Sleep quality following hematopoietic stem cell transplantation: longitudinal trajectories and biobehavioral correlates.

The present study examined changes in sleep quality following hematopoietic stem cell transplantation (HSCT) and investigated associations with biobehavioral factors. Individuals undergoing HSCT for hematologic malignancies (N=228) completed measures of sleep quality and psychological symptoms pre-transplant and 1, 3, 6 and 12 months post transplant. Circulating inflammatory cytokines (IL-6, TNF-α) were also assessed. Sleep quality was poorest at 1 month post transplant, improving and remaining relatively stable after 3 months post transplant. However, approximately half of participants continued to experience significant sleep disturbance at 6 and 12 months post transplant. Mixed-effects linear regression models indicated that depression and anxiety were associated with poorer sleep quality, while psychological well-being was associated with better sleep. Higher circulating levels of IL-6 were also linked with poorer sleep. Subject-level fixed effects models demonstrated that among individual participants, changes in depression, anxiety and psychological well-being were associated with corresponding changes in sleep after covarying for the effects of time since transplant. Sleep disturbance was most severe when depression and anxiety were greatest and psychological well-being was lowest. Findings indicate that sleep disturbance is a persistent problem during the year following HSCT. Patients experiencing depression or anxiety and those with elevated inflammation may be at particular risk for poor sleep.

Is maternal smoking during pregnancy a causal environmental risk factor for adolescent antisocial behavior? Testing etiological theories and assumptions.

BACKGROUND: Although many studies indicate that maternal smoking during pregnancy (SDP) is correlated with later offspring antisocial behavior (ASB), recent quasi-experimental studies suggest that background familial factors confound the association. The present study sought to test alternative etiological hypotheses using multiple indices of adolescent ASB, comparing differentially exposed siblings, and testing assumptions in the sibling-comparison design. METHOD: The study examined the association between maternal SDP and adolescent-reported ASB, criminal convictions and membership in a group of individuals with early-starting and chronic ASB among 6066 offspring of women from the National Longitudinal Survey of Youth, a representative sample of women in the USA. The analyses controlled for statistical covariates and examined associations while comparing differentially exposed siblings. RESULTS: At the population level, each additional pack of cigarettes per day predicted greater mean adolescent-reported ASB symptoms [ratio of means 1.15, 95% confidence interval (CI) 1.08-1.22], odds of being in the top 10% of ASB [odds ratio (OR) 1.34, 95% CI 1.10-1.65], hazard of a criminal conviction [hazard ratio (HR) 1.51, 95% CI 1.34-1.68] and odds of chronic ASB (OR 1.57, 95% CI 1.25-1.99). SDP robustly predicted most assessments of ASB while controlling for measured covariates. When siblings exposed to differing levels of SDP were compared, however, all of the associations were attenuated and were not statistically significant: adolescent-reported mean ASB (ratio of means 0.86, 95% CI 0.74-1.01), high ASB (OR 0.67, 95% CI 0.41-1.12), criminal conviction (HR 0.98, 95% CI 0.66-1.44) and chronic ASB (OR 0.80, 95% CI 0.46-1.38). CONCLUSIONS: The results strongly suggest that familial factors account for the correlation between SDP and offspring adolescent ASB, rather than a putative causal environmental influence of SDP.

Father absence and familial antisocial characteristics.

This study examined family antisocial characteristics according to whether biological fathers live at home and agree to be study participants. Antisocial symptoms were tabulated for 161 clinic-referred children and their parents. Families with fathers at home had fewer paternal, maternal, and child antisocial symptoms, and scored higher on multiple SES indicators, than did families with departed fathers. Antisocial characteristics were highest, and SES was lowest, when fathers could not be located or recruited. Results suggest that requiring father participation (as in family-trio genetic designs) screens out the more antisocial families. Of clinical interest, antisocial behavior in any family member is more likely if the father is absent and nonparticipating. The heightened antisocial behavior in children associated with absent biological fathers was not mitigated by presence of stepfathers and was not accounted for by lower SES. The ethical use of mother report on absent fathers is discussed.

Antisocial personality, substance abuse, and exposure to parental violence in males referred for domestic violence.

