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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. (JPEN J Parenter Enteral Nutr. 2018;42:872-876) [ABSTRACT FROM AUTHOR]

Objectives Faecal immunochemical test accuracy may be adversely affected when samples are exposed to high temperatures. This study evaluated the effect of two sample collection buffer formulations (OC-Sensor, Eiken) and storage temperatures on faecal haemoglobin readings. Methods Faecal immunochemical test samples returned in a screening programme and with ≥10 µg Hb/g faeces in either the original or new formulation haemoglobin stabilizing buffer were stored in the freezer, refrigerator, or at room temperature (22℃–24℃), and reanalysed after 1–14 days. Samples in the new buffer were also reanalysed after storage at 35℃ and 50℃. Results were expressed as percentage of the initial concentration, and the number of days that levels were maintained to at least 80% was calculated. Results Haemoglobin concentrations were maintained above 80% of their initial concentration with both freezer and refrigerator storage, regardless of buffer formulation or storage duration. Stability at room temperature was significantly better in the new buffer, with haemoglobin remaining above 80% for 20 days compared with six days in the original buffer. Storage at 35℃ or 50℃ in the new buffer maintained haemoglobin above 80% for eight and two days, respectively. Conclusion The new formulation buffer has enhanced haemoglobin stabilizing properties when samples are exposed to temperatures greater than 22℃. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives Positive rates in faecal immunochemical test (FIT)-based colorectal cancer screening programmes vary, suggesting that differences between programmes may affect test results. We examined whether demographic, pathological, behavioural, and environmental factors affected haemoglobin concentration and positive rates where samples are mailed. Methods A retrospective cohort study; 34,298 collection devices were sent, over five years, to screening invitees (median age 60.6). Participant demographics, temperature on sample postage day, and previous screening were recorded. Outcomes from colonoscopy performed within a year following FIT were collected. Multivariate logistic regression identified significant predictors of test positivity. Results Higher positive rate was independently associated with male gender, older age, lower socioeconomic status, and distally located neoplasia, and negatively associated with previous screening (p < 0.05). Older males had higher faecal haemoglobin concentrations and were less likely to have a false positive result at colonoscopy (p < 0.05). High temperature on the sample postage day was associated with reduced haemoglobin concentration and positivity rate (26–35℃: Odds ratio 0.78, 95% confidence interval 0.66–0.93), but was not associated with missed significant neoplasia at colonoscopy (p > 0.05). Conclusions Haemoglobin concentrations, and therefore FIT positivity, were affected by factors that vary between screening programmes. Participant demographics and high temperature at postage had significant effects. The impact of temperature could be reduced by seasonal scheduling of invitations. The importance of screening, and following up positive test results, particularly in older males, should be promoted. [ABSTRACT FROM AUTHOR]

The article discusses a study conducted to evaluate the impact of the National Bowel Cancer Screening Program (NBCSP) in South Australia. The study compared the results of patients with colorectal cancer (CRC) from the NBCSP and the South Australian Cancer Registry. It concluded that CRCs were diagnosed at an early stage in the NBCSP compared to others, leading to a reduction in CRC mortality rates in Australia.

Background: The gastrokinetic drug erythromycin is commonly administered to critically ill patients during intragastric feeding to augment small intestinal nutrient delivery. However, erythromycin has been reported to increase the prevalence of diarrhea, which may reflect reduced absorption and/or accelerated small intestinal transit. Objective: The objective was to evaluate the effects of intravenous erythromycin on small intestinal nutrient absorption and transit in the critically ill. Design: On consecutive days, erythromycin (200 mg in 20 mL 0.9% saline) or placebo (20 mL 0.9% saline) were infused intravenously between -20 and 0 min in a randomized, blinded, crossover fashion. Between 0 and 30 min, a liquid nutrient containing 3-O-methylglucose (3-OMG), [13C]triolein, and [99mTc]sulfur colloid was administered directly into the small intestine at 2 kcal/min. Serum 3-OMG concentrations and exhaled 13CO2 (indices of glucose and lipid absorption, respectively) were measured. Cecal arrival of the infused nutrient was determined by scintigraphy. Data are medians (ranges) and were analyzed by using Wilcoxon's signed-rank test. Results: Thirty-two mechanically ventilated patients were studied. Erythromycin increased small intestinal glucose absorption [3- OMG AUC360: 105.2 (28.9-157.0) for erythromycin compared with 91.8 (51.4-147.9) mmol/L• min for placebo; P = 0.029] but tended to reduce lipid absorption [cumulative percentage dose 13CO2 recovered: 10.4 (0-90.6) compared with 22.6 (0-100) %; P = 0.06]. A trend to slower transit was observed after erythromycin [300 (39- 360) compared with 228 (33-360) min; P = 0.07]. Conclusions: Acute administration of erythromycin increases small intestinal glucose absorption in the critically ill, but there was a tendency for the drug to reduce small intestinal lipid absorption and slow transit. These observations have implications for the use of erythromycin as a gastrokinetic drug in the critically ill. This trial was Registered in the Australian New Zealand Clinical Trials Registry as ACTRN 12610000615088. [ABSTRACT FROM AUTHOR]

Background & Aims: Swallowing difficulties become increasingly prevalent in older age. Differences exist in lower esophageal sphincter (LES) function between older and younger patients with dysphagia, but the contribution of aging per se to these is unclear. Methods: Esophageal motor function was measured using high resolution manometry in older (aged 81±1.7 yrs) and younger (23±1.7 yrs) asymptomatic healthy adults. After baseline recording, motility was assessed by swallowing boluses of liquid (right lateral and upright postures) and solids. Basal LES pressure, integrated relaxation pressure, distal esophageal peristaltic amplitude, distal contractile integral and velocity were measured. Data are presented as mean ± SEM. Results: Despite a trend for lower basal LES pressure (15.8±2.9 mmHg vs. 21.0±0.2 mmHg; P=0.08), completeness of LES relaxation was reduced in older subjects (liquid RL: P=0.003; UR: P=0.007; solid: P=0.03), with higher integrated relaxation pressure when upright (liquid: 6.9±1.1 vs. 3.1+0.4 mmHg; P=0.01; solids: 8.1±1.1 vs. 3.6+0.3 mmHg; P=0.001) and a longer time to recovery after liquid boluses (right lateral: P=0.01; upright: P=0.04). In young, but not older adults, esophageal peristaltic velocity was increased when upright (3.6±0.2 cm/sec; P=0.04) and reduced with solids (3.0±0.1 cm-s; P=0.03). Distal contraction amplitude was higher with solid cf. liquid in the younger individuals (51.8±7.9 mmHg vs. 41,4±6.2 mmHg; P=0.03). In elderly subjects, the distal contractile integral was higher with liquid swallows in the upright posture (P=0.006). Conclusion: There are subtle changes in LES function even in asymptomatic older individuals. These agerelated changes may contribute to the development of dysphagia. [ABSTRACT FROM AUTHOR]

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., (©2019 American Association for Cancer Research.)

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.

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., (© 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Inflammatory bowel disease (IBD) management is increasingly concentrated in units with expertise in the condition leading to substantial improvement in outcomes. Such units often employ nurses with a specialised interest in IBD with enhancements in care reflecting in part the promotion of more efficient use of medical and hospital services by this role. However, the relative contributions of nurse specialist input, and the effect of medical staff with a sub-speciality interest in IBD are unclear although this has major implications for funding. Determining the value of IBD nurses by assessing the direct impact of an IBD nurse on reducing admissions and outpatient attendances has immediate cost benefits, but the long-term sustainability of these savings has not been previously investigated. We therefore assessed the effect of an IBD nurse on patient outcomes in a tertiary hospital IBD Unit where the position has been established for 8years by measuring the number of occasions of service (OOS) and outcomes of all interactions between the nurse and patients in a tertiary hospital IBD Unit over a 12-month period. There were 4920 OOS recorded involving 566 patients. IBD nurse intervention led to avoidance of 27 hospital admissions (representing a saving of 171 occupied bed days), 32 Emergency Department presentations and 163 outpatient reviews. After deducting salary and on-costs related to the IBD nurse there was a net direct saving to the hospital of AUD $136,535. IBD nurse positions provide sustained direct cost reductions to health services via reducing hospital attendances. This is additional to benefits that accrue through better patient knowledge, earlier presentation and increased compliance., (© 2013 Elsevier B.V. All rights reserved.)

Aim: To evaluate individual components of the antro-pyloro-duodenal (APD) motor response to graded small intestinal glucose infusions in healthy humans., Methods: APD manometry was performed in 15 healthy subjects (12 male; 40 ± 5 years, body mass index 26.5 ± 1.6 kg/m(2)) during four 20-min intraduodenal infusions of glucose at 0, 0.5, 1.0 and 1.5 kcal/min, in a randomised double-blinded fashion. Glucose solutions were infused at a rate of 1 mL/min and separated by 40-min "wash-out" period. Data are mean ± SE. Inferential analyses are repeated measure analysis of variance with Bonferroni post-hoc testing., Results: At 0 kcal/min frequency of pressure waves were: antrum (7.5 ± 1.8 waves/20 min) and isolated pyloric pressure waves (IPPWs) (8.0 ± 2.3 waves/20 min) with pyloric tone (0.0 ± 0.9 mmHg). Intraduodenal glucose infusion acutely increased IPPW frequency (P < 0.001) and pyloric tone (P = 0.015), and decreased antral wave frequency (P = 0.007) in a dose-dependent fashion. A threshold for stimulation was observed at 1.0 kcal/min for pyloric phasic pressure waves (P = 0.002) and 1.5 kcal/min for pyloric tone and antral contractility., Conclusion: There is hierarchy for the activation of gastrointestinal motor responses to duodenal glucose infusion. An increase in IPPWs is the first response observed.

Aim: To examine factors influencing percutaneous endoscopic gastrostomy (PEG) uptake and outcomes in motor neuron disease (MND) in a tertiary care centre., Methods: Case notes from all patients with a confirmed diagnosis of MND who had attended the clinic at the Repatriation General Hospital between January 2007 and January 2011 and who had since died, were audited. Data were extracted for demographics (age and gender), disease characteristics (date of onset, bulbar or peripheral predominance, complications), date and nature of discussion of gastrostomy insertion, nutritional status [weight measurements, body mass index (BMI)], date of gastrostomy insertion and subsequent progress (duration of survival) and quality of life (QoL) [Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)]. In addition, the type of clinician initiating the discussion regarding gastrostomy was recorded as Nutritional Support Team (involved in providing nutrition input viz Gastroenterologist, Speech Pathologist, Dietitian) and other (involved in non-nutritional aspects of patient care). Factors affecting placement and outcomes including length of survival, change in weight and QoL were determined., Results: Case records were available for all 86 patients (49 men, mean age at diagnosis 66.4 years). Thirty-eight patients had bulbar symptoms and 48 had peripheral disease as their presenting feature. Sixty-six patients reported dysphagia. Thirty-one patients had undergone gastrostomy insertion. The major indications for PEG placement were dysphagia and weight loss. Nine patients required immediate full feeding, whereas 17 patients initially used the gastrostomy to supplement oral intake, 4 for medication administration and 1 for hydration. Initially the PEG regime met 73% ± 31% of the estimated total energy requirements, increasing to 87% ± 32% prior to death. There was stabilization of weight in patients undergoing gastrostomy [BMI at 3 mo (22.6 ± 2.2 kg/m(2)) and 6 mo (22.5 ± 2.0 kg/m(2)) after PEG placement compared to weight at the time of the procedure (22.5 ± 3.0 kg/m(2))]. However, weight loss recurred in the terminal stages of the illness. There was a strong trend for longer survival from diagnosis among MND in PEG recipients with limb onset presentation compared to similar patients who did not undergo the procedure (P = 0.063). Initial discussions regarding PEG insertion occurred earlier after diagnosis when seen by nutrition support team (NST) clinicians compared to other clinicians. (5.4 ± 7.0 mo vs 11.9 ± 13.4 mo, P = 0.028). There was a significant increase in PEG uptake (56% vs 24%, P = 0.011) if PEG discussions were initiated by the NST staff compared to other clinicians. There was no change in the ALSFRS-R score in patients who underwent PEG (pre 34.1 ± 8.6 vs post 34.8 ± 7.4), although in non-PEG recipients there was a non-significant fall in this score (33.7 ± 7.9 vs 31.6 ± 8.8). Four patients died within one month of the procedure, 4 developed bacterial site infection requiring antibiotics and 1 required endoscopic therapy for gastric bleeding. Less serious complications attributed to the procedure included persistent gastrostomy site discomfort, poor appetite, altered bowel function and bloating., Conclusion: Initial discussion with NST clinicians increases PEG uptake in MND. Gastrostomy stabilizes patient weight but weight loss recurs with advancing disease.

Aim: To characterize the effects of age on the mechanisms underlying the common condition of esophageal dysphagia in older patients, using detailed manometric analysis., Methods: A retrospective case-control audit was performed on 19 patients aged ≥ 80 years (mean age 85 ± 0.7 year) who underwent a manometric study for dysphagia (2004-2009). Data were compared with 19 younger dysphagic patients (32 ± 1.7 years). Detailed manometric analysis performed prospectively included basal lower esophageal sphincter pressure (BLESP), pre-swallow and nadir LESP, esophageal body pressures and peristaltic duration, during water swallows (5 mL) in right lateral (RL) and upright (UR) postures and with solids. Data are mean ± SE; a P-value < 0.05 was considered significant., Results: Elderly dysphagic patients had higher BLESP than younger patients (23.4 ± 3.8 vs 14.9 ± 1.2 mmHg; P < 0.05). Pre-swallow LESP was elevated in the elderly in both postures (RL: 1 and 4 s P = 0.019 and P = 0.05; UR: P < 0.05 and P = 0.05) and solids (P < 0.01). In older patients, LES nadir pressure was higher with liquids (RL: 2.3 ± 0.6 mmHg vs 0.7 ± 0.6 mmHg, P < 0.05; UR: 3.5 ± 0.9 mmHg vs 1.6 ± 0.5 mmHg, P = 0.01) with shorter relaxation after solids (7.9 ± 1.5 s vs 9.7 ± 0.4 s, P = 0.05). No age-related differences were seen in esophageal body pressures or peristalsis duration., Conclusion: Basal LES pressure is elevated and swallow-induced relaxation impaired in elderly dysphagic patients. Its contribution to dysphagia and the effects of healthy ageing require further investigation.

Introduction: Glucagon-like peptide-1 (GLP-1) attenuates the glycaemic response to small intestinal nutrient infusion in stress-induced hyperglycaemia and reduces fasting glucose concentrations in critically ill patients with type-2 diabetes. The objective of this study was to evaluate the effects of acute administration of GLP-1 on the glycaemic response to small intestinal nutrient infusion in critically ill patients with pre-existing type-2 diabetes., Methods: Eleven critically ill mechanically-ventilated patients with known type-2 diabetes received intravenous infusions of GLP-1 (1.2 pmol/kg/minute) and placebo from t = 0 to 270 minutes on separate days in randomised double-blind fashion. Between t = 30 to 270 minutes a liquid nutrient was infused intraduodenally at a rate of 1 kcal/min via a naso-enteric catheter. Blood glucose, serum insulin and C-peptide, and plasma glucagon were measured. Data are mean ± SEM., Results: GLP-1 attenuated the overall glycaemic response to nutrient (blood glucose AUC30-270 min: GLP-1 2,244 ± 184 vs. placebo 2,679 ± 233 mmol/l/minute; P = 0.02). Blood glucose was maintained at < 10 mmol/l in 6/11 patients when receiving GLP-1 and 4/11 with placebo. GLP-1 increased serum insulin at 270 minutes (GLP-1: 23.4 ± 6.7 vs. placebo: 16.4 ± 5.5 mU/l; P < 0.05), but had no effect on the change in plasma glucagon., Conclusions: Exogenous GLP-1 in a dose of 1.2 pmol/kg/minute attenuates the glycaemic response to small intestinal nutrient in critically ill patients with type-2 diabetes. Given the modest magnitude of the reduction in glycaemia the effects of GLP-1 at higher doses and/or when administered in combination with insulin, warrant evaluation in this group., Trial Registration: ANZCTR:ACTRN12610000185066.

The contribution of small intestinal motor activity to nutrient absorption is poorly defined. A reduction in duodenal flow events after hyoscine butylbromide, despite no change in pressure waves, was associated with reduced secretion of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) and a delay in glucose absorption. The aim of this study was to investigate the effect of metoclopramide on duodenal motility and flow events, incretin hormone secretion, and glucose absorption. Eight healthy volunteers (7 males and 1 female; age 29.8 ± 4.6 yr; body mass index 24.5 ± 0.9 kg/m²) were studied two times in randomized order. A combined manometry and impedance catheter was used to measure pressure waves and flow events in the same region of the duodenum simultaneously. Metoclopramide (10 mg) or control was administered intravenously as a bolus, followed by an intraduodenal glucose infusion for 60 min (3 kcal/min) incorporating the ¹⁴C-labeled glucose analog 3-O-methylglucose (3-OMG). We found that metoclopramide was associated with more duodenal pressure waves and propagated pressure sequences than control (P < 0.05 for both) during intraduodenal glucose infusion. However, the number of duodenal flow events, blood glucose concentration, and plasma 3-[¹⁴C]OMG activity did not differ between the two study days. Metoclopramide was associated with increased plasma concentrations of GLP-1 (P < 0.05) and GIP (P = 0.07) but lower plasma insulin concentrations (P < 0.05). We concluded that metoclopramide was associated with increased frequency of duodenal pressure waves but no change in duodenal flow events and glucose absorption. Furthermore, GLP-1 and GIP release increased with metoclopramide, but insulin release paradoxically decreased.

Background and Aims: Isotope breath tests are increasingly used to evaluate the effects of prokinetic drugs on gastric emptying. The aim was to assess intrasubject variability in gastric emptying, when using an isotope breath test in the critically ill., Methods: A retrospective analysis of data was undertaken in 12 patients who had gastric emptying measurements on consecutive days using a (13)C-octanoic acid breath test. The gastric emptying coefficient--GEC (a global index for the gastric emptying rate), and the t(50) (calculated time for 50% of meal to empty) were calculated, together with the coefficient of variability for these parameters. Data are mean (SD)., Results: Neither GEC (day 1: 3.3 (0.8) vs. day 2: 3.1 (0.6); P = 0.31) nor t(50) (day 1: 127 (43) min vs. day 2: 141 (48) min; P = 0.46) were significantly different between the two days. Intrasubject variability was less for GEC (15.6%) than for t(50) (31.8%)., Conclusion: There is only modest intrasubject variability in GEC measurements using the (13)C-octanoic acid breath test in critically ill patients. As such, it may be an acceptable measurement tool to assess the effects of prokinetic drugs in this group., (Copyright © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

In health, hormones secreted from the gastrointestinal tract have an important role in regulating gastrointestinal motility, glucose metabolism and immune function. Recent studies in the critically ill have established that the secretion of a number of these hormones is abnormal, which probably contributes to disordered gastrointestinal and metabolic function. Furthermore, manipulation of endogenous secretion, physiological replacement and supra-physiological treatment (pharmacological dosing) of these hormones are likely to be novel therapeutic targets in this group. Fasting ghrelin concentrations are reduced in the early phase of critical illness, and exogenous ghrelin is a potential therapy that could be used to accelerate gastric emptying and/or stimulate appetite. Motilin agonists, such as erythromycin, are effective gastrokinetic drugs in the critically ill. Cholecystokinin and peptide YY concentrations are elevated in both the fasting and postprandial states, and are likely to contribute to slow gastric emptying. Accordingly, there is a rationale for the therapeutic use of their antagonists. So-called incretin therapies (glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide) warrant evaluation in the management of hyperglycaemia in the critically ill. Exogenous glucagon-like peptide-2 (or its analogues) may be a potential therapy because of its intestinotropic properties.

Introduction: Hyperglycaemia occurs frequently in the critically ill, affects outcome adversely, and is exacerbated by enteral feeding. Furthermore, treatment with insulin in this group is frequently complicated by hypoglycaemia. In healthy patients and those with type 2 diabetes, exogenous glucagon-like peptide-1 (GLP-1) decreases blood glucose by suppressing glucagon, stimulating insulin and slowing gastric emptying. Because the former effects are glucose-dependent, the use of GLP-1 is not associated with hypoglycaemia. The objective of this study was to establish if exogenous GLP-1 attenuates the glycaemic response to enteral nutrition in patients with critical illness induced hyperglycaemia., Methods: Seven mechanically ventilated critically ill patients, not previously known to have diabetes, received two intravenous infusions of GLP-1 (1.2 pmol/kg/min) and placebo (4% albumin) over 270 minutes. Infusions were administered on consecutive days in a randomised, double-blind fashion. On both days a mixed nutrient liquid was infused, via a post-pyloric feeding catheter, at a rate of 1.5 kcal/min between 30 and 270 minutes. Blood glucose and plasma GLP-1, insulin and glucagon concentrations were measured., Results: In all patients, exogenous GLP-1 infusion reduced the overall glycaemic response during enteral nutrient stimulation (AUC30-270 min GLP-1 (2077 +/- 144 mmol/l min) vs placebo (2568 +/- 208 mmol/l min); P = 0.02) and the peak blood glucose (GLP-1 (10.1 +/- 0.7 mmol/l) vs placebo (12.7 +/- 1.0 mmol/l); P < 0.01). The insulin/glucose ratio at 270 minutes was increased with GLP-1 infusion (GLP-1 (9.1 +/- 2.7) vs. placebo (5.8 +/- 1.8); P = 0.02) but there was no difference in absolute insulin concentrations. There was a transient, non-sustained, reduction in plasma glucagon concentrations during GLP-1 infusion (t = 30 minutes GLP-1 (90 +/- 12 pmol/ml) vs. placebo (104 +/- 10 pmol/ml); P < 0.01)., Conclusions: Acute, exogenous GLP-1 infusion markedly attenuates the glycaemic response to enteral nutrition in the critically ill. These observations suggest that GLP-1 and/or its analogues have the potential to manage hyperglycaemia in the critically ill., Trial Registration: Australian New Zealand Clinical Trials Registry number: ACTRN12609000093280.

Introduction: Delayed gastric emptying occurs frequently in critically ill patients and has the potential to adversely affect both the rate, and extent, of nutrient absorption. However, there is limited information about nutrient absorption in the critically ill, and the relationship between gastric emptying (GE) and absorption has hitherto not been evaluated. The aim of this study was to quantify glucose absorption and the relationships between GE, glucose absorption and glycaemia in critically ill patients., Methods: Studies were performed in nineteen mechanically-ventilated critically ill patients and compared to nineteen healthy subjects. Following 4 hours fasting, 100 ml of Ensure, 2 g 3-O-methyl glucose (3-OMG) and 99mTc sulphur colloid were infused into the stomach over 5 minutes. Glucose absorption (plasma 3-OMG), blood glucose levels and GE (scintigraphy) were measured over four hours. Data are mean +/- SEM. A P-value < 0.05 was considered significant., Results: Absorption of 3-OMG was markedly reduced in patients (AUC240: 26.2 +/- 18.4 vs. 66.6 +/- 16.8; P < 0.001; peak: 0.17 +/- 0.12 vs. 0.37 +/- 0.098 mMol/l; P < 0.001; time to peak; 151 +/- 84 vs. 89 +/- 33 minutes; P = 0.007); and both the baseline (8.0 +/- 2.1 vs. 5.6 +/- 0.23 mMol/l; P < 0.001) and peak (10.0 +/- 2.2 vs. 7.7 +/- 0.2 mMol/l; P < 0.001) blood glucose levels were higher in patients; compared to healthy subjects. In patients; 3-OMG absorption was directly related to GE (AUC240; r = -0.77 to -0.87; P < 0.001; peak concentrations; r = -0.75 to -0.81; P = 0.001; time to peak; r = 0.89-0.94; P < 0.001); but when GE was normal (percent retention240 < 10%; n = 9) absorption was still impaired. GE was inversely related to baseline blood glucose, such that elevated levels were associated with slower GE (ret 60, 180 and 240 minutes: r > 0.51; P < 0.05)., Conclusions: In critically ill patients; (i) the rate and extent of glucose absorption are markedly reduced; (ii) GE is a major determinant of the rate of absorption, but does not fully account for the extent of impaired absorption; (iii) blood glucose concentration could be one of a number of factors affecting GE.

Purpose of Review: Enteral nutrition is frequently unsuccessful in the critically ill due to gastrointestinal dysfunction. Current treatment strategies are often disappointing. In this article upper gastrointestinal function in health together with abnormalities seen during critical illness are reviewed, and potential therapeutic options summarized., Recent Findings: Reflux oesophagitis occurs frequently due to reduced or absent lower oesophageal sphincter tone. In the stomach a number of motor patterns contribute to slow gastric emptying. The fundus has reduced compliance, there are less frequent contractions in both the proximal and distal stomach, isolated pyloric activity is increased and the organization of duodenal motor activity is abnormal. In response to nutrients, enterogastric feedback is enhanced, fundic relaxation and subsequent recovery is delayed, antral motility is further reduced and localized pyloric contractions stimulated. Elevated concentrations of hormones such as cholecystokinin and peptide YY are potential mediators for these phenomena. Rapid tachyphylaxis occurs with the commonly used prokinetics, metoclopramide and erythromycin, and novel agents are under investigation. Independent of gastric emptying, nutrient absorption is reduced., Summary: There has been considerable progress in understanding the pathogenesis of mechanisms causing feed intolerance in critical illness, but this is yet to be translated into therapeutic benefit.

Introduction: Delayed gastric emptying and feed intolerance occur frequently in the critically ill. In these patients, gastric motor responses to nutrients are disturbed. Peptide YY (PYY) slows gastric emptying. The aim of this study was to determine fasting and nutrient-stimulated plasma PYY concentrations and their relationship to cholecystokinin (CCK) in critically ill patients., Methods: Studies were performed in 19 unselected mechanically ventilated critically ill patients (12 males; 48 +/- 7 years old) in a randomised, single-blind fashion. Subjects received a 60-minute duodenal infusion of Ensure at either 1 or 2 kcal/minute. Blood samples were collected at baseline and at 20, 40, 60, and 180 minutes following commencement of the nutrient infusion for the measurement of plasma PYY and CCK concentrations (using radioimmunoassay). Patient data were compared to 24 healthy subjects (17 males; 43 +/- 2 years old)., Results: Fasting PYY concentration was higher in patients (P < 0.05), particularly in those with feed intolerance (P < 0.05). Plasma PYY concentrations were higher in patients during nutrient infusion (area under the curve [AUC] at 1 kcal/minute: 2,265 +/- 718 versus 1,125 +/- 138 pmol/l.min, P < 0.05; at 2 kcal/minute: 2,276 +/- 303 versus 1,378 +/- 210 pmol/l.min, P = 0.01) compared to healthy subjects. The magnitude of PYY elevation was greater in patients during the 1 kcal/minute infusion (AUC: 441 +/- 153 versus 186 +/- 58 pmol/l.min, P < 0.05), but not the 2 kcal/minute infusion. Fasting and nutrient-stimulated plasma CCK concentrations were higher in patients (P < 0.05). There was a relationship between plasma PYY and CCK concentrations during fasting (r = 0.52, P < 0.05) and nutrient infusion (r = 0.98, P < 0.0001)., Conclusion: In critical illness, both fasting and nutrient-stimulated plasma PYY concentrations are elevated, particularly in patients with feed intolerance, in conjunction with increased CCK concentrations.