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BackgroundEarly detection and removal of precursor lesions reduce colorectal cancer morbidity and mortality. Sessile serrated adenomas/polyps (SSP) are a recognized precursor of cancer, but there are limited studies on whether current screening techniques detect this pathology.AimsTo investigate the sensitivity of fecal immunochemical tests (FIT) and epigenetic biomarkers in blood for detection of SSP.MethodsA prospective study offered FIT and a blood test (Colvera for methylated BCAT1 and IKZF1) to adults referred for colonoscopy. Sensitivity of FIT and the blood test were determined for four types of pathology: low-risk conventional adenoma, high-risk adenoma, SSP, and absence of neoplasia. Comparisons were made for FIT positivity at 10 and 20 μg hemoglobin (Hb)/g feces.ResultsOne thousand eight hundred and eighty-two subjects completed FIT and underwent colonoscopy. One thousand four hundred and three were also tested for methylated BCAT1/IKZF1. The sensitivity of FIT (20 μg Hb/g feces) for SSP was 16.3%. This was lower than the sensitivity for high-risk adenomas (28.7%, p < 0.05), but no different to that for low-risk adenomas (13.1%) or no neoplasia (8.4%). A positive FIT result for SSP was not associated with demographics, morphology, concurrent pathology or intake of medications that increase bleeding risk. FIT sensitivity for SSP did not significantly increase through lowering the positivity threshold to 10 μg Hb/g feces (20.4%, p > 0.05). Sensitivity of the blood test for SSP was 8.8%, and 26.5% when combined with FIT.ConclusionsBoth FIT and blood-based markers of DNA hypermethylation have low sensitivity for detection of SSP. Further development of sensitive screening tests is warranted.

Background During the initial phase of critical illness, the association between the dose of nutrition support and mortality risk may vary among patients in the intensive care unit (ICU) because the prevalence of malnutrition varies widely (28 to 78%), and not all ICU patients are severely ill. Therefore, we hypothesized that a prognostic model that integrates nutritional status and disease severity could accurately predict mortality risk and classify critically ill patients into low- and high-risk groups. Additionally, in critically ill patients placed on exclusive nutritional support (ENS), we hypothesized that their risk categories could modify the association between dose of nutrition support and mortality risk. Methods A prognostic model that predicts 28-day mortality was built from a prospective cohort study of 440 patients. The association between dose of nutrition support and mortality risk was evaluated in a subgroup of 252 mechanically ventilated patients via logistic regressions, stratified by low- and high-risk groups, and days of exclusive nutritional support (ENS) [short-term (≤ 6 days) vs. longer-term (≥ 7 days)]. Only the first 6 days of ENS was evaluated for a fair comparison. Results The prognostic model demonstrated good discrimination [AUC 0.78 (95% CI 0.73–0.82), and a bias-corrected calibration curve suggested fair accuracy. In high-risk patients with short-term ENS (≤ 6 days), each 10% increase in goal energy and protein intake was associated with an increased adjusted odds (95% CI) of 28-day mortality [1.60 (1.19–2.15) and 1.47 (1.12–1.86), respectively]. In contrast, each 10% increase in goal protein intake during the first 6 days of ENS in high-risk patients with longer-term ENS (≥ 7 days) was associated with a lower adjusted odds of 28-day mortality [0.75 (0.57–0.99)]. Despite the opposing associations, the mean predicted mortality risks and prevalence of malnutrition between short- and longer-term ENS patients were similar. Conclusions Combining baseline nutritional status and disease severity in a prognostic model could accurately predict 28-day mortality. However, the association between the dose of nutrition support during the first 6 days of ENS and 28-day mortality was independent of baseline disease severity and nutritional status.

Background The promotility agents currently available to treat gastroparesis and feed intolerance in the critically ill are limited by adverse effects. The aim of this study was to assess the pharmacodynamic effects and pharmacokinetics of single doses of the novel gastric promotility agent motilin agonist camicinal (GSK962040) in critically ill feed-intolerant patients. Methods A prospective, randomized, double-blind, parallel-group, placebo-controlled, study was performed in mechanically ventilated feed-intolerant patients [median age 55 (19–84), 73 % male, APACHE II score 18 (5–37) with a gastric residual volume ≥200 mL]. Gastric emptying and glucose absorption were measured both pre- and post-treatment after intragastric administration of 50 mg ( n  = 15) camicinal and placebo ( n  = 8) using the 13 C-octanoic acid breath test (BTt 1/2 ), acetaminophen concentrations, and 3-O-methyl glucose concentrations respectively. Results Following 50 mg enteral camicinal, there was a trend to accelerated gastric emptying [adjusted geometric means: pre-treatment BTt 1/2 117 minutes vs. post- treatment 76 minutes; 95 % confidence intervals (CI; 0.39, 1.08) and increased glucose absorption (AUC 240min pre-treatment: 28.63 mmol.min/L vs. post-treatment: 71.63 mmol.min/L; 95 % CI (1.68, 3.72)]. When two patients who did not have detectable plasma concentrations of camicinal were excluded from analysis, camicinal accelerated gastric emptying (adjusted geometric means: pre-treatment BTt 1/2 121 minutes vs. post-treatment 65 minutes 95 % CI (0.32, 0.91) and increased glucose absorption (AUC 240min pre-treatment: 33.04 mmol.min/L vs. post-treatment: 74.59 mmol.min/L; 95 % CI (1.478, 3.449). In those patients receiving placebo gastric emptying was similar pre- and post-treatment. Conclusions When absorbed, a single enteral dose of camicinal (50 mg) accelerates gastric emptying and increases glucose absorption in feed-intolerant critically ill patients. Trial registration The study protocol was registered with the US NIH clinicaltrials.gov on 23 December 2009 (Identifier NCT01039805 ).

