World Association of Sleep Medicine (WASM) 2016 standards for recording and scoring leg movements in polysomnograms developed by a joint task force from the International and the European Restless Legs Syndrome Study Groups (IRLSSG and EURLSSG).

This report presents the results of the work by a joint task force of the International and European Restless Legs Syndrome Study Groups and World Association of Sleep Medicine that revised and updated the current standards for recording and scoring leg movements (LM) in polysomnographic recordings (PSG). First, the background of the decisions made and the explanations of the new rules are reported and then specific standard rules are presented for recording, detecting, scoring and reporting LM activity in PSG. Each standard rule has been classified with a level of evidence. At the end of the paper, Appendix 1 provides algorithms to aid implementation of these new standards in software tools. There are two main changes introduced by these new rules: 1) Candidate LM (CLM), are any monolateral LM 0.5-10 s long or bilateral LM 0.5-15 s long; 2) periodic LM (PLM) are now defined by runs of at least four consecutive CLM with an intermovement interval ≥10 and ≤ 90 s without any CLM preceded by an interval <10 s interrupting the PLM series. There are also new options defining CLM associated with respiratory events. The PLM rate may now first be determined for all CLM not excluding any related to respiration (providing a consistent number across studies regardless of the rules used to define association with respiration) and, subsequently, the PLM rate should also be calculated without considering the respiratory related events. Finally, special considerations for pediatric studies are provided. The expert visual scoringof LM has only been altered by the new standards to require accepting all LM > 0.5 s regardless of duration, otherwise the technician scores the LM as for the old standards. There is a new criterion for the morphology of LM that applies only to computerized LM detection to better match expert visual detection. Available automatic scoring programs will incorporate all the new rules so that the new standards should reduce technician burden for scoring PLMS.

Measuring sleep: accuracy, sensitivity, and specificity of wrist actigraphy compared to polysomnography.

OBJECTIVES: We validated actigraphy for detecting sleep and wakefulness versus polysomnography (PSG). DESIGN: Actigraphy and polysomnography were simultaneously collected during sleep laboratory admissions. All studies involved 8.5 h time in bed, except for sleep restriction studies. Epochs (30-sec; n = 232,849) were characterized for sensitivity (actigraphy = sleep when PSG = sleep), specificity (actigraphy = wake when PSG = wake), and accuracy (total proportion correct); the amount of wakefulness after sleep onset (WASO) was also assessed. A generalized estimating equation (GEE) model included age, gender, insomnia diagnosis, and daytime/nighttime sleep timing factors. SETTING: Controlled sleep laboratory conditions. PARTICIPANTS: Young and older adults, healthy or chronic primary insomniac (PI) patients, and daytime sleep of 23 night-workers (n = 77, age 35.0 ± 12.5, 30F, mean nights = 3.2). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Overall, sensitivity (0.965) and accuracy (0.863) were high, whereas specificity (0.329) was low; each was only slightly modified by gender, insomnia, day/night sleep timing (magnitude of change < 0.04). Increasing age slightly reduced specificity. Mean WASO/night was 49.1 min by PSG compared to 36.8 min/night by actigraphy (ß = 0.81; CI = 0.42, 1.21), unbiased when WASO < 30 min/night, and overestimated when WASO > 30 min/night. CONCLUSIONS: This validation quantifies strengths and weaknesses of actigraphy as a tool measuring sleep in clinical and population studies. Overall, the participant-specific accuracy is relatively high, and for most participants, above 80%. We validate this finding across multiple nights and a variety of adults across much of the young to midlife years, in both men and women, in those with and without insomnia, and in 77 participants. We conclude that actigraphy is overall a useful and valid means for estimating total sleep time and wakefulness after sleep onset in field and workplace studies, with some limitations in specificity.

Efficacy and safety of pramipexole in restless legs syndrome.

