Showing papers in "American Journal of Epidemiology in 2006"

Variable Selection for Propensity Score Models

Abstract: Despite the growing popularity of propensity score (PS) methods in epidemiology, relatively little has been written in the epidemiologic literature about the problem of variable selection for PS models. The authors present the results of two simulation studies designed to help epidemiologists gain insight into the variable selection problem in a PS analysis. The simulation studies illustrate how the choice of variables that are included in a PS model can affect the bias, variance, and mean squared error of an estimated exposure effect. The results suggest that variables that are unrelated to the exposure but related to the outcome should always be included in a PS model. The inclusion of these variables will decrease the variance of an estimated exposure effect without increasing bias. In contrast, including variables that are related to the exposure but not to the outcome will increase the variance of the estimated exposure effect without decreasing bias. In very small studies, the inclusion of variables that are strongly related to the exposure but only weakly related to the outcome can be detrimental to an estimate in a mean squared error sense. The addition of these variables removes only a small amount of bias but can increase the variance of the estimated exposure effect. These simulation studies and other analytical results suggest that standard model-building tools designed to create good predictive models of the exposure will not always lead to optimal PS models, particularly in small studies.

The Inconsistency of “Optimal” Cutpoints Obtained using Two Criteria based on the Receiver Operating Characteristic Curve

Abstract: The use of biomarkers is of ever-increasing importance in clinical diagnosis of disease. In practice, a cutpoint is required for dichotomizing naturally continuous biomarker levels to distinguish persons at risk of disease from those who are not. Two methods commonly used for establishing the "optimal" cutpoint are the point on the receiver operating characteristic curve closest to (0,1) and the Youden index, J. Both have sound intuitive interpretations--the point closest to perfect differentiation and the point farthest from none, respectively--and are generalizable to weighted sensitivity and specificity. Under the same weighting of sensitivity and specificity, these two methods identify the same cutpoint as "optimal" in certain situations but different cutpoints in others. In this paper, the authors examine situations in which the two criteria agree or disagree and show that J is the only "optimal" cutpoint for given weighting with respect to overall misclassification rates. A data-driven example is used to clarify and demonstrate the magnitude of the differences. The authors also demonstrate a slight alteration in the (0,1) criterion that retains its intuitive meaning while resulting in consistent agreement with J. In conclusion, the authors urge that great care be taken when establishing a biomarker cutpoint for clinical use.

Leukocyte Telomere Length and Cardiovascular Disease in the Cardiovascular Health Study

Abstract: The telomere length of replicating somatic cells is inversely correlated with age and has been reported to be associated cross-sectionally with cardiovascular disease (CVD) Leukocyte telomere length, as expressed by mean terminal restriction fragment (TRF) length, was measured in 419 randomly selected participants from the Cardiovascular Health Study, comprising a community-dwelling cohort recruited in four US communities The authors investigated associations between TRF length and selected measures of subclinical CVD/risk factors for CVD (data were collected at the 1992/1993 clinic visit) and incident CVD (ascertained through June 2002) In these participants (average age = 742 years (standard deviation, 52)), mean TRF length was 63 kilobase pairs (standard deviation, 062) Significant or borderline inverse associations were found between TRF length and diabetes, glucose, insulin, diastolic blood pressure, carotid intima-media thickness, and interleukin-6 Associations with body size and C-reactive protein were modified by gender and age, occurring only in men and in participants aged 73 years or younger In younger (but not older) participants, each shortened kilobase pair of TRF corresponded with a threefold increased risk of myocardial infarction (hazard ratio = 308, 95% confidence interval: 122, 773) and stroke (hazard ratio = 322, 95% confidence interval: 129, 802) These results support the hypotheses that telomere attrition may be related to diseases of aging through mechanisms involving oxidative stress, inflammation, and progression to CVD

Using Data on Social Contacts to Estimate Age-specific Transmission Parameters for Respiratory-spread Infectious Agents

Abstract: The estimation of transmission parameters has been problematic for diseases that rely predominantly on transmission of pathogens from person to person through small infectious droplets. Age-specific transmission parameters determine how such respiratory agents will spread among different age groups in a human population. Estimating the values of these parameters is essential in planning an effective response to potentially devastating pandemics of smallpox or influenza and in designing control strategies for diseases such as measles or mumps. In this study, the authors estimated age-specific transmission parameters by augmenting infectious disease data with auxiliary data on self-reported numbers of conversational partners per person. They show that models that use transmission parameters based on these self-reported social contacts are better able to capture the observed patterns of infection of endemically circulating mumps, as well as observed patterns of spread of pandemic influenza. The estimated age-specific transmission parameters suggested that school-aged children and young adults will experience the highest incidence of infection and will contribute most to further spread of infections during the initial phase of an emerging respiratory-spread epidemic in a completely susceptible population. These findings have important implications for controlling future outbreaks of novel respiratory-spread infectious agents.

