Using a longitudinal model to estimate the effect of methicillin-resistant staphylococcus aureus infection on length of stay in an intensive care unit

Healthcare-associated methicillin-resistant Staphylococcus aureus(MRSA) infection may cause increased hospital stay or, sometimes, death. Quantifying this effect is complicated because it is a time-dependent exposure: infection may prolong hospital stay, while longer stays increase the risk of infection. We overcome these problems by using a multinomial longitudinal model for estimating the daily probability of death and discharge. We then extend the basic model to estimate how the effect of MRSA infection varies over time, and to quantify the number of excess ICU days due to infection. We find that infection decreases the relative risk of discharge (relative risk ratio = 0.68, 95% credible interval: 0.54, 0.82), but is only indirectly associated with increased mortality. An infection on the first day of admission resulted in a mean extra stay of 0.3 days (95% CI: 0.1, 0.5) for a patient with an APACHE II score of 10, and 1.2 days (95% CI: 0.5, 2.0) for a patient with an APACHE II score of 30. The decrease in the relative risk of discharge remained fairly constant with day of MRSA infection, but was slightly stronger closer to the start of infection. These results confirm the importance of MRSA infection in increasing ICU stay, but suggest that previous work may have systematically overestimated the effect size.

A fully Bayesian approach to inference for Coxian phase-type distributions with covariate dependent mean

Phase-type distributions represent the time to absorption for a finite state Markov chain in continuous time, generalising the exponential distribution and providing a flexible and useful modelling tool. We present a new reversible jump Markov chain Monte Carlo scheme for performing a fully Bayesian analysis of the popular Coxian subclass of phase-type models; the convenient Coxian representation involves fewer parameters than a more general phase-type model. The key novelty of our approach is that we model covariate dependence in the mean whilst using the Coxian phase-type model as a very general residual distribution. Such incorporation of covariates into the model has not previously been attempted in the Bayesian literature. A further novelty is that we also propose a reversible jump scheme for investigating structural changes to the model brought about by the introduction of Erlang phases. Our approach addresses more questions of inference than previous Bayesian treatments of this model and is automatic in nature. We analyse an example dataset comprising lengths of hospital stays of a sample of patients collected from two Australian hospitals to produce a model for a patient's expected length of stay which incorporates the effects of several covariates. This leads to interesting conclusions about what contributes to length of hospital stay with implications for hospital planning. We compare our results with an alternative classical analysis of these data.

Beneficial effects of exercise : shifting the focus from body weight to other markers of health

Background: Exercise is widely promoted as a method of weight management, while the other health benefits are often ignored. The purpose of this study was to examine whether exercise-induced improvements in health are influenced by changes in body weight. Methods: Fifty-eight sedentary overweight/obese men and women (BMI 31.8 (SD 4.5) kg/m2) participated in a 12-week supervised aerobic exercise intervention (70% heart rate max, five times a week, 500 kcal per session). Body composition, anthropometric parameters, aerobic capacity, blood pressure and acute psychological response to exercise were measured at weeks 0 and 12. Results: The mean reduction in body weight was −3.3 (3.63) kg (p<0.01). However, 26 of the 58 participants failed to attain the predicted weight loss estimated from individuals’ exercise-induced energy expenditure. Their mean weight loss was only −0.9 (1.8) kg (p<0.01). Despite attaining a lower-than-predicted weight reduction, these individuals experienced significant increases in aerobic capacity (6.3 (6.0) ml/kg/min; p<0.01), and a decreased systolic (−6.00 (11.5) mm Hg; p<0.05) and diastolic blood pressure (−3.9 (5.8) mm Hg; p<0.01), waist circumference (−3.7 (2.7) cm; p<0.01) and resting heart rate (−4.8 (8.9) bpm, p<0.001). In addition, these individuals experienced an acute exercise-induced increase in positive mood. Conclusions: These data demonstrate that significant and meaningful health benefits can be achieved even in the presence of lower-than-expected exercise-induced weight loss. A less successful reduction in body weight does not undermine the beneficial effects of aerobic exercise. From a public health perspective, exercise should be encouraged and the emphasis on weight loss reduced.

