Study protocol for the optimisation, feasibility testing and pilot cluster randomised trial of Positive Choices: a school-based social marketing intervention to promote sexual health, prevent unintended teenage pregnancies and address health inequalities in England.

BACKGROUND: Since 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. METHODS: Design: Optimisation, feasibility testing and pilot cluster randomised trial.Interventions: The Positive Choices intervention comprises 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 with integral process evaluation will involve six different state secondary schools (four interventions and two controls) 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 and non-volitional sexEducational 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. DISCUSSION: This 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 REGISTRATION: ISRCTN registry (ISCTN12524938. Registered 03/07/2017)

Co-production of two whole-school sexual health interventions for English secondary schools: positive choices and project respect.

BACKGROUND: Whole-school interventions represent promising approaches to promoting adolescent sexual health, but they have not been rigorously trialled in the UK and it is unclear if such interventions are feasible for delivery in English secondary schools. The importance of involving intended beneficiaries, implementers and other key stakeholders in the co-production of such complex interventions prior to costly implementation and evaluation studies is widely recognised. However, practical accounts of such processes remain scarce. We report on co-production with specialist providers, students, school staff, and other practice and policy professionals of two new whole-school sexual heath interventions for implementation in English secondary schools. METHODS: Formative qualitative inquiry involving 75 students aged 13-15 and 23 school staff. A group of young people trained to advise on public health research were consulted on three occasions. Twenty-three practitioners and policy-makers shared their views at a stakeholder event. Detailed written summaries of workshops and events were prepared and key themes identified to inform the design of each intervention. RESULTS: Data confirmed acceptability of addressing unintended teenage pregnancy, sexual health and dating and relationships violence via multi-component whole-school interventions and of curriculum delivery by teachers (providing appropriate teacher selection). The need to enable flexibility for the timetabling of lessons and mode of parent communication; ensure content reflected the reality of young people's lives; and develop prescriptive teaching materials and robust school engagement strategies to reflect shrinking capacity for schools to implement public-health interventions were also highlighted and informed intervention refinements. Our research further points to some of the challenges and tensions involved in co-production where stakeholder capacity may be limited or their input may conflict with the logic of interventions or what is practicable within the constraints of a trial. CONCLUSIONS: Multi-component, whole-school approaches to addressing sexual health that involve teacher delivered curriculum may be feasible for implementation in English secondary schools. They must be adaptable to individual school settings; involve careful teacher selection; limit additional burden on staff; and accurately reflect the realities of young people's lives. Co-production can reduce research waste and may be particularly useful for developing complex interventions, like whole-school sexual health interventions, that must be adaptable to varying institutional contexts and address needs that change rapidly. When co-producing, potential limitations in relation to the representativeness of participants, the 'depth' of engagement necessary as well as the burden on participants and how they will be recompensed must be carefully considered. Having well-defined, transparent procedures for incorporating stakeholder input from the outset are also essential. Formal feasibility testing of both co-produced interventions in English secondary schools via cluster RCT is warranted. TRIAL REGISTRATION: Project Respect: ISRCTN12524938 . Positive Choices: ISRCTN65324176

An Association of Cancer Physicians' strategy for improving services and outcomes for cancer patients.

The Association of Cancer Physicians in the United Kingdom has developed a strategy to improve outcomes for cancer patients and identified the goals and commitments of the Association and its members.The ACP is very grateful to all of its members who have expressed views on the development of the strategy and to the sponsors of our workshops and publications, especially Cancer Research UK and Macmillan Cancer SupportThis is the final version of the article. It was first available from Cancer Intelligence via http://dx.doi.org/10.3332/ecancer.2016.60

The Use of Herbal Medications and Dietary Supplements by People with Mental Illness

This study examined the relationship between herbal medication and dietary supplement (HMDS) use and mental health characteristics. Data are drawn from a national household survey of the United States’ civilian, non-institutionalized population (N = 9,585). Psychiatric medication and HMDS use, psychiatric diagnoses and treatment needs, utilization and satisfaction were assessed. Compared to non-users, HMDS users were more likely to perceive themselves as having mental health needs, to have received mental health and primary care treatment, and to be dissatisfied with their overall healthcare. Psychiatric medication use was not related to HMDS use, and in multivariate analyses, HMDS use was associated with perceived mental health needs. Differences in use of specific HMDS between those with and without a psychiatric disorder were also examined. The use of HMDS warrants particular attention in persons with perceived mental health problems as these individuals may be turning to HMDS use for treatment of their symptoms

