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Michael J Thorpy,1 Isabelle Arnulf,2 Nancy Foldvary-Schaefer,3 Anne Marie Morse,4 Karel Šonka,5 Patricia Chandler,6 Luke Hickey,7 Abby Chen,6 Jed Black,6,8 Amanda Sterkel,6 Dan Chen,9 Richard K Bogan,10 Yves Dauvilliers11,12 1Albert Einstein College of Medicine, Bronx, NY, USA; 2Sleep Disorder Unit, Pitié-Salpêtrière Hospital and Sorbonne University, Paris, France; 3Cleveland Clinic Sleep Disorders Center, Department of Neurology, Lerner College of Medicine, Cleveland, OH, USA; 4Janet Weis Children’s Hospital, Geisinger, Danville, PA, USA; 5Department of Neurology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic; 6Jazz Pharmaceuticals, Palo Alto, CA, USA; 7Jazz Pharmaceuticals, Philadelphia, PA, USA; 8Stanford University Center for Sleep Sciences and Medicine, Palo Alto, CA, USA; 9Formerly Jazz Pharmaceuticals, Palo Alto, CA, USA; 10University of South Carolina School of Medicine, Columbia, SC, USA; 11Sleep and Wake Disorders Centre, Department of Neurology, Gui de Chauliac Hospital, Montpellier, France; 12University of Montpellier, INSERM Institute Neuroscience Montpellier (INM), Montpellier, FranceCorrespondence: Michael J Thorpy, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA, Tel +1 718 920-4841, Fax +1 718 798-4352, Email michael.thorpy@einsteinmed.orgPurpose: To report the efficacy and safety of lower-sodium oxybate (LXB; Xywav®) during the open-label titration and optimization period (OLT) and stable-dose period (SDP) in a clinical study for the treatment of idiopathic hypersomnia.Patients and Methods: Data were collected during treatment titration and optimization in a phase 3 randomized withdrawal trial in adults (18– 75 years of age) with idiopathic hypersomnia who took LXB treatment (once, twice, or thrice nightly, administered orally) in the OLT (10– 14 weeks), followed by the 2-week, open-label SDP. Endpoints included the Epworth Sleepiness Scale (ESS), Idiopathic Hypersomnia Severity Scale (IHSS), Patient Global Impression of Change, Clinical Global Impression of Change, Functional Outcomes of Sleep Questionnaire (FOSQ)-10, and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP).Results: The safety population included 154 participants; the modified intent-to-treat population comprised 115 participants. During open-label treatment, mean (SD) ESS scores improved (decreased) from 15.7 (3.8) at baseline to 6.1 (4.0) at end of SDP, and IHSS scores improved (decreased) from 31.6 (8.3) to 15.3 (8.5). Improvements were also observed during OLT in each individual IHSS item and in FOSQ-10 and WPAI:SHP scores. Thirty-five (22.7%) participants discontinued during OLT and SDP, 22 (14.3%) due to treatment-emergent adverse events (TEAEs) during OLT and SDP. The most frequent TEAEs in the first 4 weeks were nausea, headache, dizziness, and dry mouth; TEAE incidence decreased throughout OLT and SDP (weeks 1– 4, n = 87 [56.5%]; weeks 13– 16, n = 39 [31.7%]).Conclusion: During open-label treatment with LXB, participants showed clinically meaningful improvements in idiopathic hypersomnia symptoms and in quality of life and functional measures. TEAE incidence declined over LXB titration and optimization.Keywords: excessive daytime sleepiness, hypersomnolence, quality of life, pharmacotherapy

Brigitte Holzinger,1,2 Franziska Nierwetberg,1 Frances Chung,3 Courtney J Bolstad,4 Bjørn Bjorvatn,5 Ngan Yin Chan,6 Yves Dauvilliers,7 Colin A Espie,8 Fang Han,9 Yuichi Inoue,10 Damien Leger,11 Tainá Macêdo,12 Kentaro Matsui,13,14 Ilona Merikanto,15,16 Charles M Morin,17 Sérgio A Mota-Rolim,18 Markku Partinen,19 Giuseppe Plazzi,20,21 Thomas Penzel,22 Mariusz Sieminski,23 Yun Kwok Wing,6 Serena Scarpelli,24 Michael R Nadorff,4,25 Luigi De Gennaro24,26 1Institute for Consciousness and Dream Research, Vienna, Austria; 2Medical University Vienna, Postgraduate Master ULG Sleep Coaching, Vienna, Austria; 3Department of Anesthesiology and Pain Medicine, University Health Network, University of Toronto, Toronto, ON, Canada; 4Mississippi State University, Mississippi State, MS, USA; 5Department of Global Public Health and Primary Care, University of Bergen and Norwegian Competence Center for Sleep Disorders, Haukeland University Hospital, Bergen, Norway; 6Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region, People’s Republic of China; 7Sleep-Wake Disorders Unit, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, INM, Univ Montpellier, INSERM, Montpellier, France; 8Sir Jules Thorn Sleep & Circadian Neuroscience Institute (SCNi), University of Oxford, Oxford, UK; 9Department of Pulmonary and Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 10Tokyo Medical University, Tokyo, Japan; 11Université de Paris, APHP, Hôtel-Dieu, Centre du Sommeil et de la Vigilance, Paris, France; 12Department of Psychology, Federal University of Rio Grande do Norte, Natal, Brazil; 13Department of Laboratory Medicine, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Japan; 14Department of Psychiatry, Tokyo Women’s Medical University, Tokyo, Japan; 15SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 16Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland; 17École de Psychologie, Centre d’étude des troubles du sommeil, Centre de recherche CERVO/Brain Research Center, Université Laval, Québec, QC, Canada; 18Brain Institute, Physiology and Behavior Department, and Onofre Lopes University Hospital - Federal University of Rio Grande do Norte, Natal, Brazil; 19Helsinki Sleep Clinic, Terveystalo Healthcare, and Department of Neurosciences, Clinicum, University of Helsinki, Helsinki, Finland; 20IRCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 21Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; 22Sleep Medicine Center, Charité Universitätsmedizin Berlin, Berlin, Germany; 23Department of Emergency Medicine, Medical University of Gdansk, Gdansk, Poland; 24Department of Psychology, Sapienza University of Rome, Rome, Italy; 25Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA; 26IRCCS Fondazione Santa Lucia, Rome, ItalyCorrespondence: Brigitte Holzinger, Tel +43 699 101 99 042, Email brigitte.holzinger@meduniwien.ac.atPurpose: The COVID-19 pandemic affects mental health and sleep, resulting in frequent nightmares. Therefore, identifying factors associated with nightmare frequency is important, as it can indicate mental health issues. The study aimed to investigate increases in nightmare frequency comparing the pre-pandemic and pandemic period, and identify its risk factors. Further, the mediating role of post-traumatic stress disorder symptoms between the pandemic and nightmares is explored.Patients and Methods: For this cross-sectional survey data were obtained via self-rating online survey (ICOSS: details in Partinen et al, 2021), which was open to anyone older than 18 years. The final volunteer sample consisted of 15,292 participants, divided according to their nightmare frequency (high: ≥ 1– 2 nights/week; low: < 1– 2 nights/week). A total of 9100 participants were excluded if answers on variables of interest were missing or receiving rewards for participation. Chi-square tests identified changes of nightmare frequency. Predictors of high nightmare frequency were assessed using logistic regression and presented as Odds Ratios. Post-hoc mediation models were used to investigate the role of post-traumatic stress symptoms (PTSS).Results: The mean age was 41.63 (SD=16.55) with 64.05% females. High nightmare frequency increased significantly from 13.24% to 22.35% during the pandemic. Factors associated with it included self-reported PTSS (OR=2.11), other mental disorders and various sleep disorders or problems. Financial burden due to the pandemic, confinement, having had COVID-19, and work situation during the pandemic were associated with nightmare frequency, those relations were partly mediated through PTSS.Conclusion: Our results display the pandemic influence on nightmare frequency, which in turn connects to multiple mental health and sleep factors. These relations were partly mediated through PTSS. The COVID-19 pandemic appears to have caused traumatization of a substantial proportion of society. Health care workers should consider nightmares in their screening routines, as it might indicate PTSS and/or other mental and sleep disorders.Keywords: COVID-19, nightmares, mental health, sleep, post-traumatic stress disorder, collective trauma

