Efficient estimation for rank-based regression with clustered data

Rank-based inference is widely used because of its robustness. This article provides optimal rank-based estimating functions in analysis of clustered data with random cluster effects. The extensive simulation studies carried out to evaluate the performance of the proposed method demonstrate that it is robust to outliers and is highly efficient given the existence of strong cluster correlations. The performance of the proposed method is satisfactory even when the correlation structure is misspecified, or when heteroscedasticity in variance is present. Finally, a real dataset is analyzed for illustration.

Robust estimating functions and bias correction for longitudinal data analysis

Robust methods are useful in making reliable statistical inferences when there are small deviations from the model assumptions. The widely used method of the generalized estimating equations can be "robustified" by replacing the standardized residuals with the M-residuals. If the Pearson residuals are assumed to be unbiased from zero, parameter estimators from the robust approach are asymptotically biased when error distributions are not symmetric. We propose a distribution-free method for correcting this bias. Our extensive numerical studies show that the proposed method can reduce the bias substantially. Examples are given for illustration.

Preliminary spatiotemporal analysis of the association between socio-environmental factors and suicide

Background: The seasonality of suicide has long been recognised. However, little is known about the relative importance of socio-environmental factors in the occurrence of suicide in different geographical areas. This study examined the association of climate, socioeconomic and demographic factors with suicide in Queensland, Australia, using a spatiotemporal approach. Methods: Seasonal data on suicide, demographic variables and socioeconomic indexes for areas in each Local Government Area (LGA) between 1999 and 2003 were acquired from the Australian Bureau of Statistics. Climate data were supplied by the Australian Bureau of Meteorology. A multivariable generalized estimating equation model was used to examine the impact of socio-environmental factors on suicide. Results: The preliminary data analyses show that far north Queensland had the highest suicide incidence (e.g., Cook and Mornington Shires), while the south-western areas had the lowest incidence (e.g., Barcoo and Bauhinia Shires) in all the seasons. Maximum temperature, unemployment rate, the proportion of Indigenous population and the proportion of population with low individual income were statistically significantly and positively associated with suicide. There were weaker but not significant associations for other variables. Conclusions: Maximum temperature, the proportion of Indigenous population and unemployment rate appeared to be major determinants of suicide at a LGA level in Queensland.

Temperature variation and emergency hospital admissions for stroke in Brisbane, Australia, 1996-2005

Stroke is a leading cause of disability and death. This study evaluated the association between temperature variation and emergency admissions for stroke in Brisbane, Australia. Daily emergency admissions for stroke, meteorologic and air pollution data were obtained for the period of January 1996 to December 2005. The relative risk of emergency admissions for stroke was estimated with a generalized estimating equations (GEE) model. For primary intracerebral hemorrhage (PIH) emergency admissions, the average daily PIH for the group aged < 65 increased by 15% (95% Confidence Interval (CI): 5, 26%) and 12% (95% CI: 2, 22%) for a 1°C increase in daily maximum temperature and minimum temperature in summer, respectively, after controlling for potential confounding effects of humidity and air pollutants. For ischemic stroke (IS) emergency admissions, the average daily IS for the group aged ≥ 65 decreased by 3% (95% CI: -6, 0%) for a 1°C increase in daily maximum temperature in winter after adjustment for confounding factors. Temperature variation was significantly associated with emergency admissions for stroke, and its impact varied with different type of stroke. Health authorities should pay greater attention to possible increasing emergency care for strokes when temperature changes, in both summer and winter.

