Clonal Transitions and Phenotypic Evolution in Barrett's Esophagus.

BACKGROUND & AIMS: Barrett's esophagus (BE) is a risk factor for esophageal adenocarcinoma but our understanding of how it evolves is poorly understood. We investigated BE gland phenotype distribution, the clonal nature of phenotypic change, and how phenotypic diversity plays a role in progression. METHODS: Using immunohistochemistry and histology, we analyzed the distribution and the diversity of gland phenotype between and within biopsy specimens from patients with nondysplastic BE and those who had progressed to dysplasia or had developed postesophagectomy BE. Clonal relationships were determined by the presence of shared mutations between distinct gland types using laser capture microdissection sequencing of the mitochondrial genome. RESULTS: We identified 5 different gland phenotypes in a cohort of 51 nondysplastic patients where biopsy specimens were taken at the same anatomic site (1.0-2.0 cm superior to the gastroesophageal junction. Here, we observed the same number of glands with 1 and 2 phenotypes, but 3 phenotypes were rare. We showed a common ancestor between parietal cell-containing, mature gastric (oxyntocardiac) and goblet cell-containing, intestinal (specialized) gland phenotypes. Similarly, we have shown a clonal relationship between cardiac-type glands and specialized and mature intestinal glands. Using the Shannon diversity index as a marker of gland diversity, we observed significantly increased phenotypic diversity in patients with BE adjacent to dysplasia and predysplasia compared to nondysplastic BE and postesophagectomy BE, suggesting that diversity develops over time. CONCLUSIONS: We showed that the range of BE phenotypes represents an evolutionary process and that changes in gland diversity may play a role in progression. Furthermore, we showed a common ancestry between gastric and intestinal-type glands in BE.

Animation Supported Consent Before Elective Laparoscopic Cholecystectomy.

BACKGROUND: Patient understanding of surgical procedures is often incomplete at the time they are performed, invalidating consent, and exposing healthcare providers to complaints and claims of failure to inform. Remote consultations, language barriers and patient factors can hinder an effective consent pathway. New approaches are needed to support communication and shared decision-making. METHODS: Multi-language digital animations explaining laparoscopic cholecystectomy were introduced at The Royal London Hospital for patients who attended for elective surgery ( www.explainmyprocedure.com/lapchole ). Patients completed questionnaires on the day of their procedure both before and after introduction of the animations. We assessed patient-reported understanding of the procedure, its intended benefits, the possible risks, and alternatives to treatment in 72 consecutive patients, 37 before (no animation group) and after 35 after introducing the animations into the consent pathway (animation group). Patient understanding in the two groups was compared. RESULTS: The two groups were well matched in respect of age, sex and whether English was their first spoken language. The proportions of patients who reported they completely understood the procedure, its benefits, risks, and alternatives in the no animation group were 54, 57, 38 and 24% and in the animation group, 91, 91, 74 and 77%, respectively; p < 0.01 for each comparison. CONCLUSION: The integration of multi-language laparoscopic cholecystectomy video animations into the patient consent pathway was associated with substantial improvement in reported understanding of the procedure, benefits, risks, and alternatives to treatment. This approach can be applied across all surgical disciplines in a standardised manner in an era of accelerated elective work and remote consultations.

Microscopic gastrointestinal stromal tumours: a clinical and molecular study of 13 cases.

AIMS: Recent literature suggests that clinically silent, microscopic gastrointestinal stromal tumours (micro-GISTs) are common incidental findings. The aim of this study was to examine the histological, immunohistochemical and molecular characteristics of these tumours, which we have defined as measuring ≤20 mm, in order to determine whether the rate and spectrum of mutations are similar to those of clinically symptomatic gastrointestinal stromal tumours (GISTs). METHODS AND RESULTS: Thirteen micro-GISTs identified as incidental findings in patients undergoing management of concomitant disease were tested for KIT/PDGFRA mutations. Ten micro-GISTs (77%) were located in the stomach, two (15%) in the duodenum, and one (8%) in the rectum. The mean tumour size was 9.3 mm (range 2-19 mm). All tumours were well-circumscribed lesions showing a predominantly spindle-cell morphology and a very low mitotic rate. Twelve of 13 (92%) tumours carried mutations in either KIT (83%) or PDGFRA (17%), a rate higher than in other published series. A high mutation rate (80%) was also seen in lesions measuring ≤5 mm. CONCLUSIONS: Our results suggest that KIT/PDGFRA mutation is a very common early event in GIST development, that tumour size does not reliably predict the presence of mutation, and that one or more subsequent mutations are required for clinical manifestation.

Nurses: A Voice to Lead.

The International Council of Nurses celebrates nurses' contributions to the Sustainable Development Goals.

The nurse executive role in quality and high performing health services.

AIMS: To explore and identify the core elements of the nurse executive role and the contribution these posts make to health service organisations in terms of quality and performance. BACKGROUND: With the ongoing global reform of health services and, in particular, currently in Australia, this commentary paper explores the available evidence that explains and describes the role that nursing leaders can and do play at executive level in enabling quality services in high performing health-care organisations. EVALUATION: While the overall literature is limited in relation to the role and function of nurse executives, there are strong and recurrent themes indicating that nurses by virtue of their professional background and experience can provide effective and influential input to executive boards. Executive nurses are well positioned to influence and lead professional governance, quality improvement, service transformation and change and shared governance. CONCLUSION: At a time when the role of nursing executives may be questioned, the evidence supports the positive impact of highly skilled nursing executives in contributing to the implementation of effective health services. Successful health services should be engaging nurse executives who have the high level of expertise, education, the best leadership and management attributes to bring the art and science of nursing to produce outcomes for organisations. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse executives must remain alert to the ongoing challenges and potential questioning on the value that nurses can bring to an executive board. The framework of nursing executive influence and leadership through professional governance, quality improvement, service transformation and change and shared governance is one possible approach that nurse executives may wish to apply to articulate their contribution and value in remaining at the executive board table.

Principles in prevention of periodontal diseases: Consensus report of group 1 of the 11th European Workshop on Periodontology on effective prevention of periodontal and peri-implant diseases.

AIMS: In spite of the remarkable success of current preventive efforts, periodontitis remains one of the most prevalent diseases of mankind. The objective of this workshop was to review critical scientific evidence and develop recommendations to improve: (i) plaque control at the individual and population level (oral hygiene), (ii) control of risk factors, and (iii) delivery of preventive professional interventions. METHODS: Discussions were informed by four systematic reviews covering aspects of professional mechanical plaque control, behavioural change interventions to improve self-performed oral hygiene and to control risk factors, and assessment of the risk profile of the individual patient. Recommendations were developed and graded using a modification of the GRADE system using evidence from the systematic reviews and expert opinion. RESULTS: Key messages included: (i) an appropriate periodontal diagnosis is needed before submission of individuals to professional preventive measures and determines the selection of the type of preventive care; (ii) preventive measures are not sufficient for treatment of periodontitis; (iii) repeated and individualized oral hygiene instruction and professional mechanical plaque (and calculus) removal are important components of preventive programs; (iv) behavioural interventions to improve individual oral hygiene need to set specific Goals, incorporate Planning and Self monitoring (GPS approach); (v) brief interventions for risk factor control are key components of primary and secondary periodontal prevention; (vi) the Ask, Advise, Refer (AAR) approach is the minimum standard to be used in dental settings for all subjects consuming tobacco; (vii) validated periodontal risk assessment tools stratify patients in terms of risk of disease progression and tooth loss. CONCLUSIONS: Consensus was reached on specific recommendations for the public, individual dental patients and oral health care professionals with regard to best action to improve efficacy of primary and secondary preventive measures. Some have implications for public health officials, payers and educators.

Appreciative inquiry: a research tool for mental health services.

Appreciative inquiry (AI) provides an alternative approach to the inquisitional style of uncovering "what went wrong and who is at fault" to instead "what can be done to make things better," thus creating an environment that enables one to discover (investigate), dream (what could have been done instead), design (what needs to be done to bring about change), and deliver/ destiny (working with a whole of health and community approach to obtain the positive outcomes for mental health consumers). AI is transformational in nature and provides a way of viewing organizations from an enabling perspective. This article discusses the concept of AI, highlights opportunities and challenges that may be encountered, and explores the possibility of applying the AI concept to mental health research/inquiry.

Nurse turnover in New Zealand: costs and relationships with staffing practises and patient outcomes.

AIMS: To determine the rates and costs of nurse turnover, the relationships with staffing practises, and the impacts on outcomes for nurses and patients. BACKGROUND: In the context of nursing shortages, information on the rates and costs of nursing turnover can improve nursing staff management and quality of care. METHODS: Quantitative and qualitative data were collected prospectively for 12 months. A re-analysis of these data used descriptive statistics and correlational analysis techniques. RESULTS: The cost per registered nurse turnover represents half an average salary. The highest costs were related to temporary cover, followed by productivity loss. Both are associated with adverse patient events. Flexible management of nursing resources (staffing below budgeted levels and reliance on temporary cover), and a reliance on new graduates and international recruitment to replace nurses who left, contributed to turnover and costs. CONCLUSIONS: Nurse turnover is embedded in staffing levels and practises, with costs attributable to both. A culture of turnover was found that is inconsistent with nursing as a knowledge workforce. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers did not challenge flexible staffing practices and high turnover rates. Information on turnover and costs is needed to develop strategies that retain nurses as knowledge-based workers.

A systems perspective on nursing productivity.

PURPOSE: Recent New Zealand reports have identified the nursing workforce for its potential to make a significant contribution to increased productivity in health services. The purpose of this paper is to review critically the recent and current labour approaches to improve nursing productivity in New Zealand, in a context of international research and experience. DESIGN/METHODOLOGY/APPROACH: An examination of government documents regarding productivity, and a review of New Zealand and international literature and research on nursing productivity and its measurement form the basis of the paper. FINDINGS: It is found that productivity improvement strategies are influenced by theories of labour economics and scientific management that conceptualise a nurse as a labour unit and a cost to the organisation. Nursing productivity rose significantly with the health reforms of the 1990s that reduced nursing input costs but impacts on patient safety and nurses were negative. Current approaches to increasing nursing productivity, including the "productive ward" and reconfiguration of nursing teams, also draw on manufacturing innovations. Emerging thinking considers productivity in the context of the work environment and changing professional roles, and proposes reconceptualising the nurse as an intellectual asset to knowledge-intensive health organisations. PRACTICAL IMPLICATIONS: Strategies that take a systems approach to nursing productivity, that view nursing as a capital asset, that focus on the interface between nurse and working environment and measure patient and nurse outcomes are advocated. ORIGINALITY/VALUE: The paper shows that reframing nursing productivity brings into focus management strategies to raise productivity while protecting nursing and patient outcomes.

PD-L1 Testing in Urothelial Carcinoma: Analysis of a Series of 1401 Cases Using Both the 22C3 and SP142 Assays.

Immune checkpoint blockade (ICB) drugs are a novel, effective treatment for advanced urothelial carcinoma. Worldwide, several different ICB drugs are approved, each developed and clinically validated with a specific PD-L1 compound diagnostic assay. As a result, PD-L1 testing workflows in routine practice are complex: requiring multiple assays across two platforms, with each assay having a different method of interpretation. Our service tested 1,401 urothelial carcinoma cases for PD-L1 expression, using both the 22C3 PharmDx assay (required prior to Pembrolizumab therapy) and SP142 assay (required prior to Atezolizumab therapy). Of the 1,401 cases tested, 621 cases (44%) were tested with both the 22C3 PharmDx and SP142 assays, 492 cases (35%) with 22C3 PharmDx only, and 288 cases (21%) with SP142 only. Each assay was used and interpreted according to the manufacturer's guidelines. The rate of positivity we observed was 26% with the 22C3 assay and 31% with the SP142 assay, similar to the pre-licensing studies for both drugs. The discrepancy observed between the assays was 11%, which reinforces the requirement for utilisation of the correct assay for each agent, and limits potential cross-utility of assays. This aspect must be considered when setting up a PD-L1 testing strategy in laboratories where both Pembrolizumab and Atezolizumab are available for the treatment of urothelial carcinoma but also has broader implications for testing of other cancers where multiple ICB drugs and their respective assays are approved.

Acute haemorrhage rate in 28,000 Out-of-Hours CT heads.

OBJECTIVES: The aim of this paper is to assess the acute haemorrhage rate in patients who had CT head investigation out-of-hours with and without trauma and compare the rates of haemorrhage between warfarin and DOACs, at a busy teritary teaching hospital. METHODS: All CT heads performed between January 2008 and December 2019 were identified from the radiology information system (RIS) at Sheffield Teaching Hospitals (STH), with the requesting information being available from January 2015. The clinical information was assessed for the mention of trauma or anticoagulation, and the reports were categorised into acute and non-acute findings. RESULTS: Between 2008 and 2019 the number of scans increased by 63%, with scans performed out of hours increasing by 278%. Between 2015 and 2019, the incidence of acute ICH was similar over the 5-year period, averaging at 6.9% and ranging from 6.1 to 7.6%. The rate of detection of acute haemorrhage following trauma was greater in those not anticoagulated (6.8%), compared with patients on anticoagulants such as warfarin (5.2%) or DOACs (2.8%). CONCLUSIONS: Over 12 years, there has been a significant increase in the number of CT heads performed at STH. The rate of ICH has remained steady over the last 5 years indicating a justified increase in imaging demand. However, the incidence of ICH in patients prescribed DOACs is lower than the general population and those on warfarin. ADVANCES IN KNOWLEDGE: This finding in a large centre should prompt discussion of the risk of bleeding with DOACs in relation to CT head imaging guidelines.