Power calculation for cohort studies with improved estimation of expected numbers of deaths

Summary This paper focuses on improving the accuracy of sample size calculations for cohort studies by careful calculation of the expected number of deaths in the population, taking into account either prior information or realistic assumptions about variables which may affect the mortality or incidence. Sometimes small changes in the assumptions can dramatically alter the expected numbers and may necessitate modifications in the design of the study. Possible modification include extension of the follow-up time, and recognition that the real strength of the study may lie in the potential for pooling several similar studies. The problem will be discussed with reference to two examples of occupational cohort studies where differing prior information was available.

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Zusammenfassung Diese Arbeit beschäftigt sich mit der Genauigkeit der Berechnung des Stichprobenumfangs in Kohortenstudien, wenn detaillierte Berechnungen für die erwartete Zahl der Verstorbenen berücksichtigt werden. Dies kann entweder durch die Ausnutzung vorhandener Informationen oder durch realistische Annahmen über die Faktoren, die Mortalität oder Inzidenz beeinflussen, geschehen. Schon kleine Unterschiede in diesen Annahmen kann die erwartete Zahl der Verstorbenen erheblich verändern und es notwendig machen, das Design einer Studie zu verändern. Solche Modifikationen bestehen z.B. in der Verlängerung der Follow-up Zeit der Studie oder in der Einsicht, dass es nötig ist, Daten aus mehreren Studien zusammenzufassen. Die Probleme werden anhand von zwei Beispielen aus dem Bereich der Berufsepidemiologie diskutiert.

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Résumé Cet article concerne la précision des estimations de taille d'échantillons pour les études de cohortes. Le calcul précis du nombre de décès attendus dans la population prend en compte les variables susceptibles d'affecter la mortalité ou l'incidence, provenant soit d'une connaissance préalable, soit d'hypothèses réalistes. De modestes changements d'hypothèses peuvent parfois altérer de façon substantielle les nombres attendus et nécessiter des modifications dans le protocole de l'étude. Parmi les modifications possibles, il faut citer la prolongation du temps de suivi de l'étude ainsi que le constat que la valeur réelle de l'étude pourrait reposer sur la possibilité de mise en commun de plusieurs études similaires. Le problème est discuté à l'aide de deux exemples d'études de cohortes professionnelles pour lesquelles différentes informations préalables sont disponibles.

     

Trends in maternal mortality ratio among women of German and non-German nationality in West Germany, 1980-1996

BACKGROUND: Maternal mortality is a sensitive indicator for inequity in health. We describe recent trends in overall and cause-specific maternal mortality ratio among women of German and non-German nationality residing in West Germany. METHODS: Using birth and death register data for 1980-1996 we related 1067 cases of maternal death (ICD 9: 630-676) to 11.2 million live births. We assessed the effects of nationality and of marital status, a proxy for socioeconomic status, controlling for year of death and age of the mother in a Poisson regression model. RESULTS: Maternal mortality ratio in West Germany decreased from 13 per 100000 live births in 1980-1988 to 6.1 in 1989-1996. The crude relative risk for non-German nationality decreased from 1.9 (95% CI: 1.6-2.3) to 1.3 (1.0-1.7); after adjusting for age, year of death and marital status it was 1.7 (95% CI: 1.4-2.1) and 1.6 (95% CI: 1.2-2.1). Unmarried women incurred an adjusted relative risk of 1.8 (95% CI: 1.5-2.3). Non-German women experienced an excess mortality from abortions which largely disappeared in 1989-1996; concurrently, being unmarried no longer conveyed an additional risk to them. The risk status of German mothers developed unfavourably: increasing proportions are unmarried, which continues to be a marker of elevated relative risk in this group. CONCLUSIONS: Our findings suggest continuously improving accessibility and quality of obstetric services, in particular for women of non-German nationality. Still, inequity in maternal risk continues to exist. Maternal risk, however, is not determined by the simple distinction 'German' versus 'non-German'; its association with socioeconomic status extends beyond nationality.     

