Sleep duration and health among older adults: associations vary by how sleep is measured.

BACKGROUND: Cohort studies have found that short and long sleep are both associated with worse outcomes, compared with intermediate sleep times. While demonstrated biological mechanisms could explain health effects for short sleep, long-sleep risk is puzzling. Most studies reporting the U shape use a single question about sleep duration, a measurement method that does not correlate highly with objectively measured sleep. We hypothesised that the U shape, especially the poor outcomes for long sleepers, may be an artefact of how sleep is measured. METHODS: We examined the cross-sectional prevalence of fair/poor health by sleep hour categories (≤ 6, ≤ 7, ≤ 8, ≤ 9, > 9 h) in a national US sample of adults aged 62-90 that included several types of sleep measures (n = 727). Survey measures were: a single question; usual bedtimes and waking times; and a 3-day sleep log. Actigraphy measures were the sleep interval and total sleep time. Fair/poor health was regressed on sleep hour categories adjusted for demographics, with tests for both linear trend and U shape. RESULTS: Adjusted OR of fair/poor health across sleep hour categories from the single question were 4.6, 2.2, referent (8 h), 1.8 and 6.9. There was high prevalence of fair/poor health for ≤ 6 h for all sleep measures, but the long-sleep effect was absent for sleep logs and actigraphy measures. CONCLUSIONS: Associations between long sleep and poor health may be specific to studies measuring sleep with survey questions. As cohorts with actigraphy mature, our understanding of how sleep affects health may change.

Predicting the EQ-5D-3L Preference Index from the SF-12 Health Survey in a National US Sample: A Finite Mixture Approach.

BACKGROUND: . When data on preferences are not available, analysts rely on condition-specific or generic measures of health status like the SF-12 for predicting or mapping preferences. Such prediction is challenging because of the characteristics of preference data, which are bounded, have multiple modes, and have a large proportion of observations clustered at values of 1. METHODS: . We developed a finite mixture model for cross-sectional data that maps the SF-12 to the EQ-5D-3L preference index. Our model characterizes the observed EQ-5D-3L index as a mixture of 3 distributions: a degenerate distribution with mass at values indicating perfect health and 2 censored (Tobit) normal distributions. Using estimation and validation samples derived from the Medical Expenditure Panel Survey 2000 dataset, we compared the prediction performance of these mixture models to that of 2 previously proposed methods: ordinary least squares regression (OLS) and two-part models. RESULTS: . Finite mixture models in which predictions are based on classification outperform two-part models and OLS regression based on mean absolute error, with substantial improvement for samples with fewer respondents in good health. The potential for misclassification is reflected on larger root mean square errors. Moreover, mixture models underperform around the center of the observed distribution. CONCLUSIONS: . Finite mixtures offer a flexible modeling approach that can take into account idiosyncratic characteristics of the distribution of preferences. The use of mixture models allows researchers to obtain estimates of health utilities when only summary scores from the SF-12 and a limited number of demographic characteristics are available. Mixture models are particularly useful when the target sample does not have a large proportion of individuals in good health.

Actigraphic sleep characteristics among older Americans.

OBJECTIVES: To date, there has been no evidence about objectively measured sleep characteristics from a representative national probability sample of adults in the United States. We used actigraphy to measure the sleep characteristics of older Americans. DESIGN: Cross-sectional study. SETTING: Sleep sub-study within Wave 2 (2010-2011) of the ongoing National Social Life, Health and Aging Project (NSHAP). PARTICIPANTS: Seven hundred and thirty-nine NSHAP participants aged 62-90. INTERVENTION: Not applicable. MEASUREMENTS: Study participants wore a wrist actigraph for 72 hours and sleep properties were compared across demographic, socioeconomic, and health-behavior related lines. RESULTS: Actigraph-estimated sleep time averaged 7.2 hours (SE 0.06 hr) each night; the majority of the sample (80%) slept between 5.8 and 8.6 hours/night. Average time spent awake after sleep onset (WASO) was 39 minutes (SE 1.2 min). Women had significantly more total sleep time and lower sleep fragmentation compared to men. Total sleep time increased significantly with age although sleep percentage decreased with age. Compared with White participants, African American participants had significantly more WASO (9.2 minutes, p < 0.01) and greater sleep fragmentation (2.3 percentage points, p < 0.001). WASO was significantly higher and sleep percentage significantly lower among those with less education. CONCLUSIONS: Both short sleepers and long sleepers - often conventionally defined as obtaining <6 and >9 hrs/night, respectively - are relatively rare among older Americans when sleep is estimated by actigraphy. Sleep quality is significantly poorer among men, African Americans, and those with less education.

