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BackgroundTo determine the incidence of acute retinal necrosis (ARN) in the United Kingdom and to describe the demographics, management, and visual outcome in these patients.MethodsThis was a prospective study carried out by the British Ophthalmological Surveillance Unit (BOSU) between September 2007 and October 2008. Initial and 6-month questionnaires were sent to UK ophthalmologists who reported cases of ARN via the monthly BOSU report card system.ResultsIn all, 45 confirmed cases (52 eyes) of ARN were reported in the 14-month study period, giving a minimum incidence of 0.63 cases per million population per year. There were 20 females and 25 males. Age ranged from 10 to 94 years. Eight patients had a history of herpetic CNS disease. Aqueous sampling was carried out in 13 patients, vitreous in 27, and cerebrospinal fluid (CSF) in 4. Varicella-zoster virus followed by herpes simplex were the most common causative agents. Treatment in 76% of the cases was with intravenous antivirals; however, 24% received only oral antivirals. In all, 47% of patients had intravitreal antiviral therapy. Visual outcome at 6 months was <6/60 in 48% of the affected eyes.ConclusionThe minimum incidence of ARN in the UK is 0.63 cases per million. Patients with a history of herpetic CNS disease should be warned to immediately report any visual symptoms. There is increased use of oral and intravitreal antivirals in initial treatment. [ABSTRACT FROM AUTHOR]

Pre-clinical toxicology studies in rodents and Phase I clinical trial data are summarised for 14 novel anticancer therapies. With only one exception, an antifolate antimetabolite, rodent toxicology predicted a safe Phase I trial starting dose and the majority of the dose limiting toxicities, in particular haematological toxicity. For targeted agents with well-defined pharmacodynamic markers, illustrated in the current study by 3 anti-endocrine drugs and one resistance modifier, the definition of a maximum tolerated dose can be avoided. Together with earlier data, the current study confirms that pre-clinical toxicology studies in a non-rodent species are not routinely needed for the safe conduct of early clinical trials with new cancer chemotherapies. [Copyright &y& Elsevier]

Introduction: The reproductive years can increase women's weight-related risk. Evidence for effective postpartum weight management interventions is lacking and engaging women during this life stage is challenging. Following a promising pilot evaluation of the Supporting MumS intervention, we assess if theory-based and bidirectional text messages to support diet and physical activity behaviour change for weight loss and weight loss maintenance, are effective and cost-effective for weight change in postpartum women with overweight or obesity, compared with an active control arm receiving text messages on child health and development., Methods and Analysis: Two-arm, parallel-group, assessor-blind randomised controlled trial with cost-effectiveness and process evaluations. Women (n=888) with body mass index (BMI) ≥25 kg/m 2 and within 24 months of giving birth were recruited via community and National Health Service pathways through five UK sites targeting areas of ethnic and socioeconomic diversity. Women were 1:1 randomised to the intervention or active control groups, each receiving automated text messages for 12 months. Data are collected at 0, 6, 12 and 24 months. The primary outcome is weight change at 12 months from baseline, compared between groups. Secondary outcomes include weight change (24 months) and waist circumference (cm), proportional weight gain (>5 kg), BMI (kg/m 2 ), dietary intake, physical activity, infant feeding and mental health (6, 12 and 24 months, respectively). Economic evaluation examines health service usage and personal expenditure, health-related quality of life and capability well-being to assess cost-effectiveness over the trial and modelled lifetime. Cost-utility analysis examines cost per quality-adjusted life-years gained over 24 months. Mixed-method process evaluation explores participants' experiences and contextual factors impacting outcomes and implementation. Stakeholder interviews examine scale-up and implementation., Ethics and Dissemination: Ethical approval was obtained before data collection (West of Scotland Research Ethics Service Research Ethics Committee (REC) 4 22/WS/0003). Results will be published via a range of outputs and audiences., Trial Registration Number: ISRCTN16299220., Competing Interests: Competing interests: EMcI was a member of the NIHR PHR funding board 2017-2021 but was excluded from the decision-making process for present trial funding. CF was a member of the NIHR HTA funding board 2018-2022. JVW is a trustee of the Nutrition Society for which she does not receive payment. PH is a co-investigator on other NIHR funded trials (NIHR 129703 and NIHR 129182), and is a current or past member of several advisory groups (member of the Scottish Government Peer Support Advisory Group for infant feeding and Chair of the Trial Steering Committees for other NIHR funded projects (RP-PG-1211-20015; NIHR 300895 Fellowship Award; NIHR HSDR 130995; NIHR PHR127793; and, NIHR HTA16/143/01) for which she does not receive payment other than reimbursement of travel expenses for face-to-face meetings., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

