Insomnia is common in inflammatory bowel disease (IBD) and is associated with mental health conditions as well as IBD activity.

BACKGROUND/AIMS: Insomnia is common in people with chronic medical conditions, such as inflammatory bowel disease (IBD), and is readily treatable through cognitive behavioral therapy for insomnia. This study aimed to describe the associations with insomnia in people with IBD and its relationship to IBD-related disability. METHODS: An online questionnaire was administered through 3 tertiary IBD centers, social media, and Crohn's Colitis Australia. The questionnaire included the Insomnia Severity Index (ISI), a validated assessment of insomnia. Measures of anxiety, depression, physical activity, and disability were also included. IBD activity was assessed using validated patient reported scores. A multivariate model was constructed for clinically significant insomnia and ISI scores. Subpopulations of Crohn's disease and ulcerative colitis were considered. RESULTS: In a cohort of 670 respondents the median age was 41 years (range, 32-70 years), with the majority female (78.4%), the majority had Crohn's disease (57.3%). Increasingly severe disability was associated with worse insomnia score. Clinically significant insomnia was associated with clinically active IBD, abdominal pain, anxiety, and depression, in a multivariate model. In an ulcerative colitis population, Simple Clinical Colitis Activity Index components of general well-being and urgency were associated with worse ISI score in a model including depression and anxiety. In those with Crohn's disease, the multivariate model included Harvey Bradshaw Index score in addition to depression and anxiety. CONCLUSIONS: Insomnia is common in people with IBD and is associated with increased disability. Abdominal pain and mental health conditions should prompt consideration for screening for insomnia and referral for cognitive behavioral therapy for insomnia.

Hot Mail: Temperature Exposure during Mail Return of an Immunochemical Fecal Occult Blood Test.

BACKGROUND: Fecal immunochemical tests (FITs) are widely used for colorectal cancer (CRC) screening; however, high ambient temperatures were found to reduce test accuracy. More recently, proprietary globin stabilizers were added to FIT sample buffers to prevent temperature-associated hemoglobin (Hb) degradation, but their effectiveness remains uncertain. We aimed to determine the impact of high temperature (>30°C) on OC-Sensor FIT Hb concentration with current FITs, characterize FIT temperatures during mail transit, and determine impact of ambient temperature on FIT Hb concentration using data from a CRC screening program. METHODS: FITs were analyzed for Hb concentration after in vitro incubation at different temperatures. Data loggers packaged alongside FITs measured temperatures during mail transit. Separately, screening program participants completed and mailed FITs to the laboratory for Hb analysis. Regression analyses compared the impact of environmental variables on FIT temperatures and separately on FIT sample Hb concentration. RESULTS: In vitro incubation at 30 to 35°C reduced FIT Hb concentration after >4 days. During mail transit, maximum FIT temperature averaged 6.4°C above maximum ambient temperature, but exposure to temperature above 30°C was for less than 24 hours. Screening program data showed no association between FIT Hb concentration and maximum ambient temperatures. CONCLUSIONS: Although FIT samples are exposed to elevated temperatures during mail transit, this is brief and does not significantly reduce FIT Hb concentration. These data support continuation of CRC screening during warm weather with modern FITs with a stabilizing agent when mail delivery is ≤4 days.

Examining the influence of inflammatory bowel disease medications on sleep quality.

Background and Aim: Inflammatory bowel disease (IBD) can disrupt sleep, leading to poor sleep quality. This may in part be due to the symptoms of IBD and the influence of pro-inflammatory cytokines on sleep. This study aimed to investigate the potential influence of IBD medications on sleep quality. Methods: An online survey of adults with IBD was conducted, which included measures of sleep quality, IBD activity, anxiety, depression, and physical activity. Logistic regression was used to investigate possible associations between IBD medications (corticosteroids, immunomodulators, biologics, aminosalicyate) and outcome of poor sleep. A generalized linear model was built for outcome of sleep quality score. Results: There were 544 participants included in the final analysis, median age of 42, and 61% with Crohn's disease. Increased odds of poor sleep were seen in those taking opioids, medications for anxiety or depression, corticosteroids, vitamin D, methotrexate, and infliximab. A multivariate model was built incorporating demographic and IBD variables with opioids present in the final model and associated with increased odds of poor sleep. This was in addition to medications for sleep, depression, anxiety, IBD activity, and body weight. In a multivariate generalized linear model, opioids and methotrexate were associated with worse sleep quality scores. Conclusions: Opioids were associated with increased odds of poor sleep independent of other factors. This provides further support for avoiding these medications in people with IBD. Infliximab was associated with increased body weight and consequently increased odds of poor sleep.

Simple Novel Screening Tool for Obstructive Sleep Apnea in Inflammatory Bowel Disease.

Background: Inflammatory bowel disease (IBD) has been associated with an increased risk of obstructive sleep apnea (OSA). We aimed to examine the associations of obstructive sleep apnea, sleepiness, and IBD-related data and comorbidities, with the aim of developing a screening tool for sleep apnea in this population. Methods: An online survey of adults with IBD was administered which included measures of assessment of the risk of OSA, and measures of IBD activity, IBD-related disability, anxiety, and depression. Logistic regression was performed to investigate the associations between the risk of OSA and IBD data, medications, demographics, and mental health conditions. Further models were built for an outcome of severe daytime sleepiness and a combined outcome of risk of OSA and at least mild daytime sleepiness. A simple score was constructed for the purpose of screening for OSA. Results: There were 670 responses to the online questionnaire. The median age was 41 years, the majority had Crohn's disease (57%), the median disease duration was 11.9 years, and approximately half were on biologics (50.5%). Moderate-high risk of OSA was demonstrated in 22.6% of the cohort. A multivariate regression model for moderate-high risk of OSA included increasing age, obesity, smoking, and abdominal pain subscore. For a combined outcome of moderate-high risk of OSA and at least mild daytime sleepiness, a multivariate model included abdominal pain, age, smoking, obesity, and clinically significant depression. A simple score was constructed for screening for OSA utilizing age, obesity, IBD activity, and smoking status with an area under the receiver-operating curve of 0.77. A score >2 had a sensitivity of 89% and a specificity of 56% for moderate-high risk of OSA and could be utilized for screening for OSA in the IBD clinic. Conclusions: Over one-fifth of an IBD cohort met significantly high-risk criteria for OSA to warrant referral for a diagnostic sleep study. The risk of OSA was associated with abdominal pain, along with more traditional risk factors such as smoking, increasing age, and obesity. Consideration should be given for screening for OSA in IBD patients utilizing a novel screening tool that utilizes parameters typically available in IBD clinic.

Faecal immunochemical test mitigates risk of delayed colonoscopy in people with elevated risk of colorectal neoplasia.

BACKGROUND AND AIM: Surveillance colonoscopies may be delayed because of pressure on resources, such as the COVID-19 pandemic. This study aimed to determine whether delayed surveillance colonoscopy increases the risk for advanced neoplasia and whether interval screening with faecal immunochemical tests (FITs) and other known risk factors can mitigate this risk. METHODS: A retrospective cohort study of individuals undergoing surveillance colonoscopy for personal or family history of colorectal neoplasia was being provided with FIT between colonoscopies. Colonoscopy ≥ 6 months after the guideline-recommended interval was considered "delayed." Individuals were stratified based on prime colonoscopy findings to nonneoplastic findings, non-advanced adenoma, and advanced adenoma. The relative risk (RR) for developing advanced neoplasia was determined using a robust multivariable modified Poisson regression. RESULTS: Of 2548 surveillance colonoscopies, 1457 (57.18%) were delayed. Prior advanced adenoma, older age (> 60 years) and nonparticipation in interval FIT were associated with increased risk for advanced neoplasia (P < 0.05). There was a trend to increased risk in those with prior advanced adenoma with an increasing colonoscopy delay (P trend = 0.01). In participants who did not complete interval FIT and having advanced adenoma in the prime colonoscopy, risk of advanced neoplasia was 2.48 times higher (RR = 2.48, 95% confidence interval: 1.20-5.13) in participants who had beyond 2 years of delayed colonoscopy compared with those with on-time colonoscopy. Colonoscopy delay did not increase the risk of advanced neoplasia in participants with negative interval FIT results. CONCLUSION: Surveillance colonoscopy can be safely extended beyond 6 months in elevated colorectal cancer risk patients who do not have prior advanced adenoma diagnosis, particularly if interval FIT is negative.