Insomnia symptoms and actigraph-estimated sleep characteristics in a nationally representative sample of older adults.

BACKGROUND: Reports of insomnia symptoms are common among the elderly. However, little is known about the relationship between insomnia symptoms and objective assessments of sleep in the general population of older adults. We assessed concordance between insomnia symptoms and actigraphic sleep characteristics in a nationally representative sample of older Americans. METHODS: In a national probability sample of 727 adults aged 62-91 years in 2010-2011 from the National Social Life, Health, and Aging Project, respondents were asked how often they (a) feel rested when they wake up, (b) have trouble falling asleep, (c) have trouble with waking up during the night, and (d) have trouble waking up too early and not being able to fall asleep again. Responses to these questions were compared to sleep characteristics estimated from three nights of actigraphy for the same individuals. Statistical analyses were adjusted for age, gender, race and ethnicity, income, assets, and education. RESULTS: Feeling rested (Question (a), above) was not correlated with any actigraphy-estimated sleep characteristics. Questions (b)-(d) each had several significant correlations with the actigraphy metrics, but generally not with the specific objective sleep characteristics that each question intended to reference. In some cases, the associations were not in the expected direction. CONCLUSIONS: Although three of four questions about insomnia symptoms were significantly associated with objectively estimated sleep characteristics, responses seem to be general indicators of sleep quality rather than reports of specific sleep characteristics.

Assessment of sleep in the National Social Life, Health, and Aging Project.

OBJECTIVES: The relationship of sleep to health has been an active area of research in recent years, and the National Social Life, Health, and Aging Project (NSHAP) expanded sleep data collection in Wave 2 with enhanced core questions and a novel sleep module that included an objective measure of sleep duration and quality. METHOD: A randomly selected one-third of Wave 2 participants and their spouses or coresident partners were invited to participate in the sleep module. Objective sleep data were collected using wrist actigraphy, an accelerometer that records an integrated measure of motion over short epochs (15 s each). This information is stored and subsequently analyzed to determine sleep and wake periods by epoch. Individuals were instructed to wear the actiwatches for 72 hr. Several sleep parameters were derived from the accelerometer. Individuals concurrently kept a sleep diary. RESULTS: Sleep actigraphy data were successfully collected from 780 individuals. Many of the survey-based and the actigraph-estimated sleep parameters varied by age and gender. However, age and gender patterns often differed for sleep characteristics that were both asked and measured, such as sleep duration. DISCUSSION: The survey and actigraphy data provide different information about sleep characteristics. The opportunity to examine actigraph-estimated sleep characteristics in a nationally representative sample of older adults allows novel analyses of the associations of sleep parameters with social and health data.

Hemicraniectomy and durotomy upon deterioration from infarction-related swelling trial: randomized pilot clinical trial.