Results of Multivariable Logistic Regression, Propensity Matching, Propensity Adjustment, and Propensity-based Weighting under Conditions of Nonuniform Effect

Abstract: Observational studies often provide the only available information about treatment effects. Control of confounding, however, remains challenging. The authors compared five methods for evaluating the effect of tissue plasminogen activator on death among 6,269 ischemic stroke patients registered in a German stroke registry: multivariable logistic regression, propensity score–matched analysis, regression adjustment with the propensity score, and two propensity score–based weighted methods—one estimating the treatment effect in the entire study population (inverseprobability-of-treatment weights), another in the treated population (standardized-mortality-ratio weights). Between 2000 and 2001, 212 patients received tissue plasminogen activator. The crude odds ratio between tissue plasminogen activator and death was 3.35 (95% confidence interval: 2.28, 4.91). The adjusted odds ratio depended strongly on the adjustment method, ranging from 1.11 (95% confidence interval: 0.67, 1.84) for the standardized-mortality-ratio weighted to 10.77 (95% confidence interval: 2.47, 47.04) for the inverse-probability-of-treatment-weighted analysis. For treated patients with a low propensity score, risks of dying were high. Exclusion of patients with a propensity score of <5% yielded comparable odds ratios of approximately 1 for all methods. High levels of nonuniform treatment effect render summary estimates very sensitive to the weighting system explicit or implicit in an adjustment technique. Researchers need to be clear about the population for which an overall treatment estimate is most suitable. causality; cerebrovascular accident; confounding factors (epidemiology); data interpretation, statistical; logistic models; models, statistical; observational study

Prevalence and Determinants of Lateral and Medial Epicondylitis: A Population Study

Abstract: Epicondylitis is a common disorder of the arm, yet the role of individual- and work-related factors has not been addressed in a population study. The aims of this study were to estimate the prevalence of lateral and medial epicondylitis and to investigate their risk factors. The target population of this study comprised a representative sample of people aged 30-64 years residing in Finland during 2000-2001. Of the 5,871 subjects, 4,783 (81.5%) were included in this study. The prevalence of definite lateral epicondylitis was 1.3%, and that of medial epicondylitis was 0.4%. The prevalence did not differ between men and women and was highest in subjects aged 45-54 years. Current smoking (adjusted odds ratio (OR) = 3.4, 95% confidence interval (CI): 1.4, 8.3) and former smoking (OR = 3.0, 95% CI: 1.3, 6.6) were associated with definite lateral epicondylitis. An interaction (p = 0.002) was found between repetitive movements of the arms and forceful activities for the risk of possible or definite lateral epicondylitis (for both repetitive and forceful activities vs. no such activity: OR = 5.6, 95% CI: 1.9, 16.5). Smoking, obesity, repetitive movements, and forceful activities independently of each other showed significant associations with medial epicondylitis. Epicondylitis is relatively common among working-age individuals in the general population. Physical load factors, smoking, and obesity are strong determinants of epicondylitis.

Association between Reduced Sleep and Weight Gain in Women

Abstract: Physiologic studies suggest that sleep restriction has metabolic effects that predispose to weight gain. The authors investigated the association between self-reported usual sleep duration and subsequent weight gain in the Nurses' Health Study. The 68,183 women who reported habitual sleep duration in 1986 were followed for 16 years. In analyses adjusted for age and body mass index, women sleeping 5 hours or less gained 1.14 kg (95% confidence interval (CI): 0.49, 1.79) more than did those sleeping 7 hours over 16 years, and women sleeping 6 hours gained 0.71 kg (95% CI: 0.41, 1.00) more. The relative risks of a 15-kg weight gain were 1.32 (95% CI: 1.19, 1.47) and 1.12 (95% CI: 1.06, 1.19) for those sleeping 5 and 6 hours, respectively. The relative risks for incident obesity (body mass index: >30 kg/m(2)) were 1.15 (95% CI: 1.04, 1.26) and 1.06 (95% CI: 1.01, 1.11). These associations remained significant after inclusion of important covariates and were not affected by adjustment for physical activity or dietary consumption. These data suggest that short sleep duration is associated with a modest increase in future weight gain and incident obesity. Further research is needed to understand the mechanisms by which sleep duration may affect weight.

