Cognitive behavioural therapy for insomnia in patients with rheumatoid arthritis: protocol for the randomised, single-blinded, parallel-group Sleep-RA trial.

BACKGROUND: More than half of patients with rheumatoid arthritis complain of insomnia, which is predominantly treated with hypnotic drugs. However, cognitive behavioural therapy for insomnia is recommended as the first-line treatment in international guidelines on sleep. Patients with rheumatoid arthritis suffer from debilitating symptoms, such as fatigue and pain, which can also be linked to sleep disturbance. It remains to be determined whether cognitive behavioural therapy for insomnia can be effective in patients with rheumatoid arthritis. The aim of the Sleep-RA trial is to investigate the efficacy of cognitive behavioural therapy for insomnia on sleep and disease-related symptoms in patients with rheumatoid arthritis. The primary objective is to compare the effect of cognitive behavioural therapy for insomnia relative to usual care on changes in sleep efficiency from baseline to week 7 in patients with rheumatoid arthritis. The key secondary objectives are to compare the effect of cognitive behavioural therapy for insomnia relative to usual care on changes in sleep onset latency, wake after sleep onset, total sleep time, insomnia, sleep quality, fatigue, impact of rheumatoid arthritis and depressive symptoms from baseline to week 26 in patients with rheumatoid arthritis. METHODS: The Sleep-RA trial is a randomised controlled trial with a two-group parallel design. Sixty patients with rheumatoid arthritis, insomnia and low-to-moderate disease activity will be allocated 1:1 to treatment with cognitive behavioural therapy for insomnia or usual care. Patients in the intervention group will receive nurse-led, group-based cognitive behavioural therapy for insomnia once a week for 6 weeks. Outcome assessments will be carried out at baseline, after treatment (week 7) and at follow-up (week 26). DISCUSSION: Data on treatment of insomnia in patients with rheumatoid arthritis are sparse. The Sleep-RA trial is the first randomised controlled trial to investigate the efficacy of cognitive behavioural therapy for insomnia in patients with rheumatoid arthritis. Because symptoms of rheumatoid arthritis and insomnia have many similarities, we also find it relevant to investigate the secondary effects of cognitive behavioural therapy for insomnia on fatigue, impact of rheumatoid arthritis, depressive symptoms, pain, functional status, health-related quality of life and disease activity. If we find cognitive behavioural therapy for insomnia to be effective in patients with rheumatoid arthritis this will add weight to the argument that evidence-based non-pharmacological treatment for insomnia in rheumatological outpatient clinics is eligible in accordance with the existing international guidelines on sleep. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03766100. Registered on 30 November 2018.

Disturbed sleep in cluster headache is not the result of transient processes associated with the cluster period.

BACKGROUND AND PURPOSE: Cluster headache (CH) is characterized by severe, unilateral attacks of pain and a high nocturnal attack burden. It remains unknown whether perturbations of sleep are solely present during the CH bout. Therefore, we aimed to investigate differences in sleep between the bout and remission period in patients with episodic CH and, secondly, to compare patients in the two phases with controls. METHODS: Patients with episodic CH (aged 18-65 years), diagnosed according to the International Classification of Headache Disorders 2nd edition, were admitted for polysomnography at the Danish Center for Sleep Medicine in bout and in remission. The macrostructure of sleep, including arousals, breathing parameters, limb movements and periodic limb movements, was compared with 25 age-, sex- and body mass index-matched healthy controls. RESULTS: There were no differences in any of the sleep parameters for patients in bout (n = 32) compared with patients in remission (n = 23). Attacks were unrelated to sleep stages, presence of apnea episodes, periodic limb movements, limb movements and arousals. In bout, patients had longer sleep latency (18.8 vs. 11.7 min, P < 0.05) and rapid eye movement sleep latency (1.7 vs. 1.2 h, P < 0.05) than controls and sleep efficiency was lower (82.5% vs. 86.5%, P < 0.05). Patients in remission only had a longer sleep latency compared with controls (17.5 vs. 11.7 min, P < 0.01). CONCLUSIONS: The results support the presence of a continuing or slowly recovering disturbance of sleep outside the bout rather than a disturbance occurring secondary to attacks. Further, we confirm that there is no relation between CH attacks and specific sleep stages or between CH and breathing parameters.

Propofol sedation in Drug Induced Sedation Endoscopy without an anaesthesiologist â€" a study of safety and feasibility.

