Involving Patients and Clinicians in the Design of Wireframes for Cancer Medicines Electronic Patient Reported Outcome Measures in Clinical Care: Mixed Methods Study.

Background: Cancer treatment is a key component of health care systems, and the increasing number of cancer medicines is expanding the treatment landscape. However, evidence of the impact on patients has been focused more on chemotherapy toxicity and symptom control and less on the effect of cancer medicines more broadly on patients' lives. Evolving electronic patient-reported outcome measures (ePROMs) presents the opportunity to secure early engagement of patients and clinicians in shaping the collection of quality-of-life metrics and presenting these data to better support the patient-clinician decision-making process.

Can butyrate prevent colon cancer? The AusFAP study: A randomised, crossover clinical trial.

Increased colonic butyrate from microbial fermentation of fibre may protect from colorectal cancer (CRC). Dietary butyrylated high amylose maize starch (HAMSB) delivers butyrate to the large bowel. The objective of this clinical trial (AusFAP) is to evaluate potential chemoprotective effects of HAMSB on polyposis in individuals with a genetic form of colon cancer, Familial Adenomatous Polyposis (FAP).

Opportunities and challenges when using record linkage of routinely collected electronic health care data to evaluate outcomes of systemic anti-cancer treatment in clinical practice.

The efficacy and safety of cancer medicines as reported from randomised clinical trials do not always translate into similar benefits in routine clinical practice; hence, post-marketing studies are a useful addition to the evidence base. With recent advances in digital infrastructure and the advent of electronically available health records, linkage of routinely collected data has emerged as a promising evaluation method for these studies. This paper discusses the opportunities and challenges when applying an electronic record linkage methodology with respect to systemic anti-cancer therapy by showcasing exemplar studies conducted over a three-year period in Scotland, and highlights some of the potential pitfalls spanning the entire breadth and depth of the research process.

What matters to patients and clinicians when discussing the impact of cancer medicines on health-related quality of life? Consensus-based mixed methods approach in prostate cancer.

Objective: To identify what matters to clinicians and patients when discussing cancer medicines' impact on health-related quality of life (HRQoL).

Methods: A framework of HRQoL domain/domain elements was developed, informed by analysis of published patient reported outcome measures (PROMs), applicable to prostate cancer. Using mixed methods (eDelphi, Nominal Group Technique and questionnaire), prostate cancer clinicians and patients attending prostate cancer clinics and support groups were asked which domains/domain elements would be important to them when discussing the impact prostate cancer medicines have on their HRQoL.

Healthcare Costs for Metastatic Castration-Resistant Prostate Cancer Patients Treated with Abiraterone or Enzalutamide.

Objective: The aim was to assess the real-world healthcare resource use and direct medical costs for metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone or enzalutamide, in whom chemotherapy is not yet indicated (pre-chemotherapy) or who had previously received docetaxel-based chemotherapy (post-chemotherapy), before commencing these medicines.

Methods: A retrospective cost analysis of mCRPC patients who commenced abiraterone or enzalutamide between 2012 and 2015 was conducted. Routinely collected datasets from the largest health board in Scotland and the UK, Greater Glasgow and Clyde, were linked.

Commensal microbe-derived acetate suppresses NAFLD/NASH development via hepatic FFAR2 signalling in mice.

Background: Non-alcoholic liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, and it can progress to non-alcoholic steatohepatitis (NASH). Alterations in the gut microbiome have been implicated in the development of NAFLD/NASH, although the underlying mechanisms remain unclear.

Results: We found that the consumption of the prebiotic inulin markedly ameliorated the phenotype of NAFLD/NASH, including hepatic steatosis and fibrosis, in mice.

Optimising medication management in children and young people with ADHD using a computerised test (QbTest): a feasibility randomised controlled trial.

Background: Medication for attention deficit hyperactivity disorder (ADHD) should be closely monitored to ensure optimisation. There is growing interest in using computerised assessments of ADHD symptoms to support medication monitoring. The aim of this study was to assess the feasibility and acceptability of a randomised controlled trial (RCT) to evaluate the efficacy of one such computerised assessment, the Quantified Behavior (Qb) Test, as part of medication management for ADHD.

An acetate-yielding diet imprints an immune and anti-microbial programme against enteric infection.

Objectives: During gastrointestinal infection, dysbiosis can result in decreased production of microbially derived short-chain fatty acids (SCFAs). In response to the presence of intestinal pathogens, we examined whether an engineered acetate- or butyrate-releasing diet can rectify the deficiency of SCFAs and lead to the resolution of enteric infection.

Methods: We tested whether a high acetate- or butyrate-producing diet (HAMSA or HAMSB, respectively) condition infection in mice and assess its impact on host-microbiota interactions.

Microbiota-derived butyrate limits the autoimmune response by promoting the differentiation of follicular regulatory T cells.

Background: Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder with a high prevalence, especially in industrialized countries. Dysbiosis of the intestinal microbiota has been observed in RA patients. For instance, new-onset untreated RA (NORA) is associated with the underrepresentation of the Clostridium cluster XIVa, including Lachnospiraceae, which are major butyrate producers, although the pathological relevance has remained obscure.

Use of record linkage to evaluate treatment outcomes and trial eligibility in a real-world metastatic prostate cancer population in Scotland.

Purpose: New treatments are introduced into standard care based on clinical trial results. However, it is not clear if these benefits are reflected in the broader population. This study analysed the clinical outcomes of patients with metastatic castration-resistant prostate cancer, treated with abiraterone and enzalutamide, within the Scottish National Health Service.

