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Introduction Children with moderate or severe wasting are at particularly high risk of recurrent or persistent diarrhoea, nutritional deterioration and death following a diarrhoeal episode. Lactoferrin and lysozyme are nutritional supplements that may reduce the risk of recurrent diarrhoeal episodes and accelerate nutritional recovery by treating or preventing underlying enteric infections and/or improving enteric function.Methods and analysis In this factorial, blinded, placebo-controlled randomised trial, we aim to determine the efficacy of lactoferrin and lysozyme supplementation in decreasing diarrhoea incidence and improving nutritional recovery in Kenyan children convalescing from comorbid diarrhoea and wasting. Six hundred children aged 6–24 months with mid-upper arm circumference

Purpose Globally, the number of children/adolescents exposed to HIV but uninfected (HIV-exposed uninfected, HEU) is growing. The HEU outcomes: population-evaluation and screening strategies study was designed to provide population-level evidence of the impact of HIV and recent antiretroviral therapy regimen exposure on neurodevelopmental, hearing and mental health outcomes from infancy to adolescence.Participants The study includes a prospective mother–infant cohort and cross-sectional child/youth–caregiver cohorts conducted in Kenya.Between 2021 and 2022, the study enrolled 2000 mother–infant pairs (1000 HEU and 1000 HIV-unexposed uninfected (HUU)) for longitudinal follow-up. Infants were eligible if they were aged 4–10 weeks and healthy. Mothers were eligible if their HIV status was known and were ≥18 years. Study visits are 6 monthly until the child reaches age 3 years.Cross-sectional cohorts spanning ages 3–18 years started enrolment in 2022. Target enrolment is 4400 children/youth (4000 HEU and 400 HUU). Children and youth are eligible if they are HIV negative, maternal HIV status and timing of diagnosis is known, and caregivers are ≥18 years.Data on infant/child/youth growth, neurodevelopment, mental health, morbidity and hearing are collected at enrolment using standardised tools. Dry blood spots samples are collected for telomere length assessment at baseline and yearly for the longitudinal cohort. Growth z-scores, neurodevelopmental scores, telomere length and prevalence of developmental and hearing problems will be compared between HEU/HUU populations.Findings to date Full cohort enrolment for the longitudinal cohort is complete and participants are in follow-up. At 1 year of age, comparing HEU to HUU neurodevelopment using the Malawi developmental assessment tool, we found that HEU infants had higher language scores and comparable scores in fine motor, gross motor and social scores. The cross-sectional cohort has enrolled over 2000 participants and recruitment is ongoing.Future plans Longitudinal cohort follow-up and enrolment to the cross-sectional study will be completed in June 2024.

Methods Medline, EMBASE and the Cochrane Library were searched and supplemented with conference and grey literature searches. Eligible studies included individuals with (1) PCC or (2) a positive SARS-CoV-2 test or COVID-19 diagnosis who were followed over time. Included studies were published in English between 1 January 2020 and 14 November 2022.Findings Of 291 publications included, 175 (60%) followed individuals with confirmed COVID-19 over time for PCC and 116 (40%) used a prespecified PCC definition. There was substantial heterogeneity in study design, geography, age group, PCC conditions/symptoms assessed and their classification and duration of follow-up. Among studies using a prespecified PCC definition, author-defined criteria (51%) were more common than criteria recommended by major public health organisations (19%). Measurement periods for PCC outcomes from date of acute COVID-19 test were primarily 3 to

Objective To create case definitions for confirmed COVID-19 diagnoses, COVID-19 vaccination status and three separate definitions of high risk of severe COVID-19, as well as to assess whether the implementation of these definitions in a cohort reflected the sociodemographic and clinical characteristics of COVID-19 epidemiology in England.Design Retrospective cohort study.Setting Electronic healthcare records from primary care (Clinical Practice Research Datalink, CPRD) linked to secondary care data (Hospital Episode Statistics) data covering 24% of the population in England.Participants 2 271 072 persons aged 1 year and older diagnosed with COVID-19 in CPRD Aurum between 1 August 2020 and 31 January 2022.Main outcome measures Age, sex and regional distribution of COVID-19 cases and COVID-19 