Enabling women to access preferred methods of contraception: a rapid review and behavioural analysis.

BACKGROUND: Many pregnancies in the UK are either unplanned or ambivalent. This review aimed to (i) explore barriers and facilitators to women choosing and accessing a preferred method of contraception in the United Kingdom, and (ii) identify opportunities for behavioural interventions based on examination of interventions that are currently available nationally. METHODS: Three databases were searched, and experts contacted to identify grey literature for studies presenting barriers and facilitators to women choosing and accessing a preferred method of contraception, conducted in the UK and published between 2009 and October 2019. Information on barriers and facilitators were coded into overarching themes, which were then coded into Mechanisms of Actions (MoAs) as listed in the Theory and Techniques Tool. National interventions were identified by consulting stakeholders and coded into the Behaviour Change Wheel. The match between barriers/facilitators and intervention content was assessed using the Behaviour Change Wheel. RESULTS: We included 32 studies and identified 46 barrier and facilitator themes. The most cited MoA was Environmental Context and Resources, which primarily related to the services women had access to and care they received. Social Influences, Beliefs about Consequences (e.g., side effects) and Knowledge were also key. The behavioural analysis highlighted four priority intervention functions (Modelling, Enablement, Education and Environmental Restructuring) that can be targeted to support women to choose and access their preferred method of contraception. Relevant policy categories and behaviour change techniques are also highlighted. CONCLUSIONS: This review highlights factors that influence women's choices and access to contraception and recommends opportunities that may be targeted for future interventions in order to support women to access preferred contraception. REGISTRATION: Protocol was registered with PROSPERO (an international database of prospectively registered systematic reviews in health and social care) in December 2019, CRD42019161156 .

Therapeutic options for mucinous ovarian carcinoma.

OBJECTIVE: Mucinous ovarian carcinoma (MOC) is an uncommon ovarian cancer histotype that responds poorly to conventional chemotherapy regimens. Although long overall survival outcomes can occur with early detection and optimal surgical resection, recurrent and advanced disease are associated with extremely poor survival. There are no current guidelines specifically for the systemic management of recurrent MOC. We analyzed data from a large cohort of women with MOC to evaluate the potential for clinical utility from a range of systemic agents. METHODS: We analyzed gene copy number (n = 191) and DNA sequencing data (n = 184) from primary MOC to evaluate signatures of mismatch repair deficiency and homologous recombination deficiency, and other genetic events. Immunohistochemistry data were collated for ER, CK7, CK20, CDX2, HER2, PAX8 and p16 (n = 117-166). RESULTS: Molecular aberrations noted in MOC that suggest a match with current targeted therapies include amplification of ERBB2 (26.7%) and BRAF mutation (9%). Observed genetic events that suggest potential efficacy for agents currently in clinical trials include: KRAS/NRAS mutations (66%), TP53 missense mutation (49%), RNF43 mutation (11%), ARID1A mutation (10%), and PIK3CA/PTEN mutation (9%). Therapies exploiting homologous recombination deficiency (HRD) may not be effective in MOC, as only 1/191 had a high HRD score. Mismatch repair deficiency was similarly rare (1/184). CONCLUSIONS: Although genetically diverse, MOC has several potential therapeutic targets. Importantly, the lack of response to platinum-based therapy observed clinically corresponds to the lack of a genomic signature associated with HRD, and MOC are thus also unlikely to respond to PARP inhibition.

Paragon (ANZGOG-0903): Phase 2 Study of Anastrozole in Women With Estrogen or Progesterone Receptor-Positive Platinum-Resistant or -Refractory Recurrent Ovarian Cancer.

BACKGROUND: There is some evidence that a subset of patients with recurrent ovarian cancer may benefit from antiestrogen therapy. The Paragon study is a basket protocol that includes a series of phase 2 trials investigating the activity of anastrozole in patients with estrogen or progesterone receptor-positive recurrent gynecological cancers. We report the results of treatment in patients with platinum-resistant or -refractory recurrent epithelial ovarian cancer. METHODS: Postmenopausal women who had estrogen and/or progesterone receptor-positive platinum-resistant or platinum-refractory recurrent ovarian cancer and disease measurable by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or GCIG (Gynecologic Cancer InterGroup) CA-125 criteria were eligible. Patients received anastrozole 1 mg daily until progression or unacceptable toxicity. The study was prospectively registered (ACTRN12610000796088). RESULTS: There were 49 evaluable patients, and clinical benefit was observed in 13 (27%; 95% confidence interval [CI], 16%-40%). There were no complete or partial RECIST version 1.1 responses. Clinical benefit was associated with higher global quality-of-life scores. Median progression-free survival was 2.7 months (95% CI, 2.0-2.8 months). The median duration of clinical benefit was 2.8 months (95% CI, 2.6-5.7 months). Most patients (83%) progressed within 6 months. Seven patients continued on treatment for longer than 6 months. Anastrozole was well tolerated in most patients. Subgroup analysis suggested greater clinical benefit in patients with tumors with estrogen-receptor histoscore of more than 200, but this difference was not statistically significant. CONCLUSIONS: A subset of patients with estrogen- or progesterone-positive platinum-resistant or platinum-refractory recurrent epithelial ovarian cancers derives clinical benefit from anastrozole, with acceptable toxicity. The challenge remains how to identify them.

