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Metastasis‐directed therapy (MDT) for oligometastatic prostate cancer (PCa), including stereotactic body radiotherapy (SBRT), has shown promise but is still considered investigational. This is the 5‐year analysis of the TRANSFORM trial, the largest prospective cohort of men with oligometastatic PCa treated with SBRT‐based MDT. The primary endpoint was 5‐year treatment escalation‐free survival (TE‐FS), defined as freedom from any new cancer therapy other than further SBRT. In total, 199 men received SBRT; 76.4% were hormone‐naïve at baseline. The rate of 5‐year TE‐FS was 21.7% (95% confidence interval [CI]: 15.7%–28.7%) overall and 25.4% (95% CI: 18.1%–33.9%) in the hormone‐naïve subgroup. The subgroups with International Society of Urological Pathology Grade Groups 4–5 disease (hazard ratio [HR] = 1.48, 95% CI: 1.05–2.01, p =.026), a higher baseline prostate‐specific antigen (PSA) (HR = 1.06, 95% CI: 1.03–1.09, p <.001) and those who received prior androgen deprivation therapy (ADT) (HR = 2.13, 95% CI: 1.40–3.26, p <.001), were at greater risk of treatment escalation. Outcomes for participants with four or five initial lesions were comparable to those with one to three lesions. At last follow‐up, 18.9% (95% CI: 13.2%–25.7%) of participants were free from treatment escalation (median follow‐up of 67.9 months) and two participants had an undetectable PSA level. No treatment‐related grade three or higher adverse events were reported. The findings of this study demonstrate that SBRT‐based MDT is an effective option for delaying systemic treatment escalation in the context of oligometastatic PCa. Future randomised trials comparing SBRT‐based MDT to standard‐of‐care ADT‐based approaches are required to evaluate the impact of delaying ADT on survival. [ABSTRACT FROM AUTHOR]

Robotic surgery has expanded internationally at pace. There are multiple local robotic training pathways but there is inconsistency in standardisation of core common components for curricula internationally. A framework is required to define key objectives that can be implemented across robotic training ecosystems. This Delphi consensus aimed to provide recommendations for core considerations in robotic training design across diverse training environments internationally. A literature search was performed and an international steering committee (AG, KL, JW, HM, TC) proposed key components for contemporary robotic training design and a modified Delphi approach was used to gather stakeholder opinion. The outcomes were then discussed at a face-to-face international expert consensus at the IMRA educational session at the Society of Robotic Surgery (SRS) meeting and final voting was conducted on outstanding items. Stakeholders included robotic surgeons, proctors, trainees and robotic surgical training providers. There was consensus achieved in 139 statements organised into 15 themes. There was 100% agreement that standardised themes in robotic curricula may improve patient safety. Key take-home messages include—training curricula should be multiplatform, non-technical skills are an important component of a robotic curriculum as well as console and bedside skills, clinically relevant performance metrics should be used for assessment where available, the reliance on cadaveric and live animal models should be reduced as high-fidelity synthetic models emerge, and stepwise component training is useful for advanced procedural training. These consensus recommendations are intended to guide design of fit for purpose contemporary robotic surgical curricula. Integration of these components into robotic training pathways internationally is recommended. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we investigated the impact of lymphovascular invasion at the time of prostatectomy on oncological outcomes in patients with prostate cancer. We found that the presence of lymphovascular invasion at the time of radical prostatectomy is associated with aggressive prostate cancer disease features and is an indicator of poor oncological prognosis. Therefore, lymphovascular invasion status could be used as a factor to identify patients that have underlying disseminated disease and may benefit from systemic treatment intensification, especially those with high-risk disease. Further prospective studies need to be conducted to validate these findings. Lymphovascular invasion, whereby tumour cells or cell clusters are identified in the lumen of lymphatic or blood vessels, is thought to be an essential step in disease dissemination. It has been established as an independent negative prognostic indicator in a range of cancers. We therefore aimed to assess the impact of lymphovascular invasion at the time of prostatectomy on oncological outcomes. We performed a multicentre, retrospective cohort study of 3495 men who underwent radical prostatectomy for localised prostate cancer. Only men with negative preoperative staging were included. We assessed the relationship between lymphovascular invasion and adverse pathological features using multivariable logistic regression models. Kaplan–Meier curves and Cox proportional hazard models were created to evaluate the impact of lymphovascular invasion on oncological outcomes. Lymphovascular invasion was identified in 19% (n = 653) of men undergoing prostatectomy. There was an increased incidence of lymphovascular invasion-positive disease in men with high International Society of Urological Pathology (ISUP) grade and non-organ-confined disease (p < 0.01). The presence of lymphovascular invasion significantly increased the likelihood of pathological node-positive disease on multivariable logistic regression analysis (OR 15, 95%CI 9.7–23.6). The presence of lymphovascular invasion at radical prostatectomy significantly increased the risk of biochemical recurrence (HR 2.0, 95%CI 1.6–2.4). Furthermore, lymphovascular invasion significantly increased the risk of metastasis in the whole cohort (HR 2.2, 95%CI 1.6–3.0). The same relationship was seen across D'Amico risk groups. The presence of lymphovascular invasion at the time of radical prostatectomy is associated with aggressive prostate cancer disease features and is an indicator of poor oncological prognosis. [ABSTRACT FROM AUTHOR]

Connected by a shared endeavour to enhance understanding of the forces that shape contestation toward the EU in its peripheries and unprohibited in approach, this special section explores the concepts of contestation and periphery. Using various methodological approaches, the section showcases a series of overlapping and cross-cutting themes which contextually strengthen the phenomenon and experiences of contestation in peripheral states. In aggregating these themes, the authors attribute contestation to the growing 'absence' of the EU's normative interest in peripheral states and the growing transactional/functional features that define peripheral state relationships with the EU. The authors draw attention to the opportunities for regional rivals, such as Russia and China to capitalize on the absence of the EU's transformative power in peripheral states, the role of domestic forces in utilizing contestation as a means to preserve regime type and satisfy sovereignty concerns, and the incidences of peripheral states in shaping/reshaping their foreign policy positions in response to the Russia-Ukraine war. Taken together, our special section shows that contestation in Europe's periphery is less an overt normative resistance against the EU and more an absence of EU normative efforts in peripheral states and the increasingly functional features which define peripheral states' relationships with the EU. [ABSTRACT FROM AUTHOR]