OBJECTIVE: To evaluate the efficacy and safety of pramipexole in patients with moderate to severe restless legs syndrome (RLS) METHODS: The authors conducted a 12-week, double-blind, randomized, placebo-controlled trial of fixed doses of pramipexole (0.25, 0.50, and 0.75 mg/day). Patients (N = 344) were up-titrated to their randomized dose over 3 weeks. The primary efficacy endpoints were patient ratings of symptom severity on the International RLS Study Group Rating Scale (IRLS) and clinician ratings of improvement on the Clinical Global Impressions-Improvement (CGI-I) scale. Secondary efficacy endpoints included visual analogue ratings of sleep and quality of life (QOL) RESULTS: By both primary measures, pramipexole was superior to placebo. For IRLS, the adjusted mean (SE) change from baseline to week 12 was -9.3 (1.0) for placebo, -12.8 (1.0) for 0.25 mg/day, -13.8 (1.0) for 0.50 mg/day, and -14.0 (1.0) for 0.75 mg/day (all p < 0.01). Similarly, pramipexole increased the percentage of patients with a CGI-I rating of "very much improved" or "much improved" at the end of the trial (51.2% for placebo and 74.7%, 67.9%, and 72.9% for pramipexole; all p < 0.05). Pramipexole significantly improved ratings of symptom severity, day and night, and also ratings of sleep satisfaction and QOL. Pramipexole was well tolerated: The most frequent adverse events with higher occurrence in the pramipexole group were nausea (19.0% vs 4.7%) and somnolence (10.1% vs 4.7%) CONCLUSION: As rated by patients and by clinicians, pramipexole was efficacious and safe in reducing the symptoms of restless legs syndrome.

Considering the causes of RLS.

The pathophysiology of restless legs syndrome (RLS) is complex and remains to be fully elucidated. The condition is predominantly a disorder of the central rather than the peripheral, nervous system, and dopaminergic dysfunction in subcortical systems appears to play a central role. Conditions associated with secondary RLS, such as pregnancy or end-stage renal disease, are characterized by iron deficiency, which suggests that disturbed iron homeostasis may also play a role in the development of the condition. Although most patients with RLS have normal serum ferritin levels, concentrations of ferritin and transferrin in the cerebrospinal fluid are reduced, suggesting iron deficiency within the central nervous system. Although iron is necessary for the activity of tyrosine hydroxylase, the rate-limiting step in dopamine synthesis, it is unclear whether this relationship plays a role in the aetiology of RLS. There also appears to be a genetic component, particularly when the condition develops before the age of 45 years. Candidate genetic loci have been located on chromosomes 9p, 12q and 14q, but the genes involved have yet to be identified. How these three identified aetiological factors, namely dopaminergic dysfunction, impaired iron homeostasis and genetic disposition, are inter-related in the genesis of RLS remains unclear.

Schizophrenia, obesity, and obstructive sleep apnea.

BACKGROUND: This study evaluated the risk factors for obstructive sleep apnea in psychiatric patients. METHOD: The subjects were 364 patients referred to a sleep disorders consultation service from an inpatient psychiatric hospital. Seventy-eight percent underwent polysomnographic testing. Rates of obstructive sleep apnea in different diagnostic groups (established by clinical DSM-III-R diagnosis) were retrospectively assessed. RESULTS: Logistic regression demonstrated significant independent effects of age (p = .046), gender (p = .002), body mass index (p < .001), and chronic neuroleptic use (p = .012) on the presence of obstructive sleep apnea (defined as more than 20 instances of apnea and/or hypopnea per hour of sleep). Patients with schizophrenia were significantly heavier and had higher rates of sleep apnea than did other psychiatric patients. CONCLUSION: Obesity, male gender, and chronic neuroleptic administration are risk factors for obstructive sleep apnea in psychiatric patients. Since patients with schizophrenia are often on long-term neuroleptic treatment, they may have high rates of obstructive sleep apnea, mediated via the weight gain produced by such medications. Overweight psychiatric patients and those on chronic neuroleptic treatment (e.g., patients with schizophrenia) should be evaluated for sleep apnea if signs and symptoms of this disorder are present.

Health status in patients with disturbed sleep and obstructive sleep apnea.