Objectively Measured Sleep Characteristics among Early-Middle-Aged Adults The CARDIA Study

Abstract: Despite mounting evidence that sleep duration is a risk factor across diverse health and functional domains, little is known about the distribution and determinants of sleep. In 2003-2004, the authors used wrist activity monitoring and sleep logs to measure time in bed, sleep latency (time required to fall asleep), sleep duration, and sleep efficiency (percentage of time in bed spent sleeping) over 3 days for 669 participants at one of the four sites of the Coronary Artery Risk Development in Young Adults (CARDIA) study (Chicago, Illinois). Participants were aged 38-50 years, 58% were women, and 44% were Black. For the entire sample, mean time in bed was 7.5 (standard deviation (SD), 1.2) hours, mean sleep latency was 21.9 (SD, 29.0) minutes, mean sleep duration was 6.1 (SD, 1.2) hours, and mean sleep efficiency was 80.9 (SD, 11.3)%. All four parameters varied by race-sex group. Average sleep duration was 6.7 hours for White women, 6.1 hours for White men, 5.9 hours for Black women, and 5.1 hours for Black men. Race-sex differences (p < 0.001) remained after adjustment for socioeconomic, employment, household, and lifestyle factors and for apnea risk. Income was independently associated with sleep latency and efficiency. Sleep duration and quality, which have consequences for health, are strongly associated with race, sex, and socioeconomic status.

Bladder Cancer and Exposure to Water Disinfection By-Products through Ingestion, Bathing, Showering, and Swimming in Pools

Abstract: Bladder cancer has been associated with exposure to chlorination by-products in drinking water, and experimental evidence suggests that exposure also occurs through inhalation and dermal absorption. The authors examined whether bladder cancer risk was associated with exposure to trihalomethanes (THMs) through ingestion of water and through inhalation and dermal absorption during showering, bathing, and swimming in pools. Lifetime personal information on water consumption and water-related habits was collected for 1,219 cases and 1,271 controls in a 1998-2001 case-control study in Spain and was linked with THM levels in geographic study areas. Long-term THM exposure was associated with a twofold bladder cancer risk, with an odds ratio of 2.10 (95% confidence interval: 1.09, 4.02) for average household THM levels of >49 versus 35 micro g/day through ingestion had an odds ratio of 1.35 (95% confidence interval: 0.92, 1.99). The odds ratio for duration of shower or bath weighted by residential THM level was 1.83 (95% confidence interval: 1.17, 2.87) for the highest compared with the lowest quartile. Swimming in pools was associated with an odds ratio of 1.57 (95% confidence interval: 1.18, 2.09). Bladder cancer risk was associated with long-term exposure to THMs in chlorinated water at levels regularly occurring in industrialized countries.

Bias in Clinical Intervention Research

Abstract: Research on bias in clinical trials may help identify some of the reasons why investigators sometimes reach the wrong conclusions about intervention effects. Several quality components for the assessment of bias control have been suggested, but although they seem intrinsically valid, empirical evidence is needed to evaluate their effects on the extent and direction of bias. This narrative review summarizes the findings of methodological studies on the influence of bias in clinical trials. A number of methodological studies suggest that lack of adequate randomization in published trial reports may be associated with more positive estimates of intervention effects. The influence of double-blinding and follow-up is less clear. Several studies have found a significant association between funding sources and pro-industry conclusions. However, the methodological studies also show that bias is difficult to detect and appraise. The extent of bias in individual trials is unpredictable. A-priori exclusion of trials with certain characteristics is not recommended. Appraising bias control in individual trials is necessary to avoid making incorrect conclusions about intervention effects.

Reporting Participation in Epidemiologic Studies: A Survey of Practice

Abstract: Self-selection bias may threaten the internal validity of epidemiologic studies. Studies with a low level of participation are particularly vulnerable to this bias, and commentators note apparent declines in participation in recent years. The authors therefore conducted a retrospective review to survey the practice of reporting participation in epidemiologic studies, to assess changes in participation over time, and to evaluate the impact of increased biologic specimen collection on participation. The authors abstracted selected study characteristics from 355 peer-reviewed, original, analytic-epidemiology research articles published from January 1 to April 30, 2003, in 10 high-impact general epidemiology, public health, and medical journals. At least some information regarding participation was provided in 59% of cross-sectional studies, 44% of case-control studies, and 32% of cohort studies. Participation appears to have declined during 1970–2003 for all study designs. Participation declined most steeply for controls in population-based, case-control studies (� 1.86% per year, 95% confidence interval: � 3.03, � 0.69), with steeper declines after 1990. Proportionately more studies collected biologic specimens over time, particularly for cohort and case-control study designs (ptrend ¼ 0.06 and 0.03, respectively), yet participation was reported separately for the biologic specimen study component in only 27% of studies. The authors conclude that epidemiologists need to address declining participation and to report participation consistently, including for biologic specimen collection. blood specimen collection; case-control studies; cohort studies; cross-sectional studies; epidemiologic methods; patient participation

The Effect of Ozone and PM10 on Hospital Admissions for Pneumonia and Chronic Obstructive Pulmonary Disease: A National Multicity Study

