The Generalized Estimating Equations in the Past Ten Years: An Overview and A Biomedical Application

The Generalized Estimating Equations (GEE) proposed by Liang and Zeger (1986) have found considerable attention in the last years and several extensions have been proposed. This paper will give a more intuitive description how GEE have been developed during the last years. Additionally we will describe the advantages and disadvantages of the different parametrisations that have been proposed in the literature. We will also give a brief review of the literature available on this topic. [ Published in: Biometrical Journal 40 (2), 115-139

Familial Associations of Lipid Profiles: A Generalised Estimating Equations Approach

Elevated plasma levels of apolipoproteins A1 (apoA1) and B (apoB) are important protective factors and risk factors, respectively, for atherosclerosis and coronary heart disease. It is well known that both apoA1 and apoB reveal strong familial aggregation. Our goal was to investigate whether exogenous variables influence these associations. We used marginal regression models for the mean and association structure (Generalised Estimating Equations 2; GEE2) to analyse data from 1435 family members within 469 families of different sizes included in the Donolo-Tel Aviv Three-Generation Offspring Study. The usual robust variance matrix was approximated by extensions of jackknife estimators of variance to GEE2 models. Upon use of this approach estimation of standard errors in models with quite complex correlation structures was possible. All analyses were easily carried out using a menu-driven stand-alone software tool for marginal regression modelling. We demonstrate that a variety of hypotheses can be tested using Wald statistics by modelling regression matrices for the association structure. We show that correlation for apoB between parent-offspring pairs increased with decreasing age difference and that pairs with individuals of the same gender had more similar apoA1 levels than individuals of different gender. Associations between different relative pairs did not all agree with those expected from differences in kinship coefficients. The analysis using GEE2 models revealed structures that would not have been detected by other models and should therefore be used in addition to traditional approaches of analysing family data. GEE2 should be considered a standard method for the investigation of familial aggregation. [ Published in: Statistics in Medicine 19, Issue 24, 3345-3357

Calculating confidence intervals for impact numbers

BACKGROUND: Standard effect measures such as risk difference and attributable risk are frequently used in epidemiological studies and public health research to describe the effect of exposures. Recently, so-called impact numbers have been proposed, which express the population impact of exposures in form of specific person or case numbers. To describe estimation uncertainty, it is necessary to calculate confidence intervals for these new effect measures. In this paper, we present methods to calculate confidence intervals for the new impact numbers in the situation of cohort studies. METHODS: Beside the exposure impact number (EIN), which is equivalent to the well-known number needed to treat (NNT), two other impact numbers are considered: the case impact number (CIN) and the exposed cases impact number (ECIN), which describe the number of cases (CIN) and the number of exposed cases (ECIN) with an outcome among whom one case is attributable to the exposure. The CIN and ECIN represent reciprocals of the population attributable risk (PAR) and the attributable fraction among the exposed (AF(e)), respectively. Thus, confidence intervals for these impact numbers can be calculated by inverting and exchanging the confidence limits of the PAR and AF(e). EXAMPLES: We considered a British and a Japanese cohort study that investigated the association between smoking and death from coronary heart disease (CHD) and between smoking and stroke, respectively. We used the reported death and disease rates and calculated impact numbers with corresponding 95% confidence intervals. In the British study, the CIN was 6.46, i.e. on average, of any 6 to 7 persons who died of CHD, one case was attributable to smoking with corresponding 95% confidence interval of [3.84, 20.36]. For the exposed cases, the results of ECIN = 2.64 with 95% confidence interval [1.76, 5.29] were obtained. In the Japanese study, the CIN was 6.67, i.e. on average, of the 6 to 7 persons who had a stroke, one case was attributable to smoking with corresponding 95% confidence interval of [3.80, 27.27]. For the exposed cases, the results of ECIN = 4.89 with 95% confidence interval of [2.86, 16.67] were obtained. CONCLUSION: The consideration of impact numbers in epidemiological analyses provides additional information and helps the interpretation of study results, e.g. in public health research. In practical applications, it is necessary to describe estimation uncertainty. We have shown that the calculation of confidence intervals for the new impact numbers is possible by means of known methods for attributable risk measures. Therefore, estimated impact numbers should always be complemented by appropriate confidence intervals

Lifetime occupational exposure to metals and welding fumes, and risk of glioma: a 7-country population-based case–control study