BACKGROUND AND PURPOSE: Hemicraniectomy and Durotomy Upon Deterioration From Infarction-Related Swelling Trial (HeADDFIRST) was a randomized pilot study to obtain information necessary to design a Phase III trial to evaluate the benefit of surgical decompression for brain swelling from large supratentorial cerebral hemispheric infarction. METHODS: All patients with stroke were screened for eligibility (age 18-75 years, National Institutes of Health Stroke Scale≥18 with Item 1a<2 [responsive to minor stimulation], and CT demonstrating unilateral, complete middle cerebral artery territory infarction by specific imaging criteria). All enrolled patients were treated using a standardized medical treatment protocol. Those with both≥4 mm of pineal shift and deterioration in level of arousal or ≥7.5 mm of anteroseptal shift within 96 hours of stroke onset were randomized to continued medical treatment only or medical treatment plus surgery. Death at 21 days was the primary outcome measure. RESULTS: Among 4909 screened patients, only 66 (1.3%) patients were eligible for HeADDFIRST. Forty patients were enrolled, and 26 patients developed the requisite brain swelling for randomization. All who failed to meet randomization criteria were alive at 21 days. Mortality at 21 and 180 days was 40% (4/10) in the medical treatment only and 21% (3/14) and 36% (5/14) in the medical treatment plus surgery arms, respectively. CONCLUSIONS: HeADDFIRST randomization criteria effectively distinguished low from high risk of death from large supratentorial cerebral hemispheric infarction. Lower mortality in the medical treatment only group than in other published trials suggests a possible benefit to standardizing medical management. These results can inform the interpretation of recently completed European trials concerning patient selection and medical management. CLINICAL TRIAL REGISTRATION: This trial was not registered because enrollment began before July 1, 2005.

Sleep duration and all-cause mortality: a critical review of measurement and associations.

PURPOSE: Variation in sleep duration has been linked with mortality risk. The purpose of this review is to provide an updated evaluation of the literature on sleep duration and mortality, including a critical examination of sleep duration measurement and an examination of correlates of self-reported sleep duration. METHODS: We conducted a systematic search of studies reporting associations between sleep duration and all-cause mortality and extracted the sleep duration measure and the measure(s) of association. RESULTS: We identified 42 prospective studies of sleep duration and mortality drawing on 35 distinct study populations worldwide. Unlike previous reviews, we find that the published literature does not support a consistent finding of an association between self-reported sleep duration and mortality. Most studies have employed survey measures of sleep duration, which are not highly correlated with estimates based on physiologic measures. CONCLUSIONS: Despite a large body of literature, it is premature to conclude, as previous reviews have, that a robust, U-shaped association between sleep duration and mortality risk exists across populations. Careful attention must be paid to measurement, response bias, confounding, and reverse causation in the interpretation of associations between sleep duration and mortality.

QTc prolongation is associated with impaired right ventricular function and predicts mortality in pulmonary hypertension.

BACKGROUND: In rodent models of pulmonary hypertension (PH) and right ventricular hypertrophy (RVH), the QTc interval is prolonged, reflecting downregulation of repolarizing Kv channels in RV myocytes. The significance of QTc prolongation in human PH is unknown. We hypothesized that QTc prolongation occurs in human PH, is associated with RVH and decreased RV function, and predicts adverse prognosis. METHODS: Patients receiving a PAH-specific therapy (a prostanoid, endothelin-receptor antagonist and/or a phosphodiesterase-5 inhibitor), who had a 12-lead electrocardiogram (ECG) (n=202) were compared to age- and sex-matched controls (n=100). The duration of QTc on ECG was correlated with invasive hemodynamics (n=156) and with the status of the RV, as measured by Brain Natriuretic Peptide (NT-proBNP, n=145) and magnetic resonance imaging (n=24). Survival of the entire PH cohort and a subgroup with WHO Groups 1 and 4 PAH was prospectively determined from the Social Security Death Index. RESULTS: QTc intervals were longer in PH vs. controls (454.8 ± 29 ms vs. 429.8 ± 18 ms, p<0.001) and did not differ based on PAH-specific therapy. NT-proBNP increased proportionately with QTc and was higher for those in the upper quintile (QTc ≥ 480 ms) vs. those with QTc<480 ms (4004 ± 6682 pg/mL vs. 1501 ± 1822 pg/mL, p<0.001). The QTc interval also correlated directly with increasing RV end-diastolic volume (r=.67, p<0.001) and mass (r=.0.51, p<0.05), and inversely with RV ejection fraction (r=-.49, p<0.05). In the entire PH cohort and WHO Groups 1 and 4 subgroup, QTc ≥ 480 ms and cardiac index were independent predictors of mortality. CONCLUSIONS: QTc prolongation in PH patients reflects the status of the RV and is an independent predictor of mortality.

A systematic analysis of experimental immunotherapies on tumors differing in size and duration of growth.