Socio-environmental factors and suicide in Queensland, Australia

Suicide has drawn much attention from both the scientific community and the public. Examining the impact of socio-environmental factors on suicide is essential in developing suicide prevention strategies and interventions, because it will provide health authorities with important information for their decision-making. However, previous studies did not examine the impact of socio-environmental factors on suicide using a spatial analysis approach. The purpose of this study was to identify the patterns of suicide and to examine how socio-environmental factors impact on suicide over time and space at the Local Governmental Area (LGA) level in Queensland. The suicide data between 1999 and 2003 were collected from the Australian Bureau of Statistics (ABS). Socio-environmental variables at the LGA level included climate (rainfall, maximum and minimum temperature), Socioeconomic Indexes for Areas (SEIFA) and demographic variables (proportion of Indigenous population, unemployment rate, proportion of population with low income and low education level). Climate data were obtained from Australian Bureau of Meteorology. SEIFA and demographic variables were acquired from ABS. A series of statistical and geographical information system (GIS) approaches were applied in the analysis. This study included two stages. The first stage used average annual data to view the spatial pattern of suicide and to examine the association between socio-environmental factors and suicide over space. The second stage examined the spatiotemporal pattern of suicide and assessed the socio-environmental determinants of suicide, using more detailed seasonal data. In this research, 2,445 suicide cases were included, with 1,957 males (80.0%) and 488 females (20.0%). In the first stage, we examined the spatial pattern and the determinants of suicide using 5-year aggregated data. Spearman correlations were used to assess associations between variables. Then a Poisson regression model was applied in the multivariable analysis, as the occurrence of suicide is a small probability event and this model fitted the data quite well. Suicide mortality varied across LGAs and was associated with a range of socio-environmental factors. The multivariable analysis showed that maximum temperature was significantly and positively associated with male suicide (relative risk [RR] = 1.03, 95% CI: 1.00 to 1.07). Higher proportion of Indigenous population was accompanied with more suicide in male population (male: RR = 1.02, 95% CI: 1.01 to 1.03). There was a positive association between unemployment rate and suicide in both genders (male: RR = 1.04, 95% CI: 1.02 to 1.06; female: RR = 1.07, 95% CI: 1.00 to 1.16). No significant association was observed for rainfall, minimum temperature, SEIFA, proportion of population with low individual income and low educational attainment. In the second stage of this study, we undertook a preliminary spatiotemporal analysis of suicide using seasonal data. Firstly, we assessed the interrelations between variables. Secondly, a generalised estimating equations (GEE) model was used to examine the socio-environmental impact on suicide over time and space, as this model is well suited to analyze repeated longitudinal data (e.g., seasonal suicide mortality in a certain LGA) and it fitted the data better than other models (e.g., Poisson model). The suicide pattern varied with season and LGA. The north of Queensland had the highest suicide mortality rate in all the seasons, while there was no suicide case occurred in the southwest. Northwest had consistently higher suicide mortality in spring, autumn and winter. In other areas, suicide mortality varied between seasons. This analysis showed that maximum temperature was positively associated with suicide among male population (RR = 1.24, 95% CI: 1.04 to 1.47) and total population (RR = 1.15, 95% CI: 1.00 to 1.32). Higher proportion of Indigenous population was accompanied with more suicide among total population (RR = 1.16, 95% CI: 1.13 to 1.19) and by gender (male: RR = 1.07, 95% CI: 1.01 to 1.13; female: RR = 1.23, 95% CI: 1.03 to 1.48). Unemployment rate was positively associated with total (RR = 1.40, 95% CI: 1.24 to 1.59) and female (RR=1.09, 95% CI: 1.01 to 1.18) suicide. There was also a positive association between proportion of population with low individual income and suicide in total (RR = 1.28, 95% CI: 1.10 to 1.48) and male (RR = 1.45, 95% CI: 1.23 to 1.72) population. Rainfall was only positively associated with suicide in total population (RR = 1.11, 95% CI: 1.04 to 1.19). There was no significant association for rainfall, minimum temperature, SEIFA, proportion of population with low educational attainment. The second stage is the extension of the first stage. Different spatial scales of dataset were used between the two stages (i.e., mean yearly data in the first stage, and seasonal data in the second stage), but the results are generally consistent with each other. Compared with other studies, this research explored the variety of the impact of a wide range of socio-environmental factors on suicide in different geographical units. Maximum temperature, proportion of Indigenous population, unemployment rate and proportion of population with low individual income were among the major determinants of suicide in Queensland. However, the influence from other factors (e.g. socio-culture background, alcohol and drug use) influencing suicide cannot be ignored. An in-depth understanding of these factors is vital in planning and implementing suicide prevention strategies. Five recommendations for future research are derived from this study: (1) It is vital to acquire detailed personal information on each suicide case and relevant information among the population in assessing the key socio-environmental determinants of suicide; (2) Bayesian model could be applied to compare mortality rates and their socio-environmental determinants across LGAs in future research; (3) In the LGAs with warm weather, high proportion of Indigenous population and/or unemployment rate, concerted efforts need to be made to control and prevent suicide and other mental health problems; (4) The current surveillance, forecasting and early warning system needs to be strengthened, to trace the climate and socioeconomic change over time and space and its impact on population health; (5) It is necessary to evaluate and improve the facilities of mental health care, psychological consultation, suicide prevention and control programs; especially in the areas with low socio-economic status, high unemployment rate, extreme weather events and natural disasters.