A school-based social-marketing intervention to promote sexual health in English secondary schools: the Positive Choices pilot cluster RCT

Background The UK still has the highest rate of teenage births in western Europe. Teenagers are also the age group most likely to experience unplanned pregnancy, with around half of conceptions in those aged &lt; 18 years ending in abortion. After controlling for prior disadvantage, teenage parenthood is associated with adverse medical and social outcomes for mothers and children, and increases health inequalities. This study evaluates Positive Choices (a new intervention for secondary schools in England) and study methods to assess the value of a Phase III trial. Objectives To optimise and feasibility-test Positive Choices and then conduct a pilot trial in the south of England assessing whether or not progression to Phase III would be justified in terms of prespecified criteria. Design Intervention optimisation and feasibility testing; pilot randomised controlled trial. Setting The south of England: optimisation and feasibility-testing in one secondary school; pilot cluster trial in six other secondary schools (four intervention, two control) varying by local deprivation and educational attainment. Participants School students in year 8 at baseline, and school staff. Interventions Schools were randomised (1 : 2) to control or intervention. The intervention comprised staff training, needs survey, school health promotion council, year 9 curriculum, student-led social marketing, parent information and review of school/local sexual health services. Main outcome measures The prespecified criteria for progression to Phase III concerned intervention fidelity of delivery and acceptability; successful randomisation and school retention; survey response rates; and feasible linkage to routine administrative data on pregnancies. The primary health outcome of births was assessed using routine data on births and abortions, and various self-reported secondary sexual health outcomes. Data sources The data sources were routine data on births and abortions, baseline and follow-up student surveys, interviews, audio-recordings, observations and logbooks. Results The intervention was optimised and feasible in the first secondary school, meeting the fidelity targets other than those for curriculum delivery and criteria for progress to the pilot trial. In the pilot trial, randomisation and school retention were successful. Student response rates in the intervention group and control group were 868 (89.4%) and 298 (84.2%), respectively, at baseline, and 863 (89.0%) and 296 (82.0%), respectively, at follow-up. The target of achieving ≥ 70% fidelity of implementation of essential elements in three schools was achieved. Coverage of relationships and sex education topics was much higher in intervention schools than in control schools. The intervention was acceptable to 80% of students. Interviews with staff indicated strong acceptability. Data linkage was feasible, but there were no exact matches for births or abortions in our cohort. Measures performed well. Poor test–retest reliability on some sexual behaviour measures reflected that this was a cohort of developing adolescents. Qualitative research confirmed the appropriateness of the intervention and theory of change, but suggested some refinements. Limitations The optimisation school underwent repeated changes in leadership, which undermined its participation. Moderator analyses were not conducted as these would be very underpowered. Conclusion Our findings suggest that this intervention has met prespecified criteria for progression to a Phase III trial. Future work Declining prevalence of teenage pregnancy suggests that the primary outcome in a full trial could be replaced by a more comprehensive measure of sexual health. Any future Phase III trial should have a longer lead-in from randomisation to intervention commencement. Trial registration Current Controlled Trials ISRCTN12524938. Funding This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 9, No. 1. See the NIHR Journals Library website for further project information. </jats:sec

Proteomic Biomarkers for the Prediction of Transition to Psychosis in Individuals at Clinical High Risk: A Multi-cohort Model Development Study