Robotic surgical training is undergoing a period of transition now that new robotic operating platforms are entering clinical practice. As this occurs, training will need to be adapted to include strategies to train across various consoles. These new consoles differ in multiple ways, with some new vendors using flat screen open source 3D enhanced vision with glasses and differences in design will require surgeons to learn new skills. This process has parallels with aviation credentialling across different aircraft described as type rating. This study was designed to test the hypothesis that technical robotic console operating skills are transferrable across different robotic operating platforms. Ten participants sequentially completed four Mimic®(Surgical Science) simulation exercises on two different robotic operating platforms (DaVinci®, Intuitive Surgical and HUGO™ RAS, Medtronic). Ethical approval and informed consent were obtained for this study. Groups were balanced for key demographics including previous robotic simulator experience. Data for simulation metrics and time to proficiency were collected for each attempt at the simulated exercise and analysed. Qualitative feedback on multi-platform learning was sought via unstructured interviews and a questionnaire. Participants were divided into two groups of 5. Group 1 completed the simulation exercises on console A first then repeated these exercises on console B. Group 2 completed the simulated exercises on console B first then repeated these exercises on console A. Group 1 candidates adapted quicker to the second console and Group 2 candidates reached proficiency faster on the first console. Participants were slower on the second attempt of the final exercise regardless of their allocated group. Quality and efficiency metrics and risk and safety metrics were equivalent across consoles. The data from this investigation suggests that console operating skills are transferrable across different platforms. Overall risk and safety metrics are within acceptable limits regardless of the order of progression of console indicating that training can safely occur across multiple consoles contemporaneously. This data has implications for the design of training and certification as new platforms progress to market and supports a proficiency-based approach. [ABSTRACT FROM AUTHOR]

Background: The introduction of robotic surgical systems has significantly impacted urological surgery, arguably more so than other surgical disciplines. The focus of our study was length of hospital stay ‐ patients have traditionally been discharged day 1 post‐robot‐assisted radical prostatectomy (RARP), however, during the ongoing COVID‐19 pandemic and consequential resource limitations, our centre has facilitated a cohort of same‐day discharges with initial success. Methods: We conducted a prospective tertiary single‐centre cohort study of a series of all patients (n = 28) – undergoing RARP between January and April 2021. All patients were considered for a day zero discharge pathway which consisted of strict inclusion criteria. At follow‐up, each patient's perspective on their experience was assessed using a validated post‐operative satisfaction questionnaire. Data were reviewed retrospectively for all those undergoing RARP over the study period, with day zero patients compared to overnight patients. Results: Overall, 28 patients 20 (71%) fulfilled the objective criteria for day zero discharge. Eleven patients (55%) agreed pre‐operatively to day zero discharge and all were successfully discharged on the same day as their procedure. There was no statistically significant difference in age, BMI, ASA, Charlson score or disease volume. All patients indicated a high level of satisfaction with their procedure. Median time from completion of surgery to discharge was 426 min (7.1 h) in the day zero discharge cohort. Conclusion: Day zero discharge for RARP appears to deliver high satisfaction, oncological and safety outcomes. Therefore, our study demonstrates early success with unsupported same‐day discharge in carefully selected and pre‐counselled patients. [ABSTRACT FROM AUTHOR]

Addressing the large carbon footprint of conferences such as the United Nations Climate Change Convention Conference of the Parties (COP) will be important for maintaining public confidence in climate policy. Transparency is also a vital aspect of creating equitable outcomes in climate policies, as those most likely to be affected or who can create change on the ground are often unable to attend in person because of the high financial costs as well as having a large carbon footprint. The selection of host locations for the regular meetings of the UN Climate Change Convention is based on a rotation amongst the five UN regions, which for 2022 was Africa. Here, we present a carbon footprint calculator for travel to COP 27 in Sharm El-Sheikh, Egypt, weighing the benefits of certain routes and modes of transport. The calculator demonstrates the well-known carbon efficiency of coach and rail over flights but shows that these benefits were partly diminished in the case of COP 27 due to insufficient transport links from Europe to the conference location. However, we also highlight some of the benefits of hosting a COP in the Global South, particularly in the context of climate justice. Users of the calculator are invited to consider all their options for travel and acknowledge the issue of climate justice through careful selection of carbon offsets. [ABSTRACT FROM AUTHOR]

Climate justice is not just a financial transaction to protect the environment. It needs to be seen as the protection of the most vulnerable in society after centuries of resource exploitation. African countries disproportionately face impacts of climate change on their environments, their economies, their resources and their infrastructure. This leads to greater vulnerability and increased exposure to the negative effects of a changing climate. In this article, we highlight the importance of climate justice and its role within the United Nations negotiations, and ultimately in concrete action. We discuss current climate impacts across key sectors in the African region, with a focus on health, infrastructure, food and water scarcity, energy and finance. All sectors are affected by climate change. They are interconnected and under threat. This triggers a ripple effect, where threats in one sector have a knock-on effect on other sectors. We find that the current set of intergovernmental institutions have failed to adequately address climate justice. We also contend that a siloed approach to climate action has proven to be ineffective. As we head towards the next set of negotiations (COP27), this paper argues that the economic and social conditions in Africa can be addressed through financial and collaborative support for adaptation and localised solutions, but that this will only be achieved if climate justice is prioritised by the decision makers. This needs to include a global-scale transition in how climate finance is assessed and accessed. Climate justice underpins real, effective and sustainable solutions for climate action in Africa. [ABSTRACT FROM AUTHOR]

On the 25 March 2017, leaders of the EU27 and European Union (EU) institutions ratified the Rome Declaration. They committed to invite citizens to discuss Europe's future and to provide recommendations that would facilitate their decision-makers in shaping their national positions on Europe. In response, citizens' dialogues on the future of Europe were instituted across the Union to facilitate public participation in shaping Europe. This paper explores Ireland's set of dialogues which took place during 2018. Although event organisers in Ireland applied a relatively atypical and more systematic and participatory approach to their dialogues, evidence suggests that Irelands' dialogues were reminiscent of a public relations exercise which showcased the country's commitment to incorporating citizens into the debate on Europe while avoiding a deliberative design which could have strengthened the quality of public discourse and the quality of public recommendations. Due to an absence of elite political will for a deliberative process, as well as structural weaknesses in design, participants' recommendations lacked any clear and prescriptive direction which could shape Ireland's national position on the future of Europe in any constructive or meaningful way. [ABSTRACT FROM AUTHOR]