Abstract: A case-crossover study was conducted in 36 US cities to evaluate the effect of ozone and particulate matter with an aerodynamic diameter of < or =10 microm (PM10) on respiratory hospital admissions and to identify which city characteristics may explain the heterogeneity in risk estimates. Respiratory hospital admissions and air pollution data were obtained for 1986-1999. In a meta-analysis based on the city-specific regression models, several city characteristics were evaluated as effect modifiers. During the warm season, the 2-day cumulative effect of a 5-ppb increase in ozone was a 0.27% (95% confidence interval (CI): 0.08, 0.47) increase in chronic obstructive pulmonary disease admissions and a 0.41% (95% CI: 0.26, 0.57) increase in pneumonia admissions. Similarly, a 10-microg/m(3) increase in PM10 during the warm season resulted in a 1.47% (95% CI: 0.93, 2.01) increase in chronic obstructive pulmonary disease at lag 1 and a 0.84% (95% CI: 0.50, 1.19) increase in pneumonia at lag 0. Percentage of households with central air conditioning reduced the effect of air pollution, and variability of summer apparent temperature reduced the effect of ozone on chronic obstructive pulmonary disease. The study confirmed, in a large sample of cities, that exposure to ozone and PM10 is associated with respiratory hospital admissions and provided evidence that the effect of air pollution is modified by certain city characteristics.

Prospective Cohort Study of the Risk of Prostate Cancer among Rotating-Shift Workers: Findings from the Japan Collaborative Cohort Study

Abstract: Shift workers have been reported to have an increased risk of some cancers. However, the risk of prostate cancer in shift workers is not known to have been examined previously. This study prospectively examined the association between shift work and risk of prostate cancer incidence among 14,052 working men in Japan enrolled in a large-scale prospective cohort. A baseline survey was conducted between 1988 and 1990. Subjects were asked to indicate the most regular work schedule they had undertaken previously: day work, rotating-shift work, or fixed-night work. During 111,974 person-years, 31 cases of prostate cancer were recorded. The Cox proportional hazards model was used to estimate the risk, with adjustments for age, family history of prostate cancer, study area surveyed, body mass index, smoking, alcohol drinking, job type, physical activity at work, workplace, perceived stress, educational level, and marriage status. Compared with day workers, rotating-shift workers were significantly at risk for prostate cancer (relative risk = 3.0, 95% confidence interval: 1.2, 7.7), whereas fixed-night work was associated with a small and nonsignificant increase in risk. This report is the first known to reveal a significant relation between rotating-shift work and prostate cancer.

Individual-Level Modifiers of the Effects of Particulate Matter on Daily Mortality

Abstract: Consistent evidence has shown a positive association between particulate matter with an aerodiameter of less than or equal to 10 mum (PM(10)) and daily mortality. Less is known about the modification of this association by factors measured at the individual level. The authors examined this question in a case-crossover study of 20 US cities. Mortality events (1.9 million) were obtained for nonaccidental, respiratory, heart disease, and stroke mortality between 1989 and 2000. PM(10) concentrations were obtained from the US Environmental Protection Agency. The authors examined the modification of the PM(10)-mortality association by sociodemographics, location of death, season, and secondary diagnoses. They found different patterns of PM(10)-mortality associations by gender and age but no differences by race. The level of education was inversely related to the risk of mortality associated with PM(10). PM(10)-related, out-of-hospital deaths were more likely than were in-hospital deaths, as were those occurring during spring/fall versus summer/winter. A secondary diagnosis of diabetes modified the effect of PM(10) for respiratory and stroke mortality. Pneumonia was a positive effect modifier for deaths from all causes and stroke, while secondary stroke modified the effects for all-cause and respiratory deaths. The findings suggest that more attention must be paid to population characteristics to identify greater likelihood of exposures and susceptibility and, as a result, to improve policy making for air pollution standards.

Methylenetetrahydrofolate Reductase (MTHFR) Genetic Polymorphisms and Psychiatric Disorders: A HuGE Review

Abstract: The authors performed a meta-analysis of studies examining the association between polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, including MTHFR C677T and A1298C, and common psychiatric disorders, including unipolar depression, anxiety disorders, bipolar disorder, and schizophrenia. The primary comparison was between homozygote variants and the wild type for MTHFR C677T and A1298C. For unipolar depression and the MTHFR C677T polymorphism, the fixed-effects odds ratio for homozygote variants (TT) versus the wild type (CC) was 1.36 (95% confidence interval (CI): 1.11, 1.67), with no residual between-study heterogeneity (I(2) = 0%)--based on 1,280 cases and 10,429 controls. For schizophrenia and MTHFR C677T, the fixed-effects odds ratio for TT versus CC was 1.44 (95% CI: 1.21, 1.70), with low heterogeneity (I(2) = 42%)--based on 2,762 cases and 3,363 controls. For bipolar disorder and MTHFR C677T, the fixed-effects odds ratio for TT versus CC was 1.82 (95% CI: 1.22, 2.70), with low heterogeneity (I(2) = 42%)-based on 550 cases and 1,098 controls. These results were robust to various sensitively analyses. This meta-analysis demonstrates an association between the MTHFR C677T variant and depression, schizophrenia, and bipolar disorder, raising the possibility of the use of folate in treatment and prevention.

