Interrelationship of cytokines, hypothalamic-pituitary-adrenal axis hormones, and psychosocial variables in the prediction of preterm birth.

BACKGROUND/AIMS: To examine the relationship of biological mediators (cytokines, stress hormones), psychosocial, obstetric history, and demographic factors in the early prediction of preterm birth (PTB) using a comprehensive logistic regression model incorporating diverse risk factors. METHODS: In this prospective case-control study, maternal serum biomarkers were quantified at 9-23 weeks' gestation in 60 women delivering at <37 weeks compared to 123 women delivering at term. Biomarker data were combined with maternal sociodemographic factors and stress data into regression models encompassing 22 preterm risk factors and 1st-order interactions. RESULTS: Among individual biomarkers, we found that macrophage migration inhibitory factor (MIF), interleukin-10, C-reactive protein (CRP), and tumor necrosis factor-alpha were statistically significant predictors of PTB at all cutoff levels tested (75th, 85th, and 90th percentiles). We fit multifactor models for PTB prediction at each biomarker cutoff. Our best models revealed that MIF, CRP, risk-taking behavior, and low educational attainment were consistent predictors of PTB at all biomarker cutoffs. The 75th percentile cutoff yielded the best predicting model with an area under the ROC curve of 0.808 (95% CI 0.743-0.874). CONCLUSION: Our comprehensive models highlight the prominence of behavioral risk factors for PTB and point to MIF as a possible psychobiological mediator.

Short forms of the Benton Judgment of Line Orientation Test: development and psychometric properties.

The Benton Judgment of Line Orientation Test (BJLOT) is a widely used neuropsychological test measuring visuospatial judgment. The present study developed two 15-item short forms using data from 100 neurologic patients. The new short forms are equivalent in test construction and retain the stimulus properties of the original test. Correlational analyses revealed that each short form score related significantly to the original BJLOT (p <.001). The short forms were found to be internally consistent, with alpha reliability coefficients exceeding .82. Although kappa coefficient analyses found the short forms to lack sufficient accuracy in categorizing the cases via the BJLOT diagnostic classifications, the short forms were accurate in detecting the presence of impairment. These results suggest that the two short forms can be utilized as screening instruments for detecting the presence or absence of visuospatial impairment.

Rate of 24-hour blood pressure decline and mortality after spontaneous intracerebral hemorrhage: a retrospective analysis with a random effects regression model.

OBJECTIVE: To study the effect of decline in blood pressure on mortality in patients with spontaneous intracerebral hemorrhage (ICH). DESIGN: Retrospective chart review. SETTING: University-affiliated teaching hospital. PATIENTS: Consecutive patients admitted with spontaneous ICH over a 3-year period. MEASURES: Blood pressure recordings were obtained from the first 24 hrs. Patients (n = 105) with more than five blood pressure recordings and on average greater than one measurement per 2 hrs were included (mean measurements per patient = 20.3). Mean arterial pressure (MAP) recordings over the first 24 hrs after presentation were regressed on time for each patient. Each patient's MAP was calculated as a slope (change mm Hg/hr). We performed logistic regression analyses to determine the effect of MAP slope on mortality and functional outcome, adjusting for other predictive factors including Glasgow Coma Scale (GCS) score and hematoma volume. The effect of MAP slope on mortality was also evaluated in subsets of patients based on age, gender, initial GCS score, initial MAP, treatment status, hematoma volume, and presence of ventricular blood. MAIN RESULTS: Mean slope of change in MAP was -2.0 mm Hg/hr (+/- 1.9, range -8.5 to +0.6). The slope of MAP (faster rate of decline) within the first 24 hrs was significantly associated with higher mortality (p =.04), independent of initial GCS score and hematoma volume. In subgroup analyses, MAP slope was significantly associated with mortality in men (p = .08), patients with hematoma volume <50 mm3 (p =.08), initial MAP < or = 146 mm Hg (p = .006), and those with initial GCS score > or = 10 (p= .07). MAP slope did not predict functional outcome among survivors. CONCLUSIONS: A rapid decline in MAP within 24 hrs after presentation is independently associated with increased mortality in patients with ICH. A large, prospective, randomized trial is required to confirm these findings.

Factors related to sleep quality in healthy elderly women.

Elderly women in subjectively good health--free of acute illness and major sleep pathologies--who were self-identified as good (n = 22) and poor (n = 16) sleepers were compared on measures of physical health, psychological symptoms, psychosocial status, and life-style. Poor sleepers reported longer sleep latencies, less total sleep time, more nonrestorative sleep, and more daytime fatigue than did good sleepers. Sleep recordings confirmed subjective reports, with shorter total sleep times and trends for lower sleep efficiency, longer sleep latencies, and more wake-after-sleep onset among women with subjective poor sleep. Poor sleepers also were more frequent users of sedative-hypnotic medications in the past. Current medication use, alcohol and caffeine use, daytime napping, and exercise were equivalent in both groups. Psychosocial status failed to discriminate groups. Poor sleepers reported significantly more psychological symptoms than did good sleepers. The levels of both psychological symptoms and sleep disturbance were mild.

Measuring medical and nursing students' attitudes toward AIDS.

Investigated attitudes toward AIDS patients among medical and nursing students. Two separate cohorts of students (total N = 550) were surveyed to examine and then validate with confirmatory factor analysis the latent factor structure of such attitudes. Results indicate that a three-factor structure representing fear of contagion, negative emotions, and professional resistance provides a good fit to the data (goodness-of-fit index [GFI] = .92, parsimonious GFI = .67). We offer the resulting 15-item AIDS Attitudes Scale (AAS) as a reliable and valid measure for assessing health care students' attitudes toward working with AIDS patients. Our results suggest the presence of multiple predictors of such attitudes.

Direct measurement of daytime sleepiness after administration of cetirizine and hydroxyzine with a standardized electroencephalographic assessment.

Alertness is a vital function, and medications that do not impair this vital function are clinically desirable in terms of safety. In a comparative study to measure daytime alertness objectively, 60 men and women in good health were assigned to receive either cetirizine, 5 mg, 10 mg, or 20 mg, hydroxyzine, 25 mg, or placebo in a randomized, double-blind, parallel-group design. Subjects slept in the laboratory for 2 consecutive nights to facilitate adaptation. During the second night, the subjects' sleep patterns were recorded by electroencephalogram (EEG), electrooculogram, and chin electromyogram. After the second night, subjects were awakened at 7:30 AM and given a single dose of the assigned treatment. Multiple Sleep Latency Tests (standardized 20-minute opportunities to fall asleep in bed while EEG and eye movements are recorded) were given every 2 hours. Subjects who received cetirizine did not differ from control subjects given placebo in any measure of daytime alertness. Subjects who received hydroxyzine were significantly more sedated than were control subjects given placebo for about 4 hours after treatment. The data from this study provide evidence that cetirizine does not differ from placebo with respect to alertness. The usefulness of the specific and sensitive standardized electroencephalogram, compared with alternative assessments of daytime alertness, is discussed.

Predictors of medical and nursing students' levels of HIV-AIDS knowledge and their resistance to working with AIDS patients.

Among health professionals, knowledge about the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) is often limited, inaccurate, or both. Many health professionals also resist working with AIDS patients. This 1988 survey examined exaggerated risk estimates for HIV contagion in relationship to HIV-AIDS knowledge and resistance to working with AIDS patients among medical and nursing students at a large Northwestern teaching hospital. The results indicate that among the respondents, exaggerated risk estimates were associated both with a lack of HIV-AIDS knowledge and with greater resistance to working with AIDS patients. Results from multiple regression analyses revealed that (1) a lack of clinical experience with AIDS patients and (2) antihomosexual attitudes were significantly associated with the students' lack of HIV-AIDS knowledge, even after controlling for the effects of exaggerated risk estimates. The first two variables also were shown to be significantly predictive of the students' resistance to working with AIDS patients, as was an intolerance of drug use and drug users, beyond the influence of exaggerated risk estimates. Specific approaches of developing effective HIV-AIDS educational programs for health professionals are proposed.

Systematic 24-hr behavioral observations of sleep and wakefulness in a skilled-care nursing facility.

Sleep patterns of aged, infirm, demented, chronically institutionalized residents of a skilled-care nursing facility were studied. The purpose of this naturalistic study was to describe sleep and wakefulness (S/W) within the limits afforded by brief behavioral observations and to examine homeostasis and diurnal rhythmicity of S/W as a function of psychoactive drug intake. Observers noted S/W every 15 min, 24 hr a day for 10 days in 24 Ss. Results indicated substantial individual variation in daytime hours. Daily and weekly variation within Ss was minimal. Sleep was least likely near sunset. Ss on psychoactive drugs showed dampened diurnal variation in S/W rhythms. In Ss not on such drugs, there was a suggestion of homeostasis of S/W between sleep during the morning and evening hours. Results are discussed methodologically (viability of approach), theoretically (age-related change in sleep), and practically (potential treatments).

Profile of mood states changes during and after 5 weeks of nightly triazolam administration.

This double-blind, placebo-controlled study investigated rebound anxiety during and after 5 weeks of nightly use of triazolam 0.5 mg, a short half-life, rapidly absorbed benzodiazepine hypnotic. The study subjects were chronic insomniacs with moderate levels of psychopathology and prior use of hypnotics. Anxiety was assessed with the Profile of Mood States (POMS), instead of the anxiety scales more typically used in psychopharmacology: the Hamilton Rating Scale for Anxiety and a visual analogue scale. The POMS test was administered twice a day during the study. The results indicated that triazolam was not associated with increased anxiety the morning or the evening after previous-night drug administration. The results are discussed in view of the methodological issues in assessing anxiety in prior studies.

Sleep apnea and mortality in an aged cohort.

In the aged, sleep may be a vulnerable period for death from cardiovascular causes. Because of its high prevalence in the elderly, sleep apnea has been suggested to be one mechanism contributing to such sleep-related mortality. In this study, a cohort of 198 non-institutionalized elderly individuals (mean age at entry = 66) were followed for periods up to 12 years after initial polysomnography. The mortality ratio for sleep apnea (defined as a Respiratory Disturbance Index of over 10 events per sleep hour) was estimated to be 2.7 (95% CI = .95, 7.47). Multiple regression with the Cox proportional hazards model suggested that cardiovascular death was most clearly associated with age in this cohort. These results raise the possibility that "natural" death during sleep in the elderly may be associated with specific pathophysiological events during sleep.

Cetirizine effects on objective measures of daytime sleepiness and performance.

Sixty healthy men and women with no sleep complaints, 21 to 45 years of age (mean age 28), were randomly assigned to one of five parallel groups that received one of the following: cetirizine 5 mg (n = 13), 10 mg (n = 13), or 20 mg (n = 11); hydroxyzine 25 mg (n = 12); or placebo (n = 11). After one adaptation night in the lab, the subjects' sleep patterns were recorded from 2300 to 0730 hours. Subjects were in bed during this period. When they awoke at 0730, a test agent was administered according to double-blind technique. Multiple Sleep Latency Tests (MSLT: 20-minute opportunities to fall asleep in bed while EEG and eye movements are recorded) were given at two-hour intervals throughout the day, and a 30-minute vigilance performance test was given at 1000 and 1600 hours. Subjects receiving cetirizine in doses of 5 to 20 mg did not differ from placebo controls in any objective or subjective measure of daytime alertness. Subjects receiving hydroxyzine were significantly more sedated and showed slower reaction times than the placebo control group for at least four hours after treatment. Self-rated feelings of sleepiness, impairment, and fatigue did not differ significantly between groups. This suggests that hydroxyzine subjects may not have been aware of their sleepiness and slower reaction times.

Risk factors for sleep disordered breathing in heterogeneous geriatric populations.

This cross-sectional, multivariate study investigated associations between sleep disordered breathing (SDB) and putative risk factors in a heterogeneous group of 720 individuals over the age of 50 years studied during all-night in-lab polysomnography. Results indicated that: aged men were more likely to show impaired respiration during sleep than aged women; excessive daytime somnolence and parasomniac symptoms (snoring, gasping during sleep) were associated with SDB but insomnia was not; obesity accounted for more variance in SDB than age per se, implying that the prevalence of SDB in some elderly persons could be related to the deposition of body fat seen as individuals grow older. All four risk factors (age, sex, obesity, and symptomatic status) were statistically significant and independent predictors of impaired respiration in sleep in the elderly.

Sleep and wakefulness in aircrew before and after transoceanic flights.

Aircrew were studied before and after flying one of two routes: San Francisco (SFO) to London (LHR) or SFO to Tokyo (NRT). After an adaptation night, sleep and daytime sleepiness were objectively measured in SFO and during the first layover (L/O) of the target trip. Baseline sleep was slightly shorter than normally reported for similar age subjects and, for several reasons, is not an ideal basis for subsequent comparison. Nevertheless, L/O sleep periods tended to provide either less total sleep or less efficient sleep. Crewmembers' estimates of their sleep duration correlated well with objective measures, but their estimates of daytime sleepiness correlated poorly with objectively measured sleepiness. During baseline there was a significant midday sleep tendency as measured by the Multiple Sleep Latency Test. This tendency occurred at almost the same time (GMT) on the second L/O day in LHR. Since sleepiness has a persistent rhythm which is maximal twice per day, it is suggested that L/O sleep periods be taken at these times of maximal sleepiness and that peak workload should coincide with the subsequent periods of maximal alertness. Although the overall quality of sleep diminished only slightly on this L/O, it is possible that if this relatively small loss accumulated over successive L/Os, the effects on daytime sleepiness could be measurable.

Dose-related effects of triazolam and flurazepam on a circadian rhythm insomnia.

Forty-eight normal subjects had sleep recordings and multiple sleep latency tests (an EEG measure of sleepiness) before and after a 12-hour shift of sleep-wake schedule. After 2 baseline days, subjects postponed sleep until 12:00 noon, then for three 24-hour periods were in bed from 12:00 noon until 8:00 PM. Treatment in parallel groups were administered before shifted sleeps. Sleep disturbance was greatest in the last quarter of shifted nights (6.5 to 8.5 hours after medication). Subjects taking placebo showed significant sleep loss on shifted nights and increased sleepiness the next day. Triazolam, 0.5 mg, reversed the sleep loss and consequent daytime sleepiness associated with the shifted sleep schedule. Triazolam, 0.25 mg, was not significantly better than placebo. In a dose-related manner, flurazepam mitigated the insomnia, but carryover effects left both dose groups more sleepy than were the placebo control subjects. Whether these laboratory results are applicable to clinically occurring forms of transient insomnia remains to be seen.

Buspirone: an anxiolytic without sedative effect.

Twelve volunteers with a complaint of chronic insomnia participated in a placebo-controlled, double-blind, crossover study of the effects of buspirone t.i.d. on sleep pattern and daytime function. The drug was tested alone and in combination with flurazepam or triazolam. Buspirone alone did not impair objective measures of daytime wakefulness or performance. Impaired alertness was seen the day after bedtime administration of flurazepam but not after triazolam; buspirone did not alter these effects. Buspirone did not affect the Multiple Sleep Latency Test, a sensitive measure of changes in daytime alertness.

Measurement error in visually scored electrophysiological data: respiration during sleep.

Electrophysiological sleep studies employ the simultaneous recording of multiple physiological parameters. These data are often scored and analyzed visually, i.e. by trained human scorers. In this study, we investigated the measurement error inherent in visual evaluation of respiratory disturbances during human sleep. Three trained scorers independently evaluated twenty-eight all-night sleep recordings. Results indicated that the scorers achieved high agreement on only selected variables. Scorers' experience did not affect the reliability and independent judgements of recording quality did not account for the discrepancies. These findings, although most relevant for the specific parameters studied here, as well as for these scoring criteria, subjects, and techniques, document the unreliability of certain visually scored sleep data. The present paradigm may be useful in evaluating other types of measurement error.