We conducted a systematic analysis to determine the reason for the apparent disparity of success of immunotherapy between clinical and experimental cancers. To do this, we performed a search of PubMed using the keywords "immunotherapy" AND "cancer" for the years of 1980 and 2010. The midspread of experimental tumors used in all the relevant literature published in 2010 were between 0.5-121 mm(3) in volume or had grown for four to eight days. Few studies reported large tumors that could be considered representative of clinical tumors, in terms of size and duration of growth. The predominant effect of cancer immunotherapies was slowed or delayed outgrowth. Regression of tumors larger than 200 mm(3) was observed only after passive antibody or adoptive T cell therapy. The effectiveness of other types of immunotherapy was generally scattered. By comparison, very few publications retrieved by the 1980 search could meet our selection criteria; all of these used tumors smaller than 100 mm(3), and none reported regression. In the entire year of 2010, only 13 used tumors larger than 400 mm(3), and nine of these reported tumor regression. Together, these results indicate that most recent studies, using many diverse approaches, still treat small tumors only to report slowed or delayed growth. Nevertheless, a few recent studies indicate effective therapy against large tumors when using passive antibody or adoptive T cell therapy. For the future, we aspire to witness the increased use of experimental studies treating tumors that model clinical cancers in terms of size and duration of growth.

A marginal structural model analysis for loneliness: implications for intervention trials and clinical practice.

OBJECTIVE: Clinical scientists, policymakers, and individuals must make decisions concerning effective interventions that address health-related issues. We use longitudinal data on loneliness and depressive symptoms and a new class of causal models to illustrate how empirical evidence can be used to inform intervention trial design and clinical practice. METHOD: Data were obtained from a population-based study of non-Hispanic Caucasians, African Americans, and Latino Americans (N = 229) born between 1935 and 1952. Loneliness and depressive symptoms were measured with the UCLA Loneliness Scale-Revised and Center for Epidemiologic Studies Depression Scale, respectively. Marginal structural causal models were employed to evaluate the extent to which depressive symptoms depend not only on loneliness measured at a single point in time (as in prior studies of the effect of loneliness) but also on an individual's entire loneliness history. RESULTS: Our results indicate that if interventions to reduce loneliness by 1 standard deviation were made 1 and 2 years prior to assessing depressive symptoms, both would have an effect; together, they would result in an average reduction in depressive symptoms of 0.33 standard deviations, 95% CI [0.21, 0.44], p < .0001. CONCLUSIONS: The magnitude and persistence of these effects suggest that greater effort should be devoted to developing practical interventions on alleviating loneliness and that doing so could be useful in the treatment and prevention of depressive symptoms. In light of the persistence of the effects of loneliness, our results also suggest that, in the evaluation of interventions on loneliness, it may be important to allow for a considerable follow-up period in assessing outcomes.

Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect.

OBJECTIVE: To evaluate dextromethorphan combined with ultra low-dose quinidine (DMq) for treating pseudobulbar affect (PBA) in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). METHODS: In a 12-week randomized, double-blind trial, ALS and MS patients with clinically significant PBA (a baseline score ≥13 on the Center for Neurologic Studies-Lability Scale [CNS-LS]) were maintained, twice daily, on placebo, DMq at 30/10mg (DMq-30), or DMq at 20/10mg (DMq-20). RESULTS: In 326 randomized patients (of whom 283, or 86.8%, completed the study), the PBA-episode daily rate was 46.9% (p < 0.0001) lower for DMq-30 than for placebo and 49.0% (p < 0.0001) lower for DMq-20 than for placebo by longitudinal negative binomial regression, the prespecified primary analysis. Mean CNS-LS scores decreased by 8.2 points for DMq-30 and 8.2 for DMq-20, vs 5.7 for placebo (p= 0.0002 and p= 0.0113, respectively). Other endpoints showing statistically significant DMq benefit included, for both dosage levels, the likelihood of PBA remission during the final 14 days and, for the higher dosage, improvement on measures of social functioning and mental health. Both dosages were safe and well tolerated. INTERPRETATION: DMq markedly reduced PBA frequency and severity, decreasing the condition's detrimental impact on a patient's life, with satisfactory safety and high tolerability. The findings expand the clinical evidence that DMq may be an important treatment for patients suffering from the socially debilitating symptoms of PBA.