The World Health Organisation advocates a direct focus on adolescent men in reducing adolescent pregnancy; however, no trials have been conducted. This trial (ISRCTN11632300; NCT02092480) determines whether a novel Relationship and Sexuality Educational intervention, If I Were Jack, is acceptable and feasible to implement in mixed sex UK classrooms. The intervention is a teacher-delivered intervention that emphasises male alongside female  responsibility in preventing unintended pregnancies and is designed to prevent unprotected sex. The trial was a parallel-group cluster randomised controlled feasibility trial with embedded process and cost evaluation in eight secondary schools (unit of randomisation) among 831 pupils (mean age 14) in Northern Ireland, alongside a qualitative evaluation of transferability in ten schools in Scotland, Wales and England. The sampling strategy was a maximum variation quota sample designed to capture a range of school management types. Four schools were randomised to each arm and the control arm continued with usual practice. Study duration was 12 months (from November 2014), with follow-up 9 months post-baseline. Results demonstrated that the intervention was acceptable to schools, pupils and teachers, and could be feasibly implemented, cost-effectively, with minor enhancements. The between-group difference in incidence of unprotected sex (primary outcome at pupil level) of 1.3% (95% CI 0.5-2.2) by 9 months demonstrated a potential effect size consistent with those reported to have had meaningful impact on teenage pregnancy. The study responds to global health policy for a paradigm shift towards inclusion of men in the achievement of sexual and reproductive health goals in a practical way by demonstrating that a gender-sensitive as well as a gender transformative intervention targeting males to prevent teenage pregnancy is acceptable to adolescent men and women and implementable in formal education structures. If I Were Jack now merits further effectiveness testing.

Introduction: Teenage pregnancy remains a worldwide health concern which is an outcome of, and contributor to, health inequalities. The need for gender-aware interventions with a focus on males in addressing teenage pregnancy has been highlighted as a global health need by WHO and identified in systematic reviews of (relationship and sexuality education (RSE)). This study aims to test the effectiveness of an interactive film-based RSE intervention, which draws explicit attention to the role of males in preventing an unintended pregnancy by reducing unprotected heterosexual teenage sex among males and females under age 16 years., Methods and Analysis: A phase III cluster randomised trial with embedded process and economic evaluations. If I Were Jack encompasses a culturally sensitive interactive film, classroom materials, a teacher-trainer session and parent animations and will be delivered to replace some of the usual RSE for the target age group in schools in the intervention group. Schools in the control group will not receive the intervention and will continue with usual RSE. Participants will not be blinded to allocation. Schools are the unit of randomisation stratified per country and socioeconomic status. We aim to recruit 66 UK schools (24 in Northern Ireland; 14 in each of England, Scotland and Wales), including approximately 7900 pupils. A questionnaire will be administered at baseline and at 12-14 months postintervention. The primary outcome is reported unprotected sex, a surrogate measure associated with unintended teenage pregnancy. Secondary outcomes include knowledge, attitudes, skills and intentions relating to avoiding teenage pregnancy in addition to frequency of engagement in sexual intercourse, contraception use and diagnosis of sexually transmitted infections., Ethics and Dissemination: Ethical approval was obtained from Queen's University Belfast. Results will be published in peer-reviewed journals and disseminated to stakeholders. Funding is from the National Institute for Health Research., Trial Registration Number: ISRCTN99459996., Competing Interests: Competing interests: QUB holds copyright and the researchers do not benefit financially from its evaluation or use., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.)

Background: Urothelial bladder cancer (UBC) accounts for 10,000 new diagnoses and 5000 deaths annually in the UK (Cancer Research UK, http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bladder-cancer , Cancer Research UK, Accessed 26 Mar 2018). Cisplatin-based chemotherapy is standard of care therapy for UBC for both palliative first-line treatment of advanced/metastatic disease and radical neoadjuvant treatment of localised muscle invasive bladder cancer. However, cisplatin resistance remains a critical cause of treatment failure and a barrier to therapeutic advance in UBC. Based on supportive pre-clinical data, we hypothesised that DNA methyltransferase inhibition would circumvent cisplatin resistance in UBC and potentially other cancers., Methods: The addition of SGI-110 (guadecitabine, a DNA methyltransferase inhibitor) to conventional doublet therapy of gemcitabine and cisplatin (GC) is being tested within the phase Ib/IIa SPIRE clinical trial. SPIRE incorporates an initial, modified rolling six-dose escalation phase Ib design of up to 36 patients with advanced solid tumours followed by a 20-patient open-label randomised controlled dose expansion phase IIa component as neoadjuvant treatment for UBC. Patients are being recruited from UK secondary care sites. The dose escalation phase will determine a recommended phase II dose (RP2D, primary endpoint) of SGI-110, by subcutaneous injection, on days 1-5 for combination with GC at conventional doses (cisplatin 70 mg/m 2 , IV infusion, day 8; gemcitabine 1000 mg/m 2 , IV infusion, days 8 and 15) in every 21-day cycle. In the dose expansion phase, patients will be randomised 1:1 to GC with or without SGI-110 at the proposed RP2D. Secondary endpoints will include toxicity profiles, SGI-110 pharmacokinetics and pharmacodynamic biomarkers, and pathological complete response rates in the dose expansion phase. Analyses will not be powered for formal statistical comparisons and descriptive statistics will be used to describe rates of toxicity, efficacy and translational endpoints by treatment arm., Discussion: SPIRE will provide evidence for whether SGI-110 in combination with GC chemotherapy is safe and biologically effective prior to future phase II/III trials as a neoadjuvant therapy for UBC and potentially in other cancers treated with GC., Trial Registration: EudraCT Number: 2015-004062-29 (entered Dec 7, 2015) ISRCTN registry number: 16332228 (registered on Feb 3, 2016).