Starting a career in research nursing during a global pandemic.

In the spring of 2020, two nurses (KR and AJ) commenced their research nurse careers amid the SARS-Cov-2 (COVID-19) global pandemic. This reflective article discusses their experiences of beginning a clinical research nursing career, presented as a case study of their learning journey, rather than detailing the randomised controlled trial they delivered via GP practices. The main study compared standard care to nurse-led management of irritable bowel syndrome, the details of which will be published separately. The article identifies three overarching concepts: 'Green as grass, keen as mustard', 'Spires and steeples', and 'Down the rabbit hole'. The article offers insight from the two nurses for other professionals contemplating a career in research.

The Role of the Human Gut Microbiome in Inflammatory Bowel Disease and Radiation Enteropathy.

The human gut microbiome plays a key role in regulating host physiology. In a stable state, both the microbiota and the gut work synergistically. The overall homeostasis of the intestinal flora can be affected by multiple factors, including disease states and the treatments given for those diseases. In this review, we examine the relatively well-characterised abnormalities that develop in the microbiome in idiopathic inflammatory bowel disease, and compare and contrast them to those that are found in radiation enteropathy. We discuss how these changes may exert their effects at a molecular level, and the possible role of manipulating the microbiome through the use of a variety of therapies to reduce the severity of the underlying condition.

Patient perspectives on key symptoms and preferences for follow-up after upper gastro-intestinal cancer surgery.

PURPOSE: Long-lasting symptoms and reductions in quality of life are common after oesophago-gastric surgery. Post-operative follow-up has traditionally focussed on tumour recurrence and survival, but there is a growing need to also identify and treat functional sequelae to improve patients' recovery. METHODS: An electronic survey was circulated via a British national charity for patients undergoing oesophago-gastric surgery and their families. Patients were asked about post-operative symptoms they deemed important to their quality of life, as well as satisfaction and preferences for post-operative follow-up. Differences between satisfied and dissatisfied patients with reference to follow-up were assessed. RESULTS: Among 362 respondents with a median follow-up of 58 months since surgery (range 3-412), 36 different symptoms were reported as being important to recovery and quality of life after surgery, with a median of 13 symptoms per patient. Most (84%) respondents indicated satisfaction with follow-up. Satisfied patients were more likely to have received longer follow-up (5-year or longer follow-up 60% among satisfied patients vs 27% among unsatisfied, p < 0.001). These were also less likely to have seen a dietitian as part of routine follow-up (37% vs 58%, p = 0.005). CONCLUSION: This patient survey highlights preferences regarding follow-up after oesophago-gastrectomy. Longer follow-up and dietician involvement improved patient satisfaction. Patients reported being concerned by a large number of gastrointestinal and non-gastrointestinal symptoms, highlighting the need for multidisciplinary input and a consensus on how to manage the poly-symptomatic patient.

Impact of Pelvic Radiation Therapy for Prostate Cancer on Global Metabolic Profiles and Microbiota-Driven Gastrointestinal Late Side Effects: A Longitudinal Observational Study.

PURPOSE: Radiation therapy to the prostate and pelvic lymph nodes (PLNRT) is part of the curative treatment of high-risk prostate cancer. Yet, the broader influence of radiation therapy on patient physiology is poorly understood. We conducted comprehensive global metabolomic profiling of urine, plasma, and stools sampled from patients undergoing PLNRT for high-risk prostate cancer. METHODS AND MATERIALS: Samples were taken from 32 patients at 6 timepoints: baseline, 2 to 3 and 4 to 5 weeks of PLNRT; and 3, 6, and 12 months after PLNRT. We characterized the global metabolome of urine and plasma using 1H nuclear magnetic resonance spectroscopy and ultraperformance liquid chromatography-mass spectrometry, and of stools with nuclear magnetic resonance. Linear mixed-effects modeling was used to investigate metabolic changes between timepoints for each biofluid and assay and determine metabolites of interest. RESULTS: Metabolites in urine, plasma and stools changed significantly after PLNRT initiation. Metabolic profiles did not return to baseline up to 1 year post-PLNRT in any biofluid. Molecules associated with cardiovascular risk were increased in plasma. Pre-PLNRT fecal butyrate levels directly associated with increasing gastrointestinal side effects, as did a sharper fall in those levels during and up to 1 year postradiation therapy, mirroring our previous results with metataxonomics. CONCLUSIONS: We showed for the first time that an overall metabolic effect is observed in patients undergoing PLNRT up to 1 year posttreatment. These metabolic changes may effect on long-term morbidity after treatment, which warrants further investigation.

