Robert T. Krafty

What constitutes too long of a delay? Determining the cortisol awakening response (CAR) using self-report and PSG-assessed wake time.

The cortisol awakening response (CAR) is a burst of cortisol in response to awakening from sleep that is superimposed on the circadian rhythm of cortisol. Determination of the CAR is contingent on the timing of sample collection: a delay between waking and collection of the first sample may affect the rise of the CAR, and could explain equivocal findings reported in the literature. We evaluated the impact of a delay between wake time and collection of waking cortisol samples on the CAR. Two methods were used to identify wake time: polysomnography (PSG) and self-report (S-R). Participants (total n=207, mean age 74.0+/-7.2 years) included bereaved older adults (n=35), caregivers (n=50), patients with insomnia and co-morbid medical disorders (n=68), and the healthy older adults (n=54). We used ANOVA to test if a delay >15 min affected the CAR. We also fitted cubic spline models to assess expected cortisol levels, the expected CAR, and the expected decrease in CAR. Wake times measured by PSG and S-R did not differ significantly. Large delays were observed (for both PSG and S-R) between wake time and collection of the waking cortisol sample (24.8+/-32.2 min for PSG and 28.3+/-49.2 min for S-R). Both statistical methods indicated that a delay >15 min between wake time and first cortisol sample collection significantly affected the CAR (ps<.005); later collection times were associated with smaller CAR values. Later collection times and reduced CAR values may affect the interpretation of clinical associations. Our data also show that S-R assessments of wake time perform equally well to PSG for evaluating adherence with CAR sampling procedures.

Short-term stability of sleep and heart rate variability in good sleepers and patients with insomnia: for some measures, one night is enough.

STUDY OBJECTIVES Quantify the short-term stability of multiple indices of sleep and nocturnal physiology in good sleeper controls and primary insomnia patients. DESIGN Intra-class correlation coefficients (ICC) were used to quantify the short-term stability of study outcomes. SETTING Sleep laboratory. PARTICIPANTS Fifty-four adults with primary insomnia (PI) and 22 good sleeper controls (GSC). MEASUREMENTS Visually scored sleep outcomes included indices of sleep duration, continuity, and architecture. Quantitative EEG outcomes included power in the delta, theta, alpha, sigma, and beta bands during NREM sleep. Power spectral analysis was used to estimate high-frequency heart rate variability (HRV) and the ratio of low- to high-frequency HRV power during NREM and REM sleep. RESULTS With the exception of percent stage 3+4 sleep; visually scored sleep outcomes did not exhibit short-term stability across study nights. Most QEEG outcomes demonstrated short-term stability in both groups. Although power in the beta band was stable in the PI group (ICC = 0.75), it tended to be less stable in GSCs (ICC = 0.55). Both measures of cardiac autonomic tone exhibited short-term stability in GSCs and PIs during NREM and REM sleep. CONCLUSIONS Most QEEG bandwidths and HRV during sleep show high short-term stability in good sleepers and patients with insomnia alike. One night of data is, thus, sufficient to derive reliable estimates of these outcomes in studies focused on group differences or correlates of QEEG and/or HRV. In contrast, one night of data is unlikely to generate reliable estimates of PSG-assessed sleep duration, continuity or architecture, with the exception of slow wave sleep.

Chronotype and Diurnal Patterns of Positive Affect and Affective Neural Circuitry in Primary Insomnia

While insomnia is a well‐established risk factor for the initial onset, recurrence or relapse of affective disorders, the specific characteristics of insomnia that confer risk remain unclear. Patients with insomnia with an evening chronotype may be one particularly high‐risk group, perhaps due to alterations in positive affect and its related affective circuitry. We explored this possibility by comparing diurnal patterns of positive affect and the activity of positive affect‐related brain regions in morning‐ and evening‐types with insomnia. We assessed diurnal variation in brain activity via the relative regional cerebral metabolic rate of glucose uptake by using [18F]fluorodeoxyglucose‐positron emission tomography during morning and evening wakefulness. We focused on regions in the medial prefrontal cortex and striatum, which have been consistently linked with positive affect and reward processing. As predicted, chronotypes differed in their daily patterns in both self‐reported positive affect and associated brain regions. Evening‐types displayed diurnal patterns of positive affect characterized by phase delay and smaller amplitude compared with those of morning‐types with insomnia. In parallel, evening‐types showed a reduced degree of diurnal variation in the metabolism of both the medial prefrontal cortex and the striatum, as well as lower overall metabolism in these regions across both morning and evening wakefulness. Taken together, these preliminary findings suggest that alterations in the diurnal activity of positive affect‐related neural structures may underlie differences in the phase and amplitude of self‐reported positive affect between morning and evening chronotypes, and may constitute one mechanism for increased risk of mood disorders among evening‐type insomniacs.

Chronic stress is prospectively associated with sleep in midlife women: The SWAN sleep study

STUDY OBJECTIVES Evaluate whether levels of upsetting life events measured over a 9-y period prospectively predict subjective and objective sleep outcomes in midlife women. DESIGN Prospective cohort study. SETTING Four sites across the United States. PARTICIPANTS 330 women (46-57 y of age) enrolled in the Study of Womens Health Across the Nation (SWAN) Sleep Study. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Upsetting life events were assessed annually for up to 9 y. Trajectory analysis applied to life events data quantitatively identified three distinct chronic stress groups: low stress, moderate stress, and high stress. Sleep was assessed by self-report and in-home polysomnography (PSG) during the ninth year of the study. Multivariate analyses tested the prospective association between chronic stress group and sleep, adjusting for race, baseline sleep complaints, marital status, body mass index, symptoms of depression, and acute life events at the time of the Sleep Study. Women characterized by high chronic stress had lower subjective sleep quality, were more likely to report insomnia, and exhibited increased PSG-assessed wake after sleep onset (WASO) relative to women with low to moderate chronic stress profiles. The effect of chronic stress group on WASO persisted in the subsample of participants without baseline sleep complaints. CONCLUSIONS Chronic stress is prospectively associated with sleep disturbance in midlife women, even after adjusting for acute stressors at the time of the sleep study and other factors known to disrupt sleep. These results are consistent with current models of stress that emphasize the cumulative effect of stressors on health over time.

Time-varying correlations between delta EEG power and heart rate variability in midlife women: The SWAN Sleep Study

No studies have evaluated the dynamic, time-varying relationship between delta electroencephalographic (EEG) sleep and high frequency heart rate variability (HF-HRV) in women. Delta EEG and HF-HRV were measured during sleep in 197 midlife women (M(age)  = 52.1, SD = 2.2). Delta EEG-HF-HRV correlations in nonrapid eye movement (NREM) sleep were modeled as whole-night averages and as continuous functions of time. The whole-night delta EEG-HF-HRV correlation was positive. The strongest correlations were observed during the first NREM sleep period preceding and following peak delta power. Time-varying correlations between delta EEG-HF-HRV were stronger in participants with sleep-disordered breathing and self-reported insomnia compared to healthy controls. The dynamic interplay between sleep and autonomic activity can be modeled across the night to examine within- and between-participant differences including individuals with and without sleep disorders.

Varying Coefficient Model with Unknown Within-Subject Covariance for Analysis of Tumor Growth Curves

SUMMARY In this article we develop a nonparametric estimation procedure for the varying coefficient model when the within-subject covariance is unknown. Extending the idea of iterative reweighted least squares to the functional setting, we iterate between estimating the coefficients conditional on the covariance and estimating the functional covariance conditional on the coefficients. Smoothing splines for correlated errors are used to estimate the functional coefficients with smoothing parameters selected via the generalized maximum likelihood. The covariance is nonparametrically estimated using a penalized estimator with smoothing parameters chosen via a Kullback-Leibler criterion. Empirical properties of the proposed method are demonstrated in simulations and the method is applied to the data collected from an ovarian tumor study in mice to analyze the effects of different chemotherapy treatments on the volumes of two classes of tumors.

Bayesian semi-parametric analysis of Poisson change-point regression models: application to policy making in Cali, Colombia

A Poisson regression model with an offset assumes a constant baseline rate after accounting for measured covariates, which may lead to biased estimates of coefficients in an inhomogeneous Poisson process. To correctly estimate the effect of time-dependent covariates, we propose a Poisson change-point regression model with an offset that allows a time-varying baseline rate. When the non-constant pattern of a log baseline rate is modeled with a non-parametric step function, the resulting semi-parametric model involves a model component of varying dimensions and thus requires a sophisticated varying-dimensional inference to obtain the correct estimates of model parameters of a fixed dimension. To fit the proposed varying-dimensional model, we devise a state-of-the-art Markov chain Monte Carlo-type algorithm based on partial collapse. The proposed model and methods are used to investigate the association between the daily homicide rates in Cali, Colombia, and the policies that restrict the hours during which the legal sale of alcoholic beverages is permitted. While simultaneously identifying the latent changes in the baseline homicide rate which correspond to the incidence of sociopolitical events, we explore the effect of policies governing the sale of alcohol on homicide rates and seek a policy that balances the economic and cultural dependencies on alcohol sales to the health of the public.

Trends in Survival and Early Functional Outcomes From Hospitalized Severe Adult Traumatic Brain Injuries, Pennsylvania, 1998 to 2007

Objective:To determine trends for in-hospital survival and functional outcomes at acute care hospital discharge for patients with severe adult traumatic brain injury (SATBI) in Pennsylvania, during 1998 to 2007. Methods:Secondary analysis of the Pennsylvania trauma outcome study database. Main Outcome Measures:Survival and functional status scores of 5 domains (feeding, locomotion, expression, transfer mobility, and social interaction) fitted into logistic regression models adjusted for age, sex, race, comorbidities, injury mechanism, extracranial injuries, severity scores, hospital stay, trauma center, and hospital level. Sensitivity analyses for functional outcomes were performed. Results:There were 26 234 SATBI patients. Annual numbers of SATBI increased from 1757 to 3808 during 1998 to 2007. Falls accounted for 47.7% of all SATBI. Survival increased significantly from 72.5% to 82.7% (odds ratio [OR] = 1.10, 95% CI: 1.08–1.11, P < .001). In sensitivity analyses, trends of complete independence in functional outcomes increased significantly for expression (OR = 1.01, 95% CI: 1.00–1.02, P = .011) and social interaction (OR = 1.01, 95% CI: 1.00–1.03, P = .002). There were no significant variations over time for feeding, locomotion, and transfer mobility. Conclusions:Trends for SATBI served by Pennsylvanias established trauma system showed increases in rates but substantial reductions in mortality and significant improvements in functional outcomes at discharge for expression and social interaction.

The Association of Clinical Variables and Filter Design with Carotid Artery Stenting Thirty-Day Outcome

OBJECTIVE Patient and device selection are important for the success of carotid artery stenting (CAS). We hypothesize that distal protection filter (DPF) design characteristics that minimize blood flow resistance and maximize capture efficiency are associated with the absence of transient ischemic attack (TIA), stroke and neurologic-related death after 30 days. METHODS Records from 208 patients were reviewed retrospectively. Filter design characteristics were quantified previously in our laboratory. The association between risk factors and design characteristics with 30-day outcome was quantified using univariate analysis. RESULTS The 30-day all-cause stroke and death rate was 8.7% (asymptomatic: 7.7%, symptomatic: 10.6%). Five DPFs were used in the study: Accunet (41.3%), Angioguard (33.2%), FilterWire (24%), Emboshield (1%), and Spider (.5%). Diabetes (P = .04) and prior carotid endarterectomy (CEA, P = .03) were associated with adverse outcome. Prior stroke (P = .01) and prior CEA (P = .04) were significant for peri-procedural stroke. Design characteristics such as capture efficiency were associated with favorable outcomes. CONCLUSIONS Patients with prior CEA or stroke are more likely to have unfavorable CAS outcomes after 30 days. Filters with high capture efficiency may yield the best clinical results. Analysis of the effect of design characteristics on CAS outcome should aid the design of future devices.

Homicide and geographic access to gun dealers in the United States

BackgroundFirearms are the most commonly used weapon to commit homicide in the U.S. Virtually all firearms enter the public marketplace through a federal firearms licensee (FFL): a store or individual licensed by the federal government to sell firearms. Whether FFLs contribute to gun-related homicide in areas where they are located, in which case FFLs may be a homicide risk factor that can be modified, is not known.MethodsAnnual county-level data (1993–1999) on gun homicide rates and rates of FFLs per capita were analyzed using negative binomial regression controlling for socio-demographic characteristics. Models were run to evaluate whether the relation between rates of FFLs and rates of gun homicide varied over the study period and across counties according to their level of urbanism (defined by four groupings, as below). Also, rates of FFLs were compared against FS/S – which is the proportion of suicides committed by firearm and is thought to be a good proxy for firearm availability in a region – to help evaluate how well the FFL variable is serving as a way to proxy firearm availability in each of the county types of interest.ResultsIn major cities, gun homicide rates were higher where FFLs were more prevalent (rate ratio [RR] = 1.70, 95% CI 1.03–2.81). This association increased (p < 0.01) from 1993 (RR = 1.69) to 1999 (RR = 12.72), due likely to federal reforms that eliminated low-volume dealers, making FFL prevalence a more accurate exposure measure over time. No association was found in small towns. In other cities and in suburbs, gun homicide rates were significantly lower where FFLs were more prevalent, with associations that did not change over the years of the study period. FFL prevalence was correlated strongly (positively) with FS/S in major cities only, suggesting that the findings for how FFL prevalence relates to gun homicide may be valid for the findings pertaining to major cities but not to counties of other types.ConclusionModification of FFLs through federal, state, and local regulation may be a feasible intervention to reduce gun homicide in major cities.