The detection of patients at risk of gastrointestinal toxicity during pelvic radiotherapy by electronic nose and FAIMS : a pilot study

It is well known that the electronic nose can be used to identify differences between human health and disease for a range of disorders. We present a pilot study to investigate if the electronic nose and a newer technology, FAIMS (Field Asymmetric Ion Mobility Spectrometry), can be used to identify and help inform the treatment pathway for patients receiving pelvic radiotherapy, which frequently causes gastrointestinal side-effects, severe in some. From a larger group, 23 radiotherapy patients were selected where half had the highest levels of toxicity and the others the lowest. Stool samples were obtained before and four weeks after radiotherapy and the volatiles and gases emitted analysed by both methods; these chemicals are products of fermentation caused by gut microflora. Principal component analysis of the electronic nose data and wavelet transform followed by Fisher discriminant analysis of FAIMS data indicated that it was possible to separate patients after treatment by their toxicity levels. More interestingly, differences were also identified in their pre-treatment samples. We believe these patterns arise from differences in gut microflora where some combinations of bacteria result to give this olfactory signature. In the future our approach may result in a technique that will help identify patients at “high risk” even before radiation treatment is started

Development of machine learning support for reading whole body diffusion-weighted MRI (WB-MRI) in myeloma for the detection and quantification of the extent of disease before and after treatment (MALIMAR): protocol for a cross-sectional diagnostic test accuracy study.

INTRODUCTION: Whole-body MRI (WB-MRI) is recommended by the National Institute of Clinical Excellence as the first-line imaging tool for diagnosis of multiple myeloma. Reporting WB-MRI scans requires expertise to interpret and can be challenging for radiologists who need to meet rapid turn-around requirements. Automated computational tools based on machine learning (ML) could assist the radiologist in terms of sensitivity and reading speed and would facilitate improved accuracy, productivity and cost-effectiveness. The MALIMAR study aims to develop and validate a ML algorithm to increase the diagnostic accuracy and reading speed of radiological interpretation of WB-MRI compared with standard methods. METHODS AND ANALYSIS: This phase II/III imaging trial will perform retrospective analysis of previously obtained clinical radiology MRI scans and scans from healthy volunteers obtained prospectively to implement training and validation of an ML algorithm. The study will comprise three project phases using approximately 633 scans to (1) train the ML algorithm to identify active disease, (2) clinically validate the ML algorithm and (3) determine change in disease status following treatment via a quantification of burden of disease in patients with myeloma. Phase 1 will primarily train the ML algorithm to detect active myeloma against an expert assessment ('reference standard'). Phase 2 will use the ML output in the setting of radiology reader study to assess the difference in sensitivity when using ML-assisted reading or human-alone reading. Phase 3 will assess the agreement between experienced readers (with and without ML) and the reference standard in scoring both overall burden of disease before and after treatment, and response. ETHICS AND DISSEMINATION: MALIMAR has ethical approval from South Central-Oxford C Research Ethics Committee (REC Reference: 17/SC/0630). IRAS Project ID: 233501. CPMS Portfolio adoption (CPMS ID: 36766). Participants gave informed consent to participate in the study before taking part. MALIMAR is funded by National Institute for Healthcare Research Efficacy and Mechanism Evaluation funding (NIHR EME Project ID: 16/68/34). Findings will be made available through peer-reviewed publications and conference dissemination. TRIAL REGISTRATION NUMBER: NCT03574454

CATMoS: Collaborative Acute Toxicity Modeling Suite.

BACKGROUND: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditional rodent acute toxicity tests. In silico models built using existing data facilitate rapid acute toxicity predictions without using animals. OBJECTIVES: The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organized an international collaboration to develop in silico models for predicting acute oral toxicity based on five different end points: Lethal Dose 50 (LD50 value, U.S. Environmental Protection Agency hazard (four) categories, Globally Harmonized System for Classification and Labeling hazard (five) categories, very toxic chemicals [LD50 (LD50≤50mg/kg)], and nontoxic chemicals (LD50>2,000mg/kg). METHODS: An acute oral toxicity data inventory for 11,992 chemicals was compiled, split into training and evaluation sets, and made available to 35 participating international research groups that submitted a total of 139 predictive models. Predictions that fell within the applicability domains of the submitted models were evaluated using external validation sets. These were then combined into consensus models to leverage strengths of individual approaches. RESULTS: The resulting consensus predictions, which leverage the collective strengths of each individual model, form the Collaborative Acute Toxicity Modeling Suite (CATMoS). CATMoS demonstrated high performance in terms of accuracy and robustness when compared with in vivo results. DISCUSSION: CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for in vivo rat acute oral toxicity studies. CATMoS predictions for more than 800,000 chemicals have been made available via the National Toxicology Program's Integrated Chemical Environment tools and data sets (ice.ntp.niehs.nih.gov). The models are also implemented in a free, standalone, open-source tool, OPERA, which allows predictions of new and untested chemicals to be made. https://doi.org/10.1289/EHP8495