Correction to: Effect of mucin 4 allele on susceptibility to experimental infection with enterotoxigenic F4 in pigs fed experimental diets.

[This corrects the article DOI: 10.1186/s40104-019-0366-1.].

Effect of mucin 4 allele on susceptibility to experimental infection with enterotoxigenic F4 in pigs fed experimental diets.

Background: This study investigated the validity of the DNA-marker based test to determine susceptibility to ETEC-F4 diarrhoea by comparing the results of two DNA sequencing techniques in weaner pigs following experimental infection with F4 enterotoxigenic (ETEC-F4). The effects of diet and genetic susceptibility were assessed by measuring the incidence of piglet post-weaning diarrhoea (PWD), faecal shedding and the diarrhoea index.

Results: A DNA marker-based test targeting the mucin 4 gene () that encodes F4 fimbria receptor identified pigs as either fully susceptible (SS), partially or mildly susceptible (SR), and resistant (RR) to developing ETEC-F4 diarrhoea.

Consensus workshops on the development of an ADHD medication management protocol using QbTest: developing a clinical trial protocol with multidisciplinary stakeholders.

Background: The study design and protocol that underpin a randomised controlled trial (RCT) are critical for the ultimate success of the trial. Although RCTs are considered the gold standard for research, there are multiple threats to their validity such as participant recruitment and retention, identifying a meaningful change, and non-adherence to the protocol. For clinical RCTs, involving patients and clinicians in protocol design provides the opportunity to develop research protocols that are meaningful to their target audience and may help overcome some of the inherent threats in conducting RCTs.

Protocol investigating the clinical utility of an objective measure of attention, impulsivity and activity (QbTest) for optimising medication management in children and young people with ADHD 'QbTest Utility for Optimising Treatment in ADHD' (QUOTA): a feasibility randomised controlled trial.

Introduction: Attention-deficit hyperactivity disorder (ADHD) is characterised by symptoms of inattention, hyperactivity and impulsivity. To improve outcomes, the National Institute for Health and Care Excellence ADHD guidelines recommend regular monitoring of symptoms when children commence medication. However, research suggests that routine monitoring rarely happens, and clinicians often rely on subjective information such as reports from parents and teachers to ascertain improvement.

Erratum: Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes.

This corrects the article DOI: 10.1038/ni.3713.

Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes.

Gut dysbiosis might underlie the pathogenesis of type 1 diabetes. In mice of the non-obese diabetic (NOD) strain, we found that key features of disease correlated inversely with blood and fecal concentrations of the microbial metabolites acetate and butyrate. We therefore fed NOD mice specialized diets designed to release large amounts of acetate or butyrate after bacterial fermentation in the colon.

Dietary butyrylated high-amylose starch reduces azoxymethane-induced colonic O(6)-methylguanine adducts in rats as measured by immunohistochemistry and high-pressure liquid chromatography.

O(6)-methyl guanine (O(6)MeG) adducts are major toxic, promutagenic, and procarcinogenic adducts involved in colorectal carcinogenesis. Resistant starch and its colonic metabolite butyrate are known to protect against oncogenesis in the colon. In this study, we hypothesized that a dietary intervention that specifically delivers butyrate to the large bowel (notably butyrylated high-amylose maize starch [HAMSB]) would reduce colonic levels of O(6)MeG in rats shortly after exposure to the deoxyribonucleic acid (DNA) alkylating agent azoxymethane (AOM) when compared with a low-amylose maize starch (LAMS).

Butyrylated starch affects colorectal cancer markers beneficially and dose-dependently in genotoxin-treated rats.

Population studies suggest that greater dietary fiber intake may lower colorectal cancer (CRC) risk, possibly through the colonic bacterial fermentative production of butyrate. Butyrylated starch delivers butyrate to the colon of humans with potential to reduce CRC risk but high doses may exacerbate risk through promoting epithelial proliferation. Here we report the effects of increasing dietary butyrylated high amylose maize starch (HAMSB) on azoxymethane (AOM) induced distal colonic DNA damage, cell proliferation, mucus layer thickness and apoptosis in rats.

Housing experimental rats in solid-based cages with digestible bedding may confound outcomes of nutritional studies.

Background: Rats used in nutritional studies are often kept in wire-based cages to prevent ingestion of bedding and minimise ingestion of faeces. However, wire-based cages are criticised because of potential negative animal welfare implications. This study investigated the effects of wire and solid-based cages with corncob bedding on large bowel fermentation and microbiota.

Dietary supplementation of propionylated starch to domestic cats provides propionic acid as gluconeogenic substrate potentially sparing the amino acid valine.

In strict carnivorous domestic cats, a metabolic competition arises between the need to use amino acids for gluconeogenesis and for protein synthesis both in health and disease. The present study investigated the amino acid-sparing potential of propionic acid in cats using dietary propionylated starch (HAMSP) supplementation. A total of thirty cats were fed a homemade diet, supplemented with either HAMSP, acetylated starch (HAMSA) or celite (Control) for three adaptation weeks.

Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells.

Gut commensal microbes shape the mucosal immune system by regulating the differentiation and expansion of several types of T cell. Clostridia, a dominant class of commensal microbe, can induce colonic regulatory T (Treg) cells, which have a central role in the suppression of inflammatory and allergic responses. However, the molecular mechanisms by which commensal microbes induce colonic Treg cells have been unclear.