BACKGROUND: Propofol sedation in Drug Induced Sedation Endoscopy (DISE) of the upper airway of patients with obstructive sleep apnea (OSA) without the presence of anesthesiologist has not been done before. Propofol sedation is normally administered by an anesthesiologist. This is the first study of this new method. METHODOLOGY: Based on the positive experience with Nurse-administered Propofol Sedation (NAPS) for endoscopic procedures in the departments of gastroenterology we wanted to test the set-up as method of propofol sedation for DISE procedures in our Otorhinolaryngology (ORL) department. The ORL specialists and staff nurses that carry out DISE procedures all underwent a formalized education in Nurse-administered Propofol Sedation before the study. We included 200 patients with severe snoring and / or obstructive sleep apnea. They were referred for DISE examination prior to possible targeted surgery based on the findings. RESULTS: In our study the aforementioned ORL team successfully cared out propofol sedation without the presence of an anesthesiologist. All examinations were carried out according to plan. There were no adverse events during the procedures or in the following observational period. CONCLUSIONS: The NAPS method of sedation for DISE seems safe and feasible when performed by trained staff in a hospital setting.

Decrease in scale invariance of activity fluctuations with aging and in patients with suprasellar tumors.

Motor activity in healthy young humans displays intrinsic fluctuations that are scale-invariant over a wide range of time scales (from minutes to hours). Human postmortem and animal lesion studies showed that the intact function of the suprachiasmatic nucleus (SCN) is required to maintain such scale-invariant patterns. We therefore hypothesized that scale invariance is degraded in patients treated for suprasellar tumors that compress the SCN. To test the hypothesis, we investigated 68 patients with nonfunctioning pituitary macroadenoma and 22 patients with craniopharyngioma, as well as 72 age-matched healthy controls (age range 21.0-70.6 years). Spontaneous wrist locomotor activity was measured for 7 days with actigraphy, and detrended fluctuation analysis was applied to assess correlations over a range of time scales from minutes to 24 h. For all the subjects, complex scale-invariant correlations were only present for time scales smaller than 1.5 h, and became more random at time scales 1.5-10 h. Patients with suprasellar tumors showed a larger decrease in correlations at 1.5-10 h as compared to healthy controls. Within healthy subject, gender and age >33 year were associated with attenuated scale invariance. Conversely, activity patterns at time scales between 10 and 24 h were significantly more regular than all other time scales, and this was mostly associated with age. In conclusion, scale invariance is degraded in healthy subjects at the ages of >33 year as characterized by attenuation of correlations at time scales 1.5-10 h. In addition, scale invariance was more degraded in patients with suprasellar tumors as compared to healthy subjects.

European guideline for the diagnosis and treatment of insomnia

This European guideline for the diagnosis and treatment of insomnia was developed by a task force of the European Sleep Research Society, with the aim of providing clinical recommendations for the management of adult patients with insomnia. The guideline is based on a systematic review of relevant meta-analyses published till June 2016. The target audience for this guideline includes all clinicians involved in the management of insomnia, and the target patient population includes adults with chronic insomnia disorder. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to grade the evidence and guide recommendations. The diagnostic procedure for insomnia, and its co-morbidities, should include a clinical interview consisting of a sleep history (sleep habits, sleep environment, work schedules, circadian factors), the use of sleep questionnaires and sleep diaries, questions about somatic and mental health, a physical examination and additional measures if indicated (i.e. blood tests, electrocardiogram, electroencephalogram; strong recommendation, moderate- to high-quality evidence). Polysomnography can be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders), in treatment-resistant insomnia, for professional at-risk populations and when substantial sleep state misperception is suspected (strong recommendation, high-quality evidence). Cognitive behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (strong recommendation, high-quality evidence). A pharmacological intervention can be offered if cognitive behavioural therapy for insomnia is not sufficiently effective or not available. Benzodiazepines, benzodiazepine receptor agonists and some antidepressants are effective in the short-term treatment of insomnia (≤4 weeks; weak recommendation, moderate-quality evidence). Antihistamines, antipsychotics, melatonin and phytotherapeutics are not recommended for insomnia treatment (strong to weak recommendations, low- to very-low-quality evidence). Light therapy and exercise need to be further evaluated to judge their usefulness in the treatment of insomnia (weak recommendation, low-quality evidence). Complementary and alternative treatments (e.g. homeopathy, acupuncture) are not recommended for insomnia treatment (weak recommendation, very-low-quality evidence).

Sleep and delirium in unsedated patients in the intensive care unit.