Characterizing the Course of Low Back Pain: A Latent Class Analysis

Abstract: Understanding the course of back pain is important for clinicians and researchers, but analyses of longitudinal data from multiple time points are lacking. A prospective cohort study of consecutive back pain consulters from five general practices in the United Kingdom was carried out between 2001 and 2003 to identify groups defined by their pain pathways. Patients were sent monthly questionnaires for a year. Longitudinal latent class analysis was performed by using pain intensity scores for 342 consulters. Analysis yielded four clusters representing different pathways of back pain. Cluster 1 ("persistent mild"; n = 122) patients had stable, low levels of pain. Patients in cluster 2 ("recovering"; n = 104) started with mild pain, progressing quickly to no pain. Cluster 3 ("severe chronic"; n = 71) patients had permanently high pain. For patients in cluster 4 ("fluctuating"; n = 45), pain varied between mild and high levels. Distinctive patterns for each cluster were maintained throughout follow-up. Clusters showed statistically significant differences in disability, psychological status, and work absence (p < 0.001). This is the first time, to the authors' knowledge, that latent class analysis has been applied to longitudinal data on back pain patients. Identification of four distinct groups of patients improves understanding of the course of back pain and may provide a basis of classification for intervention.

The Birth Weight “Paradox” Uncovered?

Abstract: Low birth weight (LBW) infants have lower infant mortality in groups in which LBW is most frequent. For example, in 1991, US infants born to smokers had higher risks of both LBW and infant mortality than infants born to nonsmokers. However, among LBW infants, infant mortality was lower for infants born to smokers (relative rate = 0.79). There are competing theories regarding this so-called "paradox." One is that maternal smoking is beneficial for LBW infants. The authors use causal diagrams to show that, even in the absence of any beneficial effect of smoking, an inverse association due to stratification on birth weight can be found. This variable is affected by the exposure of interest and shares common causes with the outcome. That is, LBW infants born to smokers may have a lower risk of mortality than other LBW infants whose LBW is due to causes associated with high mortality (e.g., birth defects). Under realistic causal diagrams, adjustment for birth weight is unwarranted when the analytical goal is to estimate overall effects of prenatal variables on infant mortality. Even for estimating direct effects of prenatal variables, adjustment for birth weight may be invalid when there is an unmeasured common cause of LBW and mortality. An appropriate justification for conditioning on birth weight requires specifying 1) the causal question motivating this analytical approach and 2) the assumptions regarding the proposed underlying biologic mechanisms.

Pesticide Exposure and Self-reported Parkinson's Disease in the Agricultural Health Study

Abstract: Previous studies based on limited exposure assessment have suggested that Parkinson's disease (PD) is associated with pesticide exposure The authors used data obtained from licensed private pesticide applicators and spouses participating in the Agricultural Health Study to evaluate the relation of self-reported PD to pesticide exposure Cohort members, who were enrolled in 1993-1997, provided detailed information on lifetime pesticide use At follow-up in 1999-2003, 68% of the cohort was interviewed Cases were defined as participants who reported physician-diagnosed PD at enrollment (prevalent cases, n = 83) or follow-up (incident cases, n = 78) Cases were compared with cohort members who did not report PD (n = 79,557 at enrollment and n = 55,931 at follow-up) Incident PD was associated with cumulative days of pesticide use at enrollment (for highest quartile vs lowest, odds ratio (OR) = 23, 95% confidence interval: 12, 45; p-trend = 0009), with personally applying pesticides more than half the time (OR = 19, 95% confidence interval: 07, 47), and with some specific pesticides (ORs > or = 14) Prevalent PD was not associated with overall pesticide use This study suggests that exposure to certain pesticides may increase PD risk Findings for specific chemicals may provide fruitful leads for further investigation

Curry Consumption and Cognitive Function in the Elderly

Abstract: Curcumin, from the curry spice turmeric, has been shown to possess potent antioxidant and antiinflammatory properties and to reduce beta-amyloid and plaque burden in experimental studies, but epidemiologic evidence is lacking. The authors investigated the association between usual curry consumption level and cognitive function in elderly Asians. In a population-based cohort (n = 1,010) of nondemented elderly Asian subjects aged 60-93 years in 2003, the authors compared Mini-Mental State Examination (MMSE) scores for three categories of regular curry consumption, taking into account known sociodemographic, health, and behavioral correlates of MMSE performance. Those who consumed curry "occasionally" and "often or very often" had significantly better MMSE scores than did subjects who "never or rarely" consumed curry. The authors reported tentative evidence of better cognitive performance from curry consumption in nondemented elderly Asians, which should be confirmed in future studies.

