Continuous positive airway pressure in cluster headache: A randomized, placebo-controlled, triple-blind, crossover study.

BACKGROUND: Oxygen inhalation aborts cluster headache attacks, and case reports show the effect of continuous positive airway pressure. The aim of this study was to investigate the prophylactic effect of continuous positive airway pressure in chronic cluster headache. METHODS: This was a randomized placebo-controlled triple-blind crossover study using active and sham continuous positive airway pressure treatment for chronic cluster headache. Patients entered a one month's baseline period before randomly being assigned to two months' active continuous positive airway pressure treatment followed by a four weeks' washout period and two months' sham continuous positive airway pressure or vice versa. Primary outcome measure was number of cluster headache attacks/week. RESULTS: Of the 30 included participants (12 males, median age 49.5 years, min-max 20-66 years), 25 completed both treatment/sham cycles (two discontinued, three lost to follow-up). The median number of cluster headache attacks per week was reduced from 8.25 (0.75-89.75) attacks to 6.25 (0-56.00) attacks for active continuous positive airway pressure and to 7.50 (0.50-43.75) attacks for sham continuous positive airway pressure, but there was no difference in active versus sham (p = 0.904). One patient had a serious adverse event during active treatment, none occurred during sham treatment. CONCLUSIONS: Continuous positive airway pressure treatment did not reduce the number of cluster headache attacks compared to sham treatment in chronic cluster headache patients. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT03397563.

Pain thresholds and suprathreshold pain after sleep restriction in migraine - A blinded crossover study.

OBJECTIVE: There is an unexplained association between disturbed sleep and migraine. In this blinded crossover study, we investigate if experimental sleep restriction has a different effect on pain thresholds and suprathreshold pain in interictal migraineurs and controls. METHODS: Forearm heat pain thresholds and tolerance thresholds, and trapezius pressure pain thresholds and suprathreshold pain were measured in 39 interictal migraineurs and 31 healthy controls after two consecutive nights of partial sleep restriction and after habitual sleep. RESULTS: The effect of sleep restriction was not significantly different between interictal migraineurs and controls in the primary analyses. Pressure pain thresholds tended to be lower (i.e., increased pain sensitivity) after sleep restriction in interictal migraineurs compared to controls with a 48-hour preictal-interictal cut-off (p = 0.061). We found decreased pain thresholds after sleep restriction in two of seven migraine subgroup comparisons: heat pain thresholds decreased in migraineurs with lower pain intensity during attacks (p = 0.005) and pressure pain thresholds decreased in migraineurs with higher severity of photophobia during attacks (p = 0.031). Heat pain thresholds tended to decrease after sleep restriction in sleep-related migraine (p = 0.060). Sleep restriction did not affect suprathreshold pain measurements in either group. CONCLUSION: This study could not provide strong evidence for an increased effect of sleep restriction on pain sensitivity in migraineurs compared to healthy controls. There might be a slightly increased effect of sleep restriction in migraineurs, detectable using large samples or more pronounced in certain migraine subgroups.

Contact-free radar recordings of body movement can reflect ultradian dynamics of sleep.

This work aimed to evaluate if a contact-free radar sensor can be used to observe ultradian patterns in sleep physiology, by way of a data processing tool known as Locomotor Inactivity During Sleep (LIDS). LIDS was designed as a simple transformation of actigraphy recordings of wrist movement, meant to emphasise and enhance the contrast between movement and non-movement and to reveal patterns of low residual activity during sleep that correlate with ultradian REM/NREM cycles. We adapted the LIDS transformation for a radar that detects body movements without direct contact with the subject and applied it to a dataset of simultaneous recordings with polysomnography, actigraphy, and radar from healthy young adults (n = 12, four nights of polysomnography per participant). Radar and actigraphy-derived LIDS signals were highly correlated with each other (r > 0.84), and the LIDS signals were highly correlated with reduced-resolution polysomnographic hypnograms (rradars >0.80, ractigraph >0.76). Single-harmonic cosine models were fitted to LIDS signals and hypnograms; significant differences were not found between their amplitude, period, and phase parameters. Mixed model analysis revealed similar slopes of decline per cycle for radar-LIDS, actigraphy-LIDS, and hypnograms. Our results indicate that the LIDS technique can be adapted to work with contact-free radar measurements of body movement; it may also be generalisable to data from other body movement sensors. This novel metric could aid in improving sleep monitoring in clinical and real-life settings, by providing a simple and transparent way to study ultradian dynamics of sleep using nothing more than easily obtainable movement data.

Validation of questionnaires for restless legs syndrome in the general population: the Trøndelag Health Study (HUNT).

Questionnaires for restless legs syndrome have rarely been validated against face-to-face interviews in the general population. We aimed to validate the modified Norwegian, seven-item Cambridge-Hopkins restless legs syndrome questionnaire and a single diagnostic question for restless legs syndrome. We also aimed to stratify validity at 65 years of age. Among a random sample of 1,201 participants from the fourth wave of the Trøndelag Health Study, 232 (19%) agreed to participate, out of whom 221 had complete data for analyses. Participants completed the questionnaires for restless legs syndrome immediately before attending a face-to-face interview using the latest diagnostic criteria. We calculated sensitivity, specificity, and Cohen's kappa statistic (κ) of questionnaire- versus interview-based diagnoses. We found acceptable validity of the seven-item modified Cambridge-Hopkins diagnostic questionnaire for restless legs syndrome (κ = 0.37, 95% confidence interval [CI] 0.23-0.51) and good validity of the single diagnostic question (κ = 0.47, 95% CI 0.35-0.58). We also found good validity through the combination of modified Cambridge-Hopkins diagnostic questionnaire for restless legs syndrome items 2 and 5, while item 1 or 2 alone showed only acceptable validity. The single diagnostic question was significantly more valid among those aged <65 years (κ = 0.60 versus κ = 0.26). Both single- and two-item questionnaire-based diagnoses overestimated interview-based restless legs syndrome prevalence. The seven-item modified Cambridge-Hopkins diagnostic questionnaire for restless legs syndrome will be useful for epidemiological studies although low sensitivity may cause underestimation of true restless legs syndrome prevalence in the general population, especially among elderly. Brief questionnaire-based diagnoses of up to three items seem best utilised as an initial screen. Future studies should identify brief and even more valid questionnaire-based diagnoses for restless legs syndrome in order to estimate prevalence accurately in large epidemiological studies.

Validation of insomnia questionnaires in the general population: The Nord-Trøndelag Health Study (HUNT).

The primary aim was to validate questionnaire-based insomnia diagnoses from a modified Karolinska Sleep Questionnaire (KSQ) and the Insomnia Severity Index (ISI), by age category (< or >65 years), against a semi-structured face-to-face interview. Secondary aims were to split validity by diagnostic certainty of the interview and to compare prevalence estimates of questionnaire- and interview-based diagnoses. A total of 232 out of 1,200 invited (19.3%) from the fourth Nord-Trøndelag Health Study (HUNT4) completed questionnaires, including the KSQ and ISI, shortly before attending a face-to-face diagnostic interview for insomnia based on the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Both a tentative (DSM-5 criteria A-E) and a definite (criteria A-H) interview diagnosis was evaluated. Cohen's kappa statistic quantified questionnaire validity. In all, 33% (95% confidence interval 27-39%) of participants had definite insomnia: 40% of women and 21% of men. The ISI (cut-off 12) and several KSQ-based diagnoses showed very good validity (κ ≤0.74) against the tentative, versus good validity (κ ≤0.61) against the definite interview diagnosis. Short questionnaires, requiring a daytime symptom at least three times a week, may underestimate insomnia prevalence. Validity was consistently higher for persons aged below versus above 65 years (definite insomnia: κ ≤0.64 vs. κ ≤0.56). Our results have implications for epidemiological population-based studies utilising insomnia questionnaires.

The short-term impact of methylprednisolone on patient-reported sleep in patients with advanced cancer in a randomized, placebo-controlled, double-blind trial.

PURPOSE: Although corticosteroids are frequently used in patients with advanced cancer, few studies have examined the impact of these drugs on patient-reported sleep. We aimed to examine the short-term impact of methylprednisolone on patient-reported sleep in patients with advanced cancer. METHODS: Patient-reported sleep was a predefined secondary outcome in a prospective, randomized, placebo-controlled, double-blind trial that evaluated the analgesic efficacy of corticosteroids in advanced cancer patients (18+), using opioids, and having pain ≥ 4 past 24 h (NRS 0-10). Patients were randomized to the methylprednisolone group with methylprednisolone 16 mg × 2/day or placebo for 7 days. The EORTC QLQ-C30 (0-100) and the Pittsburgh Sleep Quality Index questionnaire (PSQI) (0-21) were used to assess the impact of corticosteroids on sleep at baseline and at day 7. RESULTS: Fifty patients were randomized of which 25 were analyzed in the intervention group and 22 in the control group. Mean age was 64 years, mean Karnofsky performance status was 67 (SD 13.3), 51% were female, and the mean oral daily morphine equivalent dose was 223 mg (SD 222.77). Mean QLQ-C30 sleep score at baseline was 29.0 (SD 36.7) in the methylprednisolone group and 24.2 (SD 27.6) in the placebo group. At day 7, there was no difference between the groups on QLQ-C30 sleep score (methylprednisolone 20.3 (SD 32.9); placebo 28.8 (SD 33.0), p = 0.173). PSQI showed similar results. CONCLUSIONS: Methylprednisolone 16 mg twice daily for 7 days had no impact on patient-reported sleep in this cohort of patients with advanced cancer. TRIAL REGISTRATION: Clinical trial information NCT00676936 (13.05.2008).

Sleep quality in hospitalized patients with advanced cancer: an observational study using self-reports of sleep and actigraphy.

PURPOSE: Although patients with advanced cancer report poor sleep quality, few studies have assessed sleep quality with a combination of subjective and objective measures. We aimed to examine sleep quality in hospitalized patients with advanced cancer by combining patient-reported outcome-measures (PROMs) and polysomnography (PSG) or actigraphy. METHODS: A one-night prospective observational study of sleep in hospitalized patients with metastatic cancer using WHO step III opioids was conducted. Total sleep time, sleep onset latency, number of awakenings, and wake after sleep onset were assessed by PROMs and actigraphy. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) (range; 0-21), where higher scores indicate worse sleep quality. RESULTS: Forty patients were monitored. Median age was 70, median oral morphine equivalent dose was 80 mg/24 h (10-1725), median Karnofsky Performance Score was 50 (20-90), and median time to death from inclusion was 38 days (4-319). Mean PSQI score was 6.5 (SD ± 3.4). PROMs and actigraphy of mean (SD) sleep onset latency were 46 (± 64) and 35 min (± 61), respectively, while mean time awake at night was 37 (± 35) and 40 min (± 21). PROMs and actigraphy differed on number of awakenings (mean 2 (± 1) vs. 24 (± 15), p Ë‚ 0.001). Bland-Altman plots showed large individual differences between PROMs and actigraphy. PSG was not feasible. CONCLUSIONS: PROMs and actigraphy documented poor sleep quality, but a lack of agreement across methods. The study demonstrates a need to improve assessment of sleep quality and treatment of sleep disturbance in hospitalized patients with advanced cancer near end of life.

Acetyl-l-carnitine versus placebo for migraine prophylaxis: A randomized, triple-blind, crossover study.

BACKGROUND: Preventive medication is indicated for many migraine patients, but is used in relatively few. The aim of the present study was to evaluate the efficacy of acetyl-l-carnitine as a prophylactic drug in migraine patients. METHODS: A single-center, randomized, triple-blind, placebo-controlled, crossover study was carried out. Men and women, age 18-65 years, with episodic migraine but otherwise healthy, were recruited mostly through advertisements. After a four-week run-in-phase, 72 participants were randomized to receive either placebo or 3 g acetyl-l-carnitine for 12 weeks. After a four-week washout, treatment was switched. The primary outcome was days with moderate or severe headache per four weeks. Secondary outcomes were days with headache, hours with headache, proportion of responders (>50% reduction in migraine days from baseline) and adverse events. RESULTS: In the complete case analyses, no statistically significant differences were found between acetyl-l-carnitine and placebo in severe or moderate headache days per month (3.0 versus 3.1, p = 0.80), headache days per month (5.1 versus 5.2, p = 0.73) or for the other secondary outcome measures. CONCLUSION: In this triple-blind crossover study no differences were found in headache outcomes between acetyl-l-carnitine and placebo. Our results do not provide evidence of benefit for efficacy of acetyl-l-carnitine as prophylactic treatment for migraine. TRIAL REGISTRATION: EUDRACT (2012-001624-36), ClinicalTrials.gov (NCT01695317).

