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BACKGROUND Sleeping pills are widely used for sleep disorders and insomnia. This population-based study aimed to evaluate the association between the use of sleeping pills and metabolic syndrome (MetS) and metabolic components in an apparently healthy Japanese cohort. METHODS We examined baseline cross-sectional data from the JMS-II Cohort Study. The criteria for MetS and its components were based on The National Cholesterol Education Program Adult Treatment Panel III. Sleep habits including the sleep duration of the subjects and the frequency of sleeping pill use were obtained using The Pittsburgh Sleep Quality Index questionnaire. For different sleep durations, the association between sleeping pill use and MetS was assessed. Odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated using multiple logistic regression models to quantify this association. RESULTS Our study included 6,153 individuals (mean age, 63.8 [standard deviation 11.2] years), and 3,348 (54.4%) among them were women. The association between sleep duration and MetS was an inverted J-shaped curve among sleeping pill users and a J-shaped curve among non-users. After adjustment for various confounders, less than 6 h of sleep among sleeping pill users was associated with increased rates of MetS (< 6 h, OR [95% CI]: 3.08 [1.29-7.34]). The frequency of sleeping pill use in individuals with short sleep duration showed a positive association with the prevalence of MetS and its components. CONCLUSIONS Sleeping pill users with a short sleep duration had a 3-fold higher chance of having MetS than non-users with a short sleep duration.

Objective To identify the patterns of nonprescription psychoactive substance (PAS) use among persons with spinal cord injury (SCI) and the relationships with demographic and injury characteristics. Design Cross-sectional, self-report assessment (SRA). Setting A medical university in the southeastern United States. Participants The participants (N=4670) were identified through a specialty hospital and 2 state-based surveillance registries. Interventions Not applicable. Main Outcome Measures Participants completed SRAs and reported the past 3 months’ use of the following substances for which they did not have a prescription: cannabis, cocaine, amphetamine-type stimulants, inhalants, sedatives/hypnotics and sleeping pills, hallucinogens, and opioids. PAS use was grouped into 4 categories: none, cannabis use only, use of cannabis and other PAS, and use of other PAS only. Results Of the 4577 participants who responded to the PAS use questions, 24.1% reported using at least 1 PAS without a prescription. Cannabis was the most frequently reported substance (16.4%), followed by sedatives or sleeping pills (8.0%). By PAS use group, 12.1% reported use of cannabis use only, followed by use of other PAS only (7.7%) and use of cannabis and other PAS (4.3%). There were significant differences among the groups of use by nearly all personal characteristics. Conclusions The use of nonprescription PASs is prevalent among adults with chronic SCI, and there are clear differences in patterns and characteristics of use.

Previous spectral analysis studies on insomnia have shown inconsistent results due to their heterogeneity and small sample sizes. We compared the difference of electroencephalogram (EEG) spectral power during sleep among participants without insomnia, insomniacs with no hypnotic use, hypnotic users with no insomnia complaints, and hypnotic users with insomnia complaints using the Sleep Heart Health Study data, which is large sample size and has good quality control. The fast Fourier transformation was used to calculate the EEG power spectrum for total sleep duration within contiguous 30-s epochs of sleep. For 1985 participants, EEG spectral power was compared among the groups while adjusting for potential confounding factors that could affect sleep EEG. The power spectra during total sleep differed significantly among the groups in all frequency bands (pcorr pcorr

Background Breast cancer survivors may experience sleep disturbances that can affect their physical and mental well-being. We sought to determine the association, if any, between yoga and sleep among breast cancer survivors in a population-based cohort. Methods The National Health Interview Survey is designed to be representative of the US civilian non-institutionalized population. We evaluated breast cancer survivors in the 2017 cohort to determine the association between yoga and self-reported quality of sleep. Results Of the 25,905 people surveyed, representing 238,738,039 in the population, 1.59% reported a previous history of breast cancer. Breast cancer survivors were less likely to report having practiced yoga in the preceding 12 months, compared to those without a history of breast cancer (9.98% vs 13.78%, P = .011). In addition, they were more likely to report having had trouble falling asleep (44.64% vs 36.32%, P = .002), staying asleep (53.72% vs 39.43%, P < .001), and using sleep medication on at least 1 day within the previous week (23.80% vs 13.49%, P < .001) than those without breast cancer. Among breast cancer survivors, there were no significant differences in difficulty falling asleep (39.16% vs 44.98%, P = .482), difficulty staying asleep (61.17% vs 52.70%, P = .305), and needing sleep medication (19.03% vs 24.53%, P = .395) between those who practiced yoga and those who did not. Controlling for sociodemographic factors, there remained no association between yoga and difficulty falling or staying asleep among breast cancer survivors. Conclusion There is no direct association between yoga and sleep quality in breast cancer survivors.