vaccine doses received prior to diagnosis were assessed separately for the cohorts of cases identified in primary care and those hospitalised for COVID-19 (primary diagnosis code of ICD-10 U07.1 ‘COVID-19’). Smoking status, body mass index and Charlson Comorbidity Index were compared for the two cohorts, as well as for three separate definitions of high risk of severe disease used in the UK (National Health Service Highest Risk, PANORAMIC trial eligibility, UK Health Security Agency Clinical Risk prioritisation for vaccination).Results Compared with national estimates, CPRD case estimates under-represented older adults in both the primary care (age 65–84: 6% in CPRD vs 9% nationally) and hospitalised (31% vs 40%) cohorts, and over-represented people living in regions with the highest median wealth areas of England (20% primary care and 20% hospital admitted cases in South East vs 15% nationally). The majority of non-hospitalised cases and all hospitalised cases had not completed primary series vaccination. In primary care, persons meeting high-risk definitions were older, more often smokers, overweight or obese, and had higher Charlson Comorbidity Index score.Conclusions CPRD primary care data are a robust real-world data source and can be used for some COVID-19 research questions, however, limitations of the data availability should be carefully considered. Included in this publication are supplemental files for a total of over 28 000 codes to define each of three definitions of high risk of severe disease.

Objectives To quantify direct costs and healthcare resource utilisation (HCRU) associated with acute COVID-19 in adults in England.Design Population-based retrospective cohort study using Clinical Practice Research Datalink Aurum primary care electronic medical records linked to Hospital Episode Statistics secondary care administrative data.Setting Patients registered to primary care practices in England.Population 1 706 368 adults with a positive SARS-CoV-2 PCR or antigen test from August 2020 to January 2022 were included; 13 105 within the hospitalised cohort indexed between August 2020 and March 2021, and 1 693 263 within the primary care cohort indexed between August 2020 and January 2022. Patients with a COVID-19-related hospitalisation within 84 days of a positive test were included in the hospitalised cohort.Main outcome measures Primary and secondary care HCRU and associated costs ≤4 weeks following positive COVID-19 test, stratified by age group, risk of severe COVID-19 and immunocompromised status.Results Among the hospitalised cohort, average length of stay, including critical care stays, was longer in older adults. Median healthcare cost per hospitalisation was higher in those aged 75–84 (£8942) and ≥85 years (£8835) than in those aged

Introduction Over 52 million children under 5 years of age become wasted each year, but only 17% of these children receive treatment. Novel methods to identify and deliver treatment to malnourished children are necessary to achieve the sustainable development goals target for child health. Mobile health (mHealth) programmes may provide an opportunity to rapidly identify malnourished children in the community and link them to care.Methods and analysis This randomised controlled trial will recruit 1200 children aged 6–12 months at routine vaccine appointments in Migori and Homa Bay Counties, Kenya. Caregiver–infant dyads will be randomised to either a maternally administered malnutrition monitoring system (MAMMS) or standard of care (SOC). Study staff will train all caregivers to measure their child’s mid-upper arm circumference (MUAC). Caregivers in the MAMMS arm will be given two colour coded and graduated insertion MUAC tapes and be enrolled in a mHealth system that sends weekly short message service (SMS) messages prompting caregivers to measure and report their child’s MUAC by SMS. Caregivers in the SOC arm will receive routine monitoring by community health volunteers coupled with a quarterly visit from study staff to ensure adequate screening coverage. The primary outcome is identification of childhood malnutrition, defined as MUAC

