Malnutrition in Parkinson's disease and an individualised approach to its management

It has been reported that poor nutritional status, in the form of weight loss and resulting body mass index (BMI) changes, is an issue in people with Parkinson's disease (PWP). The symptoms resulting from Parkinson's disease (PD) and the side effects of PD medication have been implicated in the aetiology of nutritional decline. However, the evidence on which these claims are based is, on one hand, contradictory, and on the other, restricted primarily to otherwise healthy PWP. Despite the claims that PWP suffer from poor nutritional status, evidence is lacking to inform nutrition-related care for the management of malnutrition in PWP. The aims of this thesis were to better quantify the extent of poor nutritional status in PWP, determine the important factors differentiating the well-nourished from the malnourished and evaluate the effectiveness of an individualised nutrition intervention on nutritional status. Phase DBS: Nutritional status in people with Parkinson's disease scheduled for deep-brain stimulation surgery The pre-operative rate of malnutrition in a convenience sample of people with Parkinson's disease (PWP) scheduled for deep-brain stimulation (DBS) surgery was determined. Poorly controlled PD symptoms may result in a higher risk of malnutrition in this sub-group of PWP. Fifteen patients (11 male, median age 68.0 (42.0 – 78.0) years, median PD duration 6.75 (0.5 – 24.0) years) participated and data were collected during hospital admission for the DBS surgery. The scored PG-SGA was used to assess nutritional status, anthropometric measures (weight, height, mid-arm circumference, waist circumference, body mass index (BMI)) were taken, and body composition was measured using bioelectrical impedance spectroscopy (BIS). Six (40%) of the participants were malnourished (SGA-B) while 53% reported significant weight loss following diagnosis. BMI was significantly different between SGA-A and SGA-B (25.6 vs 23.0kg/m 2, p<.05). There were no differences in any other variables, including PG-SGA score and the presence of non-motor symptoms. The conclusion was that malnutrition in this group is higher than that in other studies reporting malnutrition in PWP, and it is under-recognised. As poorer surgical outcomes are associated with poorer pre-operative nutritional status in other surgeries, it might be beneficial to identify patients at nutritional risk prior to surgery so that appropriate nutrition interventions can be implemented. Phase I: Nutritional status in community-dwelling adults with Parkinson's disease The rate of malnutrition in community-dwelling adults (>18 years) with Parkinson's disease was determined. One hundred twenty-five PWP (74 male, median age 70.0 (35.0 – 92.0) years, median PD duration 6.0 (0.0 – 31.0) years) participated. The scored PG-SGA was used to assess nutritional status, anthropometric measures (weight, height, mid-arm circumference (MAC), calf circumference, waist circumference, body mass index (BMI)) were taken. Nineteen (15%) of the participants were malnourished (SGA-B). All anthropometric indices were significantly different between SGA-A and SGA-B (BMI 25.9 vs 20.0kg/m2; MAC 29.1 – 25.5cm; waist circumference 95.5 vs 82.5cm; calf circumference 36.5 vs 32.5cm; all p<.05). The PG-SGA score was also significantly lower in the malnourished (2 vs 8, p<.05). The nutrition impact symptoms which differentiated between well-nourished and malnourished were no appetite, constipation, diarrhoea, problems swallowing and feel full quickly. This study concluded that malnutrition in community-dwelling PWP is higher than that documented in community-dwelling elderly (2 – 11%), yet is likely to be under-recognised. Nutrition impact symptoms play a role in reduced intake. Appropriate screening and referral processes should be established for early detection of those at risk. Phase I: Nutrition assessment tools in people with Parkinson's disease There are a number of validated and reliable nutrition screening and assessment tools available for use. None of these tools have been evaluated in PWP. In the sample described above, the use of the World Health Organisation (WHO) cut-off (≤18.5kg/m2), age-specific BMI cut-offs (≤18.5kg/m2 for under 65 years, ≤23.5kg/m2 for 65 years and older) and the revised Mini-Nutritional Assessment short form (MNA-SF) were evaluated as nutrition screening tools. The PG-SGA (including the SGA classification) and the MNA full form were evaluated as nutrition assessment tools using the SGA classification as the gold standard. For screening, the MNA-SF performed the best with sensitivity (Sn) of 94.7% and specificity (Sp) of 78.3%. For assessment, the PG-SGA with a cut-off score of 4 (Sn 100%, Sp 69.8%) performed better than the MNA (Sn 84.2%, Sp 87.7%). As the MNA has been recommended more for use as a nutrition screening tool, the MNA-SF might be more appropriate and take less time to complete. The PG-SGA might be useful to inform and monitor nutrition interventions. Phase I: Predictors of poor nutritional status in people with Parkinson's disease A number of assessments were conducted as part of the Phase I research, including those for the severity of PD motor symptoms, cognitive function, depression, anxiety, non-motor symptoms, constipation, freezing of gait and the ability to carry out activities of daily living. A higher score in all of these assessments indicates greater impairment. In addition, information about medical conditions, medications, age, age at PD diagnosis and living situation was collected. These were compared between those classified as SGA-A and as SGA-B. Regression analysis was used to identify which factors were predictive of malnutrition (SGA-B). Differences between the groups included disease severity (4% more severe SGA-A vs 21% SGA-B, p<.05), activities of daily living score (13 SGA-A vs 18 SGA-B, p<.05), depressive symptom score (8 SGA-A vs 14 SGA-B, p<.05) and gastrointestinal symptoms (4 SGA-A vs 6 SGA-B, p<.05). Significant predictors of malnutrition according to SGA were age at diagnosis (OR 1.09, 95% CI 1.01 – 1.18), amount of dopaminergic medication per kg body weight (mg/kg) (OR 1.17, 95% CI 1.04 – 1.31), more severe motor symptoms (OR 1.10, 95% CI 1.02 – 1.19), less anxiety (OR 0.90, 95% CI 0.82 – 0.98) and more depressive symptoms (OR 1.23, 95% CI 1.07 – 1.41). Significant predictors of a higher PG-SGA score included living alone (β=0.14, 95% CI 0.01 – 0.26), more depressive symptoms (β=0.02, 95% CI 0.01 – 0.02) and more severe motor symptoms (OR 0.01, 95% CI 0.01 – 0.02). More severe disease is associated with malnutrition, and this may be compounded by lack of social support. Phase II: Nutrition intervention Nineteen of the people identified in Phase I as requiring nutrition support were included in Phase II, in which a nutrition intervention was conducted. Nine participants were in the standard care group (SC), which received an information sheet only, and the other 10 participants were in the intervention group (INT), which received individualised nutrition information and weekly follow-up. INT gained 2.2% of starting body weight over the 12 week intervention period resulting in significant increases in weight, BMI, mid-arm circumference and waist circumference. The SC group gained 1% of starting weight over the 12 weeks which did not result in any significant changes in anthropometric indices. Energy and protein intake (18.3kJ/kg vs 3.8kJ/kg and 0.3g/kg vs 0.15g/kg) increased in both groups. The increase in protein intake was only significant in the SC group. The changes in intake, when compared between the groups, were no different. There were no significant changes in any motor or non-motor symptoms or in "off" times or dyskinesias in either group. Aspects of quality of life improved over the 12 weeks as well, especially emotional well-being. This thesis makes a significant contribution to the evidence base for the presence of malnutrition in Parkinson's disease as well as for the identification of those who would potentially benefit from nutrition screening and assessment. The nutrition intervention demonstrated that a traditional high protein, high energy approach to the management of malnutrition resulted in improved nutritional status and anthropometric indices with no effect on the presence of Parkinson's disease symptoms and a positive effect on quality of life.

