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Introduction: As effective interventions to prevent inpatient falls are lacking, a novel technological intervention was trialed. The Ambient Intelligent Geriatric Management (AmbIGeM) system used wearable sensors that detected and alerted staff of patient movements requiring supervision. While the system did not reduce falls rate, it is important to evaluate the acceptability, usability, and safety of the AmbIGeM system, from the perspectives of patients and informal carers. Methods: We conducted a mixed-methods study using semistructured interviews, a pre-survey and post-survey. The AmbIGeM clinical trial was conducted in two geriatric evaluation and management units and a general medical ward, in two Australian hospitals, and a subset of participants were recruited. Within 3 days of being admitted to the study wards and enrolling in the trial, 31 participants completed the pre-survey. Prior to discharge (post-intervention), 30 participants completed the post-survey and 27 participants were interviewed. Interview data were thematically analyzed and survey data were descriptively analyzed. Results: Survey and interview participants had an average age of 83 (SD 9) years, 65% were female, and 41% were admitted with a fall. Participants considered the AmbIGeM system a good idea. Most but not all thought the singlet and sensor component as acceptable and comfortable, with no privacy concerns. Participants felt reassured with extra monitoring, although sometimes misunderstood the purpose of AmbIGeM as detecting patient falls. Participants’ acceptability was strongly positive, with median 8+ (0–10 scale) on pre- and post-surveys. Discussion/Conclusion: Patients’ acceptability is important to optimize outcomes. Overall older patients considered the AmbIGeM system as acceptable, usable, and improving safety. The findings will be important to guide refinement of this and other similar technology developments.

The Ambient Intelligent Geriatric Management (AmbIGeM) system combines wearable sensors with artificial intelligence to trigger alerts to hospital staff before a fall. A clinical trial found no effect across a heterogenous population, but reported a reduction in the injurious falls rate in a post hoc analysis of patients on Geriatric Evaluation Management Unit (GEMU) wards. Cost-effectiveness and Value of Information (VoI) analyses of the AmbIGeM system in GEMU wards was undertaken.An Australian health-care system perspective and 5-year time horizon were used for the cost-effectiveness analysis. Implementation costs, inpatient costs and falls data were collected. Injurious falls were defined as causing bruising, laceration, fracture, loss of consciousness, or if the patient reported persistent pain. To compare costs and outcomes, generalised linear regression models were used to adjust for baseline differences between the intervention and usual care groups. Bootstrapping was used to represent uncertainty. For the VoI analysis, 10,000 different sample sizes with randomly sampled values ranging from 1 to 50,000 were tested to estimate the optimal sample size of a new trial that maximised the Expected Net Benefits of Sampling.An adjusted 0.036 fewer injurious falls (adjusted rate ratio of 0.56) and AUD$4554 lower costs were seen in the intervention group. However, uncertainty that the intervention is cost effective for the prevention of an injurious fall was present at all monetary values of this effectiveness outcome. A new trial with a sample of 4376 patients was estimated to maximise the Expected Net Benefit of Sampling, generating a net benefit of AUD$186,632 at a benefit-to-cost ratio of 1.1.The benefits to cost ratio suggests that a new trial of the AmbIGeM system in GEMU wards may not be high-value compared to other potential trials, and that the system should be implemented. However, a broader analysis of options for preventing falls in GEMU is required to fully inform decision making.Australian and New Zealand Clinical Trial Registry (ACTRN 12617000981325).

Background Caloric supplements are increasingly used by older people, aiming to increase their daily protein intake. These high caloric drinks, rich in glucose and whey-protein in particular, may result in potential harmful decreases in blood pressure (BP). The effect of ingesting whey-protein with glucose and fat on BP is unknown. It has also been assumed that the maximum fall in systolic blood pressure occurs within 2 h of a meal. Methods This study aimed to determine in older men, the effects of whey-protein, alone and mixed with other macronutrients, on systolic (SBP) and diastolic (DBP) blood pressure and heart rate (HR) in older men for 3 h. Thirteen older men (age 75 ± 2yrs; body mass index (BMI) 25.6 ± 0.6 kg/m2) ingested a drink on separate study days: (i) 70 g whey-protein (P280); (ii) 14 g whey-protein, 28 g carbohydrate, 12.4 g fat (M280); (iii) 70 g whey-protein, 28 g carbohydrate, 12.4 g fat (M504); or (iv) a non-caloric control drink (C). Results SBP decreased after all three nutrient drinks compared to the C, with the greatest reduction after the M504 drink (P = 0.008). Maximal decreases in SBP (C: -14 ± 2 mmHg, P280: -22 ± 2 mmHg, M280: -22 ± 4 mmHg, M504: -24 ± 3 mmHg) occurred about 2 h after drink ingestion and this fall was sustained thereafter (120-180 min: P280 and M504 vs. C P 504, with no differences between the effects of the P280 and M280 drinks. Conclusions The effects of whey-protein containing drinks to lower BP and increase HR appear to be primarily dependent on their energy content rather than macronutrient composition and may persist for at least 3 h after ingestion,. Pure whey-protein drinks may represent the best approach to maximize protein intake without increasing the potential for deleterious BP falls in older people. Trial registration ACTRN12614000846628, 14/03/2019.

OBJECTIVES: There is very limited information about glycemic control after discharge from the ICU. The aims of this study were to evaluate the prevalence of hypoglycemia in ICU survivors with type-2 diabetes and determine whether hypoglycemia is associated with cardiac arrhythmias. DESIGN: Prospective, observational, two-center study. Participants underwent up to 5 days of simultaneous blinded continuous interstitial glucose monitoring and ambulatory 12-lead electrocardiogram monitoring immediately after ICU discharge during ward-based care. Frequency of arrhythmias, heart rate variability, and cardiac repolarization markers were compared between hypoglycemia (interstitial glucose ≤ 3.5 mmol/L) and euglycemia (5-10 mmol/L) matched for time of day. SETTING: Mixed medical-surgical ICUs in two geographically distinct university-affiliated hospitals. PATIENTS: Patients with type-2 diabetes who were discharged from ICU after greater than or equal to 24 hours with greater than or equal to one organ failure and were prescribed subcutaneous insulin were eligible. MEASUREMENTS AND MAIN RESULTS: Thirty-one participants (mean ± sd, age 65 ± 13 yr, glycated hemoglobin 64 ± 22 mmol/mol) were monitored for 101 ± 32 hours post-ICU (total 3,117 hr). Hypoglycemia occurred in 12 participants (39%; 95% CI, 22-56%) and was predominantly nocturnal (40/51 hr) and asymptomatic (25/29 episodes). Participants experiencing hypoglycemia had 2.4 ± 0.7 discrete episodes lasting 45 minutes (interquartile range, 25-140 min). Glucose nadir was less than or equal to 2.2 mmol/L in 34% of episodes. The longest episode of nocturnal hypoglycemia was 585 minutes with glucose nadir less than 2.2 mmol/L. Simultaneous electrocardiogram and continuous interstitial glucose monitoring recordings were obtained during 44 hours of hypoglycemia and 991 hours of euglycemia. Hypoglycemia was associated with greater risk of bradycardia but did not affect atrial or ventricular ectopics, heart rate variability, or cardiac repolarization. CONCLUSIONS: In ICU survivors with insulin-treated type-2 diabetes, hypoglycemia occurs frequently and is predominantly nocturnal, asymptomatic, and prolonged.

Background Critical illness leads to muscle wasting which may be attenuated with augmented calorie delivery. The Augmented versus Routine approach to Giving Energy Trial (TARGET) randomized 4000 patients to receive energy-dense (1.5kcal/ml) or standard (1.0kcal/ml) enteral nutrition. The aim of this sub-study was to evaluate whether augmented calorie delivery attenuates muscle loss and maintains strength and physical function when compared to routine care. Methods TARGET participants from a single participating ICU were eligible for enrolment in this sub-study if consent could be obtained. Ultrasound-derived muscle layer thickness (MLT) at three landmarks (quadriceps, forearm and mid-upper arm) and handgrip strength were measured at baseline and every 7 days until hospital discharge and at 3- and 6-months following randomization. Physical function was also assessed at 3- and 6-months using the ‘get up and go’ and 6-minute walk tests. Data are presented as mean ± standard deviation. Results Eighty patients (1.5kcal: n = 38, 58 ± 14 years, 60% male, APACHE II 20 ± 7 vs. 1.0kcal: n = 42, 54 ± 18 years, 66% male, APACHE II 22 ± 10) were recruited. Although patients in the 1.5kcal group received more calories (2075 ± 344 vs 1325 ± 313 kcal/day; P P = 0.141), hospital discharge (2.47 ± 1.03 vs 2.10 ± 1.08 cm; P = 0.227) or at 3- and 6-months. Similar relationships were seen for forearm and mid-upper arm MLT and handgrip strength at all timepoints. Patients in the 1.5 kcal group took less time to complete the ‘get up and go’ test (6.66 ± 1.33 vs. 9.11 ± 2.94 secs; mean group difference (95% CI) -2.45 (-4.35, -0.55); P = 0.014), but there was no difference between groups at the 6-month follow-up. There were no differences in the distances walked in the 6-minute walk test at either 3- or 6-month timepoints. Conclusion Augmented calorie delivery compared to routine care did not attenuate loss of muscle size or strength during hospital admission or at 3- and 6-months following randomization. Patients receiving more calories had better physical function at 3- but not at 6-months when assessed using the get up and go test, but not the 6-minute walk test.