PURPOSE OF REVIEW: Insomnia affects more than 10% of the population and causes significant discomfort and disability. Suvorexant is an orexin receptor antagonist that specifically targets the wake-sleep cycle. This review summarizes recent and seminal evidence in the biological and physiological evidence of insomnia, the mechanism of action of suvorexant in treating insomnia, and clinical evidence regarding its use. RECENT FINDINGS: There is no single clear diagnosis for insomnia, and thus prevalence is not entirely clear, but it is estimated to affect 10%–30% of the adult population. Comorbidities include obesity, diabetes, and various psychiatric conditions, and insomnia likely has a contributing role in these conditions. Insomnia, by definition, impacts sleep quality and also wakefulness, including academic success and work efficiency. Insomnia is likely related to genetic susceptibility and a triggering event, leading to hyper-arousal states and functional brain disturbances. This leads to hyperactivity of the hypothalamic-pituitary-adrenal axis, over-secretion of corticotropin-releasing factor, and aberrancy in neurotransmitter release. Though several pharmacological options exist for the treatment of insomnia, there is equivocal data regarding their efficacy or limits to their use due to side effects and contraindications. Suvorexant is a novel dual orexin receptor antagonist, which is shown to improve sleep by reducing arousals. Unlike classical therapeutics, suvorexant does not alter the sleep profile; it prolongs the time spent in each sleep state. Though it may cause some somnolence, it is milder than reported with other drugs. SUMMARY: Multiple clinical studies support the use of suvorexant in insomnia. In primary insomnia, suvorexant is effective (over placebo), as measured by polysomnography and reported by patients, in both attaining and maintaining sleep. Similar, albeit to a smaller degree, results were found in secondary insomnia. Suvorexant carries two significant advantages over existing therapies; it has a much better safety profile in approved doses, and it preserves natural sleep architecture, thus promoting more restful sleep and recovery. Unfortunately, data exists mostly for suvorexant versus placebo, and head-to-head trials with common hypnotics are needed to assess the true efficacy of suvorexant over the alternatives. And while tolerance is less likely to develop, close monitoring of post-marketing data is required to evaluate for long term adverse events and efficacy.

Background To evaluate the risk factors of postoperative delirium (POD) in elderly gastric cancer (GC) patients after laparoscopic gastrectomy and construct a predictive model. Methods Elderly GC patients undergoing laparoscopic gastrectomy were enrolled and grouped based on the status of POD development within postoperative 7 days. Independent risk factors were selected out by univariate and multivariate logistic regression analyses and then enrolled in the nomogram prediction model. Results A total of 270 elderly GC patients were enrolled, and POD occurred in 74 (27.4%) patients within postoperative 7 days. The results of multivariate regression analysis indicated that age (OR: 3.30, 95% CI: 1.41–6.85, P < 0.001), sleeping pills (OR: 1.87, 95% CI: 1.12–3.09, P = 0.012), duration of ICU stay (OR: 1.55, 95% CI: 1.02–2.37, P = 0.029), albumin/fibrinogen ratio (AFR) (OR: 1.74, 95% CI: 1.03–2.76, P = 0.019), and neutrophils/lymphocytes ratio (NLR) (OR: 2.12, 95% CI: 1.11–4.01, P = 0.016) were five independent risk factors for POD in elderly GC patients. The AUC of the constructed nomogram model based on these five factors was 0.807. Conclusions This study highlighted that age, AFR, NLR, sleeping pills taking, and duration of ICU stay were independent risk factors for POD, and the nomogram model based on these factors could effectively predict POD in elderly GC patients.