Swept frequency biompedance analysis for the determination of body water compartments

Bioelectrical impedance analysis, (BIA), is a method of body composition analysis first investigated in 1962 which has recently received much attention by a number of research groups. The reasons for this recent interest are its advantages, (viz: inexpensive, non-invasive and portable) and also the increasing interest in the diagnostic value of body composition analysis. The concept utilised by BIA to predict body water volumes is the proportional relationship for a simple cylindrical conductor, (volume oc length2/resistance), which allows the volume to be predicted from the measured resistance and length. Most of the research to date has measured the body's resistance to the passage of a 50· kHz AC current to predict total body water, (TBW). Several research groups have investigated the application of AC currents at lower frequencies, (eg 5 kHz), to predict extracellular water, (ECW). However all research to date using BIA to predict body water volumes has used the impedance measured at a discrete frequency or frequencies. This thesis investigates the variation of impedance and phase of biological systems over a range of frequencies and describes the development of a swept frequency bioimpedance meter which measures impedance and phase at 496 frequencies ranging from 4 kHz to 1 MHz. The impedance of any biological system varies with the frequency of the applied current. The graph of reactance vs resistance yields a circular arc with the resistance decreasing with increasing frequency and reactance increasing from zero to a maximum then decreasing to zero. Computer programs were written to analyse the measured impedance spectrum and determine the impedance, Zc, at the characteristic frequency, (the frequency at which the reactance is a maximum). The fitted locus of the measured data was extrapolated to determine the resistance, Ro, at zero frequency; a value that cannot be measured directly using surface electrodes. The explanation of the theoretical basis for selecting these impedance values (Zc and Ro), to predict TBW and ECW is presented. Studies were conducted on a group of normal healthy animals, (n=42), in which TBW and ECW were determined by the gold standard of isotope dilution. The prediction quotients L2/Zc and L2/Ro, (L=length), yielded standard errors of 4.2% and 3.2% respectively, and were found to be significantly better than previously reported, empirically determined prediction quotients derived from measurements at a single frequency. The prediction equations established in this group of normal healthy animals were applied to a group of animals with abnormally low fluid levels, (n=20), and also to a group with an abnormal balance of extra-cellular to intracellular fluids, (n=20). In both cases the equations using L2/Zc and L2/Ro accurately and precisely predicted TBW and ECW. This demonstrated that the technique developed using multiple frequency bioelectrical impedance analysis, (MFBIA), can accurately predict both TBW and ECW in both normal and abnormal animals, (with standard errors of the estimate of 6% and 3% for TBW and ECW respectively). Isotope dilution techniques were used to determine TBW and ECW in a group of 60 healthy human subjects, (male. and female, aged between 18 and 45). Whole body impedance measurements were recorded on each subject using the MFBIA technique and the correlations between body water volumes, (TBW and ECW), and heighe/impedance, (for all measured frequencies), were compared. The prediction quotients H2/Zc and H2/Ro, (H=height), again yielded the highest correlation with TBW and ECW respectively with corresponding standard errors of 5.2% and 10%. The values of the correlation coefficients obtained in this study were very similar to those recently reported by others. It was also observed that in healthy human subjects the impedance measured at virtually any frequency yielded correlations not significantly different from those obtained from the MFBIA quotients. This phenomenon has been reported by other research groups and emphasises the need to validate the technique by investigating its application in one or more groups with abnormalities in fluid levels. The clinical application of MFBIA was trialled and its capability of detecting lymphoedema, (an excess of extracellular fluid), was investigated. The MFBIA technique was demonstrated to be significantly more sensitive, (P<.05), in detecting lymphoedema than the current technique of circumferential measurements. MFBIA was also shown to provide valuable information describing the changes in the quantity of muscle mass of the patient during the course of the treatment. The determination of body composition, (viz TBW and ECW), by MFBIA has been shown to be a significant improvement on previous bioelectrical impedance techniques. The merit of the MFBIA technique is evidenced in its accurate, precise and valid application in animal groups with a wide variation in body fluid volumes and balances. The multiple frequency bioelectrical impedance analysis technique developed in this study provides accurate and precise estimates of body composition, (viz TBW and ECW), regardless of the individual's state of health.

Pretreatment malnutrition and quality of life - association with prolonged length of hospital stay among patients with gynecological cancer: A cohort study

Background Length of hospital stay (LOS) is a surrogate marker for patients' well-being during hospital treatment and is associated with health care costs. Identifying pretreatment factors associated with LOS in surgical patients may enable early intervention in order to reduce postoperative LOS. Methods This cohort study enrolled 157 patients with suspected or proven gynecological cancer at a tertiary cancer centre (2004-2006). Before commencing treatment, the scored Patient Generated - Subjective Global Assessment (PG-SGA) measuring nutritional status and the Functional Assessment of Cancer Therapy-General (FACT-G) scale measuring quality of life (QOL) were completed. Clinical and demographic patient characteristics were prospectively obtained. Patients were grouped into those with prolonged LOS if their hospital stay was greater than the median LOS and those with average or below average LOS. Results Patients' mean age was 58 years (SD 14 years). Preoperatively, 81 (52%) patients presented with suspected benign disease/pelvic mass, 23 (15%) with suspected advanced ovarian cancer, 36 (23%) patients with suspected endometrial and 17 (11%) with cervical cancer, respectively. In univariate models prolonged LOS was associated with low serum albumin or hemoglobin, malnutrition (PG-SGA score and PG-SGA group B or C), low pretreatment FACT-G score, and suspected diagnosis of cancer. In multivariable models, PG-SGA group B or C, FACT-G score and suspected diagnosis of advanced ovarian cancer independently predicted LOS. Conclusions Malnutrition, low quality of life scores and being diagnosed with advanced ovarian cancer are the major determinants of prolonged LOS amongst gynecological cancer patients. Interventions addressing malnutrition and poor QOL may decrease LOS in gynecological cancer patients.

Upper-body morbidity following breast cancer treatment is common, may persist longer-term and adversely influences quality of life

Background: Impairments in upper-body function (UBF) are common following breast cancer. However, the relationship between arm morbidity and quality of life (QoL) remains unclear. This investigation uses longitudinal data to describe UBF in a population-based sample of women with breast cancer and examines its relationship with QoL. ---------- Methods: Australian women (n = 287) with unilateral breast cancer were assessed at three-monthly intervals, from six- to 18-months post-surgery (PS). Strength, endurance and flexibility were used to assess objective UBF, while the Disability of the Arm, Shoulder and Hand questionnaire and the Functional Assessment of Cancer Therapy- Breast questionnaire were used to assess self-reported UBF and QoL, respectively. ---------- Results: Although mean UBF improved over time, up to 41% of women revealed declines in UBF between sixand 18-months PS. Older age, lower socioeconomic position, treatment on the dominant side, mastectomy, more extensive lymph node removal and having lymphoedema each increased odds of declines in UBF by at least twofold (p < 0.05). Lower baseline and declines in perceived UBF between six- and 18-months PS were each associated with poorer QoL at 18-months PS (p < 0.05). ---------- Conclusions: Significant upper-body morbidity is experienced by many following breast cancer treatment, persisting longer term, and adversely influencing the QoL of breast cancer survivors.

Axial length charges during accommodation in myopes and emmetropes

Purpose: To investigate the influence of accommodation upon axial length (and a comprehensive range of ocular biometric parameters), in populations of young adult myopic and emmetropic subjects. Methods: Forty young adult subjects had ocular biometry measured utilizing a non-contact optical biometer (Lenstar LS 900) based upon the principle of optical low coherence reflectometry, under three different accommodation demands (0 D, 3 D and 6 D). Subjects were classified as emmetropes (n=19) or myopes (n=21) based upon their spherical equivalent refraction (mean emmetropic refraction -0.05 ± 0.27DS and mean myopic refraction -1.82 ± 0.84 DS). Results: Axial length changed significantly with accommodation, with a mean increase of 11.9 ± 12.3 µm and 24.1 ± 22.7 µm for the 3 D and 6 D accommodation stimuli respectively. A significant axial elongation associated with accommodation was still evident even following correction of the axial length data for potential error due to lens thickness change. The mean ‘corrected’ increase in axial length was 5.2 ± 11.2 µm, and 7.4 ± 18.9 µm for the 3 D and 6 D stimuli respectively. There was no significant difference between the myopic and emmetropic populations in terms of the magnitude of change in axial length with accommodation, regardless of whether the data were corrected or not. A number of other ocular biometric parameters, such as anterior chamber depth, lens thickness and vitreous chamber depth also exhibited significant change with accommodation. The myopic and emmetropic populations also exhibited no significant difference in the magnitude of change in these parameters with accommodation. Conclusions: The eye undergoes a significant axial elongation associated with a brief period of accommodation, and the magnitude of this change in eye length increases for larger accommodation demands, however there is no significant difference in the magnitude of eye elongation in myopic and emmetropic subjects.

Sustained convergence, axial length, and corneal topography

Purpose: To investigate the influence of convergence on axial length and corneal topography in young adult subjects.---------- Methods: Fifteen emmetropic young adult subjects with normal binocular vision had axial length and corneal topography measured immediately before and after a 15-min period of base out (BO) prismatic spectacle lens wear. Two different magnitude prismatic spectacles were worn in turn (8 [DELTA] BO and 16 [DELTA] BO), and for both tasks, distance fixation was maintained for the duration of lens wear. Eight subjects returned on a separate day for further testing and had axial length measured before, during, and immediately after a 15-min convergence task.---------- Results: No significant change was found to occur in axial length either during or after the sustained convergence tasks (p > 0.6). Some small but significant changes in corneal topography were found to occur after sustained convergence. The most significant corneal change was observed after the 16 [DELTA] BO prism wear. The corneal refractive power spherocylinder power vector J0 was found to change by a small (mean change of 0.03 D after the 16 [DELTA] BO task) but statistically significant (p = 0.03) amount as a result of the convergence task (indicative of a reduction in with-the-rule corneal astigmatism after convergence). Corneal axial power was found to exhibit a significant flattening in superior regions. Conclusions: Axial length appears largely unchanged by a period of sustained convergence. However, small but significant changes occur in the topography of the cornea after convergence.

Human optical axial length and defocus

Purpose: To investigate the short term influence of imposed monocular defocus upon human optical axial length (the distance from anterior cornea to retinal pigment epithelium) and ocular biometrics. Methods: Twenty-eight young adult subjects (14 myopes and 14 emmetropes) had eye biometrics measured before and then 30 and 60 minutes after exposure to monocular (right eye) defocus. Four different monocular defocus conditions were tested, each on a separate day: control (no defocus), myopic (+3 D defocus), hyperopic (-3 D defocus) and diffuse (0.2 density Bangerter filter) defocus. The fellow eye was optimally corrected (no defocus). Results: Imposed defocus caused small but significant changes in optical axial length (p<0.0001). A significant increase in optical axial length (mean change +8 ± 14 μm, p=0.03) occurred following hyperopic defocus, and a significant reduction in optical axial length (mean change -13 ± 14 μm, p=0.0001) was found following myopic defocus. A small increase in optical axial length was observed following diffuse defocus (mean change +6 ± 13 μm, p=0.053). Choroidal thickness also exhibited some significant changes with certain defocus conditions. No significant difference was found between myopes and emmetropes in the changes in optical axial length or choroidal thickness with defocus. Conclusions: Significant changes in optical axial length occur in human subjects following 60 minutes of monocular defocus. The bi-directional optical axial length changes observed in response to defocus implies the human visual system is capable of detecting the presence and sign of defocus and altering optical axial length to move the retina towards the image plane.

Water drinking influences eye length and IOP in young healthy subjects

This study aimed to investigate the influence of water loading upon intraocular pressure (IOP), ocular pulse amplitude (OPA) and axial length. Twenty one young adult subjects who were classified based on their spherical equivalent refraction as either myopes (n=11), or emmetropes (n=10) participated. Measures of IOP, OPA and ocular biometrics were collected before, and then 10, 15, 25 and 30 minutes following the ingestion of 1000 ml of water. Significant increases in both IOP and OPA were found to occur following water loading (p<0.0001), with peaks in both parameters occurring at 10 minutes after water loading (mean ± SEM increase of 2.24 ± 0.31 mmHg in IOP and 0.46 ± 0.06 mmHg in OPA). Axial length was found to reduce significantly following water loading (p=0.0005), with the largest reduction in axial length evident 10 minutes after water drinking (mean decrease 12 ± 3 µm). A significant time by refractive error group interaction (p=0.048) was found in axial length, indicative of a different pattern of change in eye length following water loading between the myopic and emmetropic populations. The largest difference in axial length change was evident at 10 minutes after water loading with a 17 ± 5 µm reduction in axial length evident in the myopes and only a 6 ± 2 µm reduction in the emmetropes. These findings illustrate significant changes in ocular parameters in young adult subjects following water loading.

Engineering an Ecosystem : Taking Cues from Nature’s Paradigm to Build Tissue in the Lab and the Body

This manuscript took a 'top down' approach to understanding survival of inhabitant cells in the ecosystem bone, working from higher to lower length and time scales through the hierarchical ecosystem of bone. Our working hypothesis is that nature “engineered” the skeleton using a 'bottom up' approach,where mechanical properties of cells emerge from their adaptation to their local me-chanical milieu. Cell aggregation and formation of higher order anisotropic struc- ture results in emergent architectures through cell differentiation and extracellular matrix secretion. These emergent properties, including mechanical properties and architecture, result in mechanical adaptation at length scales and longer time scales which are most relevant for the survival of the vertebrate organism [Knothe Tate and von Recum 2009]. We are currently using insights from this approach to har-ness nature’s regeneration potential and to engineer novel mechanoactive materials [Knothe Tate et al. 2007, Knothe Tate et al. 2009]. In addition to potential applications of these exciting insights, these studies may provide important clues to evolution and development of vertebrate animals. For instance, one might ask why mesenchymal stem cells condense at all? There is a putative advantage to self-assembly and cooperation, but this advantage is somewhat outweighed by the need for infrastructural complexity (e.g., circulatory systems comprised of specific differentiated cell types which in turn form conduits and pumps to overcome limitations of mass transport via diffusion, for example; dif-fusion is untenable for multicellular organisms larger than 250 microns in diameter. A better question might be: Why do cells build skeletal tissue? Once cooperatingcells in tissues begin to deplete local sources of food in their aquatic environment, those that have evolved a means to locomote likely have an evolutionary advantage. Once the environment becomes less aquarian and more terrestrial, self-assembled organisms with the ability to move on land might have conferred evolutionary ad-vantages as well. So did the cytoskeleton evolve several length scales, enabling the emergence of skeletal architecture for vertebrate animals? Did the evolutionary advantage of motility over noncompliant terrestrial substrates (walking on land) favor adaptations including emergence of intracellular architecture (changes in the cytoskeleton and upregulation of structural protein manufacture), inter-cellular con- densation, mineralization of tissues, and emergence of higher order architectures?How far does evolutionary Darwinism extend and how can we exploit this knowl- edge to engineer smart materials and architectures on Earth and new, exploratory environments?[Knothe Tate et al. 2008]. We are limited only by our ability to imagine. Ultimately, we aim to understand nature, mimic nature, guide nature and/or exploit nature’s engineering paradigms without engineer-ing ourselves out of existence.

Flexural and torsional rigidity of colonoscope at room and body temperatures

A series of experiments have been conducted to determine the flexural, EI, and torsional, GJ, rigidity of an Olympus colonoscope CF‐140S and torsional rigidity of a Pentax colonoscope EC‐3870 and the dependency of these properties on temperature and on the presence of loops. Along the length of the colonoscope, the Olympus colonoscope flexural rigidity varied between 260 and 400 Ncm2 and torsional rigidity varied between 68 and 88 Ncm2/deg, with an average of 76 Ncm2/deg for tests involving 0.86 Nm of anti‐clockwise torque. Results show a significant decrease of 10% in torsional rigidity between clockwise and anti‐clockwise torque. For the Pentax colonoscope flexural rigidity was not tested; its torsional rigidity varied between 34 and 76 Ncm2/deg, with an average of 46 Ncm2/deg for tests involving 0.43 Nm of anti‐clockwise torque. An increase in temperature of the Olympus colonoscope from 24°C to 37°C reduces EI by an average of 17% and GJ by an average of 7%. A right‐handed loop caused a significant increase in flexural rigidity, but other looping configurations had no significant influence.

Malnutrition and clinical outcomes in elderly patients from a Singapore acute hospital

Older adults, especially those acutely ill, are vulnerable to developing malnutrition due to a range of risk factors. The high prevalence and extensive consequences of malnutrition in hospitalised older adults have been reported extensively. However, there are few well-designed longitudinal studies that report the independent relationship between malnutrition and clinical outcomes after adjustment for a wide range of covariates. Acutely ill older adults are exceptionally prone to nutritional decline during hospitalisation, but few reports have studied this change and impact on clinical outcomes. In the rapidly ageing Singapore population, all this evidence is lacking, and the characteristics associated with the risk of malnutrition are also not well-documented. Despite the evidence on malnutrition prevalence, it is often under-recognised and under-treated. It is therefore crucial that validated nutrition screening and assessment tools are used for early identification of malnutrition. Although many nutrition screening and assessment tools are available, there is no universally accepted method for defining malnutrition risk and nutritional status. Most existing tools have been validated amongst Caucasians using various approaches, but they are rarely reported in the Asian elderly and none has been validated in Singapore. Due to the multiethnicity, cultural, and language differences in Singapore older adults, the results from non-Asian validation studies may not be applicable. Therefore it is important to identify validated population and setting specific nutrition screening and assessment methods to accurately detect and diagnose malnutrition in Singapore. The aims of this study are therefore to: i) characterise hospitalised elderly in a Singapore acute hospital; ii) describe the extent and impact of admission malnutrition; iii) identify and evaluate suitable methods for nutritional screening and assessment; and iv) examine changes in nutritional status during admission and their impact on clinical outcomes. A total of 281 participants, with a mean (+SD) age of 81.3 (+7.6) years, were recruited from three geriatric wards in Tan Tock Seng Hospital over a period of eight months. They were predominantly Chinese (83%) and community-dwellers (97%). They were screened within 72 hours of admission by a single dietetic technician using four nutrition screening tools [Tan Tock Seng Hospital Nutrition Screening Tool (TTSH NST), Nutritional Risk Screening 2002 (NRS 2002), Mini Nutritional Assessment-Short Form (MNA-SF), and Short Nutritional Assessment Questionnaire (SNAQ©)] that were administered in no particular order. The total scores were not computed during the screening process so that the dietetic technician was blinded to the results of all the tools. Nutritional status was assessed by a single dietitian, who was blinded to the screening results, using four malnutrition assessment methods [Subjective Global Assessment (SGA), Mini Nutritional Assessment (MNA), body mass index (BMI), and corrected arm muscle area (CAMA)]. The SGA rating was completed prior to computation of the total MNA score to minimise bias. Participants were reassessed for weight, arm anthropometry (mid-arm circumference, triceps skinfold thickness), and SGA rating at discharge from the ward. The nutritional assessment tools and indices were validated against clinical outcomes (length of stay (LOS) >11days, discharge to higher level care, 3-month readmission, 6-month mortality, and 6-month Modified Barthel Index) using multivariate logistic regression. The covariates included age, gender, race, dementia (defined using DSM IV criteria), depression (defined using a single question “Do you often feel sad or depressed?”), severity of illness (defined using a modified version of the Severity of Illness Index), comorbidities (defined using Charlson Comorbidity Index, number of prescribed drugs and admission functional status (measured using Modified Barthel Index; MBI). The nutrition screening tools were validated against the SGA, which was found to be the most appropriate nutritional assessment tool from this study (refer section 5.6) Prevalence of malnutrition on admission was 35% (defined by SGA), and it was significantly associated with characteristics such as swallowing impairment (malnourished vs well-nourished: 20% vs 5%), poor appetite (77% vs 24%), dementia (44% vs 28%), depression (34% vs 22%), and poor functional status (MBI 48.3+29.8 vs 65.1+25.4). The SGA had the highest completion rate (100%) and was predictive of the highest number of clinical outcomes: LOS >11days (OR 2.11, 95% CI [1.17- 3.83]), 3-month readmission (OR 1.90, 95% CI [1.05-3.42]) and 6-month mortality (OR 3.04, 95% CI [1.28-7.18]), independent of a comprehensive range of covariates including functional status, disease severity and cognitive function. SGA is therefore the most appropriate nutritional assessment tool for defining malnutrition. The TTSH NST was identified as the most suitable nutritional screening tool with the best diagnostic performance against the SGA (AUC 0.865, sensitivity 84%, specificity 79%). Overall, 44% of participants experienced weight loss during hospitalisation, and 27% had weight loss >1% per week over median LOS 9 days (range 2-50). Wellnourished (45%) and malnourished (43%) participants were equally prone to experiencing decline in nutritional status (defined by weight loss >1% per week). Those with reduced nutritional status were more likely to be discharged to higher level care (adjusted OR 2.46, 95% CI [1.27-4.70]). This study is the first to characterise malnourished hospitalised older adults in Singapore. It is also one of the very few studies to (a) evaluate the association of admission malnutrition with clinical outcomes in a multivariate model; (b) determine the change in their nutritional status during admission; and (c) evaluate the validity of nutritional screening and assessment tools amongst hospitalised older adults in an Asian population. Results clearly highlight that admission malnutrition and deterioration in nutritional status are prevalent and are associated with adverse clinical outcomes in hospitalised older adults. With older adults being vulnerable to risks and consequences of malnutrition, it is important that they are systematically screened so timely and appropriate intervention can be provided. The findings highlighted in this thesis provide an evidence base for, and confirm the validity of the current nutrition screening and assessment tools used among hospitalised older adults in Singapore. As the older adults may have developed malnutrition prior to hospital admission, or experienced clinically significant weight loss of >1% per week of hospitalisation, screening of the elderly should be initiated in the community and continuous nutritional monitoring should extend beyond hospitalisation.

Body composition and its relationship to metabolic risk factors in Asian children

Obesity is a major public health problem in both developed and developing countries. The body mass index (BMI) is the most common index used to define obesity. The universal application of the same BMI classification across different ethnic groups is being challenged due to the inability of the index to differentiate fat mass (FM) and fat�]free mass (FFM) and the recognized ethnic differences in body composition. A better understanding of the body composition of Asian children from different backgrounds would help to better understand the obesity�]related health risks of people in this region. Moreover, the limitations of the BMI underscore the necessity to use where possible, more accurate measures of body fat assessment in research and clinical settings in addition to BMI, particularly in relation to the monitoring of prevention and treatment efforts. The aim of the first study was to determine the ethnic difference in the relationship between BMI and percent body fat (%BF) in pre�]pubertal Asian children from China, Lebanon, Malaysia, the Philippines, and Thailand. A total of 1039 children aged 8�]10 y were recruited using a non�]random purposive sampling approach aiming to encompass a wide BMI range from the five countries. Percent body fat (%BF) was determined using the deuterium dilution technique to quantify total body water (TBW) and subsequently derive proportions of FM and FFM. The study highlighted the sex and ethnic differences between BMI and %BF in Asian children from different countries. Girls had approximately 4.0% higher %BF compared with boys at a given BMI. Filipino boys tended to have a lower %BF than their Chinese, Lebanese, Malay and Thai counterparts at the same age and BMI level (corrected mean %BF was 25.7�}0.8%, 27.4�}0.4%, 27.1�}0.6%, 27.7�}0.5%, 28.1�}0.5% for Filipino, Chinese, Lebanese, Malay and Thai boys, respectively), although they differed significantly from Thai and Malay boys. Thai girls had approximately 2.0% higher %BF values than Chinese, Lebanese, Filipino and Malay counterparts (however no significant difference was seen among the four ethnic groups) at a given BMI (corrected mean %BF was 31.1�}0.5%, 28.6�}0.4%, 29.2�}0.6%, 29.5�}0.6%, 29.5�}0.5% for Thai, Chinese, Lebanese, Malay and Filipino girls, respectively). However, the ethnic difference in BMI�]%BF relationship varied by BMI. Compared with Caucasians, Asian children had a BMI 3�]6 units lower for a given %BF. More than one third of obese Asian children in the study were not identified using the WHO classification and more than half were not identified using the International Obesity Task Force (IOTF) classification. However, use of the Chinese classification increased the sensitivity by 19.7%, 18.1%, 2.3%, 2.3%, and 11.3% for Chinese, Lebanese, Malay, Filipino and Thai girls, respectively. A further aim of the first study was to determine the ethnic difference in body fat distribution in pre�]pubertal Asian children from China, Lebanon, Malaysia, and Thailand. The skin fold thicknesses, height, weight, waist circumference (WC) and total adiposity (as determined by deuterium dilution technique) of 922 children from the four countries was assessed. Chinese boys and girls had a similar trunk�]to�]extremity skin fold thickness ratio to Thai counterparts and both groups had higher ratios than the Malays and Lebanese at a given total FM. At a given BMI, both Chinese and Thai boys and girls had a higher WC than Malays and Lebanese (corrected mean WC was 68.1�}0.2 cm, 67.8�}0.3 cm, 65.8�}0.4 cm, 64.1�}0.3 cm for Chinese, Thai, Lebanese and Malay boys, respectively; 64.2�}0.2 cm, 65.0�}0.3 cm, 62.9�}0.4 cm, 60.6�}0.3 cm for Chinese, Thai, Lebanese and Malay girls, respectively). Chinese boys and girls had lower trunk fat adjusted subscapular/suprailiac skinfold ratio compared with Lebanese and Malay counterparts. The second study aimed to develop and cross�]validate bioelectrical impedance analysis (BIA) prediction equations of TBW and FFM for Asian pre�]pubertal children from China, Lebanon, Malaysia, the Philippines, and Thailand. Data on height, weight, age, gender, resistance and reactance measured by BIA were collected from 948 Asian children (492 boys and 456 girls) aged 8�]10 y from the five countries. The deuterium dilution technique was used as the criterion method for the estimation of TBW and FFM. The BIA equations were developed from the validation group (630 children randomly selected from the total sample) using stepwise multiple regression analysis and cross�]validated in a separate group (318 children) using the Bland�]Altman approach. Age, gender and ethnicity influenced the relationship between the resistance index (RI = height2/resistance), TBW and FFM. The BIA prediction equation for the estimation of TBW was: TBW (kg) = 0.231�~Height2 (cm)/resistance (ƒ¶) + 0.066�~Height (cm) + 0.188�~Weight (kg) + 0.128�~Age (yr) + 0.500�~Sex (male=1, female=0) . 0.316�~Ethnicity (Thai ethnicity=1, others=0) �] 4.574, and for the estimation of FFM: FFM (kg) = 0.299�~Height2 (cm)/resistance (ƒ¶) + 0.086�~Height (cm) + 0.245�~Weight (kg) + 0.260�~Age (yr) + 0.901�~Sex (male=1, female=0) �] 0.415�~Ethnicity (Thai ethnicity=1, others=0) �] 6.952. The R2 was 88.0% (root mean square error, RSME = 1.3 kg), 88.3% (RSME = 1.7 kg) for TBW and FFM equation, respectively. No significant difference between measured and predicted TBW and between measured and predicted FFM for the whole cross�]validation sample was found (bias = �]0.1�}1.4 kg, pure error = 1.4�}2.0 kg for TBW and bias = �]0.2�}1.9 kg, pure error = 1.8�}2.6 kg for FFM). However, the prediction equation for estimation of TBW/FFM tended to overestimate TBW/FFM at lower levels while underestimate at higher levels of TBW/FFM. Accuracy of the general equation for TBW and FFM compared favorably with both BMI�]specific and ethnic�]specific equations. There were significant differences between predicted TBW and FFM from external BIA equations derived from Caucasian populations and measured values in Asian children. There were three specific aims of the third study. The first was to explore the relationship between obesity and metabolic syndrome and abnormalities in Chinese children. A total of 608 boys and 800 girls aged 6�]12 y were recruited from four cities in China. Three definitions of pediatric metabolic syndrome and abnormalities were used, including the International Diabetes Federation (IDF) and National Cholesterol Education Program (NCEP) definition for adults modified by Cook et al. and de Ferranti et al. The prevalence of metabolic syndrome varied with different definitions, was highest using the de Ferranti definition (5.4%, 24.6% and 42.0%, respectively for normal�]weight, overweight and obese children), followed by the Cook definition (1.5%, 8.1%, and 25.1%, respectively), and the IDF definition (0.5%, 1.8% and 8.3%, respectively). Overweight and obese children had a higher risk of developing the metabolic syndrome compared to normal�]weight children (odds ratio varied with different definitions from 3.958 to 6.866 for overweight children, and 12.640�]26.007 for obese children). Overweight and obesity also increased the risk of developing metabolic abnormalities. Central obesity and high triglycerides (TG) were the most common while hyperglycemia was the least frequent in Chinese children regardless of different definitions. The second purpose was to determine the best obesity index for the prediction of cardiovascular (CV) risk factor clustering across a 2�]y follow�]up among BMI, %BF, WC and waist�]to�]height ratio (WHtR) in Chinese children. Height, weight, WC, %BF as determined by BIA, blood pressure, TG, high�]density lipoprotein cholesterol (HDL�]C), and fasting glucose were collected at baseline and 2 years later in 292 boys and 277 girls aged 8�]10 y. The results showed the percentage of children who remained overweight/obese defined on the basis of BMI, WC, WHtR and %BF was 89.7%, 93.5%, 84.5%, and 80.4%, respectively after 2 years. Obesity indices at baseline significantly correlated with TG, HDL�]C, and blood pressure at both baseline and 2 years later with a similar strength of correlations. BMI at baseline explained the greatest variance of later blood pressure. WC at baseline explained the greatest variance of later HDL�]C and glucose, while WHtR at baseline was the main predictor of later TG. Receiver�]operating characteristic (ROC) analysis explored the ability of the four indices to identify the later presence of CV risk. The overweight/obese children defined on the basis of BMI, WC, WHtR or %BF were more likely to develop CV risk 2 years later with relative risk (RR) scores of 3.670, 3.762, 2.767, and 2.804, respectively. The final purpose of the third study was to develop age�] and gender�]specific percentiles of WC and WHtR and cut�]off points of WC and WHtR for the prediction of CV risk in Chinese children. Smoothed percentile curves of WC and WHtR were produced in 2830 boys and 2699 girls aged 6�]12 y randomly selected from southern and northern China using the LMS method. The optimal age�] and gender�]specific thresholds of WC and WHtR for the prediction of cardiovascular risk factors clustering were derived in a sub�]sample (n=1845) by ROC analysis. Age�] and gender�]specific WC and WHtR percentiles were constructed. The WC thresholds were at the 90th and 84th percentiles for Chinese boys and girls, respectively, with sensitivity and specificity ranging from 67.2% to 83.3%. The WHtR thresholds were at the 91st and 94th percentiles for Chinese boys and girls, respectively, with sensitivity and specificity ranging from 78.6% to 88.9%. The cut�]offs of both WC and WHtR were age�] and gender�]dependent. In conclusion, the current thesis quantifies the ethnic differences in the BMI�]%BF relationship and body fat distribution between Asian children from different origins and confirms the necessity to consider ethnic differences in body composition when developing BMI and other obesity index criteria for obesity in Asian children. Moreover, ethnicity is also important in BIA prediction equations. In addition, WC and WHtR percentiles and thresholds for the prediction of CV risk in Chinese children differ from other populations. Although there was no advantage of WC or WHtR over BMI or %BF in the prediction of CV risk, obese children had a higher risk of developing the metabolic syndrome and abnormalities than normal�]weight children regardless of the obesity index used.

Malnutrition and its impact on cost of hospitalization, length of stay, readmission and 3-year mortality

Background & aims: The confounding effect of disease on the outcomes of malnutrition using diagnosis-related groups (DRG) has never been studied in a multidisciplinary setting. This study aims to determine the prevalence of malnutrition in a tertiary hospital in Singapore and its impact on hospitalization outcomes and costs, controlling for DRG. Methods: This prospective cohort study included a matched case control study. Subjective Global Assessment was used to assess the nutritional status on admission of 818 adults. Hospitalization outcomes over 3 years were adjusted for gender, age, ethnicity, and matched for DRG. Results: Malnourished patients (29%) had longer hospital stays (6.9 ± 7.3 days vs. 4.6 ± 5.6 days, p < 0.001) and were more likely to be readmitted within 15 days (adjusted relative risk = 1.9, 95%CI 1.1–3.2, p = 0.025). Within a DRG, the mean difference between actual cost of hospitalization and the average cost for malnourished patients was greater than well-nourished patients (p = 0.014). Mortality was higher in malnourished patients at 1 year (34% vs. 4.1 %), 2 years (42.6% vs. 6.7%) and 3 years (48.5% vs. 9.9%); p < 0.001 for all. Overall, malnutrition was a significant predictor of mortality (adjusted hazard ratio = 4.4, 95% CI 3.3-6.0, p < 0.001). Conclusions: Malnutrition was evident in up to one third of the inpatients and led to poor hospitalization outcomes and survival as well as increased costs of care, even after matching for DRG. Strategies to prevent and treat malnutrition in the hospital and post-discharge are needed.