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The duration and quality of sleep are believed to significantly influence the onset of metabolic syndrome (MetS), but existing data lack consistency. The meta-analysis aims to evaluate the prevalence of the MetS in association with sleep duration. We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 guidelines. A comprehensive search of PubMed, Google Scholar, and Research Gate databases was performed to identify cohort and cross-sectional studies published in English between 2013 and 2023. We included studies that examined the association between sleep duration/quality and MetS, and two independent reviewers assessed study quality and bias using the Newcastle–Ottawa scale. The systematic review included 11 studies with a total of 343,669 participants, including 4 cohort studies and 7 cross-sectional studies. Sample sizes varied widely, ranging from 293 to 162,121 individuals. The studies had different follow-up periods, participant ages ranging from 10 to 80 years, and predominantly male populations. The prevalence of MetS was higher in average sleepers [52%, 95% confidence interval (CI): 40%–64%] compared with short sleepers (13%, 95% CI: 8%–18%) and long sleepers (15%, 95% CI: 9%–24%). Globally, North American countries exhibit the highest prevalence of MetS across short- (25.3%, 95% CI: 4.2%–72.4%) and long-sleeper (22.4%, 95% CI: 2.8%–74.1%) categories, whereas Asian countries experience the highest prevalence among the average sleeper category (58.7%, 95% CI: 44.1%–71.9%). Our meta-analysis indicates an elevated prevalence of MetS in average sleepers. Future research endeavors address delve into the underlying mechanisms and incorporate objective measures to understand the multifaceted connection between sleep patterns and MetS, guiding more effective preventive and management strategies. [ABSTRACT FROM AUTHOR]

Sleep disorders are commonly linked to various health conditions, although it remains unclear to what degree they are linked with overall mortality. We compared mortality in different self-reported sleep disorders in a large population-based prospective study. In this case-control study within the CLSA cohort, participants completed a questionnaire at baseline (2011–2015) measuring overall sleep satisfaction, daily sleep duration, sleep-onset and sleep-maintenance insomnia, daytime somnolence, REM sleep behavior disorder (RBD), restless leg syndrome (RLS), and obstructive sleep apnea (OSA). The vital status of participants was assessed in July 2019. Baseline sleep problems of participants who died (cases) were compared to those who survived (controls). For each case, five age/sex-matched controls were selected. Binary logistic regression was used to estimate the association between sleep symptoms and mortality, adjusting for age, sex, marital status, province, education, alcohol consumption, smoking, caffeine, and body mass index. In a complementary model, anxiety and depression were also added. Among 30,097 participants at baseline, 974 deaths were reported in 2019 (60.7 % male, age = 72.3 ± 9.4 years). In the initial analysis, mortality cases reported more baseline sleep-maintenance insomnia (12.1 % vs. 8.0 %, Adjusted OR[95%CI] = 1.62[1.15,2.29]), daytime somnolence (2.4 % vs. 1.1 %, AOR = 2.70[1.34,5.44]), and higher possible RLS (16.4 % vs. 12.4 %, AOR = 1.50[1.09,2.05]). They were also more likely to screen positive for possible OSA (33.8 % vs. 24.2 %, AOR = 1.32[1.07,1.64]); however, this effect was not related to core apnea symptoms. Sleep durations exceeding 10 h/day were also associated with increased mortality (3.4 % vs. 1.9 %, AOR = 1.83[1.04,3.24]). Other sleep symptoms/disorders, such as sleep-onset insomnia (7.3 % vs. 4.3 %, AOR = 1.54 [1.00,2.37]), possible RBD (5.3 % vs. 5.1 %, AOR = 1.02[0.62,1.69]), and overall sleep dissatisfaction (26.5 % vs. 22.6 %, AOR = 1.14[0.93,1.41]) were not different among these groups. After adding anxiety and depression to the adjustment model, all differences attenuated to become statistically non-significant, except for daytime somnolence disorder. When stratified by sex, the association between sleep disorders and mortality was only observed in women, with men showing no association. We confirm a relationship between numerous sleep disorders and mortality. This effect is most evident in women, and appears to be strongly related to co-existing anxiety and depression. • Insomnia and daytime somnolence were associated with increased mortality risk. • Long sleep duration (≥10 h/day) was associated with an 83 % increase in mortality. • Restless leg syndrome and sleep apnea were linked to increased mortality. • Most of these effects were observed in females and in adults aged 45–64 years. [ABSTRACT FROM AUTHOR]

Purpose: Delayed awakening after anesthetic discontinuation during awake craniotomy is associated with somnolence during functional brain mapping. However, predictors of delayed awakening in patients receiving monitored anesthesia care for awake craniotomy are unknown. Methods: This retrospective cohort study analyzed 117 adult patients with supratentorial glioma in or near eloquent areas who received monitored anesthesia care for awake craniotomy between July 2020 and January 2023 at Linkou Chang Gung Memorial Hospital. These patients were divided into two groups according to their time to awakening (ability to speak their names) after propofol cessation: longer or shorter than 20 min (median duration). Because propofol was solely used anesthetic from skin incision to dural opening, parameters in Schnider model for propofol target-controlled infusion, such as age, sex, and BMI, were adjusted or propensity-matched to compare their anesthetic, surgical, and histopathological profiles. Results: After propensity-matched comparisons of age and BMI, significant predictors of delayed awakening included IDH1 wild-type tumors and repeated craniotomies. Subgroup analysis revealed that older age and larger T2 volume were predictors in patients undergoing the first craniotomy, while lower preoperative Karnofsky performance scale scores and depression were predictors in repeated craniotomy cases. Delayed awakening was also associated with somnolence and a lower gross total resection rate. Conclusion: Our retrospective analysis of patients receiving monitored anesthesia care for awake craniotomy revealed that delayed awakening after propofol discontinuation occurred more often in patients with IDH1 wild-type tumors and repeated craniotomies. Also, delayed awakening was associated with somnolence during functional mapping and a lower gross total resection rate. [ABSTRACT FROM AUTHOR]

David J Stevens,1 Sarah Appleton,1 Kelsey Bickley,1 Louis Holtzhausen,2– 4 Robert Adams1,5 1Sleep Health, Flinders Health and Medical Research Institute, Flinders University, Bedford Park, South Australia, Australia; 2Aspetar Orthopaedic and Sports Medicine Hospital, Doha, Qatar; 3Section Sports Medicine, Faculty of Health Science, University of Pretoria, Pretoria, South Africa; 4Department of Exercise and Sport Science, University of the Free State, Bloemfontein, South Africa; 5Respiratory and Sleep Services, Southern Adelaide Local Health Network, Bedford Park, South Australia, AustraliaCorrespondence: David J Stevens, Sleep Health, Flinders Health and Medical Research Institute, Flinders University, Level 2a, 5 Laffer Dve, Bedford Park, South Australia, 5041, Australia, Tel +61 7306 1816, Email david.stevens@flinders.edu.auPurpose: Little is known about sleep after a concussion, a form of mild traumatic brain injury. Given the importance of sleep for both maintaining brain health and recovery from injury, we sought to examine sleep acutely and subacutely after concussion.Methods: Athletes who experienced a sports-related concussion were invited to participate. Participants underwent overnight sleep studies within 7 days of the concussion (acute phase), and again eight-weeks after the concussion (subacute phase). Changes in sleep from both the acute and subacute phases were compared to population normative values. Additionally, changes in sleep from acute to subacute phase were analysed.Results: When compared to normative data, the acute and subacute phases of concussion showed longer total sleep time (p < 0.005) and fewer arousals (p < 0.005). The acute phase showed longer rapid eye movement sleep latency (p = 0.014). The subacute phase showed greater total sleep spent in Stage N3% (p = 0.046), increased sleep efficiency (p < 0.001), shorter sleep onset latency (p = 0.013), and reduced wake after sleep onset (p = 0.013). Compared to the acute phase, the subacute phase experienced improved sleep efficiency (p = 0.003), reduced wake after sleep onset (p = 0.02), and reduced latencies for both stage N3 sleep (p = 0.014) and rapid eye movement sleep (p = 0.006).Conclusion: This study indicated sleep during both the acute and subacute phases of SRC was characterised by longer and less disrupted sleep, along with improvements in sleep from the acute to subacute phases of SRC.Keywords: mild traumatic brain injury, somnolence, neural trauma, nocturnal activity

Introduction: Our objective was to conduct a systematic review and meta-analysis of adverse effects on sleep in patients with schizophrenia receiving antipsychotic treatment. Methods: A systematic search was performed in PubMed, Cochrane Central, Embase, Toxline, Ebsco, Virtual Health Library, Web of Science, SpringerLink, and in Database of abstracts of Reviews of Effects of Randomized Clinical Trials to identify eligible studies published from January 1990 to October 2021. The methodological quality of the studies was evaluated using the CONSORT list, and the Cochrane bias tool. Network meta-analysis was performed using the Bayesian random-effects model, with multivariate meta-regression to assess the association of interest. Results: 87 randomized clinical trials were identified that met the inclusion criteria, and 70 articles were included in the network meta-analysis. Regarding the methodological quality of the studies, 47 had a low or moderate bias risk. The most common adverse effects on sleep reported in the studies were insomnia, somnolence, and sedation. The results of the network meta-analysis showed that ziprasidone was associated with an increased risk of insomnia (OR, 1.56; 95% credible interval CrI, 1.18-2.06). Several of the included antipsychotics were associated with a significantly increased risk of somnolence; haloperidol (OR, 1.90; 95% CrI, 1.12-3.22), lurasidone (OR, 2.25; 95% CrI, 1.28-3.97) and ziprasidone (OR, 1.79; 95% CrI, 1.06-3.02) had the narrowest confidence intervals. In addition, perphenazine (OR, 5.33; 95% CrI, 1.92-14.83), haloperidol (OR, 2.61; 95% CrI, 1.14-5.99), and risperidone (OR, 2.41; 95% CrI, 1.21-4.80) were associated with an increased risk of sedation compared with placebo, and other antipsychotics did not differ. According to the SUCRAs for insomnia, chlorpromazine was ranked as the lowest risk of insomnia (57%), followed by clozapine (20%), while flupentixol (26 %) and perospirone (22.5%) were associated with a lower risk of somnolence. On the other hand, amisulpride (89.9%) was the safest option to reduce the risk of sedation. Discussion: Insomnia, sedation, and somnolence were the most frequent adverse effects on sleep among the different antipsychotics administered. The evidence shows that chlorpromazine, clozapine, flupentixol, perospirone, and amisulpride had favorable safety profiles. In contrast, ziprasidone, perphenazine, haloperidol, and risperidone were the least safe for sleep. [ABSTRACT FROM AUTHOR]

Cette étude avait pour but d'évaluer l'effet de la sieste sur la somnolence perçue et les performances cognitives lors d'un ultra trail. Vingt-trois coureurs, ont participé à notre étude sur l'Ultra Trail du Mont Blanc ® 2021 (UTMB®). Leur somnolence (Karolinska Sleepiness Scale , KSS) et leurs performances cognitives (temps de réaction, RT) ont été évaluées au ravitaillement du 142e kilomètre (32,2 ± 2 heures de course). Deux groupes ont été formés : un groupe sieste (GS ; n = 11) et un contrôle (GC ; n = 12). Les mesures ont été effectuées à l'entrée du point de ravitaillement (ENT), à la sortie de la sieste (POST ; uniquement pour GS) et 1 km après le ravitaillement (1 km). À ENT, GS avait des temps de réaction (RT) supérieurs à ceux de GC (p < 0,05). Une baisse de RT a été observée chez le GS immédiatement après la sieste (p < 0,05). Cette amélioration était encore conservée à 1 km (p < 0,001). À 1 km il n'y avait plus de différence entre les deux groupes. Enfin le score KSS du GS a baissé entre POST et 1 km (p < 0,001). Le groupe ayant effectué une sieste au cours de la deuxième nuit de course ont produit des RT plus faibles que le groupe GC. Plus qu'une stratégie à long terme, la perception d'une moindre vigilance semble être un facteur déterminant dans la prise de décision chez les coureurs souhaitant s'arrêter pour dormir. Dans ce cadre, une sieste de 15 à 20 min, temps d'endormissement compris, semble améliorer autant les performances cognitives que la somnolence perçue. The aim of this study is to evaluate the effect of napping on perceived sleepiness and cognitive performance during an ultra-trail. Twenty-three runners participated in our study on the Ultra Trail du Mont Blanc ® 2021 (UTMB®). Their sleepiness status (Karolinska Sleepiness Scale, KSS) and cognitive performances (reaction time, RT) were evaluated at the the kilometer 142 checkpoint (28 ± 2 hrs of race). Two groups were formed: a nap group (GS, n = 11) and a control group (GC, n = 12). Measurements were made at the entrance to the checkpoint (ENT), right after the nap (POST, only for GS) and 1 km after the checkpoint (1 km). At ENT, GS runners had a longer RT than GC (P < 0.05). There was an improvement in RT immediately after the nap in the GS group (P < 0.05). This improvement was maintained at 1 km (P < 0.001). At 1 km, there was no difference between the two groups. A decrease in the KSS of the GS group was observed between POST and 1 km (P < 0.001). The participant who took a nap during the second night of UTMB had lower cognitive performances than the GC group. Beyond a long-term strategy, the perception of a lesser self-alertness seems to be a determinant in the decision making to stop for a nap. In this context, a 15 to 20 min nap, including the sleep onset duration, seems to improve cognitive performance as well as perceived sleepiness. [ABSTRACT FROM AUTHOR]

Rie Nakajima, Nana Morita, Fumiyuki Watanabe, Yasuhiro Kosuge School of Pharmacy, Nihon University, Chiba, 274-8555, JapanCorrespondence: Rie Nakajima, School of Pharmacy, Nihon University, Tel +81 47 465 7389, Fax +81 47 465 7389, Email nakajima.rie@nihon-u.ac.jpPurpose: Antihistamine over-the-counter (OTC) drugs for allergic rhinitis are widely used and cause central nervous system side effects. Most available data on anti-allergic drugs are on controlled usage. It is necessary to investigate the occurrence of side effects in the context of self-medication to avoid inappropriate use. We aimed to clarify the association between the usage of OTC anti-allergic drugs and central nervous system side effects.Patients and Methods: An online, anonymous, cross-sectional study was conducted using a structured questionnaire. People who had used OTC anti-allergic drugs in the year prior to the study were recruited. To assess the association between inappropriate drug use and the occurrence of side effects, a binary logistics regression analysis was performed according to three dosage forms (oral only, nasal only, and oral and nasal combined use).Results: Somnolence was experienced by 59.1% of the participants using the OTC drug for allergic rhinitis. Using logistic regression analysis, “drug use exceeding the upper limit” was seen to be associated with side effects in only oral (Somnolence: OR = 1.41, 95% CI = 1.17– 1.70; Dull head: OR=1.41, 95% CI = 1.16– 1.70; Loss of concentration: OR = 1.25, 95% CI = 1.04– 1.49) and oral and nasal combined use groups (Somnolence: OR = 1.33, 95% CI = 1.04– 1.71; Dull head: OR = 1.47, 95% CI = 1.15– 1.89; Loss of concentration: OR = 1.51, 95% CI = 1.19– 1.91). Furthermore, “expired drug use” was associated with side effects in the nasal spray-only group (Somnolence: OR = 1.31, 95% CI = 1.07– 1.60; Dull head: OR =1.25, 95% CI = 1.02– 1.53; Loss of concentration: OR = 1.24, 95% CI = 1.00– 1.54).Conclusion: Inappropriate use was common among users of OTC allergic rhinitis drugs. Differences in side effects depending on the dosage form used were observed.Keywords: antihistamines, adherence, oral medicine, nasal spray, somnolence

Background: Antiseizure medications (ASMs) may affect nocturnal sleep and daytime vigilance. Perampanel (PER), a third-generation ASM, showed to improve nocturnal sleep in patients with epilepsy (PWE). Although ASMs can have beneficial effects on nocturnal sleep and daytime sleepiness, no study investigated the effect of PER on both sleep–wake cycle and daytime sleepiness. Therefore, this study aimed to objectively evaluate the sleep–wake cycle and daytime sleepiness in PWE treated with PER as adjunctive therapy. Methods: This prospective study included adult PWE who received PER as add-on treatment. Sleep–wake cycle was assessed through actigraphic monitoring and daytime sleepiness by the multiple sleep latency test (MSLT) performed at the end of the actigraphic recording. All patients performed both tests at baseline and at 6-month follow-up. Results: Ten patients (mean age: 44.50 ± 22.71 years, 50.0% female) were included. The mean monthly seizure frequency was 3.20 ± 5.94. Six of ten patients started PER as a first add-on treatment. The final PER dose was 5.11 ± 2.02 mg/day, and nine of ten patients achieved seizure freedom at follow-up. There was a significant decrease in mean monthly seizure frequency from baseline to follow-up (p = 0.004). No significant changes were found in the sleep–wake cycle parameters. An increase in sleep latency mean was observed at MSLT at 6-month follow-up (p = 0.005). Conclusions: This study confirms that adjunctive PER is effective on seizures without pathologically change of the sleep–wake cycle in PWE and can even improve daytime sleepiness. This effect can be mediated by the achievement of seizure control. Therefore, PER may be promising in PWE with sleep disturbances and daytime sleepiness. [ABSTRACT FROM AUTHOR]

Sleep dysfunction is highly prevalent in Huntington's disease (HD). Increasing evidence suggests that such dysfunction not only impairs quality of life and exacerbates symptoms but may even accelerate the underlying disease process. Despite this, current HD treatment approaches neither consider the impact of commonly used medications on sleep, nor directly tackle sleep dysfunction. In this review, we discuss approaches to these two areas, evaluating not only literature from clinical studies in HD, but also that from parallel neurodegenerative conditions and preclinical models of HD. We conclude by summarizing a hierarchical framework of current medications with regard to their impact on sleep, and by outlining key emerging sleep therapies. [ABSTRACT FROM AUTHOR]

Somnolence is a common adverse effect of antipsychotic drugs used to treat psychotic disorders. It causes problems in many areas of life, such as gainful employment, driving, childcare, and social interactions. Somnolence is a major problem for a relatively new antipsychotic drug, lurasidone, whose dose-effect relationship remains unclear. Based on data from a bioequivalence study of two 40 mg lurasidone hydrochloride tablets, we designed two case-control studies to explore the correlation between somnolence and exposure to lurasidone and determine the factors associated with lurasidone-induced somnolence. In the first case-control study, lurasidone was administered to healthy volunteers; 30 experienced somnolence (as pre-defined) but 29 did not. Moreover, plasma concentration at 1 h was significantly associated with somnolence (OR = 1.124; p = 0.001). In the second case-control study, 48 volunteers administered lurasidone were classified into somnolence and no-somnolence groups based on different time-related criteria. We observed a positive association between plasma concentration at 0.75 h and somnolence (OR = 1.024; p = 0.002). Receiver operating characteristic analysis revealed that a plasma lurasidone concentration >21.65 ng/mL 1 h after administration strongly predicted somnolence. Our findings in healthy volunteers need to be further validated in patients in clinical settings to determine the optimal dose and duration of lurasidone administration.

IntroductionOur objective was to conduct a systematic review and meta-analysis of adverse effects on sleep in patients with schizophrenia receiving antipsychotic treatment.MethodsA systematic search was performed in PubMed, Cochrane Central, Embase, Toxline, Ebsco, Virtual Health Library, Web of Science, SpringerLink, and in Database of abstracts of Reviews of Effects of Randomized Clinical Trials to identify eligible studies published from January 1990 to October 2021. The methodological quality of the studies was evaluated using the CONSORT list, and the Cochrane bias tool. Network meta-analysis was performed using the Bayesian random-effects model, with multivariate meta-regression to assess the association of interest.Results87 randomized clinical trials were identified that met the inclusion criteria, and 70 articles were included in the network meta-analysis. Regarding the methodological quality of the studies, 47 had a low or moderate bias risk. The most common adverse effects on sleep reported in the studies were insomnia, somnolence, and sedation. The results of the network meta-analysis showed that ziprasidone was associated with an increased risk of insomnia (OR, 1.56; 95% credible interval CrI, 1.18–2.06). Several of the included antipsychotics were associated with a significantly increased risk of somnolence; haloperidol (OR, 1.90; 95% CrI, 1.12–3.22), lurasidone (OR, 2.25; 95% CrI, 1.28–3.97) and ziprasidone (OR, 1.79; 95% CrI, 1.06–3.02) had the narrowest confidence intervals. In addition, perphenazine (OR, 5.33; 95% CrI, 1.92–14.83), haloperidol (OR, 2.61; 95% CrI, 1.14–5.99), and risperidone (OR, 2.41; 95% CrI, 1.21–4.80) were associated with an increased risk of sedation compared with placebo, and other antipsychotics did not differ. According to the SUCRAs for insomnia, chlorpromazine was ranked as the lowest risk of insomnia (57%), followed by clozapine (20%), while flupentixol (26 %) and perospirone (22.5%) were associated with a lower risk of somnolence. On the other hand, amisulpride (89.9%) was the safest option to reduce the risk of sedation.DiscussionInsomnia, sedation, and somnolence were the most frequent adverse effects on sleep among the different antipsychotics administered. The evidence shows that chlorpromazine, clozapine, flupentixol, perospirone, and amisulpride had favorable safety profiles. In contrast, ziprasidone, perphenazine, haloperidol, and risperidone were the least safe for sleep.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42017078052, identifier: PROSPERO 2017 CRD42017078052.

Background: Insomnia is the sleep disorder with the highest incidence worldwide. It is estimated that this condition increases the risk of developing psychiatric, neurological, and cardiovascular problems. Due to this, it is important to have brief, reliable and valid psychometric instruments that allow health personnel their timely detection in first level health centers. Objectives: Analyze the psychometric properties of the Insomnia Severity Index (ISI) in its version adapted to Spanish in a sample of Mexican adults. Methods: The sample consisted of 310 adults, 223 (71.9%) women and 87 (28.1%) men. The comparison of four ISI measurement models of one, two and three factors and a bifactor model was carried out, its internal consistency was analyzed, an analysis of invariance by sex and correlation analysis with the Athens and Epworth scales. Results: The ISI bifactor model with a general factor (G) and a specific factor for insomnia impact (I) showed the best fit indices (χ2= 29.48, gl = 11, SRMR= 0.03, CFI= 0.98, TLI= 0.96, RMSEA= 0.07), and demonstrated configural, metric, and scalar invariance by sex. Adequate reliability was demonstrated by Omega coefficients (General: ωG= 0.86, Impact: ωI= 0.86) showed adequate reliability; the scale showed very strong correlations with the Athens scale (rAGoverall= 0.84; rAImpact=0.75) and weak to moderate correlations with the Epworth scale (rEGeneral= 0.39; rEImpact=0.44). Conclusions: The ISI bifactor version in Spanish presents adequate psychometric properties for the measurement of insomnia and, as it is a brief tool, it can be used at different levels of health care.

Abstract Background Encephalopathy following Ifosfamide treatment is a well-described phenomenon that is typically treated with Methylene Blue (MB). Chloroacetaldehyde, a potentially neurotoxic metabolite of Ifosfamide is hypothesized to cause this encephalopathy. Current guidelines for treatment is to stop Ifosfamide and provide supportive care. MB acts to inhibit Chloroacetaldehyde formation and has been described as a therapy and prophylaxis for Ifosfamide-encephalopathy. MB is effective within 30 min and lasts up to 3 days. Prolonged encephalopathy and MB therapy has not been described in the literature as lasting longer than 30 days following treatment. Case presentation We present the case of an 11-year-old female with autistic spectrum disorder and recurrent episodes of severe somnolence for 7 months following Ifosfamide therapy for her Non-Germinomatous Germ Cell Tumor (GCT). Periods of somnolence occurred prior to receiving cranial RT. Administration of MB gave immediate but limited response, with resolution of somnolence lasting 1-2 days between administrations. The somnolence could not be explained by neuroimaging or laboratory evaluation, but EEG indicated persistent encephalopathy. Conclusion A literature review determines that neurotoxicity is a side effect of Ifosfamide, but this effect has not been described persisting longer than 30 days. Our case continued to require treatment with MB for 7 months following cessation of therapy. We report these novel clinical findings, and hypothesize that there could be a genetic/metabolic component linking this reaction to Ifosfamide with the case patient’s pre-existing autism. This possible association may also correlate to the already-established link between autism and the development of GCTs. This hypothesis leads to further discussion on the suitable usage of Ifosfamide in children with co-morbidities and the necessity of screening prior to its usage.

BackgroundObstructive sleep apnea hypopnea syndrome (OSAHS) may cause Alzheimer’s disease (AD), t-tau, p-tau, Aβ42, and Aβ40 are important elements in the process of AD, and changes in the levels of these biomarkers may affect the cognitive functioning of patients. Our objective was to investigate whether uvulopalatopharyngoplasty could reduce the plasma levels of AD biomarkers in OSAHS patients and the potential correlations of AD biomarkers with cognitive impairment and sleepiness, and explore the independent influencing factors of cognitive function.MethodsAlzheimer’s disease biomarkers were measured in the plasma of 35 patients with severe OSAHS requiring surgical treatment and 16 healthy controls without OSAHS. The cognitive function and sleepiness of OSAHS patients was also evaluated. The case group was given uvulopalatopharyngoplasty and followed at the postoperative sixth month, the follow-up cases were 27, and plasma AD biomarker levels, cognitive function, and sleepiness were re-evaluated. The preoperative and postoperative AD biomarker levels OSAHS patients were compared with each other and those of the control group. Linear stepwise regression and lasso regression were used to explore the relationships of AD biomarkers with cognitive impairment and sleepiness.ResultsSignificantly higher Aβ40, t-tau, p-tau in plasma were observed preoperatively in OSAHS patients comparing to controls (29.24 ± 32.52 vs. 13.18 ± 10.78, p = 0.049; 11.88 ± 7.05 vs. 7.64 ± 4.17, p = 0.037; 26.31 ± 14.41 vs. 17.34 ± 9.12, p = 0.027). The sixth month of postoperation, the plasma AD biomarkers (Aβ42, Aβ40, t-tau, p-tau) in plasma levels decreased significantly (0.23 ± 0.17 vs. 0.20 ± 0.16, p = 0.0001; 29.24 ± 32.52 vs. 23.52 ± 24.46, p = 0.0046; 11.88 ± 7.05 vs. 8.88 ± 6.21, p = 0.0001;26.31 ± 14.41 vs. 20.43 ± 10.50, p = 0.0001). A comparison of MMSE and ESS scores from before to after surgery revealed obvious differences (27.14 ± 1.65 vs. 29.07 ± 1.78, p = 0.0001; 11.91 ± 4.84 vs. 5.89 ± 2.83, p = 0.0001). Changes in cognitive function and sleepiness scores from before to after uvulopalatopharyngoplasty were significantly correlated with AD biomarkers. Body mass index and t-tau were potential influencing factors cognitive function.ConclusionObstructive sleep apnea hypopnea syndrome can increase plasma AD biomarkers levels. Uvulopalatopharyngoplasty can improve patients’ cognition and sleepiness, and the mechanism may be related to changes in plasma AD biomarkers. Higher AHI and higher t-tau level were identified as independent risk factors for cognitive decline.

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Background: PFAS are persistent, bioaccumulative compounds repelling water, oil and stains which are widely used. There is mounting evidence linking exposure to a range of adverse health outcomes including renal, hepatic, immunotoxic, reproductive, endocrine disrupting and carcinogenic effects. PFAS possibly also induce neurobehavioral and developmental effects. Within Flanders Environment and Health Studies (FLEHS) internal exposure to PFAS and relevant health effects are assessed since 2008. Results: Adolescents 14–15 y (2010–2011) living in an industrially contaminated area (without known PFAS contamination) and adults 50–65 y (2014) randomly sampled from the general Flemish population using a stratified clustered multi-stage design, were recruited. For the adolescents perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were measured in serum, for the adults PFOS, PFOA, perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA) and perfluorobutane sulfonate (PFBS). In adolescents the Neurobehavioral Evaluation System (NES3) computerized battery of tests developed to study the neurological effects of an exposure to environmental agents was applied. The adults did the Stroop test, the NES3 Continuous Performance Test and the NES3 Digit Span Test. In adolescents sleepiness, masculinity and femininity were assessed via the Epworth Sleepiness Scale and Personal Attributes Questionnaires, respectively. In adolescents PFOA was associated with significantly increased somnolence, and PFOS with a significant inverse association with boys' femininity and with girls' masculinity. In adolescents, PFAS were also associated with a marginal decrease in sustained attention (PFOS) and cognitive performance (PFOA) and a significant decrease in short-term memory (PFOS). However, in older adults PFOS was associated with a significant increase in the capacity to pay attention and PFHxS with a significant increase in sustained attention. Conclusion: Our observations point to neurobehavioral and cognitive effects of PFAS. The neurobehavioral effects might in part result from the changes in sex hormone levels that have been reported to be associated with internal exposure to PFAS. Interestingly, whereas in relation to cognition some adverse effects were recorded for adolescents, for elderly persons our observations rather suggest possible weak positive effects with respect to cognition. Our observations might be in line with the view that PFAS have many, sometimes contrasting health effects. [ABSTRACT FROM AUTHOR]

Central nervous system-associated lesions can frequently be found in abusive head trauma (AHT) cases. Since there are frequently no visible signs of injury on the body surface, the diagnosis of AHT can be challenging. In particular, if the affected child shows only isolated neurological symptoms, these are often misinterpreted as a minor illness. Using a retrospective study design at three university hospitals, 72 medico-legal cases of "shaken baby syndrome" - a common variant of AHT - were analyzed. A comparison between confession cases (n=15) and non-confession cases was used in order to reduce the risk of circular reasoning. The most common neurological symptoms in the present cases were: epileptic seizures (44 %), pallor (37 %), somnolence (31 %), reduced muscle tone (25 %), vomiting (20 %) and unconsciousness (15 %). There were also no statistically significant differences between confession and non-confession cases, nor when comparing the simultaneous presence of skin or skeletal lesions. The combination of several symptoms serves as an indicator for the presence of AHT and should lead to further diagnostic measures under the hypothesis of the presence of an AHT in clinical observation., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Radiation is standard-of-care treatment for primary brain tumors but may have profound effects on sleep that have not yet been fully characterized. This systematic review aims to further our understanding of radiation therapy on risk of development of sleep disorders in patients with primary brain tumors (PBTs), as well as potential opportunities for prevention and treatment., Methods: A systematic search of PubMed, Embase, and Web of Science was performed (last Jan 2024) with predefined inclusion (PBT patients, radiation therapy, somnolence/circadian disruption) and exclusion (reviews/abstracts/cases/chapters, non-PBT cancer, lack of radiation) criteria, yielding 267 papers initially and 38 studies included. Data extraction and analysis (descriptive statistics, individual study summary) focused on incidence of sleep disturbances, radiation types/doses, and pharmacologic interventions. Risk of bias assessment was conducted with Effective Public Health Practice Project's Quality Assessment Tool for Quantitative Studies., Results: The included 38 studies (n=2948 patients) demonstrated high incidence of sleep disturbances in patients with primary brain tumors throughout radiation therapy, but primarily from the end of radiation to 6 months after. Sleep symptoms were associated with radiation (dose-dependent), and pharmacotherapies were helpful in patients with formal sleep disorder diagnoses. Terminology and incidence reporting of sleep symptoms are inconsistent, and many studies had high risk of bias., Conclusions: This systematic review highlights the ongoing challenges with sleep symptoms/disorders related to cranial irradiation treatment in the primary brain tumor population. Further investigations on the interconnectedness of sleep disturbance constructs and possible pharmacotherapies to alleviate symptoms are warranted., (Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: This review explores the interplay between comorbid insomnia and sleep apnea (COMISA) and erectile dysfunction (ED), 2 conditions that significantly impact men's health. COMISA, a recently recognized condition characterized by the coexistence of insomnia and obstructive sleep apnea, has been shown to disrupt sleep architecture and cause intermittent hypoxia. These disturbances are increasingly linked to the exacerbation of ED, a prevalent issue among men. Understanding the connection between COMISA and ED is crucial for developing integrated treatment approaches that address both sleep and sexual health., Objectives: We aim to explore the epidemiological, physiological, and potential therapeutic intersections of COMISA and ED. This review sets out to develop a better understanding of the relationship between these conditions and to emphasize the need for an integrated diagnostic and therapeutic approach that addresses both sleep and sexual health., Methods: Through a comprehensive analysis, including a detailed examination of extant studies, we address the hormonal imbalances and alterations in neural pathways that collectively contribute to the complex pathophysiology of ED and how these are particularly susceptible to the concurrent presence of COMISA., Results: Our analysis indicates that disruptions in sleep architecture and intermittent hypoxia associated with COMISA can exacerbate ED. Hormonal imbalances, endothelial dysfunction, autonomic imbalance, and increased inflammation and oxidative stress are key mechanisms through which COMISA influences ED. These factors collectively impair vascular health, reduce testosterone levels, disrupt neural control of erections, and contribute to the severity of ED., Conclusions: This review underscores the necessity for an integrated approach to diagnosis and therapy that considers both sleep and sexual health to improve overall outcomes. These insights should foster a deeper understanding of the relationship between COMISA and ED, encourage further research in this area, and potentially lead to the development of innovative treatment strategies to manage these closely intertwined health concerns., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Abstract Background The 12-item Medical Outcomes Study Sleep Scale (MOS Sleep Scale) has been used to capture patient-reported sleep problems in hundreds of studies. A revised version of the MOS Sleep Scale (MOS Sleep-R) was developed that uses simplified response sets, provides interpretable norm-based scoring, and has two recall versions (one-week or four-week). The objective of this study was to evaluate the psychometric properties (reliability and construct validity) of the MOS Sleep-R using data from a representative sample of U.S. adults. Methods Standardization of raw scores into norm-based T-scores (mean = 50, standard deviation = 10) was based on data from a 2009 U.S. internet-based general population survey. The internal consistency reliability of multi-item subscales and global sleep problems indices for both one-week and four-week recall forms of the MOS Sleep-R were examined using Cronbach’s alphas and inter-item correlations. Construct validity was tested by comparing item-scale correlations between items within subscales with item-scale correlations across subscales. Scale-level convergent validity was tested using correlations with measures including generic health-related quality of life (i.e., SF-36v2) and other relevant outcomes (e.g., job performance, number of days in bed due to illness or injury, happiness/satisfaction with life, frequency of stress/pressure in daily life, the impact of stress/pressure on health, and overall health). Results The one-week and four-week recall forms of the MOS Sleep-R were completed by 2045 and 2033 respondents, respectively. The psychometric properties of the one-week and four-week forms were similar. All multi-item subscales and global index scores showed adequate internal consistency reliability (all Cronbach’s alpha > 0.75). Patterns of inter-item and item-scale correlations support the scaling assumptions of the MOS Sleep-R. Patterns of correlations between MOS Sleep-R scores with criterion measures of health-related quality of life and other outcomes indicated adequate construct validity. Conclusions The MOS Sleep-R introduces a number of revisions to the original survey, including simplified response sets, the introduction of a one-week recall form, and norm-based scoring that enhances interpretability of scores. Both the one-week and four-week recall period forms of the MOS Sleep-R demonstrated good internal consistency reliability and construct validity in a U.S. general population sample.

Background and objective: Some studies observed a benefit of PD patients after treatment with safinamide in some non-motor symptoms. Our aim was to analyze the effectiveness of safinamide on sleep and daytime sleepiness in Parkinson's disease (PD) patients. Material and methods: SAFINONMOTOR is a prospective open-label single-arm study conducted in 5 centers from Spain. In this analysis, a secondary objective of the study, the score in the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) at V1 (baseline) and V4 (6 months ± 1 month) were compared. Results: Fifty patients were included between May/2019 and February/2020 (age 68.5 ± 9.12 years; 58% women; 6.4 ± 5.1 years from diagnosis). At 6 months, 44 patients completed the follow-up (88%). The PSQI total score was reduced by 19.8% (from 10.43 ± 4.02 at V1 to 8.36 ± 4.41 at V4; p = 0.001). By domains, improvement was observed in subjective sleep quality (PSQI-C1; − 23.9%; p = 0.009), sleep latency (PSQI-C2; − 25%; p = 0.025), sleep duration (PSQI-C3; − 40%; p = 0.001), and habitual sleep efficiency (PSQI-C4; − 25.9%; p = 0.023). A significant reduction (− 24.7%) in the ESS total score from V1 to V4 was observed as well (from 9.20 ± 5.64 to 6.93 ± 5.11; p = 0.012). Specifically, the improvement in daytime sleepiness was observed in sitting and reading (p = 0.024) and sitting inactive in a public space (p = 0.027). A total of 21 adverse events in 11 patients (22%) were reported, 5 of which were severe (not related to safinamide). Conclusion: Safinamide was well-tolerated and improved sleep and daytime sleepiness in PD patients at 6 months. [ABSTRACT FROM AUTHOR]

Background: Encephalopathy following Ifosfamide treatment is a well-described phenomenon that is typically treated with Methylene Blue (MB). Chloroacetaldehyde, a potentially neurotoxic metabolite of Ifosfamide is hypothesized to cause this encephalopathy. Current guidelines for treatment is to stop Ifosfamide and provide supportive care. MB acts to inhibit Chloroacetaldehyde formation and has been described as a therapy and prophylaxis for Ifosfamide-encephalopathy. MB is effective within 30 min and lasts up to 3 days. Prolonged encephalopathy and MB therapy has not been described in the literature as lasting longer than 30 days following treatment. Case presentation: We present the case of an 11-year-old female with autistic spectrum disorder and recurrent episodes of severe somnolence for 7 months following Ifosfamide therapy for her Non-Germinomatous Germ Cell Tumor (GCT). Periods of somnolence occurred prior to receiving cranial RT. Administration of MB gave immediate but limited response, with resolution of somnolence lasting 1-2 days between administrations. The somnolence could not be explained by neuroimaging or laboratory evaluation, but EEG indicated persistent encephalopathy. Conclusion: A literature review determines that neurotoxicity is a side effect of Ifosfamide, but this effect has not been described persisting longer than 30 days. Our case continued to require treatment with MB for 7 months following cessation of therapy. We report these novel clinical findings, and hypothesize that there could be a genetic/metabolic component linking this reaction to Ifosfamide with the case patient's pre-existing autism. This possible association may also correlate to the already-established link between autism and the development of GCTs. This hypothesis leads to further discussion on the suitable usage of Ifosfamide in children with co-morbidities and the necessity of screening prior to its usage. [ABSTRACT FROM AUTHOR]

The objectives of this study were to evaluate the duration and the quality of sleep, as well as daytime sleepiness, among different levels of Arab athletes (i.e., amateur, elite) and to compare sleep quality and duration and daytime sleepiness in athletes and sedentary individuals. A total of 409 participants, characterized as elite athletes (n = 78), amateur athletes (n = 231), and sedentary individuals (n = 100), participated in this study. Participants were asked to complete the Pittsburgh Sleep Quality Index (PSQI) questionnaire, for the evaluation of sleep quality, and the Epworth Sleepiness Scale (ESS), for the assessment of daytime sleepiness. The total PSQI score was significantly higher in sedentary (total PSQI score = 5.74 ± 2.5) vs. amateur (total PSQI score = 5 ± 2.3) (P < 0.001) and elite athletes (total PSQI score = 4.73 ± 2.3) (P < 0.01), respectively. However, there was no significant difference between elite and amateur athletes (P > 0.05). There was no significant difference (P > 0.05) between levels of daytime sleepiness reported in amateur athletes (ESS score = 9.6 ± 4.3), elite athletes (ESS score = 10 ± 3.8), and sedentary individuals (ESS score = 10.4 ± 2.4). Athletes experienced a better sleep quality compared to sedentary individuals. However, some athletes can suffer from poor sleep quality, suggesting an urgent need for the implementation of sleep hygiene education. Levels of daytime sleepiness, comparable in athletes and sedentary individuals, indicate higher normal daytime sleepiness. Thus, daily naps could be useful to prevent excessive daytime sleepiness, but future studies on this topic, efficacy, and practicality are needed. [ABSTRACT FROM AUTHOR]

Strenuous physical activity, sleep deprivation and psychological stress are common features of military field training. The present study aimed to evaluate the effects of supplementation with a synbiotic ice cream on salivary IgA, gastrointestinal symptoms, well-being indicators and gut microbiota in young military participants undergoing field training. Sixty-five military completed the study: one group was supplemented for 30 d with synbiotic ice cream containing: 2·1 × 108 CFU/g for Lactobacillus acidophilus LA-5 and 2·7 × 109 CFU/g for Bifidobacterium animalis BB-12 and 2·3 g of inulin in the 60 g of ice cream at manufacture, and the other with a placebo ice cream. Volunteers were evaluated at pre-supplementation (baseline), post-supplementation and after a 5-d military training. Bifidobacterium and Lactobacillus genera were measured in stool samples and both showed a higher differential abundance post-supplementation and training. Salivary IgA and gastrointestinal symptoms decreased at post-training in both groups (P < 0·05; main effect of time); however, supplementation with synbiotic did not mitigate this effect. Tenseness and sleepiness were decreased in the synbiotic-treated group, but not in the placebo group at post-military training (P = 0·01 and 0·009, respectively; group × time effect). The other well-being indicators were not affected by the synbiotic supplementation. In conclusion, 30 d of synbiotic ice cream supplementation containing inulin, L. acidophilus LA-5 and B. animalis BB-12 favourably modulated gut microbiota and improved tenseness and sleepiness in healthy young military undergoing a 5-d field training. These improvements may be relevant to this population as they may influence the decision-making process in an environment of high physical and psychological stress. [ABSTRACT FROM AUTHOR]

During the current opioid epidemic, the number of children with illicit toxic ingestions is increasing. Children presenting with altered mental status and neurologic, particularly cerebellar symptoms of unclear etiology, should be considered to undergo brain imaging as well as toxicology screening to not miss the possible complication of acute toxic leukoencephalopathy. We report the case of an eight-year-old child who presented with somnolence and respiratory depression of unclear etiology, responding profoundly to naloxone, quickly raising concern for drug ingestion. The toxicology screen was positive for fentanyl, cocaine metabolites, caffeine, and diphenhydramine, but not available until day 3 of the hospital stay. In the interim, head CT and brain MRI findings revealed concerning bilateral cerebellar hypodensities, suggestive of opioid-induced leukoencephalopathy. This condition has been described as potentially malignant and fatal, but very few cases of this pathology have been described in children so far. Fortunately, all neurological symptoms in our patient, including altered mental status, respiratory depression, atactic gait, blurry vision, and lower extremity pain, completely resolved within five days of presentation and the patient seemingly underwent a full clinical recovery without residual symptoms. Awareness and prompt recognition of acute toxic leukoencephalopathy in children presenting with altered mental status or neurological symptoms of unclear etiology is of utmost importance to prevent deterioration and optimize treatment, especially during times of a worsening opioid epidemic in our country., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Gale et al.)

Currently, undiagnosed insulinomas remain a difficult clinical dilemma because its symptoms in most cases can easily be misdiagnosed as other diseases. In this article, we present the case of a 14-year-old girl who presented to our hospital with recurrent episodes of excessive daytime sleepiness and abnormal behavior during sleep that had been going on for 3 months. Insulinoma is a rare neuroendocrine tumor that causes excessive release of insulin, resulting in episodes of hypoglycemia. It usually manifests as autonomic sympathetic symptoms. These symptoms resolved rapidly with the administration of glucose. After successful removal of the tumor, daytime sleepiness and abnormal nighttime behavior of the patient did not reappear. [ABSTRACT FROM AUTHOR]

Currently, undiagnosed insulinomas remain a difficult clinical dilemma because its symptoms in most cases can easily be misdiagnosed as other diseases. In this article, we present the case of a 14-year-old girl who presented to our hospital with recurrent episodes of excessive daytime sleepiness and abnormal behavior during sleep that had been going on for 3 months. Insulinoma is a rare neuroendocrine tumor that causes excessive release of insulin, resulting in episodes of hypoglycemia. It usually manifests as autonomic sympathetic symptoms. These symptoms resolved rapidly with the administration of glucose. After successful removal of the tumor, daytime sleepiness and abnormal nighttime behavior of the patient did not reappear.

• Of the 55 patients who underwent awake craniotomy, 25.5% developed somnolence during brain function mapping. • Pre-awake bispectral index value was not significantly associated with somnolence during brain function mapping. • Somnolence likely occurs in patients with a low preoperative Western Aphasia Battery aphasia quotient score. Somnolence during brain function mapping is one of the factors that inhibit the accomplishment of the goals of awake craniotomy. We examined the effect of anesthesia depth measured by bispectral index (BIS) during pre-awake phase on somnolence during brain function mapping and also explored the factors associated with somnolence. We examined the association between BIS values during pre-awake phase and somnolence during the first 30 min of brain function mapping in 55 patients who underwent awake craniotomy at Kyoto University Hospital from 2015 to 2018. The pre-awake BIS value was defined as the mean BIS value for 60 min before the removal of the airway. Somnolence during brain function mapping was the primary outcome, defined as either of the following conditions: inability to follow up, disorientation, or inability to assess speech function. Additionally, we compared patient or perioperative variables between patients with/without somnolence. Somnolence occurred in 14 patients (25.5%), of which 6 patients (10.9%) were unable to complete brain function mapping. There was no significant difference in the pre-awake BIS value between patients with/without somnolence (median: 46 vs. 49, P = 0.192). Somnolence was not significantly associated with age, gender, and the number of preoperative anticonvulsive drugs, but patients with somnolence had a significantly lower preoperative Western Aphasia Battery (WAB) aphasia quotient score (median 93.8 vs. 98.6, P = 0.011). We did not find an association between pre-awake BIS value and somnolence during brain function mapping. Somnolence likely occurs in patients with a low preoperative WAB aphasia quotient score. [ABSTRACT FROM AUTHOR]

• This is the first network meta-analysis on sleep-related side effects of smoking-cessation drugs. • Bupropion plus nicotinic acetylcholine receptor agonist (NRA) ranked first in insomnia. • NRA plus nicotine replacement therapy in abnormal dreams, NRA in nightmares, and nortriptyline in somnolence ranked first. Smoking cessation medications have the potential to affect the functioning of the nervous system, leading to sleep disturbances. Our study aimed to compare the sleep-related side effects (such as insomnia, abnormal dreams, nightmares, and somnolence) induced by different smoking cessation medications in non-psychiatric smokers. We conducted a thorough search of five electronic databases (Cochrane, EMBASE, PubMed, PsycInfo, and Web of Science) for randomized controlled trials. This study was registered with the PROSPERO (registration number CRD42022347976). A total of 79 full-text articles, encompassing 36,731 participants, were included in our analysis. Individuals using bupropion, bupropion in combination with a nicotinic acetylcholine receptor agonist (NRA), and bupropion in conjunction with nicotine replacement therapy (NRT) exhibited a higher likelihood of experiencing insomnia compared to those using NRT alone. Bupropion plus NRA had the highest ranking on the surface under the cumulative ranking curve (SUCRA) for insomnia risk, while placebo had the lowest ranking. Additionally, NRA plus NRT ranked first for abnormal dream outcomes, NRA alone for nightmares, and nortriptyline for somnolence, based on the SUCRA results. Healthcare providers should exercise caution when prescribing smoking cessation drugs, particularly in consideration of their potential sleep-related side effects. [ABSTRACT FROM AUTHOR]

During 2013–2016, a total of 32 patients were treated for Crimean-Congo hemorrhagic fever in Prishtina, Kosovo; 11 died. In the 11 patients who died, findings included viral loads >1 × 108.5/mL, lactate dehydrogenase >2,700 U/mL, bleeding, and impaired consciousness. Ribavirin therapy had no noticeable effect in this small patient sample.

• Evaluation of hypnotic dual orexin receptor antagonists (DORAs) during the rodent inactive period may prove translationally significant. • DORA-22 improved sleep measures when animals were exposed to mild stress-inducing stimuli (cage exposures) in the light/inactive period. • A minimal dose of DORA-22 initially promoted sleep yet exhibited few lingering (extended) effects. • DORA treatment of sleep pathologies may alleviate alterations during the natural sleep period, while avoiding lingering hypersomnolence. Dual orexinergic antagonists (DORAs) have been recently developed as a pharmacotherapy alternative to established hypnotics. Hypnotics are largely evaluated in preclinical rodent models in the dark/active period yet should be ideally evaluated in the light/inactive period, analogous to when sleep disruption occurs in humans. We describe here the hypnotic efficacy of DORA-22 in rodent models of sleep disturbance produced by cage changes in the light/inactive period. Rats were administered DORA-22 or the GABA receptor-targeting hypnotic eszopiclone early in the light period, then exposed to six hourly clean cage changes with measurements of NREM sleep onset latency. Both compounds initially promoted sleep (hours 1 and 2), with DORA-22 exhibiting a more rapid hypnotic onset; and exhibited extended efficacy, evident six hours after administration in a sleep latencies test. A common complaint concerning hypnotic use is lingering hypersomnolence, and this is a concern in pharmacotherapy of the elderly. A second study was designed to determine a minimal dose of DORA-22 which would initially promote sleep but exhibit minimal extended hypnotic effect. Animals were administered DORA-22, then exposed for six hours to a single cage previously dirtied by a conspecific, followed by return to home cage. EEG measures indicated that all DORA-22 doses largely promoted sleep in the first hour. The lowest dose (1 mg/kg) did not decrease sleep onset latency at the six-hour timepoint, suggesting no residual hypersomnolence. We described here DORA-22 hypnotic efficacy during the normal sleep period of nocturnal rats, and demonstrate that well-chosen (low) hypnotic doses of DORA-22 may be hypnotically effective yet have minimal lingering effects. [ABSTRACT FROM AUTHOR]

Background: The 12-item Medical Outcomes Study Sleep Scale (MOS Sleep Scale) has been used to capture patient-reported sleep problems in hundreds of studies. A revised version of the MOS Sleep Scale (MOS Sleep-R) was developed that uses simplified response sets, provides interpretable norm-based scoring, and has two recall versions (one-week or four-week). The objective of this study was to evaluate the psychometric properties (reliability and construct validity) of the MOS Sleep-R using data from a representative sample of U.S. adults. Methods: Standardization of raw scores into norm-based T-scores (mean = 50, standard deviation = 10) was based on data from a 2009 U.S. internet-based general population survey. The internal consistency reliability of multi-item subscales and global sleep problems indices for both one-week and four-week recall forms of the MOS Sleep-R were examined using Cronbach's alphas and inter-item correlations. Construct validity was tested by comparing item-scale correlations between items within subscales with item-scale correlations across subscales. Scale-level convergent validity was tested using correlations with measures including generic health-related quality of life (i.e., SF-36v2) and other relevant outcomes (e.g., job performance, number of days in bed due to illness or injury, happiness/satisfaction with life, frequency of stress/pressure in daily life, the impact of stress/pressure on health, and overall health). Results: The one-week and four-week recall forms of the MOS Sleep-R were completed by 2045 and 2033 respondents, respectively. The psychometric properties of the one-week and four-week forms were similar. All multi-item subscales and global index scores showed adequate internal consistency reliability (all Cronbach's alpha > 0.75). Patterns of inter-item and item-scale correlations support the scaling assumptions of the MOS Sleep-R. Patterns of correlations between MOS Sleep-R scores with criterion measures of health-related quality of life and other outcomes indicated adequate construct validity. Conclusions: The MOS Sleep-R introduces a number of revisions to the original survey, including simplified response sets, the introduction of a one-week recall form, and norm-based scoring that enhances interpretability of scores. Both the one-week and four-week recall period forms of the MOS Sleep-R demonstrated good internal consistency reliability and construct validity in a U.S. general population sample. [ABSTRACT FROM AUTHOR]

La santé publique a ses propres records. En effet, un rapport de Santé Publique France (2019) montre un déclin du temps de sommeil : il passe pour la première fois au-dessous de sept heures. À l'ère du numérique, les adolescents sont une population particulièrement sensible à ces évolutions : 88 % des jeunes (15–24 ans) français évoquent un manque de sommeil. Les causes de l'insomnie sont multifactorielles et – alors même qu'ils semblent concernés par les conséquences de ce trouble – les adolescents ne se plaignent pas toujours directement. Cela pourrait induire une sous-estimation des dépistages et des diagnostics. L'objectif est d'explorer les complexités du diagnostic d'insomnie à l'adolescence et de comprendre la particularité des liens entre ce trouble et certains paramètres que sont le temps de sommeil, la somnolence, l'agressivité et la symptomatologie anxio-dépressive. Une batterie de questionnaires standardisés a été proposée à une population de 1250 adolescents tout-venant français, lycéens et collégiens (12–20 ans). Elle était composée principalement de l'index de sévérité de l'insomnie, de l'échelle de somnolence d'Epworth et de la Hospital Anxiety and Depression Scale. La méthodologie a reçu l'aval de comités d'éthique et de déontologie. Les résultats confirment la proportion majeure d'insomnie dans cette population (54,9 %, n = 569) par rapport à une proportion moindre d'adolescents ayant la perception de l'être (27,4 %, n = 284). Cet écart diminue avec la sévérité de l'insomnie. L'insomnie corrèle avec la symptomatologie anxio-dépressive et l'autoagressivité, mais beaucoup moins avec le temps de sommeil total estimé, en semaine comme le week-end. La relation est significative avec d'autres dimensions comme la somnolence diurne. Cette étude souligne la particularité du diagnostic d'insomnie pour cette population et la nécessité d'affiner les critères de prévention et de dépistage. L'insomnie à l'adolescence ne peut pas être définie uniquement par rapport au vécu subjectif du malade ou par rapport à des critères temporels. Public health also has its own records. A report from Public Health France (2019) shows a decline in sleep time, which, for the first time, has fallen below seven hours. In the digital era, teenagers are susceptible to these changes: 88% of young people (15–24) are facing a lack of sleep. The causes of insomnia are multifactorial, and – even though they seem concerned with the potential consequences of the disorder – teenagers do not always complain directly. This could lead to an underestimation of screenings and diagnoses. The objective was to explore the complexities of the diagnosis in adolescence and to understand the particularity of the links between this disorder and sleep time, drowsiness, aggressivity and anxio-depressive symptomatology. A selection of standardised surveys, methodologically validated by ethics and deontology committees, was proposed to a population of 1250 French teenagers, high school and college students (12–20). It was mainly composed of the Insomnia Severity Index , the Epworth Sleepiness Scale and the Hospital Anxiety and Depression Scale. The results confirm a major proportion of insomnia in that population (54,9%, n = 569) in comparison to a smaller portion of teenagers who have the perception of having insomnia (27,4%, n = 284). The gap decreases with the severity of the insomnia. The results show a significant correlation between insomnia and anxio-depressive symptomatology and self-aggression; however, they show an insignificant relationship between diagnosis and sleep time, during the week and on weekends. The relationship between insomnia and daytime sleepiness is also very important. Finally, this research highlights the significant gap between the complaint of insomnia and the actual diagnosis. This study highlights the particularity of insomnia diagnosis for this population and the need to refine the criteria for prevention and screening. Insomnia during the teenager period cannot be defined solely by reference to the person's life or by time criteria. [ABSTRACT FROM AUTHOR]

Residual next-day effects of sleep-promoting drugs are common and an important safety issue. Lemborexant is a dual orexin receptor antagonist approved in the United States and Japan for treatment of insomnia in adults. We evaluated the potential of lemborexant for residual morning and next-day effects, including somnolence, based on lemborexant clinical study findings. This paper reports findings from 9 lemborexant clinical studies that incorporated next-day assessments of residual drug effects, based on published findings and data on file. Results are reported for healthy subjects or subjects with insomnia disorder treated with lemborexant 5 mg/day or 10 mg/day, placebo, or active comparator before bedtime. Outcomes assessed included next-morning postural stability (body sway measured by ataxiameter), cognitive performance (Cognitive Performance Assessment Battery), impact on driving (standard deviation of lateral position during highway driving test), subjective sleepiness (sleep diary entries), and adverse events of somnolence. Change from baseline in postural stability the morning after lemborexant administration did not differ from placebo. Among 4 Cognitive Performance Assessment Battery measures, only power of attention declined significantly more with lemborexant treatment compared with placebo in 1 of 2 studies, whereas zolpidem differed from placebo on multiple measures. On the highway-driving test, lemborexant did not significantly impair driving performance versus placebo, however, zopiclone did differ. In large phase 3 trials, next-morning sleep diary ratings showed significantly greater alertness with lemborexant compared with placebo after up to 6 months of treatment. As expected, somnolence was the most common adverse event reported with lemborexant treatment. Somnolence was typically mild to moderate in severity and rarely caused discontinuation of study drug. Across 9 clinical studies, lemborexant did not substantially impair next-day functioning among healthy subjects and subjects with insomnia. [ABSTRACT FROM AUTHOR]

Objective: To evaluate effects of lemborexant (LEM), a dual orexin receptor antagonist, on next-morning sleep propensity assessed by a modified Multiple Sleep Latency Test (M-MSLT) in adults with insomnia disorder. Methods: Study 107 (E2006-A001-107) was a phase 1, randomized, double-blind, four-period crossover study. Subjects (n = 69) received oral single-dose placebo, LEM 5 mg (LEM5), and LEM 10 mg (LEM10) at bedtime in periods 1-3 in a randomized crossover and open-label flurazepam 30 mg in period 4. After an 8-hour overnight sleep opportunity, the M-MSLT measured average sleep onset latency (SOL). Mean change from baseline in average SOL versus placebo of -6.0 min or more was considered clinically meaningful. Other sleep propensity assessments included the proportion of subjects with average SOL >6 min shorter than placebo. LEM plasma concentrations, safety, and tolerability were also assessed. Results: M-MSLT assay sensitivity was confirmed by a clinically meaningful decrease in average SOL with flurazepam versus placebo (least squares mean [LSM] difference -6.06 min; 1-sided p < 0.0001). In contrast, decreases in average SOL with LEM5 (LSM difference vs. placebo -1.15 min; 1-sided p = 0.0262) and LEM10 (-3.48 min; p < 0.0001) did not meet the predefined threshold for a clinically meaningful effect (LEM5, -2.12; LEM10, -4.46). Some individuals did experience higher sleep propensity (average SOL >6.0 min shorter than placebo), particularly with LEM10 (LEM10, 29.4%; LEM5, 13.2%). Conclusions: In contrast to flurazepam, LEM5 and LEM10 did not show clinically meaningful mean increases in nextmorning sleep propensity versus placebo. The possibility that some subjects may experience residual morning effects cannot be excluded. [ABSTRACT FROM AUTHOR]

Objective: This present study is design to assess the efficacy and frequency of side effects with a newer anti-epileptic agent levertiracetum while comparing an older anti- epileptic, Sodium Valproate, in the patients with generalized tonic colonic epilepsy. Material & Methods: Patients with GTC epilepsy had been allocated in two groups, A and B, Group A was given Sodium valproate while group B was given levertiracetum. Study Design: Randomized Control Trial. Setting: Fatima Memorial Hospital, Lahore and Allied Hospital, Faisalabad. Period: December, 2017 to December, 2018. Results: Seventy five subjects were taking levertiracetum from three months out of which 56(74.7%)were seizures free, 15(20%) were seizure free on higher dose,6(8%) were with dizziness, vertigo and 9(12%) were with somnolence. Fifty-four individuals were seizures free with normal dose of sodium valproate from last 3 months, and 16(21%) were seizures free on higher doses among which 53(70%) were with side effects of weight gain and 69(92%) were with hand tremors and this was the most prominent side effects among individuals who were taking sodium valproate. Conclusion: Generalized tonic colonic epilepsy is one of the most common forms of epilepsy and with the advent of newer anti- epileptic drugs like levertiracetum, such seizures can be controlled in with lesser side effects as compared to older antiepileptic agent Sodium Valproate. [ABSTRACT FROM AUTHOR]

Background Sleep is one of the most essential processes required to maintain a healthy human life, and patients experiencing psychiatric illness often experience an inability to sleep. The aim of this study is to test the hypothesis that antidepressant compounds with strong binding affinities for the serotonin 5-HT2C receptor, histamine H1 receptors, or norepinephrine transporter (NET) will be associated with the highest odds of somnolence. Methods Post-marketing cases of patient adverse drug reactions were obtained from the United States Food and Drug Administration Adverse Events Reporting System (FAERS) during the reporting window of January 2004 to September 2019. Disproportionality analyses of antidepressants reporting somnolence were calculated using the case/non-case method. The reporting odds-ratios (ROR) and corresponding 95% confidence interval (95% CI) were computed and all computations and graphing conducted in R. Results There were a total of 69,196 reported cases of somnolence out of a total of 7,366,864 cases reported from January 2004 to September 2019. Among the 30 antidepressants assessed, amoxapine (n = 16) reporting odds-ratio (ROR) = 7.1 (95% confidence interval [CI] [4.3–11.7]), atomoxetine (n = 1,079) ROR = 6.6 (95% CI [6.2–7.1]), a compound generally approved for attention deficit hyperactivity disorder (ADHD), and maprotiline (n = 18) ROR = 6.3 (95% CI, 3.9–10.1) were the top three compounds ranked with the highest reporting odds of somnolence. In contrast, vortioxetine (n = 52) ROR = 1.3 (95% CI [1.0–1.8]), milnacipran (n = 58) ROR = 2.1 (95% CI [1.7–2.8]), and bupropion (n = 1,048) ROR = 2.2 (95% CI [2.1–2.4]) are least significantly associated with somnolence. Moreover, levomilnacipran (n = 1) ROR = 0.4 (95% CI [0.1–2.9]) was not associated with somnolence. Conclusion Among the thirty tested antidepressants, consistent with the original hypothesis, amoxepine has strongest 5-HT2C receptor binding affinity and has the highest reporting odds of somnolence. Atomoxetine, ranked second in reporting odds of somnolence overall, binds to the NET with with the strongest binding affinity among the thirty compounds. Mirtazapine, a tetracyclic antidepressant, was ranked 11th in reporting odds of somnolence and had the strongest H1 receptor binding affinity. This study provides an informative ranking of somnolence among thirty antidepressant compounds with an already wide array of clinical indications as well as provides insight into potential drug repurposing in psychopharmacology.

• OE and IMT training leads significant improvements in snoring severity and frequency, sleep quality and excessive daytime sleepiness. • OE training predominantly increases expiratory muscle strength in OSAS. • OE in particular is a beneficial, practical, and inexpensive rehabilitation intervention that can be used in the treatment of OSAS patients. Inspiratory muscle training (IMT) and oropharyngeal exercises (OE) have different advantages and disadvantages and a comparison of these modalities has been recommended. The aim of this study was to compare the effects of IMT and OE on important outcomes for patients with OSAS. This was a randomized controlled clinical trial. Forty-one clinically stable OSAS patients not receiving CPAP therapy were randomly divided into three groups. Patients in the IMT group (n = 15) trained with a threshold loading device 7 days/week for 12 weeks. Patients in the OE group (n = 14) practiced exercises 5 days/week for 12 weeks. Twelve patients served as control group. Apnea–hypopnea index (AHI), respiratory muscle strength, snoring severity and frequency (Berlin Questionnaire), daytime sleepiness (Epworth Sleepiness Scale; ESS), sleep quality (Pittsburg Sleep Quality Index; PSQI), impact of sleepiness on daily life (Functional Outcomes of Sleep Questionnaire; FOSQ), and fatigue severity (Fatigue Severity Scale; FSS) were evaluated before and after the interventions. AHI and sleep efficiency did not change significantly in any of the groups. Significant decreases in snoring severity and frequency, FSS and PSQI total scores were found in the IMT and OE groups after the treatments (p < 0.05). There was a significant reduction in neck and waist circumference and significant improvement in respiratory muscle strength (MIP and MEP) in IMT group compared to control group (p < 0.05). The%MEPpred value and FOSQ total score significantly increased and ESS score reduced after the treatment in OE group compared to control group (p < 0.05). Our results indicate that both OE and IMT rehabilitation interventions are applicable in rehabilitation programs for OSAS patients who do not accept CPAP therapy. Our findings could lead to increase these methods' use among rehabilitation professionals and decrease in cost of CPAP treatment in OSAS. [ABSTRACT FROM AUTHOR]

aim of this study was to assess the safety and efficacy of tolperisone versus placebo in subjects with acute muscle spasm of the back. Methods: STAR (NCT03802565) was a double-blind, randomized, placebo-controlled phase 2 study in subjects with back pain due to acute muscle spasm. Subjects were randomized 1:1:1:1:1 to tolperisone 50, 100, 150, or 200 mg three times daily (TID) or placebo for 14 days. The primary efficacy endpoint was subject-rated pain "right now" using a numeric rating scale on day 14. Results: Subjects (tolperisone, n=337; placebo, n=78) were enrolled at 38 US clinical sites. Tolperisone was well tolerated, with AEs in 18.1% of subjects receiving tolperisone versus 14.1% of subjects receiving placebo. Headache (7.1%) and diarrhea (2.4%) were the most frequent AEs in tolperisone-treated subjects versus 3.8% and 0%, respectively, in placebo-treated subjects. Somnolence was reported in 1.2% and 2.6% of subjects treated with tolperisone and placebo, respectively. Mean change from baseline in numeric rating scale score of pain "right now" on day 14 was – 3.5 for placebo versus – 4.2, – 4.0, – 3.7, and – 4.4 for tolperisone 50, 100, 150, and 200 mg TID, respectively (linear test of trend on the least-squares mean difference [treatment-placebo]; p=0.0539). In an analysis of pairwise estimates (treatment-placebo), the greatest numerical difference and significance were observed for tolperisone 200 mg TID (p=0.0040). Several secondary endpoints trended toward significance for tolperisone 200 mg TID versus placebo. Conclusion: Tolperisone 200 mg TID may be a promising treatment for acute muscle spasm, without the somnolence associated with SMRs. The safety and efficacy of tolperisone should be evaluated in a phase 3 trial. [ABSTRACT FROM AUTHOR]

The Epworth Sleepiness Scale is used frequently to measure excessive daytime sleepiness in research and clinical settings, although there is limited evidence on test–retest reliability, particularly among sleep clinic populations. The objective of this study was to evaluate the reliability of this instrument among adult patients recruited from a public hospital sleep clinic in Sydney, Australia. English‐speaking participants self‐completed the Epworth Sleepiness Scale on two occasions, at the specialist clinic visit and on the night of diagnostic polysomnography. Of the 108 participants included in the study, the majority were male (64%) and the mean age was 51 years. The median retest interval was 64 days. The primary outcome of test–retest reliability as measured using the intraclass correlation coefficient was 0.73 (95% confidence interval, 0.61–0.82). Despite moderate statistical reliability and a low mean difference of 1.1, Bland‐Altman analysis showed an unacceptably wide distribution of between‐score differences. The 95% limits of agreement were −8.5 to +10.6, and an absolute difference in scores of at least 3 was observed in 60 (56%) of the participants. Our results suggest that the Epworth Sleepiness Scale should not be used in clinical settings to make individual‐level comparisons, such as the effect of therapeutic interventions, or to prioritise access to services. [ABSTRACT FROM AUTHOR]

What is known and objective: Polypharmacy is common, and many medications have cognitive side effects. Such effects can be transient and subside when the drug in question is discontinued or can be long‐lasting with effects present for years afterwards. Although formal assessment of cognition is feasible and often undertaken in neuropsychiatric trials, these effects are usually neglected in the evaluation of any non‐neuropsychiatric health intervention. Medication effects can be assessed within a cognitive footprint framework, to account for the magnitude and the duration of cognitive side effects, with some likely to have a greater and more lasting effect than others. Comment: Adverse event reporting suggests that many medications may be indirectly associated with cognitive effects, for example due to headaches, somnolence and 'dizziness'; however, inferring causation from adverse event reporting can be problematic. In order to better understand the impact of investigational drug and concomitant medications effect on cognition, it would be essential to ensure cognition is prioritized in drug development evaluation. It is suggested that simple instruments that can be easily incorporated into existing trial designs are used to assess the cognitive footprint of medication. What is new and conclusion: We present an overview of existing measures of cognition that can be integrated into drug trials in order to provide a cognitive footprint. Like quality of life testing, such tests should be administered as a standard throughout the key assessment stages of the design of the trial to ensure that any effects on this equally important outcome are also documented. Furthermore, employing routine cognition testing may also enable researchers to identify unanticipated beneficial and non‐beneficial effects on cognition. Provision of such a cognitive footprint profile of drugs may provide the necessary evidence to enable decision‐makers to make informed decisions on risk‐benefit analysis that can subsequently make trade‐offs between different drug regimens. [ABSTRACT FROM AUTHOR]

Background. Sleep is one of the most essential processes required to maintain a healthy human life, and patients experiencing psychiatric illness often experience an inability to sleep. The aim of this study is to test the hypothesis that antidepressant compounds with strong binding affinities for the serotonin 5-HT2C receptor, histamine H1 receptors, or norepinephrine transporter (NET) will be associated with the highest odds of somnolence. Methods. Post-marketing cases of patient adverse drug reactions were obtained from the United States Food and Drug Administration Adverse Events Reporting System (FAERS) during the reporting window of January 2004 to September 2019. Disproportionality analyses of antidepressants reporting somnolence were calculated using the case/non-case method. The reporting odds-ratios (ROR) and corresponding 95% confidence interval (95% CI) were computed and all computations and graphing conducted in R. Results. There were a total of 69,196 reported cases of somnolence out of a total of 7,366,864 cases reported from January 2004 to September 2019. Among the 30 antidepressants assessed, amoxapine (n=16) reporting odds-ratio (ROR) = 7.1 (95% confidence interval [CI] [4.3-11.7]), atomoxetine (n = 1,079) ROR = 6.6 (95% CI [6.2-7.1]), a compound generally approved for attention deficit hyperactivity disorder (ADHD), and maprotiline (n = 18) ROR = 6.3 (95% CI, 3.9-10.1) were the top three compounds ranked with the highest reporting odds of somnolence. In contrast, vortioxetine (n=52) ROR = 1.3 (95% CI [1.0-1.8]), milnacipran (n=58) ROR = 2.1 (95% CI [1.7-2.8]), and bupropion (n=1,048) ROR=2.2 (95% CI [2.1-2.4]) are least significantly associated with somnolence. Moreover, levomilnacipran (n=1) ROR = 0.4 (95% CI [0.1-2.9]) was not associated with somnolence. Conclusion. Among the thirty tested antidepressants, consistent with the original hypothesis, amoxepine has strongest 5-HT2C receptor binding affinity and has the highest reporting odds of somnolence. Atomoxetine, ranked second in reporting odds of somnolence overall, binds to the NET with with the strongest binding affinity among the thirty compounds. Mirtazapine, a tetracyclic antidepressant, was ranked 11th in reporting odds of somnolence and had the strongest H1 receptor binding affinity. This study provides an informative ranking of somnolence among thirty antidepressant compounds with an already wide array of clinical indications as well as provides insight into potential drug repurposing in psychopharmacology. [ABSTRACT FROM AUTHOR]

Antidepressants are a commonly used, easily accessible, and overall safe treatment option for post-traumatic stress disorder (PTSD). The present review aims to evaluate the efficacy and safety of antidepressants in treating sleep disturbances in patients with PTSD. PubMed and the Cochrane Library were searched (July 2022) for systematic reviews and meta-analyses on the treatment of PTSD. Moreover, PubMed and ClinicalTrials.gov were searched for individual trials investigating the antidepressant treatment of PTSD (up to September 2022), and reference lists of all possibly relevant identified studies were screened. Sleep-related outcomes, i.e., total sleep time, sleep quality, dreams/ nightmares, insomnia, and somnolence, were extracted independently by at least two reviewers. Metaanalytic evaluations were performed wherever possible. 39 randomised controlled trials (RCTs) were identified; data from pooled analyses, reviews, and observational studies were used for antidepressants with a weak evidence base or when their findings were deemed important. Overall, scarce data exist on the effects of antidepressants on sleep outcomes among patients with PTSD. Some evidence may support the use of amitriptyline, nefazodone, paroxetine, and sertraline for improving sleep in patients with PTSD. Τhere was a meta-analytical trend indicating improvement of nightmares with fluoxetine, less insomnia with amitriptyline and more with brofaromine, as well as more somnolence with paroxetine vs. placebo, respectively. However, data from more than 1 RCT with a considerable number of patients were only available for paroxetine. Evidence is insufficient to draw safe conclusions. More and better-designed RCTs, with consistent reporting of sleep-related outcomes, are needed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Guanfacine, used as a medication for attention-deficit/hyperactivity disorder (ADHD), leads to a high incidence of somnolence, in contrast to methylphenidate, which leads to a high incidence of insomnia. The impact of somnolence on continuing guanfacine treatment is unclear. Therefore, we investigated the reasons for discontinuing guanfacine and analyzed the factors associated with discontinuation caused by somnolence. We surveyed 96 patients under guanfacine from July 2017 to December 2021 at the Saga University Hospital. Patients who discontinued guanfacine by the end date of our study were divided into a median early and late group. We compared the reasons for discontinuation in both groups. Of all patients, 47 continued and 49 discontinued guanfacine. A higher percentage of patients discontinued guanfacine caused by somnolence for ≤70 d than for >70 d of treatment (44.0 vs. 8.3%; p = 0.008). When stratified by the concomitant use of other ADHD drugs, somnolence resulted in a higher discontinuation rate for ≤70 d than for >70 d of treatment without concomitant use (55.0 vs. 7.1%; p = 0.009). Nonetheless, concomitant use resulted in no difference. In conclusion, somnolence affects the early discontinuation of guanfacine as an ADHD drug. The combination of methylphenidate or atomoxetine may decrease withdrawal caused by somnolence.

• We investigated the efficacy and tolerability of perampanel in Dravet syndrome. • Seizure rate was reduced by more than 50% in five patients (50%). • Effects of perampanel occurred between 3 months and 6 months following initiation. • Adverse events (7/10 patients) were mostly mild. In the present study, we aimed to investigate the efficacy and tolerability of perampanel in patients with Dravet syndrome. We retrospectively reviewed data regarding seizure frequency and adverse effects in 10 patients (four boys, six girls) with Dravet syndrome following treatment with perampanel. Perampanel treatment was considered effective when seizure frequency had been reduced by more than 50%. The mean age of patients at perampanel introduction was 11.5 ± 2.2 years. Seizure types were as follows: generalized tonic-clonic seizure (n = 8), unilateral clonic seizure (n = 6), myoclonic seizure (n = 3), atypical absence seizure (n = 3), and focal impaired awareness seizure (n = 1). The average number of concomitant anti-epileptic drugs (AEDs) was 3 ± 0.9. The mean duration of perampanel use was 11.1 ± 3.8 months. Seizure frequency was reduced by more than 50% in five patients (50%). The efficacy of perampanel for each seizure type was as follows: generalized tonic-clonic seizure: 50% (4/8), unilateral clonic seizure: 50% (3/6), myoclonic seizure: 33% (1/3), atypical absence seizure: 33% (1/3), and focal impaired awareness seizure: 100% (1/1). The effects of perampanel in each patient occurred between 3 and 6 months following the initiation of treatment. Seizure reduction was observed beginning at perampanel doses of 0.1 ± 0.07 mg/kg/day. Adverse events were observed in seven of 10 patients. Although somnolence was noted in 50% of patients, most events were mild. The results of this retrospective observational study indicate that perampanel treatment may be promising in some patients with Dravet syndrome. Additional studies are necessary to verify the actual efficacy of perampanel for Dravet syndrome. [ABSTRACT FROM AUTHOR]

Introduction: Cancer-related drowsiness (CRD) is a distressing symptom in advanced cancer patients (ACP). The aim of this study was to determine the frequency and factors associated with severity of CRD. We also evaluated the screening performance of Edmonton Symptom Assessment Scale-drowsiness (ESAS-D) item against the Epworth Sedation Scale (ESS).Method: We prospectively assessed 180 consecutive ACP at a tertiary cancer hospital. Patients were surveyed using ESAS, ESS, Pittsburgh Sleep Quality Index, Insomnia Severity Index, and Hospital Anxiety Depression Scale.Result: Ninety of 150 evaluable patients had clinically significant CRD (ESS); median (interquartile ratio): ESS. 11 (7-14); ESAS-D. 5 (2-6); Pittsburgh Sleep Quality Index. 8 (5-11); Insomnia Severity Index. 13 (5-19); Stop Bang Scoring 3 (2-4), and Hospital Anxiety Depression Scale-D 6 (3-10). ESAS-D was associated with ESAS (r, p) sleep (0.38, <0.0001); pain (0.3, <0.0001); fatigue (0.51, <0.0001); depression (0.39, <0.0001); anxiety (0.44, <0.0001); shortness of breath (0.32, <0.0001); anorexia (0.36, <0.0001), feeling of well-being [(0.41, <0.0001), ESS (0.24, 0.001), and opioid daily dose (0.19, 0.01). Multivariate-analysis showed ESAS-D was associated with fatigue (odds ratio [OR] = 9.08, p < 0.0001), anxiety (3.0, p = 0.009); feeling of well-being (OR = 2.27, p = 0.04), and insomnia (OR = 2.35; p = 0.036). Insomnia (OR = 2.35; p = 0.036) cutoff score ≥3 (of 10) resulted in a sensitivity of 81% and 32% and specificity of 70% and 44% in the training and validation samples, respectively.Significance Of Results: Clinically significant CRD is frequent and seen in 50% of ACP. CRD was associated with severity of insomnia, fatigue, anxiety, and worse feeling of well-being. An ESAS-D score of ≥3 is likely to identify most of the ACP with significant CRD. [ABSTRACT FROM AUTHOR]

During 2013-2016, a total of 32 patients were treated for Crimean-Congo hemorrhagic fever in Prishtina, Kosovo; 11 died. In the 11 patients who died, findings included viral loads >1 × 108.5/mL, lactate dehydrogenase >2,700 U/mL, bleeding, and impaired consciousness. Ribavirin therapy had no noticeable effect in this small patient sample. [ABSTRACT FROM AUTHOR]

Hemiplegic migraine is a rare and complex disease, characterized by migraine with a reversible motor aura. Hemiplegic migraine can be easily misdiagnosed at its first presentation with an atypical severe form of migraine, a stroke, multiple sclerosis, metabolic disorders, conversion disorder or an epilepsy. We present the case of a young 24-year-old male patient, who since the age of 4 years had been having multiple episodes of migraine associated with hemiparesis, paraesthesia, prolonged somnolence, aphasia and confusion. We review the literature and discuss important diagnostic findings in hemiplegic migraine to help establishing a prompt diagnosis.