To evaluate the frequency of anxious and depressive symptoms and to determine their associated factors in a population of students enrolled at the Faculty of Medicine of Sousse (Tunisia).this is a descriptive cross-sectional study that took place at the Faculty of Medicine of Sousse over the period from 09/15/2017 to 03/15/2018. An anonymous questionnaire was administered to the students in the guided teaching rooms. The assessment of anxiety and depressive symptoms was based on the Anxiety and Depression Scale (HADS) and the quality of sleep was assessed by the PSQI questionnaire.A total of 202 medical students participated in the study. The average PSQI score was 5.62±2.87 and 47% of students had poor sleep quality (PSQI ≥ 6). Symptoms of anxiety and depression were observed in 73 (36.1%) and 45 (22.3%) students respectively. The mean HADS-A score was 9.21±4.17 and that of the HADS-D score was 7.37±4.06. In univariate analysis, the factors found to predict a high level of perceived stress were the study cycle (p=0.022) and poor quality of sleep (p 11) were the use of sleeping pills (p=0.004), the quality of sleep (p0.001), and a high level of perceived stress (p0.001). The high level of perceived stress was found to predict depression (p=0.006).In the multivariate analysis of variables in the present study, poor sleep quality was a factor independently related to high perceived stress in medical students (ORa=9.062 [4.247-19.334]) while being a medical student of the 1st cycle proved to be a protective factor (ORa=0.101 [0.025-0.406]). Use of sleeping pills (ORa=4.481 [1.135-17.682]), poor sleep quality (ORa=2.131 [1.081-4.203]) and high level of perceived stress (ORa=5.790 [2.444-13.716]) were factors independently related to anxiety symptoms. Female sex was a protective factor for depressive symptoms (ORa=0.440 [0.205-0.945]) while a high level of perceived stress was a factor independently related to depressive symptoms (ORa=3.429 [1.469-8.005]). HAD-A and HAD-D scores were correlated (r=0.631 ; p0.001).sleep disturbances, perceived stress, anxious and depressive symptoms are common among Tunisian medical students. Prevention strategies targeting the improvement of sleep quality and student stress management should be developed at the faculty and ministerial level.

Narcolepsy is a chronic disabling neurological sleep disorder that requires lifelong treatment. We have outlined the clinical features of narcolepsy, the assessment and diagnosis process and have summarised the existing treatment options for children and adolescents with narcolepsy. In the future, the approach to management of paediatric narcolepsy should ideally be in a multidisciplinary setting, involving specialists in sleep medicine, sleep physiology, neurologists and psychologists/psychiatrists. A multidisciplinary approach will help to manage the potential impact of narcolepsy on children and adolescents who are in a stage of their life that is critical to their physical, emotional and social development and their academic attainment.

Entomotoxicology is an emerging science in the forensic investigation of death; it now influences judicial activities. Briefly, carrion flies ingest various chemicals as they feed on a cadaver. In entomotoxicology, such toxicological compounds are qualitatively and quantitatively analyzed in insects recovered from carrion. Some of these chemicals can disrupt flies’ cellular physiology, leading to acceleration or delay in their developmental rate. In this study, the effect of zolpidem-contaminated tissue on the dipteran flies Chrysomya megacephala (Fabricius 1794) and Chrysomya saffranea (Bigot 1877) was assessed. Zolpidem tartrate is a sedative-hypnotic compound commonly used to treat anxiety and sleeping disorders, but it is associated with death from suicide. The effects were tested by providing the flies with liver tissue treated with various concentrations of zolpidem tartrate. The morphological parameters and development rate for all life cycle stages of treated insects were determined and used to estimate postmortem intervals. Results showed that the morphological parameters, i.e., weight, width, and length and rate of development of C. megacephala and C. saffranea was negatively associated with zolpidem tartrate concentration of C. saffranea, were negatively associated with the concentration of zolpidem tartrate, indicating that arthropod evidence evaluation can help establish the cause and time of death.