The health status of 435 consecutive patients with sleep disturbances necessitating polysomnography was investigated. Patients underwent overnight polysomnography and health status assessment, including the Medical Outcomes Study SF-36 Health Survey and the Pittsburgh Sleep Quality Index. Based on a respiratory distress index (RDI) greater than 10 to define apnea, patients with apnea were significantly (P < 0.05) more likely to be male, be older, and have higher body mass index and lower oxygen saturation levels than patients without apnea. Multiple domains of the SF-36 Health Survey and the Pittsburgh Sleep Quality Index were significantly worse (P < 0.05) for this population when normative data were compared. Although few differences were observed between the apneic and nonapneic patients when a cutoff point for apnea was defined as an RDI greater than 10 or 20, increasing RDI was significantly associated with worsening physical functioning scores. Overall, decrements in health status measures were more strongly correlated with the number of oxygen desaturations below 85% than with increasing RDI. We conclude that patients with sleep disturbances demonstrate significant decrements in general and sleep-specific health status, but these decrements are more closely associated with oxygen desaturation than RDI.

Appropriateness of prostate-specific antigen testing.

We established criteria for appropriate use of the prostate-specific antigen (PSA) assay and used them to evaluate PSA test utilization at 1 tertiary care institution. During a 6-month period, 2,330 PSA results were reported for outpatients and 95 for inpatients. We reviewed medical records for a random sample of 338 outpatient results (14.51%) and all 95 inpatient results, of which 21% (71/338) of outpatient and 17% (16/95) of inpatient results were inappropriate according to our test utilization criteria. Among outpatients, 52% of tests were done for screening and 19% for monitoring for cancer recurrence. For inpatients, workup for cancer (53/95 [56%]) was the most frequent indication for testing and screening the second (24/95 [25%]). Of tests failing the criteria, 66 (76%) of 87 resulted from excessively frequent and age-inappropriate screening. We assessed the potential effect on clinical outcome if these tests were not performed. Of the 87 tests considered inappropriate, only 1 test result influenced clinical management for patients younger than 75 years. By instituting simple limits on age and frequency, we estimate that 74% (64/87) of the inappropriate tests could have been eliminated.

Comparison of disaturated phosphatidylcholine and fetal lung maturity surfactant/albumin ratio in diabetic and nondiabetic pregnancies.

We studied fetal lung maturity (FLM) by the amniotic fluid surfactant/albumin (FLM S/A) ratio and the disaturated phosphatidylcholine (DSPC) amniotic fluid levels at different gestational ages in diabetic (179 women with type 1 diabetes mellitus antedating pregnancy; infants delivered within 72 hours after amniotic fluid testing for DSPC level and FLM S/A ratio) and nondiabetic pregnancies (2 independent nondiabetic groups, 300 for FLM S/A ratio and 1,231 for DSPC level). The degree of maternal glycemia during gestation was estimated by serial measurements of hemoglobin A1. Multiple regression analyses, including gestational age (GAs) and diabetic status as independent variables and FLM S/A ratio and DSPC level as dependent variables, revealed significant effect from diabetic status and GA for FLM S/A ratio and a significant effect from GA but not from diabetic status for DSPC level. Glucose levels were controlled adequately throughout gestation as reflected by mean total glycated hemoglobin levels. Amniotic fluid levels of DSPC, the major surface tension-lowering component of pulmonary surfactant, are not significantly different between diabetic and nondiabetic pregnancies at different GAs.

Myoglobin, creatine-kinase-MB and cardiac troponin-I 60-minute ratios predict infarct-related artery patency after thrombolysis for acute myocardial infarction: results from the Thrombolysis in Myocardial Infarction study (TIMI) 10B.

OBJECTIVES: We examined the diagnostic performance of serum myoglobin, creatine-kinase-MB (CK-MB) and cardiac troponin-I (cTnI) for predicting the infarct-related artery (IRA) patency in patients receiving TNK-tissue plasminogen activator (TNK-tPA) therapy for acute myocardial infarction (AMI) in the Thrombolysis in Myocardial Infarction (TIMI) 10B trial. BACKGROUND: A reliable noninvasive serum marker of IRA patency is desired to permit early identification of patients with a patent IRA after thrombolysis. METHODS: We measured myoglobin, CK-MB and cTnI concentrations in sera obtained just before thrombolysis (T0) and 60 min later (T60) in 442 patients given TNK-tPA and who underwent coronary angiography at 60 min. RESULTS: Angiography at 60 min showed a patent IRA (TIMI flow grade 2, 3) in 344 and occluded IRA (TIMI flow grade 0, 1) in 98 patients. The median serum T60 concentration, the ratio of the T60 and T0 serum concentration (60-min ratio) and the slope of increase over 60 min for each serum marker were significantly higher in patients with patent arteries compared with patients with occluded arteries. The area under the receiver-operating characteristic (ROC) curve for diagnosis of occlusion was 0.71, 0.70 and 0.71 for the 60-min ratio of myoglobin, cTnI and CKMB, respectively. The 60-min ratios of > or =4.0 for myoglobin, > or =3.3 for CK-MB and > or =2.0 for cTnI yielded a probability of patency of 90%, 88% and 87%, respectively. CONCLUSIONS: The diagnostic performance of serum myoglobin, CK-MB and cardiac troponin-I (cTnI) 60-min ratios was similar. The probability of a patent IRA was very high (90%) in patients with 60-min myoglobin ratio > or =4.0, and early invasive interventions to establish IRA patency may not be necessary in this group. Serum marker determinations at baseline and 60-min after thrombolysis may permit rapid triage of patients receiving thrombolytic therapy by ruling out IRA occlusion.