Background Endoscopic surveillance of Barrett’s esophagus (BE) is probably not cost-effective. A sub-population with BE at increased risk of high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) who could be targeted for cost-effective surveillance was sought. Methods The outcome for BE surveillance from 2003 to 2012 in a structured program was reviewed. Incidence rates and incidence rate ratios for developing HGD or EAC were calculated. Risk stratification identified individuals who could be considered for exclusion from surveillance. A health-state transition Markov cohort model evaluated the cost-effectiveness of focusing on higher-risk individuals. Results During 2067 person-years of follow-up of 640 patients, 17 individuals progressed to HGD or EAC (annual IR 0.8%). Individuals with columnar-lined esophagus (CLE) ≥2 cm had an annual IR of 1.2% and >8-fold increased relative risk of HGD or EAC, compared to CLE <2 cm [IR—0.14% (IRR 8.6, 95% CIs 4.5–12.8)]. Limiting the surveillance cohort after the first endoscopy to individuals with CLE ≥2 cm, or dysplasia, followed by a further restriction after the second endoscopy—exclusion of patients without intestinal metaplasia—removed 296 (46%) patients, and 767 (37%) person-years from surveillance. Limiting surveillance to the remaining individuals reduced the incremental cost-effectiveness ratio from US$60,858 to US$33,807 per quality-adjusted life year (QALY). Further restrictions were tested but failed to improve cost-effectiveness. Conclusions Based on stratification of risk, the number of patients requiring surveillance can be reduced by at least a third. At a willingness-to-pay threshold of US$50,000 per QALY, surveillance of higher-risk individuals becomes cost-effective.

Current guidelines recommend topical steroids as first-line treatment for patients with eosinophilic esophagitis (EoE). However, the evidence for this approach has been inconsistent in earlier reports. This meta-analysis aimed to clarify the efficacy of topical steroid treatment in active EoE using updated evidence. CENTRAL, MEDLINE and EMBASE databases were searched for randomized controlled trials (RCTs) published up to May 2014 that compared topical steroids with control treatments for active EoE. Study bias was assessed using the Cochrane Collaboration Tool, and outcomes were pooled using random effects models. The primary outcome was the mean change in eosinophil counts. Secondary outcomes were symptom responses and adverse events. In total, seven RCTs (226 patients) were included. Topical steroids were associated with a significant reduction in esophageal mucosal eosinophil counts compared with control therapy although substantial heterogeneity between studies was observed (weighted mean difference (WMD) -27.2, 95% confidence interval (CI) -45.3 to -9.1, I(2)=56.2%). Subgroup analysis indicated the reduction in eosinophil counts was only present in studies where a proton pump inhibitor (PPI) trial was used to exclude other diagnoses (WMD -46.3, 95% CI -61.3 to -31.4, I(2)=0.0%). Subdivision of studies on the use of a PPI trial also accounted for the majority of heterogeneity among RCTs. No clear trends in symptom resolution were observed. Eleven out of 127 patients who received topical steroids developed asymptomatic esophageal candidiasis. These data provide updated high-quality evidence that support current guidelines for first-line EoE treatment with topical steroids after an initial PPI trial to exclude non-EoE pathologies (PROSPERO ID: CRD42014008828).

Purpose Small intestinal (SI) motor patterns are often disrupted after major non-gastrointestinal (non-GI) surgery, but the impact on luminal flow and nutrient absorption is unclear. This study examines interactions between SI motility, flow and absorption in the first 3 days after surgical repair of abdominal aortic aneurysm (AAA). Methods Concurrent assessments of SI motility (manometry), flow (impedancometry) and lipid ( 13 C-triolein) and glucose [plasma 3- O -methyl-glucose (3-OMG)] absorption were performed in 13 patients (12 male; 77 ± 2 years) on days 1 and 3 post surgery during 3-h intra-duodenal nutrient infusion (Ensure ® with 200 μl 13 C-triolein, 3 g 3-OMG). Data, presented as mean ± standard error of mean (SEM), are compared with 10 healthy volunteers (9 male; 57 ± 4 years). Results On day 1 post surgery, there were more motility bursts, fewer impedance events and reduced absorption of 13 C-triolein [cumulative percent dose recovery (cPDR) 22.9 ± 2.4% versus 31.2 ± 4.2%; P  < 0.001] and 3-OMG, compared with health. By day 3, total number of bursts and flow events were similar between groups, with fewer retrograde and more antegrade flow episodes. 13 C-triolein absorption remained low in patients on day 3 (26.7 ± 2.2%, P  < 0.05), correlating positively with total number of flow events ( r  = 0.49; P  < 0.01), but negatively with prolonged events ( r  = −0.37; P  = 0.03). In patients, 3-OMG absorption increased from day 1 to 3 to a level comparable to health. Conclusions Whilst disruption in SI motility and flow (impedance) events was associated with reduced absorption of both lipid and carbohydrate, lipid malabsorption was more prolonged. This may reflect inadequate mixing of chyme from altered motility, so varying the nutrient composition of enteral feed may improve absorption in these patients.