BACKGROUND Adolescents' consumption of tranquilizers, sedatives, and sleeping pills (TSSp) has increased during the last few decades, and TSSp are currently among the substances with the lowest age-of-onset. We characterized current-use patterns of TSSp consumers by age when first taken. METHODS This study used individualized secondary data retrieved from the 2016 Spanish State Survey on Drug Use in Secondary Education (16-18-year-olds), and included all subjects who reported having taken TSSp at any point, but excluded those who had started during the previous year (n = 1502). Logistic regression models were used to obtain adjusted odds ratios (aOR) for associations between early TSSp consumption (

Narcolepsy type 1 (NT1) is a chronic neurological disorder that impairs the brain’s ability to control sleep-wake cycles. Current therapies are limited to the management of symptoms with modest effectiveness and substantial adverse effects. Agonists of the orexin receptor 2 (OX2R) have shown promise as novel therapeutics that directly target the pathophysiology of the disease. However, identification of drug-like OX2R agonists has proven difficult. Here we report cryo-electron microscopy structures of active-state OX2R bound to an endogenous peptide agonist and a small-molecule agonist. The extended carboxy-terminal segment of the peptide reaches into the core of OX2R to stabilize an active conformation, while the small-molecule agonist binds deep inside the orthosteric pocket, making similar key interactions. Comparison with antagonist-bound OX2R suggests a molecular mechanism that rationalizes both receptor activation and inhibition. Our results enable structure-based discovery of therapeutic orexin agonists for the treatment of NT1 and other hypersomnia disorders., Agonists of the orexin receptor 2 (OX2R) show promise in the treatment of narcolepsy. Cryo-EM structures of active-state OX2R bound to an endogenous peptide agonist and a small-molecule agonist suggest a molecular mechanism that rationalizes both receptor activation and inhibition.

Sleep is essential to and an integral part of life and when lacking or disrupted, a multitude of mental and physical pathologies ensue, including cardiovascular (CV) disease, which increases health care costs. Several prospective studies and meta-analyses show that insomnia, short (9h) sleep and other sleep disorders are associated with an increased risk of hypertension, metabolic syndrome, myocardial infarction, heart failure, arrhythmias, CV disease risk and/or mortality. The mechanisms by which insomnia and other sleep disorders lead to increased CV risk may encompass inflammatory, immunological, neuro-autonomic, endocrinological, genetic and microbiome perturbations. Guidelines are emerging that recommend a target of >7 h of sleep for all adults >18 years for optimal CV health. Treatment of sleep disorders includes cognitive-behavioral therapy considered the mainstay of non-pharmacologic management of chronic insomnia, and drug treatment with benzodiazepine receptor agonists binding to gamma aminobutyric acid type A (benzodiazepine and non-benzodiazepine agents) and some antidepressants. However, observational studies and meta-analyses indicate an increased mortality risk of anxiolytics and hypnotics, although bias may be involved due to confounding and high heterogeneity in these studies. Nevertheless, it seems that the risk incurred by the non-benzodiazepine hypnotic agents (Z drugs) may be relatively less than the risk of anxiolytics, with evidence indicating that at least one of these agents, zolpidem, may even confer a lower risk of mortality in adjusted models. All these issues are herein reviewed.

Background and objectives Zolpidem, a nonbenzodiazepine hypnotic, and trazodone, a sedating antidepressant, are the most common medications used to treat insomnia in the United States. Both drugs have side effect profiles (e.g., drowsiness, dizziness, and cognitive and motor impairment) that can heighten the risk of falls and fractures. Despite widespread zolpidem and trazodone use, little is known about the comparative safety of these medications in patients receiving hemodialysis, a vulnerable population with an exceedingly high fracture rate. Design, setting, participants, & measurements Using data from the United States Renal Data System registry (2013–2016), we conducted a retrospective cohort study to investigate the association between the initiation of zolpidem versus trazodone therapy and the 30-day risk of hospitalized fall-related fractures among Medicare-enrolled patients receiving maintenance hemodialysis. We used an active comparator new-user design and estimated 30-day inverse probability of treatment-weighted hazard ratios and risk differences. We treated death as a competing event. Results A total of 31,055 patients were included: 18,941 zolpidem initiators (61%) and 12,114 trazodone initiators (39%). During the 30-day follow-up period, 101 fall-related fractures occurred. Zolpidem versus trazodone initiation was associated with a higher risk of hospitalized fall-related fracture (weighted hazard ratio, 1.71; 95% confidence interval, 1.11 to 2.63; weighted risk difference, 0.17%; 95% confidence interval, 0.07% to 0.29%). This association was more pronounced among individuals prescribed higher zolpidem doses (hazard ratio, 1.85; 95% confidence interval, 1.10 to 3.01; and risk difference, 0.20%; 95% confidence interval, 0.04% to 0.38% for higher-dose zolpidem versus trazodone; and hazard ratio, 1.60; 95% confidence interval, 1.01 to 2.55 and risk difference, 0.14%; 95% confidence interval, 0.03% to 0.27% for lower-dose zolpidem versus trazodone). Sensitivity analyses using longer follow-up durations yielded similar results. Conclusions Among individuals receiving maintenance hemodialysis, zolpidem initiators had a higher risk of hospitalized fall-related fracture compared with trazodone initiators. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_12_18_CJN10070620_final.mp3