Background Gastrointestinal (GI) dysmotility impedes nutrient delivery in critically ill patients with major burns. We aimed to quantify the incidence, timing, and factors associated with GI dysmotility and subsequent nutrition delivery. Methods A 10-year retrospective observational study included mechanically ventilated, adult, critically ill patients with ≥15% total body surface area (TBSA) burns receiving nutrition support. Patients with a single gastric residual volume ≥250 mL were categorized as having GI dysmotility. Daily medical and nutrition data were extracted for ≤14 days in the intensive care unit (ICU). Data are mean (SD) or median (interquartile range). Factors associated with GI dysmotility and the effect on nutrition and clinical outcomes were assessed. Results Fifty-nine patients were eligible; 51% (n = 30) with GI dysmotility and 49% (n = 29) without. Baseline characteristics (dysmotility vs no dysmotility) were age (48 [33-60] vs 34 [26-46] years); Acute Physiology and Chronic Health Evaluation II score (16 [12-17] vs 13 [10-16]); sex ([men] 80% vs 86%); and TBSA (49% [35%-59%] vs 38% [26%-55%]). Older age was associated with increased probability of dysmotility (P = .049). GI dysmotility occurred 32 (19-63) hours after ICU admission but was not associated with reduced nutrient delivery. Postpyloric tube insertions were attempted in 83% (n = 25) of patients, with 72% (n = 18) being successful. Postpyloric feeding achieved higher nutrition adequacy than gastric feeding (energy: 82% [95% CI, 70-94] vs 68% [95% CI, 63-74], P = .036; protein: 75% [95% CI, 65-86] vs 61% [95% CI, 56-65], P = .009). Conclusion GI dysmotility occurs early in critically ill burn patients, and postpyloric feeding improves nutrition delivery.

Rationale: The long-term effects of delivering approximately 100% of recommended calorie intake via the enteral route during critical illness compared with a lesser amount of calories are unknown.O...

Background Intermittent fasting (IF) is proposed as a viable alternative to moderate calorie restriction (CR) for weight loss and metabolic health, but few long term randomized trials have been conducted. This protocol paper describes the rationale and detailed protocol for DIRECT study ( D aily versus I ntermittent R estriction of E nergy: C ontrolled T rial to Reduce Diabetes Risk), comparing long term effectiveness of IF versus CR on metabolic health in individuals who are at increased risk of developing type 2 diabetes. Methods Anticipated 260 non-diabetic men and women aged 35–75 years, BMI 25−50 kg/m2 with score ≥12 on the Australian Diabetes Risk (AUSDRISK) calculator will be recruited into this open-label, multi-arm, parallel group sequential randomized controlled trial. Participants will be randomized to one of three groups for 18 months: IF (30% of energy needs on fast days), CR (70% of energy needs daily), or standard care (SC) group. All participants will visit the clinic fortnightly for weight assessments during active intervention phase (6 months), followed by a 12-month follow-up phase. IF and CR groups will receive further diet counselling by dietitian. Two primary outcomes are the changes in glycated haemoglobin (HbA1c) and postprandial glucose area under the curve (AUC) at week 24 post-randomization. Secondary outcomes include changes in weight, body composition via dual-energy X-ray absorptiometry, gastro-intestinal hormones, cardiovascular risk factors, and dietary record by a smartphone-based application. Discussion This study will provide substantial evidence as to whether IF is an effective nutrition intervention for glycaemic control in a population at risk of developing type 2 diabetes.

Slow gastric emptying occurs frequently during critical illness and is roughly quantified at bedside by large gastric residual volumes (GRVs). A previously published trial (The Augmented versus Routine approach to Giving Energy Trial; TARGET) reported larger GRVs with energy-dense (1.5 kcal/mL) compared with standard (1.0 kcal/mL) enteral nutrition (EN), warranting further exploration.To assess the incidence, risk factors, duration, and timing of large GRVs (≥250 mL) and its relation to clinical outcomes in mechanically ventilated adults.A post-hoc analysis of TARGET data in patients with ≥1 GRV recorded. Data are n (%) or median [IQR].Of 3876 included patients, 1777 (46%) had ≥1 GRV ≥250 mL, which was more common in males (50 compared with 39%; P0.001) and in patients receiving energy-dense compared with standard EN (52 compared with 40%; RR = 1.27 (95% CI: 1.19, 1.36); P0.001) in whom it also lasted longer (1 [0-2] compared with 0 [0-1] d; P0.001), with no difference in time of onset after EN initiation (day 1 [0-2] compared with 1 [0-2]; P = 0.970). Patients with GRV ≥250 mL were more likely to have the following: vasopressor administration (88 compared with 76%; RR = 1.15 [1.12, 1.19]; P0.001), positive blood cultures (16 compared with 8%; RR = 1.92 [1.60, 2.31]; P0.001), intravenous antimicrobials (88 compared with 81%; RR = 1.09 [1.06, 1.12]; P0.001), and prolonged intensive care unit (ICU) stay (ICU-free days to day 28; 12.9 [0.0-21.0] compared with 20.0 [3.9-24.0]; P0.001), hospital stay (hospital-free days to day 28: 0.0 [0.0-12.0] compared with 7.0 [0.0-17.6] d; P0.001), ventilatory support (ventilator-free days to day 28: 16.0 [0.0-23.0] compared with 22.0 [8.0-25.0]; P0.001), and a higher 90-d mortality (29 compared with 23%; adjusted: RR = 1.17 [1.05, 1.30]; P = 0.003).Large GRVs were more common in males and those receiving energy-dense formulae, occurred early and were short-lived, and were associated with a number of negative clinical sequelae, including increased mortality, even when adjusted for illness severity. This trial was registered at clinicaltrials.gov as NCT02306746.

It is uncertain whether lixisenatide has postprandial insulinotropic effects when its effect on slowing gastric emptying is considered, in healthy subjects and type 2 diabetes mellitus (T2DM). We evaluated the effects of single administration of 10 μg sc lixisenatide on glycaemia, insulin secretion and gastric emptying (GE), measured using the 'gold standard' technique of scintigraphy following an oral glucose load (75 g glucose).Fifteen healthy subjects (nine men, six women; age 67.2 ± 2.3 years) and 15 patients with T2DM (nine men, six women; age 61.9 ± 2.3 years) had measurements of GE, plasma glucose, insulin and C-peptide for 180 min after a radiolabeled 75 g glucose drink on two separate days. All subjects received lixisenatide (10 μg sc) or placebo in a randomised, double-blind, crossover fashion 30 min before the drink. Insulin secretory response (ISR) was determined using the C-peptide deconvolution method.GE was markedly slowed by lixisenatide compared with placebo in both healthy subjects (1.45 ± 0.10 kcal/min for placebo vs. 0.60 ± 0.14 kcal/min for lixisenatide) and diabetes (1.57 ± 0.06 kcal/min for placebo vs. 0.75 ± 0.13 kcal/min for lixisenatide) (both P 0.001) with no difference between the two groups (P = 0.42). There was a moderate to strong inverse correlation between the early insulin secretory response calculated at 60 min and gastric retention at 60 min with lixisenatide treatment in healthy subjects (r = - 0.8, P = 0.0003) and a trend in type 2 diabetes (r = - 0.4, P = NS), compared with no relationships in the placebo arms (r = - 0.02, P = NS, healthy subjects) and (r = - 0.16, P = NS, type 2 diabetes).The marked slowing of GE of glucose induced by lixisenatide is associated with attenuation in the rise of postprandial glucose in both healthy subjects and diabetes and early insulin secretory response in healthy subjects.NCT02308254.

