Validation of the Kohnen Restless Legs Syndrome-Quality of Life instrument.

BACKGROUND: Due to the symptoms and the sleep disturbances it causes, Restless Legs Syndrome (RLS) has a negative impact on quality of life. Measurement of such impact can be performed by means of questionnaires, such as the Kohnen Restless Legs Syndrome-Quality of Life questionnaire (KRLS-QoL), a specific 12-item instrument that is self-applied by patients. The present study is aimed at performing a first formal validation study of this instrument. METHODS: Eight hundred ninety-one patients were included for analysis. RLS severity was assessed by the International Restless Legs Scale (IRLS), Restless Legs Syndrome-6 scales (RLS-6), and Clinical Global Impression of Severity. In addition the Epworth Sleepiness Scale (ESS) was assessed. Acceptability, dimensionality, scaling assumptions, reliability, precision, hypotheses-related validity, and responsiveness were tested. RESULTS: There were missing data in 3.58% patients. Floor and ceiling effects were low for the subscales, global evaluation, and summary index derived from items 1 to 11 after checking that scaling assumptions were met. Exploratory parallel factor analysis showed that the KRLS-QoL may be deemed unidimensional, ie, that all components of the scale are part of one overall general quality of life factor. Indexes of internal consistency (alpha = 0.88), item-total correlation (rS = 0.32-0.71), item homogeneity coefficient (0.41), and scale stability (ICC = 0.73) demonstrated a satisfactory reliability of the KRLS-QoL. Moderate or high correlations were obtained between KRLS-QoL scores and the IRLS, some components of the RLS-6, inter-KRLS-QoL domains, and global evaluations. Known-groups validity for severity levels grouping and responsiveness analysis results were satisfactory, the latter showing higher magnitudes of response for treated than for placebo arms. CONCLUSIONS: The KRLS-QoL was proven an acceptable, reliable, valid, and responsive measure to assess the impact of the RLS on quality of life.

Rating of daytime and nighttime symptoms in RLS: validation of the RLS-6 scale of restless legs syndrome/Willis-Ekbom disease.

BACKGROUND: The International Restless Legs Scale (IRLS) is the most widely used of the scales rating the severity of restless legs syndrome/Willis-Ekbom disease (RLS/WED). It has been well validated and is the primary end point for most of the therapeutic and nontherapeutic studies of RLS/WED. It has excellent psychometric properties, although it does not capture the severity of RLS under a wide variety of circumstances and times of day. Moreover, the IRLS has a large placebo effect. METHODS: The Restless Legs Syndrome-6 Scale (RLS-6), however, takes another potentially valuable approach. Six items are rated on a 0-10 scale from no symptoms at 0 to very severe at 10. In addition to questions on satisfaction with sleep and sleepiness, the scale rates the severity of RLS for the past week under four separate circumstances: while falling asleep, during the night, during the day while sitting or lying, and during the day when moving around. The purpose of the current study is to report the validation of the RLS-6 under baseline and therapeutic conditions. RESULTS: The RLS-6 seems to be an acceptable, reliable, precise, valid, and responsive instrument for the assessment of RLS severity in a specific and pragmatic manner. CONCLUSIONS: At present, we view the RLS-6 not as a replacement for the IRLS but as a supplement, as each scale provides information not captured by the other.

Bevacizumab Plus Irinotecan Versus Temozolomide in Newly Diagnosed O6-Methylguanine-DNA Methyltransferase Nonmethylated Glioblastoma: The Randomized GLARIUS Trial.