Background: Brain tumor etiology is poorly understood. Based on their ability to pass through the blood–brain barrier, it has been hypothesized that exposure to metals may increase the risk of brain cancer. Results from the few epidemiological studies on this issue are limited and inconsistent. Methods: We investigated the relationship between glioma risk and occupational exposure to five metals - lead, cadmium, nickel, chromium and iron- as well as to welding fumes, using data from the seven-country INTEROCC study. A total of 1800 incident glioma cases and 5160 controls aged 30–69 years were included in the analysis. Lifetime occupational exposure to the agents was assessed using the INTEROCC JEM, a modified version of the Finnish job exposure matrix FINJEM. Results: In general, cases had a slightly higher prevalence of exposure to the various metals and welding fumes than did controls, with the prevalence among ever exposed ranging between 1.7 and 2.2% for cadmium to 10.2 and 13.6% for iron among controls and cases, respectively. However, in multivariable logistic regression analyses, there was no association between ever exposure to any of the agents and risk of glioma with odds ratios (95% confidence intervals) ranging from 0.8 (0.7–1.0) for lead to 1.1 (0.7–1.6) for cadmium. Results were consistent across models considering cumulative exposure or duration, as well as in all sensitivity analyses conducted. Conclusions: Findings from this large-scale international study provide no evidence for an association between occupational exposure to any of the metals under scrutiny or welding fumes, and risk of glioma

Suicidality and hostility following involuntary hospital treatment

Background Psychiatric patients showing risk to themselves or others can be involuntarily hospitalised. No data is available on whether following hospitalisation there is a reduction in psychopathological indicators of risk such as suicidality and hostility. This study aimed to assess changes in suicidality and hostility levels following involuntary admission and their patient-level predictors. Methods A pooled analysis of studies on involuntary treatment, including 11 countries and 2790 patients was carried out. Suicidality and hostility were measured by the Brief Psychiatric Rating Scale. Results 2790 patients were included; 2129 followed-up after one month and 1864 after three months. 387 (13.9%) patients showed at least moderate suicidality when involuntarily admitted, 107 (5.0%) after one month and 97 (5.2%) after three months. Moderate or higher hostility was found in 1287 (46.1%) patients after admission, 307 (14.5%) after one month, and 172 (9.2%) after three months. Twenty-three (1.2%) patients showed suicidality, and 53 (2.8%) patients hostility at all time-points. Predictors of suicidality three months after admission were: suicidality at baseline, not having a diagnosis of psychotic disorder and being unemployed. Predictors of hostility were: hostility at baseline, not having a psychotic disorder, living alone, and having been hospitalized previously. Conclusions After involuntary hospital admission, the number of patients with significant levels of suicidality and hostility decreases substantially over time, and very few patients show consistently moderate or higher levels of these symptoms. In patients with psychotic disorders these symptoms are more likely to improve. Social factors such as unemployment and isolation could hamper suicidality and hostility reduction and may be targeted in interventions to reduce risk in involuntarily admitted patients

Assessment of potential effects of the electromagnetic fields of mobile phones on hearing

BACKGROUND: Mobile phones have become indispensable as communication tools; however, to date there is only a limited knowledge about interaction between electromagnetic fields (EMF) emitted by mobile phones and auditory function. The aim of the study was to assess potential changes in hearing function as a consequence of exposure to low-intensity EMF's produced by mobile phones at frequencies of 900 and 1800 MHz. METHODS: The within-subject study was performed on thirty volunteers (age 18–30 years) with normal hearing to assess possible acute effect of EMF. Participants attended two sessions: genuine and sham exposure of EMF. Hearing threshold levels (HTL) on pure tone audiometry (PTA) and transient evoked otoacoustic emissions (TEOAE's) were recorded before and immediately after 10 min of genuine and/or sham exposure of mobile phone EMF. The administration of genuine or sham exposure was double blind and counterbalanced in order. RESULTS: Statistical analysis revealed no significant differences in the mean HTLs of PTA and mean shifts of TEOAE's before and after genuine and/or sham mobile phone EMF 10 min exposure. The data collected showed that average TEOAE levels (averaged across a frequency range) changed less than 2.5 dB between pre- and post-, genuine and sham exposure. The greatest individual change was 10 dB, with a decrease in level from pre- to post- real exposure. CONCLUSION: It could be concluded that a 10-min close exposure of EMFs emitted from a mobile phone had no immediate after-effect on measurements of HTL of PTA and TEOAEs in young human subjects and no measurable hearing deterioration was detected in our study

Reporting of prognostic markers: current problems and development of guidelines for evidence-based practice in the future

Prognostic markers help to stratify patients for treatment by identifying patients with different risks of outcome (e.g. recurrence of disease), and are important tools in the management of cancer and many other diseases. Systematic review and meta-analytical approaches to identifying the most valuable prognostic markers are needed because (sometimes conflicting) evidence relating to markers is often published across a number of studies. To investigate the practicality of this approach, an empirical investigation of a systematic review of tumour markers for neuroblastoma was performed; 260 studies of prognostic markers were identified, which considered 130 different markers

Infant feeding among HIV-positive mothers and the general population mothers: comparison of two cross-sectional surveys in Eastern Uganda