Heart rate response to exercise stress testing in asymptomatic women: the st. James women take heart project.

BACKGROUND: The definition of a normal heart rate (HR) response to exercise stress testing in women is poorly understood, given that most studies describing a normative response were predominately based on male data. Measures of an attenuated HR response (chronotropic incompetence) and age-predicted HR have not been validated in asymptomatic women. We investigated the association between HR response to exercise testing and age with prognosis in 5437 asymptomatic women. METHODS AND RESULTS: Participants underwent a symptom-limited maximal stress test in 1992. HR reserve (change in HR from rest to peak), chronotropic index, and age-predicted peak HR were calculated. Deaths were identified to December 31, 2008. Mean age at baseline was 52+/-11 years, with 549 deaths (10%) over 15.9+/-2.2 years. Mean peak HR was inversely associated with age; mean peak HR=206-0.88(age). After adjusting for exercise capacity and traditional cardiac risk factors, risk of death was reduced by 3% for every 1-beat-per-minute increase in peak HR, and by 2% for every 1-beat-per-minute increase in HR reserve (P<0.001). Inability to achieve 85% age-predicted HR was not an independent predictor of mortality, but being >/=1 SD below the mean predicted HR or a chronotropic index <0.80 based on the prediction model established by this cohort were independent predictors of mortality (P<0.001 and P=0.023, respectively). CONCLUSIONS: Chronotropic incompetence is associated with an increased risk of death in asymptomatic women; however, the traditional male-based calculation overestimates the maximum HR for age in women. Sex-specific parameters of physiological HR response to exercise should be incorporated into clinical practice.

Perceived social isolation makes me sad: 5-year cross-lagged analyses of loneliness and depressive symptomatology in the Chicago Health, Aging, and Social Relations Study.

We present evidence from a 5-year longitudinal study for the prospective associations between loneliness and depressive symptoms in a population-based, ethnically diverse sample of 229 men and women who were 50-68 years old at study onset. Cross-lagged panel models were used in which the criterion variables were loneliness and depressive symptoms, considered simultaneously. We used variations on this model to evaluate the possible effects of gender, ethnicity, education, physical functioning, medications, social network size, neuroticism, stressful life events, perceived stress, and social support on the observed associations between loneliness and depressive symptoms. Cross-lagged analyses indicated that loneliness predicted subsequent changes in depressive symptomatology, but not vice versa, and that this temporal association was not attributable to demographic variables, objective social isolation, dispositional negativity, stress, or social support. The importance of distinguishing between loneliness and depressive symptoms and the implications for loneliness and depressive symptomatology in older adults are discussed.

Loneliness predicts increased blood pressure: 5-year cross-lagged analyses in middle-aged and older adults.

Loneliness is a prevalent social problem with serious physiological and health implications. However, much of the research to date is based on cross-sectional data, including our own earlier finding that loneliness was associated with elevated blood pressure (Hawkley, Masi, Berry & Cacioppo, 2006). In this study, we tested the hypothesis that the effect of loneliness accumulates to produce greater increases in systolic blood pressure (SBP) over a 4-year period than are observed in less lonely individuals. A population-based sample of 229 50- to 68-year-old White, Black, and Hispanic men and women in the Chicago Health, Aging, and Social Relations Study was tested annually for each of 5 consecutive years. Cross-lagged panel analyses revealed that loneliness at study onset predicted increases in SBP 2, 3, and 4 years later (B = 0.152, SE = 0.091, p < .05, one-tailed). These increases were cumulative such that higher initial levels of loneliness were associated with greater increases in SBP over a 4-year period. The effect of loneliness on SBP was independent of age, gender, race or ethnicity, cardiovascular risk factors, medications, health conditions, and the effects of depressive symptoms, social support, perceived stress, and hostility.

Loneliness predicts reduced physical activity: cross-sectional & longitudinal analyses.