BACKGROUND: Sleep deprivation and delirium are major problems in the ICU. We aimed to assess the sleep quality by polysomnography (PSG) in relation to delirium in mechanically ventilated non-sedated ICU patients. METHODS: Interpretation of 24-h PSG and clinical sleep assessment in 14 patients. Delirium assessment was done using the confusion assessment method for the intensive care unit (CAM-ICU). RESULTS: Of four patients who were delirium free, only one had identifiable sleep on PSG. Sleep was disrupted with loss of circadian rhythm, and diminished REM sleep. In the remaining three patients the PSGs were atypical, meaning that no sleep signs were found, and sleep could not be quantified from the PSGs. Clinical total sleep time (ClinTST) ranged from 2.0-13.1 h in patients without delirium. Six patients with delirium all had atypical PSGs, so sleep could not be quantified. Short periods of REM sleep were found. ClinTST was median 8.5 h (range 0.4-13.8 h). EEG reactivity and wakefulness was found in all but one PSG. Four patients were CAM-ICU "unassessable" (unresponsive to voice). PSGs were atypical without reactivity or wakefulness, even though clinical wakefulness was documented. ClinTST was median 18.3 h (range 3.7-19.8 h). Paroxystic EEG activity was found in this subgroup. CONCLUSIONS: The objective signs of sleep were absent in all but one PSG, so even though patients were not sedated, sleep could not be quantified. Even in patients without delirium, sleep could only be quantified in one of four patients. Paroxystic activity is frequent in unsedated patients, unresponsive to voice, but the implication is unknown.

Sleep in cluster headache - beyond a temporal rapid eye movement relationship?

BACKGROUND AND PURPOSE: Cluster headache (CH) is a primary headache disorder characterized by severe attacks of unilateral pain following a chronobiological pattern. There is a close connection with sleep as most attacks occur during sleep. Hypothalamic involvement and a particular association with rapid eye movement (REM) sleep have been suggested. Sleep in a large, well-characterized population of CH patients was investigated. METHODS: Polysomnography (PSG) was performed on two nights in 40 CH patients during active bout and one night in 25 age, sex and body mass index matched controls in hospital. Macrostructure and other features of sleep were analyzed and related to phenotype. Clinical headache characterization was obtained by semi-structured interview. RESULTS: Ninety-nine nights of PSG were analyzed. Findings included a reduced percentage of REM sleep (17.3% vs. 23.0%, P = 0.0037), longer REM latency (2.0 vs. 1.2 h, P = 0.0012) and fewer arousals (7.34 vs. 14.1, P = 0.003) in CH patients. There was no difference in prevalence of sleep apnea between patients (38%) and matched controls (32%, P = 0.64) although the apnea index in patients was numerically higher (mean apnea-hypopnea index 10.75 vs. 4.93). No temporal association between nocturnal attacks (n = 45) and particular sleep stages was observed. CONCLUSIONS: To date, this is the largest study of sleep in CH. It is demonstrated that REM sleep is affected which is in line with our current understanding of CH and hypothalamic involvement in the regulation of this sleep stage. Further, fewer arousals were found in CH patients but no association between apnea events or specific sleep stages. The findings support a central role of the hypothalamus and arousal systems in CH.

Intravenous immunoglobulin treatment and screening for hypocretin neuron-specific autoantibodies in recent onset childhood narcolepsy with cataplexy.

BACKGROUND: Narcolepsy with cataplexy (NC) is caused by substantial loss of hypocretin neurons. NC patients carry the HLA-DQB1*0602 allele suggesting that hypocretin neuron loss is due to an autoimmune attack. We tested intravenous immunoglobulin (IVIG) treatment in early onset NC. METHODS: 2 NC children received IVIG 1 g/kg/day in 2 days/month, 5 times, at 3 and 6 months disease duration, respectively. CSF and serum were analysed for hypocretin neuron autoantibodies. An association between disease duration and IVIG effect was calculated in all published NC cases. RESULTS: Autoantibodies were not detectable. Cataplexy improved in both children but only temporarily in one patient. Subjective sleepiness temporarily improved, sleep paralysis emerged and hypnagogic hallucinations and REM sleep behaviour disorder worsened in one child. Sleep parameters and CSF hypocretin-1 remained abnormal. On a group level, IVIG treatment ≤ 9 months from disease duration predicted reduction of cataplexy (p=0.004) and sleepiness (p=0.066). Sleep parameters and CSF hypocretin-1 levels were unchanged except if treated extremely early. CONCLUSION: IVIG treatment initiated before 9 months disease duration has some clinical efficiency. The unaffected CSF hypocretin-1 levels and lack of autoantibodies suggest that any autoimmune process occurs very early in NC. The final IVIG effect needs to be investigated in a placebo-controlled study.