Background The prevalence of cardiovascular disease (CVD) is rapidly increasing in the world. The present study aimed to assess the prevalence and Predictors factors of CVD based on the data of Kherameh cohort study. Methods The present cross-sectional, analytical study was done based on the data of Kherameh cohort study, as a branch of the Prospective Epidemiological Studies in Iran (PERSIAN). The participants consisted of 10,663 people aged 40–70 years. CVD was defined as suffering from ischemic heart diseases including heart failure, angina, and myocardial infarction. Logistic regression was used to model and predict the factors related to CVD. Additionally, the age-standardized prevalence rate (ASPR) of CVD was determined using the standard Asian population. Results The ASPR of CVD was 10.39% in males (95% CI 10.2–10.6%) and 10.21% in females (95% CI 9.9–10.4%). The prevalence of CVD was higher among the individuals with high blood pressure (58.3%, p p = 0.018), used opium (18.2%, p = 0.039), had high triglyceride levels (31.6%, p = 0.011), were overweight and obese (66.2%, p p p p p Conclusion The prevalence of CVD was found to be relatively higher in Kherameh (southern Iran) compared to other places. Moreover, old age, obesity, taking sleeping pills, hypertension, drug use, and chronic obstructive pulmonary disease had the highest odds ratios of CVD.

To clarify the status of insomnia and depression and the prescription of sleeping pills in hepatocellular carcinoma (HCC) patients before and after HCC diagnosis and treatment.Patients' data from a Japanese health insurance claims database were analyzed retrospectively to determine the incidence of insomnia and depression and their association with sleeping pill prescriptions during the 6 months before and after HCC diagnosis and treatment.A total of 9,109 HCC patients (median age at diagnosis = 71.5 years, 68.1% male) were analyzed. The incidences of insomnia and depression increased significantly after HCC diagnosis. Insomnia was reported in 15.0% of patients before diagnosis, and it increased to 27.6% after diagnosis. Similarly, depression was reported in 6.3% and 11.3% before and after diagnosis, respectively. The incidences of insomnia and depression before diagnosis were higher in patients with concomitant liver diseases including hepatitis, cirrhosis, and hepatic encephalopathy. However, the rate of sleeping pill prescription was significantly lower in patients with concomitant liver diseases after diagnosis. The incidence of fracture was higher in insomnia or depression patients than others and in patients treated with sleeping pills than without before and after diagnosis.HCC patients had increased risks of insomnia and depression after diagnosis. The high risk of fracture in HCC patients with insomnia and depression and treated with sleeping pills suggests that it is difficult to optimize the management of HCC patients, especially those with concomitant liver diseases.

Resumo Objetivo Verificar a prevalência e fatores associados ao uso de medicamento indutor do sono entre mulheres assistidas na Atenção Primária à Saúde (APS), Vitória, ES, Brasil. Métodos Estudo transversal com mulheres de 20-59 anos, realizado em 2014. Analisou-se a associação do uso de indutor do sono com fatores socioeconômicos e experiências de violência (regressão de Poisson). Resultados Entre 991 participantes, 18,5% usavam medicamento indutor do sono e 45,9% usaram-no alguma vez na vida. Seu uso, atualmente e ao longo da vida, associou-se a idade, escolaridade e violências psicológica, física e sexual no último ano (p-valor

