MODELING NONLINEAR DOSE-RESPONSE RELATIONSHIPS IN EPIDEMIOLOGIC STUDIES: STATISTICAL APPROACHES AND PRACTICAL CHALLENGES

Non-linear dose response relationships pose statistical challenges for their discovery. Even when an initial linear approximation is followed by other approaches, the results may be misleading and, possibly, preclude altogether the discovery of the nonlinear relationship under investigation. We review a variety of straightforward statistical approaches for detecting nonlinear relationships and discuss several factors that hinder their detection. Our specific context is that of epidemiologic studies of exposure-outcome associations and we focus on threshold and J-effect dose response relationships. The examples presented reveal that no single approach is universally appropriate; rather, these (and possibly other) nonlinearities require for their discovery a variety of both graphical and numeric techniques

Quantitative analysis of the loss of distinction between gray and white matter in comatose patients after cardiac arrest

BACKGROUND AND PURPOSE: Anecdotal reports suggest that a loss of distinction between gray (GM) and white matter (WM) as adjudged by CT scan predicts poor outcome in comatose patients after cardiac arrest. To address this, we quantitatively assessed GM and WM intensities at various brain levels in comatose patients after cardiac arrest. METHODS: Patients for whom consultation was requested within 24 hours of a cardiac arrest were identified with the use of a computerized database that tracks neurological consultations at our institution. Twenty-five comatose patients were identified for whom complete medical records and CT scans were available for review. Twenty-five consecutive patients for whom a CT scan was interpreted as normal served as controls. Hounsfield units (HUs) were measured in small defined areas obtained from axial images at the levels of the basal ganglia, centrum semiovale, and high convexity area. RESULTS: At each level tested, lower GM intensity and higher WM intensity were noted in comatose patients compared with normal controls. The GM/WM ratio was significantly lower among comatose patients compared with controls (P:\u3c0.0001, rank sum test). There was essentially no overlap in GM/WM ratios between control and study patients. The difference was greatest at the basal ganglia level. We also observed a marginally significant difference in the GM/WM ratio at the basal ganglia level between those patients who died and those who survived cardiac arrest (P:=0. 035, 1-tailed t test). Using receiver operating characteristic curve analysis, we determined that a difference in GM/WM ratio of \u3c1.18 at the basal ganglia level was 100% predictive of death. At the basal ganglia level, none of 12 patients below this threshold survived, whereas the survival rate was 46% among patients in whom the ratio was \u3e1.18. The empirical risk of death was 21.67 for comatose patients with a value below threshold. CONCLUSIONS: The ratio in HUs of GM to WM provides a reproducible measure of the distinction between gray and white matter. A lower GM/WM ratio is observed in comatose patients immediately after cardiac arrest. The basal ganglia level seems to be the most sensitive location on CT for measuring this relationship. Although a GM/WM ratio \u3c1.18 at this level predicted death in this retrospective study, the difference in this study is not robust enough to recommend that management decisions be dictated by CT results. The results, however, do warrant consideration of a prospective study to determine the reliability of CT scanning in predicting outcome for comatose patients after cardiac arrest

Temporal trends in cardiogenic shock complicating acute myocardial infarction

BACKGROUND: Limited information is available on trends in the incidence of and mortality due to cardiogenic shock complicating acute myocardial infarction. We studied the incidence of cardiogenic shock complicating acute myocardial infarction and in-hospital death rates among patients with this condition in a single community from 1975 through 1997. METHODS: We conducted an observational study of 9076 residents of metropolitan Worcester, Massachusetts, who were hospitalized with confirmed acute myocardial infarction in all local hospitals during 11 one-year periods between 1975 and 1997. Our study included periods before and after the advent of reperfusion therapy. RESULTS: The incidence of cardiogenic shock remained relatively stable over time, averaging 7.1 percent among patients with acute myocardial infarction. The results of a multivariable regression analysis indicated that the patients hospitalized during recent study years were not at a substantially lower risk for shock than patients hospitalized in the mid-to-late 1970s. Patients in whom cardiogenic shock developed had a significantly greater risk of dying during hospitalization (71.7 percent) than those who did not have cardiogenic shock (12.0 percent, P\u3c0.001). A significant trend toward an increase in in-hospital survival among patients with cardiogenic shock in the mid-to-late 1990s was found in crude and adjusted analyses. CONCLUSIONS: Our findings indicate no significant change in the incidence of cardiogenic shock complicating acute myocardial infarction over a 23-year period. However, the short-term survival rate has increased in recent years at the same time as the use of coronary reperfusion strategies has increased

Normal breast tissue of obese women is enriched for macrophage markers and macrophage-associated gene expression

Activation of inflammatory pathways is one plausible mechanism underlying the association between obesity and increased breast cancer risk. However, macrophage infiltration and local biomarkers of inflammation in breast adipose tissue have seldom been studied in association with obesity

Expectations, goals, and perceived effectiveness of child health supervision: a study of mothers in a pediatric practice

The purpose of the study was to assess parent expectations and goals in child health supervision and variability by socioeconomic status (SES), family size, social support, and pediatrician. Home interviews were conducted with mothers and their pediatricians were surveyed. Two hundred mothers with at least one child age 2-3 years who see one of five pediatricians in a staff model health maintenance organization were asked to participate. Mothers\u27 and pediatricians\u27 goals in the following seven areas of health supervision were assessed: biomedical, development, behavior, family functioning, safety education, and interpersonal and system interaction. Mothers stated physicians were their main source of parenting information. Assurance of physical health and normal development were more important than discussion of behavioral, family, or safety issues. Mothers of low SES were more likely to feel that physical aspects of health should be the focus and were less interested in psychosocial issues. Physicians stressed interpersonal, safety, and behavioral goals more than mothers. Individual physician responses did not predict the responses of mothers in their practice. Our data suggest either that mothers do not feel that psychosocial and safety issues are the highest priorities in health supervision or that physicians are not effectively reaching mothers on these issues

The TSHS Resources Portal: A Source of Real and Relevant Data for Teaching Statistics in the Health Sciences

The use of real and relevant data in the statistics classroom is an ideal for many teachers of statistics, as these offer clear benefits for engagement with the kinds of real world applications that students will encounter in the future. Yet, the time required to identify and obtain well-documented data and to prepare classroom teaching materials is often prohibitive. In this paper we review the many benefits of using real and relevant data, and use these to define the characteristics of a well-documented health sciences data resource. We review the barriers to using real and relevant data in teaching. Lastly, we introduce the Teaching of Statistics in the Health Sciences (TSHS) Resources Portal (https://www.causeweb.org/tshs/), a source for well-documented health-related datasets and teaching materials. This dynamic resource provides a means to both obtain and contribute peer-reviewed educational materials. The target audience of the tool is teachers of statistics in health sciences settings, particularly those who teach introductory and applied courses in the graduate or post-graduate setting, but we expect that other statistics educators seeking rich, well-documented datasets will also find the Portal a useful resource