Prospective study of serum cholesterol and site-specific cancers.

From 1965 to 1968, 7716 Japanese-American men were examined and tested for serum cholesterol. After 22 years, 1380 incident cancer cases were identified. Of the site-specific cancers, only colon cancer cases had a significantly lower mean serum cholesterol value than that of noncases (213.0 mg/dl vs 219.0 mg/dl). When the study subjects were separated into either a low, middle or high group, based on their serum cholesterol values, there was a significant inverse trend for cases of oral/pharyngeal/esophageal cancer combined. The association was present for cases diagnosed within 10 years of examination (p = 0.012), but not for cases diagnosed after 10 years. This suggests that the inverse association is due to the metabolic effects of undiagnosed oral/pharyngeal/esophageal cancer upon serum cholesterol levels. These results are discussed in relation to other studies on serum cholesterol.     

A Simple and Robust Way of Concluding Meta-Analysis Results Using Reported P values, Standardized Effect Sizes, or Other Statistics

Meta-analysis is a powerful tool to estimate measures of associations or effects based on published or unpublished reports. However, problems exist in many meta-analyses, particularly related to study heterogeneity. This article proposes a way of concluding meta-analysis results using P values, taking heterogeneity into account. There is little published research focused on evaluating conclusiveness of summary results of reported meta-analyses. Generally, a P value is directly linked to the test statistic z=b/s_b following a standard normal distribution with mean zero and unit variance, where b is an estimator of β and s_b is the estimated standard error of b for any study included in a meta-analysis. This forms the basis of the proposed method for deriving overall test statistics and corresponding P values used for comparing results of meta-analyses. Two published meta-analyses were chosen and specific software was applied. Results are consistent with the two published meta-analysis reports in terms of P values for significance and direction of summary measure of treatment effect. This proposed method can be utilized to safeguard against improper conclusions of published meta-analyses due to heterogeneity. Exploring more sophisticated statistical methods for situations when the key assumption applied to this proposed method is violated could be pursued and could expand the scope of applications beyond this method.     

Serum cholesterol concentrations and all-cause mortality in older people

OBJECTIVE: To study the impact of serum cholesterol concentrations on the total risk of mortality in older people. DESIGN: Retrospective cohort study with a follow-up of 8-10 years. SUBJECTS: A total of 989 subjects (367 men and 622 women) aged 65 and over, living in the Marshfield Epidemiologic Study Area at the time of their first complete serum lipid assessment. METHODS: We calculated sex-specific mean levels of serum total cholesterol, low-density lipoprotein, high-density lipoprotein and triglycerides, and the ratio of total cholesterol to high-density lipoprotein, for subjects who died of all causes and for those who survived to the end of follow-up, with adjustment for relevant covariates. We obtained estimates of the risk factor-adjusted sex-specific relative risk for all-cause mortality with approximate quartiles of serum cholesterol concentrations by proportional hazards regression models. We also evaluated the possible combined effects of age, sex and cholesterol on all-cause mortality. RESULTS: A high level of high-density lipoprotein was significantly associated with a low total risk of mortality in older men. Conversely, an elevated ratio of total cholesterol to high-density lipoprotein was directly related to an increased total risk of mortality in older men. Age and high-density lipoprotein level had a significant synergistic effect on all-cause mortality for the elderly men. We found little or no association in women between all-cause mortality and any of the lipid measures studied. CONCLUSIONS: An increased ratio of total cholesterol to high-density lipoprotein appears to be associated with an increase in risk for all-cause mortality in men aged 65 and over, while an elevated level of high-density lipoprotein, considered alone, seems to be protective against mortality from all causes in men aged 65-74 years, but this effect diminishes over the age of 75.     

Impact of diet and smoking on risk of developing intestinal metaplasia of the stomach

A cohort of Hawaii Japanese men was assembled for epidemiologic studies of heart disease and cancer. Diet and tobacco consumption data were obtained from 1965 to 1968 and from 1971 to 1975. Biopsies from sites at maximal, intermediate, and minimal risk of intestinal metaplasia were performed on 350 men. Metaplasia was found in 234 men. Gastric cancer was found in 9/234 with metaplasia (3.8%) and 1/116 men without metaplasia (0.89%). Nitrite-rich salty foods (e.g., cured meats) were directly related to metaplasia at both examinations. Vitamin C intake did not appear to have prevented the development of intestinal metaplasia. Smoking was directly related to the presence of metaplasia, but the association was weaker than was observed for cured meats. The strong association between nitrite-rich salty foods and metaplasia appears to be uniform from one study to another, as is the lack of a consistent relation between metaplasia and either smoking or vitamin C consumption. Heavy smokers were more likely to have metaplasia than were nonsmokers, but these associations were weaker than were those with cured meats.Supported by PHS grant R01 CA 33644, awarded by the National Cancer Institute, DHHS, Bethesda, Maryland.     

To early distinguish neonatal transient leukemoid proliferation from congenital leukemia by in vitro cell growth

Summary To differentiate neonatal transient leukemoid proliferation from congenital leukemia at an early stage is often difficult. Bone marrow culture is found to be helpful in this aspect. A normal in vitro growth pattern suggests transient leukemoid proliferation, while an abnormal growth pattern indicates congenital leukemia. A neonate who manifested with pictures mimicking acute myeloblastic leukemia (M₁), had a karyotype of 46, XY/46, XY, i(21 q). However, the in vitro growth pattern was normal and so only supportive treatment was given. All the leukemoid manifestations disappeared several months later and he is now a healthy 2 year old boy remaining in complete remission. A second neonate who also displayed features of acute myeloblastic leukemia (M₂), had a karyotype of 46, XY/47, XY, +21 and abnormal in vitro growth pattern. This neonate died at 18 days of age.     