Developing advanced clinical practice skills in gastrointestinal consequences of cancer treatment.

This article explores the transition from a clinical nurse specialist (CNS) towards developing advanced clinical practice skills within a gastrointestinal consequences of cancer clinic. It presents data on the first 50 patients assessed by the CNS from a prospective service evaluation, demonstrating how this informed the nurse's future learning. There is high demand for advanced clinical practice skills to address unmet health needs and improve the quality, efficiency, and sustainability of healthcare services. However, a literature review found no literature on developing advanced clinical practice skills in this setting. Emerging themes from the service evaluation focused on barriers and enablers, ongoing support, organisational commitment and working in a multidisciplinary team. Blended learning provided both structured and opportunistic learning, embedding both formal and tacit knowledge, as roles require increasing flexibility. Clinical supervision and reflective practice were key in maintaining professional and peer support.

Challenging current views on bile acid diarrhoea and malabsorption.

BACKGROUND: In 2012, the National Institute for Health and Care Excellence (NICE) assessed guidance (DG7) on the use of tauroselcholic (75selenium) acid (also known as SeHCAT) for the investigation of diarrhoea due to bile acid malabsorption (BAM) in patients with IBS-D and in patients with Crohn's disease who have not had an ileal resection. NICE concluded that tauroselcholic (75selenium) acid was recommended for use in research only. NICE will be reviewing the decision to update the guidance for tauroselcholic (75selenium) acid, for these populations, in March 2017. AIM: Our aim is to summarise advances in BAM, also known as bile acid diarrhoea (BAD), and encourage clinicians to re-evaluate their understanding of this disorder. APPROACH: We review the prevalence, diagnosis and treatment of BAD/BAM. We describe the new evidence available since the original NICE review in 2012, and discuss the economic issues associated with failure to diagnose or to treat BAD/BAM accurately. EVIDENCE UPDATE: There is new and compelling evidence available since DG7, which shows that tauroselcholic (75selenium) acid scanning is a powerful tool in the diagnosis of BAD/BAM. We summarise published prevalence data (approximately 1% prevalence in the UK, as suggested by clinical practice diagnosis rates), and highlight that the true prevalence of BAD/BAM could be far greater than this. CONCLUSION: We present evidence that challenges current opinion about this disorder, and we commend both clinicians and health technology assessment (HTA) agencies for being open to arguments and new evidence in any future HTAs.

Systematic Review: The Impact of Cancer Treatment on the Gut and Vaginal Microbiome in Women With a Gynecological Malignancy.

BACKGROUND AND AIM: Worldwide, 1,470,900 women are diagnosed yearly with a gynecological malignancy (21,000 in the UK). Some patients treated with pelvic radiotherapy develop chronic changes in their bowel function. This systematic review summarizes current research on the impact of cancer treatment on the gut and vaginal microbiome in women with a gynecological malignancy. METHODS: The Preferred reporting Items for Systematic Reviews and Meta-analyses guidelines for systematic reviews were used to ensure transparent and complete reporting. Quantitative studies exploring the gut or vaginal microbiome in this patient cohort were included. Animal studies were excluded. There were no language restrictions. RESULTS: No studies examined the possible effects of surgery or chemotherapy for gynecological cancers on the gut or vaginal microbiome.Three prospective cohort studies were identified using sequencing of changes in the gut microbiome reporting on a total of 23 women treated for gynecological cancer. All studies included patients treated with radiotherapy with a dosage ranging from 43.0 to 54.0 Gy. Two studies assessed gastrointestinal toxicity formally; 8 women (57%) developed grade 2 or 3 diarrhea during radiotherapy. The outcomes suggest a correlation between changes in the intestinal microbiome and receiving radiotherapy and showed a decrease in abundance and diversity of the intestinal bacterial species. Before radiotherapy, those who developed diarrhea had an increased abundance of Bacteroides, Dialister, and Veillonella (P < 0.01), and a decreased abundance of Clostridium XI and XVIII, Faecalibacterium, Oscillibacter, Parabacteroides, Prevotella, and unclassified bacteria (P < 0.05). CONCLUSION: The limited evidence to date implies that larger studies including both the vaginal and gut microbiome in women treated for a gynecological malignancy are warranted to explore the impact of cancer treatments on the microbiome and its relation to developing long-term gastrointestinal toxicity. This may lead to new avenues to stratify those at risk and explore personalized treatment options and prevention of gastrointestinal consequences of cancer treatments.

Improving the well-being of men by Evaluating and Addressing the Gastrointestinal Late Effects (EAGLE) of radical treatment for prostate cancer: study protocol for a mixed-method implementation project.