This study investigated whether childhood disruptive behavior (hyperactivity, oppositional-defiance, conduct problems) plus adult psychopathic adjustment are associated with domestic violence. Adult males (n = 66) in diversion programs completed the Wender Utah Rating Scale (WURS), MMPI Psychopathic Deviate scale (PD), Conflict Tactics Scales representing themselves and their parents, and substance use measures. Substance use and lifespan antisocial personality (measured by high WURS and PD scores) were robust predictors of verbal and moderate physical domestic abuse. Violence in the family of origin was associated with abuse when tested alone, but failed to exhibit unique association with abuse when other predictors were taken into account. The possibility that antisocial batterers respond to contingencies by moderating physical harm, while persisting at psychological harm, is discussed.

Emergency department utilization by noninstitutionalized elders.

OBJECTIVES: To the best of the authors' knowledge, no nationally representative, population-based study has characterized the proportion of elders using the emergency department (ED) and factors associated with ED use by elders. This article describes the proportion of elder Medicare beneficiaries using the ED and identifies attributes associated with elder ED users as compared with nonusers. METHODS: The 1993 Medicare Current Beneficiary Survey was used, a national, population-based, cross-sectional survey of Medicare beneficiaries linked with Medicare claims data. The study population was limited to 9,784 noninstitutionalized individuals aged 66 years or older. The Andersen model of health service utilization was used, which explains variation in ED use through a combination of predisposing (demographic and social), enabling (access to care), and need (comorbidity and health status) characteristics. RESULTS: Eighteen percent of the sample used the ED at least once during 1993. Univariate analysis showed ED users were older; were less educated and lived alone; had lower income and higher Charlson Comorbidity Index scores; and were less satisfied with their ability to access care than nonusers (p < 0.01, chi-square). Logistic regression identified older age, less education, living alone, higher comorbidity scores, worse reported health, and increased difficulties with activities of daily living as factors associated with ED use (p < 0.05). Need characteristics predicted ED use with the greatest accuracy. CONCLUSIONS: The proportion of elder ED users is slightly higher than previously reported among Medicare beneficiaries. Need (comorbidity and health status) characteristics predict ED utilization with the greatest accuracy.

Body mass index in a US national sample of Asian Americans: effects of nativity, years since immigration and socioeconomic status.

OBJECTIVE: To examine body mass index (BMI) and the proportion overweight and obese among adults age 18-59 in the six largest Asian American ethnic groups (Chinese, Filipino, Asian Indian, Japanese, Korean, Vietnamese), and investigate whether BMI varies by nativity (foreign-vs native-born), years in US, or socioeconomic status. DESIGN: Cross-sectional interview data were pooled from the 1992-1995 National Health Interview Survey (NHIS). SUBJECTS: 254,153 persons aged 18-59 included in the 1992-1995 NHIS. Sample sizes range from 816 to 1940 for each of six Asian American ethnic groups. MEASUREMENTS: Self-reported height and weight used to calculate BMI and classify individuals as overweight (BMI > or = 25 kg/m2) or obese (BMI > or = 30 kg/m2), age, sex, years in the US, household income and household size. RESULTS: For men, the percentage overweight ranges from 17% of Vietnamese to 42% of Japanese, while the total male population is 57% overweight. For women, the percentage overweight ranges from 9% of Vietnamese and Chinese to 25% of Asian Indians, while the total female population is 38% overweight. The percentage of Asian Americans classified as obese is very low. Adjusted for age and ethnicity, the odds ratio for obese is 3.5 for women and 4.0 for men for US-vs foreign-born. Among the foreign-born, more years in the US is associated with higher risk of being overweight or obese. The association between household income for women is similar for US-born Asian Americans and Whites and Blacks, but is much weaker for foreign-born Asian Americans. CONCLUSIONS: While these data find low proportions of Asian Americans overweight at present, they also imply the proportion will increase with more US-born Asian Americans and longer duration in the US.

Age and gender differences in oppositional behavior and conduct problems: a cross-sectional household study of middle childhood and adolescence.

