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Background Positive Choices is a whole-school social marketing intervention to promote sexual health among secondary school students. Intervention comprises school health promotion council involving staff and students coordinating delivery; student survey to inform local tailoring; teacher-delivered classroom curriculum; student-run campaigns; parent information; and review of sexual/reproductive health services to inform improvements. This trial builds on an optimisation/pilot RCT study which met progression criteria, plus findings from another pilot RCT of the Project Respect school-based intervention to prevent dating and relationship violence which concluded such work should be integrated within Positive Choices. Young people carry a disproportionate burden of adverse sexual health; most do not report competence at first sex. Relationships and sex education in schools can contribute to promoting sexual health but effects are small, inconsistent and not sustained. Such work needs to be supplemented by ‘whole-school’ (e.g. student campaigns, sexual health services) and ‘social marketing’ (harnessing commercial marketing to social ends) approaches for which there is good review-level evidence but not from the UK. Methods We will conduct a cluster RCT across 50 schools (minimum 6440, maximum 8500 students) allocated 1:1 to intervention/control assessing outcomes at 33 months. Our primary outcome is non-competent first sex. Secondary outcomes are non-competent last sex, age at sexual debut, non-use of contraception at first and last sex among those reporting heterosexual intercourse, number of sexual partners, dating and relationship violence, sexually transmitted infections, and pregnancy and unintended pregnancy for girls and initiation of pregnancy for boys. We will recruit 50 school and undertake baseline surveys by March 2022; implement the intervention over the 2022–2024 school years and conduct the economic and process evaluations by July 2024; undertake follow-up surveys by December 2024; complete analyses, all patient and policy involvement and draft the study report by March 2025; and engage in knowledge exchange from December 2024. Discussion This trial is one of a growing number focused on whole-school approaches to public health in schools. The key scientific output will be evidence about the effectiveness, costs and potential scalability and transferability of Positive Choices. Trial registration ISRCTN No: ISRCTN16723909. Trial registration summary: Date:. Funded by: National Institute for Health Research Public Health Research Programme (NIHR131487). Sponsor: LSHTM. Public/scientific contact: Chris Bonell. Public title: Positive Choices trial. Scientific title: Phase-III RCT of Positive Choices: a whole-school social marketing intervention to promote sexual health and reduce health inequalities. Countries of recruitment: UK. Intervention: Positive Choices. Inclusion criteria: Students in year 8 (age 12–13 years) at baseline deemed competent by schools to participate in secondary schools excluding pupil referral units, schools for those with special educational needs and disabilities, and schools with ‘inadequate’ Ofsted inspections. Study type: interventional study with superiority phase III cluster RCT design. Enrollment: 1/9/21-31/3/22. Sample size: 50 schools and 6440–8500 students. Recruitment status: pending. Primary outcome: binary measure of non-competent first sex. Secondary outcomes: non-competent last sex; age at sexual debut; non-use of contraception at first and last sex; number of sexual partners; dating and relationship violence (DRV) victimisation; sexually transmitted infections; pregnancy and unintended pregnancy for girls and initiation of pregnancy for boys using adapted versions of the RIPPLE measures. Ethics review: LSHTM research ethics committee (reference 26411). Completion data: 1/3/25. Sharing statement: Data will be made available after the main trial analyses have been completed on reasonable request from researchers with ethics approval and a clear protocol. Amendments to the protocol will be communicated to the investigators, sponsor, funder, research ethics committee, trial registration and the journal publishing the protocol. Amendments affecting participants’ experience of the intervention or important amendments affecting the overall design and conduct of the trial will be communicated to participants.

Approaches for rapid reviews that focus on streamlining systematic review methods are not always suitable for exploring complex policy questions, as developing and testing theories to explain these complexities requires configuring diverse qualitative, quantitative, and mixed methods studies. Our objective was therefore to provide a guide to selecting approaches for rapidly (i.e., within days to months) addressing complex questions related to health policy and system issues. We provide a two-stage, transdisciplinary collaborative process to select a rapid review approach to address complex policy questions, which consists of scoping the breadth and depth of the literature and then selecting an optimal approach to synthesis. The first stage (scoping the literature) begins with a discussion with the stakeholders requesting evidence to identify and refine the question for the review, which is then used to conduct preliminary searches and conceptually map the documents identified. In the second stage (selection of an optimal approach), further stakeholder consultation is required to refine and tailor the question and approach to identifying relevant documents to include. The approach to synthesizing the included documents is then guided by the final question, the breadth and depth of the literature, and the time available and can include a static or evolving conceptual framework to code and analyze a range of evidence. For areas already covered extensively by existing systematic reviews, the focus can be on summarizing and integrating the review findings, resynthesizing the primary studies, or updating the search and reanalyzing one or more of the systematic reviews. The choice of approaches for conducting rapid reviews is intertwined with decisions about how to manage projects, the amount of work to be done, and the knowledge already available, and our guide offers support to help make these strategic decisions. Supplementary Information The online version contains supplementary material available at 10.1186/s13643-021-01834-y.

Aim:\ud This systematic review identifies, appraises and synthesizes the evidence on the provision of fundamental nursing care to hospitalized patients with a highly infectious virus and the effectiveness of adaptations to overcome barriers to care.\ud \ud Design:\ud Systematic review.\ud \ud Data Sources:\ud In July 2020, we searched Medline, PsycINFO (OvidSP), CINAHL (EBSCOhost), BNI (ProQuest), WHO COVID-19 Database (https://search.bvsalud.org/) MedRxiv (https://www.medrxiv.org/), bioRxiv (https://www.biorxiv.org/) and also Google Scholar, TRIP database and NICE Evidence, forwards citation searching and reference checking of included papers, from 2016 onwards.\ud \ud Review Methods:\ud We included quantitative and qualitative research reporting (i) the views, perceptions and experiences of patients who have received fundamental nursing care whilst in hospital with COVID-19, MERS, SARS, H1N1 or EVD or (ii) the views, perceptions and experiences of professional nurses and non-professionally registered care workers who have provided that care. We included review articles, commentaries, protocols and guidance documents. One reviewer performed data extraction and quality appraisal and was checked by another person.\ud \ud Results:\ud Of 3086 references, we included 64 articles; 19 empirical research and 45 review articles, commentaries, protocols and guidance documents spanning five pandemics. Four main themes (and 11 sub-themes) were identified. Barriers to delivering fundamental care were wearing personal protective equipment, adequate staffing, infection control procedures and emotional challenges of care. These barriers were addressed by multiple adaptations to communication, organization of care, staff support and leadership.\ud \ud Conclusion:\ud To prepare for continuation of the COVID-19 pandemic and future pandemics, evaluative studies of adaptations to fundamental healthcare delivery must be prioritized to enable evidence-based care to be provided in future.\ud \ud Impact:\ud Our review identifies the barriers nurses experience in providing fundamental care during a pandemic, highlights potential adaptations that address barriers and ensure positive healthcare experiences and draws attention to the need for evaluative research on fundamental care practices during pandemics.

Children's mental health is deteriorating while access to child and adolescent mental health services is decreasing. Recent UK policy has focused on schools as a setting for the provision of mental health services, and counselling is the most common type of school-based mental health provision. This study examined the longer-term effectiveness of one-to-one school-based counselling delivered to children in UK primary schools. Data were drawn from a sample of children who received school-based counselling in the UK in the 2015/16 academic year, delivered by a national charitable organisation. Mental health was assessed at baseline, immediately post-intervention, and approximately 1 year post-intervention, using the Strengths and Difficulties Questionnaire (SDQ) completed by teachers and parents. Paired t tests compared post-intervention and follow-up SDQ total difficulties scores with baseline values. Propensity score matching was then used to identify a comparator group of children from a national population survey, and linear mixed effects models compared trajectories of SDQ scores in the two groups. In the intervention group, teacher and parent SDQ total difficulties scores were lower at post-intervention and longer-term follow-up compared to baseline (teacher: baseline 14.42 (SD 7.18); post-intervention 11.09 (6.93), t(739) = 13.78, p < 0.001; follow-up 11.27 (7.27), t(739) = 11.92, p < 0.001; parent: baseline 15.64 (6.49); post-intervention 11.90 (6.78), t(361 = 11.29, p < 0.001); follow-up 11.32 (7.19), t(361) = 11.29, p < 0.001). The reduction in SDQ scores was greater in the intervention compared to the comparator group (likelihood ratio test comparing models with time only versus time plus group-by-time interaction: χ2 (3) = 24.09, p < 0.001), and model-predicted SDQ scores were lower in the intervention than comparator group for 2 years post-baseline. A one-to-one counselling intervention delivered to children in UK primary schools predicted improvements in mental health that were maintained over a 2 year follow-up period.

Background Adolescent HIV and pregnancy rates in Southern Africa are amongst the highest in the world. Despite decades of sexual and reproductive health (SRH) programming targeting adolescents, recent trends suggest there is a continued need for interventions targeting condom use for this age group. Methods This review synthesises evidence from qualitative studies that describe the determinants of condom use among adolescents in Southern Africa. We conducted systematic searches in four databases. Data were extracted, appraised for quality and analysed using a ‘best-fit’ framework synthesis approach. Results We coded deductively findings from 23 original studies using an a priori framework and subsequently conducted thematic analysis. Synthesised findings produced six key themes relating to: 1) pervasive unequal gender norms and restrictive masculinities favouring male sexual decision-making and stigmatising condom use in committed relationships; 2) other social norms reflecting negative constructions of adolescent sexuality and non-traditional family planning; 3) economic and political barriers including poverty and a lack of policy support for condom use; 4) service-level barriers including a lack of youth-friendly SRH services and comprehensive sex education in schools; 5) interpersonal barriers and facilitators including unequal power dynamics in sexual partnerships, peer influences and encouraging condoning condom use, and inadequate communication about SRH from parents/caregivers; and 6) negative attitudes and beliefs about condoms and condom use among adolescents. A conceptual model was generated to describe determinants of condom use, illustrating individual-, interpersonal- and structural-level barriers and facilitating factors. Conclusion SRH programming targeting barriers and facilitators of condom use at multiple levels is recommended in Southern Africa. We present a multilevel integrated model of barriers and facilitators to guide adolescent SRH decision-making, programme planning and evaluation. Given the existence of multilevel barriers and facilitators, interventions should, likewise, take a multilevel approach that incorporates locally relevant understanding of the individual-, interpersonal- and structural-level barriers and facilitators to condom use among adolescents in the region.