The Effect of Social Engagement on Incident Dementia The Honolulu-Asia Aging Study

Abstract: The authors examined whether low levels of social engagement in midlife and late life were associated with the risk of incident dementia in 2,513 Japanese-American men who have been followed since 1965 as part of the Honolulu Heart Program and the Honolulu-Asia Aging Study. In 1991, assessment of dementia began; incident dementia cases (n = 222) were diagnosed in 1994 and 1997. Social engagement was assessed in midlife (1968) and late life (1991). The relation between social engagement and dementia risk was examined using Cox proportional hazards models. No level of midlife social engagement was associated with the risk of dementia. In late life, compared with participants in the highest quartile of late-life social engagement, those in the lowest quartile had a significantly increased risk of dementia (hazard ratio = 2.34, 95% confidence interval: 1.18, 4.65). However, compared with those who were in the highest quartile of social engagement at both midlife and late life, only decreased social engagement from midlife to late life was associated with an increased risk of dementia (hazard ratio = 1.87, 95% confidence interval: 1.12, 3.13). Although low social engagement in late life is associated with risk of dementia, levels of late-life social engagement may already have been modified by the dementing process and may be associated with prodromal dementia.

Cigarette Smoking and Nocturnal Sleep Architecture

Abstract: Cigarette smoking has been associated with a high prevalence of sleep-related complaints. However, its effects on sleep architecture have not been fully examined. The primary objective of this investigation was to assess the impact of cigarette smoking on sleep architecture. Polysomnography was used to characterize sleep architecture among 6,400 participants of the Sleep Heart Health Study (United States, 1994-1999). Sleep parameters included total sleep time, latency to sleep onset, sleep efficiency, and percentage of time in each sleep stage. The study sample consisted of 2,916 never smokers, 2,705 former smokers, and 779 current smokers. Compared with never smokers, current smokers had a longer initial sleep latency (5.4 minutes, 95% confidence interval (CI): 2.9, 7.9) and less total sleep time (14.0 minutes, 95% CI: 6.4, 21.7). Furthermore, relative to never smokers, current smokers also had more stage 1 sleep (relative proportion = 1.24, 95% CI: 1.14, 1.33) and less slow wave sleep (relative proportion = 0.86, 95% CI: 0.78, 0.95). Finally, no differences in sleep architecture were noted between former and never smokers. The results of this study show that cigarette smoking is independently associated with disturbances in sleep architecture, including a longer latency to sleep onset and a shift toward lighter stages of sleep. Nicotine in cigarette smoke and acute withdrawal from it may contribute to disturbances in sleep architecture.

Pragmatic Randomized Trial Evaluating the Clinical and Economic Effectiveness of Acupuncture for Chronic Low Back Pain

Abstract: In a randomized controlled trial plus a nonrandomized cohort, the authors investigated the effectiveness and costs of acupuncture in addition to routine care in the treatment of chronic low back pain and assessed whether the effects of acupuncture differed in randomized and nonrandomized patients. In 2001, German patients with chronic low back pain were allocated to an acupuncture group or a no-acupuncture control group. Persons who did not consent to randomization were included in a nonrandomized acupuncture group. All patients were allowed to receive routine medical care in addition to study treatment. Back function (Hannover Functional Ability Questionnaire), pain, and quality of life were assessed at baseline and after 3 and 6 months, and cost-effectiveness was analyzed. Of 11,630 patients (mean age=52.9 years (standard deviation, 13.7); 59% female), 1,549 were randomized to the acupuncture group and 1,544 to the control group; 8,537 were included in the nonrandomized acupuncture group. At 3 months, back function improved by 12.1 (standard error (SE), 0.4) to 74.5 (SE, 0.4) points in the acupuncture group and by 2.7 (SE, 0.4) to 65.1 (SE, 0.4) points among controls (difference=9.4 points (95% confidence interval 8.3, 10.5); p<0.001). Nonrandomized patients had more severe symptoms at baseline and showed improvements in back function similar to those seen in randomized patients. The incremental cost-effectiveness ratio was euro10,526 (euros) per quality-adjusted life year. Acupuncture plus routine care was associated with marked clinical improvements in these patients and was relatively cost-effective.