Brake system performance requirements of a lightweight electric/hybrid rear wheel drive vehicle

Investigates the braking performance requirements of the UltraCommuter, a lightweight series hybrid electric vehicle currently under development at the University of Queensland. With a predicted vehicle mass of 600 kg and two in-wheel motors each capable of 500 Nm of peak torque, decelerations up to 0.46 g are theoretically possible using purely regenerative braking. With 99% of braking demands less than 0.35 g, essentially all braking can be regenerative. The wheel motors have sufficient peak torque capability to lock the rear wheels in combination with front axle braking, eliminating the need for friction braking at the rear. Emergency braking levels approaching 1 g are achieved by supplementation with front disk brakes. This paper presents equations describing the peak front and rear axle braking forces which occur under straight line braking, including gradients. Conventionally, to guarantee stability, mechanical front/rear proportioning of braking effort ensures that the front axle locks first. In this application, all braking is initially regenerative at the rear, and an adaptive ''by-wire'' proportioning system presented ensures this stability requirement is still satisfied. Front wheel drive and all wheel drive systems are also discussed. Finally, peak and continuous performance measures, not commonly provided for friction brakes, are derived for the UltraCommuter's motor capability and range of operation.

An exploratory study to evaluate whether medical nutrition therapy can improve dietary intake in hospital patients who eat poorly

Background and aims The Australasian Nutrition Care Day Survey (ANCDS) reported two-in-five patients consume ≤50% of the offered food in Australian and New Zealand hospitals. After controlling for confounders (nutritional status, age, disease type and severity), the ANCDS also established an independent association between poor food intake and increased in-hospital mortality. This study aimed to evaluate if medical nutrition therapy (MNT) could improve dietary intake in hospital patients eating poorly. Methods An exploratory pilot study was conducted in the respiratory, neurology and orthopaedic wards of an Australian hospital. At baseline, percentage food intake (0%, 25%, 50%, 75%, and 100%) was evaluated for each main meal and snack for a 24-hour period in patients hospitalised for ≥2 days and not under dietetic review. Patients consuming ≤50% of offered meals due to nutrition-impact symptoms were referred to ward dietitians for MNT. Food intake was re-evaluated on the seventh day following recruitment (post-MNT). Results 184 patients were observed over four weeks; 32 patients were referred for MNT. Although baseline and post-MNT data for 20 participants (68±17years, 65% females) indicated a significant increase in median energy and protein intake post-MNT (3600kJ/day, 40g/day) versus baseline (2250kJ/day, 25g/day) (p<0.05), the increased intake met only 50% of dietary requirements. Persistent nutrition impact symptoms affected intake. Conclusion In this pilot study whilst dietary intake improved, it remained inadequate to meet participants’ estimated requirements due to ongoing nutrition-impact symptoms. Appropriate medical management and early enteral feeding could be a possible solution for such patients.

Modified alumina nanofiber membranes for protein separation

Large-scale purification/separation of bio-substances is a key technology required for rapid production of biological substances in bioengineering. Membrane filtration is a new separation process and has potential to be used for concentration (removal of solvent), desalting (removal of low molecular weight compounds), clarification (removal of particles), and fractionation (protein-protein separation). In this study, we developed an efficient membrane for protein separation based on ceramic nanofibers. Alumina nanofibers were prepared on a porous support and formed large flow passages. The radical changes in membrane structure provided new ceramic membranes with a large porosity (more than 70%) due to the replacement of bulk particles with fine fibers as building components. The pore size had an average of 11 nm and pure water flux was approximately 360 L•h-1•m-2•bar-1. Further surface modification with a self-assembled monolayer of (3-aminopropyl) triethoxysilane enhanced the membrane filtration properties. Characterization with SEM, FTIR, contact angle, and proteins separation tests indicated that the fibril layers uniformly spread on the surface of the porous support. Moreover, the membrane surface was changed from hydrophilic to hydrophobic after silane groups were grafted. It demonstrated that the silane-grafted alumina fiber membrane can reject 100% BSA protein and 92% cellulase protein. It was also able to retain 75% trypsin protein while maintaining a permeation flux of 48 L•h-1•m-2•bar-1.