AmbIGeM is a technological solution to prevent in-patient falls in patients aged >65. It has been evaluated in a 100-week stepped wedge pragmatic design in two geriatric evaluation and management (GEM) wards and a general medical ward in two Australian hospitals (Visvanathan, Ranasinghe, Wilson et al., Injury Prevention, 2017,0:1). Evaluation of acceptability of the AmbIGeM system from the perspectives of patients and staff who experienced it is reported here. 30 patients completed a 24-item survey, 27 patients were interviewed, 22 staff participated in 3 focus groups and 51 staff completed a 39-item survey. Survey data were descriptively analysed, and focus group and interview data were thematically analysed. In patient surveys, patients were overall strongly positive, with means 8+ (on 11-point scale) on most items. In patient interviews, the AmbIGeM system was considered a good idea to prevent falls. Most patients thought the singlets comfortable and had no concerns for their privacy nor impact on normal activity. Patients and families felt reassured, although sometimes they misunderstood the purpose of AmbIGeM. In staff focus groups, staff perceived AmbIGeM beneficial in that it can detect and alert movement in patients who require supervision. In both GEM wards, AmbIGeM was considered particularly beneficial,practical and valuable to use on night shift. Factors such as perceived technical limitations (false and delayed alerts) and felt staff burden impacted on acceptability. In staff surveys, 56% agreed/strongly agreed that AmbIGeM has the capability to prevent falls while 16% disagreed/strongly disagreed, 62% thought AmbIGeM would be more user friendly if it was consistently accurate and 76% believed that AmbIGeM takes a moderate/lot of extra work. Conclusion AmbIGeM is largely acceptable to patients and requires further refinement for staff. Feedback is valuable to further refine the system.

Context The bitter substance quinine modulates the release of a number of gut and gluco-regulatory hormones and upper gut motility. As the density of bitter receptors may be higher in the duodenum than the stomach, direct delivery to the duodenum may be more potent in stimulating these functions. The gastrointestinal responses to bitter compounds may also be modified by sex. Background We have characterized the effects of intragastric (IG) versus intraduodenal (ID) administration of quinine hydrochloride (QHCl) on gut and pancreatic hormones and antropyloroduodenal pressures in healthy men and women. Methods 14 men (26 ± 2 years, BMI: 22.2 ± 0.5 kg/m2) and 14 women (28 ± 2 years, BMI: 22.5 ± 0.5 kg/m2) received 600 mg QHCl on 2 separate occasions, IG or ID as a 10-mL bolus, in randomized, double-blind fashion. Plasma ghrelin, cholecystokinin, peptide YY, glucagon-like peptide-1 (GLP-1), insulin, glucagon, and glucose concentrations and antropyloroduodenal pressures were measured at baseline and for 120 minutes following QHCl. Results Suppression of ghrelin (P = 0.006), stimulation of cholecystokinin (P = 0.030), peptide YY (P = 0.017), GLP-1 (P = 0.034), insulin (P = 0.024), glucagon (P = 0.030), and pyloric pressures (P = 0.050), and lowering of glucose (P = 0.001) were greater after ID-QHCl than IG-QHCl. Insulin stimulation (P = 0.021) and glucose reduction (P = 0.001) were greater in females than males, while no sex-associated effects were found for cholecystokinin, peptide YY, GLP-1, glucagon, or pyloric pressures. Conclusion ID quinine has greater effects on plasma gut and pancreatic hormones and pyloric pressures than IG quinine in healthy subjects, consistent with the concept that stimulation of small intestinal bitter receptors is critical to these responses. Both insulin stimulation and glucose lowering were sex-dependent.

Summary Background & aims Nutrition may be important for recovery from critical illness. Gastrointestinal dysfunction is a key barrier to nutrition delivery in the Intensive Care Unit (ICU) and metabolic rate is elevated exacerbating nutritional deficits. Whether these factors persist following ICU discharge is unknown. We assessed whether delayed gastric emptying (GE) and impaired glucose absorption persist post-ICU discharge. Methods A prospective observational study was conducted in mechanically ventilated adults at 3 time-points: in ICU (V1); on the post-ICU ward (V2); and 3-months after ICU discharge (V3); and compared to age-matched healthy volunteers. On each visit, all participants received a test-meal containing 100 ml of 1 kcal/ml liquid nutrient, labelled with 0.1 g 13C-octanoic acid and 3 g 3-O-Methyl-glucose (3-OMG), and breath and blood samples were collected over 240min to quantify GE (gastric emptying coefficient (GEC)), and glucose absorption (3-OMG concentration; area under the curve (AUC)). Data are mean ± standard error of the mean (SEM) and differences shown with 95% confidence intervals (95%CI). Results Twenty-six critically ill patients completed V1 (M:F 20:6; 62.0 ± 2.9 y; BMI 29.8 ± 1.2 kg/m2; APACHE II 19.7 ± 1.9), 15 completed V2 and eight completed V3; and were compared to 10 healthy volunteers (M:F 6:4; 60.5 ± 7.5 y; BMI 26.0 ± 1.0 kg/m2). GE was significantly slower on V1 compared to health (GEC difference: −0.96 (95%CI -1.61, −0.31); and compared to V2 (−0.73 (−1.16, −0.31) and V3 (−1.03 (−1.47, −0.59). GE at V2 and V3 were not different to that in health (V2: −0.23 (−0.61, 0.14); V3: 0.10 (−0.27, 0.46)). GEC: V1: 2.64 ± 0.19; V2: 3.37 ± 0.12; V3: 3.67 ± 0.10; health: 3.60 ± 0.13. Glucose absorption (3-OMG AUC0-240) was impaired on V1 compared to V2 (−37.9 (−64.2, −11.6)), and faster on V3 than in health (21.8 (0.14, 43.4) but absorption at V2 and V3 did not differ from health. Intestinal glucose absorption: V1: 63.8 ± 10.4; V2: 101.7 ± 7.0; V3: 111.9 ± 9.7; health: 90.7 ± 3.8. Conclusion This study suggests that delayed GE and impaired intestinal glucose absorption recovers rapidly post-ICU. This requires further confirmation in a larger population. The REINSTATE trial was prospectively registered at www.anzctr.org.au . Trial ID ACTRN12618000370202.

Aim: To evaluate the effects of the prandial glucagon-like peptide-1 receptor agonist lixisenatide on gastric emptying and blood pressure (BP) and superior mesenteric artery (SMA) blood flow, and the glycaemic responses to a 75-g oral glucose load in healthy people and those with type 2 diabetes (T2DM). Materials and methods: Fifteen healthy participants (nine men, six women; mean ± SEM age 67.2 ± 2.3 years) and 15 participants with T2DM (nine men, six women; mean ± SEM age 61.9 ± 2.3 years) underwent measurement of gastric emptying, BP, SMA flow and plasma glucose 180 minutes after a radiolabelled 75-g glucose drink on two separate days. All participants received lixisenatide (10 μg subcutaneously) or placebo in a randomized, double-blind, crossover fashion 30 minutes before the glucose drink. Results: Lixisenatide slowed gastric emptying (retention at 120 minutes, P < 0.01), attenuated the rise in SMA flow (P < 0.01) and markedly attenuated the decrease in systolic BP (area under the curve [AUC] 0-120 minutes, P < 0.001) compared to placebo in healthy participants and those with T2DM. Plasma glucose (incremental AUC 0-120 minutes) was greater in participants with T2DM (P < 0.005) than in healthy participants, and lower after lixisenatide in both groups (P < 0.001). Conclusions: In healthy participants and those with T2DM, the marked slowing of gastric emptying of glucose induced by lixisenatide was associated with attenuation of the increments in glycaemia and SMA flow and decrease in systolic BP. Accordingly, lixisenatide may be useful in the management of postprandial hypotension. usc Refereed/Peer-reviewed

BACKGROUND l-Tryptophan reduces energy intake in healthy men. The underlying mechanisms, including appetite, plasma cholecystokinin (CCK), tryptophan (Trp), and the ratio of Trp to large neutral amino acids (Trp:LNAAs ratio), and whether responses differ in lean and obese individuals, are uncertain. OBJECTIVES We evaluated the effects of intragastric Trp on energy intake (primary outcome) and their potential mechanisms, pre- and postmeal, in lean men and those with obesity. METHODS Twelve lean men [mean ± SD age: 30 ± 3 y; BMI (in kg/m2): 23 ± 1] and 13 men with obesity (mean ± SD age: 31 ± 3 y; BMI: 33 ± 1) received, on 3 separate occasions, in double-blind, randomized order, 3 g ("Trp-3") or 1.5 g ("Trp-1.5") Trp, or control ("C"), intragastrically, 30 min before a buffet-meal. Energy intake from the buffet-meal, hunger, fullness, and plasma CCK and amino acid concentrations were measured in response to Trp alone and for 2 h postmeal. Data were analyzed using maximum likelihood mixed-effects models, with treatment, group, and treatment-by-group interaction as fixed effects. RESULTS Trp alone increased plasma CCK, Trp, and the Trp:LNAAs ratio (all P

Background Energy-dense formulae are often provided to critically ill patients with enteral feed intolerance with the aim of increasing energy delivery, yet the effect on gastric emptying is unknown. The rate of gastric emptying of a standard compared with an energy-dense formula was quantified in critically ill patients. Methods Mechanically ventilated adults were randomized to receive radiolabeled intragastric infusions of 200 mL standard (1 kcal/mL) or 100 mL energy-dense (2 kcal/mL) enteral formulae on consecutive days in this noninferiority, blinded, crossover trial. The primary outcome was scintigraphic measurement of gastric retention (percentage at 120 minutes). Other measures included area under the curve (AUC) for gastric retention and intestinal energy delivery (calculated from gastric retention of formulae over time), blood glucose (peak and AUC), and intestinal glucose absorption (using 3-O-methyl-D-gluco-pyranose [3-OMG] concentrations). Comparisons were undertaken using paired mixed-effects models. Data presented are mean ± SE. Results Eighteen patients were studied (male/female, 14:4; age, 55.2 ± 5.3 years). Gastric retention at 120 minutes was greater with the energy-dense formula (standard, 17.0 ± 5.9 vs energy-dense, 32.5 ± 7.1; difference, 12.7% [90% confidence interval, 0.8%-30.1%]). Energy delivery (AUC120 , 13,038 ± 1119 vs 9763 ± 1346 kcal/120 minutes; P = 0.057), glucose control (peak glucose, 10.1 ± 0.3 vs 9.7 ± 0.3 mmol/L, P = 0.362; and glucose AUC120 8.7 ± 0.3 vs 8.5 ± 0.3 mmol/L.120 minutes, P = 0.661), and absorption (3-OMG AUC120 , 38.5 ± 4.0 vs 35.7 ± 4.0 mmol/L.120 minutes; P = .508) were not improved with the energy-dense formula. Conclusion In critical illness, administration of an energy-dense formula does not reduce gastric retention, increase energy delivery to the small intestine, or improve glucose absorption or glucose control; instead, there is a signal for delayed gastric emptying.

The authors wish to correct some minor errors in this article: 1. The fasting insulin secretion rate was correctly shown in Table 1 to be slightly increased after lixisenatide treatment, whereas the text of the Results and Conclusions sections incorrectly reported that it was decreased. 2. Change …

Background International guidelines recommend critically ill adults receive more protein than most receive. We aimed to establish the feasibility of a trial to evaluate whether feeding protein to international recommendations would improve outcomes, in which 1 group received protein doses representative of international guideline recommendations (high protein) and the other received doses similar to usual practice. Methods We conducted a prospective, randomized, blinded, parallel-group, feasibility trial across 6 intensive care units. Critically ill, mechanically ventilated adults expected to receive enteral nutrition (EN) for ≥2 days were randomized to receive EN containing 63 or 100 g/L protein for ≤28 days. Data are mean (SD) or median (interquartile range). Results The recruitment rate was 0.35 (0.13) patients per day, with 120 patients randomized and data available for 116 (n = 58 per group). Protein delivery was greater in the high-protein group (1.52 [0.52] vs 0.99 [0.27] grams of protein per kilogram of ideal body weight per day; difference, 0.53 [95% CI, 0.38-0.69] g/kg/d protein), with no difference in energy delivery (difference, -26 [95% CI, -190 to 137] kcal/kg/d). There were no between-group differences in the duration of feeding (8.7 [7.3] vs 8.1 [6.3] days), and blinding of the intervention was confirmed. There were no differences in clinical outcomes, including 90-day mortality (14/55 [26%] vs 15/56 [27%]; risk difference, -1.3% [95% CI, -17.7% to 15.0%]). Conclusion Conducting a multicenter blinded trial is feasible to compare protein delivery at international guideline-recommended levels with doses similar to usual care during critical illness.

In healthy individuals, intragastric administration of the branched-chain amino acids, leucine and isoleucine, diminishes the glycaemic response to a mixed-nutrient drink, apparently by stimulating insulin and slowing gastric emptying, respectively. This study aimed to evaluate the effects of leucine and isoleucine on postprandial glycaemia and gastric emptying in type-2 diabetes mellitus (T2D).14 males with T2D received, on 3 separate occasions, in double-blind, randomised fashion, either 10 g leucine, 10 g isoleucine or control, intragastrically 30 min before a mixed-nutrient drink (500 kcal; 74 g carbohydrates, 18 g protein, 15 g fat). Plasma glucose, insulin and glucagon were measured from 30 min pre- until 120 min post-drink. Gastric emptying of the drink was also measured.Leucine and isoleucine stimulated insulin, both before and after the drink (all P 0.05; peak (mU/L): control: 70 ± 15; leucine: 88 ± 17; isoleucine: 74 ± 15). Isoleucine stimulated (P 0.05), and leucine tended to stimulate (P = 0.078), glucagon before the drink, and isoleucine stimulated glucagon post-drink (P = 0.031; peak (pg/mL): control: 62 ± 5; leucine: 70 ± 9; isoleucine: 69 ± 6). Neither amino acid affected gastric emptying or plasma glucose (peak (mmol/L): control: 12.0 ± 0.5; leucine: 12.5 ± 0.7; isoleucine: 12.0 ± 0.6).In contrast to health, in T2D, leucine and isoleucine, administered intragastrically in a dose of 10 g, do not lower the glycaemic response to a mixed-nutrient drink. This finding argues against a role for 'preloads' of either leucine or isoleucine in the management of T2D.

Aim To determine the prevalence of malnutrition on admission to the intensive care unit (ICU) and the relationship between nutritional status on admission and clinical outcomes in adult critically ill patients. Methods This was a prospective study in an adult ICU. Patients with expected length of stay (LOS) >48 hours in ICU were assessed for nutritional status using the patient generated-subjective global assessment (PG-SGA) within 48 hours of admission to ICU. Results Primary outcomes were ICU and hospital mortality, ICU and hospital LOS and length of mechanical ventilation. A total of 166 patients were enrolled in this study. Patients were aged 59 ± 17 years on average with a mean BMI of 29 ± 7 kg/m2 and a mean Acute Physiology and Chronic Health Evaluation II score of 19 ± 7. The prevalence of malnutrition in critically ill patients was 36% (n = 60). Mortality rate of malnourished patients was 9% (n = 15) compared to 7.8% (n = 13) in well-nourished patients (adjusted odds ratio, 2.17; 95% confidence interval, 0.9-5.03, P = .069). There was no difference in hospital mortality between malnourished patients and well-nourished patients (10.2% vs 10.2% adjusted odds ratio, 1.93; 95% confidence interval, 0.89-4.19, P = .096). There was no relationship between nutritional status and length of mechanical ventilation (3.0 vs 1.0 days, P = .382)or ICU LOS (4.7 vs 4.8 days, P = .59). Malnourished patients had a longer LOS in hospital than well-nourished patients (24 vs 17 days, P = .03). Conclusion Malnutrition is an independent risk factor for increased hospital LOS.

ContextImpaired lipid metabolism is linked with obesity-associated insulin resistance, which may be reversed by caloric restriction (CR).ObjectiveIn a secondary analysis of a randomized controlled trial, we compared the effects of intermittent fasting (IF) and CR on markers of lipid metabolism in muscle.DesignSeventy-six women (body mass index, 25-40 kg/m2) were randomly assigned to 1 of 3 diets for 8 weeks and provided foods at 70% (CR70 and IF70) or 100% (IF100) of energy requirements. IF groups ate breakfast prior to a 24-hour fast on 3 nonconsecutive days per week. On nonfasting days, IF70 ate at 100% and IF100 ate at 145% of energy requirements to achieve the prescribed target. Weight, body composition, insulin sensitivity by clamp, nonesterified fatty acids (NEFAs), β-hydroxybutyrate (BHB), and markers of lipid metabolism and oxidative stress in muscle by quantitative polymerase chain reaction were measured at baseline and week 8 following a 12-hour overnight fast (all groups) and 24-hour fast (IF groups).ResultsIF70 resulted in greater weight and fat loss and reduced NEFAs vs CR70 and IF100 after an overnight fast. IF70 and IF100 induced a greater reduction only in mRNA levels of antioxidant enzymes glutathione peroxidase 1 (GPX1), superoxide dismutase 1, soluble (SOD1), and SOD2 vs CR70. Fasting for 24 hours increased NEFAs and BHB in IF groups, but impaired insulin sensitivity and increased PLIN5 mRNA levels.ConclusionsIn comparison to CR, IF did not increase markers of lipid metabolism in muscle, but reduced expression of antioxidant enzymes. However, fasting-induced insulin resistance was detected, alongside increased PLIN5 expression, potentially reflecting transient lipid storage.

To evaluate the effect of energy-dense vs routine enteral nutrition on day-90 mortality by ethnic group in critically ill adults.Pre-planned subgroup analysis of the 1,257 New Zealanders in a 4,000-participant randomised trial comparing energy-dense enteral nutrition (1.5kcal/mL) with routine enteral nutrition (1kcal/mL) in mechanically ventilated intensive care unit (ICU) patients. The primary purpose of this analysis was to evaluate responses to study treatment by ethnic group (European, Māori, and Pacific Peoples) using ethnicity data recorded in the clinical records. The secondary purpose was to compare the characteristics and outcomes of patients by ethnic group. The primary outcome was day-90 mortality.Among 1,138 patients included in the primary outcome analysis, 165 of 569 (29.0%) assigned to energy-dense nutrition and 156 of 569 patients (27.4%) assigned to routine nutrition died by day 90 (odds ratio; 1.06; 95% CI, 0.92-1.22). There was no statistically significant interaction between treatment allocation and ethnicity with respect to day-90 mortality. Day-90 mortality rates did not vary statistically significantly by ethnic group.Among mechanically ventilated adults in New Zealand ICUs, the effect on day-90 mortality of energy-dense vs routine enteral nutrition did not vary by ethnicity.

OBJECTIVE Tachyphylaxis for slowing of gastric emptying is seen with continuous exposure to glucagon-like peptide 1 (GLP-1). We therefore aimed to establish whether prolonged use of a “short-acting” GLP-1 receptor agonist, lixisenatide, achieves sustained slowing of gastric emptying and reduction in postprandial glycemia. RESEARCH DESIGN AND METHODS A total of 30 patients with metformin-treated type 2 diabetes underwent assessment of gastric emptying (scintigraphy) and glucose metabolism (dual tracer technique) after a 75-g glucose drink, before and after 8 weeks’ treatment with lixisenatide (20 μg subcutaneously daily) or placebo, in a double-blind randomized parallel design. RESULTS Gastric retention of the glucose drink was markedly increased after lixisenatide versus placebo (ratio of adjusted geometric means for area under the curve [AUC] over 240 min of 2.19 [95% CI 1.82, 2.64], P < 0.001), associated with substantial reductions in the rate of systemic appearance of oral glucose (P < 0.001) and incremental AUC for blood glucose (P < 0.001). Lixisenatide suppressed both glucagon (P = 0.003) and insulin (P = 0.032), but not endogenous glucose production, over 120 min after oral glucose intake. Postprandial glucose lowering over 240 min was strongly related to the magnitude of slowing of gastric emptying by lixisenatide (r = −0.74, P = 0.002) and to the baseline rate of emptying (r = 0.52, P = 0.048) but unrelated to β-cell function (assessed by β-cell glucose sensitivity). CONCLUSIONS Eight weeks’ treatment with lixisenatide is associated with sustained slowing of gastric emptying and marked reductions in postprandial glycemia and appearance of ingested glucose. Short-acting GLP-1 receptor agonists therefore potentially represent an effective long-term therapy for specifically targeting postprandial glucose excursions.

Background Obesity is becoming more prevalent in older people. A management strategy in obese, young adults is to increase dietary protein relative to other macronutrients. It is not clear if this is effective in obese, older individuals. Obesity may be associated with diminished sensitivity to nutrients. We have reported that a 30-g whey protein drink slows gastric emptying more, and suppresses energy intake less, in older, than younger, non-obese men. The aim of this study was to determine the effect of a 30 g whey protein drink on energy intake, GE and glycaemia in obese, older and younger men. Methods In randomized, double-blind order, 10 younger (age: 27 ± 2 years; BMI: 36 ± 2 kg/m²), and 10 older (72 ± 1 years; 33 ± 1 kg/m²), obese men were studied twice. After an overnight fast, subjects ingested a test drink containing 30 g whey protein (120 kcal) or control (2 kcal). Postprandial gastric emptying (antral area, 2D Ultrasound) and blood glucose concentrations were measured for 180 min. At t = 180 min subjects were given a buffet meal and ad libitum energy intake was assessed. Results Older subjects ate non-significantly less (~20%) that the younger subjects (effect of age, P = 0.16). Whey protein had no effect on subsequent energy intake (kcal) compared to control in either the younger (decrease 3 ± 8%) or older (decrease 2 ± 8%) obese men (age effect P > 0.05, protein effect P = 0.46, age × protein interaction effect P = 0.84). Whey protein slowed gastric emptying, to a similar degree in both age groups (50% emptying time: control vs. protein young men: 255 ± 5 min vs. 40 ± 7 min; older men: 16 ± 5 min vs. 50 ± 8 min; protein effect P = 0.001, age effect P = 0.93, age × protein interaction effect P = 0.13). Conclusions Our data suggest that obesity may blunt/abolish the age-related effect of whey protein on suppression of energy intake.

Background: Pressure sensor alarm systems have shown to be ineffective in preventing falls in hospitals. The AmbIGeM system involves a novel wearable sensor (accelerometer and gyroscope) worn by patients where the data captured by the sensor is interpreted by algorithms to trigger alerts on clinician handheld mobile devices when risk movements are detected. Multiple patients in multiple locations undertaking multiple activities are monitored, augmenting best practice and affording the clinicians the opportunity to intervene before a fall. Methods: A 3-cluster stepped wedge pragmatic trial investigating the effect on the primary outcome of falls rate and secondary outcome of injurious fall and proportion of fallers. Two wards in Western Australia (WA) and one ward in South Australia (SA) were included. Patients aged > 65 years were eligible. Patients requiring palliative care were excluded. A waiver (WA) and opt-out (SA) of consent were obtained for this study. Findings: 4924 older patients were admitted to the study wards with 1076 excluded and 3240 (1995 control, 1245 intervention) enrolled. The median proportion of study duration with valid readings per patient was 49% (IQR 25-67%). There was no significant difference between intervention and control relating to the falls rate (ARR=1.41, 95% CI (0.85, 2.34; p=0.192)), proportion of fallers (OR=1.54, 95% CI (0.91, 2.61); P=0.105) and injurious falls rate (ARR=0.90, 95% CI (0.38, 2.14); p=0.807). In a post hoc analysis, falls and injurious falls rate were reduced in the Geriatric Evaluation and Management Unit (GEMU) wards when the intervention period was compared to the control period. Interpretation: The AmbIGeM system did not reduce the rate of falls, rate of injurious falls or proportion of fallers. There remains a case for further exploration and refinement of this technology given the post hoc analysis findings with the GEMU wards. Trial Registration: The trial was registered with the Australia and New Zealand Clinical Trials registry, number (ANZCTR)12617000981325. Funding Statement: Funded by the National Health and Medical Research Council of Australia (APP1082197) Declaration of Interests: Previously, there was a patent filed (mid 2013) by A/Prof Ranasinghe and Professor Visvanathan titled system, method, software application and data signal for determining movement but this has since lapsed. Professor Visvanathan is the Head of Unit of the Aged & Extended Care Services at the Queen Elizabeth Hospital in South Australia within which the GEM Unit is a service for which, Mr Stephen Hoskins is the Nurse Manager. Dr Kate Ingram is the Falls Lead at Sir Charles Gairdner Hospital in Western Australia. All others have nothing to declare. Ethics Approval Statement: Ethics and governance approval were achieved from TQEH/Lyell McEwin Hospital (LMH)/Modbury Hospital (MH) (HREC/15/TQEH/17) and Curtin University (HRE2017- 0449)/SCGH (PRN 2015-110).

Background Homonymous hemianopia post-stroke reduces independence. Objective To compare the effectiveness of a standardised program versus current individualized therapy in patients with homonymous hemianopia. Methods Single-blind randomized controlled trial, 24 patients (54% male), mean age (65±4.3), mean time since stroke (51±52.3 days), recruited from rehabilitation and vision services in Adelaide, Australia. Participants were randomized to a combined standardized scanning and mobility program of 7 weeks, 3 times per week or to individualized therapy recommended by clinicians. Primary outcome was an assessment of scanning ability whilst walking. Secondary outcomes included measures of visual scanning, reading, and vision related quality of life (QOL). Results No significant differences were found between intervention groups for the primary outcome measure of scanning ability whilst walking at 7 weeks and at 3 months (P > 0.05). However, at 3 months significant differences were found for the QOL National Eye Institute Visual functioning Questionnaire (NEI VFQ25) total score (P = 0.03) and dependency sub-score (P = 0.03) measures. Conclusions A standardized intervention of static scanning and mobility training improved QOL. Allocation of resources to visual rehabilitation services point towards the implementation of more mobility practice over a longer period of time.

BACKGROUND The Augmented Versus Routine Approach to Giving Energy Trial (TARGET) is the largest blinded enteral nutrition (EN) intervention trial evaluating energy delivery to be conducted in the critically ill. To determine the external validity of TARGET results, nutrition practices in intensive care units (ICUs) in Australia and New Zealand (ANZ) are described and compared with international practices. METHODS This was a retrospective analysis of prospectively collected data for the International Nutrition Surveys, 2007-2013. Data are presented as mean (SD). RESULTS A total of 17,154 patients (ANZ: n = 2776 vs international n = 14,378) from 923 ICUs (146 and 777, respectively) were included. EN was the most common route of feeding (ANZ: 85%, n = 2365 patients vs international: 84%, n = 12,034; P = .258), and EN concentration was also similar (

OBJECTIVES Surrogate-decision maker and patient self-reported estimates of the distances walked prior to acute illness are subjective and may be imprecise. It may be possible to extract objective data from a patient's smartphone, specifically, step and global position system data, to quantify physical activity. The objectives were to 1) assess the agreement between surrogate-decision maker and patient self-reported estimates of distance and time walked prior to resting and daily step-count and 2) determine the feasibility of extracting premorbid physical activity (step and global position system) data from critically ill patients. DESIGN Prospective cohort study. SETTING Quaternary ICU. PATIENTS Fifty consecutively admitted adult patients who owned a smartphone, who were ambulatory at baseline, and who remained in ICU for more than 48 hours participated. MEASURMENTS AND MAIN RESULTS There was no agreement between patients and surrogates for all premorbid walking metrics (mean bias 108% [99% lower to 8,700% higher], 83% [97% to 2,100%], and 71% [96% to 1,080%], for distance, time, and steps, respectively). Step and/or global position system data were successfully extracted from 24 of 50 phones (48%; 95% CI, 35-62%). Surrogate-decision makers, but not patient self-reported, estimates of steps taken per day correlated with smartphone data (surrogates: n = 13, ρ = 0.56, p < 0.05; patients: n = 13, ρ = 0.30, p = 0.317). CONCLUSION There was a lack of agreement between surrogate-decision maker and patient self-reported subjective estimates of distance walked. Obtaining premorbid physical activity data from the current-generation smartphones was feasible in approximately 50% of patients.

Aim To determine whether the placement of a post-pyloric feeding tube (PPFT) can be taught safely and effectively to a critical care dietitian. Methods This is a prospective observational study conducted in an adult intensive care unit (ICU). The intervention consisted of 19 attempts at post-pyloric intubation by the dietitian. The 10 ‘learning’ attempts were performed by the dietitian under the direction of an experienced (having completed in excess of 50 successful tube placements) user. A subsequent nine ‘consolidation’ attempts were performed under the responsibility of the intensive care consultant on duty. The primary outcome measures were success (i.e. tip of the PPFT being visible in or distal to the duodenum on X-ray) and time (minutes) to PPFT placement. Patients were observed for adverse events per standard clinical practice. Results A total of 19 post-pyloric tube placements were attempted in 18 patients (52 (23–70) years, ICU admission diagnoses: trauma n = 4; respiratory failure n = 3; and burns, pancreatitis and renal failure n = 2 each). No adverse events occurred. Most (75%) patients were sedated, and mechanically ventilated. Prokinetics were used to assist tube placement in 11% (2/19) of attempts, both of which were successful. Placement of PPFT was successful in 58% (11/19) of attempts. Whilst training, the success rate was 40% (4/10) compared with 78% (7/9) once training was consolidated (P = 0.17). In the successful attempts, the mean time to placement was 11.0 minutes (3.9–27.1 minutes). Conclusions A dietitian can be trained to safely and successfully place PPFT in critically ill patients.

Objective This study aimed to examine the effects of intermittent fasting (IF) on mRNA levels of peripheral clock genes in skeletal muscle and subcutaneous adipose tissue (SAT) in women with obesity. Methods Women were randomized to one of two IF protocols and provided with all foods at 100% or 70% of calculated weekly energy requirements for 8 weeks. Breakfast was consumed before a 24-hour fast, which was initiated on three nonconsecutive days per week. Muscle and SAT biopsies were performed at 8 am after an overnight fast at baseline and at week 8 on a refed day and again following a 24-hour fast at week 8 for analysis of the mRNA levels of key genes involved in circadian regulation. Results A group-by-time interaction was observed in Per2 in muscle (F = 3.497, P = 0.044) and SAT (F = 6.686, P = 0.008), but significance was lost upon post hoc adjustment. A time effect was observed in Rorα in muscle, which was decreased by refeeding in both groups (F = 7.225, P = 0.003). Conclusions There was no universal effect of IF to alter peripheral clocks, which may be partly because of the alignment of the fasting/feeding cycle with the biological clock. Optimizing intermittent fasting protocols could be important to prevent circadian misalignment in humans.

International audience; Aims: To evaluate the effects of 8 weeks’ administration of exenatide (EXE) once weekly on gastric emptying of solids and liquids (using the “gold standard” technique, scintigraphy), glucose absorption and postprandial glycaemia in healthy people.Material and methods: A total of 32 healthy participants were randomized to receive either EXE once weekly (2 mg/wk subcutaneously; six men, 10 women, mean age 59.9 ± 0.9 years, mean body mass index [BMI] 29.6 ± 0.6 kg/m2) or matching placebo (PBO; six men, 10 women, mean age 60.6 ± 1.2 years, mean BMI 29.5 ± 1.0 kg/m2) for 8 weeks. Gastric emptying, nausea (visual analogue scale), and plasma glucose, insulin, C-peptide and glucagon were measured for 120 min after a solid/liquid meal, comprising 100 g ground beef (radiolabelled with 20 MBq 99mTc-sulphur colloid) and 150 mL 10% glucose (radiolabelled with 7 MBq 67Ga-EDTA), and containing 5 g 3-O-methyl-glucose (3-OMG) as a marker of glucose absorption, at baseline and after 8 weeks’ treatment.Results: The study treatments were well tolerated. Scores for nausea were consistently low, with no difference between the EXE once weekly and PBO groups. EXE once weekly slowed gastric emptying of solids (area under the curve [AUC]0–120min: P

This study compared the effects of daily calorie restriction (DR) versus intermittent fasting (IF) on markers of inflammation and extracellular matrix deposition in adipose tissue and skeletal muscle in a controlled feeding trial in women with overweight or obesity.Women (N = 76) were randomised to one of three diets and provided with all foods at 100% (IF100) or 70% (IF70 and DR70) of calculated energy requirements for 8 weeks. IF groups ate breakfast prior to fasting for 24-h on 3 non-consecutive days/week. Weight, body composition, serum non-esterified fatty acids (NEFA), tumour necrosis factor-alpha (TNFα), interleukin-6 (IL-6), interleukin-10 (IL-10), M1- and M2-macrophage markers by qPCR and immunohistochemistry in adipose tissue and skeletal muscle were measured following a 12-h overnight fast (fed day, all groups) and a 24-h fast (IF groups only).IF70 resulted in greater weight and fat losses and reductions in serum NEFA versus DR70 and IF100 (P 0.05) after fed days. Markers of inflammation in serum (TNFα, IL6 and IL10), subcutaneous adipose tissue and skeletal muscle (CD68, CD40 and CD163) were unchanged by DR or IF after fed days. After fasting, NEFA, M1-macrophages (CD40Unlike caloric restriction, IF transiently elevated markers of macrophage infiltration in adipose tissue and skeletal muscle, possibly in response to marked increases in adipose tissue lipolysis.

Background People with type 2 diabetes are advised to consume an even meal distribution of carbohydrate. Whether this distribution is optimal is unknown. Objective Our objective was to show that omitting carbohydrate in the first meal after a fast would lead to an augmented lunch response. Design Two diets of 1-d duration that differed only in the breakfast-meal composition (carbohydrate or no carbohydrate) were consumed on sequential days in a randomized crossover study. The procedure was repeated in the alternate order 1 wk later. Blood glucose concentrations were tested with the use of continuous glucose monitoring. The primary endpoints were the percentage of time spent with a blood glucose concentration >10 mmol/L (%T >10) and peak blood glucose (Gmax). The following 45 adults with type 2 diabetes were recruited: subjects with glycated hemoglobin (HbA1c) ≤7% and subjects with HbA1c ≥8%. Twenty-eight adults completed the study. Results The daily Gmax was significantly lower after the no-carbohydrate breakfast than after the carbohydrate breakfast (11.0 ± 0.4 and 12.1 ± 0.4 mmol/L, respectively; P = 0.003) whereas the %T >10 throughout the day was a nonsignificant 22% less after the no-carbohydrate breakfast than after the carbohydrate breakfast (13% ± 10% compared with 10% ± 8%; P = 0.09). Gmax over 5 h after breakfast was significantly lower after the no-carbohydrate meal (by 1.9 ± 0.4 mmol/L; P 10 was lower after the no-carbohydrate meal than after the carbohydrate meal (11% ± 3% compared with 26% ± 4%, respectively; P Conclusions The withholding of carbohydrate in the first meal results in significantly decreased Gmax after the meal, but the lunch response is not affected. Overall daily control is not significantly improved. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12609000331235.

In a pilot single centre study we found that treatment of undernourished older, community dwelling people for one year with oral testosterone (placebo-controlled) and a nutritional supplement (no control) was associated with a significant reduction in hospitalizations. A larger, multicentre study was conducted to investigate further this potentially important finding. One year, randomized, placebo-controlled, multicentre, double-blind, trial. Community. 53 undernourished men and women aged 65 years and older. Oral testosterone undecanoate (40 mg/day women, 160 mg/day men) and high energy oral nutritional supplement (2108-2416 kJ/day) or placebo medication and low energy (142–191 kJ/day) “placebo” oral nutritional supplementation. Hospital admissions, falls and other variables were assessed. 53 subjects were recruited (64% male and mean age 77 years), which was substantially less than planned. Sixteen subjects (30%) were admitted to hospital at least once, with a total of 29 admissions. Eight subjects (32%) in the placebo arm were admitted to hospital, whilst in the intervention group also there were eight (29%) subjects admitted to hospital during the study period. There was no difference in the number of hospitalisations (P = 0.842), length of hospitalization (P=0.645) or quality of life [mental health P=0.195 and physical health P=0.451) between the treatment arms. In undernourished older people, treatment with testosterone and a nutritional supplementation did not reduce the number and length of hospitalisations or improve quality of life.

Ageing is associated with changes in feeding behavior. We have reported that there is suppression of energy intake three hours after whey protein drink ingestion in young, but not older, men. This study aimed to determine these effects over a time period of 9 h. Fifteen younger (27 &plusmn, 1 years, 25.8 &plusmn, 0.7 kg/m2) and 15 older (75 &plusmn, 2 years, 26.6 &plusmn, 0.8 kg/m2) healthy men were studied on three occasions on which they received, in a randomized order, a 30 g/120 kcal, 70 g/280 kcal whey-protein, or control (~2 kcal) drink. Ad-libitum energy intake (sum of breakfast, lunch, and dinner) was suppressed in a protein load responsive fashion (P = 0.001). Suppression was minimal at breakfast, substantial at lunch (~&minus, 16%, P = 0.001), no longer present by dinner, and was less in older than younger men (&minus, 3 &plusmn, 4% vs. &minus, 8 &plusmn, 4%, P = 0.027). Cumulative protein intake was increased in the younger and older men (+20% and +42%, P &lt, 0.001). Visual analogue scale ratings of fullness were higher and desire to eat and prospective food consumption were lower after protein vs. control, and these effects were smaller in older vs. younger men (interaction effect P &lt, 0.05). These findings support the use of whey-protein drink supplements in older people who aim to increase their protein intake without decreasing their overall energy intake.

Glucagon-like peptide-1 receptor agonists induce weight loss, which has been suggested to relate to the slowing of gastric emptying (GE). In health, energy intake (EI) is more strongly related to the content of the distal, than the total, stomach. We evaluated the effects of lixisenatide on GE, intragastric distribution, and subsequent EI in 15 healthy participants and 15 patients with type 2 diabetes (T2D). Participants ingested a 75-g glucose drink on two separate occasions, 30 min after lixisenatide (10 mcg) or placebo subcutaneously, in a randomised, double-blind, crossover design. GE and intragastric distribution were measured for 180 min followed by a buffet-style meal, where EI was quantified. Relationships of EI with total, proximal, and distal stomach content were assessed. In both groups, lixisenatide slowed GE markedly, with increased retention in both the proximal (p &lt, 0.001) and distal (p &lt, 0.001) stomach and decreased EI (p &lt, 0.001). EI was not related to the content of the total or proximal stomach but inversely related to the distal stomach at 180 min in health on placebo (r = &minus, 0.58, p = 0.03) but not in T2D nor after lixisenatide in either group. In healthy and T2D participants, the reduction in EI by lixisenatide is unrelated to changes in GE/intragastric distribution, consistent with a centrally mediated effect.

Protein-rich supplements are used commonly to increase energy intake in undernourished older people. This study aimed to establish age effects on energy intake, appetite, gastric emptying, blood glucose, and gut hormones in response to protein-rich drinks. In a randomized double-blind, order, 13 older men (age: 75 &plusmn, 2 yrs, body mass index (BMI): 26 &plusmn, 1 kg/m2) and 13 younger (23 &plusmn, 1 yrs, 24 &plusmn, 1 kg/m2) men consumed (i) a control drink (~2 kcal) or drinks (450 mL) containing protein/fat/carbohydrate: (ii) 70 g/0 g/0 g (280 kcal/&lsquo, P280&prime, ), (iii) 14 g/12.4 g/28 g (280 kcal/&lsquo, M280&prime, ), (iv) 70 g/12.4 g/28 g (504 kcal/&lsquo, M504&prime, ), on four separate days. Appetite (visual analog scales), gastric emptying (3D ultrasonography), blood glucose, plasma insulin, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) concentrations (0&ndash, 180 min), and ad-libitum energy intake (180&ndash, 210 min) were determined. Older men, compared to younger men, had higher fasting glucose and CCK concentrations and lower fasting GLP-1 concentrations (all p &lt, 0.05). Energy intake by P280 compared to control was less suppressed in older men (increase: 49 &plusmn, 42 kcal) than it was in younger men (suppression: 100 &plusmn, 54 kcal, p = 0.038). After the caloric drinks, the suppression of hunger and the desire to eat, and the stimulation of fullness was less (p &lt, 0.05), and the stimulation of plasma GLP-1 was higher (p &lt, 0.05) in older men compared to younger men. Gastric emptying, glucose, insulin, ghrelin, and CCK responses were similar between age groups. In conclusion, ageing reduces the responses of caloric drinks on hunger, the desire to eat, fullness, and energy intake, and protein-rich nutrition supplements may be an effective strategy to increase energy intake in undernourished older people.

Background The effect of delivering nutrition at different calorie levels during critical illness is uncertain, and patients typically receive less than the recommended amount. Methods We conducted a multicenter, double-blind, randomized trial, involving adults undergoing mechanical ventilation in 46 Australian and New Zealand intensive care units (ICUs), to evaluate energy-dense (1.5 kcal per milliliter) as compared with routine (1.0 kcal per milliliter) enteral nutrition at a dose of 1 ml per kilogram of ideal body weight per hour, commencing at or within 12 hours of the initiation of nutrition support and continuing for up to 28 days while the patient was in the ICU. The primary outcome was all-cause mortality within 90 days. Results There were 3957 patients included in the modified intention-to-treat analysis (1971 in the 1.5-kcal group and 1986 in the 1.0-kcal group). The volume of enteral nutrition delivered during the trial was similar in the two groups; however, patients in the 1.5-kcal group received a mean (±SD) of 1863±478 kcal per day as compared with 1262±313 kcal per day in the 1.0-kcal group (mean difference, 601 kcal per day; 95% confidence interval [CI], 576 to 626). By day 90, a total of 523 of 1948 patients (26.8%) in the 1.5-kcal group and 505 of 1966 patients (25.7%) in the 1.0-kcal group had died (relative risk, 1.05; 95% CI, 0.94 to 1.16; P=0.41). The results were similar in seven predefined subgroups. Higher calorie delivery did not affect survival time, receipt of organ support, number of days alive and out of the ICU and hospital or free of organ support, or the incidence of infective complications or adverse events. Conclusions In patients undergoing mechanical ventilation, the rate of survival at 90 days associated with the use of an energy-dense formulation for enteral delivery of nutrition was not higher than that with routine enteral nutrition. (Funded by National Health and Medical Research Institute of Australia and the Health Research Council of New Zealand; TARGET ClinicalTrials.gov number, NCT02306746 .).

Summary Background & aims Oral intake is diminished immediately after ICU discharge, yet factors affecting nutritional intake after hospital discharge have not been evaluated. The aim of this study was to evaluate dietary intake and factors which may influence intake - appetite and gastric emptying - 3-months after ICU discharge. Methods Inception cohort study with ICU survivors compared to healthy subjects. Following an overnight fast, all participants consumed a standardized carbohydrate drink, containing 13C-octanoic acid, to measure gastric emptying. Dietary intake was assessed by recall of the preceding day and a standard weighed buffet meal 4-h post-drink. Appetite was assessed pre-drink (fasting) and pre- and post-buffet using visual analogue scales. Results Fifty-one ICU survivors (82% male; 70 ± 9 y; BMI 28 ± 6 kg/m2) and 25 healthy subjects (60% male; 67 ± 12 y; BMI 27 ± 4 kg/m2) were evaluated. From the 24-h recall ICU survivors consumed less calories (ICU 1876 (708) vs. healthy subjects 2291 (834) kcal; p = 0.025) with no difference in macronutrient intake, however reported a lower preference for fat (p Conclusions ICU survivors reported less preference for fat and less calorie consumption than healthy subjects. However, intake of calories and macronutrients at a weighed meal was similar in the two groups, as was the rate of gastric emptying. ICU survivors reported being less full after the test meal, suggesting factors other than appetite may influence intake.

Context: The early glycemic response during a 75-g oral glucose tolerance test (OGTT) is directly related to the rate of gastric emptying (GE). There is little information about the effect of GE on the blood glucose at either 60 min (a predictor of diabetes) or 120 min (used diagnostically). Objective: This study aimed to evaluate the relationships between glycemic responses at 30, 60, and 120 min and GE following a 75-g OGTT in subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (T2D). Design, Setting, and Subjects: Eighty-two subjects in the general community without diabetes (57 NGT, 25 IGT) and 16 with T2D consumed a 75-g glucose drink labeled with 99mTc-sulfur colloid. GE (by scintigraphy) and glycemia were measured from t = 0-120 min and relationships between blood glucose (absolute, change from baseline, and area under the curve) and GE at 30, 60, and 120 min determined. Results: There were no differences in GE. There were relationships between the blood glucose at 30 min and GE (NGT: r = 0.40; P < .01; IGT: r = 0.49; P = .02; T2D: r = 0.62; P = .01). There was also a relationship between the blood glucose at 60 min and GE in IGT (r = 0.52; P = .02) and T2D (r = 0.77; P < .01), but not NGT (r = 0.16; P = .24). In NGT, there was an inverse relationship between blood glucose at 120 min and GE (r=-0.30; P = .02), but not in IGT (r = 0.05; P = .82) or T2D (r = 0.37; P = .16). Conclusions: GE is a determinant of the glycemic response to an OGTT in NGT, IGT, and T2D but these relationships differ and are time dependent. Refereed/Peer-reviewed

Aim In healthy subjects, the oral disposition index (ratio of insulin response to insulin sensitivity) is predictive of the development of Type 2 diabetes. Gastric emptying, which exhibits a substantial interindividual variation, is a major determinant of postprandial glycaemia in health and diabetes. We sought to determine whether the rate of intraduodenal glucose delivery affects the disposition index in people without diabetes. Methods Nineteen Caucasian males received glucose infusions via an intraduodenal catheter at either 2 kcal/min (ID2) or 4 kcal/min (ID4) for 120 min, on two separate days with measurements of blood glucose (G) and plasma insulin (I) at frequent intervals. The insulin response was estimated by the ratio of the change in insulin to that of change in glucose at 30 min (∆I0–30/∆G0–30) and 60 min (∆I0–60/∆G0–60). Insulin sensitivity was estimated as 1/fasting insulin. The oral disposition index (DI) was calculated as ∆I0–30/∆G0–30 × 1/fasting insulin and ∆I0–60/∆G0–60 × 1/fasting insulin. Results The overall glycaemic response was comparable on both days, but the insulin response was much greater at ID4 when calculated at either 30 or 60 min (P

Introduction It has been proposed that nutritional therapy in critically ill patients after major burn reduces mortality. However, the actual practice of nutrient delivery, and the effect on outcome, has not been described. Study objectives To evaluate international practices related to nutritional support and outcomes in mechanically ventilated patients with burn injury. Methods Data from the International Nutrition Surveys (2007–2011) for patients with a primary diagnosis of burn were extracted and analysed. Results Eighty-eight of 90 patients (aged 16–84 years) received enteral nutrition. The median time for initiation of enteral feeding was 17 h [range 0–65]. Fifty patients (57%) had interruptions to nutrient delivery, most often these interruptions were fasting for operative procedures. There were substantive energy and protein deficits [943 (654) kcal/day and 49 (41) g/day, respectively; mean (SD)]. Nineteen (21%) patients died within 60 days of admission, and the energy and protein deficits were greater in those that died compared with survivors [died vs. survived, energy: 1251 (742) vs. 861 (607) kcal/d; p = 0.02; and protein 67(42) vs. 44(39) g/d; p = 0.03]. Energy and protein deficits were associated with increased mortality with the greater the deficit, the stronger the association with death (odds ratio for death: energy deficit/100 kcal 1.10 (1.01, 1.19); p = 0.028 and protein/10 g 1.16 (1.01, 1.33); p = 0.037). Results were similar and remained significant after adjusting for severity of illness. Conclusions Mechanically ventilated patients following burn develop substantial energy and protein deficits, with lesser deficits observed in survivors.

Aim This study evaluated the safety and efficacy of influenza vaccination in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Methods Thirty-one patients who were in remission were randomized to receive either a trivalent influenza vaccine or no vaccine. Vaccine efficacy was assessed at 28 days. Patients were followed for 6 months for signs of reactivation of disease. In addition, 67 healthy individuals were randomized to receive either the influenza vaccine or no vaccine to assess its potential for triggering the formation of autoantibodies. Results Compared with patients who did not receive the vaccine, vaccinated patients achieved effective responses to all three influenza vaccine antigens. There was no significant change in levels of anti-neutrophil cytoplasmic antibody post-vaccination. There was no significant change in disease activity in vaccinated patients compared with non-vaccinated patients. Among vaccinated healthy individuals, we did not observe any significant change in the level of autoantibodies measured. Conclusion This study shows that the administration of influenza vaccine to patients in remission with anti-neutrophil cytoplasmic antibody-associated vasculitis is both safe and modestly efficacious.

usc Postprandial hypotension occurs frequently in diabetes. We show in 9 type 2 patients, that the fall in systolic blood pressure is greater in response to intraduodenal glucose infused at 4 kcal/min than 2 kcal/min, implying that strategies to slow gastric emptying may be effective in the management of postprandial hypotension. Refereed/Peer-reviewed

Background Optimising nutrition support in critically ill patients with an open abdomen is challenging. Objectives The aims of this study were to (i) quantify the amount and adequacy of nutrition support administered and (ii) determine any relationships that exist between mode of nutrition support delivery and clinical outcomes in critically ill patients with an open abdomen. Methods A retrospective review of critically ill patients mechanically ventilated for at least 48 h with an open abdomen in a mixed quaternary referral intensive care unit. Enteral and parenteral nutrition (ml) administered daily to patients was recorded for up to 21 days. Length of stay in the intensive care unit and hospital and duration of mechanical ventilation (days) were reported. Results Thirty patients were studied [14 male, 68 y (15–90 y), body mass index 25 kg/m2 (11–51 kg/m2), Acute Physiology and Chronic Health Evaluation II score 20 (7–41), energy goal 1860 kcal/d (1250–2712 kcal/d)]. Patients received 55% (0–117%) of energy goal and 56% (0–105%) protein goal from either enteral or parenteral nutrition. When enteral nutrition was delivered alone or in combination with parenteral nutrition, patients received 48% (0–146%) of their energy and 59% (19–105%) of their protein goal. Patients fed parenteral nutrition, either alone or as supplementary to enteral nutrition (n = 18), received more energy when compared with those who only received enteral nutrition (n = 9) [65 (27–117) vs 49 (15–89) % energy goal, P = 0.025]. Parenteral nutrition was associated with an increased length of stay in hospital [63 (45–156) vs 45 (17–93) d, P = 0.037]. Conclusion Patients with an open abdomen receive about half of their nutrition requirements when fed exclusively via the enteral route. Providing combination enteral and parenteral nutrition to reach nutritional goals may not result in better clinical outcomes for patients with an open abdomen.