Purpose Endoscopic surveillance for Barrett’s oesophagus is undertaken to detect dysplasia and early cancer, and to facilitate early intervention. Evidence supporting current practice is of low quality and often influenced by opinion. This study investigated the preferences of patients for surveillance of Barrett’s oesophagus in an Australian cohort. Methods Four Barrett’s oesophagus surveillance characteristics/attributes were evaluated within a discrete choice experiment based on literature and expert opinion: (1) surveillance method (endoscopy vs a blood test vs a novel breath test), (2) risk of missing a cancer over a 10-year period, (3) screening interval, and (4) out-of-pocket cost. The data from the discrete choice experiment was analysed within the framework of random utility theory using a mixed logit regression model. Results The study sample comprised patients ( n  = 71) undergoing endoscopic surveillance for Barrett’s oesophagus of whom n  = 65 completed the discrete choice experiment. The sample was predominantly male (77%) with average age of 65 years. All attributes except surveillance method significantly influenced respondents’ preference for Barrett’s oesophagus surveillance. Policy analyses suggested that compared to the reference case (i.e. endoscopy provided annually at no upfront cost and with a 4% risk of missing cancer), increasing test sensitivity to 0.5% risk of missing cancer would increase participation by up to 50%; surveillance every 5 years would lead to 26% reduction, while every 3 to 3.5 years would result in 7% increase in participation. Respondents were highly averse to paying A$500 for the test, resulting in 48% reduction in participation. None of the other surveillance methods was preferred to endoscopy, both resulting in 11% reduction in participation. Conclusion Test sensitivity, test frequency and out-of-pocket cost were the key factors influencing surveillance uptake. Patients prefer a test with the highest sensitivity, offered frequently, that incurs no upfront costs.

Participation rates in colorectal cancer (CRC) screening programmes using faecal occult blood tests (FOBTs) are low. Nonparticipation is commonly attributed to psychosocial factors, but some medical conditions also prevent screening. These barriers might be partially overcome if a blood test for CRC screening was available. This study determined whether people who had always declined screening by FOBT would participate if offered a blood test. An audit of registrants within a personalized CRC screening programme was undertaken to determine the reasons for regular nonparticipation in FOBT. Consistent nonparticipants ( n =240) were randomly selected and invited for CRC screening with a blood test. Demographic characteristics and the reasons for prior FOBT nonparticipation were collected by means of a questionnaire. Nonparticipation in the screening programme could be classified as either behavioural (8.6%), with consistent noncompliance, or due to medical contraindications (8.5%), which included chronic rectal bleeding, being deemed unsuitable by a health professional, and needing personal assistance. Blood test uptake was 25%, with participation in the medical contraindications group greater than that in the behavioural group (43 vs. 12%, P <0.001). Reported behavioural reasons for nonparticipation in faecal immunochemical test included procrastination and dislike of the test, but these were not associated with blood test uptake ( P >0.05). There is a subgroup of the community who have medical reasons for nonparticipation in CRC screening with FOBT but will participate if offered a blood test. The option of a blood test does not, however, improve uptake in those who admit to behavioural reasons for noncompliance with screening.

This time-motion study explored the amount of time clinicians spent on wound assessments in a real-world environment using wound assessment digital application utilizing Artificial Intelligence (AI) vs. manual methods. The study also aimed at comparing the proportion of captured quality wound images on the first attempt by the assessment method. Clinicians practicing at Valley Wound Center who agreed to join the study were asked to record the time needed to complete wound assessment activities for patients with active wounds referred for a routine evaluation on the follow-up days at the clinic. Assessment activities included: labelling wounds, capturing images, measuring wounds, calculating surface areas, and transferring data into the patient's record. A total of 91 patients with 115 wounds were assessed. The average time to capture and access wound image with the AI digital tool was significantly faster than a standard digital camera with an average of 62 seconds (P<0.001). The digital application was significantly faster by 77% at accurately measuring and calculating the wound surface area with an average of 45.05 seconds (P<0.001). Overall, the average time to complete a wound assessment using Swift was significantly faster by 79%. Using the AI application, the staff completed all steps in about half of the time (54%) normally spent on manual wound evaluation activities. Moreover, acquiring acceptable wound image was significantly more likely to be achieved the first time using the digital tool than the manual methods (92.2% vs. 75.7%, P<0.004). Using the digital assessment tool saved significant time for clinicians in assessing wounds. It also successfully captured quality wound images at the first attempt.