Characterisation of Polycaprolatone-Based Scaffold Plus Recombinant Human Morphogenetic Protein - 2 (RHBMP-2) in an Ovine Thoracic Spine Model

This thesis represents a step forward in the development of a pre-clinical model investigating a suitable substitute for host bone for use in human spinal fusion. By way of an animal model, it examines the biological performance of a novel bone graft substitute comprised of a combination of a custom-designed biodegradable material and biologics.

Timing and distribution of protein ingestion during prolonged recovery from resistance exercise alters myofibrillar protein synthesis

Quantity and timing of protein ingestion are major factors regulating myofibrillar protein synthesis (MPS). However, the effect of specific ingestion patterns on MPS throughout a 12 h period is unknown. We determined how different distributions of protein feeding during 12 h recovery after resistance exercise affects anabolic responses in skeletal muscle. Twenty-four healthy trained males were assigned to three groups (n = 8/group) and undertook a bout of resistance exercise followed by ingestion of 80 g of whey protein throughout 12 h recovery in one of the following protocols: 8 × 10 g every 1.5 h (PULSE); 4 × 20 g every 3 h (intermediate: INT); or 2 × 40 g every 6 h (BOLUS). Muscle biopsies were obtained at rest and after 1, 4, 6, 7 and 12 h post exercise. Resting and post-exercise MPS (l-[ring-(13)C6] phenylalanine), and muscle mRNA abundance and cell signalling were assessed. All ingestion protocols increased MPS above rest throughout 1-12 h recovery (88-148%, P < 0.02), but INT elicited greater MPS than PULSE and BOLUS (31-48%, P < 0.02). In general signalling showed a BOLUS>INT>PULSE hierarchy in magnitude of phosphorylation. MuRF-1 and SLC38A2 mRNA were differentially expressed with BOLUS. In conclusion, 20 g of whey protein consumed every 3 h was superior to either PULSE or BOLUS feeding patterns for stimulating MPS throughout the day. This study provides novel information on the effect of modulating the distribution of protein intake on anabolic responses in skeletal muscle and has the potential to maximize outcomes of resistance training for attaining peak muscle mass.

Daytime pattern of post-exercise protein intake affects whole-body protein turnover in resistance-trained males

Background The pattern of protein intake following exercise may impact whole-body protein turnover and net protein retention. We determined the effects of different protein feeding strategies on protein metabolism in resistance-trained young men. Methods: Participants were randomly assigned to ingest either 80g of whey protein as 8x10g every 1.5h (PULSE; n=8), 4x20g every 3h (intermediate, INT; n=7), or 2x40g every 6h (BOLUS; n=8) after an acute bout of bilateral knee extension exercise (4x10 repetitions at 80% maximal strength). Whole-body protein turnover (Q), synthesis (S), breakdown (B), and net balance (NB) were measured throughout 12h of recovery by a bolus ingestion of [ 15N]glycine with urinary [15N]ammonia enrichment as the collected end-product. Results PULSE Q rates were greater than BOLUS (?19%, P<0.05) with a trend towards being greater than INT (?9%, P=0.08). Rates of S were 32% and 19% greater and rates of B were 51% and 57% greater for PULSE as compared to INT and BOLUS, respectively (P<0.05), with no difference between INT and BOLUS. There were no statistical differences in NB between groups (P=0.23); however, magnitude-based inferential statistics revealed likely small (mean effect90%CI; 0.590.87) and moderate (0.800.91) increases in NB for PULSE and INT compared to BOLUS and possible small increase (0.421.00) for INT vs. PULSE. Conclusion We conclude that the pattern of ingested protein, and not only the total daily amount, can impact whole-body protein metabolism. Individuals aiming to maximize NB would likely benefit from repeated ingestion of moderate amounts of protein (?20g) at regular intervals (?3h) throughout the day.

