Cost-utility analysis of operative versus non-operative treatment for colorectal liver metastases

Abstract Background Surgical resection of colorectal liver metastases (CRLMs) is the standard of care when possible, although this strategy has not been compared with non-operative interventions in controlled trials. Although survival outcomes are clear, the cost-effectiveness of surgery is not. This study aimed to estimate the cost-effectiveness of resection for CRLMs compared with non-operative treatment (palliative care including chemotherapy). Methods Operative and non-operative cohorts were identified from a prospectively maintained database. Patients in the operative cohort had a minimum of 10 years of follow-up. A model-based cost–utility analysis was conducted to quantify the mean cost and quality-adjusted life-years (QALYs) over a lifetime time horizon. The analysis was conducted from a healthcare provider perspective (UK National Health Service) in a secondary care (hospital) setting. Results Median survival was 41 and 21 months in the operative and non-operative cohorts respectively (P &amp;lt; 0·001). The operative strategy dominated non-operative treatments, being less costly (€22 200 versus €32 800) and more effective (4·017 versus 1·111 QALYs gained). The results of extensive sensitivity analysis showed that the operative strategy dominated non-operative treatment in every scenario. Conclusion Operative treatment of CRLMs yields greater survival than non-operative treatment, and is both more effective and less costly. </jats:sec

The ABCD of usability testing

We introduce a methodology for tracking and auditing feedback, errors and suggestions for software packages. This short paper describes how we innovate on the evaluation mechanism, introducing an (Antecedent, Barrier, Consequence and Development) ABCD form, embedded within an eParticipation platform to enable end users to easily report on any usability issues. This methodology will be utilised to improve the STEP cloud eParticipation platform (part of the current STEP Horizon2020 project http://step4youth.eu. The platform is currently being piloted in real life contexts, with the participation of public authorities that are integrating the eParticipation platform into their regular decision-making practices. The project is involving young people, through engagement and motivation strategies and giving them a voice in Environmental decision making at the local level. The pilot evaluation aims to demonstrate how open engagement needs to be embedded within public sector processes and the usability methodology reported here will help to identify the key barriers for wide scale deployment of the platform

Vitamin D deficiency in traumatic brain injury and its relationship with severity of injury and quality of life: a prospective, observational study

This single-centre prospective observational study aims to describe the prevalence of vitamin D deficiency (VDD) in the traumatic brain injury (TBI) population and identify any relationship between vitamin D and severity of head injury or quality of life. 124 TBI patients had serum vitamin D (25-OHD) levels measured at the local post-TBI endocrine screening clinic over 20 months. Quality of Life after Brain Injury (QOLIBRI) questionnaires were completed by the patient concurrently. A multivariate regressional analysis was performed, controlling for age, season, ethnicity, time since injury, TBI severity and gender. 34% (n=42) of the cohort were vitamin D deficient (25-OHD <25nmol/L) with a further 23% (n=29) having insufficient levels (25-OHD 25-50nmol/L). Vitamin D was significantly lower in severe TBI compared to mild TBI (n=95, p=0.03, CI 95% -23.60 to -1.21, mean effect size 12.40 nmol/L). There was a trend for self-reported quality of life to be better in patients with optimum vitamin D levels compared to patients with deficient vitamin D levels, controlling for severity of injury (n=81, p=0.05, CI 95% -0.07 to 21.27). This is the first study to identify a significant relationship between vitamin D levels and severity of head injury. Clinicians should actively screen for and treat VDD in head injured patients to reduce the risk of further morbidity such as osteomalacia and cardiovascular disease. Future research should establish the natural history of vitamin D levels following TBI to identify at which stage VDD develops and whether vitamin D replacement could have a beneficial effect on recovery and quality of life

Covert dissemination of carbapenemase-producing Klebsiella pneumoniae (KPC) in a successfully controlled outbreak: long and short-read whole-genome sequencing demonstrate multiple genetic modes of transmission

Background: Carbapenemase-producing Enterobacteriaceae (CPE), including KPC-producing Klebsiella pneumoniae (KPC-Kpn), are an increasing threat to patient safety. Objectives: To use WGS to investigate the extent and complexity of carbapenemase gene dissemination in a controlled KPC outbreak. Materials and methods: Enterobacteriaceae with reduced ertapenem susceptibility recovered from rectal screening swabs/clinical samples, during a 3 month KPC outbreak (2013–14), were investigated for carbapenemase production, antimicrobial susceptibility, variable-number-tandem-repeat profile and WGS [short-read (Illumina), long-read (MinION)]. Short-read sequences were used for MLST and plasmid/Tn4401 fingerprinting, and long-read sequence assemblies for plasmid identification. Phylogenetic analysis used IQTree followed by ClonalFrameML, and outbreak transmission dynamics were inferred using SCOTTI. Results: Twenty patients harboured KPC-positive isolates (6 infected, 14 colonized), and 23 distinct KPC-producing Enterobacteriaceae were identified. Four distinct KPC plasmids were characterized but of 20 KPC-Kpn (from six STs), 17 isolates shared a single pKpQIL-D2 KPC plasmid. All isolates had an identical transposon (Tn4401a), except one KPC-Kpn (ST661) with a single nucleotide variant. A sporadic case of KPC-Kpn (ST491) with Tn4401a-carrying pKpQILD2 plasmid was identified 10 months before the outbreak. This plasmid was later seen in two other species and other KPC-Kpn (ST14,ST661) including clonal spread of KPC-Kpn (ST661) from a symptomatic case to nine ward contacts. Conclusions: WGS of outbreak KPC isolates demonstrated blaKPC dissemination via horizontal transposition (Tn4401a), plasmid spread (pKpQIL-D2) and clonal spread (K. pneumoniae ST661). Despite rapid outbreak control, considerable dissemination of blaKPC still occurred among K. pneumoniae and other Enterobacteriaceae, emphasizing its high transmission potential and the need for enhanced control efforts

The screening and management of pituitary dysfunction following traumatic brain injury in adults: British Neurotrauma Group guidance.

Pituitary dysfunction is a recognised, but potentially underdiagnosed complication of traumatic brain injury (TBI). Post-traumatic hypopituitarism (PTHP) can have major consequences for patients physically, psychologically, emotionally and socially, leading to reduced quality of life, depression and poor rehabilitation outcome. However, studies on the incidence of PTHP have yielded highly variable findings. The risk factors and pathophysiology of this condition are also not yet fully understood. There is currently no national consensus for the screening and detection of PTHP in patients with TBI, with practice likely varying significantly between centres. In view of this, a guidance development group consisting of expert clinicians involved in the care of patients with TBI, including neurosurgeons, neurologists, neurointensivists and endocrinologists, was convened to formulate national guidance with the aim of facilitating consistency and uniformity in the care of patients with TBI, and ensuring timely detection or exclusion of PTHP where appropriate. This article summarises the current literature on PTHP, and sets out guidance for the screening and management of pituitary dysfunction in adult patients with TBI. It is hoped that future research will lead to more definitive recommendations in the form of guidelines

An Experimental Method for Stereolithic Mandible Fabrication and Image Preparation

Reproduction of anatomical structures by rapid prototyping has proven to be a valid adjunct for craniofacial surgery, providing alternative methods to produce prostheses and development of surgical guides. The aim of this study was to introduce a methodology to fabricate asymmetric human mandibles by rapid prototyping to be used in future studies for evaluating mandibular symmetries. Stereolithic models of human mandibles were produced with varying amounts of asymmetry in the condylar neck, ramus and body of the mandible by means of rapid prototyping. A method for production of the synthetic mandibles was defined. Model preparation, landmark description and development of the experimental model were described. A series of synthetic mandibles ranging in asymmetry were accurately produced from a scanned human mandible. A method for creating the asymmetries, fabricating, coating and landmarking the synthetic mandibles was formulated. A description for designing a reproducible experimental model for image acquisition was also outlined. Production of synthetic mandibles by stereolithic modeling is a viable method for creating skeletal experimental models with known amounts of asymmetry

A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota

Objective; Omega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22). Design A randomised, open-label, cross-over trial of 8 weeks’ treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week ‘washout’ period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing. Red blood cell (RBC) fatty acid analysis was performed by liquid chromatography tandem mass spectrometry. Results; Both omega-3 PUFA formulations induced similar changes in RBC fatty acid content, except that drinks were associated with a larger, and more prolonged, decrease in omega-6 PUFA arachidonic acid than the capsule intervention (p=0.02). There were no significant changes in α or β diversity, or phyla composition, associated with omega-3 PUFA supplementation. However, a reversible increased abundance of several genera, including Bifidobacterium, Roseburia and Lactobacillus was observed with one or both omega-3 PUFA interventions. Microbiome changes did not correlate with RBC omega-3 PUFA incorporation or development of omega-3 PUFA-induced diarrhoea. There were no treatment order effects. Conclusion; Omega-3 PUFA supplementation induces a reversible increase in several short-chain fatty acid-producing bacteria, independently of the method of administration. There is no simple relationship between the intestinal microbiome and systemic omega-3 PUFA exposure. Trial registration number; ISRCTN18662143

Automatic Hip Fracture Identification and Functional Subclassification with Deep Learning

Purpose: Hip fractures are a common cause of morbidity and mortality. Automatic identification and classification of hip fractures using deep learning may improve outcomes by reducing diagnostic errors and decreasing time to operation. Methods: Hip and pelvic radiographs from 1118 studies were reviewed and 3034 hips were labeled via bounding boxes and classified as normal, displaced femoral neck fracture, nondisplaced femoral neck fracture, intertrochanteric fracture, previous ORIF, or previous arthroplasty. A deep learning-based object detection model was trained to automate the placement of the bounding boxes. A Densely Connected Convolutional Neural Network (DenseNet) was trained on a subset of the bounding box images, and its performance evaluated on a held out test set and by comparison on a 100-image subset to two groups of human observers: fellowship-trained radiologists and orthopaedists, and senior residents in emergency medicine, radiology, and orthopaedics. Results: The binary accuracy for fracture of our model was 93.8% (95% CI, 91.3-95.8%), with sensitivity of 92.7% (95% CI, 88.7-95.6%), and specificity 95.0% (95% CI, 91.5-97.3%). Multiclass classification accuracy was 90.4% (95% CI, 87.4-92.9%). When compared to human observers, our model achieved at least expert-level classification under all conditions. Additionally, when the model was used as an aid, human performance improved, with aided resident performance approximating unaided fellowship-trained expert performance. Conclusions: Our deep learning model identified and classified hip fractures with at least expert-level accuracy, and when used as an aid improved human performance, with aided resident performance approximating that of unaided fellowship-trained attendings.Comment: Presented at Orthopaedic Research Society, Austin, TX, Feb 2, 2019, currently in submission for publicatio

Oncolytic reovirus as a combined antiviral and anti-tumour agent for the treatment of liver cancer

Objective: Oncolytic viruses (OVs) represent promising, proinflammatory cancer treatments. Here, we explored whether OV-induced innate immune responses could simultaneously inhibit HCV while suppressing hepatocellular carcinoma (HCC). Furthermore, we extended this exemplar to other models of virus-associated cancer. Design and results: Clinical grade oncolytic orthoreovirus (Reo) elicited innate immune activation within primary human liver tissue in the absence of cytotoxicity and independently of viral genome replication. As well as achieving therapy in preclinical models of HCC through the activation of innate degranulating immune cells, Reo-induced cytokine responses efficiently suppressed HCV replication both in vitro and in vivo. Furthermore, Reo-induced innate responses were also effective against models of HBV-associated HCC, as well as an alternative endogenous model of Epstein–Barr virus-associated lymphoma. Interestingly, Reo appeared superior to the majority of OVs in its ability to elicit innate inflammatory responses from primary liver tissue. Conclusions: We propose that Reo and other select proinflammatory OV may be used in the treatment of multiple cancers associated with oncogenic virus infections, simultaneously reducing both virus-associated oncogenic drive and tumour burden. In the case of HCV-associated HCC (HCV-HCC), Reo should be considered as an alternative agent to supplement and support current HCV-HCC therapies, particularly in those countries where access to new HCV antiviral treatments may be limited

Impaired Glucose Tolerance and Insulin Resistance Are Associated With Increased Adipose 11β-Hydroxysteroid Dehydrogenase Type 1 Expression and Elevated Hepatic 5α-Reductase Activity

OBJECTIVE—The precise molecular mechanisms contributing to the development of insulin resistance, impaired glucose tolerance (IGT), and type 2 diabetes are largely unknown. Altered endogenous glucocorticoid metabolism, including 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which generates active cortisol from cortisone, and 5α-reductase (5αR), which inactivates cortisol, has been implicated