Socioeconomic status amplifies genetic effects in middle childhood in a large German twin sample.

The Scarr-Rowe hypothesis predicts that the heritability of cognitive abilities is higher in more privileged socioeconomic conditions, meaning that genetic potential can be more fully expressed in environments characterized by high socioeconomic status (SES) compared to low SES. This gene × SES interaction, however, has been replicated mostly in the United States, but not in other Western nations like the United Kingdom. In the current study, we tested the interaction between childhood SES and the heritability of cognitive ability in 3,074 German twin pairs comprising three age cohorts at different developmental stages (mean ages of 11, 17, and 23 years). Higher SES was associated with significantly higher mean cognitive ability scores in the two younger cohorts, with reduced variances at higher SES levels. Results further support the Scarr-Rowe hypothesis in middle childhood, and to some degree in adolescence, but not in adulthood. This indicates that the role of family SES as a moderator of the heritability of cognitive ability changes as children grow older. Moreover, children's shared experiences appear to be explain more variance in cognitive ability at the lower end of the SES distribution in middle childhood and adolescence.

Gene-environment interplay in depressive symptoms: moderation by age, sex, and physical illness.

BACKGROUND: Numerous factors influence late-life depressive symptoms in adults, many not thoroughly characterized. We addressed whether genetic and environmental influences on depressive symptoms differed by age, sex, and physical illness. METHOD: The analysis sample included 24 436 twins aged 40-90 years drawn from the Interplay of Genes and Environment across Multiple Studies (IGEMS) Consortium. Biometric analyses tested age, sex, and physical illness moderation of genetic and environmental variance in depressive symptoms. RESULTS: Women reported greater depressive symptoms than men. After age 60, there was an accelerating increase in depressive symptom scores with age, but this did not appreciably affect genetic and environmental variances. Overlap in genetic influences between physical illness and depressive symptoms was greater in men than in women. Additionally, in men extent of overlap was greater with worse physical illness (the genetic correlation ranged from near 0.00 for the least physical illness to nearly 0.60 with physical illness 2 s.d. above the mean). For men and women, the same environmental factors that influenced depressive symptoms also influenced physical illness. CONCLUSIONS: Findings suggested that genetic factors play a larger part in the association between depressive symptoms and physical illness for men than for women. For both sexes, across all ages, physical illness may similarly trigger social and health limitations that contribute to depressive symptoms.

Direct medical care costs among pegylated interferon plus ribavirin-treated and untreated chronic hepatitis C patients.

BACKGROUND: Hepatitis C virus (HCV) is a common and expensive infectious disease. The current standard of care for HCV infection, pegylated interferon with ribavirin (PEG-RBV), is costly and has a significant adverse event profile. AIM: To quantify the direct economic burden of HCV infection and PEG-RBV treatment for HCV. METHODS: Using a large administrative claims database, we evaluated the medical and prescription drug costs of patients with HCV from 2002 to 2007. A cohort of patients with PEG-RBV was 1:1 propensity score-matched to a cohort of untreated HCV patients. Multivariate models adjusted for demographic and clinical characteristics in evaluating the effect of PEG-RBV treatment on direct medical expenditure. RESULTS: The matched analysis included 20,002 patients. PEG-RBV-treated patients had higher total direct medical costs ($28,547 vs. $21,752; P < 0.001), outpatient pharmacy costs ($17,419 vs. $2,900; P < 0.001), and outpatient physician visit costs ($894 vs. $787; P < 0.001), but lower inpatient costs ($3,942 vs. $9,543; P < 0.001) and emergency room costs ($366 vs. $505; P < 0.001). After multivariate adjustment, PEG-RBV use was associated with an additional $9,423 in total direct medical costs and an additional $12,244 in HCV-related total medical costs. CONCLUSION: Total HCV-related medical costs are higher for treated than untreated patients, driven mostly by higher outpatient pharmacy costs, which outweigh higher HCV-related inpatient costs incurred by untreated patients.

Patient preferences and assessment of likely adherence to hepatitis C virus treatment.

To estimate patient preferences for attributes of hepatitis C virus (HCV) treatment and patients' assessment of the likely effect of treatment attributes on treatment adherence, HCV patients ≥18 years old completed an online survey that included nine 2-alternative choice questions. Each choice question was defined by the probability of sustained viral response (Efficacy), injection frequency (Frequency), duration of flu-like symptoms after every injection (Flu), injection device (Device), average number of days of work missed each week (Lost Work Days), probability of reversible hair thinning while on treatment (Alopecia) and probability of developing clinical depression while on treatment (Depression). We estimated a mean relative importance weight for each attribute. Patients also answered three rating questions to assess the extent to which treatment attributes might affect adherence. Hundred and fifty patients completed the survey. Efficacy was the most important attribute with a mean relative importance weight of 10 [95% CI: 7.9-12.1]. The remaining attributes were ranked in order of importance as follows: Depression (4.4 [95% CI: 3.6-5.1]), Flu Days(Frequency×Flu) (3.7 [95% CI: 2.2-5.3]), Lost Work Days (2.9 [95% CI: 2.3-3.5]), Alopecia (1.3 [95% CI: 0.7-1.9]) and Device (1.2 [95% CI: 0.4-2.0]). Patients with prior treatment experience were less likely to indicate that treatment attributes would affect adherence. Patients also indicated that increases in the number of flu days would increase the likelihood of nonadherence to treatment. Sustained viral response is the most important treatment attribute to patients but treatment side effects might affect treatment adherence.

Risk factors for coronary heart disease in men 18 to 39 years of age.

BACKGROUND: Few studies have evaluated the long-term predictive capacity of risk factors for death from coronary heart disease in men younger than 40 years of age. OBJECTIVE: To assess the predictive capacity and discriminatory ability of major coronary risk factors in predicting death from coronary heart disease in young men. DESIGN: Prospective cohort study with 20 years of follow-up. SETTING: 84 companies in the Chicago area that participated in the Chicago Heart Association Detection Project in Industry (1967-1973). PARTICIPANTS: 11 016 men 18 to 39 years of age (mean age, 29.7 years) at baseline were the primary focus of this report; 8955 men 40 to 59 years of age at baseline served as a reference group. MEASUREMENTS: The main end point was death from coronary heart disease. RESULTS: All major risk factors-age, serum cholesterol level, systolic blood pressure, and cigarette smoking-were significantly associated with death from coronary heart disease over 20 years in young men. Relative risks for the major risk factors were of generally similar magnitude in young and middle-aged men. Receiver-operating characteristic curves for the best predictive model yielded an area under the curve of 0.82, indicating that standard risk factors were highly predictive of long-term outcome in young men. CONCLUSIONS: Major coronary disease risk factors, many of which are modifiable, are strong contributors to prediction of future risk, even in young men. These data may help in formulating appropriate strategies to identify young men at heightened risk for death from coronary heart disease in later adulthood.

Power Doppler imaging: initial evaluation as a screening examination for carotid artery stenosis.

PURPOSE: To evaluate power Doppler imaging as a possible screening examination for carotid artery stenosis. MATERIALS AND METHODS: In the principal pilot study, a prospective, blinded comparison of power Doppler imaging with duplex Doppler imaging, the reference-standard method, was conducted in 100 consecutive patients routinely referred for carotid artery imaging at a large, private multispecialty clinic. In the validation pilot study, a prospective, blinded comparison of power Doppler imaging with digital subtraction angiography, the reference-standard method, was conducted in 20 consecutive patients routinely referred at a teaching hospital. Using conservative assumptions, the authors performed cost-effectiveness analysis. RESULTS: Power Doppler imaging produced diagnostic-quality images in 89% of patients. When the images of the patients with nondiagnostic examinations were regarded as positive, power Doppler imaging had an area under the receiver operating characteristic curve, A(z), of 0.87, sensitivity of 70%, and specificity of 91%. The validation study results were very similar. The cost-effectiveness of screening and, as indicated, duplex Doppler imaging as the definitive diagnostic examination and endarterectomy was $47,000 per quality-adjusted life-year. CONCLUSION: The A(z) value for power Doppler imaging compares well with that for mammography, a generally accepted screening examination, and with most other imaging examinations. Power Doppler imaging is likely to be a reasonably accurate and cost-effective screening examination for carotid artery stenosis in asymptomatic populations.