The evoked heart rate response to periodic leg movements of sleep.

STUDY OBJECTIVES: Periodic leg movements of sleep are currently subdivided based upon whether or not they are associated with EEG arousal. "Autonomic" arousals, characterized by elevations in heart rate and blood pressure without AASM-defined EEG changes, have been associated with daytime somnolence in experimental protocols. In this study, we will describe the heart rate response to periodic leg movements of sleep, both with and without associated arousals. DESIGN: Heart rate was averaged for each of the ten cardiac cycles before, and after, the onset of individual periodic leg movements occurring in non-REM sleep for eight patients with Periodic Limb Movement Disorder (PLMD). Records were blindly scored (without EKG data) to determine if AASM-defined EEG arousals occurred within two seconds of leg movement onset. Leg movements during wakefulness were performed by four non-patient controls as a control condition. SETTING: Sleep Disorders Center INTERVENTIONS: None MEASUREMENTS AND RESULTS: A significant rise in heart rate was observed following the onset of individual leg movements of sleep (N = 796), which was also significantly larger than that seen after waking leg movements (N = 275). Although heart rate elevation was 10%-40% higher when leg movements were associated with AASM-defined arousal, these differences did not reach statistical significance. CONCLUSIONS: Periodic leg movements of sleep are associated with cardiac acceleration, even in the absence of AASM-defined arousal. It appears premature to conclude that periodic leg movements of sleep not associated with visible EEG arousal are clinically insignificant.

The laboratory-clinical interface: point-of-care testing.

POC testing provides an opportunity for clinicians and laboratorians to work together to consider how best to serve the patients within an individual institution. Each health system has unique characteristics relative to patient population, as well as a unique laboratory structure. If physicians, nurses, laboratorians, and pathologists work collaboratively, the best interests of patients will be served. In some institutions that cater to specific patient groups, POC testing may offer clear and distinct advantages. In other institutions with sophisticated transport systems and established rapid response capabilities, the quality resulting from central laboratory testing may outweigh any advantages of bedside testing. Clearly, attention to regulatory issues, QC issues, the importance of proper documentation, proficiency testing, performance enhancement, and cost-effectiveness is requisite. As the technology for diagnostic testing advances through more microcomputerization, microchemistry, and enhanced test menus, the concept of POC testing will need perpetual revisiting. We hope that the information provided here will aid clinicians, laboratorians, and administrators in their quest to best serve their patients.

The prevalence of sleep-related eating disorder in psychiatric and non-psychiatric populations.

BACKGROUND: Sleep-related eating disorder is a little-described syndrome combining features of sleep disorders and eating disorders. The behaviour consists of partial arousals from sleep followed by rapid ingestion of food, commonly with at least partial amnesia for the episode the following day. The aim of this study was to provide an estimate of the prevalence of sleep-related eating disorder. METHODS: The Inventory of Nocturnal Eating, a self-report questionnaire addressing nocturnal eating and sleep disturbance, was administered to out-patients (N = 126) and in-patients (N = 24) with eating disorders, obese subjects (N = 126) in a trial of an anorexic agent, depressed subjects (N = 207) in an antidepressant trial, and an unselected group (N = 217) of college students. Sleep-related eating disorder was operationally defined as nocturnal eating with a self-reported reduced level of awareness, occurring at least once per week. RESULTS: Almost 5.0% (33/700) of the sample described symptoms consistent with sleep-related eating disorder. The in-patient eating disorders group had nearly twice the prevalence (16.7%) of the out-patient eating disorder sample (8.7%), which had nearly twice the prevalence of the next highest group, the student sample (4.6%). Subjects with sleep-related eating disorder endorsed more symptoms consistent with sleep disorders and had higher levels of depression and dissociation than those without nocturnal eating. CONCLUSIONS: Sleep-related eating disorder is more common than is generally recognized, especially in those with a daytime eating disorder. Sleep disorder symptoms are often associated with sleep-related eating disorder, as are depression and dissociation. Evaluation of individuals with eating disorders should include assessment for sleep-related eating.

What proportion of common diagnostic tests appear redundant?

PURPOSE: To identify ancillary tests for which there are criteria defining the earliest interval at which a repeat test might be indicated, to determine how often each test is repeated earlier than these intervals and, if repeated, provides useful information. SUBJECTS AND METHODS: We performed a retrospective cohort study of 6,007 adults discharged from a large teaching hospital during a 3-month period in 1991. We measured the proportion of commonly performed diagnostic tests that were redundant, and their associated charges. RESULTS: Of the 6,007 patients discharged, 5,289 (88%) had at least one of 12 target tests performed. Overall, 78,798 of the target tests were performed during the study period, of which 22,237 (28%) were repeated earlier than test-specific predefined intervals. This percentage varied substantially by test (range, 2% to 62%). To assess how many early repeats were justified, we performed chart reviews in a random sample stratified by test. For two tests, nearly all the initial results in the sample were abnormal, and all repeats were considered justified. Of early repeats following a normal initial result for the remaining 10 tests, chart review found no clinical indication for 92%, and a weighted mean of 40% appeared redundant. Overall, 8.6% of these 10 tests appeared redundant; if these were not performed, the annual charge reductions would be $930,000 at our hospital, although the impact on costs would be much smaller. CONCLUSIONS: For some tests, an important proportion are repeated too early to provide useful clinical information. Most such tests might be eliminated using computerized reminder systems.

Clinical and polysomnographic features of sleep-related eating disorder.

BACKGROUND: Sleep-related eating disorder is a recently described clinical syndrome that combines characteristics of both eating and sleep disorders. Nocturnal partial arousals are followed by rapid ingestion of food and subsequent poor memory for the episode. Only two case series examining this disorder have been published, and both are from the same sleep disorders center in a general hospital. METHOD: The author describes 23 consecutive cases of sleep-related eating disorder that presented to the Sleep Disorders Center at McLean Hospital. All patients were administered at a standardized clinical sleep disorders evaluation followed by a semistructured interview to elicit information regarding characteristics of sleep-related eating disorder. Polysomnographic evaluation was performed on all patients with clinical histories of sleep-related eating disorder. RESULTS: Eighty-three percent (N = 19) of the 23 patients were female. For most of the patients, the disorder had begun in adolescence (mean +/- SD = 21.6 +/- 10.9 years) and had been chronic, with a mean duration of 15.8 +/- 11.2 years. Nearly all patients reported eating on a nightly basis (1-6 times per night), and all episodes followed a period of sleep. All patients described their eating as "out of control," and two thirds stated that they "binged" during the night. Over 90% (21/23) reported their state at the time of nocturnal eating as "half-awake, half-asleep" or "asleep", and over 90% reported "consistent" or "occasional" amnesia for the event. Nearly half (11/23) of the sample were given a polysomnographic diagnosis of somnambulism. Thirty-five percent (8/23) had a lifetime eating disorder diagnosis. CONCLUSION: Sleep-related eating disorder appears to be a relatively homogeneous syndrome combining features of somnambulism and daytime eating disorders. However, no current nosology accurately characterizes these patients. Physicians should be aware of the existence of the disorder and the value of referring patients with sleep-related eating disorder to a sleep disorders center.

Myoglobin, creatine kinase MB, and cardiac troponin-I to assess reperfusion after thrombolysis for acute myocardial infarction: results from TIMI 10A.

