Human development index, children's health-related quality of life and movement behaviors: a compositional data analysis.

PURPOSE: Health-related quality of life has been related to physical activity, sedentary behavior, and sleep among children from developed nations. These relationships have rarely been assessed in developing nations, nor have behaviors been considered in their true context, as mutually exclusive and exhaustive parts of the movement behavior composition. This study aimed to explore whether children's health-related quality of life is related to their movement behavior composition and if the relationship differs according to human development index. METHODS: Children aged 9-11 years (n = 5855), from the 12-nation cross-sectional observational International Study of Childhood Obesity, Lifestyle and the Environment 2011-2013, self-reported their health-related quality of life (KIDSCREEN-10). Daily movement behaviors were from 24-h, 7-day accelerometry. Isometric log-ratio mixed-effect linear models were used to calculate estimates for difference in health-related quality of life for the reallocation of time between daily movement behaviors. RESULTS: Children from countries of higher human development index reported stronger positive relationships between health-related quality of life and moderate-to-vigorous physical activity, relative to the remaining behaviors (r = 0.75, p = 0.005) than those from lower human development index countries. In the very high human development index strata alone, health-related quality of life was significantly related to the movement behavior composition (p = 0.005), with moderate-to-vigorous physical activity (relative to remaining behaviors) being positively associated with health-related quality of life. CONCLUSIONS: The relationship between children's health-related quality of life and their movement behaviors is moderated by their country's human development index. This should be considered when 24-h movement behavior guidelines are developed for children around the world.

Adiposity and the isotemporal substitution of physical activity, sedentary time and sleep among school-aged children: a compositional data analysis approach.

BACKGROUND: Daily activity data are by nature compositional data. Accordingly, they occupy a specific geometry with unique properties that is different to standard Euclidean geometry. This study aimed to estimate the difference in adiposity associated with isotemporal reallocation between daily activity behaviours, and to compare the findings from compositional isotemporal subsitution to those obtained from traditional isotemporal substitution. METHODS: We estimated the differences in adiposity (body fat%) associated with reallocating fixed durations of time (isotemporal substitution) between accelerometer-measured daily activity behaviours (sleep, sedentary time and light and moderate-to-vigorous physical activity (MVPA)) among 1728 children aged 9-11 years from Australia, Canada, Finland and the UK (International Study of Childhood Obesity, Lifestyle and the Environment, 2011-2013). We generated estimates from compositional isotemporal substitution models and traditional non-compositional isotemporal substitution models. RESULTS: Both compositional and traditional models estimated a positive (unfavourable) difference in body fat% when time was reallocated from MVPA to any other behaviour. Unlike traditional models, compositional models found the differences in estimated adiposity (1) were not necessarily symmetrical when an activity was being displaced, or displacing another (2) were not linearly related to the durations of time reallocated, and (3) varied depending on the starting composition. CONCLUSION: The compositional isotemporal model caters for the constrained and therefore relative nature of activity behaviour data and enables all daily behaviours to be included in a single statistical model. The traditional model treats data as real variables, thus the constrained nature of time is not accounted for, nor reflected in the findings. Findings from compositional isotemporal substitution support the importance of MVPA to children's health, and suggest that while interventions to increase MVPA may be of benefit, attention should be directed towards strategies to avoid decline in MVPA levels, particularly among already inactive children. Future applications of the compositional model can extend from pair-wise reallocations to other configurations of time-reallocation, for example, increasing MVPA at the expense of multiple other behaviours.

Informed baseline subtraction of proteomic mass spectrometry data aided by a novel sliding window algorithm.