A systematic review and meta-analysis of the prevalence of poor sleep in inflammatory bowel disease.

Study Objectives: Poor sleep-in people with inflammatory bowel disease (IBD) has been associated with worse quality of life, along with anxiety, depression, and fatigue. This meta-analysis aimed to determine the pooled prevalence of poor sleep-in IBD. Methods: Electronic databases were searched for publications from inception to November 1st 2021. Poor sleep was defined according to subjective sleep measures. A random effects model was used to determine the pooled prevalence of poor sleep-in people with IBD. Heterogeneity was investigated through subgroup analysis and meta-regression. Publication bias was assessed by funnel plot and Egger's test. Results: 519 Studies were screened with 36 studies included in the meta-analysis incorporating a total of 24 209 people with IBD. Pooled prevalence of poor sleep-in IBD was 56%, 95% CI (51-61%) with significant heterogeneity. The prevalence did not differ based on the definition of poor sleep. Meta-regression was significant for increased prevalence of poor sleep with increase in age and increased of prevalence of poor sleep with objective IBD activity but not subjective IBD activity, depression, or disease duration. Conclusions: Poor sleep is common in people with IBD. Further research is warranted to investigate if improving sleep quality in people with IBD will improve IBD activity and quality of life.

A Randomized Controlled Trial Testing Provision of Fecal and Blood Test Options on Participation for Colorectal Cancer Screening.

Suboptimal participation is commonly observed in colorectal cancer screening programs utilizing fecal tests. This randomized controlled trial tested whether the offer of a blood test as either a "rescue" strategy for fecal test nonparticipants or an upfront choice, could improve participation. A total of 1,800 people (50-74 years) were randomized to control, rescue, or choice groups (n = 600/group). All were mailed a fecal immunochemical test (FIT, OC-Sensor, Eiken Chemical Company) and a survey assessing awareness of the screening tests. The rescue group was offered a blood test 12 weeks after FIT nonparticipation. The choice group was given the opportunity to choose to do a blood test (Colvera, Clinical Genomics) instead of FIT at baseline. Participation with any test after 24 weeks was not significantly different between groups (control, 37.8%; rescue, 36.9%; choice, 33.8%; P > 0.05). When the rescue strategy was offered after 12 weeks, an additional 6.5% participated with the blood test, which was greater than the blood test participation when offered as an upfront choice (1.5%; P < 0.001). Awareness of the tests was greater for FIT than for blood (96.2% vs. 23.1%; P < 0.0001). In a population familiar with FIT screening, provision of a blood test either as a rescue of FIT nonparticipants or as an upfront choice did not increase overall participation. This might reflect a lack of awareness of the blood test for screening compared with FIT.

The association between nutritional adequacy and 28-day mortality in the critically ill is not modified by their baseline nutritional status and disease severity.

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.

Low Sensitivity of Fecal Immunochemical Tests and Blood-Based Markers of DNA Hypermethylation for Detection of Sessile Serrated Adenomas/Polyps.

BACKGROUND: Early 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. AIMS: To investigate the sensitivity of fecal immunochemical tests (FIT) and epigenetic biomarkers in blood for detection of SSP. METHODS: A 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. RESULTS: One 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. CONCLUSIONS: Both FIT and blood-based markers of DNA hypermethylation have low sensitivity for detection of SSP. Further development of sensitive screening tests is warranted.

Preferences for Surveillance of Barrett's Oesophagus: a Discrete Choice Experiment.

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.

When timing and dose of nutrition support were examined, the modified Nutrition Risk in Critically Ill (mNUTRIC) score did not differentiate high-risk patients who would derive the most benefit from nutrition support: a prospective cohort study.

BACKGROUND: The timing and dose of exclusive nutrition support (ENS) have not been investigated in previous studies aimed at validating the modified Nutrition Risk in Critically Ill (mNUTRIC) score. We therefore evaluated the mNUTRIC score by determining the association between dose of nutrition support and 28-day mortality in high-risk patients who received short- and longer-term ENS (≤ 6 days vs. ≥ 7 days). METHODS: A prospective cohort study included data from 252 adult patients with > 48 h of mechanical ventilation in a tertiary care institution in Singapore. The dose of nutrition support (amount received ÷ goal: expressed in percentage) was calculated for a maximum of 14 days. Associations between the dose of energy (and protein) intake and 28-day mortality were evaluated with multivariable Cox regressions. Since patients have different durations of ENS, only the first 6 days of ENS in patients with short- and longer-term ENS were assessed in the Cox regressions to ensure a valid comparison of the associations between energy (and protein) intake and 28-day mortality. RESULTS: In high-risk patients with short-term ENS (n = 106), each 10% increase in goal energy intake was associated with an increased hazard of 28-day mortality [adj-HR 1.37 (95% CI 1.17, 1.61)], and this was also observed for protein intake [adj-HR 1.31 (95% CI 1.10, 1.56)]. In contrast, each 10% increase in goal protein intake in high-risk patients with longer-term ENS (n = 146) was associated with a lower hazard of 28-day mortality [adj-HR 0.78 (95% CI 0.66, 0.93)]. The mean mNUTRIC scores in these two groups of patients were similar. CONCLUSION: When timing and dose of nutrition support were examined, the mNUTRIC did not differentiate high-risk patients who would derive the most benefit from nutrition support.

Uptake of a colorectal cancer screening blood test in people with elevated risk for cancer who cannot or will not complete a faecal occult blood test.

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.

Combining 2 Commonly Adopted Nutrition Instruments in the Critical Care Setting Is Superior to Administering Either One Alone.

BACKGROUND: This study aimed to determine the agreement between the modified Nutrition Risk in Critically ill Score (mNUTRIC) and the Subjective Global Assessment (SGA) and compare their ability in discriminating and quantifying mortality risk independently and in combination. METHODS: Between August 2015 and October 2016, all patients in a Singaporean hospital received the SGA within 48 hours of intensive care unit admission. Nutrition status was dichotomized into presence or absence of malnutrition. The mNUTRIC of patients was retrospectively calculated at the end of the study, and high mNUTRIC was defined as scores ≥5. RESULTS: There were 439 patients and 67.9% had high mNUTRIC, whereas only 28% were malnourished. Hospital mortality was 29.6%, and none was lost to follow-up. Although both tools had poor agreement (κ statistics: 0.13, P < .001), they had similar discriminative value for hospital mortality (C-statistics [95% confidence interval (CI)], 0.66 [0.62-0.70] for high mNUTRIC and 0.61 [0.56-0.66] for malnutrition, P = .12). However, a high mNUTRIC was associated with higher adjusted odds for hospital mortality compared with malnutrition (adjusted odds ratio [95% CI], 5.32 [2.15-13.17], P < .001, and 4.27 [1.03-17.71], P = .046, respectively). Combination of both tools showed malnutrition and high mNUTRIC were associated with the highest adjusted odds for hospital mortality (14.43 [5.38-38.78], P < .001). CONCLUSION: The mNUTRIC and SGA had poor agreement. Although they individually provided a fair discriminative value for hospital mortality, the combination of these approaches is a better discriminator to quantify mortality risk.

Association Between Malnutrition and Clinical Outcomes in the Intensive Care Unit: A Systematic Review [Formula: see text].

Malnutrition is associated with poor clinical outcomes among hospitalized patients. However, studies linking malnutrition with poor clinical outcomes in the intensive care unit (ICU) often have conflicting findings due in part to the inappropriate diagnosis of malnutrition. We primarily aimed to determine whether malnutrition diagnosed by validated nutrition assessment tools such as the Subjective Global Assessment (SGA) or Mini Nutritional Assessment (MNA) is independently associated with poorer clinical outcomes in the ICU and if the use of nutrition screening tools demonstrate a similar association. PubMed, CINAHL, Scopus, and Cochrane Library were systematically searched for eligible studies. Search terms included were synonyms of malnutrition, nutritional status, screening, assessment, and intensive care unit. Eligible studies were case-control or cohort studies that recruited adults in the ICU; conducted the SGA, MNA, or used nutrition screening tools before or within 48 hours of ICU admission; and reported the prevalence of malnutrition and relevant clinical outcomes including mortality, length of stay (LOS), and incidence of infection (IOI). Twenty of 1168 studies were eligible. The prevalence of malnutrition ranged from 38% to 78%. Malnutrition diagnosed by nutrition assessments was independently associated with increased ICU LOS, ICU readmission, IOI, and the risk of hospital mortality. The SGA clearly had better predictive validity than the MNA. The association between malnutrition risk determined by nutrition screening was less consistent. Malnutrition is independently associated with poorer clinical outcomes in the ICU. Compared with nutrition assessment tools, the predictive validity of nutrition screening tools were less consistent.

Assessing the clinical and economic impact of increasing treatment uptake in chronic hepatitis B infection using a Markov model.

Treatment uptake in chronic hepatitis B virus (HBV) infection is low in South Australia, and the cost-effectiveness of increasing treatment uptake rates in this population has not been assessed. AIMS AND METHODS: Using a cohort Markov model, cost-effectiveness was assessed for three different treatment uptake scenarios: 2.9% (current level-scenario 1), 10% (scenario 2), and 15% (scenario 3). The initial HBV population included 2550 treatment eligible patients who transitioned between six different health states over a 10-year period. Treatment transition probabilities were based on tenofovir therapy, while those not assigned to treatment followed the natural history transition probabilities. We estimated the incremental cost per quality adjusted life year gained using the prevented number of deaths, hepatocellular carcinoma, and liver transplants. RESULTS: Scenario 3 was associated with the lowest mean cost/person over 10 years (AU$60 133), compared with scenario 2 (AU$61 964) and scenario 1 (AU$64 597). Scenario 3 was also associated with the highest quality adjusted life year gained (8.196) compared with scenario 2 (7.985) and scenario 1 (7.684). Scenario 3 would result in 50% reduction in hepatocellular carcinoma and 30% reduction in HBV-related mortality compared with scenario 1, over a 10-year period. Higher treatment uptake was found to be cost-effective with at least 2 years of treatment at either 10% or 15% of the target population. CONCLUSION: Maximizing the treatment uptake in the existing HBV population from 2.9% to 15% was cost-effective for periods of 2 years or more. This was due to a reduction in the number of expected clinical events.

Toward More Efficient Surveillance of Barrett's Esophagus: Identification and Exclusion of Patients at Low Risk of Cancer.

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.

The effect of camicinal (GSK962040), a motilin agonist, on gastric emptying and glucose absorption in feed-intolerant critically ill patients: a randomized, blinded, placebo-controlled, clinical trial.

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 (BTt1/2), 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 BTt1/2 117 minutes vs. post- treatment 76 minutes; 95 % confidence intervals (CI; 0.39, 1.08) and increased glucose absorption (AUC240min 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 BTt1/2 121 minutes vs. post-treatment 65 minutes 95 % CI (0.32, 0.91) and increased glucose absorption (AUC240min 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 ).

Percutaneous thermal ablation for primary hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND AND AIM: Percutaneous thermal ablation using radiofrequency ablation (RFA) and microwave ablation (MWA) are both widely available curative treatments for hepatocellular carcinoma. Despite significant advances, it remains unclear which modality results in better outcomes. This meta-analysis of randomized controlled trials (RCT) and observational studies was undertaken to compare the techniques in terms of effectiveness and safety. METHODS: Electronic reference databases (Medline, EMBASE and Cochrane Central) were searched between January 1980 and May 2014 for human studies comparing RFA and MWA. The primary outcome was the risk of local tumor progression (LTP). Secondary outcomes were complete ablation (CA), overall survival, and major adverse events (AE). The ORs were combined across studies using the random-effects model. RESULTS: Ten studies (two prospective and eight retrospective) were included, and the overall LTP rate was 13.6% (176/1298). There was no difference in LTP rates between RFA and MWA [OR (95% CI): 1.01(0.67-1.50), P = 0.9]. The CA rate, 1- and 3-year overall survival and major AE were similar between the two modalities (P > 0.05 for all). In subgroup analysis, there was no difference in LTP rates according to study quality, but LTP rates were lower with MWA for treatment of larger tumors [1.88(1.10-3.23), P = 0.02]. There was no significant publication bias or inter-study heterogeneity (I(2) < 50% and P > 0.1) observed in any of the measured outcomes. CONCLUSION: Overall, both RFA and MWA are equally effective and safe, but MWA may be more effective compared to RFA in preventing LTP when treating larger tumors. Well-designed, larger, multicentre RCTs are required to confirm these findings.