A response to industrial maturity and energetic issues: a possible solution based on constructal law

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Predictors of the experience of a Cytosponge test: analysis of patient survey data from the BEST3 trial

Availability of data and materials: The trial protocol, statistical analysis plan, and statistical report are available via the University of Cambridge data repository (https://www.data.cam.ac.uk/repository). Datasets will be available from R Fitzgerald ([email protected]) on request.Copyright © The Author(s) 2023. Background: The Cytosponge is a cell-collection device, which, coupled with a test for trefoil factor 3 (TFF3), can be used to diagnose Barrett’s oesophagus, a precursor condition to oesophageal adenocarcinoma. BEST3, a large pragmatic, randomised, controlled trial, investigated whether offering the Cytosponge-TFF3 test would increase detection of Barrett’s. Overall, participants reported mostly positive experiences. This study reports the factors associated with the least positive experience. Methods: Patient experience was assessed using the Inventory to Assess Patient Satisfaction (IAPS), a 22-item questionnaire, completed 7–14 days after the Cytosponge test. Study cohort: All BEST3 participants who answered ≥ 15 items of the IAPS (N = 1458). Statistical analysis: A mean IAPS score between 1 and 5 (5 indicates most negative experience) was calculated for each individual. ‘Least positive’ experience was defined according to the 90th percentile. 167 (11.4%) individuals with a mean IAPS score of ≥ 2.32 were included in the ‘least positive’ category and compared with the rest of the cohort. Eleven patient characteristics and one procedure-specific factor were assessed as potential predictors of the least positive experience. Multivariable logistic regression analysis using backwards selection was conducted to identify factors independently associated with the least positive experience and with failed swallow at first attempt, one of the strongest predictors of least positive experience. Results: The majority of responders had a positive experience, with an overall median IAPS score of 1.7 (IQR 1.5–2.1). High (OR = 3.01, 95% CI 2.03–4.46, p < 0.001) or very high (OR = 4.56, 95% CI 2.71–7.66, p < 0.001) anxiety (relative to low/normal anxiety) and a failed swallow at the first attempt (OR = 3.37, 95% CI 2.14–5.30, p < 0.001) were highly significant predictors of the least positive patient experience in multivariable analyses. Additionally, sex (p = 0.036), height (p = 0.032), alcohol intake (p = 0.011) and education level (p = 0.036) were identified as statistically significant predictors. Conclusion: We have identified factors which predict patient experience. Identifying anxiety ahead of the procedure and discussing particular concerns with patients or giving them tips to help with swallowing the capsule might help improve their experience. Trial registration ISRCTN68382401.The BEST3 trial was funded by Cancer Research UK (C14478/A21047), National Institute for Health Research covering service support costs, the UK National Health Service funding excess treatment costs and Medtronic providing funding for Cytosponge devices and TFF3 antibodies. RCF is funded by a Programme Grant from the Medical Research Council (RG84369) and is CI for the BEST3 trial and the Innovate UK funded DELTA study. JO was supported by PDS’s Cancer Research UK programme Grant (C8162/A16892) and is currently supported by the Barts Charity (EMSG1K1R). RM was supported by PDS’ Cancer Research UK Cancer Prevention Clinical Trials Unit funding (Grant No.: C8162/A25356). SGS is supported by a Yorkshire Cancer Research Fellowship. JW is funded by a Cancer Research UK career development fellowship (C7492/A17219). BG was funded as part of the DELTA study by Innovate UK (Grant No. 41162). FW is supported by the Cancer Research UK CanTest Grant [C8640/A23385]. RL is supported by the Intramural Research Program of the US National Institutes of Health/National Cancer Institute

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Abdominal distension in female patients with irritable bowel syndrome: exploration of possible mechanisms.

Abdominal distension is a common but little understood symptom of the irritable bowel syndrome. The authenticity of the symptom was confirmed by appreciable increases in girth measurement during the day in 20 patients with the irritable bowel syndrome compared with 20 control subjects. Objective corroboration of this finding was shown in the group with the irritable bowel syndrome by a highly significant increase in lateral abdominal 'profile' on computed tomography. Previously postulated mechanisms for distension--namely, retention of gas, depression of the diaphragm, and excess lumbar lordosis--were excluded by the radiological findings. Voluntary protrusion of the abdomen produced a completely different pattern on computed tomography to that observed in the irritable bowel syndrome. These observations suggest that abdominal distension may be related to changes in motility or tone of gastrointestinal smooth muscle

Functional bowel symptoms in diabetes--the role of autonomic neuropathy.

The autonomic nervous system may have a role in the pathogenesis of irritable bowel syndrome. If so, the occurrence of irritable bowel symptomatology in patients with autonomic neuropathy might indicate which, if any, of these symptoms are dependent on autonomic innervation. The prevalence of abdominal pain, abdominal distension and an abnormal bowel habit was recorded in 200 patients with diabetes, screened for autonomic neuropathy, and 200 matched controls. Constipation was significantly more common in patients with autonomic neuropathy than in those without, or controls (22.0% vs 9.2% vs 6.8%). The prevalence of abdominal pain and abdominal distension was no different in patients with and without autonomic neuropathy and their respective controls. The results of this study suggest that control of bowel habit is more dependent on the total integrity of the autonomic nervous system than the perception of pain or the production of distension