Methods for pooling results of epidemiologic studies: The pooling project of prospective studies of diet and cancer

Abstract: With the growing number of epidemiologic publications on the relation between dietary factors and cancer risk, pooled analyses that summarize results from multiple studies are becoming more common. Here, the authors describe the methods being used to summarize data on diet-cancer associations within the ongoing Pooling Project of Prospective Studies of Diet and Cancer, begun in 1991. In the Pooling Project, the primary data from prospective cohort studies meeting prespecified inclusion criteria are analyzed using standardized criteria for modeling of exposure, confounding, and outcome variables. In addition to evaluating main exposure-disease associations, analyses are also conducted to evaluate whether exposure-disease associations are modified by other dietary and nondietary factors or vary among population subgroups or particular cancer subtypes. Study-specific relative risks are calculated using the Cox proportional hazards model and then pooled using a random- or mixed-effects model. The study-specific estimates are weighted by the inverse of their variances in forming summary estimates. Most of the methods used in the Pooling Project may be adapted for examining associations with dietary and nondietary factors in pooled analyses of case-control studies or case-control and cohort studies combined.

Arsenic Exposure from Drinking Water and Risk of Premalignant Skin Lesions in Bangladesh: Baseline Results from the Health Effects of Arsenic Longitudinal Study

Abstract: Millions of persons around the world are exposed to low doses of arsenic through drinking water. However, estimates of health effects associated with low-dose arsenic exposure have been extrapolated from high-dose studies. In Bangladesh, many persons have been exposed to a wide range of doses of arsenic from drinking water over a significant period of time. The authors evaluated dose-response relations between arsenic exposure from drinking water and premalignant skin lesions by using baseline data on 11,746 participants recruited in 2000-2002 for the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh. Several measures of arsenic exposure were estimated for each participant based on well-water arsenic concentration and usage pattern of the wells and on urinary arsenic concentration. In different regression models, consistent dose-response effects were observed for all arsenic exposure measures. Compared with drinking water containing <8.1 microg/liter of arsenic, drinking water containing 8.1-40.0, 40.1-91.0, 91.1-175.0, and 175.1-864.0 microg/liter of arsenic was associated with adjusted prevalence odds ratios of skin lesions of 1.91 (95% confidence interval (CI): 1.26, 2.89), 3.03 (95% CI: 2.05, 4.50), 3.71 (95% CI: 2.53, 5.44), and 5.39 (95% CI: 3.69, 7.86), respectively. The effect seemed to be influenced by gender, age, and body mass index. These findings provide information that should be considered in future research and policy decisions.

Psychosocial Work Environment and Incidence of Severe Depressive Symptoms: Prospective Findings from a 5-Year Follow-up of the Danish Work Environment Cohort Study

Abstract: The authors analyzed the impact of psychosocial work characteristics on the incidence of severe depressive symptoms among 4,133 (49% women) employees from a representative sample of the Danish workforce between 1995 and 2000. Psychosocial work characteristics at baseline included quantitative demands, influence at work, possibilities for development, social support from supervisors and coworkers, and job insecurity. Severe depressive symptoms were measured with the five-item Mental Health Inventory of the 36-item Short-Form Health Survey, with a cutoff point of 52. Women with low influence at work (relative risk (RR) = 2.17, 95% confidence interval (CI): 1.23, 3.82) and low supervisor support (RR = 2.03, 95% CI: 1.20, 3.43) were at increased risk for severe depressive symptoms after exclusion of cases at baseline and adjustment for sociodemographic factors, baseline depression score, and health behaviors. Further adjustments for socioeconomic position did not change the result substantially. Additional analyses showed that a one-standard deviation increase on the influence scale resulted in a 27% decreased risk of severe depressive symptoms. Among men, job insecurity predicted severe depressive symptoms (RR = 2.04, 95% CI: 1.02, 4.07). The findings indicate that the work environment influences the risk of developing severe depressive symptoms and that different factors play a role for men and women.

Reproducible Epidemiologic Research

Abstract: The replication of important findings by multiple independent investigators is fundamental to the accumulation of scientific evidence. Researchers in the biologic and physical sciences expect results to be replicated by independent data, analytical methods, laboratories, and instruments. Epidemiologic studies are commonly used to quantify small health effects of important, but subtle, risk factors, and replication is of critical importance where results can inform substantial policy decisions. However, because of the time, expense, and opportunism of many current epidemiologic studies, it is often impossible to fully replicate their findings. An attainable minimum standard is "reproducibility," which calls for data sets and software to be made available for verifying published findings and conducting alternative analyses. The authors outline a standard for reproducibility and evaluate the reproducibility of current epidemiologic research. They also propose methods for reproducible research and implement them by use of a case study in air pollution and health.

