The impact of malnutrition and decreased food intake on length of stay, readmission, and mortality in acute care patients

Rationale: The Australasian Nutrition Care Day Survey (ANCDS) evaluated if malnutrition and decreased food intake are independent risk factors for negative outcomes in hospitalised patients. Methods: A multicentre (56 hospitals) cross-sectional survey was conducted in two phases. Phase 1 evaluated nutritional status (defined by Subjective Global Assessment) and 24-hour food intake recorded as 0, 25, 50, 75, and 100% intake. Phase 2 data, which included length of stay (LOS), readmissions and mortality, were collected 90 days post-Phase 1. Logistic regression was used to control for confounders: age, gender, disease type and severity (using Patient Clinical Complexity Level scores). Results: Of 3122 participants (53% males, mean age: 65±18 years) 32% were malnourished and 23% consumed�25% of the offered food. Median LOS for malnourished (MN) patients was higher than well-nourished (WN) patients (15 vs. 10 days, p<0.0001). Median LOS for patients consuming �25% of the food was higher than those consuming �50% (13 vs. 11 days, p<0.0001). MN patients had higher readmission rates (36% vs. 30%, p = 0.001). The odds ratios of 90-day in-hospital mortality were 1.8 times greater for MN patients (CI: 1.03 3.22, p = 0.04) and 2.7 times greater for those consuming �25% of the offered food (CI: 1.54 4.68, p = 0.001). Conclusion: The ANCDS demonstrates that malnutrition and/or decreased food intake are associated with longer LOS and readmissions. The survey also establishes that malnutrition and decreased food intake are independent risk factors for in-hospital mortality in acute care patients; and highlights the need for appropriate nutritional screening and support during hospitalisation. Disclosure of Interest: None Declared.

Effect of chronic exercise on appetite control in overweight and obese individuals

Purpose: The effect of exercise on body mass is likely to be partially mediated through changes in appetite control. However, no studies have examined the effect of chronic exercise on obestatin and cholecystokinin (CCK) plasma concentrations or the sensitivity to detect differences in preload energy in obese individuals. The objective of this study was to investigate the effects of chronic exercise on 1) fasting and postprandial plasma concentrations of obestatin, CCK, leptin, and glucose insulinotropic peptide (GIP) and 2) the accuracy of energy compensation in response to covert preload manipulation. Methods: This study used a 12-wk supervised exercise program in 22 sedentary overweight/obese individuals. Fasting/postprandial plasma concentrations of obestatin, CCK, leptin, and GIP were assessed before and after the intervention. Energy compensation at a 30-min test meal after a high-energy (607 kcal) or a low-energy (246 kcal) preload and for the rest of the day (cumulative energy intake [EI]) was also measured. Results: There was a significant reduction in the plasma concentration of fasting plasma GIP and both fasting and postprandial leptin concentrations after the exercise intervention (P < 0.05 for all). No significant changes were observed for CCK or obestatin. A significant preload–exercise interaction (P = 0.011) was observed on cumulative EI and energy compensation for the same period (−87% ± 196% vs 68% ± 165%, P = 0.011). Weight loss (3.5 ± 1.4 kg, P < 0.0001) was not correlated with changes in energy compensation. Conclusions: This study suggests that exercise improves the accuracy of compensation for previous EI, independent of weight loss. Unexpectedly, and in contrast to GIP and leptin, exercise-induced weight loss had no effect on obestatin or CCK concentrations.

The effects of acute exercise-induced cortisol on CCR2 expression on human monocytes

CC-chemokine receptor 2 (CCR2) and its ligand, monocyte chemotactic protein-1 (MCP-1, also known as CCL2), are crucial for the recruitment of monocytes/macrophages to sites of inflammation. We conducted a series of experiments to investigate the relationship between stress, monocyte CCR2 expression and migration activity. First, we collected peripheral blood mononuclear cells (PBMC) from untrained subjects (n=8) and measured CCR2 expression on CD14(+) monocytes cultured with cortisol, epinephrine and norepinephrine. Second, we collected PBMC from the subjects before and after they cycled for 60 min at 70% peak O(2) uptake (VO2(peak)), and measured alterations in CCR2 expression on monocytes following exercise. Third, we cultured PBMC with serum obtained before and after exercise and the glucocorticoid antagonist RU-486 to determine the effect of cortisol on CCR2 expression in vitro. Last, we measured the ability of PBMC treated with serum or cortisol to migrate through membrane filters in response to CCL2. Cortisol (but not epinephrine or norepinephrine) increased CCR2 expression on monocytes in a dose- and time-dependent manner. Exercise did not influence CCR2 expression on PBMC, whereas incubation of PBMC with post-exercise serum significantly increased CCR2 expression. Both cortisol and post-exercise serum increased the migration of PBMC toward CCL2. The increase in CCR2 expression on PBMC following stimulation with cortisol and serum was blocked by the glucocorticoid receptor antagonist RU-486. In conclusion, cortisol released during exercise increased monocyte CCR2 expression and migration activity in vitro. These alterations may influence inflammation and regeneration of damaged tissue after acute stress.

Effect of consecutive repeated sprint and resistance exercise bouts on acute adaptive responses in human skeletal muscle

We examined acute molecular responses in skeletal muscle to repeated sprint and resistance exercise bouts. Six men [age, 24.7 ± 6.3 yr; body mass, 81.6 ± 7.3 kg; peak oxygen uptake, 47 ± 9.9 ml·kg -1 ·min -1; one repetition maximum (1-RM) leg extension 92.2 ± 12.5 kg; means ± SD] were randomly assigned to trials consisting of either resistance exercise (8 × 5 leg extension, 80% 1-RM) followed by repeated sprints (10 × 6 s, 0.75 N·m torque·kg -1) or vice-versa. Muscle biopsies from vastus lateralis were obtained at rest, 15 min after each exercise bout, and following 3-h recovery to determine early signaling and mRNA responses. There was divergent exercise order-dependent phosphorylation of p70 S6K (S6K). Specifically, initial resistance exercise increased S6K phosphorylation (?75% P < 0.05), but there was no effect when resistance exercise was undertaken after sprints. Exercise decreased IGF-I mRNA following 3-h recovery (?50%, P = 0.06) independent of order, while muscle RING finger mRNA was elevated with a moderate exercise order effect (P < 0.01). When resistance exercise was followed by repeated sprints PGC-1? mRNA was increased (REX1-SPR2; P = 0.02) with a modest distinction between exercise orders. Repeated sprints may promote acute interference on resistance exercise responses by attenuating translation initiation signaling and exacerbating ubiquitin ligase expression. Indeed, repeated sprints appear to generate the overriding acute exercise-induced response when undertaking concurrent repeated sprint and resistance exercise. Accordingly, we suggest that sprint-activities are isolated from resistance training and that adequate recovery time is considered within periodized training plans that incorporate these divergent exercise modes.

Bronchiectasis exacerbation study on azithromycin and amoxycillin-clavulanate for respiratory exacerbations in children (BEST-2) : study protocol for a randomized controlled trial

Background Bronchiectasis unrelated to cystic fibrosis (CF) is being increasingly recognized in children and adults globally, both in resource-poor and in affluent countries. However, high-quality evidence to inform management is scarce. Oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations, because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis. Azithromycin has a prolonged half-life, and with its unique anti-bacterial, immunomodulatory, and anti-inflammatory properties, presents an attractive alternative. Our proposed study will test the hypothesis that oral azithromycin is non-inferior (within a 20% margin) to amoxycillin-clavulanate at achieving resolution of non-severe respiratory exacerbations by day 21 of treatment in children with non-CF bronchiectasis. Methods This will be a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group trial involving six Australian and New Zealand centers. In total, 170 eligible children will be stratified by site and bronchiectasis etiology, and randomized (allocation concealed) to receive: 1) azithromycin (5 mg/kg daily) with placebo amoxycillin-clavulanate or 2) amoxycillin-clavulanate (22.5 mg/kg twice daily) with placebo azithromycin for 21 days as treatment for non-severe respiratory exacerbations. Clinical data and a parent-proxy cough-specific quality of life (PC-QOL) score will be obtained at baseline, at the start and resolution of exacerbations, and on day 21. In most children, blood and deep-nasal swabs will also be collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 21. The main secondary outcome is the PC-QOL score. Other outcomes are: time to next exacerbation; requirement for hospitalization; duration of exacerbation, and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood inflammatory markers will be reported where available. Discussion Currently, there are no published randomized controlled trials (RCT) to underpin effective, evidence-based management of acute respiratory exacerbations in children with non-CF bronchiectasis. To help address this information gap, we are conducting two RCTs. The first (bronchiectasis exacerbation study; BEST-1) evaluates the efficacy of azithromycin and amoxycillin-clavulanate compared with placebo, and the second RCT (BEST-2), described here, is designed to determine if azithromycin is non-inferior to amoxycillin-clavulanate in achieving symptom resolution by day 21 of treatment in children with acute respiratory exacerbations. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR) number ACTRN12612000010897. http://www.anzctr.org.au/trial_view.aspx?id=347879

Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis : protocol for a randomised controlled trial

Background Recurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children. Methods A multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW(135)) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (<6 years and >= 6 years) and aetiology (recurrent PBB or CSLD/bronchiectasis). Clinical histories, respiratory status (including spirometry in children aged >= 6 years), nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine-related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function in children aged >= 6 years; and vaccine safety. Discussion As H. influenzae is the most common bacterial pathogen associated with these chronic respiratory diseases in children, a novel pneumococcal conjugate vaccine that also impacts upon H. influenzae and helps prevent respiratory exacerbations would assist clinical management with potential short- and long-term health benefits. Our study will be the first to assess vaccine efficacy targeting H. influenzae in children with recurrent PBB, CSLD and bronchiectasis.

Characterisation of a human skin equivalent model to study the effects of ultraviolet B radiation on keratinocytes

The incidences of skin cancers resulting from chronic ultraviolet radiation (UVR) exposure are on the incline both in Australia and globally. Hence, the cellular and molecular pathways associated with UVR-induced photocarcinogenesis urgently need to be elucidated, in order to develop more robust preventative and treatment strategies against skin cancers. In vitro investigations into the effects of UVR (in particular the highly-mutagenic UVB wavelength) have, to date, mainly involved the use of cell culture and animal models. However, these models possess biological disparities to native skin, which to some extent have limited their relevance to the in vivo situation. To address this, we characterised a 3-dimensional, tissue-engineered human skin equivalent (HSE) model (consisting of primary human keratinocytes cultured on a dermal-derived scaffold) as a representation of a more physiologically-relevant platform to study keratinocyte responses to UVB. Significantly, we demonstrate that this model retains several important epidermal properties of native skin. Moreover, UVB-irradiation of the HSE constructs was shown to induce key markers of photodamage in the HSE keratinocytes, including the formation of cyclobutane pyrimidine dimers, the activation of apoptotic pathways, the accumulation of p53 and the secretion of inflammatory cytokines. Importantly, we also demonstrate that the UVB-exposed HSE constructs retain the capacity for epidermal repair and regeneration following photodamage. Together, our results demonstrate the potential of this skin equivalent model as a tool to study various aspects of the acute responses of human keratinocytes to UVB radiation damage.