BACKGROUND: Proteomic matrix-assisted laser desorption/ionisation (MALDI) linear time-of-flight (TOF) mass spectrometry (MS) may be used to produce protein profiles from biological samples with the aim of discovering biomarkers for disease. However, the raw protein profiles suffer from several sources of bias or systematic variation which need to be removed via pre-processing before meaningful downstream analysis of the data can be undertaken. Baseline subtraction, an early pre-processing step that removes the non-peptide signal from the spectra, is complicated by the following: (i) each spectrum has, on average, wider peaks for peptides with higher mass-to-charge ratios (m/z), and (ii) the time-consuming and error-prone trial-and-error process for optimising the baseline subtraction input arguments. With reference to the aforementioned complications, we present an automated pipeline that includes (i) a novel 'continuous' line segment algorithm that efficiently operates over data with a transformed m/z-axis to remove the relationship between peptide mass and peak width, and (ii) an input-free algorithm to estimate peak widths on the transformed m/z scale. RESULTS: The automated baseline subtraction method was deployed on six publicly available proteomic MS datasets using six different m/z-axis transformations. Optimality of the automated baseline subtraction pipeline was assessed quantitatively using the mean absolute scaled error (MASE) when compared to a gold-standard baseline subtracted signal. Several of the transformations investigated were able to reduce, if not entirely remove, the peak width and peak location relationship resulting in near-optimal baseline subtraction using the automated pipeline. The proposed novel 'continuous' line segment algorithm is shown to far outperform naive sliding window algorithms with regard to the computational time required. The improvement in computational time was at least four-fold on real MALDI TOF-MS data and at least an order of magnitude on many simulated datasets. CONCLUSIONS: The advantages of the proposed pipeline include informed and data specific input arguments for baseline subtraction methods, the avoidance of time-intensive and subjective piecewise baseline subtraction, and the ability to automate baseline subtraction completely. Moreover, individual steps can be adopted as stand-alone routines.

Biological therapies for psoriasis: Adherence and outcome analysis from a clinical perspective.

We evaluated and compared patients' long-term adherence to biological therapies in a real-life clinical setting. Secondary aims included weight changes on biological therapy and reporting adverse effects. This prospective case-note review included 58 patients, undergoing 84 treatment series including etanercept (21), adalimumab (24), infliximab (14) and ustekinumab (25). Patients' adherence was greatest with ustekinumab (being 6.7-fold less likely to withdraw from treatment than etanercept, P = 0.014), while the difference in treatment adherence of adalimumab and infliximab compared to etanercept was not statistically significant. Adalimumab and infliximab were associated with an increase in weight, while ustekinumab was associated with weight loss compared with etanercept (not statistically significant). Long-term patient adherence to biologic therapy in patients with psoriasis is greatest with ustekinumab.

Investigating self-report and neuropsychological assessments of cognitive flexibility in people with and without persistent pain: An online, cross-sectional, observational study.

Introduction: People with persistent pain experience problems modifying their cognition and behaviours when task or environmental demands change - abilities otherwise known as cognitive flexibility. However, limitations and inconsistent results of previous studies raise concerns over the quality of that evidence. We aimed to determine whether people with and without persistent pain differ on two assessments that are commonly used to assess cognitive flexibility. We also examined the relationship between the two assessments and explored whether people with and without persistent pain are distinguishable based on their scores on these assessments. Methods: Participant demographics and symptoms of anxiety and depression were assessed. Participants completed the Cognitive Flexibility Inventory (CFI) and the Wisconsin Card Sorting Test (WCST). Multiple linear regression on the two outcome variables: CFI (total score) and WCST (% perseverative responses) was applied using backward stepwise selection. Both outcomes were calculated as a standardised proportion of the outcome scale and log-odds transformed to meet the model assumptions. Correlation analysis and logistic regression were used to investigate our secondary and exploratory aims. Results: Data were available from 128 participants with persistent pain and 68 pain-free controls. After adjusting for covariates, no differences were found between people with and without persistent pain on either assessment of cognitive flexibility. No significant correlations were detected between the two assessments in either group. The probability of having persistent pain was also not associated with scores on either or both assessments. Conclusion: 'Cognitive flexibility' appears similar in people with and without persistent pain.