Colony-Stimulating Factor-1: A Potential Biomarker for Lupus Nephritis

A noninvasive means to predict the onset and recurrence of lupus nephritis (LN) before overt renal injury is needed to optimize and individualize treatment. Colony-stimulating factor-1 (CSF-1) is expressed by kidney tubules at the onset of LN, increases with disease progression, and spills into the circulation in lupus-prone mice. We tested the hypothesis that amplified expression of CSF-1 detected in the serum or urine correlates with intrarenal CSF-1 expression and histopathology (increased macrophage accumulation, activity indices) and clinical kidney disease activity and predicts the onset and recurrence of nephritis in patients with systemic lupus erythematosus (SLE). We found increased serum or urine CSF-1 levels in patients with cutaneous, serositis, and musculoskeletal disease; however, the increase in CSF-1 levels was far greater in LN. Moreover, an elevation in serum or urine CSF-1 levels correlated with increasing intrarenal CSF-1 expression and histopathology. By longitudinally tracking patients, we found that elevated serum CSF-1 heralded the initial onset of disease, and a rise in serum or urine CSF-1 predicted recurrences of LN before clinical evidence of glomerular dysfunction and conventional serologic measures, even in patients with other manifestations of SLE. These findings indicate that serial monitoring for a rise in serum or urine CSF-1 levels in patients with SLE reflects kidney histopathology and may predict renal disease activity and the onset and recurrence of LN more accurately than conventional laboratory measures.     

Association between body mass index and dental health in 1,290 children of elementary schools in a German city

The aim of the present study was to investigate the association between caries frequency and body mass index (BMI) in German elementary school children. A total of 1,290 elementary school children (648 boys, 642 girls) were examined. The dental examination included the determination of caries frequency (DF-T/df-t values). The medical evaluation assessed the pupils’ general health and BMI. The study showed that 3.6% of the children were underweight, 74.8% had a normal weight, 11.9% were overweight, and 9.7% were obese. Underweight children showed natural healthy teeth in 44.7%, those with normal weight in 40.7%, whereas children with high weight and obese children showed natural healthy teeth in 30.5% and 31.7%, respectively. A significant association between high weight and caries frequency in the first dentition (p = 0.0067) and in the permanent dentition (p = 0.0002) could be observed. The association remains statistically significant after adjusting for age. The number of natural healthy teeth decreased with age (p = 0.001) and BMI (p = 0.0061) and was different between girls and boys (p = 0.0334). This study demonstrated a significant association between caries frequency and weight in school children. In future preventive programs, the importance of nutrition should not only be emphasized with respect to general diseases but also with regard to carious lesions.     

Psychoonkologie

In recent years, the psychosocial stresses and sequelae of cancer have been increasingly focused on by the public interest. Psychosocial counseling and interventions are now an integrated and essential part of modern cancer therapy, although in Germany a large gap exists between the scientific state of the art and real-world psychosocial care. Psychooncology is a young discipline dealing with the intercorrelations of physical, psychological, and social factors in the etiology and course of cancer. Based on many scientific studies, specific psychosocial interventions regarding prevention, diagnosis, treatment, and aftercare have been developed to support cancer patients. This article gives an overview of the young field of psychooncology, focusing on its development during the last decades.     

The performance of methods for correcting measurement error in case-control studies

BACKGROUND: It is generally agreed that adjustment for measurement error (when feasible) can substantially increase the validity of epidemiologic analyses. Although a broad variety of methods for measurement error correction has been developed, application in practice is rare. One reason may be that little is known about the robustness of these methods against violations of their restrictive assumptions. METHODS: We carried out a simulation study to assess the performance of two error correction methods (a regression calibration method and a semiparametric approach) as compared with standard analyses without measurement error correction in case-control studies with internal validation data. Performance was assessed over a wide range of model parameters including varying degrees of violations of assumptions. RESULTS: In nearly all the settings assessed, the semiparametric estimate performed better than all alternatives under investigation. The regression calibration method is sensitive to violations of the assumptions of nondifferential error and small error variance. CONCLUSIONS: The semiparametric method is a very robust method to correct for measurement error in case-control studies, but lack of functional software hinders widespread use. If the assumptions for the regression calibration method are fulfilled, application of this method, originally developed for cohort studies, in case-control studies may be a useful alternative that is easy to implement.     

