Pancreatectomy is underused in NSW regions with low institutional surgical volumes: A population data linkage study

© 2017 AMPCo Pty Ltd. Produced with Elsevier B.V. All rights reserved. Objective: To examine differences in the proportions of people diagnosed with pancreatic cancer who underwent pancreatectomy, post-operative outcomes and 5-year survival in different New South Wales administrative health regions of residence. Design, setting and participants: Retrospective analysis of NSW data on pancreatic cancer incidence and surgery, 2005e2013. Main outcome measures: The proportion of newly diagnosed patients with pancreatic cancer who were resected in each region; 90-day post-operative mortality; one-year post-operative survival; 5-year post-diagnosis survival. Results: 14% of people diagnosed with pancreatic cancer during 2010e2013 (431 of 3064) underwent pancreatectomy, an average of 108 resections per year. After adjusting for age, sex and comorbidities, the proportion that underwent resection varied significantly between regions, ranging between 8% and 21% (P<0.001). Higher resection rates were not associated with higher post-operative 90-day mortality or lower one-year survival (unadjusted and risk-adjusted analyses). Higher resection rates were associated with higher 5-year post-diagnosis survival: the mean survival in regions with resection rates below 10% was 3.4%, compared with 7.2% in regions with rates greater than 15% (unadjusted and adjusted survival analyses; P<0.001). There was a positive association between regional resection rate and the pancreatectomy volume of hospitals during 2005e2009. An additional 32 people would be resected annually if resection rates in low rate regions were increased to the 80th percentile regional resection rate (18%). Conclusion: There is significant geographic variation in the proportion of people with pancreatic cancer undergoing pancreatectomy, and the 5-year survival rate is higher in regions where this proportion is higher

Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

Precision oncology in surgery: patient selection for operable pancreatic cancer

Objective: We aimed to define preoperative clinical and molecular characteristics that would allow better patient selection for operative resection. Background: Although we use molecular selection methods for systemic targeted therapies, these principles are not applied to surgical oncology. Improving patient selection is of vital importance for the operative treatment of pancreatic cancer (pancreatic ductal adenocarcinoma). Although surgery is the only chance of long-term survival, 80% still succumb to the disease and approximately 30% die within 1 year, often sooner than those that have unresected local disease. Method: In 3 independent pancreatic ductal adenocarcinoma cohorts (total participants = 1184) the relationship between aberrant expression of prometastatic proteins S100A2 and S100A4 and survival was assessed. A preoperative nomogram based on clinical variables available before surgery and expression of these proteins was constructed and compared to traditional measures, and a postoperative nomogram. Results: High expression of either S100A2 or S100A4 was independent poor prognostic factors in a training cohort of 518 participants. These results were validated in 2 independent patient cohorts (Glasgow, n = 198; Germany, n = 468). Aberrant biomarker expression stratified the cohorts into 3 distinct prognostic groups. A preoperative nomogram incorporating S100A2 and S100A4 expression predicted survival and nomograms derived using postoperative clinicopathological variables. Conclusions: Of those patients with a poor preoperative nomogram score, approximately 50% of patients died within a year of resection. Nomograms have the potential to improve selection for surgery and neoadjuvant therapy, avoiding surgery in aggressive disease, and justifying more extensive resections in biologically favorable disease

Development of a novel motivational interviewing (MI) informed peer-support intervention to support mothers to breastfeed for longer

Background: Many women in the UK stop breastfeeding before they would like to, and earlier than is recommended by the World Health Organization (WHO). Given the potential health benefits for mother and baby, new ways of supporting women to breastfeed for longer are required. The purpose of this study was to develop and characterise a novel Motivational Interviewing (MI) informed breastfeeding peer-support intervention. Methods: Qualitative interviews with health professionals and service providers (n=14), and focus groups with mothers (n=14), fathers (n=3), and breastfeeding peer-supporters (n=15) were carried out to understand experiences of breastfeeding peer-support and identify intervention options. Data were audio-recorded, transcribed, and analysed thematically. Consultation took place with a combined professional and lay Stakeholder Group (n=23). The Behaviour Change Wheel (BCW) guided intervention development process used the findings of the qualitative research and stakeholder consultation, alongside evidence from existing literature, to identify: the target behaviour to be changed; sources of this behaviour based on the Capability, Opportunity and Motivation (COM-B) model; intervention functions that could alter this behaviour; and; mode of delivery for the intervention. Behaviour change techniques included in the intervention were categorised using the Behaviour Change Technique Taxonomy Version 1 (BCTTv1). Results: Building knowledge, skills, confidence, and providing social support were perceived to be key functions of breastfeeding peer-support interventions that aim to decrease early discontinuation of breastfeeding. These features of breastfeeding peer-support mapped onto the BCW education, training, modelling and environmental restructuring intervention functions. Behaviour change techniques (BCTTv1) included social support, problem solving, and goal setting. The intervention included important inter-personal relational features (e.g. trust, honesty, kindness), and the BCTTv1 needed adaptation to incorporate this. Conclusions: The MI-informed breastfeeding peer-support intervention developed using this systematic and user-informed approach has a clear theoretical basis and well-described behaviour 3 change techniques. The process described could be useful in developing other complex interventions that incorporate peer-support and/or MI

Optimising antimicrobial use in humans – review of current evidence and an interdisciplinary consensus on key priorities for research

