Sleep improves when patients with chronic OA pain are managed with morning dosing of once a day extended-release morphine sulfate (AVINZA): findings from a pilot study.

STUDY OBJECTIVE: To investigate the effect of once-a-day extended release of morphine sulfate AVINZA (A-MQD) on polysomnographic measures of sleep in a population of chronic osteoarthritic pain patients with sleep difficulties. DESIGN: Single-center, single-blind, placebo-lead-in, 30 mg or 60 mg. Patients' sleep and neurocognition were objectively measured at a sleep laboratory, and patients self-rated their pain, sleep, and other functions. PARTICIPANTS: Thirty-four participants (26 to 75 years old) complaining of sleep difficulties and chronic, stable pain secondary to hip or knee osteoarthritis. INTERVENTIONS: Participants had a screening visit on current pain medication and then, following a single-blind placebo run-in period, received 30 mg/d of A-MQD for six days. At day 6, doses for participants with incomplete pain relief on the Brief-Pain-Inventory (BPI) pain scale were increased to 60 mg/d. Treatment continued for another eight days at the new dose level (14 days for a subgroup at 60 mg/d). Sleep was objectively measured by all-night polysomnography (PSG) at screening while on the participants' current pain therapy, at baseline following a placebo run-in and at the end of treatment while on A-MQD. OUTCOME MEASURES: PSG parameters evaluated included Total-Sleep-Time (TST), Wake-timeafter-Sleep-Onset (WASO), Sleep-Efficiency (SE), Latency-to-Persistent Sleep (LPS), Latency-to-REM-sleep, the Number-of-Awakenings (NAW), the time spent in each stage of sleep, and REM-sleep-latency. Subjective evaluations included participants' estimations of sleep time and sleep quality, the Epworth-Sleepiness-Scale (ESS), the BPI, and participant acceptance of and relief due to current therapy. Assessments of neurocognitive function were also made. RESULTS: Sleep initiation and maintenance tended to improve with A-MQD as demonstrated by the increases in TST and SE and decreases in WASO and NAW as compared with placebo-baseline values. Sleep architecture was preserved by the study drug and some increases in stage 2 and 3/4 sleep were seen compared with placebo baseline. Subjective ratings of sleep quality and sleep time were significantly improved with treatment, as were BPI scores and ratings of medication acceptance and pain relief. A-MQD was generally well tolerated. CONCLUSIONS: A-MQD was an effective treatment for pain, and this study treatment was associated with improvement of both objective and subjective sleep parameters in participants with chronic osteoarthritic pain.

Assessing the trade-offs between crossover and parallel group designs in sleep research.

Sleep researchers invariably struggle with decisions regarding the optimal design for their studies. Whether such studies involve treatment for insomnia, obstructive sleep apnea, or any other sleep disorder, questions arise regarding the respective trade-offs between a parallel group and a crossover design. This study analyzed the variance structure of commonly measured polysomnographic variables in an effort to describe the statistical impact of these alternate designs. The study examined the effects of opioids on sleep and employed multiple crossovers between placebo, MS-contin, and methadone using a double-blind, randomized crossover design. Thirty-seven healthy subjects were studied. Four of the subjects were unable to complete the protocol for a variety of reasons, and polysomnogram data was unavailable for one subject. Data from 37 subjects provide the basis for this analysis. Despite dropouts, the crossover study was approximately four times as efficient as the parallel group design in terms of being able to recognize differences in deep sleep across these conditions. Other polysomnographic variables also favored the crossover design to varying extents. Despite the operational complexity of a crossover design, the statistical efficiency of this approach makes it a preferable approach for designing intervention studies in sleep research.

Twenty-five-year-old man with a giant left ventricular mass.

We report a rare case of a massive 7- x 3.25-cm thrombus in the left ventricle of a 25-year-old man. He presented with a subacute febrile illness for 1 month with a sudden worsening respiratory distress and chest pain. His initial evaluation in the emergency department diagnosed an interstitial lung process. Two-dimensional echocardiography demonstrated a previously undiagnosed cardiomyopathy and a massive left ventricular thrombus.

Nasal CPAP treatment for obstructive sleep apnea: developing a new perspective on dosing strategies and compliance.

Nasal continuous positive airway pressure (CPAP) is presently considered as the "treatment of choice" for obstructive sleep apnea (OSA). Though some OSA patients adhere to treatment recommendations and ultimately respond quite well to CPAP therapy, there is a substantial subgroup for which compliance is a particularly difficult issue. Despite receiving recommendations to the contrary and for reasons that are incompletely understood, the majority of OSA patients settle for a partial compliance pattern. Whether a partial compliance schedule is beneficial or harmful is virtually unexamined: Unlike other medical treatments, there are few data concerning the "dose-response relationship" of CPAP to its desired effects. We argue that CPAP "dose" is a function not only of CPAP pressure but of time-on-CPAP as well. Critical questions that remain unanswered are what "dose" of CPAP is needed to effect an appropriate treatment outcome and which treatment outcomes should form the basis of our recommendations. Recent placebo-controlled studies comparing CPAP to suboptimal CPAP pressures may be informative in this regard. Directions for future research are suggested.

Effect of ethnicity on sleep: complexities for epidemiologic research.

STUDY OBJECTIVES: The goal of this study was to examine whether there were ethnic differences in polysomnographically recorded sleep, either in the controlled laboratory environment or in the home setting. DESIGN: Prospective study of ethnic differences in stress physiology and sleep. SETTING: Two sleep recordings were performed on consecutive nights in a hospital-based sleep laboratory, followed 1 to 4 weeks later by a third sleep recording in the subject's home. PARTICIPANTS: 51 employed healthy adult subjects, aged 15 to 50 years. 24 self-identified as black, and 27 as white. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Blacks had less slow wave sleep than did whites in both the sleep laboratory and in the home. Blacks had significantly more slow wave sleep at home compared to the hospital setting, while the reverse was true for whites. This location-by-ethnicity interaction could not be accounted for by depression ratings or social class. CONCLUSIONS: The home setting is generally considered to be more ecologically valid than the controlled hospital-based laboratory setting for the monitoring of sleep. These data suggest that ethnicities may respond differentially to the sleeping environment. This observation may need to be taken into account in future epidemiologic studies of sleep.

Fatigue in obstructive sleep apnea: driven by depressive symptoms instead of apnea severity?

OBJECTIVE: Obstructive sleep apnea is a common and frequently devastating illness that often includes significant fatigue. Fatigue is also a hallmark depressive symptom. The authors wondered if depressive symptoms in patients with obstructive sleep apnea would account for some of the fatigue beyond that explained by obstructive sleep apnea severity. METHOD: Sixty patients with obstructive sleep apnea-i.e., score >/=15 on the respiratory disturbance index (mean score=49; range=15-111)-underwent polysomnography and completed the Center for Epidemiological Studies Depression Scale (CES-D Scale), Profile of Mood States (POMS), and Medical Outcomes Study surveys. Data were analyzed by using hierarchical regression, with POMS fatigue score as the dependent variable (step 1, forced entry of apnea severity variables; step 2, forced entry of CES-D Scale score). RESULTS: Whereas score on the respiratory disturbance index and the percent of time oxygen saturation was <90% together accounted for 4.2% of variance in scores on the POMS fatigue scale, the CES-D Scale score accounted for 10 times the variance (i.e., an additional 42.3%) in POMS fatigue scale score. CONCLUSIONS: After obstructive sleep apnea severity was controlled, higher levels of depressive symptoms were dramatically and independently associated with greater levels of fatigue. Assessment and treatment of mood symptoms-not just treatment of the disordered breathing itself-might reduce the fatigue experienced by patients with obstructive sleep apnea.

Predictors of mood response to acute tryptophan depletion. A reanalysis.

Acute tryptophan depletion (ATD) induces depressive symptoms in 50-60% of selective serotonin reuptake inhibitor (SSRI) treated, recovered depressed patients. However, no reliable predictors of mood response to ATD have been established. In the present study, individual subject data of six ATD studies were pooled ('mega-analysis') in order to investigate the mediating role of clinical, demographic and biochemical characteristics in the mood response to ATD. A procedure was developed to make different versions of the Hamilton scale comparable. Recurrent depressive episodes, female gender, prior exposure to SSRI antidepressant treatment and previous serious suicidal thoughts/attempts all appear to be independent predictors of mood response to ATD. Chronicity of illness is the most powerful predictor. Residual symptoms of depression were not found to predict response to ATD. ATD may be useful to study the mechanism of action of SSRI antidepressants and individual biological vulnerability of the serotonin system. Whether the effects of ATD represent a reversal of the action of SSRI antidepressants or individual vulnerability probably depends upon the timing of the procedure in the course of remission of a depressive episode.

Psychologic correlates of compliance with continuous positive airway pressure.

STUDY OBJECTIVES: To explore the relationship between psychologic variables measured prior to continuous positive airway pressure (CPAP) treatment and subsequent CPAP compliance. DESIGN: Participants were assigned to a CPAP treatment group. Psychologic questionnaires administered prior to the start of treatment assessed depression, anxiety, stress, anger or hostility, social support, social desirability, and coping. Polysomnography was performed on admission (prior to start of treatment) and at the end of 1 week of treatment. Compliance was measured nightly by an intemal clock counter in the CPAP unit and averaged over the 1-week treatment period. SETTING: N/A. PARTICIPANTS: Twenty-three CPAP-naive patients with obstructive sleep apnea were enrolled in a study of the effects of CPAP on sympathetic nervous system functioning, quality of life, and psychologic functioning. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Objectively measured average daily compliance was significantly associated with a measure of coping strategies. Multiple regression analyses revealed that Active Ways of Coping accounted for a significant amount of variance in CPAP compliance, even after the respiratory disturbance index, daytime sleepiness, and Passive Ways of Coping were taken into account. No other psychologic variable assessed prior to CPAP treatment was associated with subsequent CPAP compliance. CONCLUSIONS: These results suggest that individuals who engage in active coping strategies with new and difficult situations used CPAP more. It may be that encouraging patients to use coping techniques, such as planful problem solving, will help to improve compliance with CPAP.