The aims of this study are to examine the changes of tongue thickness and distance of two lingual arteries through drug-induced sleep ultrasound, and explore the relationship between sonographic measurements and clinical data.A total of 26 confirmed obstructive sleep apnea patients were recruited in this one-year study. All patients received ultrasound examination twice (wakefulness and drug-induced sleep) in sleep center under level 1 polysomnographic monitor. Drug-induced sleep was performed by administration of one Stilnox (Zolpidem, 2 mg/tablet) and ultrasound procedure commenced once stage 2 sleep shown in polysomnography. Ultrasound imaging was implemented via submental approach with transducer position at the sagittal midline of the submental area (sagittal view) to measure thickness of the tongue. Transducer was then moved at a transverse midpoint between the inferior border of the mandible and the hyoid bone (transverse view) to measure the distance between 2 lingual arteries.The distance between 2 lingual arteries elongated significantly (p .001) and thickness of tongue muscle became thinner during drug-induced sleep. The distance between 2 lingual arteries (sleep) had positive correlation with apnea/hypopnea index (AHI, r = 0.51, p = .008) and body mass index (BMI, r = 0.46, p = .018).Drug-induced sleep ultrasound is feasible to measure changes of tongue in OSA patients. Ultrasound imaging showed that tongue muscle became thinner in conjunction with significant widening in distance between two lingual arteries during hypnotic-induced sleep and that was positively correlated with AHI and BMI. Drug-induced sleep ultrasound may be helpful to enhance safety in tongue surgery for OSA patients.

Rugby is characterized by frequent high-intensity collisions, resulting in muscle soreness. Players consequently seek strategies to reduce soreness and accelerate recovery, with an emerging method being cannabidiol (CBD), despite anti-doping risks. The prevalence and rationale for CBD use in rugby has not been explored; therefore, we recruited professional male players to complete a survey on CBD. Goodness of fit chi-square (χ2) was used to assess CBD use between codes and player position. Effects of age on use were determined using χ2 tests of independence. Twenty-five teams provided 517 player responses. While the majority of players had never used CBD (p V = 0.24), 26% had either used it (18%) or were still using it (8%). Significantly more CBD use was observed in rugby union compared with rugby league (p = .004, V = 0.13), but player position was not a factor (p = .760, V = 0.013). CBD use increased with players’ age (p V = 0.28), with mean use reaching 41% in the players aged 28 years and older category (p

An analytical method for the detection of 40 benzodiazepines, (±)-zopiclone, zaleplon and zolpidem in blood and urine by solid-phase extraction liquid chromatography–tandem mass spectrometry was developed and validated. Twenty-nine of 43 analytes were quantified in 0.5 mL whole blood for investigating postmortem, drug-facilitated sexual assault (DFSA) and driving under the influence of drugs cases (DUID). The four different dynamic ranges of the seven-point, linear, 1/x weighted calibration curves with lower limits of quantification of 2, 5, 10 and 20 μg/L across the analytes encompassed the majority of our casework encountered in postmortem, DFSA and DUID samples. Reference materials were available for all analytes except α-hydroxyflualprazolam, a hydroxylated metabolite of flualprazolam. The fragmentation of α-hydroxyflualprazolam was predicted from the fragmentation pattern of α-hydroxyalprazolam, and the appropriate transitions were added to the method to enable monitoring for this analyte. Urine samples were hydrolyzed at 55°C for 30 min with a genetically modified β-glucuronidase enzyme, which resulted in >95% efficiency measured by oxazepam glucuronide. Extensive sample preparation included combining osmotic lysing and protein precipitation with methanol/acetonitrile mixture followed by freezing and centrifugation resulted in exceptionally high signal-to-noise ratios. Bias and between-and within-day imprecision for quality controls (QCs) were all within ±15%, except for clonazolam and etizolam that were within ±20%. All 29 of the 43 analytes tested for QC performance met quantitative reporting criteria within the dynamic ranges of the calibration curves, and 14 analytes, present only in the calibrator solution, were qualitatively reported. Twenty-five analytes met all quantitative reporting criteria including dilution integrity. The ability to analyze quantitative blood and qualitative urine samples in the same batch is one of the most useful elements of this procedure. This sensitive, specific and robust analytical method was routinely employed in the analysis of >300 samples in our laboratory over the last 6 months.