Zhongxing Zhang,1 Yves Dauvilliers,2– 4 Giuseppe Plazzi,5,6 Geert Mayer,7 Gert Jan Lammers,8,9 Joan Santamaria,10 Markku Partinen,11 Sebastiaan Overeem,12,13 Rafael del Rio Villegas,14 Karel Sonka,15 Rosa Peraita-Adrados,16 Raphaël Heinzer,17 Aleksandra Wierzbicka,18 Birgit Högl,19 Mauro Manconi,20 Eva Feketeova,21 Antonio Martins da Silva,22 Jitka Bušková,23 Claudio LA Bassetti,24,25 Lucie Barateau,2– 4 Fabio Pizza,5,26 Elena Antelmi,5,6 Jari K Gool,8,9 Rolf Fronczek,8,9 Carles Gaig,10 Ramin Khatami1,24 1Center for Sleep Medicine, Sleep Research and Epileptology, Klinik Barmelweid AG, Barmelweid, Aargau, Switzerland; 2Sleep-Wake Disorders Unit, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, Montpellier, France; 3National Reference Centre for Orphan Diseases, Narcolepsy, Idiopathic Hypersomnia, and Kleine-Levin Syndrome, Montpellier, France; 4Institute for Neurosciences of Montpellier INM, Univ Montpellier, INSERM, Montpellier, France; 5Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; 6IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 7Neurology Department, Hephata Klinik, Schwalmstadt, Germany; 8Sleep Wake Center SEIN Heemstede, Stichting Epilepsie Instellingen Nederland, Heemstede, the Netherlands; 9Department of Neurology and Clinical Neurophysiology, Leiden University Medical Center, Leiden, the Netherlands; 10Neurology Service, Institut de Neurociències Hospital Clínic, University of Barcelona, Barcelona, Spain; 11Helsinki Sleep Clinic, Vitalmed Research Center, Helsinki, Finland; 12Sleep Medicine Center Kempenhaeghe, Heeze, the Netherlands; 13Eindhoven University of Technology, Eindhoven, the Netherlands; 14Neurophysiology and Sleep Disorders Unit, Hospital Vithas Nuestra Señora de América, Madrid, Spain; 15Neurology Department and Centre of Clinical Neurosciences, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic; 16Sleep and Epilepsy Unit – Clinical Neurophysiology Service, University General Hospital Gregorio Marañón, Research Institute Gregorio Marañón, University Complutense of Madrid, Madrid, Spain; 17Center for Investigation and Research in Sleep, Lausanne University Hospital, Lausanne, Vaud, Switzerland; 18Department of Clinical Neurophysiology, Institute of Psychiatry and Neurology, Warsaw, Poland; 19Neurology Department, Sleep Disorders Clinic, Innsbruck Medical University, Innsbruck, Austria; 20Neurology Department, EOC, Ospedale Regionale di Lugano, Lugano, Ticino, Switzerland; 21Neurology Department, Medical Faculty of P. J. Safarik University, University Hospital of L. Pasteur Kosice, Kosice, Slovak Republic; 22Serviço de Neurofisiologia, Hospital Santo António/Centro Hospitalar Universitário do Porto and UMIB-Instituto Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal; 23Department of Sleep Medicine, National Institute of Mental Health, Klecany, Czech Republic; 24Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; 25Department of Neurology, Sechenov First Moscow State University, Moscow, Russia; 26Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, ItalyCorrespondence: Yves Dauvilliers, National Reference Network for Narcolepsy, Sleep-Disorders Center, Department of Neurology, Hopital Gui de Chauliac, INSERM U1061, Montpellier, UM1, France, Email ydauvilliers@yahoo.fr Ramin Khatami, Center for Sleep Medicine, Sleep Research and Epileptology, Klinik Barmelweid AG, Barmelweid, CH-5017, Switzerland, Email ramin.khatami@barmelweid.chPurpose: Narcolepsy type-1 (NT1) is a rare chronic neurological sleep disorder with excessive daytime sleepiness (EDS) as usual first and cataplexy as pathognomonic symptom. Shortening the NT1 diagnostic delay is the key to reduce disease burden and related low quality of life. Here we investigated the changes of diagnostic delay over the diagnostic years (1990– 2018) and the factors associated with the delay in Europe.Patients and Methods: We analyzed 580 NT1 patients (male: 325, female: 255) from 12 European countries using the European Narcolepsy Network database. We combined machine learning and linear mixed-effect regression to identify factors associated with the delay.Results: The mean age at EDS onset and diagnosis of our patients was 20.9± 11.8 (mean ± standard deviation) and 30.5± 14.9 years old, respectively. Their mean and median diagnostic delay was 9.7± 11.5 and 5.3 (interquartile range: 1.7− 13.2 years) years, respectively. We did not find significant differences in the diagnostic delay over years in either the whole dataset or in individual countries, although the delay showed significant differences in various countries. The number of patients with short (≤ 2-year) and long (≥ 13-year) diagnostic delay equally increased over decades, suggesting that subgroups of NT1 patients with variable disease progression may co-exist. Younger age at cataplexy onset, longer interval between EDS and