INTRODUCTION: Radiotherapy treatment for prostate cancer can cause bowel problems, which may lead to severe difficulties for cancer survivors including limiting travel, work or socialising. These symptoms can appear at any time following radiotherapy. This study focuses on the early identification and protocol-based management of effects known to cause long-term, or even permanent, changes to the well-being of prostate cancer survivors. The rationale of this study is to improve the care offered to men and their families following pelvic radiotherapy for prostate cancer. METHOD AND ANALYSIS: Implementation research methodology will be used to adopt a multicomponent intervention at three UK centres. The intervention package comprises a standardised clinical assessment of relevant symptoms in oncology outpatient clinics and rapid referral to an enhanced gastroenterological service for patients identified with bowel problems. Gastroenterology staff will be trained to use an expert-practice algorithm of targeted gastroenterology investigations and treatments. The evaluation of the intervention and its embedding within local practices will be conducted using a mixed-methods design. The effect of the new service will be measured in terms of the following outcomes: acceptability to staff and patients; quality of life; symptom control and cost-effectiveness. Data collection will take place at baseline, 6 months (±2 months), and 12 months (±2 months) after entry into the study. ETHICS AND DISSEMINATION: The study has ethical approval from the North West-Liverpool East Research Ethics Committee and the appropriate NHS governance clearance. All participants provide written informed consent. The study team aim to publish the results of the study in peer-reviewed journals as well as at national and international conferences. TRIAL REGISTRATION NUMBER: UKCRN16974.

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.

Guidance on the management of diarrhoea during cancer chemotherapy.

Diarrhoea induced by chemotherapy in cancer patients is common, causes notable morbidity and mortality, and is managed inconsistently. Previous management guidelines were based on poor evidence and neglect physiological causes of chemotherapy-induced diarrhoea. In the absence of level 1 evidence from randomised controlled trials, we developed practical guidance for clinicians based on a literature review by a multidisciplinary team of clinical oncologists, dietitians, gastroenterologists, medical oncologists, nurses, pharmacist, and a surgeon. Education of patients and their carers about the risks associated with, and management of, chemotherapy-induced diarrhoea is the foundation for optimum treatment of toxic effects. Adequate--and, if necessary, repeated--assessment, appropriate use of loperamide, and knowledge of fluid resuscitation requirements of affected patients is the second crucial step. Use of octreotide and seeking specialist advice early for patients who do not respond to treatment will reduce morbidity and mortality. In view of the burden of chemotherapy-induced diarrhoea, appropriate multidisciplinary research to assess meaningful endpoints is urgently required.

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.

Organ-specific management and supportive care in chronic graft-versus-host disease.

A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology and the British Society for Bone Marrow Transplantation has reviewed the available literature and made recommendations for the supportive care and management of organ-specific complications of chronic graft-versus-host disease (cGvHD). This guideline includes recommendations for the specific therapy of skin, oral, liver, gut, lung, ocular and genital manifestations of cGvHD and for the supportive care of these patients, including vaccinations and prophylaxis against infection. The goal of treatment should be effective control of GvHD while minimizing the risk of toxicity and relapse.

Can diet combined with treatment scheduling achieve consistency of rectal filling in patients receiving radiotherapy to the prostate?

BACKGROUND AND PURPOSE: This pilot study investigates whether an individualized fluid and fibre prescription combined with a constant treatment can improve rectal filling consistency during radiotherapy. METHODS AND MATERIALS: Fibre, fluid intake and bowel function were assessed in 22 patients at a standard planning scan (SCT) and individualized dietary advice was prescribed to regularize bowel habit. Patients were requested to record frequency and type of bowel movements, fibre and fluid intake daily. Two subsequent CT scans were acquired at 7 (CCT1) and 10 days (CCT2) after SCT at a similar time. Rectal volume and gas were measured planning CT's and 'on treatment' cone beam CT scans. We hypothesised that the difference in volume between CCT1 and CCT2 would be less than the difference between SCT and CCT1. RESULTS: The mean (SD) change in volume between SCT to CCT1 and CCT1 to CCT2 was 5.68 cm(3) (26.2) and -8.6 cm(3) (40.1), respectively (p=0.292). Of the 22 patients scanned 20 provided a complete record of dietary intake and bowel motion. The majority of patients either achieved or exceeded prescription. Change in rectal gas was the only correlation with change in rectal volume. CONCLUSION: Patient self reporting of bowel motion, fibre, fluid intake was achievable but consistency of rectal filling was not improved. Improved understanding of the aetiology and management of rectal gas is indicated.