Disease recurrence is common following prostatectomy in patients with localised prostate cancer with highrisk features. We conducted an open label phase II study of the combination of FGFR inhibition (3 months) and androgen deprivation therapy (4 months) in this patient cohort. Although there was a possible enhanced anti-tumour effect following combination therapy, the poor tolerability in this patient population prohibits the use of this combination in this setting. Background: Disease recurrence is common following prostatectomy in patients with localised prostate cancer with high-risk features. Although androgen deprivation therapy increases the rates of organ-confined disease and negative surgical margins, there is no significant benefit on disease recurrence. Multiple lines of evidence suggest that (Fibroblast Growth Factor/Fibroblast Growth Factor Receptor) FGF/FGFR-signalling is impor tant in suppor ting prostate epithelial cell survival in hostile conditions, including acute androgen deprivation. Given the recent availability of oral FGFR inhibitors, we investigated whether combination therapy could improve tumour response in the neo-adjuvant setting. Methods: We conducted an open label phase II study of the combination of erdafitinib (3 months) and androgen deprivation therapy (4 months) in men with localised prostate cancer with high-risk features prior to prostatectomy using a Simon's 2 stage design. The co-primary endpoints were safety and tolerability and pathological response in the prostatectomy specimen. The effect of treatment on residual tumours was explored by global transcriptional profiling with RNA-sequencing. Results: Nine patients were enrolled in the first stage of the trial. The treatment combination was poorly tolerated. Erdafitinib treatment was discontinued early in six patients, three of whom also required dose interruptions/reductions. Androgen deprivation therapy for 4 months was completed in all patients. The most common adverse events were hyperphosphataemia, taste disturbance, dry mouth and nail changes. No patients achieved a complete pathological response, although patients who tolerated erdafitinib for longer had smaller residual tumours, associated with reduced transcriptional signatures of epithelial cell proliferation. Conclusions: Although there was a possible enhanced anti-tumour effect of androgen deprivation therapy in combination with erdafitnib in treatment naïve prostate cancer, the poor tolerability in this patient population prohibits the use of this combination in this setting. [ABSTRACT FROM AUTHOR]

Background: Nurturing care, including adequate nutrition, responsive caregiving and early learning, is critical to early childhood development. In Nepal, national surveys highlight inequity in feeding and caregiving practices for young children. Our objective was to describe infant and young child feeding (IYCF) and cognitive and socio-emotional caregiving practices among caregivers of children under five in Dhanusha district, Nepal, and to explore socio-demographic and economic factors associated with these practices.Methods: We did a cross-sectional analysis of a subset of data from the MIRA Dhanusha cluster randomised controlled trial, including mother-child dyads (N = 1360), sampled when children were median age 46 days and a follow-up survey of the same mother-child dyads (N = 1352) when children were median age 38 months. We used World Health Organization IYCF indicators and questions from the Multiple Indicator Cluster Survey-4 tool to obtain information on IYCF and cognitive and socio-emotional caregiving practices. Using multivariable logistic regression models, potential explanatory household, parental and child-level variables were tested to determine their independent associations with IYCF and caregiving indicators.Results: The prevalence of feeding indicators varied. IYCF indicators, including ever breastfed (99%), exclusive breastfeeding (24-hour recall) (89%), and vegetable/fruit consumption (69%) were common. Problem areas were early initiation of breastfeeding (16%), colostrum feeding (67%), no pre-lacteal feeding (53%), timely introduction of complementary feeding (56%), minimum dietary diversity (49%) and animal-source food consumption (23%). Amongst caregiving indicators, access to 3+ children's books (7%), early stimulation and responsive caregiving (11%), and participation in early childhood education (27%) were of particular concern, while 64% had access to 2+ toys and 71% received adequate care. According to the Early Child Development Index score, only 38% of children were developmentally on track. Younger children from poor households, whose mothers were young, had not received antenatal visits and delivered at home were at higher risk of poor IYCF and caregiving practices.Conclusions: Suboptimal caregiving practices, inappropriate early breastfeeding practices, delayed introduction of complementary foods, inadequate dietary diversity and low animal-source food consumption are challenges in lowland Nepal. We call for urgent integrated nutrition and caregiving interventions, especially as interventions for child development are lacking in Nepal. [ABSTRACT FROM AUTHOR]

We conducted a comprehensive review of surgical simulation models used in robotic surgery education. We present an assessment of the validity and cost-effectiveness of virtual and augmented reality simulation, animal, cadaver and synthetic organ models. Face, content, construct, concurrent and predictive validity criteria were applied to each simulation model. There are six major commercial simulation machines available for robot-assisted surgery. The validity of virtual reality (VR) simulation curricula for psychomotor assessment and skill acquisition for the early phase of robotic surgery training has been demonstrated. The widespread adoption of VR simulation has been limited by the high cost of these machines. Live animal and cadavers have been the accepted standard for robotic surgical simulation since it began in the early 2000s. Our review found that there is a lack of evidence in the literature to support the use of animal and cadaver for robotic surgery training. The effectiveness of these models as a training tool is limited by logistical, ethical, financial and infection control issues. The latest evolution in synthetic organ model training for robotic surgery has been driven by new 3D-printing technology. Validated and cost-effective high-fidelity procedural models exist for robotic surgery training in urology. The development of synthetic models for the other specialties is not as mature. Expansion into multiple surgical disciplines and the widespread adoption of synthetic organ models for robotic simulation training will require the ability to engineer scalability for mass production. This would enable a transition in robotic surgical education where digital and synthetic organ models could be used in place of live animals and cadaver training to achieve robotic surgery competency. [ABSTRACT FROM AUTHOR]

There is an urgent need for population-based interventions to slow the growth of the diabetes epidemic in low-and middle-income countries. We tested the effectiveness of a population-based mHealth voice messaging intervention for T2DM prevention and control in rural Bangladesh through a cluster randomised controlled trial. mHealth improved knowledge and awareness about T2DM but there was no detectable effect on T2DM occurrence. We conducted mixed-methods research to understand this result. Exposure to messages was limited by technological faults, high frequency of mobile phone number changes, message fatigue and (mis)perceptions that messages were only for those who had T2DM. Persistent social norms, habits and desires made behaviour change challenging, and participants felt they would be more motivated by group discussions than mHealth messaging alone. Engagement with mHealth messages for T2DM prevention and control can be increased by (1) sending identifiable messages from a trusted source (2) using participatory design of mHealth messages to inform modelling of behaviours and increase relevance to the general population (3) enabling interactive messaging. mHealth messaging is likely to be most successful if implemented as part of a multi-sectoral, multi-component approach to address T2DM and non-communicable disease risk factors. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first COVID-19 case was reported in Wuhan, China, in December 2019. In March 2020, the World Health Organization (WHO) declared COVID-19 a global pandemic. The first COVID-19 case in Nepal was reported in January 2020 in a Nepalese man who had returned from Wuhan to Nepal. This study aims to evaluate the government of Nepal's (GoN) response to the COVID-19 pandemic and explore ways to prevent COVID-19 and other pandemic diseases in the future. As of May 2022, a total of 979,140 cases and 11,951 deaths associated with COVID-19 have been reported in Nepal. To prevent the spread of the virus, the GoN initiated various preventive and control measures, including lockdown strategies. The effects of COVID-19 are expected to persist for many years; the best strategies a resource-limited country such as Nepal can implement to control pandemic diseases such as COVID-19 in the pre-vaccine stage are to increase testing, tracing, and isolation capacity. [ABSTRACT FROM AUTHOR]