Purpose Depression is the most common psychiatric disorder and the largest contributor to global disability. The Australian Genetics of Depression study was established to recruit a large cohort of individuals who have been diagnosed with depression at some point in their lifetime. The purpose of establishing this cohort is to investigate genetic and environmental risk factors for depression and response to commonly prescribed antidepressants.Participants A total of 20 689 participants were recruited through the Australian Department of Human Services and a media campaign, 75% of whom were female. The average age of participants was 43 years±15 years. Participants completed an online questionnaire that consisted of a compulsory module that assessed self-reported psychiatric history, clinical depression using the Composite Interview Diagnostic Interview Short Form and experiences of using commonly prescribed antidepressants. Further voluntary modules assessed a wide range of traits of relevance to psychopathology. Participants who reported they were willing to provide a DNA sample (75%) were sent a saliva kit in the mail.Findings to date 95% of participants reported being given a diagnosis of depression by a medical practitioner and 88% met the criteria for a lifetime depressive episode. 68% of the sample report having been diagnosed with another psychiatric disorder in addition to depression. In line with findings from clinical trials, only 33% of the sample report responding well to the first antidepressant they were prescribed.Future plans A number of analyses to investigate the genetic architecture of depression and common comorbidities will be conducted. The cohort will contribute to the global effort to identify genetic variants that increase risk to depression. Furthermore, a thorough investigation of genetic and psychosocial predictors of antidepressant response and side effects is planned.

Objectives: To assess greenhouse gas (GHG) emissions from a regional hospital laundry unit, and model ways in which these can be reduced., Design: A cradle to grave process-based attributional life-cycle assessment., Setting: A large hospital laundry unit supplying hospitals in Southwest England., Population: All laundry processed through the unit in 2020-21 and 2021-22 financial years., Primary Outcome Measure: The mean carbon footprint of processing one laundry item, expressed as in terms of the global warming potential over 100 years, as carbon dioxide equivalents (CO 2 e)., Results: Average annual laundry unit GHG emissions were 2947 t CO 2 e. Average GHG emissions were 0.225 kg CO 2 e per item-use and 0.5080 kg CO 2 e/kg of laundry. Natural gas use contributed 75.7% of on-site GHG emissions. Boiler electrification using national grid electricity for 2020-2022 would have increased GHG emissions by 9.1%, however by 2030 this would reduce annual emissions by 31.9% based on the national grid decarbonisation trend. Per-item transport-related GHG emissions reduce substantially when heavy goods vehicles are filled at ≥50% payload capacity. Single-use laundry item alternatives cause significantly higher per-use GHG emissions, even if reusable laundry were transported long distances and incinerated at the end of its lifetime., Conclusions: The laundry unit has a large carbon footprint, however the per-item GHG emissions are modest and significantly lower than using single-use alternatives. Future electrification of boilers and optimal delivery vehicle loading can reduce the GHG emissions per laundry item., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The effective implementation of a fast-changing healthcare delivery innovation, such as robotic-assisted surgery (RAS), into a healthcare system, can be affected (both positively and negatively) by external contextual factors. As part of a wider project investigating ways to optimise the implementation of RAS, this qualitative study aimed to uncover current issues of RAS and predictions about the future of robotic surgery. We refer to 'current issues' as the topical and salient challenges and opportunities related to the introduction of RAS in the UK healthcare system, from the perspectives of key stakeholders involved in the delivery and implementation of RAS., Design: Semi-structured interviews and focus groups were conducted. A thematic analysis was conducted to summarise salient issues that were articulated by the participants., Setting and Participants: The interview sample (n=35) comprised surgeons, wider theatre staff and other relevant personnel involved in the introduction and delivery of RAS services across the UK, including service managers and policymakers/commissioners. Two focus groups were also conducted with surgical trainees (n=7) and members of the public (n=8), respectively., Results: The results revealed a largely positive attitude towards the introduction of RAS technology and an expectation of continued rapid expansion. Areas perceived to be particularly pertinent and requiring ongoing attention were also highlighted, including the need to achieve improved quality control, expertise quantification and training issues and the need to educate the public. Issues of centralisation, service organisation and equity of access were