Releasing the self from the diagnostic straitjacket: Making meaning & creating understanding through dialogic autobiography

ABSTRACT To understand just one life, you have to swallow the world. (Rushdie, 2006, pg. 121) Mental health care in the Western world is situated firmly within a biomedical paradigm. Disorder is assumed, and symptoms are viewed as dis-abling deviations from normal. A disease-based model of care informs the treatment options that are most available and accessible. I argue that bio-medical care separates the person from her/his experiences, the self from the individual. I advocate for the addition of a non-biomedical approach to health education that enables a connection between the individual and her/his experiences; one that does not replace the self with a diagnostic profile. The creation of a meaningful understanding of that referred to as an illness experience, is recommended as essential to the process of moving away from illness and disability and towards wellness and ability. I ask two overarching questions: 1) How might the exploration of a personal narrative of the self facilitate the process of constructing a meaningful understanding of experience in one who has been diagnosed with what they are told is mental illness? 2) How might this process enable the individual to move beyond a state of compromised emotional wellbeing and perceived dis-ability to a state of overall wellness and perceived ability? Three separate but interrelated articles are included in this dissertation. My theoretical study examines the interrelatedness of meaningful learning, constructivism and Bakhtinian dialogism. I propose a theoretical framework for use in individualized approaches to meaning making for those who experience what they are told is mental illness. Critical autobiographical narrative, the methodology supporting this research, is used to facilitate a wide variety of vicarious experiences. Dialogue, self-analysis, and self-reflexivity are recommended as key to the creation of autobiographical research that is effective and evocative. My findings include an autobiographical account of the experience of being given electroshock, and a multi-voiced dialogue that includes two characters from Mary Shelley’s literary classic, ‘Frankenstein’. A self-reflective dialogue is woven throughout this section. Photographic images serve as metaphors to support dialogic musings. This research aims to evoke thoughts and feelings, and to contribute new conversation to the ongoing dialogue on the nature of the narrative self in those who experience compromised emotional wellbeing

Systematic review: the efficacy of nutritional interventions to counteract acute gastrointestinal toxicity during therapeutic pelvic radiotherapy

Background Radiotherapy-induced damage to noncancerous gastrointestinal mucosa has effects on secretory and absorptive functions and can interfere with normal gastrointestinal physiology. Nutrient absorption and digestion may be compromised. Dietary manipulation is an attractive option for the prevention and management of symptoms. Aim To synthesise the evidence for the use of elemental formula low- or modified-fat diets, fibre, lactose restriction and probiotics, prebiotics and synbiotics to protect the gastrointestinal tract during pelvic radiotherapy. Methods Four electronic databases were searched. Randomised controlled trials (RCT), controlled trials (CT) and case series in adult patients receiving radiotherapy for pelvic cancers employing nutritional interventions to reduce gastrointestinal toxicity were included. Methodological quality was assessed using a bespoke tool. Results Twenty-two original studies (2446 patients) were identified. Study quality was highly variable with only 37% scoring 10 points (maximum 17: bespoke scale). Few studies assessed compliance with the intervention. End-points varied and included symptom scales (IBDQ, CTC, Bristol Stool and RTOG). Evidence from RCTs was weak for elemental, low- or modified-fat, fibre and low-lactose interventions with 1/4, 3/4, 1/2, 0/1 trials respectively reporting favourable outcomes. Evidence for probiotics as prophylactic interventions was more promising (4/5 favourable), but dose, strains and methodologies varied. Conclusions There is insufficient high-grade evidence to recommend nutritional intervention during pelvic radiotherapy. Total replacement of diet with elemental formula may be appropriate in severe toxicity. Probiotics offer promise, but cannot be introduced into clinical practice without rigorous safety analysis, not least in immunocompromised patients. The methodological quality of nutritional intervention studies needs to be improved

A systematic review: Effectiveness of rectal emptying preparation in prostate cancer patients

While the importance of a consistent rectal volume during radiation therapy planning and treatment for patients receiving radiation therapy to the prostate is recognized, there is no clear guidance as to the most effective method. This review examines the evidence for the efficacy of rectal preparations. Eighteen papers were found where the primary aim was to investigate a rectal emptying intervention and included 5 different strategies. These included evacuation techniques, dietary interventions, laxatives, and enemas and were either investigated alone or in combination. There is no robust evidence to recommend one rectal emptying strategy over another. Further investigation in adequately powered clinical trials is advised. (C) 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.Biological, physical and clinical aspects of cancer treatment with ionising radiatio