Mortality due to Influenza in the United States—An Annualized Regression Approach Using Multiple-Cause Mortality Data

Abstract: Influenza is an important cause of mortality in temperate countries, but there is substantial controversy as to the total direct and indirect mortality burden imposed by influenza viruses The authors have extracted multiple-cause death data from public-use data files for the United States from 1979 to 2001 The current research reevaluates attribution of deaths to influenza, by use of an annualized regression approach: comparing measures of excess deaths with measures of influenza virus prevalence by subtype over entire influenza seasons and attributing deaths to influenza by a regression model This approach is more conservative in its assumptions than is earlier work, which used weekly regression models, or models based on fitting baselines, but it produces results consistent with these other methods, supporting the conclusion that influenza is an important cause of seasonal excess deaths The regression model attributes an annual average of 41,400 (95% confidence interval: 27,100, 55,700) deaths to influenza over the period 1979-2001 The study also uses regional death data to investigate the effects of cold weather on annualized excess deaths

Impact of violations and deviations in Hardy-Weinberg equilibrium on postulated gene-disease associations.

Abstract: The authors evaluated whether statistically significant violations of Hardy-Weinberg equilibrium (HWE) or the magnitude of deviations from HWE may contribute to the problem of replicating postulated gene-disease associations across different studies Forty-two gene-disease associations assessed in meta-analyses of 591 studies were examined Studies with disease-free controls in which HWE was violated gave significantly different results from HWE-conforming studies in five instances Exclusion of the former studies resulted in loss of statistical significance of the overall meta-analysis in three instances and more than a 10% change in the summary odds ratio in six Exclusion of HWE-violating studies changed the formal significance of the estimated between-study heterogeneity in three instances After adjustment for the magnitude of the deviation from HWE for the controls, formal significance was lost in another three instances Studies adjusted for the magnitude of deviation from HWE tended to become more heterogeneous among themselves, and, for seven gene-disease associations, between-study heterogeneity became significant, while it was not so in the unadjusted analyses Gene-disease association studies and meta-analyses thereof should routinely scrutinize the potential impact of HWE violations as well as nonsignificant deviations from the exact frequencies expected under HWE Postulated genetic associations with modest-sized odds ratios and borderline statistical significance may not be robust in such sensitivity analyses

Epidemiologic Evidence for the Fetal Overnutrition Hypothesis: Findings from the Mater-University Study of Pregnancy and Its Outcomes

Abstract: The fetal overnutrition hypothesis proposes that greater maternal adiposity results in increased obesity throughout life in the offspring. The authors examined the associations between parental prepregnancy body mass index (BMI; weight (kg)/height (m)(2)), based on height and weight reported by the mother at her first antenatal clinic visit, and offspring BMI (height and weight measured at age 14 years) in 3,340 parent-offspring trios from a birth cohort based in Brisbane, Australia (mothers were recruited in 1981-1984). The maternal-offspring BMI association was stronger than the paternal-offspring BMI association. In the fully adjusted model, the increase in standardized offspring BMI at age 14 for a one-standard-deviation (SD) increase in maternal BMI was 0.362 SD (95% confidence interval: 0.323, 0.402), and the corresponding result for a one-SD increase in paternal BMI was 0.239 SD (95% confidence interval: 0.197, 0.282). There was statistical support for a difference in the magnitude of the association between maternal-offspring BMI and paternal-offspring BMI in all confounder-adjusted models tested (all p's < 0.0001). In sensitivity analyses taking account of different plausible levels of nonpaternity (up to 15%), the greater maternal effect remained. These findings provide some support for the fetal overnutrition hypothesis.

Association of Body Mass Index and Weight Change with All-Cause Mortality in the Elderly

Abstract: The authors explored the relation of body mass index (BMI; weight (kg)/height (m)(2)) and weight change to all-cause mortality in the elderly, using data from a large, population-based California cohort study, the Leisure World Cohort Study. They estimated relative risks of mortality associated with self-reported BMI at study entry, BMI at age 21 years, and weight change between age 21 and study entry. Participants were categorized as underweight (BMI or=30). Of 13,451 participants aged 73 years (on average) at study entry (1981-1985), 11,203 died during 23 years of follow-up (1981-2004). Relative to normal weight, being underweight (relative risk (RR) = 1.51, 95% confidence interval (CI): 1.38, 1.65) or obese (RR = 1.25, 95% CI: 1.13, 1.38) at study entry was associated with increased mortality. People who were either overweight or obese at age 21 also had increased mortality (RR = 1.17, 95% CI: 1.09, 1.25). Participants who lost weight between age 21 and study entry had increased mortality regardless of their BMI category at age 21. Obesity was significantly associated with increased mortality only among persons under age 75 years and among never or past smokers. This study highlights the influence on older-age mortality risk of being overweight or obese in young adulthood and underweight or obese in later life.