Psychosis risk prediction is one of the leading challenges in psychiatry. Previous investigations have suggested that plasma proteomic data may be useful in accurately predicting transition to psychosis in individuals at clinical high risk (CHR). We hypothesized that an a priori-specified proteomic prediction model would have strong predictive accuracy for psychosis risk and aimed to replicate longitudinal associations between plasma proteins and transition to psychosis. This study used plasma samples from participants in 3 CHR cohorts: the North American Prodrome Longitudinal Studies 2 and 3, and the NEURAPRO randomized control trial (total n = 754). Plasma proteomic data were quantified using mass spectrometry. The primary outcome was transition to psychosis over the study follow-up period. Logistic regression models were internally validated, and optimism-corrected performance metrics derived with a bootstrap procedure. In the overall sample of CHR participants (age: 18.5, SD: 3.9; 51.9% male), 20.4% (n = 154) developed psychosis within 4.4 years. The a priori-specified model showed poor risk-prediction accuracy for the development of psychosis (C-statistic: 0.51 [95% CI: 0.50, 0.59], calibration slope: 0.45). At a group level, Complement C8B, C4B, C5, and leucine-rich α-2 glycoprotein 1 (LRG1) were associated with transition to psychosis but did not surpass correction for multiple comparisons. This study did not confirm the findings from a previous proteomic prediction model of transition from CHR to psychosis. Certain complement proteins may be weakly associated with transition at a group level. Previous findings, derived from small samples, should be interpreted with caution

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Effect of a Perioperative, Cardiac Output-Guided Hemodynamic Therapy Algorithm on Outcomes Following Major Gastrointestinal Surgery A Randomized Clinical Trial and Systematic Review

Importance: small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm.Objective: to evaluate the clinical effectiveness of a perioperative, cardiac output–guided hemodynamic therapy algorithm.Design, setting, and participants: OPTIMISE was a pragmatic, multicenter, randomized, observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom. An updated systematic review and meta-analysis were also conducted including randomized trials published from 1966 to February 2014.Interventions: patients were randomly assigned to a cardiac output–guided hemodynamic therapy algorithm for intravenous fluid and inotrope (dopexamine) infusion during and 6 hours following surgery (n=368) or to usual care (n=366).Main outcomes and measures: the primary outcome was a composite of predefined 30-day moderate or major complications and mortality. Secondary outcomes were morbidity on day 7; infection, critical care–free days, and all-cause mortality at 30 days; all-cause mortality at 180 days; and length of hospital stay.Results: baseline patient characteristics, clinical care, and volumes of intravenous fluid were similar between groups. Care was nonadherent to the allocated treatment for less than 10% of patients in each group. The primary outcome occurred in 36.6% of intervention and 43.4% of usual care participants (relative risk [RR], 0.84 [95% CI, 0.71-1.01]; absolute risk reduction, 6.8% [95% CI, ?0.3% to 13.9%]; P?=?.07). There was no significant difference between groups for any secondary outcomes. Five intervention patients (1.4%) experienced cardiovascular serious adverse events within 24 hours compared with none in the usual care group. Findings of the meta-analysis of 38 trials, including data from this study, suggest that the intervention is associated with fewer complications (intervention, 488/1548 [31.5%] vs control, 614/1476 [41.6%]; RR, 0.77 [95% CI, 0.71-0.83]) and a nonsignificant reduction in hospital, 28-day, or 30-day mortality (intervention, 159/3215 deaths [4.9%] vs control, 206/3160 deaths [6.5%]; RR, 0.82 [95% CI, 0.67-1.01]) and mortality at longest follow-up (intervention, 267/3215 deaths [8.3%] vs control, 327/3160 deaths [10.3%]; RR, 0.86 [95% CI, 0.74-1.00]).Conclusions and relevance: in a randomized trial of high-risk patients undergoing major gastrointestinal surgery, use of a cardiac output–guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and 30-day mortality. However, inclusion of these data in an updated meta-analysis indicates that the intervention was associated with a reduction in complication rate

Functional antibody and T-cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study (NCT03226886) integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2-positive, 94 were symptomatic and 2 patients died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies, 82% had neutralizing antibodies against WT, whereas neutralizing antibody titers (NAbT) against the Alpha, Beta, and Delta variants were substantially reduced. Whereas S1-reactive antibody levels decreased in 13% of patients, NAbT remained stable up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment-specific, but presented compensatory cellular responses, further supported by clinical. Overall, these findings advance the understanding of the nature and duration of immune response to SARS-CoV-2 in patients with cancer