cataplexy onsets, lower cataplexy frequency, shorter duration of irresistible daytime sleep, lower daytime REM sleep propensity, and being female are associated with longer diagnostic delay.Conclusion: Our findings contrast the results of previous studies reporting shorter delay over time which is confounded by calendar year, because they characterized the changes in diagnostic delay over the symptom onset year. Our study indicates that new strategies such as increasing media attention/awareness and developing new biomarkers are needed to better detect EDS, cataplexy, and changes of nocturnal sleep in narcolepsy, in order to shorten the diagnostic interval.Keywords: cataplexy, diagnostic delay, misdiagnosis, symptom onset, machine learning

Yves Dauvilliers,1,2 Richard K Bogan,3 Karel Šonka,4 Markku Partinen,5 Nancy Foldvary-Schaefer,6 Michael J Thorpy7 1Sleep and Wake Disorders Centre, Department of Neurology, Gui de Chauliac Hospital, Montpellier, France; 2University of Montpellier, INSERM Institute Neuroscience Montpellier (INM), Montpellier, France; 3University of South Carolina School of Medicine, Columbia, SC, USA; 4Department of Neurology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic; 5Helsinki Sleep Clinic, Terveystalo Healthcare, and Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland; 6Sleep Disorders Center, Department of Neurology, Cleveland Clinic, Cleveland, OH, USA; 7Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USACorrespondence: Yves Dauvilliers, 80 Avenue Augustin Fliche, Montpellier, 34295, France, Tel +334 67 33 72 77, Email ydauvilliers@yahoo.frAbstract: Lower-sodium oxybate (LXB) is an oxybate medication approved to treat cataplexy or excessive daytime sleepiness (EDS) in patients with narcolepsy 7 years of age and older in the United States. LXB was developed as an alternative to sodium oxybate (SXB), because the incidence of cardiovascular comorbidities is higher in patients with narcolepsy and there is an elevated cardiovascular risk associated with high sodium consumption. LXB has a unique formulation of calcium, magnesium, potassium, and sodium ions, containing 92% less sodium than SXB. Whereas the active oxybate moiety is the same for LXB and SXB, their pharmacokinetic profiles are not bioequivalent; therefore, a phase 3 trial in participants with narcolepsy was conducted for LXB. This review summarizes the background on oxybate as a therapeutic agent and its potential mechanism of action on the gamma-aminobutyric acid type B (GABAB) receptor at noradrenergic and dopaminergic neurons, as well as at thalamocortical neurons. The rationale leading to the development of LXB as a lower-sodium alternative to SXB and the key efficacy and safety data supporting its approval for both adult and pediatric patients with narcolepsy are also discussed. LXB was approved in August 2021 in the United States for the treatment of idiopathic hypersomnia in adults. Potential future developments in the field of oxybate medications may include novel formulations and expanded indications for other diseases.Graphical Abstract: Keywords: narcolepsy, therapeutics, drug development, cataplexy, excessive daytime sleepiness, idiopathic hypersomnia

Serena Scarpelli,1 Michael R Nadorff,2,3 Bjørn Bjorvatn,4 Frances Chung,5 Yves Dauvilliers,6 Colin A Espie,7 Yuichi Inoue,8 Kentaro Matsui,9,10 Ilona Merikanto,11,12 Charles M Morin,13 Thomas Penzel,14 Mariusz Sieminski,15 Han Fang,16 Tainá Macêdo,17 Sérgio A Mota-Rolim,18 Damien Leger,19 Giuseppe Plazzi,20,21 Ngan Yin Chan,22 Markku Partinen,23 Courtney J Bolstad,2 Brigitte Holzinger,24,25 Luigi De Gennaro1,26 1Department of Psychology, Sapienza University of Rome, Rome, Italy; 2Mississippi State University, Mississippi State, MS, USA; 3Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA; 4Department of Public Health and Primary Care, University of Bergen and Norwegian Competence Center for Sleep Disorders, Haukeland University Hospital, Bergen, Norway; 5Department of Anesthesiology and Pain Medicine, University Health Network, University of Toronto, Toronto, Canada; 6Sleep-Wake Disorders Unit, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, INM, Univ Montpellier, INSERM, Montpellier, France; 7Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; 8Tokyo Medical University, Tokyo, Japan; 9Department of Laboratory Medicine, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Japan; 10Department of Psychiatry, Tokyo Women’s Medical University, Tokyo, Japan; 11SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 12Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland; 13École de Psychologie, Centre d’étude des troubles du sommeil, Centre de recherche CERVO/Brain Research Center, Université Laval, Québec, Canada; 14Sleep Medicine Center, Charité Universitätsmedizin Berlin, Berlin, Germany; 15Department of Emergency Medicine, Medical University of Gdansk, Gdansk, Poland; 16Department of Pulmonary and Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 17Department of Psychology, Federal University of Rio Grande do Norte, Natal, Brazil; 18Brain Institute, Physiology and Behavior Department, and Onofre Lopes University Hospital - Federal University of Rio Grande do Norte, Natal, Brazil; 19Université de Paris, APHP, Hôtel-Dieu, Centre du Sommeil et de la Vigilance, Paris, France; 20IRCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 21Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; 22Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Regions, People’s Republic of China; 23Helsinki Sleep Clinic, Terveystalo Healthcare, and Department of Neurosciences, Clinicum, University of Helsinki, Helsinki, Finland; 24Institute for Consciousness and Dream Research, Vienna, Austria; 25Medical University Vienna, Postgraduate Master Program Medical Sleep Coaching, ZK-Schlafcoaching, Vienna, Austria; 26IRCCS Fondazione Santa Lucia, Rome, ItalyCorrespondence: Luigi De Gennaro, Tel +39-06-49917647, Fax +39-06-49917711, Email luigi.degennaro@uniroma1.itIntroduction: A growing number of studies have demonstrated that the coronavirus disease-19 (COVID-19) pandemic has severely affected sleep and dream activity in healthy people. To date, no investigation has examined dream activity specifically in COVID-19 patients.Methods: As part of the International COVID-19 Sleep Study (ICOSS), we compared 544 COVID-19 participants with 544 matched-controls. A within-subjects comparison between pre-pandemic and pandemic periods computed separately for controls and COVID-19 participants were performed on dream recall and nightmare frequency (DRF; NF). Also, non-parametric comparisons between controls and COVID-19 participants were carried out. Further, we compared psychological measures between the groups collected during pandemic. Ordinal logistic regression to detect the best predictors of NF was performed.Results: We found that people reported greater dream activity during the pandemic. Comparisons between controls and COVID-19 participants revealed a) no difference between groups concerning DRF in the pre-pandemic period and during the pandemic; b) no difference between groups concerning nightmare frequency in the pre-pandemic period; and c) COVID-19 participants reported significantly higher NF than controls during pandemic (p = 0.003). Additionally, we showed that a) anxiety, depression, post-traumatic stress-disorder (PTSD) symptom scores were higher in COVID-19 participants than controls; and b) quality of life and health as well as wellbeing (WHO-5) scores were significantly higher in controls than COVID-19 participants. Finally, ordinal logistic regression indicates that DRF (p < 0.001), PTSD (p < 0.001), anxiety (p = 0.018), insomnia (p = 0.039), COVID-19 severity (p = 0.014), sleep duration (p = 0.003) and age (p = 0.001) predicted NF.Discussion: Our work shows strong associations between increased nightmares in those reporting having had COVID-19. This suggests that the more that people were affected by COVID-19, the greater the impact upon dream activity and quality of life.Keywords: dreaming, pandemic, sleep, PTSD, anxiety, COVID-19 severity

Luiz Eduardo Mateus Brandão,1 Teemu Martikainen,1 Ilona Merikanto,2– 4 Brigitte Holzinger,5,6 Charles M Morin,7– 9 Colin A Espie,10,11 Courtney J Bolstad,12 Damien Leger,13 Frances Chung,14 Giuseppe Plazzi,15 Yves Dauvilliers,16 Kentaro Matsui,17,18 Luigi De Gennaro,19– 21 Mariusz Sieminski,22 Michael R Nadorff,12,23 Ngan Yin Chan,24 Yun Kwok Wing,24 Sérgio Arthuro Mota-Rolim,25– 27 Yuichi Inoue,28 Markku Partinen,29,30 Christian Benedict,31 Bjorn Bjorvatn,32,33 Jonathan Cedernaes1,34 1Department of Medical Sciences, Uppsala University, Uppsala, Sweden; 2Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland; 3Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland; 4Orton Orthopaedic Hospital, Helsinki, Finland; 5ZK-Schlafcoaching, Medical University Vienna, Vienna, Austria; 6Institute for Consciousness and Dream Research, Vienna, Austria; 7École de Psychologie, Université Laval, Québec, Canada; 8Centre d’étude des troubles du sommeil, Université Laval, Québec, Canada; 9Centre de recherche CERVO/Brain Research Center, Université Laval, Québec, Canada; 10Sleep & Circadian Institute, University of Oxford, Oxford, UK; 11Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; 12Department of Psychology, Mississippi State University, Starkville, MS, USA; 13APHP, VIFASOM, Hôtel-Dieu, Centre du Sommeil et de la Vigilance, Université de Paris, Paris, France; 14Department of Anesthesia and Pain Medicine, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada; 15Department of Biomedical, Metabolic and Neural Science, University of Modena and Reggio Emilia, Modena, Italy; 16Sleep-Wake Disorders Center, Department of Neurology, Gui-de-Chauliac Hospital, Institute for Neurosciences of Montpellier INM, INSERM, University of Montpellier, Montpellier, France; 17National Center of Neurology and Psychiatry National Institute of Mental Health, Department of Clinical Laboratory and Department of Sleep-Wake Disorders, Tokyo, Japan; 18Tokyo Women’s Medical University, Department of Psychiatry, Tokyo, Japan; 19Department of Psychology, Sapienza University of Rome, Rome, Italy; 20IRCCS Fondazione Santa Lucia, Rome, Italy; 21IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 22Department of Emergency Medicine, Medical University of Gdansk, Gdansk, Poland; 23Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA; 24Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 25Brain Institute, Federal University of Rio Grande do Norte, Natal, RN, Brazil; 26Physiology and Behaviour Department, Federal University of Rio Grande do Norte, Natal, RN, Brazil; 27Onofre Lopes University Hospital, Federal University of Rio Grande do Norte, Natal, RN, Brazil; 28Department of Somnology, Tokyo Medical University, Tokyo, Japan; 29Helsinki Sleep Clinic, Vitalmed Research Center, Terveystalo Biobank and Research, Helsinki, Finland; 30Department of Neurosciences, Clinicum, University of Helsinki, Helsinki, Finland; 31Sleep Science Laboratory, Department of Neuroscience, Uppsala University, Uppsala, Sweden; 32Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; 33Norwegian Competence Center for Sleep Disorders, Haukeland University Hospital, Bergen, Norway; 34Department of Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USACorrespondence: Jonathan Cedernaes Email jonathan.cedernaes@medsci.uu.sePurpose: Lifestyle and work habits have been drastically altered by restrictions due to the COVID-19 pandemic. Whether the associated changes in sleep timing modulate the risk of suffering from symptoms of insomnia, the most prevalent sleep disorder, is however incompletely understood. Here, we evaluate the association between the early pandemic-associated change in 1) the magnitude of social jetlag (SJL) – ie, the difference between sleep timing on working vs free days – and 2) symptoms of insomnia.Patients and Methods: A total of 14,968 anonymous participants (mean age: 40 years; 64% females) responded to a standardized internet-based survey distributed across 14 countries. Using logistic multivariate regression, we examined the association between the degree of social jetlag and symptoms of insomnia, controlling for important confounders like social restriction extension, country specific COVID-19 severity and psychological distress, for example.Results: In response to the pandemic, participants reported later sleep timing, especially during workdays. Most participants (46%) exhibited a reduction in their SJL, whereas 20% increased it; and 34% reported no change in SJL. Notably, we found that both increased and decreased SJL, as a result of the COVID-19 pandemic, were associated with later sleep midpoint (indicating a later chronotype) as well as more recurrent and moderate-to-severe symptoms of insomnia (about 23– 54% higher odds ratio than subjects with unchanged SJL). Primarily those with reduced SJL shifted their bedtimes to a later timepoint, compared with those without changes in SJL.Conclusion: Our findings offer important insights into how self-reported changes to the stability of sleep/wake timing, as reflected by changes in SJL, can be a critical marker of the risk of experiencing insomnia-related symptoms – even when individuals manage to reduce their social jetlag. These findings emphasize the clinical importance of analyzing sleep-wake regularity.Keywords: BNSQ, ISI, midsleep, MSFsc, PHQ-4, psychological distress

Eirin Fränkl,1 Serena Scarpelli,2 Michael R Nadorff,3,4 Bjørn Bjorvatn,5 Courtney J Bolstad,3 Ngan Yin Chan,6 Frances Chung,7 Yves Dauvilliers,8 Colin A Espie,9 Yuichi Inoue,10,11 Damien Leger,12,13 Tainá Macêdo,14 Kentaro Matsui,15,16 Ilona Merikanto,17– 19 Charles M Morin,20 Sérgio Mota-Rolim,21 Markku Partinen,22,23 Thomas Penzel,24 Giuseppe Plazzi,25,26 Mariusz Sieminski,27 Yun Kwok Wing,6 Luigi De Gennaro,2,28 Brigitte Holzinger1,29 1Institute for Consciousness and Dream Research, Vienna, Austria; 2Department of Psychology, Sapienza University of Rome, Rome, Italy; 3Mississippi State University, Mississippi State, MS, USA; 4Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA; 5Department of Global Public Health and Primary Care, University of Bergen, and Norwegian Competence Center for Sleep Disorders, Haukeland University Hospital, Bergen, Norway; 6Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 7Department of Anesthesiology and Pain Medicine, University Health Network, University of Toronto, Toronto, Canada; 8Sleep-Wake Disorders Center, Department of Neurology, Gui-de-Chauliac Hospital, Institute for Neurosciences of Montpellier INM, INSERM, University of Montpellier, Montpellier, France; 9Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; 10Department of Somnology, Tokyo Medical University, Tokyo, Japan; 11Japan Somnology Center, Neuropsychiatric Research Institute, Tokyo, Japan; 12Université de Paris, VIFASOM (EA 7331 Vigilance Fatigue, Sommeil et Santé Publique), Paris, France; 13APHP, Hotel-Dieu de Paris, Centre du Sommeil et de la Vigilance, Paris, France; 14Department of Psychology, Federal University of Rio Grande do Norte, Natal, Brazil; 15Department of Clinical Laboratory and Department of Sleep-Wake Disorders, National Center of Neurology and Psychiatry National Institute of Mental Health, Kodaira, Japan; 16Department of Psychiatry, Tokyo Women’s Medical University, Tokyo, Japan; 17Sleep Well Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 18Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland; 19Orton Orthopaedics Hospital, Helsinki, Finland; 20École de Psychologie, Centre d’étude des troubles du sommeil, Centre de recherche CERVO/Brain Research Center, Université Laval, Québec, Canada; 21Brain Institute, Physiology and Behavior Department, and Onofre Lopes University Hospital, Federal University of Rio Grande do Norte, Natal, Brazil; 22Helsinki Sleep Clinic, Terveystalo Healthcare, Helsinki, Finland; 23Department of Neurosciences, Clinicum, University of Helsinki, Helsinki, Finland; 24Sleep Medicine Center, Charité Universitätsmedizin Berlin, Berlin, Germany; 25IRCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 26Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; 27Department of Emergency Medicine, Medical University of Gdansk, Gdansk, Poland; 28IRCCS Fondazione Santa Lucia, Rome, Italy; 29Medical University Vienna, ZK-Schlafcoaching, Vienna, AustriaCorrespondence: Brigitte HolzingerInstitute for Consciousness and Dream Research, Canongasse 13/1, Vienna, 1180, AustriaTel +43699-101 99 042Fax +4301-25330334600Email brigitte.holzinger@meduniwien.ac.atObjective: Many have reported odd dreams during the pandemic. Given that dreams are associated with mental health, understanding these changes could provide crucial information about wellbeing during the pandemic. This study explored associations between COVID-19 and dream recall frequency (DRF), and related social, health, and mental health factors.Methods: We conducted a cross-sectional web survey of 19,355 individuals in 14 countries from May to July 2020. We collected data on COVID-19, mental health, sleep and DRF during the pandemic. We performed McNemar Tests to compare low (< 3 nights per week) and high DRF (≥ 3 nights per week) before and during COVID-19 and to evaluate changes in sleep variables segmented by DRF. Chi-square tests were conducted to compare characteristics between low and high DRF. Logistic regression analyses were conducted to examine associations between various independent variables and DRF.Results: Reports of high DRF during the pandemic were higher than before the pandemic (P< 0.001). Female gender (aOR=1.25, 95% CI 1.10– 1.41), nightmares (aOR=4.22, 95% CI 3.45– 5.17), sleep talking (aOR= 2.36, 1.73– 3.23), sleep maintenance problems (aOR=1.34, 95% CI 1.15– 1.56), symptoms of REM sleep behavior disorder (RBD; aOR=1.24, 95% CI 1.09– 1.41) and repeated disturbing thoughts (posttraumatic stress disorder (PTSD) symptoms) were associated with high DRF. Age group 55– 64 years (aOR=0.69, 95% CI 0.58– 0.83) reported less high DRF than younger participants. Unadjusted OR showed associations between depression, anxiety, and DRF; however, in adjusted regression depression (aOR= 0.71, 0.59– 0.86) and anxiety (aOR=0.79, 95% CI 0.66– 0.94) were negatively associated with high DRF.Conclusion and Relevance: DRF was higher than pre-pandemic levels across four continents. DRF was associated with gender and parasomnias like nightmares and RBD symptoms, sleep maintenance problems, PTSD symptoms and negatively associated with depression and anxiety. The results implicate that COVID-19 is reflected in our dreams as an expression of the emotional intensity of the pandemic.Keywords: sleep, sleep disorder, mental health, parasomnia, collective threat

ObjectivesWe aimed to provide a consensus statement by the International Rapid Eye Movement Sleep Behavior Disorder Study Group (IRBD-SG) on devising controlled active treatment studies in rapid eye movement sleep behavior disorder (RBD) and devising studies of neuroprotection against Parkinson disease (PD) and related neurodegeneration in RBD.MethodsThe consensus statement was generated during the fourth IRBD-SG symposium in Marburg, Germany in 2011. The IRBD-SG identified essential methodologic components for a randomized trial in RBD, including potential screening and diagnostic criteria, inclusion and exclusion criteria, primary and secondary outcomes for symptomatic therapy trials (particularly for melatonin and clonazepam), and potential primary and secondary outcomes for eventual trials with disease-modifying and neuroprotective agents. The latter trials are considered urgent, given the high conversion rate from idiopathic RBD (iRBD) to Parkinsonian disorders (i.e., PD, dementia with Lewy bodies [DLB], multiple system atrophy [MSA]).ResultsSix inclusion criteria were identified for symptomatic therapy and neuroprotective trials: (1) diagnosis of RBD needs to satisfy the International Classification of Sleep Disorders, second edition, (ICSD-2) criteria; (2) minimum frequency of RBD episodes should preferably be ⩾2 times weekly to allow for assessment of change; (3) if the PD-RBD target population is included, it should be in the early stages of PD defined as Hoehn and Yahr stages 1-3 in Off (untreated); (4) iRBD patients with soft neurologic dysfunction and with operational criteria established by the consensus of study investigators; (5) patients with mild cognitive impairment (MCI); and (6) optimally treated comorbid OSA. Twenty-four exclusion criteria were identified. The primary outcome measure for RBD treatment trials was determined to be the Clinical Global Impression (CGI) efficacy index, consisting of a four-point scale with a four-point side-effect scale. Assessment of video-polysomnographic (vPSG) changes holds promise but is costly and needs further elaboration. Secondary outcome measures include sleep diaries; sleepiness scales; PD sleep scale 2 (PDSS-2); serial motor examinations; cognitive indices; mood and anxiety indices; assessment of frequency of falls, gait impairment, and apathy; fatigue severity scale; and actigraphy and customized bed alarm systems. Consensus also was established for evaluating the clinical and vPSG aspects of RBD. End points for neuroprotective trials in RBD, taking lessons from research in PD, should be focused on the ultimate goal of determining the performance of disease-modifying agents. To date no compound with convincing evidence of disease-modifying or neuroprotective efficacy has been identified in PD. Nevertheless, iRBD patients are considered ideal candidates for neuroprotective studies.ConclusionsThe IRBD-SG provides an important platform for developing multinational collaborative studies on RBD such as on environmental risk factors for iRBD, as recently reported in a peer-reviewed journal article, and on controlled active treatment studies for symptomatic and neuroprotective therapy that emerged during the 2011 consensus conference in Marburg, Germany, as described in our report.