BACKGROUND: The availability of a reliable, noninvasive serum marker of reperfusion may permit early identification of patients with occlusion after thrombolysis who might benefit from further interventions. METHODS: We measured myoglobin, creatine kinase MB (CK-MB), and cardiac troponin-I (cTnI) concentrations in sera obtained just before thrombolysis (T0) and 60 minutes later (T60) in 30 patients given TNK-tPA for acute myocardial infarction as part of the Thrombolysis in Myocardial Infarction (TIMI) 10A trial. RESULTS: Angiography at T60 showed reperfusion (TIMI flow grade 2 to 3; n = 19) or occlusion (TIMI flow grade 0 to 1; n = 8). The median serum T60 concentration, the ratio of the T60 and T0 serum concentration, and the slope of increase over a 60-minute period for each serum marker were significantly higher in patients with patent arteries compared with patients with occluded arteries. The areas under the receiver operator characteristics curve for diagnosis of occlusion were 0.96, 0.91, and 0.87 for the T60 concentration of myoglobin, CK-MB and cTnI, respectively. Although the T60 levels of <469 ng/ml for myoglobin, <11.5 ng/ml for CK-MB, and < 1.1 ng/ml for cTnI identified all patients with occlusion, the specificity of myoglobin (94%) was higher than that of CK-MB (61%) and cTnI (67%). Similar results were obtained for the 60-minute ratios and 60-minute slopes for each marker, with indexes for myoglobin having the highest specificity. CONCLUSIONS: In this pilot study, noninvasive diagnosis of occlusion 60 minutes after thrombolysis was achieved with a high degree of sensitivity and specificity with the myoglobin, CK-MB, and cTnI concentrations measured at that time point. These preliminary findings may permit a new strategy for assessment of the success of reperfusion, with triage to rescue angioplasty for patients in whom the 60-minute cardiac marker values or indexes are consistent with occlusion of the infarct-related artery.

How fast is fast enough for clinical laboratory turnaround time? Measurement of the interval between result entry and inquiries for reports.

We measured the time interval from result entry by the clinical laboratory to inquiry for reports by clinicians as a proxy for the actual turnaround time required to meet current patient care needs and to determine whether different patterns of report inquiry occur among clinical departments. The study included 4,004 complete blood cell (CBC) count reports that were sought by the clinical services using the hospital information system. The median time to report inquiry was 90 minutes for routine inpatient tests, 35 minutes for stat inpatient tests, and 30 minutes for the stat outpatient CBC counts. Most reports (range, 86%-94%) from these three subgroups were requested within 4 hours from entry of the results in the hospital information system. Of the routine outpatient test reports, 14%, 23%, and 31% were requested within the first 2 hours, 4 hours, and 8 hours, respectively. Although the interdepartmental variations in the median time for report inquiry were statistically significant for routine inpatient tests, stat inpatient tests, and stat outpatient tests, inquiries for the preponderance of reports for all three groups were within the first 1.5 to 3 hours from entry of the results in the hospital information system. We conclude that the majority of CBC counts and other tests with effects on immediate patient care management must be performed very rapidly on site and cannot be moved off site without compromising current standards of medical practice.

Photodynamic therapy using a protoporphyrinogen oxidase inhibitor.

The use of endogenously created porphyrins as an alternative to photosensitizer injection for photodynamic therapy is a rapidly evolving area of study. One common method to induce porphyrin synthesis and accumulation in cells is the topical, oral, or parenteral administration of 5-aminolevulinic acid, a precursor for heme biosynthesis. Porphyrin accumulation may also be elicited by the use of enzyme inhibitors of the heme biosynthetic pathway. Groups of DBA/2 mice bearing SMT-F mammary tumors were placed on a diet containing 0-4000 ppm of a protoporphyrinogen oxidase inhibitor, FP-846. This agent blocks a critical step in porphyrin metabolism and results in elevated intracellular levels of protoporphyrin IX. Light treatment of tumors produced both initial and long-term regression that was dependent on the amount of inhibitor, the duration of inhibitor exposure to animals, and the amount of light used in PDT. Tumor regression occurred without significant destruction of normal tissues in the treatment field and without initial vascular constriction or blood flow stasis. Tumor cure in animals given 4000 ppm FP-846 in feed for 3 days and 300 J/cm2 602-670 nm light (23% cure) was similar to the response in animals given 10 mg/kg Photofrin and the same light dose (20%).