<p>Abstract</p> <p>Background</p> <p>Infant feeding recommendations for HIV-positive mothers differ from recommendations to mothers of unknown HIV-status. The aim of this study was to compare feeding practices, including breastfeeding, between infants and young children of HIV-positive mothers and infants of mothers in the general population of Uganda.</p> <p>Methods</p> <p>This study compares two cross-sectional surveys conducted in the end of 2003 and the beginning of 2005 in Eastern Uganda using analogous questionnaires. The first survey consisted of 727 randomly selected general-population mother-infant pairs with unknown HIV status. The second included 235 HIV-positive mothers affiliated to The Aids Support Organisation, TASO. In this article we compare early feeding practices, breastfeeding duration, feeding patterns with dietary information and socio-economic differences in the two groups of mothers.</p> <p>Results</p> <p>Pre-lacteal feeding was given to 150 (64%) infants of the HIV-positive mothers and 414 (57%) infants of general-population mothers. Exclusive breastfeeding of infants under the age of 6 months was more common in the general population than among the HIV-positive mothers (186 [45%] vs. 9 [24%] respectively according to 24-hour recall). Mixed feeding was the most common practice in both groups of mothers. Solid foods were introduced to more than half of the infants under 6 months old among the HIV-positive mothers and a quarter of the infants in the general population. Among the HIV-positive mothers with infants below 12 months of age, 24 of 90 (27%) had stopped breastfeeding, in contrast to 9 of 727 (1%) in the general population. The HIV-positive mothers were poorer and had less education than the general-population mothers.</p> <p>Conclusion</p> <p>In many respects, HIV-positive mothers fed their infants less favourably than mothers in the general population, with potentially detrimental effects on both the child's nutrition and the risk of HIV transmission. Mixed feeding and pre-lacteal feeding were widespread. Breastfeeding duration was shorter among HIV-positive mothers. Higher educational level and being socio-economically better off were associated with more beneficial infant feeding practices.</p

Conduct of a personal radiofrequency electromagnetic field measurement study: proposed study protocol

Background: The development of new wireless communication technologies that emit radio frequency electromagnetic fields (RF-EMF) is ongoing, but little is known about the RF-EMF exposure distribution in the general population. Previous attempts to measure personal exposure to RF-EMF have used different measurement protocols and analysis methods making comparisons between exposure situations across different study populations very difficult. As a result, observed differences in exposure levels between study populations may not reflect real exposure differences but may be in part, or wholly due to methodological differences. Methods: The aim of this paper is to develop a study protocol for future personal RF-EMF exposure studies based on experience drawn from previous research. Using the current knowledge base, we propose procedures for the measurement of personal exposure to RF-EMF, data collection, data management and analysis, and methods for the selection and instruction of study participants. Results: We have identified two basic types of personal RF-EMF measurement studies: population surveys and microenvironmental measurements. In the case of a population survey, the unit of observation is the individual and a randomly selected representative sample of the population is needed to obtain reliable results. For microenvironmental measurements, study participants are selected in order to represent typical behaviours in different microenvironments. These two study types require different methods and procedures. Conclusion: Applying our proposed common core procedures in future personal measurement studies will allow direct comparisons of personal RF-EMF exposures in different populations and study areas

Feasibility of a cohort study on health risks caused by occupational exposure to radiofrequency electromagnetic fields

Breckenkamp J, Berg-Beckhoff G, Muenster E, et al. Feasibility of a cohort study on health risks caused by occupational exposure to radiofrequency electromagnetic fields. Environmental Health. 2009;8(1):23.Background: The aim of this study was to examine the feasibility of performing a cohort study on health risks from occupational exposure to radiofrequency electromagnetic fields (RF-EMF) in Germany. Methods: A set of criteria was developed to evaluate the feasibility of such a cohort study. The criteria aimed at conditions of exposure and exposure assessment (level, duration, preferably on an individual basis), the possibility to assemble a cohort and the feasibility of ascertaining various disease endpoints. Results: Twenty occupational settings with workers potentially exposed to RF-EMF and, in addition, a cohort of amateur radio operators were considered. Based on expert ratings, literature reviews and our set of predefined criteria, three of the cohorts were identified as promising for further evaluation: the personnel (technicians) of medium/short wave broadcasting stations, amateur radio operators, and workers on dielectric heat sealers. After further analyses, the cohort of workers on dielectric heat sealers seems not to be feasible due to the small number of exposed workers available and to the difficulty of assessing exposure (exposure depends heavily on the respective working process and mixture of exposures, e.g. plastic vapours), although exposure was highest in this occupational setting. The advantage of the cohort of amateur radio operators was the large number of persons it includes, while the advantage of the cohort of personnel working at broadcasting stations was the quality of retrospective exposure assessment. However, in the cohort of amateur radio operators the exposure assessment was limited, and the cohort of technicians was hampered by the small number of persons working in this profession. Conclusion: The majority of occupational groups exposed to RF-EMF are not practicable for setting up an occupational cohort study due to the small numbers of exposed subjects or due to exposure levels being only marginally higher than those of the general public