A longitudinal study of the impact of chronic psychological stress on health-related quality of life and clinical biomarkers : protocol for the Australian Healthy Aging of Women Study

BACKGROUND: Despite advancements in our understanding of the importance of stress reduction in achieving good health, we still only have limited insight into the impact of stress on cellular function. Recent studies have suggested that exposure to prolonged psychological stress may alter an individual's physiological responses, and contribute to morbidity and mortality. This paper presents an overview of the study protocol we are using to examine the impact of life stressors on lifestyle factors, health-related quality of life and novel and established biomarkers of stress in midlife and older Australian women.The primary aim of this study is to explore the links between chronic psychological stress on both subjective and objective health markers in midlife and older Australian women. The study examines the extent to which exposure frightening, upsetting or stressful events such as natural disasters, illness or death of a relative, miscarriage and relationship conflict is correlated with a variety of objective and subjective health markers.Methods/design: This study is embedded within the longitudinal Healthy Aging of Women's study which has collected data from midlife and older Australian women at 5 yearly intervals since 2001, and uses the Allostastic model of women's health by Groer and colleagues in 2010. The current study expands the focus of the HOW study and will assess the impact of life stressors on quality of life and clinical biomarkers in midlife and older Australian women to explain the impact of chronic psychological stress in women. DISCUSSION: The proposed study hypothesizes that women are at increased risk of exposure to multiple or repeated stressors, some being unique to women, and the frequency and chronicity of stressors increases women's risk of adverse health outcomes. This study aims to further our understanding of the relationships between stressful life experiences, perceived quality of life, stress biomarkers, chronic illness, and health status in women.

Efficacy of a children's procedural preparation and distraction device on healing in acute burn wound care procedures : study protocol for a randomized controlled trial

BACKGROUND: The intense pain and anxiety triggered by burns and their associated wound care procedures are well established in the literature. Non-pharmacological intervention is a critical component of total pain management protocols and is used as an adjunct to pharmacological analgesia. An example is virtual reality, which has been used effectively to dampen pain intensity and unpleasantness. Possible links or causal relationships between pain/anxiety/stress and burn wound healing have previously not been investigated. The purpose of this study is to investigate these relationships, specifically by determining if a newly developed multi-modal procedural preparation and distraction device (Ditto) used during acute burn wound care procedures will reduce the pain and anxiety of a child and increase the rate of re-epithelialization. METHODS/DESIGN: Children (4 to 12 years) with acute burn injuries presenting for their first dressing change will be randomly assigned to either the (1) Control group (standard distraction) or (2) Ditto intervention group (receiving Ditto, procedural preparation and Ditto distraction). It is intended that a minimum of 29 participants will be recruited for each treatment group. Repeated measures of pain intensity, anxiety, stress and healing will be taken at every dressing change until complete wound re-epithelialization. Further data collection will aid in determining patient satisfaction and cost effectiveness of the Ditto intervention, as well as its effect on speed of wound re-epithelialization. DISCUSSION: Results of this study will provide data on whether the disease process can be altered by reducing stress, pain and anxiety in the context of acute burn wounds. TRIAL REGISTRATION: ACTRN12611000913976.

The effect of deprivation and disease-severity on malnutrition risk in chronic obstructive pulmonary disease (COPD)

Deprivation has previously been shown to be an independent risk factor for the high prevalence of malnutrition observed in COPD (Collins et al., 2010). It has been suggested the socioeconomic gradient observed in COPD is greater than any other chronic disease (Prescott & Vestbo, 1999). The current study aimed to examine the infl uence of disease severity and social deprivation on malnutrition risk in outpatients with COPD. 424 COPD outpatients were screened using the ‘Malnutrition Universal Screening Tool’ (‘MUST’). COPD disease severity was recorded in accordance with the GOLD criteria and deprivation was established according to the patient’s geographical location (postcode) at the time of nutritional screening using the UK Government’s Index of Multiple Deprivation (IMD). IMD ranks postcodes from 1 (most deprived) to 32,482 (least deprived). Disease severity was posi tively associated with an increased prevalence of malnutrition risk (p < 0.001) both within and between groups, whilst rank IMD was negatively associated with malnutrition (p = 0.020), i.e. those residing in less deprived areas were less likely to be malnourished. Within each category of disease severity the prevalence of malnutrition was two-fold greater in those residing in the most deprived areas compared to those residing in the least deprived areas. This study suggests that deprivation and disease severity are independent risk factors for malnutrition in COPD both contributing to the widely variable prevalence of malnutrition. Consideration of these issues could assist with the targeted nutritional management of these patients.