Background Conceptual and theoretical links between politics and public health are longstanding. Internationally comparative systematic review evidence has shown links between four key political exposures – the welfare state, political tradition, democracy and globalisation – on population health outcomes. However, the pathways through which these influences may operate have not been systematically appraised. Therefore, focusing on child and maternal health outcomes, we present a realist re-analysis of the dataset from a recent systematic review. Methods The database from a recent systematic review on the political determinants of health was used as the data source for this realist review. Included studies from the systematic review were re-evaluated and those relating to child and/or maternal health outcomes were included in the realist synthesis. Initial programme theories were generated through realist engagement with the prior systematic review. These programme theories were adjudicated and refined through detailed engagement with the evidence base using a realist re-synthesis involving two independent reviewers. The revised theories that best corresponded to the evidence base formed the final programme theories. Results Out of the 176 included studies from the systematic review, a total of 67 included child and/or maternal health outcomes and were included in the realist re-analysis. Sixty-three of these studies were ecological and data were collected between 1950 and 2014. Six initial programme theories were generated. Following theory adjudication, three theories in revised form were supported and formed the final programme theories. These related to a more generous welfare state leading to better child and maternal health especially in developed countries through progressive social welfare policies, left-of-centre political tradition leading to lower child mortality and low birth weight especially in developed countries through greater focus on welfare measures, and increased globalisation leading to greater child and infant mortality and youth smoking rates in LMECs through greater influence of multinational corporations and neoliberal trade organisations. Conclusion We present a realist re-analysis of a large systematically identified body of evidence on how four key political exposures – the welfare state, democracy, political tradition and globalisation – relate to child and maternal health outcomes. Three final programme theories were supported.

The UK National Institute for Health and Care Excellence (NICE) considered evidence for voretigene neparvovec (VN; Luxturna®) for the treatment of RPE65-mediated inherited retinal dystrophies (IRD) within its highly specialised technology programme. This paper summarises the evidence provided by the company; the appraisal of the evidence by the Peninsula Technology Appraisal Group, who were commissioned to act as the independent evidence review group (ERG); and the development of the NICE guidance by the appraisal committee. The evidence presented by the company highlighted the significant lifelong burden of IRD for patients and carers. Evidence to support the effectiveness of VN was lacking, but the available evidence showed a modest, sustained improvement across a variety of vision-related outcomes. While patients would remain visually impaired, the committee considered that VN would prevent further deterioration in vision. The modelling approach used by the company had a number of limitations and relied heavily upon a large volume of clinical expert input to produce cost-effectiveness estimates with large uncertainty around long-term effectiveness. The ERG's main concerns revolved around these long-term outcomes and the plausibility of utility values. The NICE committee were convinced that the clinical benefits of VN were important and an appropriate use of national health service resources within a specialised service. The committee concluded that a high unmet need existed in patients with RPE65-mediated IRD and that VN represents a step change in the management of this condition.

Isolating sick patients, tracing their contacts and placing them into quarantine is a strategy used by generations of public health physicians in their fight against infectious disease. As coronavirus lockdowns around the world start to ease, new systems based on this strategy are being rolled out to prevent a resurgence of the pandemic. If these systems do not consider the behavioural issues posed by symptom reporting and quarantine, they will struggle to meet their goals.The goals of this commentary are to outline the key behavioural issues that a test, trace and isolate system for the management of COVID-19 will face, and to suggest specific ways that system design can address these. In this paper, we highlight five areas in which these behavioural issues should be taken into account, structured to follow the steps of the test, trace and isolate process: development of symptoms; reporting of symptoms; isolation; reporting of contacts; and quarantining contacts. The issues we highlight largely apply regardless of the modality of system, be it via an app, website or in-person consultation.

This study evaluated The Grassroot Project, a middle school sexual health promotion program in Washington, DC that uses university-level athlete role models and sports-based games. Seven schools we...

Despite new, effective biomedical technologies to prevent the transmission of HIV, social and structural factors still impact the opportunity for gay, bisexual and other men who have sex with men (GBMSM) to access safe sexual health services. Within this paper we describe findings of a pilot analysis that seeks to identify relationships between country level homophobia, individual-level sexualised drug use and key sexual health protective behaviours in a sample of HIV negative men from 45 countries recruited via a large online survey. Responses to questions relating to HIV and STI testing history, use of pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP) and engagement in sexualised drug use were treated as dependent variables within generalised linear mixed-effects model with logit link analysis, with country level homophobia (drawn from a recently published international index) operating as the dependent variable. In total, data from 9,356 respondents were included for analysis. Overall, uptake of behaviours known to be protective of sexual health overall was significantly lower in countries with high levels of homophobia. This paper is unique in linking a robust measure of country-level homophobia to engagement in health protective behaviours on a large-scale, multi-country level basis.

Background Women with previous gestational diabetes have an increased risk of developing type 2 diabetes later in life. Recommendations therefore urge these women to participate in follow-up screening, 4–12 weeks postpartum and every 1–3 years thereafter. We sought to theorize how reminder interventions to support early detection of diabetes work, for whom, and in what circumstances. Methods We used a method informed by realist review and synthesis. A systematic, iterative search in six electronic databases (PubMed, MEDLINE Ovid, The Cochrane Library, CINAHL, EMBASE) had a primary focus on experimental intervention studies and included additional information in relation to identified intervention studies. Analysis inductively identified context-mechanism-outcome configurations present in the evidence. Results We located 16 articles eligible for inclusion. A cross-case comparison identified seven grouped context-mechanism-outcome configurations leading to intervention mechanisms relating to changes in women’s reasoning and behavior. Configurations were thematically ordered in relation to Systems Resources, Women’s Circumstances, and Continuity of Care. These were mapped onto a socio-ecological model and discussed according to identified middle-range theories. Conclusion Our findings adds to the body of evidence, that reminders have the potential to be effective in increasing participation in the recommended follow-up screening. Our study may assist researchers and policy and decision makers to analyze and judge if reminders are feasible and/or likely to succeed in their specific context. Further research into the perspective of socially disadvantaged and overweight women is needed to avoid unintended consequences such as social inequality in service use and stigmatization in future programs.

Objective Launched to assist in achieving universal health coverage, provider payment reform (PPR) is one of the most important policy tools deployed to transform incentives within a health system that is plagued with allocative inefficiency and high out-of-pocket payments to one that is able to deliver basic services and be cost-efficient. However, the black box of such reform – that is, the contexts in which reform operates, the mechanisms by which it changes health systems and behaviour within health systems, and the outcome patterns that arise from – remains unexplored. This review aims to examine the implementation mechanisms underlying PPR in Asian developing countries. Methods A realist synthesis approach was employed to tease out the configurative elements of PPR in developing countries. A multimethod and retrospective search was conducted to locate the evidence. A programme theory and data extraction framework were developed. Data were analysed using thematic synthesis to inform an overarching realist synthesis, expressed as a set of synthesized context-mechanism-outcome configurations. Results This review found that the policy design of PPR, policy capacity, willingness of policy adoption at the local government level and provider autonomy are critical contextual factors that could trigger different policy mechanisms leading to either intended theoretical outcomes or perverse incentives. Conclusions Our findings, demonstrating the PPR implementation contexts and mechanisms that have worked in Asian countries, have implications in terms of policy learning for most developing countries that are contemplating rolling out similar reforms in the future.

cited By 1; Background: A review of therapies for advanced cancers licenced by the EMA between 2009 and 2013 concluded that for more than half of these drugs there was little evidence of overall survival or quality of life benefit. Recent years have witnessed a growing number of licensed second-line pharmacotherapies for advanced/metastatic non-small cell lung cancer (NSCLC). With the aim of gauging patient survival benefit, we conducted a systematic review of randomised controlled trials (RCT) and compared survival outcomes from available licensed treatments for patients with advanced/metastatic NSCLC. Methods: RCTs of second/third line treatments in participants with advanced/metastatic NSCLC and negative/low expression of Anaplastic Lymphoma Kinase (ALK) and of Epidermal Growth Factor Receptor (EGFR) were included. We searched electronic databases (MEDLINE; EMBASE; Web of Science) from January, 2000 up to July, 2017. Two or more independent reviewers screened bibliographic records, extracted data, and assessed risk of bias of studies. Published Kaplan Meier plots for OS and PFS along with restricted-mean-survival methods and parametric modelling were used to estimate the survival outcomes as mean number of months of survival. Network meta-analysis was undertaken to rank interventions and to make indirect comparisons. Results: We included 11 RCTs with data for 7581 participants that compared nine different drugs. In studies of patients regardless of histology groups, targeted drugs (ramucirumab and nintedanib) yielded small overall survival gains of < 2.5 months over docetaxel, erlotinib provided no benefit, while immunotherapies (atezolizumab and pembrolizumab) delivered 5 to 6 months gain. Studies with patients stratified by histology confirmed the apparent superiority of immunotherapy (nivolumab and atezolizumab) over targeted treatments (ramucirumab, nintedanib, afatinib) providing between about 4 to 8 months OS gain over docetaxel. In network analysis immunotherapies consistently ranked higher than alternatives irrespective of population histology and outcome measure. Conclusion: Our review indicates that nivolumab, pembrolizumab and atezolizumab provide superior survival benefits compared to other licensed drugs for late stage NSCLC. Patient gains from these immunotherapies are substantial compared to the expected average survival with chemotherapy (docetaxel) of < 1 year for people with squamous histology and about 1.25 year for those with non-squamous histology. © 2019 The Author(s).

Qualitative comparative analysis (QCA) was originally developed as a tool for cross-national comparisons in macrosociology, but its use in evaluation and evidence synthesis of complex interventions is rapidly developing. QCA is theory-driven and relies on Boolean logic to identify pathways to an outcome (eg, is the intervention effective or not?). We use the example of two linked systematic reviews on weight management programs (WMPs) for adults-one focusing on user views (a "views synthesis") and one focusing on the effectiveness of WMPs incorporating dietary and physical activity-to demonstrate how a synthesis of user views can supply a working theory to structure a QCA. We discuss how a views synthesis is especially apt to supply this working theory because user views can (a) represent a "middle-range theory" of the intervention; (b) bring a participatory, democratic perspective; and (c) provide an idiographic understanding of how the intervention works that external taxonomies may not be able to furnish. We then discuss the practical role that the views synthesis played in our QCA examining pathways to effectiveness: (a) by suggesting specific intervention features and sharpening the focus on the most salient features to be examined, (b) by supporting interpretation of findings, and (c) by bounding data analysis to prevent data dredging.

IntroductionPatient experience of nursing care is correlated with safety, clinical effectiveness, care quality, treatment outcomes and service use. Effective nursing care includes actions to develop nurse–patient relationships and deliver physical and psychosocial care to patients. The high risk of transmission of the SARS-CoV-2 virus compromises nursing care. No evidence-based nursing guidelines exist for patients infected with SARS-CoV-2, leading to potential variations in patient experience, outcomes, quality and costs.Methods and analysiswe aim to recruit 840 in-patient participants treated for infection with the SARS-CoV-2 virus from 14 UK hospitals, to a cluster randomised controlled trial, with embedded process and economic evaluations, of care as usual and a fundamental nursing care protocol addressing specific areas of physical, relational and psychosocial nursing care where potential variation may occur, compared with care as usual. Our coprimary outcomes are patient-reported experience (Quality from the Patients’ Perspective; Relational Aspects of Care Questionnaire); secondary outcomes include care quality (pressure injuries, falls, medication errors); functional ability (Barthell Index); treatment outcomes (WHO Clinical Progression Scale); depression Patient Health Questionnaire-2 (PHQ-2), anxiety General Anxiety Disorder-2 (GAD-2), health utility (EQ5D) and nurse-reported outcomes (Measure of Moral Distress for Health Care Professionals). For our primary analysis, we will use a standard generalised linear mixed-effect model adjusting for ethnicity of the patient sample and research intensity at cluster level. We will also undertake a planned subgroup analysis to compare the impact of patient-level ethnicity on our primary and secondary outcomes and will undertake process and economic evaluations.Ethics and disseminationResearch governance and ethical approvals are from the UK National Health Service Health Research Authority Research Ethics Service. Dissemination will be open access through peer-reviewed scientific journals, study website, press and online media, including free online training materials on the Open University’s FutureLearn web platform.Trial registration numberISRCTN13177364; Pre-results.

To understand associations between location of sex and sexual risk, it is most helpful to compare sexual encounters within persons. We systematically reviewed within-subjects comparisons of sexual encounters reported by men who have sex with men (MSM) with respect to location of sex. Within-subjects comparisons of sexual risk and location of sex were eligible if they collected data post-1996 from samples of MSM. We independently screened results and full-text records in duplicate. Of 6,336 deduplicated records, we assessed 138 full-text studies and included six, most of which compared unprotected anal intercourse against other anal intercourse. This small, but high quality, body of evidence suggests that associations between attendance at sex-on-premises venues and person-level sexual risk may be due to overall propensity towards unprotected sex. However, there may be some location factors that promote or are associated with serononconcordant unprotected anal intercourse. Health promoters may wish to focus on person-level characteristics.

Background Sexual risk, substance use, and mental ill health constitute a syndemic of co-occurring, mutually reinforcing epidemics amongst men who have sex with men (MSM). Developed since 1995, e-health interventions offer accessible, anonymous support and can be effective in addressing these outcomes, suggesting the potential value of developing e-health interventions that address these simultaneously amongst MSM. We conducted a systematic review of e-health interventions addressing one or more of these outcomes amongst MSM and in this paper describe the theories of change underpinning relevant interventions, what these offer and how they might complement each other. Methods We identified eligible reports via expert requests, reference-checking and database and Google searches. Results were screened for reports published in 1995 or later; focused on MSM; reporting on e-health interventions providing ongoing support to prevent HIV/STIs, sexual risk behaviour, substance use, anxiety or depression; and describing intervention theories of change. Reviewers assessed report quality, extracted intervention and theory of change data, and developed a novel method of synthesis using diagrammatic representations of theories of change. Results Thirty-three reports on 22 intervention theories of change were included, largely of low/medium-quality. Inductively grouping these theories according to their core constructs, we identified three distinct groupings of theorised pathways. In the largest, the ‘cognitive/skills’ grouping, interventions provide information and activities which are theorised to influence behaviour via motivation/intention and self-efficacy/perceived control. In the ‘self-monitoring’ grouping, interventions are theorised to trigger reflection, self-reward/critique and self-regulation. In the ‘cognitive therapy’ grouping, the theory of change is rooted in cognitive therapy techniques, aiming to reframe negative emotions to improve mental health. Conclusions The synthesised theories of change provide a framework for developing e-health interventions that might holistically address syndemic health problems amongst MSM. Improving reporting on theories of change in primary studies of e-health interventions would enable a better understanding of how they are intended to work and the evidence supporting this. The novel diagrammatic method of theory of change synthesis used here could be used for future reviews where interventions are driven by existing well-defined behaviour and behaviour change theories. Systematic review registration PROSPERO CRD42018110317

Background: The role of children and young people (CYP) in transmission of SARS-CoV-2 in household and educational settings remains unclear. We undertook a systematic review and meta-analysis of contact-tracing and population-based studies at low risk of bias. Methods: We searched 4 electronic databases on 5 April for contact-tracing studies and population-based studies informative about transmission of SARS-CoV-2 from 0-19 year olds in household or educational settings. We excluded studies at high risk of bias, including from under-ascertainment of asymptomatic infections. We undertook multilevel random effects meta-analyses of secondary attack rates (SAR: contact-tracing studies) and school infection prevalence, and used meta-regression to examine the impact of community SARS-CoV-2 incidence, mitigations and attendance on school infection prevalence. Findings: 4179 abstracts were reviewed, resulting in 37 included studies (17 contact-tracing; 18 population studies; 2 mixed studies). The pooled relative transmissibility of CYP compared with adults was 1.00 (0.73, 1.37) in adjusted household studies. The pooled SAR from 0CYP was significantly lower in school studies (0.5% (0.1, 1.6) than household studies (7.3% (2.5, 21.8) – p

Background Opioid overdose is a leading cause of death in the United States. Emergency medical services (EMS) encounters following overdose may serve as a critical linkage to care for people who use drugs (PWUD). However, many overdose survivors refuse EMS transport to hospitals, where they would presumably receive appropriate follow-up services and referrals. This study aims to (1) identify reasons for refusal of EMS transport after opioid overdose reversal; (2) identify conditions under which overdose survivors might be more likely to accept these services; and (3) describe solutions proposed by both PWUD and EMS providers to improve post-overdose care. Methods The study comprised 20 semi-structured, qualitative in-depth interviews with PWUD, followed by two semi-structured focus groups with eight EMS providers. Results PWUD cited intolerable withdrawal symptoms; anticipation of inadequate care upon arrival at the hospital; and stigmatizing treatment by EMS and hospital providers as main reasons for refusal to accept EMS transport. EMS providers corroborated these descriptions and offered solutions such as titration of naloxone to avoid harsh withdrawal symptoms; peer outreach or community paramedicine; and addressing provider burnout. PWUD stated they might accept EMS transport after overdose reversal if they were offered ease for withdrawal symptoms, at either a hospital or non-hospital facility, and treated with respect and empathy. Conclusion Standard of care by EMS and hospital providers following overdose reversal should include treatment for withdrawal symptoms, including buprenorphine induction; patient-centered communication; and effective linkage to prevention, treatment, and harm reduction services.

© 2020 World Health Organization; licensed by IAS. Introduction: As adolescents transition from childhood to adulthood, they experience major physical, social and psychological changes, and are at heightened risk for developing mental health conditions and engaging in health-related risk behaviours. For adolescents living with HIV (ALHIV), these risks may be even more pronounced. Research shows that this population may face additional mental health challenges related to the biological impact of the disease and its treatment, the psychosocial burdens of living with HIV and HIV-related social and environmental stressors. Discussion: Psychosocial interventions delivered to adolescents can promote positive mental health, prevent mental health problems and strengthen young people’s capacity to navigate challenges and protect themselves from risk. It is likely that these interventions can also benefit at-risk populations, such as ALHIV, yet there is little research on this. There is an urgent need for more research evaluating the effects of interventions designed to improve the mental health of ALHIV. We highlight four priorities moving forward. These include: generating more evidence about preventive mental health interventions for ALHIV; including mental health outcomes in research on psychosocial interventions for ALHIV; conducting intervention research that is sensitive to differences among ALHIV populations and involving adolescents in intervention design and testing. Conclusions: More robust research on promotive and preventive mental health interventions is needed for ALHIV. Programmes should be informed by adolescent priorities and preferences and responsive to the specific needs of these groups.

Background Men who have sex with men (MSM) face disproportionate risks concerning HIV and other sexually transmitted infections, substance use, and mental health. These outcomes constitute an interacting syndemic among MSM; interventions addressing all 3 together could have multiplicative effects. eHealth interventions can be accessed privately, and evidence from general populations suggests these can effectively address all 3 health outcomes. However, it is unclear how useable, accessible, or acceptable eHealth interventions are for MSM and what factors affect this. Objective We undertook a systematic review of eHealth interventions addressing sexual risk, substance use, and common mental illnesses among MSM and synthesized evidence from process evaluations. Methods We searched 19 databases, 3 trials registers, OpenGrey, and Google, and supplemented this by reference checks and requests to experts. Eligible reports were those that discussed eHealth interventions offering ongoing support to MSM aiming to prevent sexual risk, substance use, anxiety or depression; and assessed how intervention delivery or receipt varied with characteristics of interventions, providers, participants, or context. Reviewers screened citations on titles, abstracts, and then full text. Reviewers assessed quality of eligible studies, and extracted data on intervention, study characteristics, and process evaluation findings. The analysis used thematic synthesis. Results A total of 12 reports, addressing 10 studies of 8 interventions, were eligible for process synthesis. Most addressed sexual risk alone or with other outcomes. Studies were assessed as medium and high reliability (reflecting the trustworthiness of overall findings) but tended to lack depth and breadth in terms of the process issues explored. Intervention acceptability was enhanced by ease of use; privacy protection; use of diverse media; opportunities for self-reflection and to gain knowledge and skills; and content that was clear, interactive, tailored, reflective of MSM’s experiences, and affirming of sexual-minority identity. Technical issues and interventions that were too long detracted from acceptability. Some evidence suggested that acceptability varied by race or ethnicity and educational level; findings on variation by socioeconomic status were mixed. No studies explored how intervention delivery or receipt varied by provider characteristics. Conclusions Findings suggest that eHealth interventions targeting sexual risk, substance use, and mental health are acceptable for MSM across sociodemographic groups. We identified the factors shaping MSM’s receipt of such interventions, highlighting the importance of tailored content reflecting MSM’s experiences and of language affirming sexual-minority identities. Intervention developers can draw on these findings to increase the usability and acceptability of integrated eHealth interventions to address the syndemic of sexual risk, substance use, and mental ill health among MSM. Evaluators of these interventions can draw on our findings to plan evaluations that explore the factors shaping usability and acceptability.

Schools have closed worldwide as part of measures to prevent SARS-CoV-2 transmission but are beginning to reopen in some countries. Various measures are being pursued to minimise transmission but existing guidance has not developed a comprehensive framework or theory of change. We present a framework informed by the occupational health hierarchy of control and a theory of change informed by realist approaches. We present measures focused on elimination, substitution, engineering, administration, education and personal protective equipment. We theorise that such measures offer a means of disrupting SARS-CoV-2 transmission via routes involving fomites, faeco-oral routes, droplets and aerosols., Highlights • Schools have been closed worldwide as part of lock-down measures to prevent SARS-CoV-2 transmission but are beginning to reopen in a number of countries. • Various measures are being pursued to minimise transmission but existing guidance has not aimed to develop a comprehensive framework or theory of change. • We present a framework for measures informed by the occupational health hierarchy of control (elimination, substitution, engineering, administration, education and personal protective equipment) and a theory of change. • We theorise that, together, such measures offer a means of disrupting SARS-CoV-2 transmission via routes involving fomites, faeco-oral routes, droplets and aerosols.

ImportanceThe degree to which children and young people are infected by and transmit the SARS-CoV-2 virus is unclear. The role of children and young people in transmission of SARS-CoV-2 is dependent on susceptibility, symptoms, viral load, social contact patterns and behaviour.ObjectiveWe undertook a rapid systematic review to address the question “What is the susceptibility to and transmission of SARS-CoV-2 by children and adolescents compared with adults?”Data sourcesWe searched PubMed and medRxiv up to 28 July 2020 and identified 13,926 studies, with additional studies identified through handsearching of cited references and professional contacts.Study SelectionWe included studies which provided data on the prevalence of SARS-CoV-2 in children and young people (Data extraction and SynthesisWe followed PRISMA guidelines for abstracting data, independently by 2 reviewers. Quality was assessed using a critical appraisal checklist for prevalence studies. Random effects meta-analysis was undertaken.Main OutcomesSecondary infection rate (contact-tracing studies) or prevalence or seroprevalence (population-screening studies) amongst children and young people compared with adults.Results32 studies met inclusion criteria; 18 contact-tracing and 14 population-screening. The pooled odds ratio of being an infected contact in children compared with adults was 0.56 (0.37, 0.85) with substantial heterogeneity (95%). Three school contact tracing studies found minimal transmission by child or teacher index cases. Findings from population-screening studies were heterogenous and were not suitable for meta-analysis. The majority of studies were consistent with lower seroprevalence in children compared with adults, although seroprevalence in adolescents appeared similar to adults.ConclusionsThere is preliminary evidence that children and young people have lower susceptibility to SARS-CoV-2, with a 43% lower odds of being an infected contact. There is weak evidence that children and young people play a lesser role in transmission of SARS-CoV-2 at a population level. Our study provides no information on the infectivity of children.Key pointsQuestionWhat is the evidence on the susceptibility and transmission of children and young people to SARS-CoV-2 in comparison with adults?FindingsIn this systematic review and meta-analysis, children and young people under 18-20 years had an 435 lower odds of secondary infection of with SARS-CoV-2 compared to adults 20 years plus, a significant difference. This finding was most marked in children under 12-14 years. Data were insufficient to conclude whether transmission of SARS-CoV-2 by children is lower than by adults.MeaningWe found preliminary evidence that children have a lower susceptibility for SARS-CoV-2 infection compared with adults, although data for adolescents is less clear. The role that children and young people play in transmission of this pandemic remains unclear.

Background Despite recent improvements in the burden of cardiovascular disease (CVD) in the UK, deaths from CVD are relatively high compared with other high-income countries. An estimated 7 million people in the UK are living with CVD, and the healthcare cost is approximately £11 billion annually. In more than 90% of cases, the risk of a first heart attack is thought to be related to modifiable risk factors including smoking, poor diet, lipidemia, high blood pressure, inactivity, obesity and excess alcohol consumption. The aim of the study is to synthesise evidence for the comparative effectiveness and cost-effectiveness of different interventions for the primary prevention of CVD. Methods We will systematically search databases (for example, MEDLINE (Ovid), Embase (Ovid), Cochrane Library) and the reference lists of previous systematic reviews for randomised controlled trials that assess the effectiveness and cost-effectiveness of any form of intervention aimed at adult populations for the primary prevention of CVD, including but not limited to lipid lowering medications, blood pressure lowering medications, antiplatelet agents, nutritional supplements, dietary interventions, health promotion programmes, physical activity interventions or structural and policy interventions. Interventions may or may not be targeted at high-risk groups. Publications from any year will be considered for inclusion. The primary outcome will be all cause mortality. Secondary outcomes will be cardiovascular diseases related mortality, major cardiovascular events, coronary heart disease, incremental costs per quality-adjusted life years gained. If data permits, we will use network meta-analysis to compare and rank effectiveness of different interventions, and test effect modification of intervention effectiveness using subgroup analyses and meta-regression analyses. Discussion The results will be important for policymakers when making decisions between multiple possible alternative strategies to prevent CVD. Compared to results from existing multiple separate pairwise meta-analyses, this overarching synthesis of all relevant work will enhance decision-making. The findings will be crucial to inform evidence-based priorities and guidelines for policies and planning prevention strategies of CVD. Systematic review registration PROSPERO CRD42019123940.

Background: Pregnancy and parenthood are known to be high-risk times for mental health. However, less is known about the mental health of pregnant adolescents or adolescent parents. Despite the substantial literature on the risks associated with adolescent pregnancy, there is limited evidence on best practices for preventing poor mental health in this vulnerable group. This systematic review therefore aimed to identify whether psychosocial interventions can effectively promote positive mental health and prevent mental health conditions in pregnant and parenting adolescents. Methods: We used the standardized systematic review methodology based on the process outlined in the World Health Organization's Handbook for Guidelines Development. This review focused on randomized controlled trials of preventive psychosocial interventions to promote the mental health of pregnant and parenting adolescents, as compared to treatment as usual. We searched PubMed/Medline, PsycINFO, ERIC, EMBASE and ASSIA databases, as well as reference lists of relevant articles, grey literature, and consultation with experts in the field. GRADE was used to assess the quality of evidence. Results: We included 17 eligible studies (n = 3245 participants). Interventions had small to moderate, beneficial effects on positive mental health (SMD = 0.35, very low quality evidence), and moderate beneficial effects on school attendance (SMD = 0.64, high quality evidence). There was limited evidence for the effectiveness of psychosocial interventions on mental health disorders including depression and anxiety, substance use, risky sexual and reproductive health behaviors, adherence to antenatal and postnatal care, and parenting skills. There were no available data for outcomes on self-harm and suicide; aggressive, disruptive, and oppositional behaviors; or exposure to intimate partner violence. Only two studies included adolescent fathers. No studies were based in low- or middle-income countries. Conclusion: Despite the encouraging findings in terms of effects on positive mental health and school attendance outcomes, there is a critical evidence gap related to the effectiveness of psychosocial interventions for improving mental health, preventing disorders, self-harm, and other risk behaviors among pregnant and parenting adolescents. There is an urgent need to adapt and design new psychosocial interventions that can be pilot-tested and scaled with pregnant adolescents and adolescent parents and their extended networks, particularly in low-income settings.

AIMS AND OBJECTIVES: To evaluate the process of implementing an oral care intervention in nursing homes in a Danish municipality.BACKGROUND: Older people with aged natural dentition require preventive and curative oral health care. An intervention based on principles of situated learning was implemented to establish closer cooperation between dental and nursing staff in nursing homes, leading to improved oral hygiene in nursing home residents.DESIGN: An embedded multiple-case study combined with principles of realist evaluation unfolded in three phases: Formulation of initial programme theory, Testing and Refining the programme theory. The COREQ checklist is followed in reporting.METHODS: Observations, six group interviews and 22 face-to-face interviews with dentists, dental practitioners, nursing home managers, care professionals and residents were conducted in three nursing homes (n = 41).RESULTS: Three main outcomes of a programme theory were identified, relating to (a) residents, in the form of new oral care routines; (b) interdisciplinary working, in the form of professional pride in performing sufficient oral care; (c) organisational level changes, in the form of increased interdisciplinary knowledge sharing. The overarching supportive mechanisms were the creation of relationships between residents, dental practitioners and care professionals as well as nursing home management taking responsibility for structure, planning and knowledge sharing.CONCLUSION: The situated learning perspective supported residents and care professionals' competencies in performing sufficient oral care. The shared oral care intervention supports an individual and multidisciplinary assessment of nursing home residents' ability to self-care concerning oral care. Contextual factors, supportive and restraining mechanisms influence the intervention's success.RELEVANCE TO CLINICAL PRACTICE: Understanding the complexity within interdisciplinary cooperation in primary nursing and unravelling the necessary properties to enhance nursing home residents' oral health care are areas of improvement for care service in nursing homes.

Background Establishing typologies of drug use among gay and bisexual men who have sex with men (GBMSM) who are living with HIV, as well as differences in health outcomes between them, is important in addressing health inequalities within this population. We sought to determine how use of non-prescription drugs is clustered for these individuals and to establish differences in their broader health and well-being, including STI diagnosis, mental health, and physical health. Method We examined past-year drug use reported by 747 GBMSM in Australia as part of the HIV Futures 8 survey, a large cross-sectional survey of people living with HIV. We tested between two and five latent class models of specific drug use and conducted cross-class comparisons of past-year STI diagnosis and self-reported mental and physical health. Results We identified four distinct drug use typologies: ‘chemsex-related use’, ‘minimal use’, ‘analgesic and sedative use’, and ‘diverse use’. The ‘chemsex use’ and ‘diverse use’ classes had a markedly higher likelihood of STI diagnosis relative to the other two classes, while the ‘analgesic and sedative use’ class reported markedly poorer physical and mental health scores than the other classes. Conclusions While GBMSM living with HIV in Australia have higher rates of drug use compared to other GBMSM, and the general population, our analysis indicates that patterns of drug use are not uniform within this group. Specific patterns of drug use are related to distinct health inequalities, and this should be accounted for when addressing the needs of men who use drugs differently.