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Objectives: To assess the concordance between biopsy and radical prostatectomy (RP) specimens using the 2005 Gleason score (GS) and the International Society of Urological Pathology (ISUP) 2014/World Health Organization 2016 modified system, accounting for the introduction of transperineal biopsy and pre‐biopsy multiparametric magnetic resonance imaging (mpMRI). Patients and Methods: Between 2002 and 2019, we identified 2431 patients with paired biopsy and RP histopathology from a prospectively recorded and maintained prostate cancer database. Biopsy specimens were graded according to the 2005 GS or ISUP 2014 modified system, according to the year of diagnosis. Multivariable logistic regression analysis was conducted to retrospectively assess the impact of prostate‐specific antigen (PSA), PSA density, age, pre‐biopsy mpMRI, and biopsy method, on the rate of upgraded disease. The kappa coefficient was used to establish the degree of change in concordance between groups. Results: Overall, 24% of patients had upgraded disease and 8% of patients had downgraded disease when using the modified ISUP 2014 criteria. Agreement in the updated ISUP 2014 cohort was 68%, compared with 55% in the 2005 GS group, which was validated by a kappa coefficient that was good (k = 0.5 ± 0.4) and poor (k = 0.3 ± 0.1), respectively. In multivariable models, a change in grading system independently improved overall disease concordance (P = 0.02), and there were no other co‐segregated patient or pathological factors such as PSA, total number of cores, maximum cancer length, biopsy route or the use of mpMRI that impacted this finding. Conclusion: The 2014 ISUP modifed system improves overall concordance between biopsy and surgical specimens, and thus allows more accurate prognostication and management in high‐grade disease, independent of more extensive prostate sampling and the use of mpMRI. [ABSTRACT FROM AUTHOR]

Objective: To offer a quantitative risk–benefit analysis of two doses of SARS-CoV-2 vaccination among adolescents in England. Setting: England. Design: Following the risk–benefit analysis methodology carried out by the US Centers for Disease Control, we calculated historical rates of hospital admission, Intensive Care Unit admission and death for ascertained SARS-CoV-2 cases in children aged 12–17 in England. We then used these rates alongside a range of estimates for incidence of long COVID, vaccine efficacy and vaccine-induced myocarditis, to estimate hospital and Intensive Care Unit admissions, deaths and cases of long COVID over a period of 16 weeks under assumptions of high and low case incidence. Participants: All 12–17 year olds with a record of confirmed SARS-CoV-2 infection in England between 1 July 2020 and 31 March 2021 using national linked electronic health records, accessed through the British Heart Foundation Data Science Centre. Main outcome measures: Hospitalisations, Intensive Care Unit admissions, deaths and cases of long COVID averted by vaccinating all 12–17 year olds in England over a 16-week period under different estimates of future case incidence. Results: At high future case incidence of 1000/100,000 population/week over 16 weeks, vaccination could avert 4430 hospital admissions and 36 deaths over 16 weeks. At the low incidence of 50/100,000/week, vaccination could avert 70 hospital admissions and two deaths over 16 weeks. The benefit of vaccination in terms of hospitalisations in adolescents outweighs risks unless case rates are sustainably very low (below 30/100,000 teenagers/week). Benefit of vaccination exists at any case rate for the outcomes of death and long COVID, since neither have been associated with vaccination to date. Conclusions: Given the current (as at 15 September 2021) high case rates (680/100,000 population/week in 10–19 year olds) in England, our findings support vaccination of adolescents against SARS-CoV2. [ABSTRACT FROM AUTHOR]

Climate change is threatening the health of current and future generations of children. The most recent evidence from the Lancet Countdown: Tracking Progress on Health and Climate Change finds declining trends in yield potential of major crops, rising heatwave exposures, and increasing climate suitability for the transmission of infectious diseases, putting at risk the health and wellbeing of children around the world. However, if children are considered at the core of planning and implementation, the policy responses to climate change could yield enormous benefits for the health and wellbeing of children throughout their lives. Child health professionals have a role to play in ensuring this, with the beneficiaries of their involvement ranging from the individual child to the global community. The newly established Children in All Policies 2030 initiative will work with the Lancet Countdown to provide the evidence on the climate change responses necessary to protect and promote the health of children. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer is caused by genomic aberrations in normal epithelial cells, however clinical translation of findings from analyses of cancer cells alone has been very limited. A deeper understanding of the tumour microenvironment is needed to identify the key drivers of disease progression and reveal novel therapeutic opportunities.Results: In this study, the experimental enrichment of selected cell-types, the development of a Bayesian inference model for continuous differential transcript abundance, and multiplex immunohistochemistry permitted us to define the transcriptional landscape of the prostate cancer microenvironment along the disease progression axis. An important role of monocytes and macrophages in prostate cancer progression and disease recurrence was uncovered, supported by both transcriptional landscape findings and by differential tissue composition analyses. These findings were corroborated and validated by spatial analyses at the single-cell level using multiplex immunohistochemistry.Conclusions: This study advances our knowledge concerning the role of monocyte-derived recruitment in primary prostate cancer, and supports their key role in disease progression, patient survival and prostate microenvironment immune modulation. [ABSTRACT FROM AUTHOR]

PURPOSE: Androgen receptor (AR) signaling is important in prostate cancer progression, and therapies that target this pathway have been the mainstay of treatment for advanced disease for over 70 years. Tumors eventually progress despite castration through a number of well-characterized mechanisms; however, little is known about what determines the magnitude of response to short-term pathway inhibition. METHODS: We evaluated a novel combination of AR-targeting therapies (degarelix, abiraterone, and bicalutamide) and noted that the objective patient response to therapy was highly variable. To investigate what was driving treatment resistance in poorly responding patients, as a secondary outcome we comprehensively characterized pre- and post-treatment samples using both whole-genome and RNA sequencing. RESULTS: We find that resistance following short-term treatment differs molecularly from typical progressive castration-resistant disease, associated with transcriptional reprogramming, to a transitional epithelial-to-mesenchymal transition (EMT) phenotype rather than an upregulation of AR signaling. Unexpectedly, tolerance to therapy appears to be the default state, with treatment response correlating with the prevalence of tumor cells deficient for SNAI2 , a key regulator of EMT reprogramming. CONCLUSION: We show that EMT characterizes acutely resistant prostate tumors and that deletion of SNAI2 , a key transcriptional regulator of EMT, correlates with clinical response. [ABSTRACT FROM AUTHOR]

