Pain in sickle cell disease. Rates and risk factors.

BACKGROUND AND METHODS: Acute episodes of pain are the principal symptom of sickle cell disease, but little is known about the epidemiologic features of these episodes or risk factors for them, nor is it known whether patients with high rates of such episodes die prematurely. We prospectively studied the natural history of sickle cell disease in 3578 patients ranging from newborns to persons up to 66 years old who were followed at clinical centers across the United States. RESULTS: There were 12,290 episodes of pain in 18,356 patient-years. The average rate was 0.8 episode per patient-year in sickle cell anemia, 1.0 episode per patient-year in sickle beta 0-thalassemia, and 0.4 episode per patient-year in hemoglobin SC disease and sickle beta(+)-thalassemia. The rate varied widely within each of these four groups--e.g., 39 percent of patients with sickle cell anemia had no episodes of pain, and 1 percent had more than six episodes per year. The 5.2 percent of patients with 3 to 10 episodes per year had 32.9 percent of all episodes. Among patients with sickle cell anemia who were more than 20 years old, those with high rates of pain episodes tended to die earlier than those with low rates. High rates were associated with a high hematocrit and low fetal hemoglobin levels. alpha-Thalassemia had no effect on pain apart from its association with an increased hematocrit. CONCLUSIONS: The "pain rate" (episodes per year) is a measure of clinical severity and correlates with early death in patients with sickle cell anemia over the age of 20. Even when the fetal hemoglobin level is low, one can predict that small increments in the level may have an ameliorating effect on the pain rate and may ultimately improve survival. This outcome is particularly encouraging to investigators studying hydroxyurea and other treatments designed to increase the fetal hemoglobin level.

The accuracy of substitution rules for health risk appraisals.

Abstract Health Risk Appraisals (HRAs) have been in increasingly wide use over the past 20 years as health education tools designed to encourage healthy behaviors. A major criticism of HRAs has been the error introduced by missing or incorrectly-specified responses by clients, especially regarding physiological measures such as blood pressure and cholesterol. Four HRAs were randomly assigned to members of a random sample of Massachusetts residents as part of a trial to assess the reliability and validity of HRA instruments. Two rules for substituting unknown physiological measures were evaluated: the existing rule for an HRA and a new rule, which simply substitutes the age- and gender-specific mean physiological values. Ordinary least squares regression was used to compare risk scores generated from known physiological measures, taken in respondents' homes, with risk scores generated by substitution. Regression slopes were mostly close to 1.0, most intercepts were relatively close to 0.0, and correlations were all extremely high, suggesting good performance of substitution rules on a group level. However, outliers from the regressions tended to be individuals at high risk whose risk was underestimated by the substitution rules. These results raise ethical questions about the use of substitution rules and reinforce the need for taking actual physiological measurements.

The validity of health risk appraisal instruments for assessing coronary heart disease risk.

This study evaluated the validity of the scoring systems employed by 41 health risk assessment instruments (HRAs) with respect to the probability of death due to coronary heart disease. Validity was assessed by comparing predictions of mortality risk produced by each HRA to estimates from the Framingham Heart Study and the Risk Factor Update Project. Correlations with both epidemiologic estimates indicated that instruments employing logistic regression or the Geller/Gesner methodology had the highest validity coefficients, while validity was lowest for self-administered general health status and lifestyle questionnaires. However, most instruments using the Geller/Gesner technique appear to systematically overestimate the probability of CHD mortality. For HRAs based on additive risk scales, validity was often attenuated by the crude categorization of some risk factors and by the omission of the effects of age from the scoring system.