Preexercise aminoacidemia and muscle protein synthesis after resistance exercise

PURPOSE We have previously shown that the aminoacidemia caused by the consumption of a rapidly digested protein after resistance exercise enhances muscle protein synthesis (MPS) more than the amino acid (AA) profile associated with a slowly digested protein. Here, we investigated whether differential feeding patterns of a whey protein mixture commencing before exercise affect postexercise intracellular signaling and MPS. METHODS Twelve resistance-trained males performed leg resistance exercise 45 min after commencing each of three volume-matched nutrition protocols: placebo (PLAC, artificially sweetened water), BOLUS (25 g of whey protein + 5 g of leucine dissolved in artificially sweetened water; 1× 500 mL), or PULSE (15× 33-mL aliquots of BOLUS drink every 15 min). RESULTS The preexercise rise in plasma AA concentration with PULSE was attenuated compared with BOLUS (P < 0.05); this effect was reversed after exercise, with two-fold greater leucine concentrations in PULSE compared with BOLUS (P < 0.05). One-hour postexercise, phosphorylation of p70 S6K and rpS6 was increased above baseline with BOLUS and PULSE, but not PLAC (P < 0.05); furthermore, PULSE > BOLUS (P < 0.05). MPS throughout 5 h of recovery was higher with protein ingestion compared with PLAC (0.037 ± 0.007), with no differences between BOLUS or PULSE (0.085 ± 0.013 vs. 0.095 ± 0.010%•h, respectively, P = 0.56). CONCLUSIONS Manipulation of aminoacidemia before resistance exercise via different patterns of intake of protein altered plasma AA profiles and postexercise intracellular signaling. However, there was no difference in the enhancement of the muscle protein synthetic response after exercise. Protein sources producing a slow AA release, when consumed before resistance exercise in sufficient amounts, are as effective as rapidly digested proteins in promoting postexercise MPS.

Sex-based comparisons of myofibrillar protein synthesis after resistance exercise in the fed state

Sex-based comparisons of myofibrillar protein synthesis after resistance exercise in the fed state. J Appl Physiol 112: 1805-1813, 2012. First published March 1, 2012; doi:10.1152/japplphysiol.00170.2012.- We made sex-based comparisons of rates of myofibrillar protein synthesis (MPS) and anabolic signaling after a single bout of high-intensity resistance exercise. Eight men (20 ± 10 yr, BMI = 24.3 ± 2.4) and eight women (22 ± 1.8 yr, BMI = 23.0 ± 1.9) underwent primed constant infusions of L-[ring-13C6]phenylalanine on consecutive days with serial muscle biopsies. Biopsies were taken from the vastus lateralis at rest and 1, 3, 5, 24, 26, and 28 h after exercise. Twenty-five grams of whey protein was ingested immediately and 26 h after exercise. We also measured exercise-induced serum testosterone because it is purported to contribute to increases in myofibrillar protein synthesis (MPS) postexercise and its absence has been hypothesized to attenuate adaptative responses to resistance exercise in women. The exercise-induced area under the testosterone curve was 45-fold greater in men than women in the early (1 h) recovery period following exercise (P < 0.001). MPS was elevated similarly in men and women (2.3- and 2.7-fold, respectively) 1-5 h postexercise and after protein ingestion following 24 h recovery. Phosphorylation of mTORSer2448 was elevated to a greater extent in men than women acutely after exercise (P = 0.003), whereas increased phosphorylation of p70S6K1Thr389 was not different between sexes. Androgen receptor content was greater in men (main effect for sex, P = 0.049). Atrogin-1 mRNA abundance was decreased after 5 h recovery in both men and women (P < 0.001), and MuRF-1 expression was elevated in men after protein ingestion following 24 h recovery (P = 0.003). These results demonstrate minor sex-based differences in signaling responses and no difference in the MPS response to resistance exercise in the fed state. Interestingly, our data demonstrate that exerciseinduced increases in MPS are dissociated from postexercise testosteronemia and that stimulation of MPS occurs effectively with low systemic testosterone concentrations in women.