also emphasised., Conclusions: Our study has highlighted a range of issues perceived to be particularly pertinent to the current and future provision of RAS which should be addressed. The areas outlined can enable healthcare managers and surgeons to plan for the adoption and/or expansion of RAS services., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study aimed to understand and explore patient and general practitioner (GP) experiences of 'traditional' and 'one-stop' prostate cancer diagnostic pathways in England., Design: Qualitative study using semi-structured interviews, analysed using inductive thematic analysis SETTING: Patients were recruited from National Health Service (NHS) Trusts in London and in Devon; GPs were recruited via National Institute for Health Research (NIHR) Clinical Research Networks. Interviews were conducted in person or via telephone., Participants: Patients who had undergone a MRI scan of the prostate as part of their diagnostic work-up for possible prostate cancer, and GPs who had referred at least one patient for possible prostate cancer in the preceding 12 months., Results: 22 patients (aged 47-80 years) and 10 GPs (6 female, aged 38-58 years) were interviewed. Patients described three key themes: cancer beliefs in relation to patient's attitudes towards prostate cancer ;communication with their GP and specialist having a significant impact on experience of the pathway and pathway experience being influenced by appointment and test burden. GP interview themes included: the challenges of dealing with imperfect information in the current pathway; managing uncertainty in identifying patients with possible prostate cancer and sharing this uncertainty with them, and other social, cultural and personal contextual influences ., Conclusions: Patients and GPs reported a range of experiences and views of the current prostate cancer diagnostic pathways in England. Patients valued 'one-stop' pathways integrating prostate MRI and diagnostic consultations with specialists over the more traditional approach of several hospital appointments. GPs remain uncertain how best to identify patients needing referral for urgent prostate cancer testing due to the lack of accurate triage and risk assessment strategies., Competing Interests: Competing interests: HUA was a paid medical consultant for Sophiris Biocorp in the previous 3 years. The remaining authors have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objective: To investigate whether sleep disparities vary by birthplace among non-Hispanic White (NHW) and Hispanic/Latino adults in the USA and to investigate language preference as an effect modifier., Design: Cross-sectional., Setting: USA., Participants: 254 699 men and women., Methods: We used pooled 2004-2017 National Health Interview Survey data. Adjusting for sociodemographic and behavioural/clinical characteristics, survey-weighted Poisson regressions with robust variance estimated prevalence ratios (PRs) and 95% CIs of self-reported sleep characteristics (eg, sleep duration, trouble staying asleep) among (1) foreign-born NHW adults and Hispanic/Latino heritage groups versus US-born NHW adults and (2) Hispanic/Latino heritage groups versus foreign-born NHW adults. We further stratified by language preference in comparisons of Hispanic/Latino heritage groups with the US-born NHW group., Results: Among 254 699 participants with a mean age±SE 47±0.9 years, 81% self-identified their race/ethnicity as NHW, 12% Mexican, 2% Puerto Rican, 1% Cuban, 1% Dominican and 3% Central/South American. Compared with US-born NHW adults, foreign-born NHW adults were more likely to report poor sleep quality (eg, PR trouble staying asleep =1.27 (95% CI: 1.17 to 1.37)), and US-born Mexican adults were no more likely to report non-recommended sleep duration while foreign-born Mexican adults were less likely (eg, PR ≤5-hours =0.52 (0.47 to 0.57)). Overall, Mexican adults had lower prevalence of poor sleep quality versus US-born NHW adults, and PRs were lowest for foreign-born Mexican adults. US-born Mexican adults were more likely than foreign-born NHW adults to report shorter sleep duration. Regardless of birthplace, Puerto Rican adults were more likely to report shorter sleep duration versus NHW adults. Generally, sleep duration and quality were better among Cuban and Dominican adults versus US-born NHW adults but were similar versus foreign-born NHW adults. Despite imprecision in certain estimates, Spanish language preference was generally associated with increasingly better sleep among Hispanic/Latino heritage groups compared with US-born NHW adults., Conclusion: Sleep disparities varied by birthplace, Hispanic/Latino heritage and language preference, and each characteristic should be considered in sleep disparities research., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Survival in men diagnosed with de novo synchronous metastatic prostate cancer has increased following the use of upfront systemic treatment, using chemotherapy and other novel androgen receptor targeted agents, in addition to standard androgen deprivation therapy (ADT). Local cytoreductive and metastasis-directed interventions are hypothesised to confer additional survival benefit. In this setting, IP2-ATLANTA will explore progression-free survival (PFS) outcomes with the addition of sequential multimodal local and metastasis-directed treatments compared with standard care alone., Methods: A phase II, prospective, multicentre, three-arm randomised controlled trial incorporating an embedded feasibility pilot. All men with new histologically diagnosed, hormone-sensitive, metastatic prostate cancer, within 4 months of commencing ADT and of performance status 0 to 2 are eligible. Patients will be randomised to Control (standard of care (SOC)) OR Intervention 1 (minimally invasive ablative therapy to prostate±pelvic lymph node dissection (PLND)) OR Intervention 2 (cytoreductive radical prostatectomy±PLND OR prostate radiotherapy±pelvic lymph node radiotherapy (PLNRT)). Metastatic burden will be prespecified using the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease (CHAARTED) definition. Men with low burden disease in intervention arms are eligible for metastasis-directed therapy, in the form of stereotactic ablative body radiotherapy (SABR) or surgery. Standard systemic therapy will be administered in all arms with ADT±upfront systemic chemotherapy or androgen receptor agents. Patients will be followed-up for a minimum of 2 years., Primary Outcome: PFS. Secondary outcomes include predictive factors for PFS and overall survival; urinary, sexual and rectal side effects. Embedded feasibility sample size is 80, with 918 patients required in the main phase II component. Study recruitment commenced in April 2019, with planned follow-up completed by April 2024., Ethics and Dissemination: Approved by the Health Research Authority (HRA) Research Ethics Committee Wales-5 (19/WA0005). Study results will be submitted for publication in peer-reviewed journals., Trial Registration Number: NCT03763253; ISCRTN58401737., Competing Interests: Competing interests: MJC’s research is support by University College London Hospitals (UCLH) Charity and the Wellcome Trust.KTJ is currently supported by a research grant from the UK National Institute of Health Research (NIHR) Clinical Research Network Eastern. He has received educational and travel grants from Bayer UK, Janssen Oncology, Pfizer; Roche, Takeda.HUA’s research is supported by core funding from the United Kingdom’s National Institute of Health Research (NIHR) Imperial Biomedical Research Centre. HUA currently receives funding from the Wellcome Trust, Prostate Cancer UK, MRC (UK), Cancer Research UK, Sonacare Inc., Trod Medical and Sophiris Biocorp for trials in prostate cancer. HUA was a paid medical consultant for Sophiris Biocorp, Sonacare Inc. and BTG in the past 3 years., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objective: Although there is much focus on burnout and psychological distress among doctors, studies about stress and well-being in medical students are limited but could inform early intervention and prevention strategies., Design: The primary aim of this mixed-method, cross-sectional survey was to compare objective and subjective levels of stress in final-year medical students (2017) and to explore their perspectives on the factors they considered relevant to their well-being., Setting: University College Dublin, the largest university in Ireland., Participants: 161 of 235 medical students participated in this study (response rate 69%)., Results: 65.2% of students scored over accepted norms for the Perceived Stress Scale (34.8% low, 55.9% moderate and 9.3% high). 