Cross-sectional associations between 24-hour movement behaviors and cardiometabolic health among adults with type 2 diabetes mellitus: A comparison according to weight status.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) is a chronic disease associated with overweight and obesity. Evidence suggests that 24-hour movement behaviors (24 h-MBs) play a crucial role in cardiometabolic health. However, it is not yet known if 24 h-MBs differ between weight status groups among people with T2DM (PwT2DM) and how 24 h-MBs are associated with their cardiometabolic health. DESIGN: Cross-sectional study. METHODS: Cardiometabolic variables (i.e. Body Mass Index (BMI), waist circumference (WC), HbA1c, fasting glucose, triglycerides, total-cholesterol, HDL-cholesterol, LDL-cholesterol, blood pressure) and 24 h-MBs (accelerometry and sleep-diary) of 1001 PwT2DM were collected. Regression models using compositional data analysis explored differences in 24 h-MBs between weight status groups and analyzed associations with cardiometabolic variables. RESULTS: The 24 h-MBs of PwT2DM being obese consisted of less sleep, light physical activity (LPA) and moderate to vigorous physical activity (MVPA) and more sedentary time (ST) per day as compared to PwT2DM being overweight or normal weight (p < 0.001). Regardless of weight status, the largest associations were found when reallocating 20 min a day from ST into MVPA for BMI (-0.32 kg/m2; [-0.55; -0.09], -1.09 %), WC (-1.44 cm, [-2.26; -0.62], -1.35 %) and HDL-cholesterol (0.02 mmol/l, [0.01, 0.02], +1.59 %), as well as from ST into LPA for triglycerides (-0.04 mmol/l, [-0.05; -0.03], -2.3 %). Moreover, these associations were different when stratifying people by short-to-average (7.7 h/night) versus long sleep (9.3 h/night) period. CONCLUSIONS: This study highlights the importance of 24 h-MBs in the cardiometabolic health of PwT2DM. Shifting time from ST and/or sleep toward LPA or MVPA might theoretically benefit cardiometabolic health among relatively inactive PwT2DM, irrespective of weight status.

The Goldilocks Day for healthy adiposity measures among children and adolescents.

Background: The optimal balance of time spent on daily movement behaviors ("The Goldilocks Day") associated with childhood obesity remains unknown. Objective: To estimate the optimal durations of sleep, sedentary behavior (SB), light physical activity (LPA), and moderate-to-vigorous physical activity (MPVA) associated with excess adiposity in a paediatric population. Methods: Accelerometer-measured 24-h movement behaviors were obtained from 659 Czech children and adolescents (8-18-year-olds). Adiposity indicators were body mass index z-score, fat mass percentage, fat-free mass index, and visceral adipose tissue. Excess adiposity was defined as exceeding the 85th percentile for an adiposity indicator. Compositional regression analyses were used investigate the associations between movement behaviors and adiposity indicators and estimating "The Goldilocks Day." Results: The movement behavior composition was associated with visceral adipose tissue (Fdf1 = 3,df2 = 317 = 3.672, p = 0.013) and fat mass percentage (Fdf1 = 3,df2 = 289 = 2.733, p = 0.044) among children and adolescents. The Goldilocks Day consisted of 8.5 h of sleep, 10.8 h of SB, 3.9 h of LPA, and 0.8 h of MVPA among children and 7.5 h of sleep, 12.4 h of SB, 3.6 h of LPA, and 0.5 h of MVPA among adolescents. Conclusion: Optimizing the time spent sleeping, and in sedentary and physical activities appears to be important in the prevention of excess adiposity.

Impact of Introducing Infliximab Biosimilars on Total Infliximab Consumption and Originator Infliximab Prices in Eight Regions: An Interrupted Time-Series Analysis.

OBJECTIVE: We aimed to assess whether the introduction of the first infliximab biosimilar was associated with changes in overall infliximab consumption (originator and biosimilars) and price changes to the originator infliximab. METHODS: An interrupted time series analysis using infliximab sales data from 2010 to 2020 from the IQVIA Multinational Integrated Data Analysis System for eight selected regions: Australia, Canada, Hong Kong, Korea, India, Japan, the UK, and the USA. Quarterly measures of infliximab consumption and list prices were respectively defined as the number of standard units (SU)/1000 inhabitants and as 2020 USA dollars (USD)/SU. RESULTS: Following the introduction of infliximab biosimilars, overall infliximab consumption increased in Australia [immediate change: 0.145 SU/1000 inhabitants (P = 0.014); long-term change: 0.022 SU/1000 inhabitants per quarter (P < 0.001)], Canada [immediate change 0.415 (P = 0.008)], the UK [long-term change 0.024 (P < 0.001)], and Hong Kong [immediate change: 0.042 (P < 0.001)]. The list price of originator infliximab also decreased following biosimilar introduction in Australia [immediate change: - 187.84 USD/SU (P < 0.001); long-term change - 6.46 USD/SU per quarter (P = 0.043)], Canada [immediate change: - 145.58 (P < 0.001)], the UK [immediate change: - 34.95 (P = 0.010); long-term change: - 4.77 (P < 0.001)], and Hong Kong [long-term change: - 4.065 (P = 0.046)]. Consumption and price changes were inconsistent in India, Japan, Korea, and the USA. CONCLUSIONS: Introduction of the first infliximab biosimilar was not consistently associated with increased consumption across regions. Additional policy and healthcare system interventions to support biosimilar infliximab adoption are needed.

Cross-sectional analysis of association between socioeconomic status and utilization of primary total hip joint replacements 2006-7: Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: The utilization of total hip replacement (THR) surgery is rapidly increasing, however few data examine whether these procedures are associated with socioeconomic status (SES) within Australia. This study examined primary THR across SES for both genders for the Barwon Statistical Division (BSD) of Victoria, Australia. METHODS: Using the Australian Orthopaedic Association National Joint Replacement Registry data for 2006-7, primary THR with a diagnosis of osteoarthritis (OA) among residents of the BSD was ascertained. The Index of Relative Socioeconomic Disadvantage was used to measure SES; determined by matching residential addresses with Australian Bureau of Statistics census data. The data were categorised into quintiles; quintile 1 indicating the most disadvantaged. Age- and sex-specific rates of primary THR per 1,000 person years were reported for 10-year age bands using the total population at risk. RESULTS: Females accounted for 46.9% of the 642 primary THR performed during 2006-7. THR utilization per 1,000 person years was 1.9 for males and 1.5 for females. The highest utilization of primary THR was observed in those aged 70-79 years (males 6.1, and females 5.4 per 1,000 person years). Overall, the U-shaped pattern of THR across SES gave the appearance of bimodality for both males and females, whereby rates were greater for both the most disadvantaged and least disadvantaged groups. CONCLUSIONS: Further work on a larger scale is required to determine whether relationships between SES and THR utilization for the diagnosis of OA is attributable to lifestyle factors related to SES, or alternatively reflects geographic and health system biases. Identifying contributing factors associated with SES may enhance resource planning and enable more effective and focussed preventive strategies for hip OA.

Monoclonal antibodies and Fc-fusion protein biologic medicines: A multinational cross-sectional investigation of accessibility and affordability in Asia Pacific regions between 2010 and 2020.

Background: Monoclonal antibody (mAb) and Fc-fusion protein (FcP) are highly effective therapeutic biologics. We aimed to analyse consumption and expenditure trends in 14 Asia-Pacific countries/regions (APAC) and three benchmark countries (the UK, Canada, and the US). Methods: We analysed 440 mAb and FcP biological products using the IQVIA-MIDAS global sales database. For each year between 2010 and 2020 inclusive, we used standard units (SU) sold per 1000 population and manufacture level price (standardised in 2019 US dollars) to evaluate consumption (accessibility) and expenditure (affordability). Changes of consumption and expenditure were estimated using compound annual growth rate (CAGR). Correlations between consumption, country's economic and health performance indicators were measured using Spearman correlation coefficient. Findings: Between 2010 and 2020, CAGRs of consumption in each region ranged from 7% to 34% and the CAGRs of expenditure ranged from 9% to 31%. The median consumption of biologics was extremely low in lower-middle-income economies (0·29 SU/1000 population) compared with upper-middle-income economies (1·20), high-income economies (40·94) and benchmark countries (109·55), although the median CAGRs of biologics consumption in lower-middle-income economies (31%) was greater than upper-middle-income (14%), high-income economies (13%) and benchmark countries (9%). Consumption was correlated with GDP per capita [Spearman's rank correlation coefficient (r) = 0·75, p < 0·001], health expenditure as a percentage of total (r = 0·83, p < 0·001) and medical doctors' density (r = 0·85, p < 0·001). Interpretation: There have been significant increases in mAb and FcP biologics consumption and expenditure, however accessibility of biological medicines remains unequal and is largely correlated with country's income level. Funding: This research was funded by NHMRC Project Grant GNT1157506 and GNT1196900; Enhanced Start-up Fund for new academic staff and Internal Research Fund, Department of Medicine, LKS Faculty of Medicine, University of Hong Kong.

Poor outcome of revised resurfacing hip arthroplasty.

BACKGROUND AND PURPOSE: Recent years have seen a rapid increase in the use of resurfacing hip arthroplasty despite the lack of literature on the long-term outcome. In particular, there is little evidence regarding the outcome of revisions of primary resurfacing. The purpose of this analysis was to examine the survivorship of primary resurfacing hip arthroplasties that have been revised. PATIENTS AND METHODS: Over 12,000 primary resurfacing hip arthroplasties were recorded by the Australian Orthopaedic Association National Joint Replacement Registry between September 1, 1999 and December 31, 2008. During this time, 397 revisions for reasons other than infection were reported for these primary resurfacings and classified as acetabular, femoral, or both acetabular and femoral revisions. The survivorship of the different types of revisions was estimated using the Kaplan-Meier method and compared using proportional hazard models. Additionally, the outcome of a femoral-only revision was compared to that of primary conventional total hip arthroplasty. RESULTS: Acetabular-only revision had a high risk of re-revision compared to femoral-only and both acetabular and femoral revision (5-year cumulative per cent revision of 20%, 7%, and 5% respectively). Femoral-only revision had a risk of re-revision similar to that of revision of both the acetabular and femoral components. Femoral-only revision had over twice the risk of revision of primary conventional total hip arthroplasty. INTERPRETATION: Revision of a primary resurfacing arthroplasty is associated with a major risk of re-revision. The best outcome is achieved when either the femoral-only or both the acetabular and femoral components are revised. Technically straightforward femoral-only revisions generally have a worse outcome than a primary conventional total hip arthroplasty.

Outcome of revision of unicompartmental knee replacement.

BACKGROUND AND PURPOSE: Despite concerns regarding a higher risk of revision, unicompartmental knee arthroplasty (UKA) continues to be used as an alternative to total knee arthroplasty (TKA). There are, however, limited data on the subsequent outcome when a UKA is revised. We examined the survivorship for primary UKA procedures that have been revised. METHODS: We used data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) to analyze the survivorship of 1,948 revisions of primary UKA reported to the Registry between September 1999 and December 2008. This was compared to the results of revisions of primary TKA reported during the same period where both the femoral and tibial components were revised. The Kaplan-Meier method for modeling survivorship was used. RESULTS: When a primary UKA was revised to another UKA (both major and minor revisions), it had a cumulative per cent revision (CPR) of 28 and 30 at 3 years, respectively. The CPR at 3 years when a UKA was converted to a TKA was 10. This is similar to the 3-year CPR (12) found earlier for primary TKA where both the femoral and tibial components were revised. INTERPRETATION: When a UKA requires revision, the best outcome is achieved when it is converted to a TKA. This procedure does, however, have a major risk of re-revision, which is similar to the risk of re-revision of a primary TKA that has had both the femoral and tibial components revised.

Clinical evaluation of the APAS® Independence: Automated imaging and interpretation of urine cultures using artificial intelligence with composite reference standard discrepant resolution.

BACKGROUND: This study reports the outcome of the first evaluation of the APAS® Independence for automated reading and preliminary interpretation of urine cultures in the routine clinical microbiology laboratory. In a 2-stage evaluation involving 3000 urine samples, two objectives were assessed; 1) the sensitivity and specificity of the APAS® Independence compared to microbiologists using colony enumeration as the primary determinant, and 2) the variability between microbiologists in enumerating bacterial cultures using traditional culture reading techniques, performed independently to APAS® Independence interpretation. METHODS: Routine urine samples received into the laboratory were processed and culture plates were interpreted by standard methodology and with the APAS® Independence. Results were compared using typical discrepant result resolution and with a composite reference standard, which provided an alternative assessment of performance. RESULTS: The significant growth sensitivity of the APAS® Independence was determined to be 0.919 with a 95% confidence interval of (0.879, 0.948), and the growth specificity was 0.877 with a 95% confidence interval of (0.827, 0.916). Variability between microbiologists was demonstrated with microbiologist bi-plate enumerations in agreement with the consensus 88.6% of the time. CONCLUSION: The APAS® Independence appears to offer microbiology laboratories a mechanism to standardise the processing and assessment of urine cultures whilst augmenting the skills of specialist microbiology staff.

The compositional isotemporal substitution model: A method for estimating changes in a health outcome for reallocation of time between sleep, physical activity and sedentary behaviour.

How people use their time has been linked with their health. For example, spending more time being physically active is known to be beneficial for health, whereas long durations of sitting have been associated with unfavourable health outcomes. Accordingly, public health messages have advocated swapping strategies to promote the reallocation of time between parts of the time-use composition, such as "Move More, Sit Less", with the aim of achieving optimal distribution of time for health. However, the majority of research underpinning these public health messages has not considered daily time use as a composition, and has ignored the relative nature of time-use data. We present a way of applying compositional data analysis to estimate change in a health outcome when fixed durations of time are reallocated from one part of a particular time-use composition to another, while the remaining parts are kept constant, based on a multiple linear regression model on isometric log ratio coordinates. In an example, we examine the expected differences in Body Mass Index z-scores for reallocations of time between sleep, physical activity and sedentary behaviour.

Characteristics of Adopters of an Online Social Networking Physical Activity Mobile Phone App: Cluster Analysis.

BACKGROUND: To date, many online health behavior programs developed by researchers have not been translated at scale. To inform translational efforts, health researchers must work with marketing experts to design cost-effective marketing campaigns. It is important to understand the characteristics of end users of a given health promotion program and identify key market segments. OBJECTIVE: This study aimed to describe the characteristics of the adopters of Active Team, a gamified online social networking physical activity app, and identify potential market segments to inform future research translation efforts. METHODS: Participants (N=545) were Australian adults aged 18 to 65 years who responded to general advertisements to join a randomized controlled trial (RCT) evaluating the Active Team app. At baseline they provided demographic (age, sex, education, marital status, body mass index, location of residence, and country of birth), behavioral (sleep, assessed by the Pittsburgh Quality Sleep Index) and physical activity (assessed by the Active Australia Survey), psychographic information (health and well-being, assessed by the PERMA [Positive Emotion, Engagement, Relationships, Meaning, Achievement] Profile; depression, anxiety and stress, assessed by the Depression, Anxiety, and Stress Scale [DASS-21]; and quality of life, assessed by the 12-Item Short Form Health Survey [SF-12]). Descriptive analyses and a k-medoids cluster analysis were performed using the software R 3.3.0 (The R Foundation) to identify key characteristics of the sample. RESULTS: Cluster analyses revealed four clusters: (1) younger inactive women with poor well-being (218/545), characterized by a higher score on the DASS-21, low mental component summary score on the SF-12, and relatively young age; (2) older, active women (153/545), characterized by a lower score on DASS-21, a higher overall score on the SF-12, and relatively older age; (3) young, active but stressed men (58/545) with a higher score on DASS-21 and higher activity levels; and (4) older, low active and obese men (30/545), characterized by a high body mass index and lower activity levels. CONCLUSIONS: Understanding the characteristics of population segments attracted to a health promotion program will guide the development of cost-effective research translation campaigns. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12617000113358; https://www.anzctr.org .au/Trial/Registration/TrialReview.aspx?id=371463. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12889-017-4882-7.

Compositional data analysis for physical activity, sedentary time and sleep research.

The health effects of daily activity behaviours (physical activity, sedentary time and sleep) are widely studied. While previous research has largely examined activity behaviours in isolation, recent studies have adjusted for multiple behaviours. However, the inclusion of all activity behaviours in traditional multivariate analyses has not been possible due to the perfect multicollinearity of 24-h time budget data. The ensuing lack of adjustment for known effects on the outcome undermines the validity of study findings. We describe a statistical approach that enables the inclusion of all daily activity behaviours, based on the principles of compositional data analysis. Using data from the International Study of Childhood Obesity, Lifestyle and the Environment, we demonstrate the application of compositional multiple linear regression to estimate adiposity from children's daily activity behaviours expressed as isometric log-ratio coordinates. We present a novel method for predicting change in a continuous outcome based on relative changes within a composition, and for calculating associated confidence intervals to allow for statistical inference. The compositional data analysis presented overcomes the lack of adjustment that has plagued traditional statistical methods in the field, and provides robust and reliable insights into the health effects of daily activity behaviours.

Effect of increasing protein content of human milk fortifier on growth in preterm infants born at <31 wk gestation: a randomized controlled trial.

BACKGROUND: Preterm human milk-fed infants often experience suboptimal growth despite the use of human milk fortifier (HMF). The extra protein supplied in fortifiers may be inadequate to meet dietary protein requirements for preterm infants. OBJECTIVE: We assessed the effect of human milk fortified with a higher-protein HMF on growth in preterm infants. DESIGN: This is a randomized controlled trial in 92 preterm infants born at <31 wk gestation who received maternal breast milk that was fortified with HMF containing 1.4 g protein/100 mL (higher-protein group) or 1.0 g protein/100 mL (current practice) until discharge or estimated due date, whichever came first. The HMFs used were isocaloric and differed only in the amount of protein or carbohydrate. Length, weight, and head-circumference gains were assessed over the study duration. RESULTS: Length gains did not differ between the higher- and standard-protein groups (mean difference: 0.06 cm/wk; 95% CI: -0.01, 0.12 cm/wk; P = 0.08). Infants in the higher-protein group achieved a greater weight at study end (mean difference: 220 g; 95% CI: 23, 419 g; P = 0.03). Secondary analyses showed a significant reduction in the proportion of infants who were less than the 10th percentile for length at the study end in the higher-protein group (risk difference: 0.186; 95% CI: 0.370, 0.003; P = 0.047). CONCLUSIONS: A higher protein intake results in less growth faltering in human milk-fed preterm infants. It is possible that a higher-protein fortifier than used in this study is needed. This trial was registered with the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au/) as ACTRN12606000525583.

Utilisation of primary total knee joint replacements across socioeconomic status in the Barwon Statistical Division, Australia, 2006-2007: a cross-sectional study.

OBJECTIVES: There are few Australian data that examine the association between total knee joint replacement (TKR) utilisation and socioeconomic status (SES). This study examined TKR surgeries with a diagnosis of osteoarthritis (OA) performed for residents of Barwon Statistical Division (BSD) for 2006-2007. DESIGN: Cross-sectional. SETTING: BSD, South-eastern Victoria, Australia PARTICIPANTS: All patients who underwent a TKR for OA, 2006-2007, and whose residential postcode was identified as within the BSD of Australia, and for whom SES data were available, were eligible for inclusion. PRIMARY OUTCOME MEASURE: Primary TKR data ascertained from the Australian Orthopaedic Association National Joint Replacement Registry. Residential addresses were matched with the Australian Bureau of Statistics census data, and the Index of Relative Socioeconomic Disadvantage was used to determine SES, categorised into quintiles whereby quintile 1 indicated the most disadvantaged and quintile 5 the least disadvantaged. Age-specific and sex-specific rates of TKR utilisation per 1000 person-years were reported for 10-year age bands. RESULTS: Females accounted for 62.7% of the 691 primary TKR surgeries performed during 2006-2007. The greatest utilisation rates of TKR in males was 7.6 observed in those aged >79 years, and in 10.2 in females observed in those aged 70-79 years. An increase in TKR was observed for males in SES quintile four compared to quintile 1 in which the lowest utilisation which was observed (p=0.04). No differences were observed in females across SES quintiles. CONCLUSIONS: Further investigation is warranted on a larger scale to examine the role that SES may play in TKR utilisation, and to determine whether any social disparities in TKR utilisation reflect health system biases or geographic differences.

Utility of saccadic eye movement analysis as an objective biomarker to detect the sedative interaction between opioids and sleep deprivation in opioid-naive and opioid-tolerant populations.

Analysis of saccadic eye movements (SEMs) has previously been used to detect drug- and sleep-deprivation-induced sedation, but never in combination. We compared the effects of sleep deprivation and opioids on 10 opioid-naive with nine opioid-tolerant participants. The naive-participant study evaluated the effects of sleep deprivation alone, morphine alone and the combination; the tolerant-participant study compared day-to-day effects of alternate-daily-dosed buprenorphine and the combination of buprenorphine on the dosing day with sleep deprivation. Psychomotor impairment was measured using SEMs, a 5-minute pupil adaptation test (PAT), pupil light reflex (PLR) and alertness visual analogue scale (AVAS). The PAT and PLR did not detect sleep deprivation, in contrast to previous studies. Whilst consistently detecting sleep deprivation, the AVAS also detected buprenorphine in the tolerant study, but not morphine in the naive study. SEMs detected morphine alone and sleep deprivation alone as well as an additive interaction in the naive study and the effect of sleep deprivation in the tolerant study. The alternate-day buprenorphine dosing did not alter SEMs. The current study revealed greater SEMs, but not AVAS impairment in tolerant versus naive participants. The current study demonstrates that objective measures provide additional information to subjective measures and thus should be used in combination.