Validation of Trøndelag Apnoea Score Proxy for Obstructive Sleep Apnoea in the General Population of Norway: The HUNT Study.

The aim was to validate a new seven-item "TASC" (Trøndelag Apnoea Score) proxy for obstructive sleep apnoea (OSA) against polysomnography in the general population. Objectives included validation against different polysomnographic criteria, stratification by age and gender, and estimation of OSA prevalence. From the fourth wave of the Trøndelag Health Study (HUNT4), 1,201 participants were randomly invited to a substudy focusing on sleep and headaches, of whom 232 accepted and 84 (64% women, mean age 55.0 years, and standard deviation 11.5 years) underwent polysomnography. The TASC proxy sums seven binary items for snoring, observed breathing pauses, restricted daytime activities, hypertension, body mass index (≥30 kg/m2), age (≥50 years), and gender (male). A single night of ambulatory (home) polysomnography was analysed using both the recommended and optional hypopnoea criteria of the American Academy of Sleep Medicine (AASM). We found 65% sensitivity and 87% specificity (Cohen's κ = 0.53, 95% confidence interval 0.34-0.72) for TASC ≥ 3 against AHI ≥ 15 (recommended AASM criteria). Validity was similar against AHI ≥ 30 but lower against AHI ≥ 5 and against the optional AASM criteria. Sensitivity and overall validity were higher among men and those above 50 years of age. The prevalence of an apnoea-hypopnoea index (AHI) of at least 5, 15, or 30 using the recommended (and optional) AASM criteria was 73% (46%), 37% (18%), or 15% (5%). A seven-item TASC proxy for OSA showed good validity and may be useful in screening and epidemiological settings. Sensitivity, specificity, and validity vary considerably by cut-off, by polysomnographic scoring criteria, and by gender and age strata.

Answer to comment on "sleep quality, arousal and pain thresholds in migraineurs: a blinded controlled polysomnographic study".

We discuss the comments on our article "Sleep quality, arousal and pain thresholds in migraineurs. A blinded controlled polysomnographic study" published in JHP 2013 Feb 14;14(1):12. We hypothesize that migraineurs need more sleep than healthy controls and more sleep than they manage to achieve. Some migraineurs probably have a decreased ability to process incoming stimuli. Increased spontaneous pain may follow either sleep restriction or sleep disturbance. A comparison of migraineurs with attack onset related to sleep, migraineurs with attack onset not related to sleep and controls will be reported in another paper.

The impact of headache and chronic musculoskeletal complaints on the risk of insomnia: longitudinal data from the Nord-Trøndelag health study.

BACKGROUND: A strong relationship between insomnia and painful disorders has been found, but it is still unclear whether chronic pain leads to insomnia. There is a need of large-scale prospective studies to evaluate if there is a causal relationship between painful disorders and insomnia. METHODS: All inhabitants aged ≥ 20 years in Nord-Trøndelag County of Norway were invited to participate in two surveys (n = 92,566 and 93,860, respectively). 27,185 subjects participated in both surveys, and 19,271 of these were insomnia-free at baseline (population at risk). Using logistic regression, we evaluated the influence of headache, CMSCs and coexisting headache and CMSCs on the subsequent risk of insomnia. RESULTS: Compared to subjects without headache and CMSCs, there was an increased risk of insomnia among those with headache, most pronounced among those with headache ≥ 7 days / month (OR = 2.2, 95% CI = 1.9 - 2.6). Similarly, an increased risk among those with CMSCs was found, most evident for those with widespread CMSCs (OR = 2.0, 95% CI = 1.8 - 2.2). Having coexistent CMSCs and headache (OR = 2.0, 95% CI = 1.8 - 2.2) predisposed more strongly to insomnia than having headache (OR = 1.5, 95% CI = 1.3 - 1.6) and CMSCs (OR = 1.6, 95% CI = 1.4 - 1.7) alone. CONCLUSION: In this prospective study headache and CMSCs were risk factors for insomnia 11 years later.

Sleep-related and non-sleep-related migraine: interictal sleep quality, arousals and pain thresholds.

BACKGROUND: The mechanisms associating sleep and migraine are unknown. No previous polysomnographic (PSG) or pain-threshold (PT) study has compared patients with sleep-related migraine attacks (SM), non-sleep related migraine attacks (NSM) and healthy controls. METHODS: We have performed a blinded, prospective exploratory study with case-control design. Thirty-four healthy controls, 15 patients with SM and 18 patients with NSM had interictal PSG heat-, cold- and pressure PT (HPT, CPT, PPT) recordings and completed diary- and questionnaire on sleep and headache related aspects. RESULTS: NSM patients had more slow-wave sleep (SWS) and more K-bursts than SM patients (K-bursts: p = 0.023 and SWS: p = 0.030) and controls (K-bursts: p = 0.009 and SWS: 0.041). NSM patients also had lower HPT and CPT than controls (p = 0.026 and p = 0.021). In addition, SM patients had more awakenings and less D-bursts than controls (p = 0.025 and p = 0.041). CONCLUSION: SM- and NSM patients differed in objective-, but not subjective sleep quality. NSM patients had PSG findings indicating foregoing sleep deprivation. As foregoing sleep times were normal, a relative sleep deficit might explain reduced PT among NSM patients. The SM patients had signs of slightly disturbed sleep.

Sleep quality, arousal and pain thresholds in migraineurs: a blinded controlled polysomnographic study.

BACKGROUND: Our aim was to compare subjective and objective sleep quality and arousal in migraine and to evaluate the relationship between sleep quality and pain thresholds (PT) in controls, interictal, preictal and postictal migraine. METHODS: Polysomnography and PT (to pressure, heat and cold) measurements were done in 34 healthy controls and 50 migraineurs. Subjective sleep quality was assessed by sleep diaries, Epworth sleepiness scale, Karolinska sleep questionnaire and Pittsburgh sleep quality index. Migraineurs who had their sleep registration more than 48 h from an attack were classified as interictal while those who were less than 48 h from an attack were classified as either preictal or postictal. RESULTS: Migraineurs reported more insomnia and other sleep-related symptoms than controls, but the objective sleep differences were smaller and we found no differences in daytime sleepiness. Interictal migraineurs had more awakenings (p=0.048), a strong tendency for more slow-wave sleep (p=0.050), lower thermal pain thresholds (TPT) (heat pain thresholds p=0.043 and cold pain thresholds p=0.031) than controls. Migraineurs in the preictal phase had shorter latency to sleep onset than controls (p=0.003). Slow-wave sleep correlated negatively with pressure PT and slow bursts correlated negatively with TPT. CONCLUSION: Lower PT in interictal migraineurs seems related to increased sleep pressure. We hypothesize that migraineurs on the average suffer from a relative sleep deprivation and need more sleep than healthy controls. Lack of adequate rest might be an attack-precipitating- and hyperalgesia-inducing factor.

[Polysomnography (PSG) for studying sleep disorders]. / Polysomnografi ved utredning av søvnlidelser.

BACKGROUND: Sleeping problems are very common, and many patients need a comprehensive assessment with polysomnography, possibly followed by a sleep latency test. These methods and indications for the tests are described below. METHOD: The article is based on the authors' own literature archives, clinical experience and Retningslinjer for metoder i klinisk neurofysiologi [Guidelines for methodology in clinical neurophysiology] RESULTS: Polysomnography involves monitoring sleep through the course of one night and scoring the stages of sleep on the basis of EEG activity, eye movements and muscular tension. Also recorded are inter alia respiratory variables. Polysomnography followed by a multiple sleep latency test (MSLT) is used when narcolepsy or excessive daytime sleepiness is suspected. If parasomnia is suspected, the examination should include polysomnography, preferably with video recording. If sleep apnoea is suspected in adults, respiratory polygraphy is often sufficient. As a rule, polysomnography is preferable to respiratory polygraphy for studying sleep disorders in children. INTERPRETATION: Sleep disorders take many forms and are dealt with by many different specialities. Good cooperation between the different specialities is necessary to ensure an optimal result for the patients.

Association Between Cardiorespiratory Fitness and Incident Purchase of Hypnotic Drugs in Adults: The HUNT Study.

OBJECTIVE: To assess whether cardiorespiratory fitness (CRF) is associated with first purchase of a prescribed hypnotic drug in the adult population. METHODS: A total of 34,357 adult participants (53.9% women) with a mean age of 51.5 years (SD 15.6 years) from the third Trøndelag Health Study (HUNT) of 2006 to 2008 were observed until January 1, 2018. Cardiorespiratory fitness was estimated from a validated nonexercise algorithm. Data on first hypnotics prescription were obtained through linkage to the National Norwegian Prescription Database. Cox regression with 95% CIs was used to estimate hazard ratios (HRs). RESULTS: After 304,899 person-years of follow-up, 5791 participants had their first registered purchase of prescribed hypnotics, corresponding to an incidence rate of 1.90 per 100 person-years. Each 1-metabolic equivalent of task increase in CRF was significantly associated with 5% (HR, 0.95; 95% CI, 0.91 to 0.99; P=.02) and 4% (HR, 0.96; 95% CI, 0.92 to 1.00; P=.046) risk reduction for incident use of hypnotics in men and women, respectively. When CRF was categorized into tertiles with lowest CRF as the reference group, reduced risk was 13% (HR, 0.87; 95% CI, 0.79 to 0.96; P=.006) and 15% (HR, 0.85; 95% CI, 0.77 to 0.95; P=.003) for men in the intermediate and highest CRF category, respectively. In women with highest CRF, the reduced risk was 5% (HR, 0.95; 95% CI, 0.87 to 1.03; P=.22). CONCLUSION: Cardiorespiratory fitness in adulthood is associated with incident purchase of prescription medication commonly used for sleep problems. These findings suggest that fitness should be considered a target for preventing sleep problems in adults.

Exercise and obstructive sleep apnoea: a 24-week follow-up study.

Objective: Report on long-term follow-up results in the apnoea hypopnea index (AHI) and self-reported daytime sleepiness in participants with moderate to severe obstructive sleep apnoea at 12 weeks after completion of a high-intensity exercise training or control intervention. Methods: Twenty-six participants with obstructive sleep apnoea (body mass index (BMI) 37 (36-39) kg/m, age 52 (49-55) years, apnoea-hypopnoea index 40.5 (31.3-50.2) events/hour), randomised to either 12 weeks of supervised high-intensity interval training (HIIT) (4×4 min of treadmill running or walking at 90%-95% of maximal heart rate) or no intervention (control), underwent a sleep evaluation follow-up 24 weeks after intervention initiation. Respiratory measures during sleep were registered at baseline, 12 weeks (postintervention) and 24 weeks (long-term follow-up). Results: At the 24-week follow-up, there were no statistically significant differences between the groups in the AHI (HIIT 30.7 (17.2-44.1) and control 38.7 (22.8-54.5) events/hour), Epworth score (HIIT 7.0 (4.7-9.3) and control 5.5 (3.9-7.0)), mean oxygen saturation (HIIT 93.2 (92.5-93.9) and control 92.0 (91.1-92.8)) or oxygen desaturation events (HIIT 32.9 (20.4-45.4) and control 44.3 (27.3-61.3) n/hour). BMI remained unchanged from the baseline in both groups. In the HIIT group, only two participants reported having continued with HIIT at 24 weeks. Conclusion: The effect of 12 weeks of supervised high-intensity exercise training on AHI and self-reported daytime sleepiness was lost at the 24-week follow-up.