The impact of delayed blood centrifuging, choice of collection tube, and type of assay on 25-hydroxyvitamin D concentrations

Studies have examined the associations between cancers and circulating 25-hydroxyvitamin D [25(OH)D], but little is known about the impact of different laboratory practices on 25(OH)D concentrations. We examined the potential impact of delayed blood centrifuging, choice of collection tube, and type of assay on 25(OH)D concentrations. Blood samples from 20 healthy volunteers underwent alternative laboratory procedures: four centrifuging times (2, 24, 72, and 96 h after blood draw); three types of collection tubes (red top serum tube, two different plasma anticoagulant tubes containing heparin or EDTA); and two types of assays (DiaSorin radioimmunoassay [RIA] and chemiluminescence immunoassay [CLIA/LIAISON®]). Log-transformed 25(OH)D concentrations were analyzed using the generalized estimating equations (GEE) linear regression models. We found no difference in 25(OH)D concentrations by centrifuging times or type of assay. There was some indication of a difference in 25(OH)D concentrations by tube type in CLIA/LIAISON®-assayed samples, with concentrations in heparinized plasma (geometric mean, 16.1 ng ml−1) higher than those in serum (geometric mean, 15.3 ng ml−1) (p = 0.01), but the difference was significant only after substantial centrifuging delays (96 h). Our study suggests no necessity for requiring immediate processing of blood samples after collection or for the choice of a tube type or assay.

The effect of monocular and binocular cataract blur on postural stability among older adults

Purpose: First-eye cataract surgery can reduce the rate of falls among older adults, yet the effect of second-eye surgery on the rate of falling remains unclear. The present study investigated the effect of monocular and binocular simulated cataract blur on postural stability among older adults. Methods: Postural stability was assessed on 34 healthy older adults (mean 68.2 years, SD 3.5) with normal vision, using a portable force platform (BT4, HUR Labs, Finland) which collected data on centre of pressure (COP) displacement. Stability was assessed on firm and foam surfaces under four binocular viewing conditions using Vistech filters to simulate cataract blur: [1] best-corrected vision both eyes; [2] blur over non-dominant eye, [3] blur over dominant eye and [4] blur over both eyes. Binocular logMAR visual acuity, Pelli-Robson contrast sensitivity and stereoacuity were also measured under these viewing conditions and ocular dominance measured using the hole-in-card test. Generalized estimating equations with an exchangeable correlation structure examined the effect of the surface and vision conditions on postural stability. Results: Visual acuity and contrast sensitivity were significantly reduced under monocular and binocular cataract blur compared to normal viewing. All blur conditions resulted in loss of stereoacuity. Binocular cataract blur significantly reduced postural stability compared to normal vision on the firm (COP path length; p=0.013) and foam surface (anterior-posterior COP RMS, COP path length and COP area; p<0.01). However, no significant differences in postural stability were found between the monocular blur conditions compared to normal vision, or between the dominant and non-dominant monocular blur conditions on either the firm or foam surfaces. Conclusions: Findings indicate that binocular blur significantly impairs postural stability, and suggests that improvements in postural stability may justify first-eye cataract surgery, particularly during somatosensory disruption. Postural stability was not significantly impaired in the monocular cataract blur conditions compared to the normal vision condition, nor was there any effect of ocular dominance on postural stability in the presence of monocular cataract blur.