Data sharing: The data used to inform this policy paper can be made able, upon reasonable request from Esmita Charani, [email protected] © 2021 The Author(s). Addressing the silent pandemic of antimicrobial resistance (AMR) is a focus of the 2021 G7 meeting. A major driver of AMR and poor clinical outcomes is suboptimal antimicrobial use. Current research in AMR is inequitably focused on new drug development. To achieve antimicrobial security we need to balance AMR research efforts between development of new agents and strategies to preserve the efficacy and maximise effectiveness of existing agents. Combining a review of current evidence and multistage engagement with diverse international stakeholders (including those in healthcare, public health, research, patient advocacy and policy) we identified research priorities for optimising antimicrobial use in humans across four broad themes: policy and strategic planning; medicines management and prescribing systems; technology to optimise prescribing; and context, culture and behaviours. Sustainable progress depends on: developing economic and contextually appropriate interventions; facilitating better use of data and prescribing systems across healthcare settings; supporting appropriate and scalable technological innovation. Implementing this strategy for AMR research on the optimisation of antimicrobial use in humans could contribute to equitable global health security.Wellcome Trust; Economic and Social Research Council (ESRC); National Institute for Health Research ASPIRES project (Antibiotic use across Surgical Pathways: Investigating, Redesigning and Evaluating Systems) (https://www.imperial.ac.uk/arc/aspires/); National Institute for Health Research, UK Department of Health [HPRU-2012-10047] in partnership with Public Health England

Genomic insights into the origin of farming in the ancient Near East

We report genome-wide ancient DNA from 44 ancient Near Easterners ranging in time between ~12,000 and 1,400 BC, from Natufian hunter–gatherers to Bronze Age farmers. We show that the earliest populations of the Near East derived around half their ancestry from a ‘Basal Eurasian’ lineage that had little if any Neanderthal admixture and that separated from other non-African lineages before their separation from each other. The first farmers of the southern Levant (Israel and Jordan) and Zagros Mountains (Iran) were strongly genetically differentiated, and each descended from local hunter–gatherers. By the time of the Bronze Age, these two populations and Anatolian-related farmers had mixed with each other and with the hunter–gatherers of Europe to greatly reduce genetic differentiation. The impact of the Near Eastern farmers extended beyond the Near East: farmers related to those of Anatolia spread westward into Europe; farmers related to those of the Levant spread southward into East Africa; farmers related to those of Iran spread northward into the Eurasian steppe; and people related to both the early farmers of Iran and to the pastoralists of the Eurasian steppe spread eastward into South Asia

Biodiversity of the Deep-Sea Continental Margin Bordering the Gulf of Maine (NW Atlantic): Relationships among Sub-Regions and to Shelf Systems

Background: In contrast to the well-studied continental shelf region of the Gulf of Maine, fundamental questions regarding the diversity, distribution, and abundance of species living in deep-sea habitats along the adjacent continental margin remain unanswered. Lack of such knowledge precludes a greater understanding of the Gulf of Maine ecosystem and limits development of alternatives for conservation and management. Methodology/Principal Findings: We use data from the published literature, unpublished studies, museum records and online sources, to: (1) assess the current state of knowledge of species diversity in the deep-sea habitats adjacent to the Gulf of Maine (39–43uN, 63–71uW, 150–3000 m depth); (2) compare patterns of taxonomic diversity and distribution of megafaunal and macrofaunal species among six distinct sub-regions and to the continental shelf; and (3) estimate the amount of unknown diversity in the region. Known diversity for the deep-sea region is 1,671 species; most are narrowly distributed and known to occur within only one sub-region. The number of species varies by sub-region and is directly related to sampling effort occurring within each. Fishes, corals, decapod crustaceans, molluscs, and echinoderms are relatively well known, while most other taxonomic groups are poorly known. Taxonomic diversity decreases with increasing distance from the continental shelf and with changes in benthic topography. Low similarity in faunal composition suggests the deep-sea region harbours faunal communities distinct from those of the continental shelf. Non-parametric estimators of species richness suggest a minimum of 50% of the deep-sea species inventory remains to be discovered. Conclusions/Significance: The current state of knowledge of biodiversity in this deep-sea region is rudimentary. Our ability to answer questions is hampered by a lack of sufficient data for many taxonomic groups, which is constrained by sampling biases, life-history characteristics of target species, and the lack of trained taxonomists

Evidence-based Kernels: Fundamental Units of Behavioral Influence

This paper describes evidence-based kernels, fundamental units of behavioral influence that appear to underlie effective prevention and treatment for children, adults, and families. A kernel is a behavior–influence procedure shown through experimental analysis to affect a specific behavior and that is indivisible in the sense that removing any of its components would render it inert. Existing evidence shows that a variety of kernels can influence behavior in context, and some evidence suggests that frequent use or sufficient use of some kernels may produce longer lasting behavioral shifts. The analysis of kernels could contribute to an empirically based theory of behavioral influence, augment existing prevention or treatment efforts, facilitate the dissemination of effective prevention and treatment practices, clarify the active ingredients in existing interventions, and contribute to efficiently developing interventions that are more effective. Kernels involve one or more of the following mechanisms of behavior influence: reinforcement, altering antecedents, changing verbal relational responding, or changing physiological states directly. The paper describes 52 of these kernels, and details practical, theoretical, and research implications, including calling for a national database of kernels that influence human behavior

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe