Boosting obstructive sleep apnea therapy by non-pharmacological approaches: A network meta-analysis.

INTRODUCTION: Obstructive sleep apnea (OSA) is the most common breathing-related sleep disorder with a considerable economic burden, low diagnosis and treatment rates. Continuous positive airway pressure (CPAP/PAP) is the principal therapy for OSA treatment; nevertheless, effectiveness is often limited by suboptimal adherence. The present network meta-analysis aims to systematically summarize and quantify different interventions' effects on CPAP/PAP adherence (such as mean usage CPAP or PAP in hours per night) in OSA patients, comparing Behavioral, Educational, Supportive and Mixed interventions in Randomized Control Trials (RCT). METHODS: We conducted a computer-based search using the electronic databases of Pubmed, Psycinfo, Scopus, Embase, Chinal and Medline until August 2022, selecting 50 RCT. RESULTS: By means of a random effect model network meta-analysis, results suggested that the most effective treatment in improving CPAP/PAP adherence was the Supportive approach followed by Behavioral Therapy focused on OSA treatment adherence. CONCLUSION: This network meta-analysis might encourage the most experienced clinicians and researchers in the field to collaborate and implement treatments for improving CPAP/PAP treatment adherence. Moreover, these results support the importance of multidisciplinary approaches for OSA treatment, which should be framed within a biopsychological model.

Challenging subjective excessive daytime sleepiness as an insomnia symptom: a retrospective study.

Diagnostic manuals describe insomnia disorder (ID) characterised by fatigue and sleepiness as diurnal consequences of nocturnal symptoms. However, patients with ID do not frequently report sleepiness in the clinical setting. The present study aimed to investigate subjective sleepiness in ID measured through the Epworth Sleepiness Scale (ESS) and its independence towards daytime functioning and fatigue, and to evaluate cognitive behavioural therapy for insomnia (CBT-I) improvement in daytime consequences and their relationship to sleepiness and fatigue. We retrospectively collected the ESS evaluation in a large sample of 105 healthy controls (HCs), 671 patients with ID, and 602 patients with sleep disorders characterised by excessive daytime sleepiness (EDS). Moreover, we conducted a pre-post evaluation of the ESS in a sub-sample of patients with ID who underwent CBT-I. Component 2 of the Insomnia Severity Index and Profile of Mood States-Fatigue Inertia Scale was used to evaluate daytime functioning and fatigue. Patients with ID reported ESS levels comparable to that observed in HCs and significantly lower than the EDS group. No significant correlation arose between ESS and the diurnal impact of the disorder, suggesting the independence between daytime functioning and sleepiness in ID. Contrarily, insomnia severity and diurnal impact significantly correlated with fatigue. Data showed a statistically significant increase in sleepiness after CBT-I, despite significantly improving daytime consequences and fatigue. Although diagnostic manuals report sleepiness and fatigue as daytime consequences of sleep symptoms in patients with ID, these retrospective data indicate a dissociation between these entities. This evidence aligns with the core feature of ID: the hyperarousal status that pervades patients also during wakefulness.

NEURO-COVAX: An Italian Population-Based Study of Neurological Complications after COVID-19 Vaccinations.

OBJECTIVE: In this Italian population-based study, we aimed to evaluate the neurological complications after the first and/or second dose of COVID-19 vaccines and factors potentially associated with these adverse effects. METHODS: Our study included adults aged 18 years and older who received two vaccine doses in the vaccination hub of Novegro (Milan, Lombardy) between 7 and 16 July 2021. The NEURO-COVAX questionnaire was able to capture the neurological events, onset and duration. That data that were digitized centrally by the Lombardy region were used to match the demographic/clinical characteristics and identify a vulnerability profile. Associations between vaccine lines and the development of complications were assessed. Digital healthcare system matching was also performed to evaluate severe neurological complications (Guillain-Barrè syndrome, Bell's palsy, transverse myelitis, encephalitis) and the incidence of hospital admissions and/or the mortality rate after two doses of the vaccines. RESULTS: The NEURO-COVAX-cohort included 19.108 vaccinated people: 15.368 with BNT162b2, 2077 with mRNA-1273, 1651 with ChAdOx1nCov-19, and 12 with Ad26.COV2.S who were subsequently excluded. Approximately 31.2% of our sample developed post-vaccination neurological complications, particularly with ChAdOx1nCov-19. A vulnerable clinical profile emerged, where over 40% of the symptomatic people showed comorbidities in their clinical histories. Defining the neurological risk profile, we found an increased risk for ChAdOx1nCov-19 of tremors (vs. BNT162b2, OR: 5.12, 95% CI: 3.51-7.48); insomnia (vs. mRNA-1273, OR: 1.87, 95% CI: 1.02-3.39); muscle spasms (vs. BNT162b2, OR: 1.62, 95% CI: 1.08-2.46); and headaches (vs. BNT162b2, OR: 1.49, 95% CI: 0.96-1.57). For mRNA-1273, there were increased risks of parethesia (vs. ChAdOx1nCov-19, OR: 2.37, 95% CI: 1.48-3.79); vertigo (vs. ChAdOx1nCov-19, OR: 1.68, 95% CI: 1.20-2.35); diplopia (vs. ChAdOx1nCov-19, OR: 1.55, 95% CI: 0.67-3.57); and sleepiness (vs. ChAdOx1nCov-19, OR: 1.28, 95% CI: 0.98-1.67). In the period that ranged from March to August 2021, no one was hospitalized and/or died of severe complications related to COVID-19 vaccinations. DISCUSSION: This study estimates the prevalence and risk for neurological complications potentially associated with COVID-19 vaccines, thus improving the vaccination guidelines and loading in future personalized preventive medicine.

Non-pharmacological and melatonin interventions for pediatric sleep initiation and maintenance problems: A systematic review and network meta-analysis.

Sleep initiation and maintenance problems are common in the pediatric population and while behavioral interventions are recommended, their efficacy remains to be evaluated in clinical trials. We conducted a systematic review and network meta-analysis to assess the efficacy of non-pharmacological treatments and melatonin for sleep initiation and maintenance problems in healthy pediatric populations. We included 30 studies in the systematic review and 15 in the meta-analysis. Three network meta-analyses were conducted for sleep onset latency (SOL), wake after sleep onset (WASO), and total sleep time (TST). For SOL variable, the results support greater effectiveness of light therapy and melatonin than evidence-based psychological interventions, whether implemented in combination with light therapy or not. Regarding WASO variable, evidence-based psychological interventions and a combination of those techniques plus light treatment were the most efficacious. Finally, for TST variable, a larger effect was shown for the combined treatment of evidence-based psychological intervention with light therapy in comparison to other interventions. In conclusion, we found a high variability between study protocols likely impacting the results of the meta-analysis. Future randomized control trials studies, stratified by pediatric age classes, are needed in order to provide clear suggestions in clinical settings.

Electrophysiological and Neuropsychological Indices of Cognitive Dysfunction in Patients with Chronic Insomnia and Severe Benzodiazepine Use Disorder.

Benzodiazepine (BDZ) misuse is a growing health problem, with 1-2% of patients under BDZ treatment meeting the criteria for use disorder or dependence. Although BDZ addiction potential has been known for decades, much remains unknown its effects on brain functions. The aim of this study was to assess the neuropsychological and neurophysiological profile of a group of chronic insomniacs taking long-term high doses of benzodiazepine. We recruited 17 consecutive patients admitted to our third-level Sleep Medicine Unit for drug discontinuation (7 males, mean age 49.2 ± 11.2 years, mean education 13.7 ± 3.9 years, mean daily diazepam-equivalent BDZ: 238.1 ± 84.5 mg) and 17 gender/age-matched healthy controls (7 males, mean age 46.8 ± 14.1 years, mean education 13.5 ± 4.5 years). We performed a full neuropsychological evaluation of all subjects and recorded their scalp event-related potentials (Mismatch-Passive Oddball-Paradigm and Active Oddball P300 Paradigm). Patients with chronic insomnia and BDZ use disorder showed a profound frontal lobe executive dysfunction with significant impairment in the cognitive flexibility domain, in face of a preserved working, short and long-term memory. In patients, P300 amplitude tended to be smaller, mainly over the frontal regions, compared to controls. BDZ use disorder has a severe cognitive impact on chronic insomnia patients. Long-term high-dose BDZ intake should be carefully evaluated and managed by clinicians in this specific patient population, especially in relation to risky activities.

Sleep disturbances and restless legs syndrome in postmenopausal women with early breast cancer given adjuvant aromatase inhibitor therapy.

INTRODUCTION: Whether adjuvant therapy with aromatase inhibitors (AIs) causes sleep disturbances or not in postmenopausal women with early breast cancer (EBC) is still a controversial issue. METHODS: Between March 2014 and November 2017, validated questionnaires for assessing insomnia, anxiety, depression, quality of life (QoL) and restless legs syndrome (RLS) were administered to 160 EBC patients at baseline and after 3, 6, 12, and 24 months of AI therapy. RESULTS: AI therapy significantly decreased the patients' QoL, but did not influence insomnia, anxiety or depression. However, it significantly increased the frequency and severity of RLS. Patients with RLS at baseline (19%) or who developed RLS during AI therapy (26.3%) reported statistically lower quality of sleep, higher anxiety and depression, and worse QoL compared to patients who never reported RLS (54.7%). CONCLUSION: Although AI therapy does not affect sleep quality, it may increase RLS frequency. The presence of RLS could identify a group of EBC patients who may benefit from psychological support.

"Thinking About Thinking" in Insomnia Disorder: The Effect of Cognitive-Behavioral Therapy for Insomnia on Sleep-Related Metacognition.

Metacognition is defined as the ability to reflect on one's mental state and to govern thoughts and beliefs. Metacognitive dysfunctions are typical of several psychopathologic conditions, and also a feature of insomnia disorder, possibly playing a crucial role in its genesis and maintenance. In the context of insomnia, metacognition describes how individuals react to their own sleep-related thoughts and beliefs, boosting the hyperarousal state experienced by these patients. Up to now, no studies evaluated the effect of cognitive behavioral therapy for insomnia (CBT-I) on metacognitive functioning. Therefore, the aim of our study was to evaluate the effect of CBT-I administered in group format in patients with insomnia disorder. As expected, all patients showed significant improvements in both insomnia and sleep diary parameters after treatment. Furthermore, an improvement was observed also in dysfunctional metacognitive levels, assessed by means of the Metacognitions Questionnaire-Insomnia (MCQ-I). However, 63% of patients still showed a MCQ-I score above the clinical cutoff after treatment. Dividing the sample on the basis of MCQ-I questionnaire scores after CBT-I, we found that patients, who still presented metacognitive impairment, received significant beneficial effects from CBT-I both on insomnia symptoms and on dysfunctional beliefs, but not on dysfunctional metacognitive functioning. These findings suggest that metacognition should be carefully evaluated in insomnia patients and further studies are needed to evaluate long-term implications of this remaining dysfunction.

Microstructural changes in normal-appearing white matter in male sleep apnea patients are reversible after treatment: A pilot study.

Visually appreciable white matter (WM) changes have been described in obstructive sleep apnea (OSA). However, few data exist on the involvement of silent WM abnormalities. This prospective study investigated the microstructural integrity of normal-appearing white matter (NAWM) in male OSA patients before and after continuous positive airway pressure (CPAP) treatment, using a neuroimaging approach. Magnetic resonance imaging (MRI) was acquired from 32 participants (16 severe never-treated OSA and 16 controls). Diffusion tensor imaging (DTI) and Tract-Based Spatial Statistics (TBSS) were used to assess the microstructural NAWM changes in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). In order to evaluate the efficacy of the therapy, OSA patients underwent MRI evaluations at baseline and after 3 months of treatment (follow-up). CPAP treatment significantly increased the FA in NAWM of the brain stem, corpus callosum and bilateral internal capsule of OSA patients at follow-up compared to baseline (p < 0.05, TFCE-corrected). OSA patients also showed increases in AD in the corpus callosum, superior corona radiata, and internal capsule of the right hemisphere (p < 0.05, TFCE-corrected) after CPAP treatment. A significant negative correlation was found between the FA of the corona radiata, corpus callosum, internal capsule, limbic structures, and neuropsychological scores at follow-up evaluation. No significant differences were found in MD and RD of NAWM in our patients after treatment. Our results demonstrate that FA and AD of NAWM in major tracts such as the corpus callosum and the internal capsule increased significantly after CPAP treatment, as a potential beneficial effect of ventilatory therapy. The recovery of NAWM alterations might also be related to the improvement in the neurocognitive profile, suggesting that nonclearly visible WM alterations may contribute to the physiopathology of OSA-related cognitive impairment.

Extreme sleep state misperception: From psychopathology to objective-subjective sleep measures.

STUDY OBJECTIVES: We tested the hypothesis that patients with extreme sleep state misperception display higher levels of psychopathology and reduced quantitative estimation abilities compared to other patients with insomnia. Secondary aims included the evaluation of group differences in subjective self-reported quality of life and sleep quality and objective sleep parameters. METHODS: In this cross-sectional, observational study, 249 patients with insomnia underwent a video-polysomnography with a subsequent morning interview to assess self-reported sleep estimates and filled in a large battery of questionnaires. Patients were classified into High Misperception (HM) and Moderate Misperception (MM) groups, according to the complement of the ratio between self-reported total sleep time and objective total sleep time (Misperception Index). RESULTS: No significant differences emerged in any of the psychopathological measures considered between the HM and the MM group. Similarly, no effect was observed in quantitative estimation abilities. HM patients displayed a significantly increased number of awakenings per hour of sleep and a reduced dream recall rate. Their overall sleep quality and quality of life was significantly impaired. CONCLUSIONS: Future research on sleep misperception should focus on factors other than the level of psychopathology and estimation abilities, in particular sleep microstructure and quantitative EEG studies in both REM and NREM sleep.

Depressive and stress symptoms in insomnia patients predict group cognitive-behavioral therapy for insomnia long-term effectiveness: A data-driven analysis.

BACKGROUND: Insomnia Disorder is characterized by high degree of phenotypic heterogeneity, that might influence treatment response. METHODS: 123 of 294 insomnia patients initially recruited (66.7% females, age=40.59±11.89) were assessed before and after group Cognitive-Behavioral Therapy for Insomnia (CBT-I), as well as at follow-up (7.8±1.6 years after the end-of-treatment). By use of latent class analysis (LCA) we identified insomnia subtypes according with baseline scores of insomnia severity and features, anxiety, depression, stress and sleepiness symptoms, circadian rhythm, and treatment effectiveness (Delta score of Insomnia Severity Index-ISI between baseline and end-of-treatment). RESULTS: By LCA we revealed three classes: "PURE INSOMNIA", "INSOMNIA+ANXIETY+DEPRESSION+STRESS", and "INSOMNIA+ANXIETY". The improvements in insomnia severity was maintained up to 10 years after the end-of-treatment, but with differences between classes (p<0.05). Class "INSOMNIA+ANXIETY+DEPRESSION+STRESS" showed at the end-of-treatment the largest percentage of responders (63.5% = Insomnia Severity Index decrease ≥8). However, at follow up the effect was less and 48.1% had a moderate or severe insomnia (Insomnia Severity Index >14). LIMITATIONS: The lack of a control group and the absence of a complete clinical assessment at the follow-up limit the interpretability of our results. CONCLUSIONS: Our data driven analysis suggest insomnia heterogeneity can be categorized into sub-classes by depression, anxiety, and stress symptoms. In addition, insomnia patients with stress and depression symptoms maintained highest percentage of clinical depression at the end-of-treatment and insomnia at follow-up, in comparison with others classes. Stress and depression symptoms should be considered risk factors that play an important role in the long-term outcome of CBT-I.

The reliability of objective total sleep time in predicting the effectiveness of cognitive-behavioral therapy for insomnia.

BACKGROUND: Despite insomnia diagnosis is based only on subjective sleep assessment, recent literature suggested the usefulness of objective sleep duration for the identification of two insomnia phenotypes based on objective total sleep time (oTST). In particular, insomnia with short sleep duration (SS) (oTST<6 h) seems to receive less benefit from Cognitive-Behavioral Therapy for Insomnia (CBT-I) compared to patients with normal sleep duration (NS) (oTST≥6 h). The aim of this study is to evaluate CBT-I response of patients previously divided into SS and NS and to assess the agreement between oTST measured by polysomnography (PSG) and by actigraphy in identifying the two subgroups. METHODS: Fifty-three insomnia patients (50.9% females; mean age 56.53 ± 11.43) underwent a baseline PSG and an actigraphic evaluation to identify SS and NS subjects. Insomnia Severity Index (ISI) and sleep diaries data (wakefulness after sleep onset) were considered primary outcomes. All the other sleep diaries variables were used as secondary outcomes. RESULTS: Throughout PSG we identified 22 NS (41.5%) and 31 SS (58.5%) patients, whereas actigraphic evaluation identified 38 NS (71.7%) and 15 SS (28.3%) patients. All subjects showed significant improvement after treatment, however, no effect of group membership was found to influence CBT-I response. Strikingly, actigraphy and PSG differed in identifying the two subgroups. Specifically, only 27 out 53 (51%) were consistently classified as SS [K = 0.086, 95% confidence interval: -0.132 to 0.305, p = 0.448]. CONCLUSIONS: Our results challenge the reliability and usefulness of oTST in predicting CBT-I effectiveness. Future studies might focus on night-to-night variability experienced by insomnia patients for the prediction of CBT-I outcomes.

Impact of pre-sleep habits on adolescent sleep: an Italian population-based study.

OBJECTIVE: Several evidences demonstrate that pre-sleep habits may negatively impact adolescent sleep, yet few data exist on Italian population. This study aimed to investigate the relationship between pre-sleep habits, use of technology/activity and sleep in Italian adolescents. METHODS: Self-report questionnaires including Italian version of School Sleep Habits Survey and use of technology/activity (eg smartphone, PC) at bedtime were administered to 972 adolescents (13-19 years) from Lombardia. We stratified the sample in five groups according to the age: Group I (13-14 years), Group II (15 years), Group III (16 years), Group IV (17 years), Group V (18-19 years). RESULTS: Our descriptive analysis reveals a different sleep profile across age-groups: Group III showed highest percentage of bad sleep (26.7%) and frequent nocturnal awakenings (24.1%), Group V had the highest percentage of insufficient sleep (40,4%) and difficulty falling asleep (42.7%) and Group IV presented an elevated difficulty in waking up in the morning (70.1%). A significant negative correlation was found in total group between use of smartphone, internet and studying/doing homework and total sleep time. The use of smartphone, internet videogames, listening to music and studying/doing homework was positively associated with delayed bedtime. CONCLUSIONS: This study confirms the great impact of pre-sleep habits, and in particular the use of technology on adolescent sleep. Our results demonstrate that sleep is strongly altered among Italian adolescents using electronic devices in evening. The type of technology may be related to specific sleep profile, emphasizing the importance of stratification analyses to identify associated factors to sleep problems.

Insomnia disorder: clinical and research challenges for the 21st century.

BACKGROUND AND PURPOSE: Insomnia is a common and debilitating disorder that is frequently associated with important consequences for physical health and well-being. METHODS: An international expert group considered the current state of knowledge based on the most relevant publications in the previous 5 years, discussed the current challenges in the field of insomnia and identified future priorities. RESULTS: The association of trajectories of insomnia with subsequent quality of life, health and mortality should be investigated in large populations. Prospective health economics studies by separating the costs driven specifically by insomnia and costs attributable to its long-term effects are needed. Ignoring the heterogeneity of insomnia patients leads to inadequate diagnosis and inefficient treatment. Individualized interventions should be promoted. More data are needed on both the impact of sleep on overnight effects, such as emotion regulation, and the potential compensatory effort to counteract diurnal impairments. Another gap is the definition of neurocognitive deficits in insomnia patients compared to normal subjects after chronic sleep loss. There are also a number of key gaps related to insomnia treatment. Expert guidelines indicate cognitive-behavioural therapy for insomnia as first-line treatment. They neglect, however, the reality of major healthcare providers. The role of combined therapy, cognitive-behavioural therapy for insomnia plus pharmacological treatment, should be evaluated more extensively. CONCLUSION: Whilst insomnia disorder might affect large proportions of the population, there are a number of significant gaps in the epidemiological/clinical/research studies carried out to date. In particular, the identification of different insomnia phenotypes could allow more cost-effective and efficient therapies.

Impact of COVID-19 lockdown on sleep quality in university students and administration staff.

INTRODUCTION: In Italy, lockdown due to COVID-19 health emergency started on March 10 and partially ended on May 3rd, 2020. There was a significant increase of psychological distress and symptoms of mental illness, and worsening of quality of sleep in the general population. METHODS: Participants completed an anonymous web-based survey that include questionnaires about sleep and anxiety and depression symptoms. Our sample included 400 subjects: 307 students (mean age 22.84 ± 2.68) and 93 university administration staff workers (mean age 37.02 ± 12.46). RESULTS: we found an increase in Bed Time hour, Sleep Latency, and Wake-Up time between before and during COVID-19 emergency and a worsening of sleep quality and of insomnia symptoms. In particular, during the lockdown, the impact of the delay in Bed Time and in Wake-Up was more pronounced in students. In workers, we observed a prevalence of maintenance insomnia before COVID-19 of 24% that significantly increase during COVID-19 reaching 40%, while workers with difficulties in sleep initiation were only 15% that increased to 42%. In our sample, 27.8% showed depressive symptoms, while 34.3% showed anxious symptoms, in particular in students. CONCLUSION: The impact of lockdown was greater in students than in workers, and in females than in males. Concerning the psycho-emotional aspects, about one-third of our sample showed depressive or anxious symptoms. The results of our study may provide support for the implementation of some interventions for well-being in pandemic condition.

Insomnia Patients With Subjective Short Total Sleep Time Have a Boosted Response to Cognitive Behavioral Therapy for Insomnia Despite Residual Symptoms.

Background: Two distinct insomnia disorder (ID) phenotypes have been proposed, distinguished on the basis of an objective total sleep time less or more than 6 hr. In particular, it has been recently reported that patients with objective short sleep duration have a blunted response to cognitive behavioral therapy for insomnia (CBT-I). The aim of this study was to investigate the differences of CBT-I response in two groups of ID patients subdivided according to total sleep time. Methods: Two hundred forty-six ID patients were subdivided into two groups, depending on their reported total sleep time (TST) assessed by sleep diaries. Patients with a TST greater than 6 hr were classified as "normal sleepers" (NS), while those with a total sleep time less than 6 hr were classified as "short sleepers" (SS). Results: The delta between Insomnia Severity Index scores and sleep efficiency at the beginning as compared to the end of the treatment was significantly higher for SS in comparison to NS, even if they still exhibit more insomnia symptoms. No difference was found between groups in terms of remitters; however, more responders were observed in the SS group in comparison to the NS group. Conclusions: Our results demonstrate that ID patients with reported short total sleep time had a beneficial response to CBT-I of greater magnitude in comparison to NS. However, these patients may still experience the presence of residual insomnia symptoms after treatment.

Impact Of Phenotypic Heterogeneity Of Insomnia On The Patients' Response To Cognitive-Behavioral Therapy For Insomnia: Current Perspectives.

Insomnia is one of the most common mental disorders and the most frequent sleep disorder encountered in clinical practice, with a prevalence of about 7% in the European population. Insomnia Disorder (ID) is defined as a disturbance of sleep initiation or maintenance, followed by a feeling of non-restorative sleep and several diurnal consequences ranging from occupational and social difficulties to cognitive impairment. Cognitive-Behavioral Therapy for Insomnia (CBT-I) is considered the first-choice therapy for this disorder because its effectiveness has been proven to be greater in the long term with fewer side effects in comparison to pharmacotherapy. Although its effectiveness has been well established, it has been reported that nearly 40% of patients do not achieve remission after treatment. This finding could be the consequence of heterogeneity of ID between patients. It has been proposed that this heterogeneity might be ascribable to indices that are not related to sleep quality and quantity, such as comorbidities, life events, and personality traits. However, several works focused on the role of sleep markers, in particular objective total sleep time, for the phenotypization of ID and treatment response. The aim of this work is to summarize the available scientific literature regarding the impact of ID subtype on CBT-I response.

The paradox of paradoxical insomnia: A theoretical review towards a unifying evidence-based definition.

Paradoxical insomnia is one of the most intriguing yet challenging subtypes of insomnia. Despite being recognized for a long time by the international community, it is still unclear whether this entity really exists, which are its features and boundaries. Much of the debate is fuelled by the lack of a consensus on its precise definition. To help filling some of the existing gaps, a systematic review of the literature was conducted, through which 19 different quantitative definitions were obtained. These definitions were then applied to two distinct datasets. The first consisted of 200 chronic primary insomnia patients, diagnosed according to the DSM-IV-TR criteria. The second consisted of 200 age- and sex-matched healthy persons without insomnia. For each dataset, available data from the objective sleep parameters and their subjective estimation were imported and analysed in MATLAB. Depending on the definition used, the prevalence of paradoxical insomnia ranged from 8 to 66%, while agreement between different definitions ranged from -0.19 to 0.9 (using Cohen's kappa coefficient). Based on the results garnered, necessary features for a quantitative definition of paradoxical insomnia were identified. Several open questions remain, such as whether there is a minimum number of hours a patient should sleep to fulfill the criteria for a diagnosis of paradoxical insomnia, and whether sleep latency can be used in the definition along with total sleep time. We conclude by advocating continued study of paradoxical insomnia and sleep state misperception and by providing specific directions for future research. STATEMENT OF SIGNIFICANCE: The current understanding of paradoxical insomnia and, more broadly, of sleep state misperception, is greatly hampered by the lack of agreement on a quantitative and evidence-base measure of the discrepancy between subjective and objective sleep evaluation. The current study provides a critical analysis about the strength and the limitations of the available definitions, using both a data-driven and a theory-driven approach. The overarching goal is to motivate a rigorous discussion involving the main experts of the field, to build a consensus, and develop an evidence-based measure of sleep state misperception and/or of paradoxical insomnia.

Sleep apnea: Altered brain connectivity underlying a working-memory challenge.

Obstructive sleep apnea (OSA) is characterized by the frequent presence of neuro-cognitive impairment. Recent studies associate cognitive dysfunction with altered resting-state brain connectivity between key nodes of the executive and default-mode networks, two anti-correlated functional networks whose strength of activation increases or decreases with cognitive activity, respectively. To date no study has investigated a relationship between cognitive impairment in OSA and brain connectivity during an active working-memory challenge. We thus investigated the effect of OSA on working-memory performance and underlying brain connectivity. OSA patients and matched healthy controls underwent functional magnetic resonance imaging (fMRI) scanning while performing a 2-back working-memory task. Standard fMRI analyses highlighted the brain regions activated at increasing levels of working-memory load, which were used as seeds in connectivity analyses. The latter were based on a multiregional Psycho-Physiological-Interaction (PPI) approach, to unveil group differences in effective connectivity underlying working-memory performance. Compared with controls, in OSA patients normal working-memory performance reflected in: a) reduced interhemispheric effective connectivity between the frontal "executive" nodes of the working-memory network, and b) increased right-hemispheric connectivity among regions mediating the "salience-based" switch from the default resting-state mode to the effortful cognitive activity associated with the executive network. The strength of such connections was correlated, at increasing task-demands, with executive (Stroop test) and memory (Digit Span test) performance in neuro-cognitive evaluations. The analysis of effective connectivity changes during a working-memory challenge provides a complementary window, compared with resting-state studies, on the mechanisms supporting preserved performance despite functional and structural brain modifications in OSA.

Long-term clinical effect of group cognitive behavioral therapy for insomnia: a case series study.

OBJECTIVE: Cognitive-behavioral therapy for insomnia (CBT-I) is recognized as the first-choice intervention for insomnia. One of the best-known advantages of CBT-I in comparison with pharmacotherapy is its long-term effect. However, only few studies have assessed its benefits with follow-up periods of longer than three years. In this clinical case series study we aimed to describe the long-term effects of group CBT-I after a mean 7.8 ± 1.6 years of follow-up (range 4-10 years). METHODS: A total of 292 insomnia disorder (ID) patients were consecutively enrolled at the Sleep Disorders Center of San Raffaele Hospital, Milan; 123 patients (82 (66.7%) females and 41 (33.3%) males, mean age 40.59 ± 11.89 years) completed the follow-up evaluation within a range of 4-10 years. RESULTS: In the 258 patients who completed the treatment, insomnia severity index (ISI) total score improved significantly as well as all variables of the sleep diaries. Using ISI as the primary outcome, we demonstrated that the effect of CBT-I is maintained up to 10 years after the end of treatment. Furthermore, we found that patients that used only CBT-I techniques to deal with relapses were the ones with better outcomes, in particular compared to the patients that re-used medications. CONCLUSION: To the best of our knowledge this is the longest follow-up evaluation in the literature, both for group and individual CBT-I. These findings have an important clinical implication both suggesting and confirming that CBT-I can be considered the treatment of choice for insomnia.