Longing to belong : social inclusion and wellbeing among youth with refugee backgrounds in the first three years in Melbourne, Australia

For young people with refugee backgrounds, establishing a sense of belonging to their family and community, and to their country of resettlement is essential for wellbeing. This paper describes the psychosocial factors associated with subjective health and wellbeing outcomes among a cohort of 97 refugee youth (aged 11-19) during their first three years in Melbourne, Australia. The findings reported here are drawn from the Good Starts Study, a longitudinal investigation of settlement and wellbeing among refugee youth conducted between 2004 and 2008. The overall aim of Good Starts was to identify the psychosocial factors that assist youth with refugee backgrounds in making a good start in their new country. A particular focus was on key transitions: from pre-arrival to Australia, from the language school to mainstream school, and from mainstream school to higher education or to the workforce. Good Starts used a mix of both method and theory from anthropology and social epidemiology. Using standardized measures of wellbeing and generalised estimating equations to model the predictors of wellbeing over time, this paper reports that key factors strongly associated with wellbeing outcomes are those that can be described as indicators of belonging e the most important being subjective social status in the broader Australian community, perceived discrimination and bullying. We argue that settlement specific policies and programs can ultimately be effective if embedded within a broader socially inclusive society - one that offers real opportunities for youth with refugee backgrounds to flourish.

Quality of life after total laparoscopic hysterectomy versus total abdominal hysterectomy for stage I endometrial cancer (LACE) : a randomised trial

Background: The two-stage Total Laparoscopic Hysterectomy (TLH) versus Total Abdominal Hysterectomy (TAH) for stage I endometrial cancer (LACE) randomised controlled trial was initiated in 2005. The primary objective of stage 1 was to assess whether TLH results in equivalent or improved QoL up to 6 months after surgery compared to TAH. The primary objective of stage 2 was to test the hypothesis that disease-free survival at 4.5 years is equivalent for TLH and TAH. Results addressing the primary objective of stage 1 of the LACE trial are presented here. Methods: The first 361 LACE participants (TAH n= 142, TLH n=190) were enrolled in the QoL substudy at 19 centres across Australia, New Zealand and Hong Kong, and 332 completed the QoL analysis. Randomisation was performed centrally and independently from other study procedures via a computer generated, web-based system (providing concealment of the next assigned treatment) using stratified permuted blocks of 3 and 6, and assigned patients with histologically confirmed stage 1 endometrioid endometrial adenocarcinoma and ECOG performance status <2 to TLH or TAH stratified by histological grade and study centre. No blinding of patients or study personnel was attempted. QoL was measured at baseline, 1 and 4 weeks (early), and 3 and 6 months (late) after surgery using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. The primary endpoint was the difference between the groups in QoL change from baseline at early and late time points (a 5% difference was considered clinically significant). Analysis was performed according to the intention-to-treat principle using generalized estimating equations on differences from baseline for the early and late QoL recovery. The LACE trial is registered with clinicaltrials.gov (NCT00096408) and the Australian New Zealand Clinical Trials Registry (CTRN12606000261516). Patients for both stages of the trial have now been recruited and are being followed up for disease-specific outcomes. Findings: The proportion of missing values at the 5%, 10% 15% and 20% differences in the FACT-G scale was 6% (12/190) in the TLH and 14% (20/142) in the TAH group. There were 8/332 conversions (2.4%, 7 of which were from TLH to TAH). In the early phase of recovery, patients undergoing TLH reported significantly greater improvement of QoL from baseline compared to TAH in all subscales except the emotional and social well-being subscales. Improvements in QoL up to 6 months post-surgery continued to favour TLH except for the emotional and social well-being of the FACT and the visual analogue scale of the EuroQoL five dimensions (EuroQoL-VAS). Length of operating time was significantly longer in the TLH group (138±43 mins), than in the TAH group at (109±34 mins; p=0.001). While the proportion of intraoperative adverse events was similar between the treatment groups (TAH 8/142, 5.6%; TLH 14/190, 7.4%; p=0.55), postoperatively, twice as many patients in the TAH group experienced adverse events of CTC grade 3+ than in the TLH group (33/142, 23.2% and 22/190, 11.6%, respectively; p=0.004). Postoperative serious adverse events occurred more frequently in patients who had a TAH (27/142, 19.0%) than a TLH (15/190, 7.9%) (p=0.002). Interpretation: QoL improvements from baseline during early and later phases of recovery, and the adverse event profile significantly favour TLH compared to TAH for patients treated for Stage I endometrial cancer.