Background We systematically reviewed the comparative effectiveness of injectable beta-interferons (IFN-β) and glatiramer acetate (GA) on annualised relapse rate (ARR), progression and discontinuation due to adverse events (AEs) in RRMS, using evidence from within the drugs’ recommended dosages. Methods We updated prior comprehensive reviews, checked references of included studies, contacted experts in the field, and screened websites for relevant publications to locate randomised trials of IFN-β and GA with recommended dosages in RRMS populations, compared against placebo or other recommended dosages. Abstracts were screened and assessed for inclusion in duplicate and independently. Studies were appraised using the Cochrane risk of bias tool. Rate ratios for ARR, hazard ratios for time to progression, and risk ratios for discontinuation due to AEs were synthesised in separate models using random effects network meta-analysis. Results We identified 24 studies reported in 42 publications. Most studies were at high risk of bias in at least one domain. All drugs had a beneficial effect on ARR as compared to placebo, but not compared to each other, and findings were robust to sensitivity analysis. We considered time to progression confirmed at 3 months and confirmed at 6 months in separate models; while both models suggested that the included drugs were effective, findings were not consistent between models. Discontinuation due to AEs did not appear to be different between drugs. Conclusions Meta-analyses confirmed that IFN-β and GA reduce ARR and generally delay progression as defined in these trials, though there was no clear ‘winner’ across outcomes. Findings are additionally tempered by the high risk of bias across studies, and the use of an impairment/mobility scale to measure disease progression. Future research should consider more relevant measures of disability and, given that most trials have been short-term, consider a longitudinal approach to comparative effectiveness. Review registration PROSPERO CRD42016043278. Electronic supplementary material The online version of this article (10.1186/s12883-018-1162-9) contains supplementary material, which is available to authorized users.

Background. The estimated lifetime prevalence of physical or sexual intimate partner violence (IPV) is 30% among women worldwide. Understanding risk and protective factors is essential for designing effective prevention strategies. Objectives. To quantify the associations between prospective–longitudinal risk and protective factors and IPV and identify evidence gaps. Search methods. We conducted systematic searches in 16 databases including MEDLINE and PsycINFO from inception to June 2016. The study protocol is registered with PROSPERO (CRD42016039213). Selection criteria. We included published and unpublished studies available in English that prospectively analyzed any risk or protective factor(s) for self-reported IPV victimization among women and controlled for at least 1 other variable. Data collection and analysis. Three reviewers were involved in study screening. One reviewer extracted estimates of association and study characteristics from each study and 2 reviewers independently checked a random subset of extractions. We assessed study quality with the Cambridge Quality Checklists. When studies investigated the same risk or protective factor using similar measures, we computed pooled odds ratios (ORs) by using random-effects meta-analyses. We summarized heterogeneity with I2 and τ2. We synthesized all estimates of association, including those not meta-analyzed, by using harvest plots to illustrate evidence gaps and trends toward negative or positive associations. Main results. Of 18 608 studies identified, 60 were included and 35 meta-analyzed. Most studies were based in the United States. The strongest evidence for modifiable risk factors for IPV against women were unplanned pregnancy (OR = 1.66; 95% confidence interval [CI] = 1.20, 1.31) and having parents with less than a high-school education (OR = 1.55; 95% CI = 1.10, 2.17). Being older (OR = 0.96; 95% CI = 0.93, 0.98) or married (OR = 0.93; 95% CI = 0.87, 0.99) were protective. Conclusions. To our knowledge, this is the first systematic, meta-analytic review of all risk and protective factors for IPV against women without location, time, or publication restrictions. Unplanned pregnancy and having parents with less than a high-school education, which may indicate lower socioeconomic status, were shown to be risk factors, and being older or married were protective. However, no prospective–longitudinal study investigated the associations between IPV against women and any community or structural factor outside the United States, and more studies investigated risk factors related to women as opposed to their partners. Public health implications. This review highlights that prospective evidence for perpetrator- and context-related risk and protective factors for women’s experiences of IPV outside of the United States is lacking and urgently needed to inform global policy recommendations. The current evidence base of prospective studies suggests that, at least in the United States, education and sexual health interventions may be effective targets for preventing IPV against women, with young, unmarried women at greatest risk.

Background: Prevention of substance (alcohol, tobacco, illegal/legal drug) use in adolescents is a public health priority. As the scope for school ‐ based health education is constrained in school timetables, interventions integrating academic and health education have gained traction in the UK and elsewhere, though evidence for their effectiveness remains unclear. We sought to syn- thesize the effectiveness of interventions integrating academic and health education for the pre- vention of substance use. Methods: We searched 19 databases between November and December 2015, among other methods. We included randomized trials of interventions integrating academic and health educa- tion targeting school students aged 4 – 18 and reporting substance use outcomes. We excluded interventions for specific health ‐ related subpopulations (e.g., children with behavioural difficul- ties). Data were extracted independently in duplicate. Outcomes were synthesized by school key stage (KS) using multilevel meta ‐ analyses, for substance use, overall and by type. Results: We identified 7 trials reporting substance use. Interventions reduced substance use generally in years 7 – 9 (KS3) based on 5 evaluations ( d = − 0.09, 95% CI [ − 0.17, − 0.01], I 2 = 35%), as well as in years 10 – 11 (KS4) based on 3 evaluations ( − 0.06, [ − 0.09, − 0.02]; I 2 = 0%). Interventions were broadly effective for reducing specific alcohol, tobacco, and drug use in both KS groups. Conclusions: Evidence quality was highly variable. Findings for years 3 – 6 and 12 – 13 could not be meta ‐ analysed, and we could not assess publication bias. Interventions appear to have a small but significant effect reducing substance use. Specific methods of integrating academic and health education remain poorly understood.

This study aimed to identify critical features of successful lifestyle weight management interventions for overweight children (0-11years). Eleven qualitative UK-based studies examining children's, parents' and providers' perspectives and experiences of programmes were synthesised to identify components felt to be critical. Studies for this views synthesis were identified from existing reviews and an update of one review's search, which was run in December 2015. The identified components were then explored in a synthesis of intervention evaluations (five 'most effective' and 15 'least effective') conducted in western Europe, North America, Australia or New Zealand. The intervention evaluations were identified from existing reviews and an update of one review's search, which was run in March 2016. This evaluation synthesis was carried out using Qualitative Comparative Analysis. Three important mechanisms were present in all the most effective interventions but absent in all the least effective: 1/ showing families how to change: a) providing child physical activity sessions, b) delivering practical behaviour change strategy sessions, c) providing calorie intake advice; 2/ ensuring all the family are on board: a) delivering discussion/education sessions for both children and parents, b) delivering child-friendly sessions, c) aiming to change behaviours across the whole family; 3/ enabling social support for both parents and children by delivering both child group sessions and parent group sessions. To conclude, programmes should ensure the whole family is on board the programme, that parents and children can receive social support and are not just told what to change, but shown how.

Background: During the COVID-19 pandemic, it has been necessary to deliver mental health care using technologies (e-mental health). But there have been difficulties in its application. Quantitative systematic reviews such as meta-analysis doesn’t allow us to fully identify and properly describe this subject. Thus, our study has two main objectives: a) "to determine what evidence is available for synchronous e-mental health implementation"; and b) "to develop a framework informed by a realist analysis for the implementation of synchronous e-mental health".Methods: We will search MEDLINE, EBM Reviews, PsycINFO, EMBASE, SCOPUS, CINAHL Complete, and Web of Science databases from 1st January 2015 to September 2020, with no language restriction. A systematic review with a narrative description and a realist synthesis will be conducted. Primary studies relating to adults with common mental health problems using any type of mobile mental health intervention that includes a synchronic component and communication with a mental health professional will be included. For the analysis, we will make a realist synthesis of the systematic reviews, using a grounded theory approach with an emergent approach to synthesize the information, prioritizing the systematic reviews with a lower risk of bias in the AMSTAR-2 tool. The realist synthesis will be based on the interpretation, integration, and inference of the evaluated elements and the generation of hypotheses to better understand the implementation process of synchronous e-mental health. Finally, we will present the overall assessment in a Summary of Qualitative Findings table.Conclusion:Our results will allow a better understanding of the facilitator and limitations in implementing e-mental health.

BackgroundAt the time of publication of the most recent National Institute for Health and Care Excellence (NICE) guidance [technology appraisal (TA) 32] in 2002 on beta-interferon (IFN-β) and glatiramer acetate (GA) for multiple sclerosis, there was insufficient evidence of their clinical effectiveness and cost-effectiveness.ObjectivesTo undertake (1) systematic reviews of the clinical effectiveness and cost-effectiveness of IFN-β and GA in relapsing–remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) and clinically isolated syndrome (CIS) compared with best supportive care (BSC) and each other, investigating annualised relapse rate (ARR) and time to disability progression confirmed at 3 months and 6 months and (2) cost-effectiveness assessments of disease-modifying therapies (DMTs) for CIS and RRMS compared with BSC and each other.Review methodsSearches were undertaken in January and February 2016 in databases including The Cochrane Library, MEDLINE and the Science Citation Index. We limited some database searches to specific start dates based on previous, relevant systematic reviews. Two reviewers screened titles and abstracts with recourse to a third when needed. The Cochrane tool and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and Philips checklists were used for appraisal. Narrative synthesis and, when possible, random-effects meta-analysis and network meta-analysis (NMA) were performed. Cost-effectiveness analysis used published literature, findings from the Department of Health’s risk-sharing scheme (RSS) and expert opinion. A de novo economic model was built for CIS. The base case used updated RSS data, a NHS and Personal Social Services perspective, a 50-year time horizon, 2014/15 prices and a discount rate of 3.5%. Outcomes are reported as incremental cost-effectiveness ratios (ICERs). We undertook probabilistic sensitivity analysis.ResultsIn total, 6420 publications were identified, of which 63 relating to 35 randomised controlled trials (RCTs) were included. In total, 86% had a high risk of bias. There was very little difference between drugs in reducing moderate or severe relapse rates in RRMS. All were beneficial compared with BSC, giving a pooled rate ratio of 0.65 [95% confidence interval (CI) 0.56 to 0.76] for ARR and a hazard ratio of 0.70 (95% CI, 0.55 to 0.87) for time to disability progression confirmed at 3 months. NMA suggested that 20 mg of GA given subcutaneously had the highest probability of being the best at reducing ARR. Three separate cost-effectiveness searches identified > 2500 publications, with 26 included studies informing the narrative synthesis and model inputs. In the base case using a modified RSS the mean incremental cost was £31,900 for pooled DMTs compared with BSC and the mean incremental quality-adjusted life-years (QALYs) were 0.943, giving an ICER of £33,800 per QALY gained for people with RRMS. In probabilistic sensitivity analysis the ICER was £34,000 per QALY gained. In sensitivity analysis, using the assessment group inputs gave an ICER of £12,800 per QALY gained for pooled DMTs compared with BSC. Pegylated IFN-β-1 (125 µg) was the most cost-effective option of the individual DMTs compared with BSC (ICER £7000 per QALY gained); GA (20 mg) was the most cost-effective treatment for CIS (ICER £16,500 per QALY gained).LimitationsAlthough we built a de novo model for CIS that incorporated evidence from our systematic review of clinical effectiveness, our findings relied on a population diagnosed with CIS before implementation of the revised 2010 McDonald criteria.ConclusionsDMTs were clinically effective for RRMS and CIS but cost-effective only for CIS. Both RCT evidence and RSS data are at high risk of bias. Research priorities include comparative studies with longer follow-up and systematic review and meta-synthesis of qualitative studies.Study registrationThis study is registered as PROSPERO CRD42016043278.FundingThe National Institute for Health Research Health Technology Assessment programme.

Background: Adolescents with asthma face unique challenges due to hormonal changes, psychosocial development and healthcare transition. Peer-led self-management programmes may increase treatment adherence and social adjustment by addressing these challenges. The purpose of this study was to assess whether peer-led self-management programmes improve health outcomes for adolescents with asthma. Methods: Sixteen databases were searched in May 2015 for published and unpublished studies. Studies had to be randomised controlled trials (RCTs), include participants aged 10–19 years old with asthma, use a peer-led educational intervention that addressed self-management of asthma, and report a measure of health status or behaviour as an outcome. Trial quality and data extraction were based on pre-specified criteria. Results were pooled using a random-effects model with mean differences (MDs). Subgroup analysis was not possible due to limited data. Results: Of the 1,887 articles retrieved, 4 studies ( n = 1,937 participants) met the inclusion criteria. One study was excluded from meta-analysis due to unextractable data. There was a small, statistically non-significant increase in participants’ quality of life (MD = 0.70, 95% confidence interval [CI] = −0.29, 1.69, p = .16), and a small, statistically non-significant decrease in lung function (MD = −1.36, 95% CI = −9.98, 7.26, p = .76). In one RCT, interventions reduced asthma symptoms and improved self-management. Scarcity of data made meta-analysis unfeasible, and studies had unclear or high risk of bias. Discussion: There is limited evidence that peer-led self-management programmes improve quality of life or lung function for adolescents with asthma. RCTs investigating more diverse and longer term outcomes are needed.

CONTEXT: Although adolescent mental health interventions are widely implemented, little consensus exists about elements comprising successful models. OBJECTIVE: We aimed to identify effective program components of interventions to promote mental health and prevent mental disorders and risk behaviors during adolescence and to match these components across these key health outcomes to inform future multicomponent intervention development. DATA SOURCES: A total of 14 600 records were identified, and 158 studies were included. STUDY SELECTION: Studies included universally delivered psychosocial interventions administered to adolescents ages 10 to 19. We included studies published between 2000 and 2018, using PubMed, Medline, PsycINFO, Scopus, Embase, and Applied Social Sciences Index Abstracts databases. We included randomized controlled, cluster randomized controlled, factorial, and crossover trials. Outcomes included positive mental health, depressive and anxious symptomatology, violence perpetration and bullying, and alcohol and other substance use. DATA EXTRACTION: Data were extracted by 3 researchers who identified core components and relevant outcomes. Interventions were separated by modality; data were analyzed by using a robust variance estimation meta-analysis model, and we estimated a series of single-predictor meta-regression models using random effects. RESULTS: Universally delivered interventions can improve adolescent mental health and reduce risk behavior. Of 7 components with consistent signals of effectiveness, 3 had significant effects over multiple outcomes (interpersonal skills, emotional regulation, and alcohol and drug education). LIMITATIONS: Most included studies were from high-income settings, limiting the applicability of these findings to low- and middle-income countries. Our sample included only trials. CONCLUSIONS: Three program components emerged as consistently effective across different outcomes, providing a basis for developing future multioutcome intervention programs.

Background Rapid infant weight gain (RIWG) is a very strong predictor of childhood overweight and obesity (COO). Socioeconomic position (SEP) is also related to the risk of COO and parents of different SEP may differ in their reaction to accelerated infant weight gain. Together this could lead to differences in how weight gain and COO risk relate across SEP. This study aimed to analyse possible interaction of SEP and RIWG on COO risk. Methods A register-based longitudinal cohort study followed 19,894 healthy, term infants, born in Denmark between December 2011 and May 2015. Logistic regression models were used to estimate odds ratios (OR) of COO risk at 2 years (22–26 months) of age with 95% confidence intervals (95% CI) for categories of infancy weight gain based on changes in weight-for-age z-scores between 0 and 8–10 months of age (slow ( 0.67–1.34) and very rapid (> 1.34)). Possible multiplicative and additive interaction of SEP (based on household income and maternal education) on the relationship between infancy weight gain and COO were analysed. Results In total, 19.1 and 15.1% experienced rapid or very rapid weight gain, respectively, and 1497 (7.5%) children were classified with COO at follow-up. These prevalences were higher in those with lower levels of SEP. Adjusted OR for COO were 3.09 (95% CI [2.66–3.59]) and 7.58 (95% CI [6.51–8.83]) for rapid and very rapid weight gain, respectively, when household income was included in the model. Results were similar in the model including maternal education. No signs of interactions were detected on a multiplicative scale. Weak signs of additive interaction were present, but these values did not reach significance. Conclusion Both rapid and very rapid weight gain were associated with substantially higher risks of COO but these associations were not modified by SEP. This indicates that promotion of healthy weight gain should take place in all population groups irrespective of their SEP. Electronic supplementary material The online version of this article (10.1186/s12889-019-7537-z) contains supplementary material, which is available to authorized users.

Background Attention to women’s and girls’ menstrual needs is critical for global health and gender equality. The importance of this neglected experience has been elucidated by a growing body of qualitative research, which we systematically reviewed and synthesised. Methods and findings We undertook systematic searching to identify qualitative studies of women’s and girls’ experiences of menstruation in low- and middle-income countries (LMICs). Of 6,892 citations screened, 76 studies reported in 87 citations were included. Studies captured the experiences of over 6,000 participants from 35 countries. This included 45 studies from sub-Saharan Africa (with the greatest number of studies from Kenya [n = 7], Uganda [n = 6], and Ethiopia [n = 5]), 21 from South Asia (including India [n = 12] and Nepal [n = 5]), 8 from East Asia and the Pacific, 5 from Latin America and the Caribbean, 5 from the Middle East and North Africa, and 1 study from Europe and Central Asia. Through synthesis, we identified overarching themes and their relationships to develop a directional model of menstrual experience. This model maps distal and proximal antecedents of menstrual experience through to the impacts of this experience on health and well-being. The sociocultural context, including menstrual stigma and gender norms, influenced experiences by limiting knowledge about menstruation, limiting social support, and shaping internalised and externally enforced behavioural expectations. Resource limitations underlay inadequate physical infrastructure to support menstruation, as well as an economic environment restricting access to affordable menstrual materials. Menstrual experience included multiple themes: menstrual practices, perceptions of practices and environments, confidence, shame and distress, and containment of bleeding and odour. These components of experience were interlinked and contributed to negative impacts on women’s and girls’ lives. Impacts included harms to physical and psychological health as well as education and social engagement. Our review is limited by the available studies. Study quality was varied, with 18 studies rated as high, 35 medium, and 23 low trustworthiness. Sampling and analysis tended to be untrustworthy in lower-quality studies. Studies focused on the experiences of adolescent girls were most strongly represented, and we achieved early saturation for this group. Reflecting the focus of menstrual health research globally, there was an absence of studies focused on adult women and those from certain geographical areas. Conclusions Through synthesis of extant qualitative studies of menstrual experience, we highlight consistent challenges and developed an integrated model of menstrual experience. This model hypothesises directional pathways that could be tested by future studies and may serve as a framework for program and policy development by highlighting critical antecedents and pathways through which interventions could improve women’s and girls’ health and well-being. Review protocol registration The review protocol registration is PROSPERO: CRD42018089581., Julie Hennegan and colleagues reveal the experiences and challenges facing women and girls in low- and middle-income countries when menstruating., Author summary Why was this study done? A growing body of qualitative research has highlighted the importance of menstrual experiences for the health and well-being of women and girls in low- and middle-income countries (LMICs). Qualitative research has identified an array of factors contributing to experiences but has not developed clear theory to direct intervention and evaluation. What did the researchers do and find? We systematically searched and critically appraised the body of qualitative studies of menstrual experience in LMICs. We identified overarching themes and mapped the relationships between them to develop a directional model of menstrual experience. Women and girls reported impacts of negative menstrual experiences on physical and psychological health, education, employment, and social participation. Both resource limitations and the sociocultural context contribute to menstrual experience. What do these findings mean? Women’s and girls’ menstrual experiences are complex and multifaceted, but across LMICs, consistent factors contribute to experiences. Findings advance the development of problem theory in menstrual health, and the developed model can be used as a framework for developing interventions and evaluation. Future interventions should seek to address identified antecedents of menstrual experience, including knowledge, social support, restrictive behavioural expectations, and the physical and economic environment.