Normal levels of cerebrospinal fluid hypocretin-1 and daytime sleepiness during attacks of relapsing-remitting multiple sclerosis and monosymptomatic optic neuritis.

There is emerging evidence that multiple sclerosis (MS), the hypothalamic sleep-wake regulating neuropeptide hypocretin-1 (hcrt-1) and the sleep disorder narcolepsy may be connected. Thus, the major pathophysiological component of narcolepsy is lack of hcrt-1. Dysfunction of the hypocretin system has been reported in MS case reports with attacks of hypothalamic lesions, undetectable cerebrospinal fluid (CSF) hcrt-1 and hypersomnia, but not found during remission in small samples. Finally, daytime sleepiness, the major symptom of narcolepsy, is reported in several MS populations, and there are case reports of co-existent narcolepsy and MS. However, it is unknown whether hcrt-1 and daytime sleepiness generally change during MS attacks. We therefore analyzed whether daytime sleepiness (using the Epworth Sleepiness Scale (ESS)) and CSF hcrt-1 levels differed between MS attack and remission, in 48 consecutively referred patients with relapsing-remitting MS (RRMS) or monosymptomatic optic neuritis (MON). Twenty-seven patients were in attack and 21 in remission. ESS was normal both during attacks (5.4 +/- 3.0) and remission (5.8 +/- 2.6), and mean CSF hcrt-1 was normal (456 +/- 41 pg/ml). No statistically significant differences were found between attack and remission. MRI scans revealed no hypothalamic lesions. The results show that the hypocretin system is intact and sleepiness is not typical in RRMS and MON without hypothalamic lesions on MRI.

[Whiplash injury syndrome. A prospective study of 39 patients with whiplash injury]. / Piskesmaeldsyndromet. En prospektiv undersøgelse af 39 patienter med piskesmaeldlaesioner.

The acute symptoms after whiplash trauma can be explained by the neck sprain, but the pathogenesis of the "late whiplash syndrome" and the reasons why only some people have persistent symptoms more than six months are still unknown. Thirty-four consecutive cases of piskesmaeld injury were examined clinically three times; respectively within 14 days, after one month and finally seven months post-injury. In addition, MRI of the brain and the cervical spine, neuropsychological tests and motor evoked potentials (MEP) were done one month post-injury and repeated after six months, if abnormalities were found. We found the total recovery rate (asymptomatic patients) was 29% after seven months. All MEP examinations were normal. The correlation between MRI and the clinical findings was poor. Cognitive dysfunction as a symptom of brain injury was not found. Stress at the same time as the accident predicted more symptoms at follow-up. We conclude that long-lasting distress and poor outcome were more related to the occurrence of stressful life events than to clinical and paraclinical findings.

[Cognitive symptoms in persons with snoring and sleep apnea. An epidemiologic study of 1.504 women and men aged 30-60 years. The Dan-MONICA II study]. / Kognitive symptomer hos personer med snorken og søvnapnø. En epidemiologisk undersøgelse af 1.504 kvinder og moend i alderen 30-60 år. Dan-MONICA II-undersøgelsen.

The objective of the study was to evaluate the relation between every-night (habitual) snoring, sleep apnoea and cognitive complaints (concentration and memory complaints) in an adult population-based sample. In the DAN-MONICA (MONItoring trends in CArdiovascular iseases) 1504 males and females aged 30, 40, 50 and 60 years were classified according to their snoring habits. Nocturnal respiration was measured in 748 participants. The following measures were regarded as potential confounders: age, gender, unintended sleepiness, insomnia, depression, hypnotic use, alcohol consumption by questionnaire, body mass index (BMI) and blood pressure. Concentration and memory problems were both related to depression, insomnia and unintended sleepiness. Snoring and sleep apnoea (defined as a respiratory distress index-RDI > or = 5) were associated with concentration problems and unintended sleepiness. The odds ratios (95% confidence intervals) between snoring, concentration and memory problems, calculated by logistic regression analysis after adjustments for the above confounders, were 1.90 (1.23-2.91, p < 0.01) and 1.38 (0.97-1.99, NS). For those with sleep apnoea, the odds ratios were 3.53 (1.42-8.73. p < 0.001) and 1.51 (0.81-2.14, NS) for concentration and memory problems, respectively. The main conclusion drawn from this study is that cognitive complaints show a high correlation to mood, insomnia and hypersomnia. Habitual snoring and sleep apnoea show a correlation to concentration problems, but not to memory problems. This suggests that part of the association between snoring, sleep apnoea and cognitive dysfunction is related to the presence of sleep disturbances and daytime sleepiness.