Persistence of income inequality : does child mortality matter?

Many developing countries are afflicted by persistent inequality in the distribution of income. While a growing body of literature emphasizes differential fertility as a channel through which income inequality persists, this paper investigates differential child mortality – differences in the incidence of child mortality across socioeconomic groups – as a critical link in this regard. Using evidence from cross-country data to evaluate this linkage, we find that differential child mortality serves as a stronger channel than differential fertility in the transmission of income inequality over time. We use random effects and generalized estimating equations techniques to account for temporal correlation within countries. The results are robust to the use of an alternate definition of fertility that reflects parental preference for children instead of realized fertility.

Quality of life detriments through self-reported swelling associated with gynaecological cancer

Background and aims: Lower-limb lymphoedema is a serious and feared sequela after treatment for gynaecological cancer. Given the limited prospective data on incidence of and risk factors for lymphoedema after treatment for gynaecological cancer we initiated a prospective cohort study in 2008. Methods: Data were available for 353 women with malignant disease. Participants were assessed before treatment and at regular intervals after treatment for two years. Follow-up visits were grouped into time-periods of six weeks to six months (time 1), nine months to 15 months (time 2), and 18 months to 24 months (time 3). Preliminary data analyses were undertaken up to time 2 using generalised estimating equations to model the repeated measures data of Functional Assessment of Cancer Therapy-General (FACT-G) quality of life (QoL) scores and self-reported swelling at each follow-up period (best-fitting covariance structure). Results: Depending on the time-period, between 30% and 40% of patients self-reported swelling of the lower limb. The QoL of those with self-reported swelling was lower at all time-periods compared with those who did not have swelling. Mean (95% CI) FACT-G scores at time 0, 1 and 2 were 80.7 (78.2, 83.2), 83.0 (81.0, 85.0) and 86.3 (84.2, 88.4), respectively for those with swelling and 85.0 (83.0, 86.9), 86.0 (84.1, 88.0) and 88.9 (87.0, 90.7), respectively for those without swelling. Conclusions: Lower-limb swelling adversely influences QoL and change in QoL over time in patients with gynaecological cancer.

Working for a better life : longitudinal evidence on the predictors of employment among recently arrived refugee migrant men living in Australia

Although a number of studies have investigated the predictors of employment among refugee migrants, there is a dearth of evidence from longitudinal data. This study investigated the cross-sectional and longitudinal predictors of employment among 233 adult refugee men living in South-East Queensland, Australia. Participants were interviewed four times at six-month intervals between 2008 and 2010. Using a conceptual model developed from the literature, Generalised Estimating Equations were used to model the predictors of employment. Over time, the employment rate increased from 44 percent to 56 percent. Region of birth, length of time in Australia, seeking employment through job service providers and informal networks, and owning a car were significant predictors of employment. Contrary to previous research, English language proficiency was not a significant predictor when other variables were controlled for. Recognition of overseas skills and qualifications decreased the chances of finding employment. The policy and program implications are discussed.

