The impact of admission diagnosis on gastric emptying in critically ill patients

Introduction Disturbed gastric emptying (GE) occurs commonly in critically ill patients. Admission diagnoses are believed to influence the incidence of delayed GE and subsequent feed intolerance. Although patients with burns and head injury are considered to be at greater risk, the true incidence has not been determined by examination of patient groups of sufficient number. This study aimed to evaluate the impact of admission diagnosis on GE in critically ill patients. Methods A retrospective review of patient demographics, diagnosis, intensive care unit (ICU) admission details, GE, and enteral feeding was performed on an unselected cohort of 132 mechanically ventilated patients (94 males, 38 females; age 54 ± 1.2 years; admission Acute Physiology and Chronic Health Evaluation II [APACHE II] score of 22 ± 1) who had undergone GE assessment by 13C-octanoic acid breath test. Delayed GE was defined as GE coefficient (GEC) of less than 3.20 and/or gastric half-emptying time (t50) of more than 140 minutes. Results Overall, 60% of the patients had delayed GE and a mean GEC of 2.9 ± 0.1 and t50 of 163 ± 7 minutes. On univariate analysis, GE correlated significantly with older age, higher admission APACHE II scores, longer length of stay in ICU prior to GE measurement, higher respiratory rate, higher FiO2 (fraction of inspired oxygen), and higher serum creatinine. After these factors were controlled for, there was a modest relationship between admission diagnosis and GE (r = 0.48; P = 0.02). The highest occurrence of delayed GE was observed in patients with head injuries, burns, multi-system trauma, and sepsis. Delayed GE was least common in patients with myocardial injury and non-gastrointestinal post-operative respiratory failure. Patients with delayed GE received fewer feeds and stayed longer in ICU and hospital compared to those with normal GE. Conclusion Admission diagnosis has a modest impact on GE in critically ill patients, even after controlling for factors such as age, illness severity, and medication, which are known to influence this function.Nam Q Nguyen, Mei P Ng, Marianne Chapman, Robert J Fraser and Richard H Hollowa

Fasting and nutrient-stimulated plasma peptide-YY levels are elevated in critical illness and associated with feed intolerance: an observational, controlled study

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

The relationship between gastric emptying, plasma cholecystokinin, and peptide YY in critically ill patients

© 2007 Nguyen et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background Cholecystokinin (CCK) and peptide YY (PYY) are released in response to intestinal nutrients and play an important physiological role in regulation of gastric emptying (GE). Plasma CCK and PYY concentrations are elevated in critically ill patients, particularly in those with a history of feed intolerance. This study aimed to evaluate the relationship between CCK and PYY concentrations and GE in critical illness. Methods GE of 100 mL of Ensure® meal (106 kcal, 21% fat) was measured using a 13C-octanoate breath test in 39 mechanically ventilated, critically ill patients (24 males; 55.8 ± 2.7 years old). Breath samples for 13CO2 levels were collected over the course of 4 hours, and the GE coefficient (GEC) (normal = 3.2 to 3.8) was calculated. Measurements of plasma CCK, PYY, and glucose concentrations were obtained immediately before and at 60 and 120 minutes after administration of Ensure. Results GE was delayed in 64% (25/39) of the patients. Baseline plasma CCK (8.5 ± 1.0 versus 6.1 ± 0.4 pmol/L; P = 0.045) and PYY (22.8 ± 2.2 versus 15.6 ± 1.3 pmol/L; P = 0.03) concentrations were higher in patients with delayed GE and were inversely correlated with GEC (CCK: r = -0.33, P = 0.04, and PYY: r = -0.36, P = 0.02). After gastric Ensure, while both plasma CCK (P = 0.03) and PYY (P = 0.02) concentrations were higher in patients with delayed GE, there was a direct relationship between the rise in plasma CCK (r = 0.40, P = 0.01) and PYY (r = 0.42, P < 0.01) from baseline at 60 minutes after the meal and the GEC. Conclusion In critical illness, there is a complex interaction between plasma CCK, PYY, and GE. Whilst plasma CCK and PYY correlated moderately with impaired GE, the pathogenetic role of these gut hormones in delayed GE requires further evaluation with specific antagonists.Nam Q Nguyen, Robert J Fraser, Laura K Bryant, Marianne J Chapman, Judith Wishart, Richard H Holloway, Ross Butler, and Michael Horowit

Increasing cardiovascular medication adherence:A Medical Research Council complex mHealth intervention mixed-methods feasibility study to inform global practice

AimsTo evaluate a mHealth intervention to increase medication adherence among Iranian coronary heart disease patients.DesignQuantitative-dominant mixed-methods study.Data SourceIranian coronary heart disease patients’ responses and most recent clinical documents as well as responses from Iranian cardiac nurses who participated in this study.MethodsThe study was conducted between September 2015–April 2016 drawing on the Medical Research Council's Framework. Phase one comprised of a patients’ survey and focus groups with cardiac nurses. The automated short message service reminder was piloted in phase two. We recruited 78 patients and randomized to receive either 12-week daily reminders or usual care. The primary outcome was the effect on medication adherence; secondary outcomes were self-efficacy, ejection fraction, functional capacity, readmission rate and quality of life.ResultsFeasibility was evidenced by high ownership of mobile phones and high interest in receiving reminders. Participants in the intervention group showed significantly higher medication adherence compared with the control group.ConclusionThe mHealth intervention was well accepted and feasible with early evidence of effectiveness that needs to be confirmed in a fully powered future randomized clinical trial