[Muscle biopsies in patients with fibromyalgia. A study based on light and electron microscopy]. / Muskelbiopsier hos patienter med fibromyalgi. En undersøgelse baseret på lys- og elektronmikroskopi.

The value of muscle biopsy in fibromyalgia is still questioned. In this study we obtained 49 quadriceps biopsies from 20 patients and compared them blindly to 15 biopsies from five normal controls. Using light microscopy, histochemical and immunoenzymatic methods we found no definite evidence of muscle disease. Nevertheless, we subjected biopsies from nine of the patients and five other controls for further ultrastructural evaluations and demonstrated pathologic findings e.g. empty sleeves of basement membrane, many lipofuscin bodies and other degenerative changes. We conclude that ultrastructural evaluation cannot yet be used for diagnostic purposes, but the negative findings at light microscopy, including histochemical and immunoenzymatic techniques, might be of importance in evaluating difficult cases.

[Preoperative EEG in medically intractable epilepsy]. / Praeoperativt eeg ved medicinsk intraktabel epilepsi.

The aim of the preoperative neurophysiological investigations is to identify the primary epileptogenic focus and its relation to functional cortical areas. The investigations include interictal and ictal extracranial (scalp) electroencephalography (EEG) and invasive methods (depth, subdural, foramen ovale electrodes and peroperative electrocorticography). If an epileptic focus is located in the anterior part of the temporal lobe by the use of scalp EEG, this is normally regarded as sufficient for an anterior lobectomy. However, because of poor spatial resolution by scalp EEG, it is difficult to separate mesial from lateral foci, identify the exact extent of posterior temporal or extra-temporal foci, identify the primary focus in patients with bilateral abnormalities and identify cases with minor scalp EEG-changes. As invasive EEG shows higher spatial resolution and gives an opportunity to evaluate functional areas, invasive EEG has significant advantages in these patients. Use of invasive EEG bears a slightly increased risk and discomfort to the patient, but is necessary in the presurgical evaluation of some patients suffering from medically intractable epilepsy.

[Cardiovascular risk factors in snorers. The Copenhagen Male Study]. / Kardiovaskulaere risikofaktorer hos snorkere. The Copenhagen Male Study.

Former studies on the association between snoring and cardiovascular disease (CVD) have only partly taken established CVD risk factors into consideration. In the Copenhagen Male Study, 3323 men aged 54-74 years were classified according to self-reported snoring habits. Eleven CVD risk factors were examined. The prevalence of snoring decreased with age, with a 50% higher frequency of snorers in the youngest quintile than in the oldest, p < 0.00001. Snoring, age adjusted, was positively associated with tobacco smoking, p < 0.001, alcohol consumption p < 0.0001, body mass index (BMI), p < 0.0001, serum triglyceride level, p < 0.01, systolic blood pressure, p < 0.05 and diastolic blood pressure, p = 0.07. Snorers were less physically active in leisure time than others, p < 0.01. The association between self-reported snoring and blood pressure disappeared when other factors, including BMI, were taken into consideration. No significant associations were found between snoring and social class, snoring and low or high density lipoprotein, nor between snoring and hypertension. We conclude that snoring is associated with major cardiovascular risk factors. Accordingly, it is evident that in studies on snoring and cardiovascular disease, proper controlling for the influence of potential confounders is a sine qua non.

White lead exposure among Danish police officers employed in fingerprint detection.

White lead exposure among Danish police officers employed in fingerprint detection. Scand j work environ health 9 (1983) 511-513. White lead is often used by police officers employed in fingerprint detection (dactylography). On the basis of a case of mild lead intoxication in a police officer all 22 exposed police officers at the Bureau of Dactylographic Identification in Copenhagen were examined. All went through a clinical examination and blood lead determination. None of the participants showed any sign of lead intoxication. The median blood lead concentration was 0.97 mumol/l (10th-90th percentiles 0.72-1.44 mumol/l), a value definitely higher than the average of the general population matched for age and sex. A correlation between the weekly white lead exposure and blood lead concentration (r = 0.87, p less than 0.0001) was found among the participants.