A sequential chart for the audit-based evaluation of screening mammogram interpretation.

RATIONALE AND OBJECTIVES: Auditing has received much attention recently as a method for radiologists to use to evaluate their interpretation of screening mammograms. U.S. Food and Drug Administration regulations require that some sort of audit be in place before a mammography screening facility can receive accreditation. Auditing presents a unique opportunity to monitor accuracy continually and identify problems early. Audit data present unique challenges, however, and appropriate methods must be used to control the risk of errors. MATERIALS AND METHODS: This article introduces a simple method for the task of deciding if a radiologist yields an acceptable positive predictive value based on audit. The method is based on "sequential" decision-making techniques that have found wide application in quality control problems. These techniques are developed for diagnostic radiology and embodied in an easy-to-use decision-making chart. RESULTS: Several examples, based on audit data from actual mammography facilities, provide insights into the use of these charts and the influence of (a) the selection of standards, (b) the selection of error risks, and (c) radiologist variability. The examples also serve to demonstrate another important property of this method--that is, it specifies the minimum amount of data that has to be collected before any decision can reliably be made. CONCLUSION: The chart presented in this article provides a method by which audit data can be used objectively to evaluate the accuracy of screening mammogram interpretation. The method controls the risk of either falsely accepting an unqualified radiologist or falsely rejecting a qualified radiologist. It should be a useful tool to radiologists who must evaluate their own practices.

Analysis of clustered data in receiver operating characteristic studies.

Clustered data is not simply correlated data, but has its own unique aspects. In this paper, various methods for correlated receiver operating characteristic (ROC) curve data that have been extended specifically to clustered data are reviewed. For those methods that have not yet been extended, suggestions for their application to clustered ROC studies are provided. Various methods with respect to their ability to meet either of two objectives of the analysis of clustered ROC data are compared to consider a variety of ROC indices and their accessibility to researchers. The available statistical methods for clustered data vary in the range of indices that can be considered and in their accessibility to researchers. Parametric models permit all indices to be considered but, owing to computational complexity, are the least accessible of available methods. Nonparametric methods are much more accessible, but only permit estimation and inference about ROC curve area. The jackknife method is the most accessible and permits any index to be considered. Future development of methods for clustered ROC studies should consider the continuation ratio model, which will permit the application of widely available software for the analysis of mixed generalized linear models. Another area of development should be in the adoption of bootstrapping methods to clustered ROC data.

Effect of human variability on independent double reading in screening mammography.

RATIONALE AND OBJECTIVES: To demonstrate the range of gains and losses that radiologists might experience from independent double reading in screening mammography. METHODS: From a national random sample of radiologists, the authors formed 131 pairs. For each radiologist, the authors analyzed the increase relative to his or her individual true-positive rate (TPR) or false-positive rate (FPR), number of additional cancers detected, and change to negative biopsy rate that would result from independent double reading after pairing. RESULTS: The average radiologist can expect an 8%-14% gain in TPR and a 4%-10% increase in FPR with pairing. For some radiologists, double reading increased the TPR with a small concomitant increase in FPR. Other radiologists, however, realized small gains in TPR with large increases in FPR. Adding the reading from a more experienced radiologist did not necessarily improve the TPR of a radiologist with less experience. CONCLUSION: Radiologists can form complementary and noncomplementary pairs for double reading. Use of this procedure must be decided on an individual basis.

Variability in the interpretation of screening mammograms by US radiologists. Findings from a national sample.

OBJECTIVE: To evaluate the effectiveness of screening mammography by estimating the variability in radiologists' ability to detect breast cancer within the US population of radiologists at mammography centers accredited by the American College of Radiology. METHODS: A two-way sample survey design was used as follows. Fifty mammography centers having an American College of Radiology-accredited unit were randomly sampled from across the United States. One hundred eight radiologists from these centers gave blinded interpretation to the same set of 79 randomly selected screening mammograms. The mammograms were from women who had been screened at a large screening center. Before their sampling, these women had been stratified by their breast disease status, established either by biopsy or by 2-year follow-up. Rates of biopsy recommendations were summarized by the mean, median, minimum, maximum, and range of sensitivity and specificity. Overall cancer detection ability was summarized by similar statistics for receiver operating characteristic curve areas. Ninety-five percent lower confidence bounds on the ranges in accuracy measures were established by boo-strapping. RESULTS: There is a range of at least 40% among US radiologists in their screening sensitivity. There is a range of at least 45% in the rates at which women without breast cancer are recommended for biopsy. As indicated by receiver operating characteristic curve areas, the ability of radiologists to detect cancer mammograms varies by as much as 11%. CONCLUSIONS: Our findings indicate that there is wide variability in the accuracy of mammogram interpretation in the population of US radiologists. Current accreditation programs that certify the technical quality of radiographic equipment and images but not the accuracy of the interpretation given to mammograms may not be sufficient to help mammography fully realize its potential to reduce breast cancer mortality.

Evaluation of the quality of clinical research studies of magnetic resonance angiography: 1991-1994.

To evaluate the quality of clinical research studies of magnetic resonance angiography (MRA), the authors reviewed studies of carotid, renal, and lower extremity MRA published in English during 1991-1994. The purpose, design, and implementation of the study, and the type of statistical information presented, were evaluated. The results were compared with those of previous studies that assessed the quality of MRI research. Fifty-nine studies of renal (n = 10), carotid (n = 29), and lower extremity (n = 20) MRA were identified; 30 met the inclusion criteria for the analysis. In these papers, presentation of a reference standard was routine, observer blinding was usual, information often was given about patient selection and exclusion, sample sizes were always given, and parameter estimates and statistical analyses were common. However, evidence of research planning was not routine, measurement of interobserver variability was occasional, variability of parameter estimates was usually not estimated, and validation of statistical assumptions was uncommon. On balance the authors conclude that the scientific quality of recent investigations of MRA is better than that of older studies of MRI.

Surrogates' predictions of seriously ill patients' resuscitation preferences.

BACKGROUND: Seriously or terminally ill patients are frequently incapacitated and unable to express their preferences regarding cardiopulmonary resuscitation (CPR). In this situation, family members or other surrogate decision makers are often asked whether they believe the patient would want to be resuscitated. We evaluated the concordance of patient CPR preferences and surrogate perceptions of the patient preferences in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT), a large, multicenter study of seriously ill hospitalized patients. METHODS: We compared patient preferences and surrogate perceptions in 1226 pairings in which both patient and surrogate responded to CPR decision questions. We also examined factors that might influence patient-surrogate concordance. RESULTS: Twenty-nine percent of patients with paired data did not want to be resuscitated; 26% of surrogates did not believe the patient they represented would want to be resuscitated. Within pairs, the overall exact agreement with respect to CPR decisions was 74%. For patients favoring CPR, only 16% of the surrogates misconstrued the patient's wishes. For patients who did not want to be resuscitated, however, 50% of the surrogates did not reflect the patient's wishes. If patients reported telling surrogates their CPR preference, concordance was significantly improved if the surrogate believed the patient did not want to be resuscitated and was significantly worsened if the surrogate believed the patient wanted CPR. This finding is likely an artifact of patients being more likely to report their preference to surrogates if that preference was not to be resuscitated. CONCLUSIONS: Surrogates' perceptions of patient CPR preferences are often inaccurate, particularly for those patients who do not want to be resuscitated. Methods to improve communication between patients and surrogates on CPR preferences should be developed and evaluated.