Calculating the "number needed to be exposed" with adjustment for confounding variables in epidemiological studies

The number needed to treat (NNT) is a popular summary statistic to describe the absolute effect of a new treatment compared with a standard treatment or control concerning the risk of an adverse event. The NNT concept can be applied whenever the risk of an adverse event is compared between two groups; for the comparison of exposed with unexposed subjects in epidemiological studies, we propose the term "number needed to be exposed" (NNE). Whereas in randomized clinical trials NNT can be calculated on the basis of a simple 2 x 2 table, in epidemiological studies methods to adjust for confounders are required in most applications. We derive a method based upon multiple logistic regression analysis to perform point and interval estimation of NNE with adjustment for confounding variables. The adjusted NNE can be calculated from the adjusted odds ratio (OR) and the unexposed event rate (UER) estimated by means of an appropriate multiple logistic regression model. As UER is dependent on the confounders, the adjusted NNEs also vary with the values of the confounding variables. Two methods are proposed to take the dependence of NNE on the values of the confounders into account. The adjusted number needed to be exposed can be a useful complement to the commonly presented results in epidemiological studies, such as ORs and attributable risks.     

Sun exposure and number of nevi in 5- to 6-year-old European children

The occurrence and number of melanocytic nevi are among the most important known risk factors for the development of malignant melanoma. Studying the causes of nevi should lead to successful strategies in the prevention of melanoma. Among 11,478 white German children of preschool age the association between benign melanocytic nevi and a number of risk factors for skin cancer was examined. We found that subjects with a reported history of increased sun exposure, for example, painful sunburns, and an increased number of holidays in foreign countries with a sunny climate had significantly higher nevus counts than individuals without these characteristics. Our results provide further evidence that nevus counts may not only be part of a genetic predisposition but also a result of increased exposure to ultraviolet radiation. Together with the fact that a high nevus count is the most relevant risk factor for malignant melanoma, the results strongly indicate a connection between UV-radiation and the development of melanocytic skin cancer. In conclusion, strategies to reduce the incidence of melanoma should begin with young children.     

Contacts with animals and humans as risk factors for adult brain tumours. An international case-control study

While numerous studies have addressed the possible role of farming and related exposures as risk factors for brain tumours in adults, few of them have examined the potential effect of exposure to farm animals or pets. In an international multicentre case-control study, we investigated whether residence on a farm, contact with animals, or working in occupations with a high degree of potential contact with animals or humans were associated with brain tumours. Using a common questionnaire, 1177 cases of glioma, 330 with meningioma and 2478 controls from eight centres were interviewed about the exposures and, in particular, about their contacts with nine species of animals: dairy cattle, beef cattle, pigs, horses, sheep, goats, poultry, dogs and cats. Living or working on a farm was not a risk factor, for either glioma or meningioma. Except in some centres, there was no relationship between having contacts with farm animals or pets and the risk of brain tumour, for either type of tumour or either sex. In relation to seven industrial groups involving frequent human and/or animal contacts, no association was apparent for either glioma or meningioma. In relation to 25 occupational groups with potential frequent contact with humans and/or animals, for glioma there was a reduced risk for biological technicians (Odds Ratio (OR)/=0, P=0.01), and general farm workers (OR=0.66, 95% Confidence Interval (CI): 0.5-0.9). For meningioma, there was an increased risk for cooks (OR=2.0; CI: 1.2-3.4). With some exceptions, these results indicate no association between either the type of brain tumour and contacts with animals, or with occupations that include a high level of contact with animals or a high level of contact with humans.     

Dietary carcinogens and the risk for glioma and meningioma in Germany

A population-based case-control study was performed in South-West Germany in 1987/88 with 115 histological confirmed glioma and 81 meningioma cases and 418 randomly selected controls. On the basis of information from a foodfrequency questionnaire and questions on food preparation and food supply, the role of dietary carcinogens, in particular N-nitroso compounds or their precursors, on risk for glioma and meningioma were analyzed by multiple logistic regression. Eleven food groups were investigated. The intake of processed meat was significantly associated with an increased risk of glioma. The intake of any food group was not significantly related to meningioma risk. Among single meat products, a significantly higher risk of glioma was found for cooked ham, processed pork meat and fried bacon. For the consumption of 3 N-nitrosamines, assessed from the intake of processed meat and cheese, significant positive relations to glioma risk were found. These N-nitrosamines were also related to meningioma risk, although to a less pronounced extent. The risk for occurrence of glioma was significantly increased for those using vegetable fat frequently for deep frying, as compared with non-users. For the dietary intake of nitrate, nitrite, vitamin C, specific alcoholic beverages, total alcohol, and water from a non-central supply, no elevated risk was found in this study.