Implementing the United Kingdom's ten-year teenage pregnancy strategy for England (1999-2010): How was this done and what did it achieve?

BACKGROUND: In 1999, the UK Labour Government launched a 10-year Teenage Pregnancy Strategy for England to address the country's historically high rates and reduce social exclusion. The goal was to halve the under-18 conception rate. This study explores how the strategy was designed and implemented, and the features that contributed to its success. METHODS: This study was informed by examination of the detailed documentation of the strategy, published throughout its 10-year implementation. RESULTS: The strategy involved a comprehensive programme of action across four themes: joined up action at national and local level; better prevention through improved sex and relationships education and access to effective contraception; a communications campaign to reach young people and parents; and coordinated support for young parents (The support programme for young parents was an important contribution to the strategy. In the short term by helping young parents prevent further unplanned pregnancies and, in the long term, by breaking intergenerational cycles of disadvantage and lowering the risk of teenage pregnancy.). It was implemented through national, regional and local structures with dedicated funding for the 10-year duration. The under-18 conception rate reduced steadily over the strategy's lifespan. The 2014 under-18 conception rate was 51% lower than the 1998 baseline and there have been significant reductions in areas of high deprivation. One leading social commentator described the strategy as 'The success story of our time' (Toynbee, The drop in teenage pregnancies is the success story of our time, 2013). CONCLUSIONS: As rates of teenage pregnancy are influenced by a web of inter-connected factors, the strategy was necessarily multi-faceted in its approach. As such, it is not possible to identify causative pathways or estimate the relative contributions of each constituent part. However, we conclude that six key features contributed to the success: creating an opportunity for action; developing an evidence based strategy; effective implementation; regularly reviewing progress; embedding the strategy in wider government programmes; and providing leadership throughout the programme. The learning remains relevant for the UK as England's teenage birth rate remains higher than in other Western European countries. It also provides important lessons for governments and policy makers in other countries seeking to reduce teenage pregnancy rates.

Teenage pregnancy and sexual health.

The under-18 conception rate in England is at a 40-year low but a further reduction is needed to reach levels in comparable western European countries. Sexually transmitted infections are common among young people, with chlamydia the most prevalent STI in the UK. To challenge this, a multi-agency approach is needed, with high-quality sex and relationships education, easy access to contraception and sexual health services and an open culture around relationships and sexual health. Nurses play a crucial role in supporting young people within both contraception and sexual health services and as trusted practitioners in a range of settings.

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.

What and how: doing good research with young people, digital intimacies, and relationships and sex education.

As part of a project funded by the Wellcome Trust, we held a one-day symposium, bringing together researchers, practitioners, and policymakers, to discuss priorities for research on relationships and sex education (RSE) in a world where young people increasingly live, experience, and augment their relationships (whether sexual or not) within digital spaces. The introduction of statutory RSE in schools in England highlights the need to focus on improving understandings of young people and digital intimacies for its own sake, and to inform the development of learning resources. We call for more research that puts young people at its centre; foregrounds inclusivity; and allows a nuanced discussion of pleasures, harms, risks, and rewards, which can be used by those working with young people and those developing policy. Generating such research is likely to be facilitated by participation, collaboration, and communication with beneficiaries, between disciplines and across sectors. Taking such an approach, academic researchers, practitioners, and policymakers agree that we need a better understanding of RSE's place in lifelong learning, which seeks to understand the needs of particular groups, is concerned with non-sexual relationships, and does not see digital intimacies as disconnected from offline everyday 'reality'.

When is a GIST not a GIST? A case report of synchronous metastatic gastrointestinal stromal tumor and fibromatosis.