The effect of testing protocol on immature bovine thoracic spine segment stiffness

Introduction. In vitro spine biomechanical testing has been central to many advances in understanding the physiology and pathology of the human spine. Owing to the difficulty in obtaining sufficient numbers of human samples to conduct these studies, animal spines have been accepted as a substitute model. However, it is difficult to compare results from different studies, as they use different preparation, testing and data collection methods. The aim of this study was to identify the effect of repeated cyclic loading on bovine spine segment stiffness. It also aimed to quantify the effect of multiple freeze-thaw sequences, as many tests would be difficult to complete in a single session [1-3]. Materials and Methods. Thoracic spines from 6-8 week old calves were used. Each spine was dissected and divided into motion segments including levels T4-T11 (n=28). These were divided into two equal groups. Each segment was potted in polymethylemethacrylate. An Instron Biaxial materials testing machine with a custom made jig was used for testing. The segments were tested in flexion/extension, lateral bending and axial rotation at 37 degrees C and 100% humidity, using moment control to a maximum plus/minus 1.75 Nm with a loading rate of 0.3 Nm per second. Group (A) were tested with continuous repeated cyclic loading for 500 cycles with data recorded at cycles 3, 5, 10, 25, 100, 200, 300, 400 and 500. Group (B) were tested with 10 load cycles after each of 5 freeze thaw sequences. Data was collected from the tenth load cycle after each sequence. Statistical analysis of the data was performed using paired samples t-tests, ANOVA and generalized estimating equations. Results. The data were confirmed as having a normal distribution. 1. There were significant reductions in mean stiffness in flexion/extension (-20%; P=0.001) and lateral bending (-17%; P=0.009) over the 500 load cycles. However, there was no statistically significant change in axial rotation (P=0.152) 2. There was no statistically significant difference between mean stiffness over the five freeze-thaw sequences in flexion/extension (p=0.879) and axial rotation (p=0.07). However, there was a significant reduction in stiffness in lateral bending (-26%; p=0.007) Conclusion. Biomechanical testing of immature bovine spine motion segments requires careful interpretation. The effect of the number of load cycles as well as the number of freeze-thaw cycles on the stiffness of the motion segments depends on the axis of main movement.

Shrinkage empirical likelihood estimator in longitudinal analysis with time-dependent covariates-application to modeling the health of Filipino children

The method of generalized estimating equations (GEE) is a popular tool for analysing longitudinal (panel) data. Often, the covariates collected are time-dependent in nature, for example, age, relapse status, monthly income. When using GEE to analyse longitudinal data with time-dependent covariates, crucial assumptions about the covariates are necessary for valid inferences to be drawn. When those assumptions do not hold or cannot be verified, Pepe and Anderson (1994, Communications in Statistics, Simulations and Computation 23, 939–951) advocated using an independence working correlation assumption in the GEE model as a robust approach. However, using GEE with the independence correlation assumption may lead to significant efficiency loss (Fitzmaurice, 1995, Biometrics 51, 309–317). In this article, we propose a method that extracts additional information from the estimating equations that are excluded by the independence assumption. The method always includes the estimating equations under the independence assumption and the contribution from the remaining estimating equations is weighted according to the likelihood of each equation being a consistent estimating equation and the information it carries. We apply the method to a longitudinal study of the health of a group of Filipino children.

Intra-cluster correlation structure in longitudinal data analysis: Selection criteria and misspecification tests

Selection criteria and misspecification tests for the intra-cluster correlation structure (ICS) in longitudinal data analysis are considered. In particular, the asymptotical distribution of the correlation information criterion (CIC) is derived and a new method for selecting a working ICS is proposed by standardizing the selection criterion as the p-value. The CIC test is found to be powerful in detecting misspecification of the working ICS structures, while with respect to the working ICS selection, the standardized CIC test is also shown to have satisfactory performance. Some simulation studies and applications to two real longitudinal datasets are made to illustrate how these criteria and tests might be useful.