Behavior problems among youths cannot be understood without explaining their age and gender differences, but age and gender differences cannot be explained until they have been accurately described. In a household survey of 1,285 youths aged 9 to 17 years, there were no gender differences in oppositional behavior, but aggression, property offenses, and status offenses were more common among boys. Levels of oppositional behavior were greater at younger ages, aggression peaked near the middle of this age range, and property and status offenses were more prevalent at older ages. These findings are generally consistent with developmental models of conduct problems but are inconsistent with a recent model of gender differences and raise questions about the external validity of current taxonomies.

Low salivary cortisol and persistent aggression in boys referred for disruptive behavior.

BACKGROUND: Persistent antisocial behavior in adulthood is often preceded by childhood-onset aggressive conduct disorder. Aggressive syndromes in both children and adults have previously been associated with abnormalities in peripheral responses to stress. One peripheral measure, salivary cortisol concentration, may reflect individual differences in the hypothalamic-pituitary-adrenal axis that underlie propensities for aggression, socialization, and adaptation to stress. METHODS: The relationship between salivary cortisol levels and aggression was tested in 38 clinic-referred school-aged boys. Persistent aggression was measured by collecting disruptive behavior disorder symptoms in 4 annual clinical evaluations and peer nominations of aggression in the first 2 annual evaluations. Salivary cortisol levels were measured during years 2 and 4 of the study. RESULTS: Low cortisol levels were associated with persistence and early onset of aggression, particularly when measures of cortisol concentrations were pooled. Boys with low cortisol concentrations at both time points exhibited triple the number of aggressive symptoms and were named as most aggressive by peers 3 times as often as boys who had higher cortisol concentrations at either sampling time. CONCLUSIONS: This suggests that low hypothalamic-pituitary-adrenal axis activity is a correlate of severe and persistent aggression in male children and adolescents. A restricted (low) range of cortisol variability may be more indicative of persistent aggression than a low concentration of cortisol at any single point in time.

Evidence of environmental suppression of familial resemblance: height among US Civil War brothers.

This study examines, with historical data, whether within family correlations in height varied across environments and whether variability in height was greater in worse environments. To investigate these hypotheses, brothers were identified who were mustered into the Union Army of the US Civil War, using linked records from the 1850 and 1860 censuses and military and medical records. Heights were available for 3898 men aged 18 and older, of whom 595 were further identified as belonging to 288 family sets of two, three or four brothers. Generalized estimating equations were used to concurrently model the mean height, the variance and the correlation between brothers as a function of county population. Heights decreased as county population size increased (p<0.001). The correlation between brothers' heights decreased significantly (p = 0.032) with increasing county population, and the variance increased (p = 0.026). The correlation ranged approximately from 0.63 in the least populous to 0.24 in the most populous counties. The degree of familial resemblance was lower in environments where mean height was lower, and the variability in height was greater, suggesting that the environmental contribution to the variability in height is of greater relative importance in populations reared, on average, in worse environments.

Site specificity of colorectal neoplasms in families without an inherited syndrome.

BACKGROUND: Relatives of patients with bowel neoplasia have an increased risk of bowel neoplasia. If there were concordance in location of neoplasia between relatives, then location-specific screening could be used. Such concordance might also assist in the understanding of the etiology of neoplasia within individual families. METHODS: We have investigated the concordance in anatomic location of colonic neoplasia between first-degree relatives using a new statistical technique for paired data called alternating logistic regression. RESULTS: A total of 146 families were ascertained, none of which had clinical evidence of a hereditary predisposition to edon neoplasia. Among those with neoplasia, there was an increased risk for right-sided disease with older age (40% for less than age 60 vs. 58% for at least 70 years of age, p = 0.008). As assessed by the odds ratio, we found no significant concordance within families for location of neoplasia (odds ratio = 1.2: CI [0.7, 2.2]), although there was a suggestion that location in family members of the same generation was more strongly associated (odds ratio 1.87: CI [0.82, 4.25]). CONCLUSIONS: The lack of concordance within families for location argues against considering family-specific bowel screening protocols and indicates that the most important causes of bowel neoplasia are not sufficiently focused on one anatomic site to facilitate etiologic research.

Hypothesis testing under mixture models: application to genetic linkage analysis.

In this paper we propose a new class of statistics to test a simple hypothesis against a family of alternatives characterized by a mixture model. Unlike the likelihood ratio statistic, whose large sample distribution is still unknown in this situation, these new statistics have a simple asymptotic distribution to which to refer under the null hypothesis. Simulation results suggest that it has adequate power in detecting the alternatives. Its application to genetic linkage analysis in the presence of the genetic heterogeneity that motivated this work is emphasized.