BACKGROUND: A number of non-malignant diseases that share similar morphological features as gastrointestinal stromal tumor (GIST) have been reported. Co-existence of GIST with these other diseases is rarely recognized or reported. CASE PRESENTATION: We report a case of a 62 year-old man with long-term stable control of metastatic GIST with systemic therapy, presented with an apparent intra-abdominal progression but not supported by imaging with positron emission tomography. Subsequent resection of the intra-abdominal tumor identified a non-malignant fibroid. CONCLUSION: Differentiating localized progression of GIST from other diseases has important prognostic and therapeutic implications. The potential for co-existence of non-malignant soft tissue neoplasm should always be considered.

The molecular origin and taxonomy of mucinous ovarian carcinoma.

Mucinous ovarian carcinoma (MOC) is a unique subtype of ovarian cancer with an uncertain etiology, including whether it genuinely arises at the ovary or is metastatic disease from other organs. In addition, the molecular drivers of invasive progression, high-grade and metastatic disease are poorly defined. We perform genetic analysis of MOC across all histological grades, including benign and borderline mucinous ovarian tumors, and compare these to tumors from other potential extra-ovarian sites of origin. Here we show that MOC is distinct from tumors from other sites and supports a progressive model of evolution from borderline precursors to high-grade invasive MOC. Key drivers of progression identified are TP53 mutation and copy number aberrations, including a notable amplicon on 9p13. High copy number aberration burden is associated with worse prognosis in MOC. Our data conclusively demonstrate that MOC arise from benign and borderline precursors at the ovary and are not extra-ovarian metastases.

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).

Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma.

Accurately identifying patients with high-grade serous ovarian carcinoma (HGSOC) who respond to poly(ADP-ribose) polymerase inhibitor (PARPi) therapy is of great clinical importance. Here we show that quantitative BRCA1 methylation analysis provides new insight into PARPi response in preclinical models and ovarian cancer patients. The response of 12 HGSOC patient-derived xenografts (PDX) to the PARPi rucaparib was assessed, with variable dose-dependent responses observed in chemo-naive BRCA1/2-mutated PDX, and no responses in PDX lacking DNA repair pathway defects. Among BRCA1-methylated PDX, silencing of all BRCA1 copies predicts rucaparib response, whilst heterozygous methylation is associated with resistance. Analysis of 21 BRCA1-methylated platinum-sensitive recurrent HGSOC (ARIEL2 Part 1 trial) confirmed that homozygous or hemizygous BRCA1 methylation predicts rucaparib clinical response, and that methylation loss can occur after exposure to chemotherapy. Accordingly, quantitative BRCA1 methylation analysis in a pre-treatment biopsy could allow identification of patients most likely to benefit, and facilitate tailoring of PARPi therapy.

The need to improve fertility awareness.

Women and men globally are delaying the birth of their first child. In the UK, the average age of first conception in women is 29 years. Women experience age-related fertility decline so it is important that men and women are well-informed about this, and other aspects of fertility. A group of UK stakeholders have established the Fertility Education Initiative to develop tools and information for children, adults, teachers, parents and healthcare professionals dedicated to improving knowledge of fertility and reproductive health.

Implementing the United Kingdom Government's 10-Year Teenage Pregnancy Strategy for England (1999-2010): Applicable Lessons for Other Countries.

PURPOSE: Teenage pregnancy is an issue of inequality affecting the health, well-being, and life chances of young women, young men, and their children. Consequently, high levels of teenage pregnancy are of concern to an increasing number of developing and developed countries. The UK Labour Government's Teenage Pregnancy Strategy for England was one of the very few examples of a nationally led, locally implemented evidence-based strategy, resourced over a long duration, with an associated reduction of 51% in the under-18 conception rate. This article seeks to identify the lessons applicable to other countries. METHODS: The article focuses on the prevention program. Drawing on the detailed documentation of the 10-year strategy, it analyzes the factors that helped and hindered implementation against the World Health Organization (WHO) ExpandNet Framework. The Framework strives to improve the planning and management of the process of scaling-up of successful pilot programs with a focus on sexual and reproductive health, making it particularly suited for an analysis of England's teenage pregnancy strategy. RESULTS: The development and implementation of the strategy matches the Framework's key attributes for successful planning and scaling up of sexual and reproductive health programs. It also matched the attributes identified by the Centre for Global Development for scaled up approaches to complex public health issues. CONCLUSIONS: Although the strategy was implemented in a high-income country, analysis against the WHO-ExpandNet Framework identifies many lessons which are transferable to low- and medium-income countries seeking to address high teenage pregnancy rates.