PURPOSE: Androgen receptor (AR) signaling is important in prostate cancer progression, and therapies that target this pathway have been the mainstay of treatment for advanced disease for over 70 years. Tumors eventually progress despite castration through a number of well-characterized mechanisms; however, little is known about what determines the magnitude of response to short-term pathway inhibition. METHODS: We evaluated a novel combination of AR-targeting therapies (degarelix, abiraterone, and bicalutamide) and noted that the objective patient response to therapy was highly variable. To investigate what was driving treatment resistance in poorly responding patients, as a secondary outcome we comprehensively characterized pre- and post-treatment samples using both whole-genome and RNA sequencing. RESULTS: We find that resistance following short-term treatment differs molecularly from typical progressive castration-resistant disease, associated with transcriptional reprogramming, to a transitional epithelial-to-mesenchymal transition (EMT) phenotype rather than an upregulation of AR signaling. Unexpectedly, tolerance to therapy appears to be the default state, with treatment response correlating with the prevalence of tumor cells deficient for SNAI2 , a key regulator of EMT reprogramming. CONCLUSION: We show that EMT characterizes acutely resistant prostate tumors and that deletion of SNAI2 , a key transcriptional regulator of EMT, correlates with clinical response. [ABSTRACT FROM AUTHOR]

WHO recommends participatory learning and action cycles with women's groups as a cost-effective strategy to reduce neonatal deaths. Coverage is a determinant of intervention effectiveness, but little is known about why cost-effectiveness estimates vary significantly. This article reanalyses primary cost data from six trials in India, Nepal, Bangladesh and Malawi to describe resource use, explore reasons for differences in costs and cost-effectiveness ratios, and model the cost of scale-up. Primary cost data were collated, and costing methods harmonized. Effectiveness was extracted from a meta-analysis and converted to neonatal life-years saved. Cost-effectiveness ratios were calculated from the provider perspective compared with current practice. Associations between unit costs and cost-effectiveness ratios with coverage, scale and intensity were explored. Scale-up costs and outcomes were modelled using local unit costs and the meta-analysis effect estimate for neonatal mortality. Results were expressed in 2016 international dollars. The average cost was $203 (range: $61-$537) per live birth. Start-up costs were large, and spending on staff was the main cost component. The cost per neonatal life-year saved ranged from $135 to $1627. The intervention was highly cost-effective when using income-based thresholds. Variation in cost-effectiveness across trials was strongly correlated with costs. Removing discounting of costs and life-years substantially reduced all cost-effectiveness ratios. The cost of rolling out the intervention to rural populations ranges from 1.2% to 6.3% of government health expenditure in the four countries. Our analyses demonstrate the challenges faced by economic evaluations of community-based interventions evaluated using a cluster randomized controlled trial design. Our results confirm that women's groups are a cost-effective and potentially affordable strategy for improving birth outcomes among rural populations. [ABSTRACT FROM AUTHOR]

Background: The mortality impact of pulse oximetry use during infant and childhood pneumonia management at the primary healthcare level in low-income countries is unknown. We sought to determine mortality outcomes of infants and children diagnosed and referred using clinical guidelines with or without pulse oximetry in Malawi.Methods and Findings: We conducted a data linkage study of prospective health facility and community case and mortality data. We matched prospectively collected community health worker (CHW) and health centre (HC) outpatient data to prospectively collected hospital and community-based mortality surveillance outcome data, including episodes followed up to and deaths within 30 days of pneumonia diagnosis amongst children 0-59 months old. All data were collected in Lilongwe and Mchinji districts, Malawi, from January 2012 to June 2014. We determined differences in mortality rates using <90% and <93% oxygen saturation (SpO2) thresholds and World Health Organization (WHO) and Malawi clinical guidelines for referral. We used unadjusted and adjusted (for age, sex, respiratory rate, and, in analyses of HC data only, Weight for Age Z-score [WAZ]) regression to account for interaction between SpO2 threshold (pulse oximetry) and clinical guidelines, clustering by child, and CHW or HC catchment area. We matched CHW and HC outpatient data to hospital inpatient records to explore roles of pulse oximetry and clinical guidelines on hospital attendance after referral. From 7,358 CHW and 6,546 HC pneumonia episodes, we linked 417 CHW and 695 HC pneumonia episodes to 30-day mortality outcomes: 16 (3.8%) CHW and 13 (1.9%) HC patients died. SpO2 thresholds of <90% and <93% identified 1 (6%) of the 16 CHW deaths that were unidentified by integrated community case management (iCCM) WHO referral protocol and 3 (23%) and 4 (31%) of the 13 HC deaths, respectively, that were unidentified by the integrated management of childhood illness (IMCI) WHO protocol. Malawi IMCI referral protocol, which differs from WHO protocol at the HC level and includes chest indrawing, identified all but one of these deaths. SpO2 < 90% predicted death independently of WHO danger signs compared with SpO2 ≥ 90%: HC Risk Ratio (RR), 9.37 (95% CI: 2.17-40.4, p = 0.003); CHW RR, 6.85 (1.15-40.9, p = 0.035). SpO2 < 93% was also predictive versus SpO2 ≥ 93% at HC level: RR, 6.68 (1.52-29.4, p = 0.012). Hospital referrals and outpatient episodes with referral decision indications were associated with mortality. A substantial proportion of those referred were not found admitted in the inpatients within 7 days of referral advice. All 12 deaths in 73 hospitalised children occurred within 24 hours of arrival in the hospital, which highlights delay in appropriate care seeking. The main limitation of our study was our ability to only match 6% of CHW episodes and 11% of HC episodes to mortality outcome data.Conclusions: Pulse oximetry identified fatal pneumonia episodes at HCs in Malawi that would otherwise have been missed by WHO referral guidelines alone. Our findings suggest that pulse oximetry could be beneficial in supplementing clinical signs to identify children with pneumonia at high risk of mortality in the outpatient setting in health centres for referral to a hospital for appropriate management. [ABSTRACT FROM AUTHOR]