Bile acid malabsoption: a forgotten diagnosis?

Bile acid malabsorption (BAM) is never life threatening but can cause chronic symptoms. A survey of senior British gastroenterologists was conducted to examine their approach to patients with potential BAM. Of the 706 gastroenterologists contacted, 62% replied. Gastroenterologists see on average 500 new patients in clinic annually; 34% have chronic diarrhoea and 1% are diagnosed with BAM. In those with chronic diarrhoea, 6% of gastroenterologists investigate for BAM first line, while 61% consider the diagnosis only in selected patients or not at all. Sixty-one per cent of patients are diagnosed with type 1 BAM (secondary to terminal ileal disease), 22% have type 2 (idiopathic bile acid malabsorption) and 15% type 3 (unrelated to terminal ileal disease). Only one third of gastroenterologists use a definitive diagnostic test for BAM. BAM (particularly type 2) is under-diagnosed because it is frequently not considered and even when considered, many patients are not subjected to definitive diagnostic testing.

Factitiously elevated blood chromium.

CONTEXT: Chromium toxicity is rare in individuals who do not have a history of occupational or deliberate exposure to chromium or chromium-containing compounds. CASE REPORT: A 39-year-old female with confirmed bile acid malabsorption had an elevated whole blood chromium concentration of 76.3 nmol/L (normal < 40 nmol/L). There was no history of chromium exposure and no clinical signs of chromium toxicity. Two repeat samples drawn through a butterfly needle, after discarding of an initial blood draw, also revealed an elevated blood chromium concentration (60.1, 122.7 nmol/L). A subsequent sample collected through a plastic intravenous cannula revealed a normal whole blood chromium concentration of 35 nmol/L. DISCUSSION: The elevated chromium concentrations were likely because of exogenous contamination from chromium within the venepuncture and butterfly needles. An appropriate sampling technique involving plastic cannula should be used when measuring blood chromium concentrations.

A comparison of dose-volume constraints derived using peak and longitudinal definitions of late rectal toxicity.

BACKGROUND AND PURPOSE: Accurate reporting of complications following radiotherapy is an important part of the feedback loop to improve radiotherapy techniques. The definition of toxicity is normally regarded as the maximum or peak (P) grade of toxicity reported over the follow-up period. An alternative definition (integrated longitudinal toxicity (ILT)) is proposed which takes into account both the severity and the duration of the complication. METHODS AND MATERIALS: In this work, both definitions of toxicity were used to derive dose-volume constraints for six specific endpoints of late rectal toxicity from a cohort of patients who received prostate radiotherapy in the MRC RT01 trial. The dose-volume constraints were derived using ROC analysis for 30, 40, 50, 60, 65 and 70 Gy. RESULTS: Statistically significant dose-volume constraints were not derived for all dose levels tested for each endpoint and toxicity definition. However, where both definitions produced constraints, there was generally good agreement. Variation in the derived dose-volume constraints was observed to be larger between endpoints than between the two definitions of toxicity. For one endpoint (stool frequency (LENT/SOM)) statistically significant dose-volume constraints were only derived using ILT. CONCLUSIONS: The longitudinal definition of toxicity (ILT) produced results consistent with those derived using peak toxicity and in some cases provided additional information which was not seen by analysing peak toxicity alone.

Gastrointestinal symptoms after pelvic radiotherapy: a new understanding to improve management of symptomatic patients.

Gastrointestinal symptoms after pelvic radiotherapy, which affect quality of life, are substantially more common than generally recognised and are frequently poorly managed. These symptoms develop because radiation can induce change in one or more specific physiological functions in widely separated parts of the gastrointestinal tract that lie in the path of the radiotherapy beam. Radiation-induced changes are not confined by normal anatomical boundaries. Furthermore, pre-existing subclinical disease might be destabilised because of minor gastrointestinal changes induced by radiotherapy. New diseases might manifest after radiotherapy and be confused with symptoms induced by radiotherapy. Different functional deficits might cause the same symptoms. Many patients have more than one cause for their symptoms, which sometimes need very different treatments. Simple diagnostic tests that are used in other contexts, if applied appropriately to patients with new gastrointestinal symptoms after radiotherapy, can identify the underlying causes of new-onset symptoms. Starting treatment without knowing the cause of the symptom is commonly ineffective because prediction of the combination of treatments needed is difficult. Evidence suggests that many patients have unusual but highly treatable malfunctions of gastrointestinal physiology, which if correctly diagnosed may enable a patient with difficult symptoms to be helped.