Machine Learning Creates a Simple Endoscopic Classification System that Improves Dysplasia Detection in Barrett's Oesophagus amongst Non-expert Endoscopists

INTRODUCTION: Barrett’s oesophagus (BE) is a precursor to oesophageal adenocarcinoma (OAC). Endoscopic surveillance is performed to detect dysplasia arising in BE as it is likely to be amenable to curative treatment. At present, there are no guidelines on who should perform surveillance endoscopy in BE. Machine learning (ML) is a branch of artificial intelligence (AI) that generates simple rules, known as decision trees (DTs). We hypothesised that a DT generated from recognised expert endoscopists could be used to improve dysplasia detection in non-expert endoscopists. To our knowledge, ML has never been applied in this manner. METHODS: Video recordings were collected from patients with non-dysplastic (ND-BE) and dysplastic Barrett’s oesophagus (D-BE) undergoing high-definition endoscopy with i-Scan enhancement (PENTAX®). A strict protocol was used to record areas of interest after which a corresponding biopsy was taken to confirm the histological diagnosis. In a blinded manner, videos were shown to 3 experts who were asked to interpret them based on their mucosal and microvasculature patterns and presence of nodularity and ulceration as well as overall suspected diagnosis. Data generated were entered into the WEKA package to construct a DT for dysplasia prediction. Non-expert endoscopists (gastroenterology specialist registrars in training with variable experience and undergraduate medical students with no experience) were asked to score these same videos both before and after web-based training using the DT constructed from the expert opinion. Accuracy, sensitivity, and specificity values were calculated before and after training where p < 0 05 was statistically significant. RESULTS: Videos from 40 patients were collected including 12 both before and after acetic acid (ACA) application. Experts’ average accuracy for dysplasia prediction was 88%. When experts’ answers were entered into a DT, the resultant decision model had a 92% accuracy with a mean sensitivity and specificity of 97% and 88%, respectively. Addition of ACA did not improve dysplasia detection. Untrained medical students tended to have a high sensitivity but poor specificity as they “overcalled” normal areas. Gastroenterology trainees did the opposite with overall low sensitivity but high specificity. Detection improved significantly and accuracy rose in both groups after formal web-based training although it did it reach the accuracy generated by experts. For trainees, sensitivity rose significantly from 71% to 83% with minimal loss of specificity. Specificity rose sharply in students from 31% to 49% with no loss of sensitivity. CONCLUSION: ML is able to define rules learnt from expert opinion. These generate a simple algorithm to accurately predict dysplasia. Once taught to non-experts, the algorithm significantly improves their rate of dysplasia detection. This opens the door to standardised training and assessment of competence for those who perform endoscopy in BE. It may shorten the learning curve and might also be used to compare competence of trainees with recognised experts as part of their accreditation process

Health care costs, utilization and patterns of care following Lyme disease

BACKGROUND:Lyme disease is the most frequently reported vector borne infection in the United States. The Centers for Disease Control have estimated that approximately 10% to 20% of individuals may experience Post-Treatment Lyme Disease Syndrome - a set of symptoms including fatigue, musculoskeletal pain, and neurocognitive complaints that persist after initial antibiotic treatment of Lyme disease. Little is known about the impact of Lyme disease or post-treatment Lyme disease symptoms (PTLDS) on health care costs and utilization in the United States. OBJECTIVES:1) to examine the impact of Lyme disease on health care costs and utilization, 2) to understand the relationship between Lyme disease and the probability of developing PTLDS, 3) to understand how PTLDS may impact health care costs and utilization. METHODS:This study utilizes retrospective data on medical claims and member enrollment for persons aged 0-64 years who were enrolled in commercial health insurance plans in the United States between 2006-2010. 52,795 individuals treated for Lyme disease were compared to 263,975 matched controls with no evidence of Lyme disease exposure. RESULTS:Lyme disease is associated with $2,968 higher total health care costs (95$3,798 higher total health care costs (95% CI: 3,542-4,055, p<.001) and 66% more outpatient visits (95% CI: 64%-69%, p<.001) over a 12-month period, relative to those with no PTLDS-related diagnoses. CONCLUSIONS:Lyme disease is associated with increased costs above what would be expected for an easy to treat infection. The presence of PTLDS-related diagnoses after treatment is associated with significant health care costs and utilization

Whether weather matters: Evidence of association between in utero meteorological exposures and foetal growth among Indigenous and non-Indigenous mothers in rural Uganda