Background: Engaging citizens and communities to make services accountable is vital to achieving health development goals. Community participation in health management committees can increase public accountability of health services. We conducted a cluster randomised controlled trial to test the impact of strengthened health management committees (HMCs) and community mobilisation through women's groups on institutional deliveries and deliveries by trained health workers in rural Nepal.Methods: The study was conducted in all Village Development Committee clusters in the hills district of Makwanpur (population of 420,500). In 21 intervention clusters, we conducted three-day workshops with HMCs to improve their capacity for planning and action and supported female community health volunteers to run women's groups. These groups met once a month and mobilised communities to address barriers to institutional delivery through participatory learning and action cycles. We compared this intervention with 22 control clusters. Prospective surveillance from October 2010 to the end of September 2012 captured complete data on 13,721 deliveries in intervention and control areas. Analysis was by intention to treat.Results: The women's group intervention was implemented as intended, but we were unable to support HMCs as planned because many did not meet regularly. The activities of community based organisations were systematically targeted at control clusters, which meant that there were no true 'control' clusters. 39% (5403) of deliveries were in health institutions and trained health workers attended most of them. There were no differences between trial arms in institutional delivery uptake (1.45, 0.76-2.78) or attendance by trained health workers (OR 1.43, 95% CI 0.74-2.74).Conclusions: The absence of a true counterfactual and inadequate coverage of the HMC strengthening intervention impedes our ability to draw conclusions. Further research is needed to test the effectiveness of strengthening public accountability mechanisms on increased utilisation of services at delivery.Trial Registration: Current Controlled Trials ISRCTN99834806. Date of registration:28/09/10. [ABSTRACT FROM AUTHOR]

Stereotactic body radiotherapy (SBRT) can delay escalation to systemic treatment in men with oligometastatic prostate cancer (PCa). However, large, prospective studies are still required to evaluate the efficacy of this approach in different patient groups. This is the interim analysis of a prospective, single institution study of men relapsing with up to five synchronous lesions following definitive local treatment for primary PCa. Our aim was to determine the proportion of patients not requiring treatment escalation following SBRT. In total, 199 patients were enrolled to receive fractionated SBRT (50 Gray in 10 fractions) to each visible lesion. Fourteen patients were castration resistant at enrolment. The proportion of patients not requiring treatment escalation 2 years following SBRT was 51.7% (95% CI: 44.1–59.3%). The median length of treatment escalation‐free survival over the entire follow‐up period was 27.1 months (95% CI; 21.8–29.4 months). Prior androgen deprivation therapy (ADT) predicted a significantly lower rate of freedom from treatment escalation at 2 years compared to no prior ADT (odds ratio = 0.21, 95% CI: 0.08–0.54, p = 0.001). There was no difference in the efficacy of SBRT when treating 4–5 vs. 1–3 initial lesions. A prostate‐specific antigen (PSA) decline was induced in 75% of patients, with PSA readings falling to an undetectable level in six patients. No late grade three toxicities were observed. These interim results suggest that SBRT can be used to treat up to five synchronous PCa oligometastases to delay treatment escalation. What's new? Metastasis‐directed therapy (MDT), involving surgery or stereotactic ablative radiotherapy, is a promising alternative treatment strategy for prostate cancer patients with metastatic disease. It remains unclear, however, which subsets of patients most benefit from MDT. Here, interim analysis of a large prospective trial involving fractionated stereotactic body radiotherapy (SBRT) for prostate cancer patients with up to five synchronous oligometastases shows that 2 years following SBRT, about half of patients did not require treatment escalation. In addition, nearly one‐quarter of patients had prostate‐specific antigen levels below baseline. The findings highlight the promise of SBRT for long‐term suppression of oligometastatic prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Recent data suggest that case fatality from severe acute malnutrition (SAM) in India may be lower than the 10%-20% estimated by the World Health Organization (WHO). A contemporary quantification of mortality and recovery from acute malnutrition in Indian community settings is essential to inform policy regarding the benefits of scaling up prevention and treatment programmes.Methods and Findings: We conducted a cohort study using data collected during a recently completed cluster-randomised controlled trial in 120 geographical clusters with a total population of 121,531 in rural Jharkhand and Odisha, eastern India. Children born between October 1, 2013, and February 10, 2015, and alive at 6 months of age were followed up at 9, 12, and 18 months. We measured the children's anthropometry and asked caregivers whether children had been referred to services for malnutrition in the past 3 months. We determined the incidence and prevalence of moderate acute malnutrition (MAM) and SAM, as well as mortality and recovery at each follow-up. We then used Cox-proportional models to estimate mortality hazard ratios (HRs) for MAM and SAM. In total, 2,869 children were eligible for follow-up at 6 months of age. We knew the vital status of 93% of children (2,669/2,869) at 18 months. There were 2,704 children-years of follow-up time. The incidence of MAM by weight-for-length z score (WLZ) and/or mid-upper arm circumference (MUAC) was 406 (1,098/2,704) per 1,000 children-years. The incidence of SAM by WLZ, MUAC, or oedema was 190 (513/2,704) per 1,000 children-years. There were 36 deaths: 12 among children with MAM and six among children with SAM. Case fatality rates were 1.1% (12/1,098) for MAM and 1.2% (6/513) for SAM. In total, 99% of all children with SAM at 6 months of age (227/230) were alive 3 months later, 40% (92/230) were still SAM, and 18% (41/230) had recovered (WLZ ≥ -2 standard deviation [SD]; MUAC ≥ 12.5; no oedema). The adjusted HRs using all anthropometric indicators were 1.43 (95% CI 0.53-3.87, p = 0.480) for MAM and 2.56 (95% CI 0.99-6.70, p = 0.052) for SAM. Both WLZ < -3 and MUAC ≥ 11.5 and < 12.5 were associated with increased mortality risk (HR: 3.33, 95% CI 1.23-8.99, p = 0.018 and HR: 3.87, 95% CI 1.63-9.18, p = 0.002, respectively). A key limitation of our analysis was missing WLZ or MUAC data at all time points for 2.5% of children, including for two of the 36 children who died.Conclusions: In rural eastern India, the incidence of acute malnutrition among children older than 6 months was high, but case fatality following SAM was 1.2%, much lower than the 10%-20% estimated by WHO. Case fatality rates below 6% have now been recorded in three other Indian studies. Community treatment using ready-to-use therapeutic food may not avert a substantial number of SAM-related deaths in children aged over 6 months, as mortality in this group is lower than expected. Our findings strengthen the case for prioritising prevention through known health, nutrition, and multisectoral interventions in the first 1,000 days of life, while ensuring access to treatment when prevention fails. [ABSTRACT FROM AUTHOR]