PURPOSE: In patients with newly diagnosed glioblastoma that harbors a nonmethylated O(6)-methylguanine-DNA methyltransferase promotor, standard temozolomide (TMZ) has, at best, limited efficacy. The GLARIUS trial thus explored bevacizumab plus irinotecan (BEV+IRI) as an alternative to TMZ. PATIENTS AND METHODS: In this phase II, unblinded trial 182 patients in 22 centers were randomly assigned 2:1 to BEV (10 mg/kg every 2 weeks) during radiotherapy (RT) followed by maintenance BEV (10 mg/kg every 2 weeks) plus IRI(125 mg/m(2) every 2 weeks) or to daily TMZ (75 mg/m(2)) during RT followed by six courses of TMZ (150-200 mg/m(2)/d for 5 days every 4 weeks). The primary end point was the progression-free survival rate after 6 months (PFS-6). RESULTS: In the modified intention-to-treat (ITT) population, PFS-6 was increased from 42.6% with TMZ (95% CI, 29.4% to 55.8%) to 79.3% with BEV+IRI (95% CI, 71.9% to 86.7%; P <.001). PFS was prolonged from a median of 5.99 months (95% CI, 2.7 to 7.3 months) to 9.7 months (95% CI, 8.7 to 10.8 months; P < .001). At progression, crossover BEV therapy was given to 81.8% of all patients who received any sort of second-line therapy in the TMZ arm. Overall survival (OS) was not different in the two arms: the median OS was 16.6 months (95% CI, 15.4 to 18.4 months) with BEV+IRI and was 17.5 months (95% CI, 15.1 to 20.5 months) with TMZ. The time course of quality of life (QOL) in six selected domains of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (QLQ) -C30 and QLQ-BN20 (which included cognitive functioning), of the Karnofsky performance score, and of the Mini Mental State Examination score was not different between the treatment arms. CONCLUSION: BEV+IRI resulted in a superior PFS-6 rate and median PFS compared with TMZ. However, BEV+IRI did not improve OS, potentially because of the high crossover rate. BEV+IRI did not alter QOL compared with TMZ.

Validation of the Multiple Suggested Immobilization Test: A Test for the Assessment of Severity of Restless Legs Syndrome (Willis-Ekbom Disease).

STUDY OBJECTIVES: To validate the Multiple Suggested Immobilization Test (m-SIT), a symptom-provocation test measuring restless legs syndrome (RLS) severity multiple times a day while the patient is awake and resting under controlled conditions. The m-SIT was designed to overcome some limitations in measuring RLS severity with rating scales. DESIGN: Patients completed two m-SITs on 2 consecutive days while on 24-h dopaminergic medication. After treatment discontinuation, they completed one more m-SIT 3 days later. Controls performed only one m-SIT. SETTING: Sleep laboratory. PARTICIPANTS: Nineteen patients with RLS and 10 healthy controls. INTERVENTIONS: The original m-SIT consisted of seven modified 60-min SITs performed every 2 h between noon and midnight. During each SIT, the subject reclined quietly but could move his or her legs without restriction to alleviate symptoms. Every 10 min, periodic leg movements during wakefulness (PLMW) were evaluated and the m-SIT Disturbance Scale (m-SIT-DS; range 0-10) was completed. MEASUREMENTS AND RESULTS: The m-SIT, composed of 6:00pm, 8:00pm, 10:00pm, and 12:00pm SITs, discriminated patients from controls (mean m-SIT-DS: 2.68 ± 2.35 versus 0.08 ± 0.26; mean PLMW/h, P = 0.0001) and between treatment groups (on medication versus taken off medication; mean m-SIT-DS, P = 0.0001; mean PLMW/h, P < 0.01). It proved reliable on retest and covariated well with the International Restless Legs Scale (IRLS) and scales measuring daytime symptoms (Spearman ρ > 0.4). CONCLUSIONS: The m-SIT is a valid and reliable test to evaluate RLS severity and treatment response, and could be useful in the future to confirm diagnosis and identify daytime symptoms. Although it was primarily designed for clinical trials, it might be useful in clinical settings because it provides a standardized testing condition to measure RLS symptoms. CITATION: Garcia-Borreguero D; Kohnen R; Boothby L; Tzonova D; Larrosa O; Dunkl E. Validation of the Multiple Suggested Immobilization Test: a test for the assessment of severity of restless legs syndrome (Willis-Ekbom disease). SLEEP 2013;36(7):1101-1109.

Creatine monohydrate in myotonic dystrophy: a double-blind, placebo-controlled clinical study.

We assessed safety and efficacy of creatine monohydrate (Cr) in myotonic dystrophy (DM1) in a double-blind, cross-over trial. Thirty-four patients with defined DM1 were randomized to receive Cr and placebo for eight weeks (10.6 g day 1-10, 5.3 g day 11-56) in one of 2 treatment sequences. There was no significant improvement using manual and quantitative muscle strength, daily-life activities, and patients' own global assessment comparing verum with placebo administration. Cr supplementation was well tolerated without clinically relevant side effects, but did not result in significant improvement of muscle strength or daily-life activities.