Regulation of the Epithelial Sodium Channel by Serine Proteases in Human Airways

The epithelial sodium channel (ENaC) constitutes the rate-limiting step for sodium absorption across airway epithelia, which in turn regulates airway surface liquid (ASL) volume and the efficiency of mucociliary clearance. This role in ASL volume regulation suggests that ENaC activity is influenced by local factors rather than systemic signals indicative of total body volume homeostasis. Based on reports that ENaC may be regulated by extracellular serine protease activity in Xenopus and mouse renal epithelia, we sought to identify proteases that serve similar functions in human airway epithelia. Homology screening of a human airway epithelial cDNA library identified two trypsin-like serine proteases (prostasin and TMPRSS2) that, as revealed by in situ hybridization, are expressed in airway epithelia. Functional studies in the Xenopus oocyte expression system demonstrated that prostasin increased ENaC currents 60--80%, whereas TMPRSS2 markedly decreased ENaC currents and protein levels. Studies of primary nasal epithelial cultures in Ussing chambers revealed that inhibition of endogenous serine protease activity with aprotinin markedly decreased ENaC-mediated currents and sensitized the epithelia to subsequent channel activation by exogenous trypsin. These data, therefore, suggest that protease-mediated regulation of sodium absorption is a function of human airway epithelia, and prostasin is a likely candidate for this activity

Concentrations and Sources of Organic Carbon Aerosol in the Free Troposphere over North America

Aircraft measurements of water-soluble organic carbon (WSOC) aerosol over NE North America during summer 2004 (ITCT-2K4) are simulated with a global chemical transport model (GEOS-Chem) to test our understanding of the sources of organic carbon (OC) aerosol in the free troposphere (FT). Elevated concentrations were observed in plumes from boreal fires in Alaska and Canada. WSOC aerosol concentrations outside of these plumes average 0.9 ± 0.9 μg C m−3 in the FT (2–6 km). The corresponding model value is 0.7 ± 0.6 μg C m−3, including 42% from biomass burning, 36% from biogenic secondary organic aerosol (SOA), and 22% from anthropogenic emissions. Previous OC aerosol observations over the NW Pacific in spring 2001 (ACE-Asia) averaged 3.3 ± 2.8 μg C m−3 in the FT, compared to a model value of 0.3 ± 0.3 μg C m−3. WSOC aerosol concentrations in the boundary layer (BL) during ITCT-2K4 are consistent with OC aerosol observed at the IMPROVE surface network. The model is low in the boundary layer by 30%, which we attribute to secondary formation at a rate comparable to primary anthropogenic emission. Observed WSOC aerosol concentrations decrease by a factor of 2 from the BL to the FT, as compared to a factor of 10 decrease for sulfate, indicating that most of the WSOC aerosol in the FT originates in situ. Despite reproducing mean observed WSOC concentrations in the FT to within 25%, the model cannot account for the variance in the observations (R = 0.21). Covariance analysis of FT WSOC aerosol with other measured chemical variables suggests an aqueous-phase mechanism for SOA generation involving biogenic precursors.Earth and Planetary SciencesEngineering and Applied Science

UBF levels determine the number of active ribosomal RNA genes in mammals

In mammals, the mechanisms regulating the number of active copies of the ∼200 ribosomal RNA (rRNA) genes transcribed by RNA polymerase I are unclear. We demonstrate that depletion of the transcription factor upstream binding factor (UBF) leads to the stable and reversible methylation-independent silencing of rRNA genes by promoting histone H1–induced assembly of transcriptionally inactive chromatin. Chromatin remodeling is abrogated by the mutation of an extracellular signal-regulated kinase site within the high mobility group box 1 domain of UBF1, which is required for its ability to bend and loop DNA in vitro. Surprisingly, rRNA gene silencing does not reduce net rRNA synthesis as transcription from remaining active genes is increased. We also show that the active rRNA gene pool is not static but decreases during differentiation, correlating with diminished UBF expression. Thus, UBF1 levels regulate active rRNA gene chromatin during growth and differentiation

The “Outcome Reporting in Brief Intervention Trials: Alcohol” (ORBITAL) core outcome set:International consensus on outcomes to measure in efficacy and effectiveness Trials of alcohol brief interventions

Objective: The purpose of this study was to report the “Outcome Reporting in Brief Intervention Trials: Alcohol” (ORBITAL) recommended core outcome set (COS) to improve efficacy and effectiveness trials/evaluations for alcohol brief interventions (ABIs). Method: A systematic review identified 2,641 outcomes in 401 ABI articles measured by 1,560 different approaches. These outcomes were classified into outcome categories, and 150 participants from 19 countries participated in a two-round e-Delphi outcome prioritization exercise. This process prioritized 15 of 93 outcome categories for discussion at a consensus meeting of key stakeholders to decide the COS. A psychometric evaluation determined how to measure the outcomes. Results: Ten outcomes were voted into the COS at the consensus meeting: (a) typical frequency, (b) typical quantity, (c) frequency of heavy episodic drinking, (d) combined consumption measure summarizing alcohol use, (e) hazardous or harmful drinking (average consumption), (f) standard drinks consumed in the past week (recent, current consumption), (g) alcohol-related consequences, (h) alcohol-related injury, (i) use of emergency health care services (impact of alcohol use), and (j) quality of life. Conclusions: The ORBITAL COS is an international consensus standard for future ABI trials and evaluations. It can improve the synthesis of new findings, reduce redundant/selective reporting (i.e., reporting only some, usually significant outcomes), improve between-study comparisons, and enhance the relevance of trial and evaluation findings to decision makers. The COS is the recommended minimum and does not exclude other, additional outcomes

A high-resolution map of human evolutionary constraint using 29 mammals.

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease