economic growth targets and social priorities that would be aided by increased attention to NCDs, and it linked these targets and priorities to the economic analysis.

Background: Promoting physical activity (PA) via primary care exercise referral schemes (ERS) is common but there is no rigorous evidence for long term changes in PA (Pavey et al, 2011) among those with chronic conditions. From July 2015, for 15 months, the e-coachER trial began to recruit 1400 patients (in SW England, Birmingham and Glasgow) with one or more chronic conditions including diabetes, obesity, hypertension, osteoarthritis, or depression, who are eligible and about to attend an ERS. The two-arm parallel RCT is powered to determine if the addition of a web-based, interactive, theory-driven and evidence-based support system called e-coachER (hosted on the ‘LifeGuide’ platform) will result in at least 10% more patients who do 150 mins or more per week of accelerometer assessed moderate or vigorous physical activity (MVPA) at 12 months. Recruitment into the trial is within primary care, using both mail-merged patient invitations and opportunistic GP invitations (and exercise referrals). Within the trial, after participants are screened, provide consent and complete baseline assessments, they are randomised to receive usual ERS at each site or usual ERS plus a mailed Welcome Pack with registration details to access e-coachER on-line. Inclusion criteria for entering the trial are: (1) Aged 16-74 years; (2) with one or more of the following: obesity (BMI 30-35), hypertension (SBP 140-179 or DBP 90-109, type 2 diabetes, lower limb osteoarthritis, recent history of treatment for depression; (3) Participants who are in the two lowest (of four) groups using the GP Physical Activity Questionnaire; (4) have an e-mail address and access to the internet; (5) Eligible for an ERS. The intervention rationale, design and content are reported in another presentation. Aims: This presentation will provide initial findings from a 3 month internal pilot phase with a focus on trial recruitment and initial intervention engagement. We will present data on the achievement of our targets for recruiting 180 participants across the three sites and proportion who initially go online to register and use e-coachER. We also aim, based on detailed process evaluation work, to present a summary of factors influencing recruitment and intervention engagement, and any adaptations needed for the recruitment process. Methods: Data is being captured to inform a CONSORT chart with details on number of patient invitations, number and reasons for trial exclusion, and numbers and characteristics of those recruited. The LifeGuide system will provide data on numbers/proportion assigned to the intervention arm who register and start to use e-coachER. Qualitative data on recruitment processes and intervention engagement, as part of the process evaluation, will be summarised. Results: Due to a number of factors recruitment began 2-4 months later than planned across the 3 sites. Data will be presented on achieved recruitment and e-coachER engagement relative to our targets in the internal pilot trial. Qualitative data will be presented on the acceptability and feasibility of the trial methods and intervention. Conclusion: A summary of what we have learned about recruitment and intervention engagement will be presented and ideas for improvement, as appropriate. Supported with funding from the NIHR (HTA) Project: 13/25/20

Histone deacetylase inhibitors (HDACis) are emerging as promising and selective antitumor agents. However, HDACis can lead to tumor stasis rather than shrinkage, in which case, traditional imaging methods are not adequate to monitor response. Consequently, novel approaches are needed. We have shown in cells that 19 F magnetic resonance spectroscopy (MRS)-detectable levels of the HDAC substrate Boc-Lys-TFA-OH (BLT) are inversely correlated with HDAC activity. We extended our investigations to a tumor xenograft model. Following intraperitoneal injection of BLT, its accumulation within the tumor was monitored by in vivo 19 F MRS. In animals treated with the HDACi suberoylanilide hydroxamic acid (SAHA), tumoral BLT levels were higher by 77% and 132% on days 2 and 7 of treatment compared with pretreatment levels ( n = 6; p < .05). In contrast, tumoral BLT levels remained unchanged in control animals and in normal tissue. Thus, 19 F MRS of BLT detected the effect of HDACi treatment as early as day 2 of treatment. Importantly, tumor size confirmed that SAHA treatment leads to inhibition of tumor growth. However, difference in tumor size reached significance only on day 6 of treatment. Thus, this work identifies BLT as a potential molecular imaging agent for the early noninvasive MRS detection of HDAC inhibition in vivo.