Blended care to discontinue benzodiazepine receptor agonists use in patients with chronic insomnia disorder: a pragmatic cluster randomized controlled trial in primary careCoteur, Kristien; Henrard, Gilles; Schoenmakers, Birgitte; Laenen, Annouschka; Van den Broeck, Kris; De Sutter, An; Anthierens, Sibyl; Devroey, Dirk; Kacenelenbogen, Nadine; Offermans, Anne-Marie; Van Nuland, Marc
doi: 10.1093/sleep/zsac278pmid: 36413221
Study ObjectivesInternational guidelines recommend using benzodiazepine receptor agonists (BZRA) for maximally four weeks. Nevertheless, long-term use for chronic insomnia disorder remains a common practice. This study aimed to test the effectiveness of blended care for discontinuing long-term BZRA use in general practice.MethodsA pragmatic cluster randomized controlled superiority trial compared blended care to usual care through urine toxicology screening. In the intervention, care by the general practitioner (GP) was complemented by an interactive e-learning program, based on cognitive behavioral therapy for insomnia. Adults using BZRA daily for minimally 6 months were eligible. Participants were clustered at the level of the GP surgery for allocation (1:1). Effectiveness was measured as the proportion of patients who had discontinued at one-year follow-up. Data analysis followed intention-to-treat principles.ResultsIn total, 916 patients in 86 clusters, represented by 99 GPs, were randomized. Primary outcome data was obtained from 727 patients (79%). At one-year follow-up, 82 patients (18%) in blended care, compared to 91 patients (20%) in usual care, had discontinued. There was no statistically significant effect for the intervention (OR: 0.924; 95% CI: 0.60; 1.43). No adverse events were reported to the research team.ConclusionsThe findings did not support the superiority of blended care over usual care. Both strategies showed clinical effectiveness, with an average of 19% of patients having discontinued at one-year follow-up. Further research is important to study the effect of structurally implementing digital interventions in general practice.Clinical trialBig Bird trial; KCE-17016. This trial is registered at clinicaltrials.gov (NCT03937180).
Sleep spindle and slow wave activity in Parkinson disease with excessive daytime sleepinessSchreiner, Simon J; Werth, Esther; Ballmer, Leonie; Valko, Philipp O; Schubert, Kai M; Imbach, Lukas L; Baumann, Christian R; Maric, Angelina; Baumann-Vogel, Heide
doi: 10.1093/sleep/zsac165pmid: 35877159
Study ObjectivesExcessive daytime sleepiness (EDS) is a common and devastating symptom in Parkinson disease (PD), but surprisingly most studies showed that EDS is independent from nocturnal sleep disturbance measured with polysomnography. Quantitative electroencephalography (EEG) may reveal additional insights by measuring the EEG hallmarks of non-rapid eye movement (NREM) sleep, namely slow waves and spindles. Here, we tested the hypothesis that EDS in PD is associated with nocturnal sleep disturbance revealed by quantitative NREM sleep EEG markers.MethodsPatients with PD (n = 130) underwent polysomnography followed by spectral analysis to calculate spindle frequency activity, slow-wave activity (SWA), and overnight SWA decline, which reflects the dissipation of homeostatic sleep pressure. We used the Epworth Sleepiness Scale (ESS) to assess subjective daytime sleepiness and define EDS (ESS > 10). All examinations were part of an evaluation for deep brain stimulation.ResultsPatients with EDS (n = 46) showed reduced overnight decline of SWA (p = 0.036) and reduced spindle frequency activity (p = 0.032) compared with patients without EDS. Likewise, more severe daytime sleepiness was associated with reduced SWA decline (ß= −0.24 p = 0.008) and reduced spindle frequency activity (ß= −0.42, p < 0.001) across all patients. Reduced SWA decline, but not daytime sleepiness, was associated with poor sleep quality and continuity at polysomnography.ConclusionsOur data suggest that daytime sleepiness in PD patients is associated with sleep disturbance revealed by quantitative EEG, namely reduced overnight SWA decline and reduced spindle frequency activity. These findings could indicate that poor sleep quality, with incomplete dissipation of homeostatic sleep pressure, may contribute to EDS in PD.
The memory sources of dreams: serial awakenings across sleep stages and time of nightPicard-Deland, Claudia; Konkoly, Karen; Raider, Rachel; Paller, Ken A; Nielsen, Tore; Pigeon, Wilfred R; Carr, Michelle
doi: 10.1093/sleep/zsac292pmid: 36462190
Memories of waking-life events are incorporated into dreams, but their incorporation is not uniform across a night of sleep. This study aimed to elucidate ways in which such memory sources vary by sleep stage and time of night. Twenty healthy participants (11 F; 24.1 ± 5.7 years) spent a night in the laboratory and were awakened for dream collection approximately 12 times spread across early, middle, and late periods of sleep, while covering all stages of sleep (N1, N2, N3, REM). In the morning, participants identified and dated associated memories of waking-life events for each dream report, when possible. The incorporation of recent memory sources in dreams was more frequent in N1 and REM than in other sleep stages. The incorporation of distant memories from over a week ago, semantic memories not traceable to a single event, and anticipated future events remained stable throughout sleep. In contrast, the relative proportions of recent versus distant memory sources changed across the night, independently of sleep stage, with late-night dreams in all stages having relatively less recent and more remote memory sources than dreams earlier in the night. Qualitatively, dreams tended to repeat similar themes across the night and in different sleep stages. The present findings clarify the temporal course of memory incorporations in dreams, highlighting a specific connection between time of night and the temporal remoteness of memories. We discuss how dream content may, at least in part, reflect the mechanisms of sleep-dependent memory consolidation.
Dysfunction of the cardiac parasympathetic system in fatal familial insomnia: a heart rate variability studyCui, Yue; Huang, Zhaoyang; Chu, Min; Xie, Kexin; Zhan, Shuqin; Ghorayeb, Imad; Garay, Arturo; Chen, Zhongyun; Jing, Donglai; Wang, Yingtao; Wu, Liyong
doi: 10.1093/sleep/zsac294pmid: 36472576
Study ObjectivesAlthough sympathetic hyperactivity with preserved parasympathetic activity has been extensively recognized in fatal familial insomnia (FFI), the symptoms of parasympathetic nervous system failure observed in some patients are difficult to explain. Using heart rate variability (HRV), this study aimed to discover evidence of parasympathetic dysfunction in patients with FFI and the difference of parasympathetic activity between patients with FFI and Creutzfeldt–Jakob disease (CJD).MethodsThis study enrolled nine patients with FFI, eight patients with CJD and 18 healthy controls (HCs) from May 2013 to August 2020. All participants underwent a nocturnal video-polysomnography with lead II electrocardiography, and the data were analyzed using linear and nonlinear indices of HRV during both wake and sleep states.ResultsCompared to the HC and CJD groups, the FFI group had a continuously higher heart rate with a lower amplitude of oscillations. The low frequency (LF)/high frequency (HF) ratio and ratio of SD1 to SD2 and correlation dimension D2 (CD2) were significantly different in the FFI group compared to the HC group. The root mean square of successive differences (RMSSD), HF and SD1 in the FFI group were significantly lower than in the HC group. RMSSD, SD1, and CD2 in the FFI group were all significantly lower than in the CJD group.ConclusionsCardiovascular dysautonomia in FFI may be partly attributable to parasympathetic abnormalities, not just sympathetic activation. HRV may be helpful as a noninvasive, quantitative, and effective autonomic function test for FFI diagnosis.
Association between insomnia phenotypes and subclinical myocardial injury: the Multi-Ethnic Study of AtherosclerosisSigurdardottir, Fjola D; Bertisch, Suzanne M; Reid, Michelle L; deFilippi, Christopher R; Lima, Joao A C; Redline, Susan; Omland, Torbjørn
doi: 10.1093/sleep/zsac318pmid: 36579654
Study ObjectivesTo assess whether the association between insomnia and subclinical myocardial injury, as measured by cardiac troponin T (cTnT), differs across insomnia phenotypes.MethodsWe measured cTnT in 2188 participants in the Multi-Ethnic Study of Atherosclerosis study who had completed sleep questionnaires and undergone unattended polysomnography (PSG) and 7-day actigraphy. Insomnia symptoms were defined as reporting at least one of the following ≥5 nights/week over the past 4 weeks: trouble falling asleep, waking up several times a night, having trouble getting back to sleep after waking up too early, or taking sleeping pills to help falling asleep. Obstructive sleep apnea (OSA) was defined as an apnea-hypopnea index (AHI >15 events/h). Participants were classified into insomnia phenotypes, including comorbid insomnia and OSA (COMISA) and insomnia associated with actigraphy-estimated short sleep (<6 h) or sleep fragmentation.ResultsThe mean age was 68.8 (SD 9.2) years, 53.6% were male. In total, 47.8% met threshold levels for insomnia symptoms, and 43.1% had an AHI >15. In adjusted linear regression models COMISA (β 0.08 [standard error (SE) 0.03], p < .01) and insomnia with short sleep duration (β 0.07 [SE 0.03], p < .05) were each associated with higher cTnT compared to a reference group with no insomnia. Insomnia with fragmented sleep (β 0.03 [SE 0.02]) was not associated with higher cTnT (p > .05) in adjusted analyses. OSA was associated with higher cTnT (β 0.09 [SE 0.03], p < .01) in adjusted models.ConclusionsCOMISA and insomnia with short sleep duration, but not insomnia symptoms alone or fragmented sleep, were associated with increased circulating cTnT in older adults.