Participatory community-based women's group interventions have been successful in improving maternal and newborn survival. In rural Makwanpur, Nepal, exposure to these Participatory Learning and Action groups resulted in a thirty-percent reduction in neonatal mortality rate and significantly fewer maternal deaths. It is often theorised that participatory approaches are more likely to be sustained than top-down approaches, but this is rarely evaluated after the withdrawal of external support. We sought to understand how participatory learning and action (PLA) groups in Makwanpur fared after the supporting non-governmental organisation withdrew their support as well as factors affecting their sustainability. We used mixed methods, conducting a cross-sectional survey of 239 groups, thirty focus group discussions with group members and thirty key informant interviews within twelve–seventeen months after support was withdrawn. Eighty percent of groups were still active which suggests that PLA groups have a high chance of being sustained over time. Groups were more likely to be sustained if the group had local importance and members continued to acquire new knowledge. However, the participatory nature of the group and local embeddedness were not enough to sustain all groups. They also needed leadership capacity, a unifying activity such as a fund, and a strong belief in the value of their meeting to sustain. These key factors should be considered when seeking to enable sustainability of participatory interventions. [ABSTRACT FROM AUTHOR]

The Millennium Development Goals era achieved substantial improvements in the health of women and children. Yet progress was uneven and many women and children still suffer from preventable mortality and morbidity. The United Nations Secretary General's Global Strategy for Women's, Children's and Adolescents' Health (2016–2030) set out an ambitious 'survive, thrive and transform' agenda for countries as they accelerate progress towards the health-related Sustainable Development Goals. This review highlights aspects of 'survive, thrive and transform' that have had strong traction globally, namely quality of care and humanitarian settings for 'survive', early childhood development and adolescent health for 'thrive' and community engagement and a sustainable environment for 'transform'. [ABSTRACT FROM AUTHOR]

Participatory learning and action women's groups (PLA) have proven effective in reducing neonatal mortality in rural, high-mortality settings, but their impacts on women's agency in the household remain unknown. Cash transfer programmes have also long targeted female beneficiaries in the belief that this empowers women. Drawing on data from 1309 pregnant women in a four-arm cluster-randomised controlled trial in Nepal, we found little evidence for an impact of PLA alone or combined with unconditional food or cash transfers on women's agency in the household. Caution is advised before assuming PLA women's groups alone or with resource transfers necessarily empower women. [ABSTRACT FROM AUTHOR]

Objective: To characterise the pattern of late biochemical recurrence (BCR) in the largest contemporary cohort of patients with localised prostate cancer treated with radical prostatectomy (RP) in the active surveillance era. Patients and methods: Consecutive patients who underwent RP for localised prostate cancer between 2003 and 2017 were identified from a prospectively recorded, dedicated prostate cancer database. Patients who received neoadjuvant androgen‐deprivation therapy were excluded. These patients were categorised into the following groups: no BCR, BCR at <12 months (early), BCR at 12–60 months (intermediate), and BCR at >60 months (late), after RP. Clinicopathological characteristics were analysed using the Student's t‐test, Mann–Whitney U‐test, or chi‐squared test where appropriate. Multivariable binomial logistic regression models were used to assess predictors of BCR at various time‐points. Results: In all, 2312 patients were included in the final analysis with up to 12 years of follow‐up data. The average patient had clinically localised prostate cancer, an elevated PSA level, and International Society of Urological Pathology (ISUP) Grade Group 2 on biopsy. In all, 88.7% of patients had ISUP Grade Group ≥2 at RP. A subgroup of 446 patients had undetectable PSA levels at 5 years after RP; 11.7% of them progressed to experience BCR. In this subgroup, late recurrers had significantly higher‐grade tumours on ISUP and Gleason sum (P <0.001 and P = 0.001, respectively), higher rates of extraprostatic extension (P = 0.022), and larger tumour volumes (P = 0.032). Logistic regression showed that RP ISUP Grade Group was a significant predictor of BCR (odds ratio 2.14, 95% confidence interval 1.43–3.20; P <0.001). Conclusion: This study characterises the pattern of late BCR in the largest contemporary active surveillance era cohort. We have identified that RP ISUP Grade Group is a strong predictive indicator for late BCR. We also propose that timing of BCR resides on a continuum of risk and that the potential concept of dormant micrometastatic involvement requires further research and evaluation. [ABSTRACT FROM AUTHOR]

Models of household decision-making commonly focus on nuclear family members as primary decision-makers. If extended families shape the objectives and constraints of households, then neglecting the role of this network may lead to an incomplete understanding of health-seeking behaviour. Understanding the decision-making processes behind care-seeking may improve behaviour change interventions, better intervention targeting and support health-related development goals. This paper uses data from a cluster randomised trial of a participatory learning and action cycle (PLA) through women's groups, to assess the role of extended family networks as a determinant of gains in health knowledge and health practice. We estimate three models along a continuum of health-seeking behaviour: one that explores access to PLA groups as a conduit of knowledge, another measuring whether women's health knowledge improves after exposure to the PLA groups and a third exploring the determinants of their ability to act on knowledge gained. We find that, in this context, a larger network of family is not associated with women's likelihood of attending groups or acquiring new knowledge, but a larger network of husband's family is negatively associated with the ability to act on that knowledge during pregnancy and the postpartum period. [ABSTRACT FROM AUTHOR]

Background: In poor settings, where many births and neonatal deaths occur at home, prediction models of neonatal mortality in the general population can aid public-health policy-making. No such models are available in the international literature. We developed and validated a prediction model for neonatal mortality in the general population in India, Nepal and Bangladesh.Methods: Using data (49 632 live births, 1742 neonatal deaths) from rural and urban surveillance sites in South Asia, we developed regression models to predict the risk of neonatal death with characteristics known at (i) the start of pregnancy, (ii) start of delivery and (iii) 5 minutes post partum. We assessed the models' discriminative ability by the area under the receiver operating characteristic curve (AUC), using cross-validation between sites.Results: At the start of pregnancy, predictive ability was moderate {AUC 0.59 [95% confidence interval (CI) 0.58-0.61]} and predictors of neonatal death were low maternal education and economic status, short birth interval, primigravida, and young and advanced maternal age. At the start of delivery, predictive ability was considerably better [AUC 0.73 (95% CI 0.70-0.76)] and prematurity and multiple pregnancy were strong predictors of death. At 5 minutes post partum, predictive ability was good [AUC: 0.85 (95% CI 0.80-0.89)]; very strong predictors were multiple birth, prematurity and a poor condition of the infant at 5 minutes.Conclusions: We developed good performing prediction models for neonatal mortality. Neonatal deaths are highly concentrated in a small group of high-risk infants, even in poor settings in South Asia. Risk assessment, as supported by our models, can be used as a basis for improving community- and facility-based newborn care and prevention strategies in poor settings. [ABSTRACT FROM AUTHOR]