35% scored low, 28.7% moderate and 36.3% high on the Subjective Stress Scale. Thematic analysis identified worry about exams, relationships, concern about the future, work-life balance and finance; one in three students reported worry, irritability and hostility; many felt worn out. Cognitive impacts included overthinking, poor concentration, sense of failure, hopelessness and procrastination. Almost a third reported sleep and appetite disturbance, fatigue and weariness. A quarter reported a 'positive reaction' to stress. Positive strategies to manage stress included connection and talking, exercise, non-study activity and meditation. Unhelpful strategies included isolation and substance use. No student reported using the college support services or sought professional help., Conclusion: Medical students experience high levels of psychological distress, similar to their more senior doctor colleagues. They are disinclined to avail of traditional college help services. Toxic effects of stress may impact their cognition, learning, engagement and empathy and may increase patient risk and adverse outcomes. The focus of well-being in doctors should be extended upstream and embedded in the curriculum where it could prevent future burnout, improve retention to the profession and deliver better outcomes for patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Bladder cancer is the most frequently occurring tumour of the urinary system. Ta, T1 tumours and carcinoma in situ (CIS) are grouped as non-muscle invasive bladder cancer (NMIBC), which can be effectively treated by transurethral resection of bladder tumour (TURBT). There are limitations to the visualisation of tumours with conventional TURBT using white light illumination within the bladder. Incomplete resections occur from the failure to identify satellite lesions or the full extent of the tumour leading to recurrence and potential risk of disease progression. To improve complete resection, photodynamic diagnosis (PDD) has been proposed as a method that can enhance tumour detection and guide resection. The objective of the current research is to determine whether PDD-guided TURBT is better than conventional white light surgery and whether it is cost-effective., Methods and Analysis: PHOTO is a pragmatic multicentre randomised controlled trial (open parallel group, non-masked and superiority trial) comparing the intervention of PDD-guided TURBT with standard white light resection in newly diagnosed intermediate and high risk NMIBC within the UK National Health Service setting. Clinical effectiveness is measured with time to recurrence. Cost-effectiveness is assessed within trial via the calculation of incremental cost per recurrence avoided and incremental cost per quality-adjusted life per year gained over 3 years and over long term through a modelling exercise over patients' lifetime., Ethics and Dissemination: Formal ethics review was undertaken with a favourable opinion, in line with UK regulatory procedures (REC reference number: 14/NE/1062). If reductions in time to recurrence is associated with long-term patient benefits, the cost-effectiveness evaluation will provide further evidence to inform adoption of the technology. Findings will be shared in lay media such as patient and charity forums and will be presented at key meetings and published in academic literature.Trial registration number ISRCTN84013636., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Cocreation, coproduction and codesign are advocated as effective ways of involving citizens in the design, management, provision and evaluation of health and social care services. Although numerous case studies describe the nature and level of coproduction in individual projects, there remain three significant gaps in the evidence base: (1) measures of coproduction processes and their outcomes, (2) mechanisms that enable inclusivity and reciprocity and (3) management systems and styles. By focusing on these issues, we aim to explore, enhance and measure the value of coproduction for improving the health and well-being of citizens., Methods and Analysis: Nine ongoing coproduction projects form the core of an interactive research programme ('Samskapa') during a 6-year period (2019-2024). Six of these will take place in Sweden and three will be undertaken in England to enable knowledge exchange and cross-cultural comparison. The programme has a longitudinal case study design using both qualitative and quantitative methods. Cross-case analysis and a sensemaking process will generate relevant lessons both for those participating in the projects and researchers. Based on the findings, we will develop explanatory models and other outputs to increase the sustained value (and values) of future coproduction initiatives in these sectors., Ethics and Dissemination: All necessary ethical approvals will be obtained from the regional Ethical Board in Sweden and from relevant authorities in England. All data and personal data will be handled in accordance with General Data Protection Regulations. Given the interactive nature of the research programme, knowledge dissemination to participants and stakeholders in the nine projects will be ongoing throughout the 6 years. External workshops-facilitated in collaboration with participating case studies and citizens-both during and at the end of the