Patients with chronic kidney disease (CKD) have worse cardiovascular outcomes than those without CKD. The prognostic utility of myocardial perfusion single-photon emission CT (MPS) in patients with ...varying degrees of renal dysfunction and the impact of CKD on cardiac death prediction in patients undergoing MPS have not been investigated.
We followed up 1652 consecutive patients who underwent stress MPS (32% exercise, 95% gated) for cardiac death for a mean of 2.15+/-0.8 years. MPS defects were defined with a summed stress score (normal summed stress score <4, abnormal summed stress score>or=4). Ischemia was defined as a summed stress score >or=4 plus a summed difference score >or=2, and scar was defined as a summed difference score <2 plus a summed stress score >or=4. Renal function was calculated with the Modified Diet in Renal Disease equation. CKD (estimated glomerular filtration rate <60 mL . min(-1) . 1.73 m(-2)) was present in 36%. Cardiac death increased with worsening levels of perfusion defects across the entire spectrum of renal function. Presence of ischemia was independently predictive of cardiac death, all-cause mortality, and nonfatal myocardial infarction. Patients with normal MPS and CKD had higher unadjusted cardiac death event rates than those with no CKD and normal MPS (2.7% versus 0.8%, P=0.001). Multivariate Cox proportional hazards models revealed that both perfusion defects (hazard ratio 1.90, 95% CI 1.47 to 2.46) and CKD (hazard ratio 1.96, 95% CI 1.29 to 2.95) were independent predictors of cardiac death after accounting for risk factors, left ventricular dysfunction, pharmacological stress, and symptom status. Both MPS and CKD had incremental power for cardiac death prediction over baseline risk factors and left ventricular dysfunction (global chi(2) 207.5 versus 169.3, P<0.0001).
MPS provides effective risk stratification across the entire spectrum of renal function. Renal dysfunction is also an important independent predictor of cardiac death in patients undergoing MPS. Renal function and MPS have additive value in risk stratisfying patients with suspected coronary artery disease. Patients with CKD appear to have a relatively less benign prognosis than those without CKD, even in the presence of a normal scan.
The critical need for pediatric research on drugs and biological products underscores the responsibility to ensure that children are enrolled in clinical research that is both scientifically ...necessary and ethically sound. In this chapter, we review key ethical considerations concerning the participation of children. We review a basic ethical framework to guide pediatric research, and suggest how this framework might be operationalized in linking science and ethics. Topics examined include: the status of children as a vulnerable population; the appropriate balance of risk and potential benefit in research; and parental permission and child assent to participate in research.
Grounded on the ethical principle of respect for persons, parental permission and child assent function together to protect the child and to foster the development of the child's self-determination. ...Although both parental permission and child assent involve the same components of information sharing, comprehension, and voluntariness, how these three components are understood and operationalized should differ depending on the developmental level of the child. For example, the amount of information that a child must comprehend to provide meaningful and developmentally appropriate child assent (or dissent) should be allowed to vary with the age and maturity of the child. By understanding child assent together with the important protections of parental permission, child assent does not need to be burdened with the same informational and process requirements. As a result, the age (as a proxy for developmental stage) at which a child is deemed capable of assent would be lower (i.e., 5 to 7 years old). By assuming a lack of capacity, the potential arises to dishonor and disregard a child's wishes by failing to solicit meaningful assent or dissent. Further research needs to be done on how best to obtain truly informed and voluntary parental permission and child assent for research participation.
The critical need for pediatric research on drugs and biological products underscores the responsibility to ensure that children are enrolled in clinical research that is both scientifically ...necessary and ethically sound. In this chapter, we review key ethical considerations concerning the participation of children in clinical research. We propose a basic ethical framework to guide pediatric research, and suggest how this framework might be operationalized in linking science and ethics. Topics examined include: the status of children as a vulnerable population; the appropriate balance of risk and potential benefit in research; ethical considerations underlying study design, including clinical equipoise, placebo controls, and non-inferiority designs; the use of data monitoring committees; compensation; and parental permission and child assent to participate in research. We incorporate selected national (USA) and international guidelines, as well as regulatory approaches to pediatric studies that have been adopted in the USA, Canada, and Europe.
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