OBJECTIVE: To determine cross-sectional and prospective associations between loneliness and physical activity, and to evaluate the roles of social control and emotion regulation as mediators of these associations. DESIGN: A population-based sample of 229 White, Black, and Hispanic men and women, age 50 to 68 years at study onset, were tested annually for each of 3 years. MAIN OUTCOME MEASURES: Physical activity probability, and changes in physical activity probability over a 3-year period. RESULTS: Replicating and extending prior cross-sectional research, loneliness was associated with a significantly reduced odds of physical activity (OR = 0.65 per SD of loneliness) net of sociodemographic variables (age, gender, ethnicity, education, income), psychosocial variables (depressive symptoms, perceived stress, hostility, social support), and self-rated health. This association was mediated by hedonic emotion regulation, but not by social control as indexed by measures of social network size, marital status, contact with close ties, group membership, or religious group affiliation. Longitudinal analyses revealed that loneliness predicted diminished odds of physical activity in the next two years (OR = 0.61), and greater likelihood of transitioning from physical activity to inactivity (OR = 1.58). CONCLUSION: Loneliness among middle and older age adults is an independent risk factor for physical inactivity and increases the likelihood that physical activity will be discontinued over time.

VLDL best predicts aortic root atherosclerosis in LDL receptor deficient mice.

Hyperlipidemia is a major risk factor for developing atherosclerosis in humans, and epidemiological studies have correlated specific lipoprotein levels with cardiovascular disease risk. Murine models of atherosclerosis rely on the induction of hyperlipidemia for vascular lesions to form, but the pathogenic contributions attributed to different lipoprotein populations are not well defined. To address this issue, we analyzed over 300 LDL receptor (LDLR) deficient mice that have been fed a high-fat diet and for which a full lipoprotein profile and aortic root atherosclerosis values were assessed. Overall, aortic root atherosclerosis is best predicted by plasma VLDL cholesterol levels with less predictive value derived from either LDL or HDL cholesterol. Triglyceride levels are more atherogenic in female mice, especially immune competent females, and depletion of the adaptive immune system leads to a global reduction in plasma lipid levels and aortic root lesion size yet does not appear to alter the atherogenic potential of individual lipoprotein subspecies. In contrast, HDL-cholesterol is a better predictor of aortic root atherosclerosis in apoE-deficient mice. In summary, this large scale analysis of high-fat diet fed LDLR deficient mice highlight the relationship between different plasma lipid components, especially VLDL-cholesterol, and aortic root atherosclerosis.

From social structural factors to perceptions of relationship quality and loneliness: the Chicago health, aging, and social relations study.

OBJECTIVE: The objective of this study was to test a conceptual model of loneliness in which social structural factors are posited to operate through proximal factors to influence perceptions of relationship quality and loneliness. METHODS: We used a population-based sample of 225 White, Black, and Hispanic men and women aged 50 through 68 from the Chicago Health, Aging, and Social Relations Study to examine the extent to which associations between sociodemographic factors and loneliness were explained by socioeconomic status, physical health, social roles, stress exposure, and, ultimately, by network size and subjective relationship quality. RESULT: Education and income were negatively associated with loneliness and explained racial/ethnic differences in loneliness. Being married largely explained the association between income and loneliness, with positive marital relationships offering the greatest degree of protection against loneliness. Independent risk factors for loneliness included male gender, physical health symptoms, chronic work and/or social stress, small social network, lack of a spousal confidant, and poor-quality social relationships. DISCUSSION: Longitudinal research is needed to evaluate the causal role of social structural and proximal factors in explaining changes in loneliness.

Dextromethorphan and quinidine in adult patients with uncontrolled painful diabetic peripheral neuropathy: a 29-day, multicenter, open-label, dose-escalation study.

BACKGROUND: Pain associated with diabetic peripheral neuropathy (DPN) has a substantial negative impact on patients' quality of life. OBJECTIVES: The primary objective of this study was to evaluate the tolerability of capsules containing dextromethorphan (DM) and quinidine (Q) in patients with painful DPN. A secondary objective was to perform a preliminary assessment of the efficacy of DM/Q in this patient population. METHODS: This was a multicenter, open-label, dose-escalation study. Eligible patients were aged between 18 and 80 years, had a confirmed diagnosis of diabetes with acceptable glycemic control, had been receiving established diabetic therapy for at least 3 months, and had a clinical diagnosis of distal symmetric sensory neuropathy with daily DPN-associated pain for the previous 3 months. On study entry, patient-rated diabetic pain had to be moderate or greater. Patients who met the inclusion criteria underwent a 2-week washout period during which all analgesics were discontinued, followed by 29 days of treatment with capsules containing DM 30 mg and Q 30 mg (DM30/Q30), beginning with 1 capsule/d and escalating at approximately 1-week intervals, as tolerated, to a maximum dose of 4 capsules/d (DM120/Q120). Tolerability was assessed based on adverse events and changes in clinical and laboratory parameters and nerve conduction velocity. Preliminary efficacy assessments included changes from baseline in scores on the pain intensity rating scale (PIRS), pain relief rating scale (PRRS), peripheral neuropathy quality-of-life instrument, and patients' diary assessments of sleep, present pain intensity, pain, and activity. RESULTS: The study included 36 men and women (mean age, 58 years; mean body mass index, 32.8 kg/m(2)). Of the 33 subjects who completed the study, 23 (69.7%) did so at the highest permitted dose (DM120/Q120). The most commonly reported adverse events (occurring in > or =5% of subjects) were nausea (27.8%), dizziness (25.0%), and headache (25.0%). Three patients experienced 5 serious adverse events, only 1 of which was considered possibly related to study drug. The most commonly occurring laboratory abnormalities (involving glycosylated hemoglobin, serum glucose, triglycerides, and cholesterol) were considered typical of a population with diabetes. Improvements from baseline in scores on the PIRS, PRRS, and other exploratory efficacy measures were noted (P < 0.001). CONCLUSIONS: The results of this open-label study indicated that the combination of DMIQ (dose range, DM30/Q30-DM120/Q120) was well tolerated in patients with pain associated with DPN. Based on the preliminary efficacy results, a randomized, controlled, double-blind trial is warranted to assess the tolerability and efficacy of this combination in patients with DPN.

Randomized, controlled trial of dextromethorphan/quinidine for pseudobulbar affect in multiple sclerosis.

OBJECTIVE: To evaluate the efficacy and safety of DM/Q (capsules containing dextromethorphan [DM] and quinidine [Q]) compared with placebo, taken twice daily, for the treatment of pseudobulbar affect over a 12-week period in multiple sclerosis patients. METHODS: A total of 150 patients were randomized in a double-blind, placebo-controlled study to assess pseudobulbar affect with the validated Center for Neurologic Study-Lability Scale. Each patient also recorded the number of episodes experienced between visits, estimated quality of life and quality of relationships on visual analog scales, and completed a pain rating scale. RESULTS: Patients receiving DM/Q had greater reductions in Center for Neurologic Study-Lability Scale scores than those receiving placebo (p < 0.0001) at all clinic visits (days 15, 29, 57, and 85). All secondary end points also favored DM/Q, including the number of crying or laughing episodes (p

Loneliness as a specific risk factor for depressive symptoms: cross-sectional and longitudinal analyses.

The extent to which loneliness is a unique risk factor for depressive symptoms was determined in 2 population-based studies of middle-aged to older adults, and the possible causal influences between loneliness and depressive symptoms were examined longitudinally in the 2nd study. In Study 1, a nationally representative sample of persons aged 54 and older completed a telephone interview as part of a study of health and aging. Higher levels of loneliness were associated with more depressive symptoms, net of the effects of age, gender, ethnicity, education, income, marital status, social support, and perceived stress. In Study 2, detailed measures of loneliness, social support, perceived stress, hostility, and demographic characteristics were collected over a 3-year period from a population-based sample of adults ages 50-67 years from Cook County, Illinois. Loneliness was again associated with more depressive symptoms, net of demographic covariates, marital status, social support, hostility, and perceived stress. Latent variable growth models revealed reciprocal influences over time between loneliness and depressive symptomatology. These data suggest that loneliness and depressive symptomatology can act in a synergistic effect to diminish well-being in middle-aged and older adults.