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.

     

A comparison of tympanic thermometer readings to pulmonary artery catheter core temperature recordings

The purpose of this study was to determine the accuracy of FirstTemp (Intelligent Medical Systems, Carlsbad, CA) tympanic thermometer readings compared with core body temperatures obtained via pulmonary artery catheter (PAC). Five measurements were obtained on 19 cardiovascular surgery patients. Tympanic thermometer measurements tended to be higher than PAC measurements. However, most of the differences were not clinically significant. Differences found between right and left ear measurements were most likely due to poor measurement technique. When the correct technique is used, nurses can be confident that tympanic temperature readings are clinically accurate.     

Symptomatic treatment in the fragile X-associated tremor/ataxia syndrome.

There is no established treatment for the neurological features of the recently discovered fragile X-associated tremor/ataxia syndrome (FXTAS). Fifty-six patients with FXTAS completed a questionnaire to determine whether any medications had been effective for neurological symptoms. Of 11 subjects with definite FXTAS, 8 (70%) were on medications for their neurological symptoms, whereas most subjects with possible or probable FXTAS, 31 (70%) of 45 subjects, were not on medications. Although no therapy was uniformly effective for intention tremor, ataxia, Parkinsonism, memory loss, or anxiety, some subjects with intention tremor or Parkinsonism reported improvement with medications frequently used in other movement disorders. Overall, all 22 subjects on medications reported improvement in one or more symptoms. Lack of insight, recall bias, and cognitive impairment may have resulted in an underestimation of the beneficial effect of medical therapy. This study suggests that patients with FXTAS can derive improvement from medication treatment for some of their symptoms.     

Use of Water-Soluble Vitamins in Patients with Chronic Renal. Failure

Little is actually known about the minimum daily requirement for most vitamins in the patient with end-stage renal disease. Many of the studies reviewed suffer from lack of adequate control populations and differing methodologies, making comparisons between these studies difficult. However, patients with renal failure have many restrictions on their dietary intake, frequently suffer from intercurrent illness, and would seem to be at risk for vitamin deficiency. Also, metabolic abnormalities associated with the loss of kidney function may increase the daily requirements for certain vitamins. It is unlikely that dialysis losses of the water-soluble vitamins alone could account for vitamin depletion, and these other factors are likely to play a much more important role. It is of interest to note that the studies which demonstrate little or no vitamin deficiencies are those studies which have been carried out more recently (8, 9, 17). The patients were usually given some vitamin supplementation prior to or during the period of study and thus it is not surprising that most patients failed to demonstrate vitamin deficiency. It is also likely that heightened awareness regarding the propensity for patients with renal failure to develop deficiencies of the water-soluble vitamins has resulted in better dietary instruction and earlier intervention with vitamin supplementation. More efficient dialytic methods have also reduced the restrictions on many foods, and patients are no longer instructed to boil all their fresh vegetables. Although there may be the risk of toxicity when vitamin supplementation is overzealously administered to patients with reduced renal excretory function, it seems prudent to administer some of these water-soluble vitamins to patients with end-stage renal disease who are treated with intermittent dialysis therapy (Table 1). Certainly, this is not a very costly approach. Further studies should be carried out to better evaluate vitamin nutriture in chronically uremic and maintenance dialysis patients and to more rigorously define the minimum dose that would prevent deficiency and avoid toxicity.     

Cyclooxygenase 2 expression in serous tumors of the ovary.

This study was designed to investigate the expression of cyclooxygenase (COX)-2 in ovarian serous tumors (benign, borderline tumors, and carcinomas) and primary peritoneal serous carcinomas. Cases diagnosed between 1995 and 2001 were reviewed; 47 benign tumors, 6 borderline tumors, and 39 carcinomas were examined, as well as 12 normal ovaries that served as controls. Blocks were stained with anti COX-2 polyclonal antibody and staining was graded qualitatively. The staining intensity was assessed as weak (score of 1), moderate (score of 2), or strong (score of 3). Normal ovarian and tubal epithelium, inclusion cysts, benign serous tumors, and borderline tumors had a uniform score 3 staining pattern. Serous ovarian carcinomas had variable staining scores, tending to correlate with the level of tumor differentiation. Well-differentiated carcinomas had more intense COX-2 staining than poorly differentiated carcinomas, which had only weak COX-2 staining. The degree of COX-2 staining was not significantly related to overall survival. In conclusion, COX-2 expression is present in serous tumors, including benign tumors, borderline tumors, and carcinomas. Similar to the findings in other neoplasms, COX-2 expression is strongest in well-differentiated tumors and is much less evident in those that are poorly differentiated. The clinical utility of these findings is related to the potential role of nonsteroidal anti-inflammatory drugs, which are COX-2 inhibitors, in treating and/or preventing some forms of ovarian carcinoma.