programme will provide an additional dissemination mechanism and involve health and social care practitioners, policymakers and third-sector organisations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Recent reviews have found substantial links between a toxic childhood environment including child abuse and severe household dysfunction and adult cardiovascular disease (CVD). Collectively referred to as adverse childhood experiences (ACEs), this toxic environment is prevalent among children, with recent Canadian estimates of child abuse at 27%-32%, and severe household dysfunction at 49%. Based on these prevalence rates, the potential effect of ACEs on CVD is more significant than previously thought. Yet, how ACEs amplify the risk for later CVD remains unclear. Lifestyle risk factors only partially account for this connection, instead directing attention to the interaction between psychosocial factors and physiological mechanisms such as inflammation. The Niagara Longitudinal Heart Study (NLHS) examines how ACEs influence cardiovascular health (CVH) from childhood to early adulthood. Integrating the stress process and biological embedding models, this study examines how psychosocial and physiological factors in addition to lifestyle factors explain the relationship between ACEs and CVH., Methods: This follow-up study combines three baseline studies from 2007 to 2012 that collected CVH measures including child blood pressure, heart rate, left ventricular structure and function, arterial stiffness indices and baroreflex sensitivity on 564 children. Baseline data also include anthropometric, biological, lifestyle, behavioural, and psychosocial measures that varied across primary studies. Now over 18 years of age, we will recruit and retest as many participants from the baseline studies as possible collecting data on ACEs, CVH, anthropometric, lifestyle and psychosocial measures as well as blood, saliva and hair for physiological biostress markers., Ethics and Dissemination: Ethics approval has been received for the NLHS follow-up. Written consent to participate in the follow-up study is obtained from each participant. Results testing all proposed hypotheses will be submitted for publication in peer-reviewed journals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Bladder cancer (BC) is a common malignancy and one of the most expensive to manage. Radical cystectomy (RC) with pelvic lymphadenectomy is a gold standard treatment for high-risk BC. Reductions in morbidity and mortality from RC may be achieved through robot-assisted RC (RARC). Prospective comparisons between open RC (ORC) and RARC have been limited by sample size, use of extracorporeal reconstruction and use of outcomes important for ORC. Conversely, while RARC is gaining in popularity, there is little evidence to suggest it is superior to ORC. We are undertaking a prospective randomised controlled trial (RCT) to compare RARC with intracorporeal reconstruction (iRARC) and ORC using multimodal outcomes to explore qualitative and quantitative recovery after surgery. METHODS AND ANALYSIS: iROC is a multicentre prospective RCT in English National Health Service (NHS) cancer centres. We will randomise 320 patients undergoing RC to either iRARC or ORC. Treatment allocation will occur after trial entry and consent. The primary outcome is days alive and out of hospital within the first 90 days from surgery. Secondary outcomes will measure functional recovery (activity trackers, chair-to-stand tests and health related quality of life (HRQOL) questionnaires), morbidity (complications and readmissions), cost-effectiveness (using EuroQol-5 Domain-5 levels (EQ-5D-5L) and unit costs) and surgeon fatigue. Patients will be analysed according to intention to treat. The primary outcome will be transformed and analysed using regression. All statistical assumptions will be investigated. Secondary outcomes will be analysed using appropriate regression methods. An internal feasibility study of the first 30 patients will evaluate recruitment rates, acceptance of randomised treatment choice, compliance outcome collection and to revise our sample size., Ethics and Dissemination: The study has ethical approval (REC reference 16/NE/0418). Findings will be made available to patients, clinicians, funders and the NHS through peer-reviewed publications, social media and patient support groups., Trial Registration Numbers: ISRCTN13680280 and NCT03049410., Competing Interests: Competing interests: Within iROC, robotic consumables are provider without cost from Intuitive Surgical. JMcG has received educational funding from Intuitive Surgical., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The Nineteen