Rapid aminoacidemia enhances myofibrillar protein synthesis and anabolic intramuscular signaling responses after resistance exercise

Background: Ingestion of whey or casein yields divergent patterns of aminoacidemia that influence whole-body and skeletal muscle myofibrillar protein synthesis (MPS) after exercise. Direct comparisons of the effects of contrasting absorption rates exhibited by these proteins are confounded by their differing amino acid contents. Objective: Our objective was to determine the effect of divergent aminoacidemia by manipulating ingestion patterns of whey protein alone on MPS and anabolic signaling after resistance exercise. Design: In separate trials, 8 healthy men consumed whey protein either as a single bolus (BOLUS; 25-g dose) or as repeated, small, "pulsed" drinks (PULSE; ten 2.5-g drinks every 20 min) to mimic a more slowly digested protein. MPS and phosphorylation of signaling proteins involved in protein synthesis were measured at rest and after resistance exercise. Results: BOLUS increased blood essential amino acid (EAA) concentrations above those of PULSE (162% compared with 53%, P < 0.001) 60 min after exercise, whereas PULSE resulted in a smaller but sustained increase in aminoacidemia that remained elevated above BOLUS amounts later (180-220 min after exercise, P < 0.05). Despite an identical net area under the EAA curve, MPS was elevated to a greater extent after BOLUS than after PULSE early (1-3 h: 95% compared with 42%) and later (3-5 h: 193% compared with 121%) (both P < 0.05). There were greater changes in the phosphorylation of the Akt-mammalian target of rapamycin pathway after BOLUS than after PULSE. Conclusions: Rapid aminoacidemia in the postexercise period enhances MPS and anabolic signaling to a greater extent than an identical amount of protein fed in small pulses that mimic a more slowly digested protein. A pronounced peak aminoacidemia after exercise enhances protein synthesis.

Nutrient provision increases signalling and protein synthesis in human skeletal muscle after repeated sprints

The effect of nutrient availability on the acute molecular responses following repeated sprint exercise is unknown. The aim of this study was to determine skeletal muscle cellular and protein synthetic responses following repeated sprint exercise with nutrient provision. Eight healthy young male subjects undertook two sprint cycling sessions (10 × 6 s, 0.75 N m torque kg -1, 54 s recovery) with either pre-exercise nutrient (24 g whey, 4.8 g leucine, 50 g maltodextrin) or non-caloric placebo ingestion. Muscle biopsies were taken from vastus lateralis at rest, and after 15 and 240 min post-exercise recovery to determine muscle cell signalling responses and protein synthesis by primed constant infusion of L-[ring- 13C 6] phenylalanine. Peak and mean power outputs were similar between nutrient and placebo trials. Post-exercise myofibrillar protein synthetic rate was greater with nutrient ingestion compared with placebo ( ? 48%, P<0.05) but the rate of mitochondrial protein synthesis was similar between treatments. The increased myofibrillar protein synthesis following sprints with nutrient ingestion was associated with coordinated increases in Akt-mTOR-S6KrpS6 phosphorylation 15 min post-exercise (?200-600%, P<0.05), while there was no effect on these signalling molecules when exercise was undertaken in the fasted state. For the first time we report a beneficial effect of nutrient provision on anabolic signalling and muscle myofibrillar protein synthesis following repeated sprint exercise. Ingestion of protein/carbohydrate in close proximity to high-intensity sprint exercise provides an environment that increases cell signalling and protein synthesis.

Contraction-induced changes in TNFα and Akt-mediated signalling are associated with increased myofibrillar protein in rat skeletal muscle

Resistance training results in skeletal muscle hypertrophy, but the molecular signalling mechanisms responsible for this altered phenotype are incompletely understood. We used a resistance training (RT) protocol consisting of three sessions [day 1 (d1), day 3 (d3), day 5 (d5)] separated by 48 h recovery (squat exercise, 4 sets × 10 repetitions, 3 min recovery) to determine early signalling responses to RT in rodent skeletal muscle. Six animals per group were killed 3 h after each resistance training session and 24 and 48 h after the last training session (d5). There was a robust increase in TNF? protein expression, and IKKSer180/181 and p38MAPK Thr180/Tyr182 phosphorylation on d1 (P < 0.05), which abated with subsequent RT, returning to control levels by d5 for TNF? and IKK Ser180/181. There was a trend for a decrease in MuRF-1 protein expression, 48 h following d5 of training (P = 0.08). Notably, muscle myofibrillar protein concentration was elevated compared to control 24 and 48 h following RT (P < 0.05). AktSer473 and mTORSer2448 phosphorylation were unchanged throughout RT. Phosphorylation of p70S6k Thr389 increased 3 h post-exercise on d1, d3 and d5 (P < 0.05), whilst phosphorylation of S6Ser235/236 increased on d1 and d3 (P < 0.05). Our results show a rapid attenuation of inflammatory signalling with repeated bouts of resistance exercise, concomitant with summation in translation initiation signalling in skeletal muscle. Indeed, the cumulative effect of these signalling events was associated with myofibrillar protein accretion, which likely contributes to the early adaptations in response to resistance training overload in the skeletal muscle.

Encouraging, assisting, and time to eat : comparison of mealtime assistance interventions in elderly medical inpatients