Pregnancy and birth outcomes have been found to be sensitive to meteorological variation, yet few studies explore this relationship in sub-Saharan Africa where infant mortality rates are the highest in the world. We address this research gap by examining the association between meteorological factors and birth weight in a rural population in southwestern Uganda. Our study included hospital birth records (n = 3197) from 2012 to 2015, for which we extracted meteorological exposure data for the three trimesters preceding each birth. We used linear regression, controlling for key covariates, to estimate the timing, strength, and direction of meteorological effects on birth weight. Our results indicated that precipitation during the third trimester had a positive association with birth weight, with more frequent days of precipitation associated with higher birth weight: we observed a 3.1g (95% CI: 1.0–5.3g) increase in birth weight per additional day of exposure to rainfall over 5mm. Increases in average daily temperature during the third trimester were also associated with birth weight, with an increase of 41.8g (95% CI: 0.6–82.9g) per additional degree Celsius. When the sample was stratified by season of birth, only infants born between June and November experienced a significant associated between meteorological exposures and birth weight. The association of meteorological variation with foetal growth seemed to differ by ethnicity; effect sizes of meteorological were greater among an Indigenous subset of the population, in particular for variation in temperature. Effects in all populations in this study are higher than estimates of the African continental average, highlighting the heterogeneity in the vulnerability of infant health to meteorological variation in different contexts. Our results indicate that while there is an association between meteorological variation and birth weight, the magnitude of these associations may vary across ethnic groups with differential socioeconomic resources, with implications for interventions to reduce these gradients and offset the health impacts predicted under climate change

Aerosolized Human Extracellular Superoxide Dismutase Prevents Hyperoxia-Induced Lung Injury

An important issue in critical care medicine is the identification of ways to protect the lungs from oxygen toxicity and reduce systemic oxidative stress in conditions requiring mechanical ventilation and high levels of oxygen. One way to prevent oxygen toxicity is to augment antioxidant enzyme activity in the respiratory system. The current study investigated the ability of aerosolized extracellular superoxide dismutase (EC-SOD) to protect the lungs from hyperoxic injury. Recombinant human EC-SOD (rhEC-SOD) was produced from a synthetic cassette constructed in the methylotrophic yeast Pichia pastoris. Female CD-1 mice were exposed in hyperoxia (FiO2>95%) to induce lung injury. The therapeutic effects of EC-SOD and copper-zinc SOD (CuZn-SOD) via an aerosol delivery system for lung injury and systemic oxidative stress at 24, 48, 72 and 96 h of hyperoxia were measured by bronchoalveolar lavage, wet/dry ratio, lung histology, and 8-oxo-2′-deoxyguanosine (8-oxo-dG) in lung and liver tissues. After exposure to hyperoxia, the wet/dry weight ratio remained stable before day 2 but increased significantly after day 3. The levels of oxidative biomarker 8-oxo-dG in the lung and liver were significantly decreased on day 2 (P<0.01) but the marker in the liver increased abruptly after day 3 of hyperoxia when the mortality increased. Treatment with aerosolized rhEC-SOD increased the survival rate at day 3 under hyperoxia to 95.8%, which was significantly higher than that of the control group (57.1%), albumin treated group (33.3%), and CuZn-SOD treated group (75%). The protective effects of EC-SOD against hyperoxia were further confirmed by reduced lung edema and systemic oxidative stress. Aerosolized EC-SOD protected mice against oxygen toxicity and reduced mortality in a hyperoxic model. The results encourage the use of an aerosol therapy with EC-SOD in intensive care units to reduce oxidative injury in patients with severe hypoxemic respiratory failure, including acute respiratory distress syndrome (ARDS)

The development, design, testing, refinement, simulation and application of an evaluation framework for communities of practice and social-professional networks

Background. Communities of practice and social-professional networks are generally considered to enhance workplace experience and enable organizational success. However, despite the remarkable growth in interest in the role of collaborating structures in a range of industries, there is a paucity of empirical research to support this view. Nor is there a convincing model for their systematic evaluation, despite the significant potential benefits in answering the core question: how well do groups of professionals work together and how could they be organised to work together more effectively? This research project will produce a rigorous evaluation methodology and deliver supporting tools for the benefit of researchers, policymakers, practitioners and consumers within the health system and other sectors. Given the prevalence and importance of communities of practice and social networks, and the extent of investments in them, this project represents a scientific innovation of national and international significance. Methods and design. Working in four conceptual phases the project will employ a combination of qualitative and quantitative methods to develop, design, field-test, refine and finalise an evaluation framework. Once available the framework will be used to evaluate simulated, and then later existing, health care communities of practice and social-professional networks to assess their effectiveness in achieving desired outcomes. Peak stakeholder groups have agreed to involve a wide range of members and participant organisations, and will facilitate access to various policy, managerial and clinical networks. Discussion. Given its scope and size, the project represents a valuable opportunity to achieve breakthroughs at two levels; firstly, by introducing novel and innovative aims and methods into the social research process and, secondly, through the resulting evaluation framework and tools. We anticipate valuable outcomes in the improved understanding of organisational performance and delivery of care. The project's wider appeal lies in transferring this understanding to other health jurisdictions and to other industries and sectors, both nationally and internationally. This means not merely publishing the results, but contextually interpreting them, and translating them to advance the knowledge base and enable widespread institutional and organisational application

Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer

Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal diversity of tumours changes during metastasis and progression to lethality is poorly understood. Here we reveal the precise direction of metastatic spread across four lethal prostate cancer patients using whole-genome and ultra-deep targeted sequencing of longitudinally collected primary and metastatic tumours. We find one case of metastatic spread to the surgical bed causing local recurrence, and another case of cross-metastatic site seeding combining with dynamic remoulding of subclonal mixtures in response to therapy. By ultra-deep sequencing end-stage blood, we detect both metastatic and primary tumour clones, even years after removal of the prostate. Analysis of mutations associated with metastasis reveals an enrichment of TP53 mutations, and additional sequencing of metastases from 19 patients demonstrates that acquisition of TP53 mutations is linked with the expansion of subclones with metastatic potential which we can detect in the blood.M.K.H.H. was supported by scholarships from the National Health and Medical Research Council, Australia, University of Melbourne (Melville Hughes Scholarship) and the Royal Australasian College of Surgeons (Foundation of Surgery Catherine Marie Enright Kelly and ANZ Journal of Surgery Research Scholarships). N.M.C. is the recipient of a David Bickart Clinician Research Fellowship from the Faculty of Medicine, Dentistry and Health Sciences at the University of Melbourne. M.K. is supported by the Carlo Vaccari Scholarship and APCR.This work is supported by NHMRC project grants 1024081 (N.M.C., J.S.P., A.J.C. and C.M.H.) and 1047581 (C.M.H., G.M., I.H., J.S.P., A.J.C., N.M.C.), as well as a federal grant from the Australian Department of Health and Aging to the Epworth Cancer Centre, Epworth Hospital (A.J.C., N.M.C., C.M.H.). In carrying out this research, we received funding and support from the Victoria Research Laboratory of National ICT Australia (NICTA) and the University of Melbourne, Australia. NICTA is funded by the Australian Government through the Department of Communications and the Australian Research Council through the ICT Centre of Excellence Programme. K.P. is supported by an Addenbrooke’s Charitable Trust Clinical Research Training Fellowship. We thank the Cambridge Urological Biorepository, the Human Research Tissue Bank and Biomedical Research Centre for tissue processing and storage. The Cambridge Urological Biorepostory is supported by the Cambridge Cancer Centre and Human Research Tissue Bank is supported by the NIHR Cambridge Biomedical Research Centre. Research performed at Los Alamos National Laboratory was carried out under the auspices of the National Nuclear Security Administration of the US Department of Energy. We thank the Cambridge Institute Genomics Core and the Australian Genomics Research Facility for their support with this work. This work was supported by funding from Cancer Research UK C14303/A17197

E-NTPDases in human airways: Regulation and relevance for chronic lung diseases

Chronic obstructive lung diseases are characterized by the inability to prevent bacterial infection and a gradual loss of lung function caused by recurrent inflammatory responses. In the past decade, numerous studies have demonstrated the importance of nucleotide-mediated bacterial clearance. Their interaction with P2 receptors on airway epithelia provides a rapid ‘on-and-off’ signal stimulating mucus secretion, cilia beating activity and surface hydration. On the other hand, abnormally high ATP levels resulting from damaged epithelia and bacterial lysis may cause lung edema and exacerbate inflammatory responses. Airway ATP concentrations are regulated by ecto nucleoside triphosphate diphosphohydrolases (E-NTPDases) which are expressed on the mucosal surface and catalyze the sequential dephosphorylation of nucleoside triphosphates to nucleoside monophosphates (ATP → ADP → AMP). The common bacterial product, Pseudomonas aeruginosa lipopolysaccharide (LPS), induces an acute reduction in azide-sensitive E-NTPDase activities, followed by a sustained increase in activity as well as NTPDase 1 and NTPDase 3 expression. Accordingly, chronic lung diseases, including cystic fibrosis (CF) and primary ciliary dyskinesia, are characterized by higher rates of nucleotide elimination, azide-sensitive E-NTPDase activities and expression. This review integrates the biphasic regulation of airway E-NTPDases with the function of purine signaling in lung diseases. During acute insults, a transient reduction in E-NTPDase activities may be beneficial to stimulate ATP-mediated bacterial clearance. In chronic lung diseases, elevating E-NTPDase activities may represent an attempt to prevent P2 receptor desensitization and nucleotide-mediated lung damage

The personal and contextual contributors to school belongingness among primary school students

School belongingness has gained currency among educators and school health professionals as an important determinant of adolescent health. The current cross-sectional study presents the 15 most significant personal and contextual factors that collectively explain 66.4% (two-thirds) of the variability in 12-year old students' perceptions of belongingness in primary school. The study is part of a larger longitudinal study investigating the factors associated with student adjustment in the transition from primary to secondary school. The study found that girls and students with disabilities had higher school belongingness scores than boys, and their typically developing counterparts respectively; and explained 2.5% of the variability in school belongingness. The majority (47.1% out of 66.4%) of the variability in school belongingness was explained by student personal factors, such as social acceptance, physical appearance competence, coping skills, and social affiliation motivation; followed by parental expectations (3% out of 66.4%), and school-based factors (13.9% out of 66.4%) such as, classroom involvement, task-goal structure, autonomy provision, cultural pluralism, and absence of bullying. Each of the identified contributors of primary school belongingness can be shaped through interventions, system changes, or policy reforms