Importance The degree to which children and adolescents are infected by and transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. The role of children and adolescents in transmission of SARS-CoV-2 is dependent on susceptibility, symptoms, viral load, social contact patterns, and behavior. Objective To systematically review the susceptibility to and transmission of SARS-CoV-2 among children and adolescents compared with adults. Data Sources PubMed and medRxiv were searched from database inception to July 28, 2020, and a total of 13 926 studies were identified, with additional studies identified through hand searching of cited references and professional contacts. Study Selection Studies that provided data on the prevalence of SARS-CoV-2 in children and adolescents (younger than 20 years) compared with adults (20 years and older) derived from contact tracing or population screening were included. Single-household studies were excluded. Data Extraction and Synthesis PRISMA guidelines for abstracting data were followed, which was performed independently by 2 reviewers. Quality was assessed using a critical appraisal checklist for prevalence studies. Random-effects meta-analysis was undertaken. Main Outcomes and Measures Secondary infection rate (contact-tracing studies) or prevalence or seroprevalence (population screening studies) among children and adolescents compared with adults. Results A total of 32 studies comprising 41 640 children and adolescents and 268 945 adults met inclusion criteria, including 18 contact-tracing studies and 14 population screening studies. The pooled odds ratio of being an infected contact in children compared with adults was 0.56 (95% CI, 0.37-0.85), with substantial heterogeneity (I2 = 94.6%). Three school-based contact-tracing studies found minimal transmission from child or teacher index cases. Findings from population screening studies were heterogenous and were not suitable for meta-analysis. Most studies were consistent with lower seroprevalence in children compared with adults, although seroprevalence in adolescents appeared similar to adults. Conclusions and Relevance In this meta-analysis, there is preliminary evidence that children and adolescents have lower susceptibility to SARS-CoV-2, with an odds ratio of 0.56 for being an infected contact compared with adults. There is weak evidence that children and adolescents play a lesser role than adults in transmission of SARS-CoV-2 at a population level. This study provides no information on the infectivity of children.

IntroductionThe mental health and well-being of children and young people who have been in care (ie, care-experienced) are a priority. There are a range of interventions aimed at addressing these outcomes, but the international evidence-base remains ambiguous. There is a paucity of methodologically robust systematic reviews of intervention effectiveness, with few considering the contextual conditions under which evaluations were conducted. This is important in understanding the potential transferability of the evidence-base across contexts. The present systematic review will adopt a complex systems perspective to synthesise evidence reporting evaluations of mental health and well-being interventions for care-experienced children and young people. It will address impact, equity, cost-effectiveness, context, implementation and acceptability. Stakeholder consultation will prioritise a programme theory, and associated intervention, that may progress to further development and evaluation in the UK.Methods and analysisWe will search 16 bibliographic databases from 1990 to June 2020. Supplementary searching will include citation tracking, author recommendation, and identification of evidence clusters relevant to included evaluations. The eligible population is children and young people (aged ≤25 years) with experience of being in care. Outcomes are (1) mental, behavioural or neurodevelopmental disorders; (2) subjective well-being; (3) self-harm; suicidal ideation; suicide. Study quality will be appraised with methodologically appropriate tools. We will construct a taxonomy of programme theories and intervention types. Thematic synthesis will be used for qualitative data reporting context, implementation and acceptability. If appropriate, meta-analysis will be conducted with outcome and economic data. Convergent synthesis will be used to integrate syntheses of qualitative and quantitative data.Ethics and disseminationWe have a comprehensive strategy for engagement with care-experienced children and young people, carers and social care professionals. Dissemination will include academic and non-academic publications and conference presentations. Ethical approval from Cardiff University’s School of Social Sciences REC will be obtained if necessary.PROSPERO registration numberCRD42020177478.

Objectives To explore user perspectives on applying the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to systematic reviews of complex interventions. Study Design and Setting Thirty-three authors of recent (2013 onward) systematic reviews were contacted regarding their perspectives on using GRADE from three Cochrane review groups: Cochrane Developmental, Psychosocial, and Learning Problems Group; Cochrane Public Health Group; and Cochrane Depression, Anxiety, and Neurosis Group. Framework Analysis was applied to the data to identify the challenges in applying GRADE and suggestions for its extension, that is, adaptation. These two themes were cross-compared between the groups of answers from “simple” vs. “complex” intervention review authors to identify the specific perspectives on using GRADE in reviews of complex interventions. Results Specific challenges were identified in applying GRADE to reviews of complex interventions. These were related to the assessment of nonrandomized studies and performance bias in GRADE. Authors perceived these challenges to contribute to frequent downgrading of the “best evidence possible” for complex interventions. Meanwhile, GRADE was found to lack an analytic approach to enable adequate evidence synthesis and assessment of intervention implementation elements. Conclusion Users suggest that the GRADE guidance be extended to address-specific considerations for complex interventions.

Background: Posttraumatic stress (PTS) results in significant distress or functional impairment. Prevalence studies report higher rates of PTS in forcibly displaced children (FDC). Current evidence deriving mainly from cross-sectional studies is unable to make causal attributions. Given rising rates of forcible displacement reported by the United Nations High Commissioner for Refugees (UNHCR) in 2014, there is increasing need to determine the best policies and practice for engaging mental health needs of FDC. Methods: This systematic review identifies (1) longitudinal risk and protective factors and correlates for PTS and (2) its natural history in FDC, contributing to research identifying vulnerable subgroups and malleable factors for PTS and understanding its natural history. No meta-analysis was conducted due to heterogeneity; results were analyzed through narrative synthesis. Results: Eleven longitudinal studies were identified. All but one were prospective cohort designs. They identified prevalence rates between 20% and 48.7% at baseline, 10% and 48.3% at 1 year ( k = 7), 18% and 48% at 2–3 years ( k = 2), 8% and 38% at 6 years ( k = 2), and 35% at 12 years using nine measurement methods in seven independent samples. Evidence from multiple associations supported the following risk factors: exposure to traumatic stressors or other stress, older age, and prior psychopathology. Evidence predominantly supported the stability of PTS with some decline. Conclusion: While results should be interpreted with caution given small or unrepresentative samples, they suggest regular mental health screenings should be conducted for FDC, who are a vulnerable subgroup with variable onset and remission. Risk associations with prior psychopathology also suggest that screening upon arrival may be advisable for early intervention and prevention.

Background:During the COVID-19 pandemic, it has been necessary to incorporate technologies in the care of mental health problems. But there have been difficulties in the application of technology-based interventions in mental health. Some quantitative systematic reviews don’t allow us to fully identify and properly describe this subject. In order to answer the question "how do electronic interventions apply in mental health and what makes the application of any of these interventions work", this study will carry out an overview of systematic reviews, which will make it possible to develop a theoretical framework on the implementation of electronic care in mental health problems.Methods:We will search MEDLINE, EBM Reviews, PsycINFO, EMBASE, SCOPUS, CINAHL Complete, and Web of Science databases from 1st January 2015 to September 2020, with no language restriction. We will follow a qualitative method approach and include systematic reviews that assess primary studies relating to adults with common mental health problems using any type of mobile mental health intervention that includes a synchronic component and communication with a mental health professional. For the analysis, we will make a meta-synthesis of the systematic reviews, using an emergent grounded theory approach to synthesize the information, prioritizing the systematic reviews with the lowest risk of bias in the AMSTAR-2 tool. The meta-synthesis will be based on interpreting, integrating, and inferring the evaluation elements to understand better the e-health implementation process for patients with mental health problems. Finally, we will present the overall assessment in a Summary of Qualitative Findings table.Conclusion:Our results will allow a better understanding of the facilitator and limitations in implementing e-health interventions for mental health problems.

There is increasing interest in what evidence is needed to inform decisions about transporting interventions evaluated as effective to new settings. There has been less attention to how local decision-makers decide whether to implement such interventions immediately or subject to further evaluation. Using the example of school-based social and emotional learning, we consider this drawing on realist methods. We suggest decisions need to assess existing evaluations not merely in terms of whether the intervention was effective but also: how the intervention was implemented and what contextual factors affected this (drawing on process evaluation); and for whom the intervention was effective and through what mechanisms (drawing on mediation, moderation and qualitative comparative analyses from primary studies and/or systematic reviews). We contribute new insights to local needs assessments, suggesting that these should assess: the potential, capability, contribution and capacity present in the new setting for implementation; and whether similar ‘aetiological mechanisms’ underlie adverse outcomes locally as in previous evaluations. We recommend that where there is uncertainty concerning whether an intervention can feasibly be implemented this indicates the need for piloting of implementation. Where there is uncertainty concerning whether implementation of the intervention will trigger intended mechanisms, this suggests the need for a new effectiveness trial. Where there is uncertainty concerning whether intervention mechanisms, even if triggered, will generate the intended outcomes, this suggests that decision-makers may need to look to other types of intervention as being needed for their setting instead.

ObjectivesTo systematically review evidence on the effectiveness of interventions including integration of academic and health education for reducing physical aggression and violence, and describe the content of these interventions.Data sourcesBetween November and December 2015, we searched 19 databases and 32 websites and consulted key experts in the field. We updated our search in February 2018.Eligibility criteriaWe included randomised trials of school-based interventions integrating academic and health education in students aged 4–18 and not targeted at health-related subpopulations (eg, learning or developmental difficulties). We included evaluations reporting a measure of interpersonal violence or aggression.Data extraction and analysisData were extracted independently in duplicate, interventions were analysed to understand similarities and differences and outcomes were narratively synthesised by key stage (KS).ResultsWe included 13 evaluations of 10 interventions reported in 20 papers. Interventions included either full or partial integration, incorporated a variety of domains beyond the classroom, and used literature, local development or linking of study skills and health promoting skills. Evidence was concentrated in KS2, with few evaluations in KS3 or KS4, and evaluations had few consistent effects; evaluations in KS3 and KS4 did not suggest effectiveness.DiscussionIntegration of academic and health education may be a promising approach, but more evidence is needed. Future research should consider the ‘lifecourse’ aspects of these interventions; that is, do they have a longitudinal effect? Evaluations did not shed light on the value of different approaches to integration.

Background Increasingly constrained school timetables mean that there is often little space for specifically timetabled health education lessons. Interventions that integrate health education into academic lessons may prove more appealing to schools, and may be a promising means of addressing outcomes such as violence and substance use while also promoting academic attainment. This evidence has not yet been systematically reviewed. We synthesised evidence for these interventions’ effectiveness and analysed their components. Methods We searched 19 bibliographic databases and 32 websites. References were extracted from the reference lists of included studies and authors were contacted.We included reports with no restrictions on language or date. References were screened on title/abstract and those passing this screening were then screened on full report. Data extraction and appraisal were informed by the Cochrane risk of bias tool. Outcome evaluations were synthesised by key stage (KS) using multilevel meta-analysis where possible; otherwise, evidence was narratively synthesised. Components were analysed inductively. This study is registered as PROSPERO 2015:CRD42015026464. Results 78 451 unique references were identified, of which 35 (13 studies) evaluated outcomes. Quality of evidence was highly variable, and often related to whether meta-analysis was possible. The strongest evidence for the effectiveness of interventions integrating academic and health education was found in the reduction of substance use in KS2 and KS3, and a meta-analysis for the effectiveness of these interventions in reducing violence victimisation in KS2 did not find an effect. We described intervention components in terms of a) the number of domains (school, classroom, family) targeted, b) the planned duration of the intervention, c) how integration was specified (using literature, teaching study skills, supporting teachers to integrate in their own classrooms). Discussion There is under-theorisation and understanding of characteristics affecting implementation of integrated academic and health curricula as well as appreciation of how academic attainment and reduced risk-taking may be linked. However, available data suggest that multi-level interventions that aim to erode boundaries—or rather, strengthen pro-social relationships—between academic and health curricula, teachers and students, classrooms and schools and schools and families are likely to have the greatest impact on reducing risk-taking and improving academic outcomes. These programmes may be effective in reducing substance use but do not appear to reduce outcomes related to violence.