BACKGROUND: The prevalence of protein-energy malnutrition in older adults is reported to be as high as 60% and is associated with poor health outcomes. Inadequate feeding assistance and mealtime interruptions may contribute to malnutrition and poor nutritional intake during hospitalisation. Despite being widely implemented in practice in the United Kingdom and increasingly in Australia, there have been few studies examining the impact of strategies such as Protected Mealtimes and dedicated feeding assistant roles on nutritional outcomes of elderly inpatients. AIMS: The aim of this research was to implement and compare three system-level interventions designed to specifically address mealtime barriers and improve energy intakes of medical inpatients aged ≥65 years. This research also aimed to evaluate the sustainability of any changes to mealtime routines six months post-intervention and to gain an understanding of staff perceptions of the post-intervention mealtime experience. METHODS: Three mealtime assistance interventions were implemented in three medical wards at Royal Brisbane and Women's Hospital: AIN-only: Additional assistant-in-nursing (AIN) with dedicated nutrition role. PM-only: Multidisciplinary approach to meals, including Protected Mealtimes. PM+AIN: Combined intervention: AIN + multidisciplinary approach to meals. An action research approach was used to carefully design and implement the three interventions in partnership with ward staff and managers. Significant time was spent in consultation with staff throughout the implementation period to facilitate ownership of the interventions and increase likelihood of successful implementation. A pre-post design was used to compare the implementation and nutritional outcomes of each intervention to a pre-intervention group. Using the same wards, eligible participants (medical inpatients aged ≥65 years) were recruited to the preintervention group between November 2007 and March 2008 and to the intervention groups between January and June 2009. The primary nutritional outcome was daily energy and protein intake, which was determined by visually estimating plate waste at each meal and mid-meal on Day 4 of admission. Energy and protein intakes were compared between the pre and post intervention groups. Data were collected on a range of covariates (demographics, nutritional status and known risk factors for poor food intake), which allowed for multivariate analysis of the impact of the interventions on nutritional intake. The provision of mealtime assistance to participants and activities of ward staff (including mealtime interruptions) were observed in the pre-intervention and intervention groups, with staff observations repeated six months post-intervention. Focus groups were conducted with nursing and allied health staff in June 2009 to explore their attitudes and behaviours in response to the three mealtime interventions. These focus group discussions were analysed using thematic analysis. RESULTS: A total of 254 participants were recruited to the study (pre-intervention: n=115, AIN-only: n=58, PM-only: n=39, PM+AIN: n=42). Participants had a mean age of 80 years (SD 8), and 40% (n=101) were malnourished on hospital admission, 50% (n=108) had anorexia and 38% (n=97) required some assistance at mealtimes. Occasions of mealtime assistance significantly increased in all interventions (p<0.01). However, no change was seen in mealtime interruptions. No significant difference was seen in mean total energy and protein intake between the preintervention and intervention groups. However, when total kilojoule intake was compared with estimated requirements at the individual level, participants in the intervention groups were more likely to achieve adequate energy intake (OR=3.4, p=0.01), with no difference noted between interventions (p=0.29). Despite small improvements in nutritional adequacy, the majority of participants in the intervention groups (76%, n=103) had inadequate energy intakes to meet their estimated energy requirements. Patients with cognitive impairment or feeding dependency appeared to gain substantial benefit from mealtime assistance interventions. The increase in occasions of mealtime assistance by nursing staff during the intervention period was maintained six-months post-intervention. Staff focus groups highlighted the importance of clearly designating and defining mealtime responsibilities in order to provide adequate mealtime care. While the purpose of the dedicated feeding assistant was to increase levels of mealtime assistance, staff indicated that responsibility for mealtime duties may have merely shifted from nursing staff to the assistant. Implementing the multidisciplinary interventions empowered nursing staff to "protect" the mealtime from external interruptions, but further work is required to empower nurses to prioritise mealtime activities within their own work schedules. Staff reported an increase in the profile of nutritional care on all wards, with additional non-nutritional benefits noted including improved mobility and functional independence, and better identification of swallowing difficulties. IMPLICATIONS: The PhD research provides clinicians with practical strategies to immediately introduce change to deliver better mealtime care in the hospital setting, and, as such, has initiated local and state-wide roll-out of mealtime assistance programs. Improved nutritional intakes of elderly inpatients was observed; however given the modest effect size and reducing lengths of hospital stays, better nutritional outcomes may be achieved by targeting the hospital-to-home transition period. Findings from this study suggest that mealtime assistance interventions for elderly inpatients with cognitive impairment and/or functional dependency show promise.

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.

Cyclooxygenase-2 protein levels are independent of epidermal growth factor receptor expression or activation in operable non-small cell lung cancer

Both cyclooxygenase (COX)-2 and epidermal growth factor receptor (EGFR) are thought to play important roles in the pathogenesis of non-small cell lung cancer (NSCLC). A number of in vitro studies have postulated a link between EGFR activation and subsequent COX-2 upregulation. The relationship between these factors has not been established in patients with NSCLC. COX-2 and EGFR expression were studied in 172 NSCLC specimens using standard immunohistochemical techniques. Western blotting was used to determine COX-2 and EGFR levels in five NSCLC cell lines. The effect of treatment with EGF on COX-2 expression in A549 cells was assessed. Results: Both EGFR and COX-2 are overexpressed in NSCLC. The predominant pattern of COX-2 and EGFR staining was cytoplasmic. Membranous EGFR staining was seen in 23.3% of cases. There was no relationship between COX-2 and EGFR expression and survival or any clinicopathological features. No correlation was seen between EGFR expression and COX-2 expression in the immunohistochemical series or in the cell lines. Treatment with EGF did not upregulate COX-2 levels in A549 cells, either in serum free or serum-supplemented conditions. Conclusions: Although COX-2 and EGFR are over-expressed in NSCLC neither was of prognostic significance in this series of cases. There is no correlation between these two factors in either tumour samples or cell lines. Although these factors show no correlation in NSCLC, they remain potential, though independent targets for treatment. © 2004 Elsevier Ireland Ltd. All rights reserved.