Short-term consistency in self-reported physical functioning among elderly women: the Women's Health and Aging Study.

The assessment of physical functioning and disability is integral to population-based and clinical research carried out among elderly people. Typically, functional status is measured through self-reported responses to questions of the form "Do you have difficulty [doing a specific task]?" Knowledge of the reliability and validity of these self-report measures is key to the interpretation of many research efforts, but data on these measurement parameters are sparse. This paper addresses this deficiency through analyses of data from the Weekly Substudy of the Women's Health and Aging Study, a cohort of Baltimore-area women aged > or =65 years with moderate to severe physical disability. Self-reported data on 20 activities, obtained weekly over a 6-month period in 1993 or 1994, were analyzed to investigate how time intervals between assessments and a subject's age and baseline level of disability influenced the consistency of self-reports of disability at both the population level and the individual level. The prevalence of self-reported difficulty increased with baseline disability and, to a lesser extent, with age group. Consistency for all items was very high over short time intervals, but it decreased substantially with increasing intervals between responses (although associations between responses remained significant at 24 weeks). Consistency did not vary with age or baseline disability. Graphic techniques and statistical methods for use with repeated binary data are also illustrated.

Discarded needles do not increase soon after the opening of a needle exchange program.

This study examines the effect of a Needle Exchange Program (NEP) on the quantity and geographic distribution of discarded needles on the streets of Baltimore, Maryland, and presents methods to survey discarded needles in the community. A random sample of 32 city blocks located within high-drug-use census tracts, stratified by east and west sides of the city and by proximity to the NEP, was selected for survey. Three teams surveyed the number of needles and the number of drug vials and unbroken glass bottles ("trash") to control for practice effects. Surveillance was conducted prior to initiation of the NEP in August 1994 and 1 and 2 months thereafter. Over the three study periods, the absolute count of discarded needles was 106, 130, and 128, respectively; the number of vials and bottles was 3,048, 3,825, and 3,796, respectively. The initial nonstatistically significant increase in needles (mean change = 0.38, 95% confidence interval (CI) -0.18 to 0.93) was offset by accounting for background trash. Regression models fitted with the generalized estimating equation method, which accounted for within-block correlation over time, showed no significant increase in the number of needles after adjustment for trash during the first 2 months of the NEP's operation. These data suggest that the initiation of NEPs does not result in an increase in the number of discarded needles on the street.

Determining linkage and mode of inheritance: mode scores and other methods.

The lod score method remains a popular approach for detecting linkage and estimating the recombination fraction theta between a marker locus and a trait locus. However, its implementation requires knowledge of all parameters of the genetic mechanism, including the number of loci involved and the genotype specific penetrance, which could depend on factors such as age. When some of the penetrance parameters phi are unknown, several methods are available, and have been reviewed by Hodge and Elston [(1994) Genet Epidemiol 11:329-342]. These include the "wrod score" (lod score maximized over theta under a wrong value of phi) and "mod score" (lod score maximized over both theta and phi) methods for inference on theta. It has further been proposed that the mod score also be used for estimating phi. In this paper, we review and assess the adequacy of these two methods for inferences on both phi and theta. In particular, all of the methods can be seen as variations on likelihood inference, using the information in the conditional likelihood for the marker data, given the trait data. The loss of efficiency of the mod is compared to that of the full likelihood, which utilizes all information available in the trait data. We also propose an alternative, based on the pseudo-likelihood, where phi is estimated via the trait information and plugged into the conditional likelihood. This method is compared to the mod score method, and the advantages and disadvantages of each are elucidated. In particular, it is seen that the pseudo-likelihood method can be more efficient than the mod score method if the ascertainment scheme can be modeled. As examples, both a random sample and a multiplex ascertainment scheme are considered. In addition, the pseudo-likelihood method leads to likelihood ratio tests for detecting linkage with a simple, known asymptotic reference distribution, a feature not shared by the mod score. Finally, we discuss the advantages of using the pseudo-likelihood method over the full likelihood method, both of which are valid when the ascertainment scheme is known.