Ixazomib is an oral proteasome inhibitor used in combination with lenalidomide plus dexamethasone (IXA-LEN-DEX) and licensed for relapsed or refractory multiple myeloma. As part of a single technology appraisal (ID807) undertaken by the National Institute of Health and Care Excellence, the Evidence Review Group, Warwick Evidence was invited to independently review the evidence submitted by the manufacturer of ixazomib, Takeda UK Ltd. The main source of clinical effectiveness data about IXA-LEN-DEX came from the Tourmaline-MM1 randomized controlled trial in which 771 patients with relapsed or refractory multiple myeloma received either IXA-LEN-DEX or placebo-LEN-DEX as their second-, third-, or fourth-line treatment. Takeda estimated the cost effectiveness of IXA-LEN-DEX using a de-novo partitioned-survival model with three health states (pre-progression, post-progression, and dead). In their first submission, this model was used to estimate the cost effectiveness of IXA-LEN-DEX vs. bortezomib plus dexamethasone (BORT-DEX) in second-line treatment, and of IXA-LEN-DEX vs. LEN-DEX in third-line treatment. To estimate the relative clinical performance of IXA-LEN-DEX vs. BORT-DEX, Takeda conducted network meta-analyses for important outcomes. The network meta-analysis for overall survival was found to be flawed in several respects, but mainly because a hazard ratio input for one of the studies in the network had been inverted, resulting in a large inflation of the claimed superiority of IXA-LEN-DEX over BORT-DEX and a considerable overestimation of its cost effectiveness. In subsequent submissions, Takeda withdrew second-line treatment as an option for IXA-LEN-DEX. The manufacturer’s first submission comparing IXA-LEN-DEX with LEN-DEX for third-line therapy employed Tourmaline-MM1 data from third- and fourth-line patients as proxy for a third-line population. The appraisal committee did not consider this reasonable because randomization in Tourmaline-MM1 was stratified according to one previous treatment and two or more previous treatments. A further deficiency was considered to be the manufacturer’s use of interim survival data rather than the most mature data available. A second submission from the company focussed on IXA-LEN-DEX vs. LEN-DEX as third- or fourth-line treatment (the two or more previous lines population) and a new patient access scheme was introduced. Covariate modeling of survival outcomes was proposed using the most mature survival data. The Evidence Review Group’s main criticisms of the new evidence included: the utility associated with the pre-progression health state was overestimated, treatment costs of ixazomib were underestimated, survival models were still associated with great uncertainty, leading to clinically implausible anomalies and highly variable incremental cost-effectiveness ratio estimates, and the company had not explored a strong assumption that the survival benefit of IXA-LEN-DEX over LEN-DEX would be fully maintained for a further 22 years beyond the observed data, which encompassed only approximately 2.5 years of observation. The appraisal committee remained unconvinced that ixazomib represented a cost-effective use of National Health Service resources. Takeda’s third submission offered new base-case parametric models for survival outcomes, a new analysis of utilities, and proposed a commercial access agreement. In a brief critique of the third submission, the Evidence Review Group agreed that the selection of appropriate survival models was problematic and at the request of the National Institute for Health Care and Excellence investigated external sources of evidence regarding survival outcomes. The Evidence Review Group considered that some cost and utility estimates in the submission may have remained biased in favor of ixazomib. As a result of their third appraisal meeting, the committee judged that for the two to three prior therapies population, and at the price agreed in a commercial access agreement, ixazomib had the potential to be cost effective. It was referred to the Cancer Drugs Fund so that further data could accrue with the aim of diminishing the clinical uncertainties.

Purpose\ud \ud This systematic review with network meta-analysis compared the efficacy and safety of currently licensed second-line treatments in patients with late stage non-small cell lung cancer (NSCLC).\ud \ud Methods\ud \ud Randomised controlled trials (RCTs) of participants with advanced/metastatic NSCLC receiving second/third line treatments were screened. We searched electronic databases (MEDLINE; EMBASE; Web of Science) from January, 2000 to July, 2017.\ud \ud Two reviewers screened bibliographic records, extracted data, and assessed risk of bias of included studies. The outcomes were overall survival (OS), progression-free survival (PFS), and drug-related grade 3–5 adverse-events (AEs). We pooled study-specific hazard ratios (HR; for OS and PFS) and risk ratios (RR; for AEs) using conventional and network-meta-analyses, and ranked interventions by the surface under the cumulative ranking curve.\ud \ud Findings\ud \ud We included 11 RCTs (7,581 participants) comparing nine drugs. All drugs except for erlotinib significantly improved OS compared to docetaxel. Nivolumab was the highest ranking drug followed by atezolizumab and pembrolizumab. There was no significant difference in OS across these three drugs (HR = 0.98, 95% CI 0.79, 1.21 for nivolumab vs atezolizumab; HR = 0.98, 95% CI 0.77, 1.25 for nivolumab vs pembrolizumab). For PFS, ramucirumab + docetaxel and nivolumab were the drugs with the highest ranking. All interventions except ramucirumab + docetaxel had a reduced risk for severe drug-related AEs vs. docetaxel. Of the drugs with the highest ranking on AEs, nivolumab was significantly safer compared to atezolizumab (RR = 0.55, 95% CI 0.38, 0.79) or pembrolizumab (RR = 0.52, 95% CI 0.34, 0.81).\ud \ud Implications\ud \ud Nivolumab, pembrolizumab and atezolizumab exhibited superior benefit/risk balance compared to other licensed drugs used late stage NSCLC. Our results indicate that the use of immunotherapies in people diagnosed with non-specific late stage NSCLC should be promoted. The use of docetaxel may now be judged irrelevant as a comparator intervention for approval of new drugs for second line treatment of NSCLC.\ud \ud

Background Within increasingly constrained school timetables, interventions that integrate academic and health education to reduce substance use and violence may hold promise as a category of intervention that can positively affect both academic and health outcomes. There are no current systematic reviews exploring the effectiveness of such interventions or factors that affect their implementation. Methods A total of 19 bibliographic databases and 32 websites were searched. References were also extracted from the reference lists of included studies, and experts and authors were contacted to identify relevant studies. We included reports with no restrictions on language or date. References were screened on title/abstract and those not thus excluded were screened on full report. Data extraction and appraisal followed the Critical Appraisal Skills Programme, Evidence for Policy and Practice Information and Co-ordinating Centre and Cochrane tools. Extracted process data were qualitatively meta-synthesised for common themes. Results Seventy-eight thousand four hundred fifty-one unique references were identified, and 62 reports were included. A total of 16 reports (reporting on 15 studies of 12 interventions) evaluated process. Key facilitators of integrated academic and health curricula were supportive senior management and alignment of the intervention with school ethos; a positive teaching environment, including positive perceptions around the ability to be flexible in the adaptation and delivery of integrated academic and health curricula; positive pre-existing student and teacher attitudes towards intervention content; and parental support of interventions, largely through reinforcement of messaging at home. Important barriers were over-burdened teachers, with little time to learn and implement integrated curricula. Conclusion Several useful facilitating and inhibiting factors linked to the implementation of interventions that integrate academic and health education for reduced substance use and/or violence were identified, providing tentative but insightful evidence of context-specific issues that may impact intervention success. However, overall, there is still a considerable gap in our understanding of how to achieve the successful implementation of these interventions. Electronic supplementary material The online version of this article (10.1186/s13643-018-0886-3) contains supplementary material, which is available to authorized users.

BackgroundSince the introduction of the Teenage Pregnancy Strategy (TPS), England’s under-18 conception rate has fallen by 55%, but a continued focus on prevention is needed to maintain and accelerate progress. The teenage birth rate remains higher in the UK than comparable Western European countries. Previous trials indicate that school based social marketing interventions are a promising approach to addressing teenage pregnancy and improving sexual health. Such interventions are yet to be trialled in the UK. This study aims to optimise and establish the feasibility and acceptability of one such intervention: Positive Choices.MethodsDesign: Optimisation, feasibility testing and pilot cluster randomised trialInterventions: The Positive Choices intervention consists of: a student needs survey; a student/staff led School Health Promotion Council (SHPC); a classroom curriculum for year nine students covering social and emotional skills and sex education; student led social marketing activities; parent information; and a review of school sexual health services. Systematic optimisation of Positive Choices will be carried out with the National Children’s Bureau Sex Education Forum (NCB SEF), one state secondary school in England and other youth and policy stakeholders. Feasibility testing will involve the same state secondary school and will assess progression criteria to advance to the pilot cluster RCT.Pilot cluster RCT will involve six different state secondary schools (four intervention and two control) and will assess the feasibility and utility of progressing to a full effectiveness trial. The following outcome measures will be trialled as part of the pilot:•self-reported pregnancy and unintended pregnancy (initiation of pregnancy for boys) and sexually transmitted infections, •age of sexual debut; number of sexual partners; use of contraception at first and last sex; non-volitional sex;•educational attainmentThe feasibility of linking administrative data on births and termination to self-report survey data to measure our primary outcome (unintended teenage pregnancy) will also be tested. DiscussionThis will be the first UK based pilot trial of a school-wide social marketing intervention to reduce unintended teenage pregnancy and improve sexual health. If this study indicates feasibility and acceptability of the optimised Positive Choices intervention in English secondary schools, plans will be initiated for a phase III trial and economic evaluation of the intervention. Trial RegistrationISRCTN registry (ISCTN 12524938. Registered 03/07/2017) Keywords: teenage pregnancy; sexual health; SRE; RSE; school intervention; adolescent; cluster-randomised trial.