and Up study (19Up) assessed a range of mental health and behavioural problems and associated risk factors in a genetically informative Australian cohort of young adult twins and their non-twin siblings. As such, 19Up enables detailed investigation of genetic and environmental pathways to mental illness and substance misuse within the Brisbane Longitudinal Twin Sample (BLTS)., Participants: Twins and their non-twin siblings from Queensland, Australia; mostly from European ancestry. Data were collected between 2009 and 2016 on 2773 participants (age range 18-38, 57.8% female, 372 complete monozygotic pairs, 493 dizygotic pairs, 640 non-twin siblings, 403 singleton twins)., Findings to Date: A structured clinical assessment (Composite International Diagnostic Interview) was used to collect lifetime prevalence of diagnostic statistical manual (4th edition) (DSM-IV) diagnoses of major depressive disorder, (hypo)mania, social anxiety, cannabis use disorder, alcohol use disorder, panic disorder and psychotic symptoms. Here, we further describe the comorbidities and ages of onset for these mental disorders. Notably, two-thirds of the sample reported one or more lifetime mental disorder.In addition, the 19Up study assessed general health, drug use, work activity, education level, personality, migraine/headaches, suicidal thoughts, attention deficit hyperactivity disorder (ADHD) symptomatology, sleep-wake patterns, romantic preferences, friendships, familial environment, stress, anorexia and bulimia as well as baldness, acne, asthma, endometriosis, joint flexibility and internet use.The overlap with previous waves of the BLTS means that 84% of the 19Up participants are genotyped, 36% imaged using multimodal MRI and most have been assessed for psychological symptoms at up to four time points. Furthermore, IQ is available for 57%, parental report of ADHD symptomatology for 100% and electroencephalography for 30%., Future Plans: The 19Up study complements a phenotypically rich, longitudinal collection of environmental and psychological risk factors. Future publications will explore hypotheses related to disease onset and development across the waves of the cohort. A follow-up study at 25+years is ongoing., Competing Interests: Competing interests: BCD is supported by an UQI scholarship, VOC by a UQ winter scholarship. SEM is supported by an NHMRC fellowship (APP1103623), JGS by a NHMRC Practitioner Fellowship (1105807), JJMG by a NHMRC John Cade Fellowship (APP1056929), BPZ is supported by an ARC Discovery Early Career Research Award (DE120100562), NAG by NIH/NIDA grants (5R00DA023549, R21DA038852)., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: There is growing evidence that delusional-like experiences (DLE) are associated with common mental disorders. In particular, a National Mental Health Survey conducted in Australia during 2007 reported an association between DLE and both anxiety disorder and major depressive disorder (MDD). However, the previous study did not examine this association with respect to subtypes of anxiety disorder nor with severity of MDD. The aim of this study was to examine the associations between DLE and both anxiety disorder and MDD in more detail based on an independent population sample., Design: Cross-sectional study., Setting: Subjects were drawn from the Australian Survey of Mental Health and Wellbeing 1997 using a stratified multistage area sampling of persons living in private dwellings in all States and Territories of Australia., Participants: Approximately 13 600 private dwellings were initially selected with one person aged 18 years or older from each dwelling invited to participate. In total, 10 641 individuals participated in the survey., Primary and Secondary Outcome Measures: The Composite International Diagnostic Interview was used to identify individuals with DLE and Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition (DSM IV) lifetime diagnoses of anxiety disorders and MDD. The influence of various anxiety disorders and MDD on DLE was assessed with logistic regression., Results: Having a lifetime diagnosis of either any anxiety disorder or MDD was significantly associated with the endorsement of DLE. The association was found for each of the main anxiety disorders when examined separately. There was a dose-response relationship between increasing severity of MDD and higher odds of DLE endorsement., Conclusions: DLE are associated with a wide range of anxiety disorders and are more prevalent in those with MDD. Understanding the relationship between DLE, anxiety disorders and depression may provide insights into shared pathways that underpin both psychotic disorders and common mental disorders.