Accuracy of noninvasive ejection fraction measurement in a large community-based clinic

OBJECTIVE: Compare the agreement of two dimensional echocardiography (echocardiography) and electrocardiogram (ECG)-gated single photon emission computed tomography (SPECT), with left ventricular contrast angiography (angiography) for the evaluation of left ventricular ejection fraction (LVEF). DESIGN: Retrospective cohort study. DATA SOURCE: American College of Cardiology National Cardiovascular Data Registry(TM) (ACC-NCDR). PARTICIPANTS: Patients from a large, community-based clinic in central Wisconsin. METHODS: Consecutive patients (1999-2002) were identified from the ACC-NCDR dataset who underwent angiography and echocardiography or SPECT within 1 month of each other for evaluation of LVEF. Noninvasive LVEF values were compared to those obtained by angiography using the paired t-test. Regression analysis was used to assess the relation between the compared methods. Bland-Altman analyses were performed to assess the agreement between LVEF values obtained by the noninvasive techniques and angiography. Sensitivity and specificity of detecting depressed LVEF were determined for noninvasive techniques. Regression equations were determined for estimating angiographic values from the echocardiographic or SPECT values. RESULTS: Five hundred thirty-four patients underwent 542 angiographic studies: SPECT in all 534 patients, combined SPECT and echocardiographic studies in 201 patients, and combined angiographic and echocardiographic studies in 202 patients. Correlation of angiographic LVEFs with both echocardiographic and SPECT LVEFs was significant (r = 0.70 and r = 0.69, respectively; p < 0.0001). Echocardiographic LVEFs were lower than those determined by angiography (49% +/- 1.0% versus 54% +/- 1.0%; p < 0.0001). SPECT LVEFs were also lower than angiographic LVEFs (49% +/- 0.6% versus 57% +/- 0.6%; p < 0.0001). For 201 patients who underwent both SPECT and echocardiography, SPECT LVEFs were lower (47% +/- 1.0% for SPECT versus 49% +/- 1.0% for echocardiography; p < 0.05). Bland-Altman analysis revealed widely varying differences between techniques with broad confidence intervals. Nonetheless, sensitivity and specificity for determining LVEFs of <40% for SPECT and echocardiography were 90% and 86%, and 75% and 89%, respectively. LVEF of < or = 35% was correctly assessed by both SPECT and echocardiography. Sensitivity and specificity for SPECT were 82% and 89%, and 81% and 88% for echocardiography. CONCLUSION: At our institution, LVEFs obtained noninvasively by echocardiography or SPECT are lower than angiographic LVEFs with widely fluctuating differences. Regression equations can be used to correct the noninvasive readings. Although lower, noninvasive techniques appear to accurately assess depressed LVEFs (<40% and <35%). The accuracy of noninvasive techniques for the evaluation of LVEF should be considered when managing and determining prognoses of patients with cardiac conditions. Individual institutions should determine the validity of the noninvasive techniques they use to assess LVEF.     

Applying case definition criteria to irritable bowel syndrome

Objective: The quality of documentation of signs and symptoms and validation of the diagnosis of irritable bowel syndrome (IBS) according to case definition criteria of Manning, Rome I and Rome II in an office setting has not been previously described. We sought to identify and validate cases of IBS based on the Manning, Rome I and Rome II diagnostic criteria in a rural practice setting.     

Patterns of bias due to differential misclassification by case–control status in a case–control study

BACKGROUND: Case-control study is still one of the most commonly used study designs in epidemiological research. Misclassification of case-control status remains a significant issue because it will bias the results of a case-control study. There exist two types of misclassification, differential versus nondifferential. It is commonly accepted that nondifferential misclassification will bias the results of the study towards the null hypothesis. Conversely, no reports have assessed the impact and direction of differential misclassification on odds ratio (OR) estimate. The goal of the present study is to demonstrate by statistical derivation that patterns exist on the bias induced by differential misclassification. METHODS: Based on a 2 x 2 case-control study design, we derive the odds ratio without misclassification, and those with misclassification according to: (1) controls are misclassified as cases by exposure status; (2) cases are misclassified as controls by exposure status; and (3) both controls and cases are misclassified by exposure status simultaneously. Furthermore, mathematical derivations are shown for each of the ratios of the two odds ratios with and without misclassification. These methods are carried out by simulation analyses. RESULTS: Simulation analyses show that quite a number of biased odds ratios tend to move away from the null hypothesis and result in approaching zero or infinity with increasing proportion of misclassification among cases, controls, or both. These patterns are associated with the exposure status and the values of unbiased odds ratio (<1, 1, or >1). CONCLUSIONS: Our findings suggest that, unlike nondifferential misclassification, differential misclassification of case-control status in a case-control study may not weaken the exposure-outcome association towarding the null hypothesis. Care needs to be taken for interpreting the results of a case-control study when there exists differential misclassification bias, a practical issue in epidemiological research.