Background: Socioeconomic inequalities in neonatal mortality are substantial in many developing countries. Little is known about how to address this problem. Trials in Asia and Africa have shown strong impacts on neonatal mortality of a participatory learning and action intervention with women's groups. Whether this intervention also reduces mortality inequalities remains unknown. We describe the equity impact of this women's groups intervention on the neonatal mortality rate (NMR) across socioeconomic strata.Methods: We conducted a meta-analysis of all four participatory women's group interventions that were shown to be highly effective in cluster randomized trials in India, Nepal, Bangladesh and Malawi. We estimated intervention effects on NMR and health behaviours for lower and higher socioeconomic strata using random effects logistic regression analysis. Differences in effect between strata were tested.Results: Analysis of 69120 live births and 2505 neonatal deaths shows that the intervention strongly reduced the NMR in lower (50-63% reduction depending on the measure of socioeconomic position used) and higher (35-44%) socioeconomic strata. The intervention did not show evidence of 'elite-capture': among the most marginalized populations, the NMR in intervention areas was 63% lower [95% confidence interval (CI) 48-74%] than in control areas, compared with 35% (95% CI: 15-50%) lower among the less marginalized in the last trial year (P-value for difference between most/less marginalized: 0.009). The intervention strongly improved home care practices, with no systematic socioeconomic differences in effect.Conclusions: Participatory women's groups with high population coverage benefit the survival chances of newborns from all socioeconomic strata, and perhaps especially those born into the most deprived households. [ABSTRACT FROM AUTHOR]

Introduction Participatory postnatal women’s groups have been shown to have a significant impact on maternal and neonatal mortality in low-income countries. However, it is not clear whether this approach can be translated to high-income countries (HICs). We conducted a systematic review to answer the question: “Can postnatal women’s groups improve health outcomes for mothers and children in high-income countries?” Methods MEDLINE, EMBASE and Cochrane databases were searched for randomised controlled trials testing any group-based intervention during the postnatal period, in HICs. No limitations were applied to stated outcomes. Results Nine trials, including 3029 women, fulfilled the criteria. Group-based interventions, facilitated by health professionals, ranged from didactic to participant-led. Three trials addressed postnatal depression, one addressed physical activity, whilst the remainder looked at multiple health or social outcomes. Three trials reported a significant association between their intervention and at least one outcome measure. Study limitations included poor and inequitable intervention uptake, low participant retention, small sample size and incomplete intervention description. Discussion This review found limited and incompletely described evidence testing the use of postnatal group-based interventions to improve health outcomes in HICs. Promising results were reported when the obstacles of sample size and group attendance were overcome. Studies reporting positive impacts on primary outcomes reported higher attendance rates and involved a psychoeducational or cognitive behavioural component in their group approaches. Further research should design and evaluate implementation strategies, assess the use of lay support workers in community settings to improve attendance and retention, and examine the effect of the group environment on outcomes. [ABSTRACT FROM AUTHOR]

Background/objectives: Understanding of the patterns and predictors of intra-household food allocation could enable nutrition programmes to better target nutritionally vulnerable individuals. This study aims to characterise the status and determinants of intra-household food and nutrient allocation in Nepal.Subjects/methods: Pregnant women, their mothers-in-law and male household heads from Dhanusha and Mahottari districts in Nepal responded to 24-h dietary recalls, thrice repeated on non-consecutive days (n = 150 households; 1278 individual recalls). Intra-household inequity was measured using ratios between household members in food intakes (food shares); food-energy intake proportions ('food shares-to-energy shares', FS:ES); calorie-requirement proportions ('relative dietary energy adequacy ratios', RDEARs) and mean probability of adequacy for 11 micronutrients (MPA ratios). Hypothesised determinants were collected during the recalls, and their associations with the outcomes were tested using multivariable mixed-effects linear regression models.Results: Women's diets (pregnant women and mothers-in-law) consisted of larger FS:ES of starchy foods, pulses, fruits and vegetables than male household heads, whereas men had larger FS:ES of animal-source foods. Pregnant women had the lowest MPA (37%) followed by their mothers-in-law (52%), and male household heads (57%). RDEARs between pregnant women and household heads were 31% higher (log-RDEAR coeff=0.27 (95% CI 0.12, 0.42), P < 0.001) when pregnant women earned more or the same as their spouse, and log-MPA ratios between pregnant women and mothers-in-law were positively associated with household-level calorie intakes (coeff=0.43 (0.23, 0.63), P < 0.001, per 1000 kcal).Conclusions: Pregnant women receive inequitably lower shares of food and nutrients, but this could be improved by increasing pregnant women's cash earnings and household food security. [ABSTRACT FROM AUTHOR]

Few data exist on the prevalence of autism in low-income countries. We translated, adapted and tested the acceptability of a Nepali-language version of a screening tool for autism (Autism Quotient-10). Using this tool, we estimated autism prevalence in 4098 rural Nepali children aged 9-13 years. Fourteen children scored > 6 out of 10, indicative of elevated autistic symptomatology, of which 13 also screened positive for disability. If the AQ-10 screening tool is as sensitive and specific in the Nepali population as it is in the UK, this would yield an estimated true prevalence of 3 in 1000 (95% confidence interval 2-5 in 1000). Future research is required to validate this tool through in-depth assessments of high-scoring children. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to describe our initial Australian single surgeon experience with robotic‐assisted radical cystectomy (RARC) and intracorporeal urinary diversion (ICUD) and to compare the outcomes with open radical cystectomy (ORC). Methods: Between January 2014 and June 2016, consecutive patients diagnosed with muscle invasive and high‐risk non‐muscle invasive bladder cancer undergoing radical cystectomy were included. Treatment modalities included either RARC with ICUD or ORC. ICUD consisted of either intracorporeal ileal conduit or orthotopic neobladder formation. Prospectively collected perioperative and oncological outcomes were analysed. Results: Twenty‐six RARC and 13 ORC were performed. Median operating times were 362 and 240 min for RARC and ORC, respectively (P < 0.001). Estimated blood loss for RARC was 300 mL compared with 500 mL for ORC (P = 0.01). Post‐operative haemoglobin drop was less in the RARC cohort (20% versus 24%, P = 0.03). There was no statistical difference in overall 90‐day complication rates (81% versus 62%, P = 0.25) and 90‐day major complication rates (19% versus 23%, P = 0.67) between the RARC and ORC groups, respectively. Positive surgical margins for RARC were 4% and 8% for ORC (P = 1.0). Conclusion: Early results demonstrate that the safe introduction of RARC with ICUD in Australia is potentially feasible without compromising perioperative and oncological outcomes. Future randomized trial with larger numbers will be required for further analysis in the Australian setting. [ABSTRACT FROM AUTHOR]