Despite the importance of sleep and the evidence on its relationship with various chronic diseases, quality of sleep is not considered in patients with lumbar spinal stenosis (LSS). This prospective comparative study aimed to investigate the changes in sleep disturbance after treatment in patients with LSS. Patients with LSS and sleep disturbance (n = 201; 147 conservatively treated and 54 patients with surgical treatment) were included. The Pittsburgh sleep quality index (PSQI) was used to evaluate sleep quality. Propensity score matching was used to attenuate the potential bias. Clinical outcome of surgery, as determined by the Oswestry disability index, and the PSQI was compared between the two groups at 6 weeks, 3 months, and 6 months after enrollment. Multivariate logistic analysis was performed to adjust for possible confounders within the matched cohorts. Among the 201 patients, 96 (47.7%) patients were finally matched (48 patients in each group). Sleep quality was initially improved after treatment, regardless of the treatment method. Sleep quality in the surgical group was improved by 6 weeks after surgery and consistently improved during the 6-month follow-up period, despite less use of pain killer. Conversely, the improvement in sleep quality at 6-weeks following conservative treatment was not maintained during the follow-up, although the treatment outcome for LSS measured by ODI was continuously improved. After multivariate logistic regression analysis within propensity score matched cohorts, surgical treatment had a significantly greater chance to improve sleep quality compared to conservative treatment. The failure of sleep improvement in conservative group was significantly associated with depression presented by worse score in Hamilton depression rating scale, and more severe degree of foraminal-type stenosis, which should be carefully considered for conservative treatment of LSS patients with sleep disturbance.

The purpose of this study was to examine the impact of prescription sleep medications on physical activity (PA) participation among diabetic older adults. We analyzed cross-sectional data of 1,581 respondents ≥ 50 years from the 2006-2014 waves of the Health and Retirement Study. The respondents self-reported frequency of their PA from light, moderate and vigorous activity and whether they regularly took prescription sleep medications. We found that 381 of 1,581 respondents (24%) reported regular use of prescription medications for sleep. Hierarchical linear regression models revealed that use of prescription sleep medications significantly predicted less participation in PA after controlling for demographic variables, personality traits, social support, environmental factors, social integration, sensory functions, presence of pain, prescription pain medication use, body mass index, and health conditions. The finding highlights that use of prescription sleep medications may be an important risk factor of physical inactivity in diabetic older adults.

Insomnia is a widespread sleep disorder in the general population, and it is a risk factor for impaired function, the development of other medical and mental disorders, and causes an increase in health care costs. In view of the health hazards of insomnia and the shortcomings of western medicine, Complementary and Alternative Medicine (CAM) should be considered in the management of insomnia. The present overview reports the potential role of herbal medicine and non-pharmacological therapies in the treatment of insomnia and summarizes the scientific evidence reported from 2008 to 2018. PubMed and Web of Science databases were searched for studies published from 2008 to 2018. 17 randomized controlled trials and 22 non-pharmacological therapies were included in this review, and the results showed that CAM had certain advantages in the treatment of insomnia. The safety of CAM for insomnia was acceptable. Meanwhile, based on pre-clinical trial, the possible mechanisms of CAM for insomnia were modulation of circadian rhythm, GABA receptor activation, antagonisms of 5-HT receptors, inhibition of glutamate-mediated pathways, and attenuation of inflammation. CAM for insomnia has made some progress, but high quality evidence-based medical evidence is still needed to provide guidance for clinical application.

Objectives: To investigate the use of sleep medication and concomitant psychotropic medication in children and adolescents placed under residential care (RC). Methods: Participants were youth 0–20 years of age placed in RC institutions at least once during 2016. Data on filled prescriptions were taken from the Norwegian Prescription Database to compare the use of sleep medication in RC with the general child population (GenPop) and how it covaried with gender, age, reasons for RC placement, and concomitant use of other psychotropic medications (antidepressants, anxiolytics, antipsychotics, and psychostimulants). Results: A total of 2171 youths were identified in RC at mean age 14 years (82% ≥ 13 years). Seventeen percent (371/2171) used sleep medications (melatonin 11%, alimemazine 7%, and benzodiazepines/z-hypnotics 2%) significantly more than the 2.3% who used in GenPop. The girl/boy ratio for medication use in RC was 1.8 (95% confidence interval [CI] = 1.5–2.2), not significantly different from the corresponding ratio in GenPop (1.4; 95% CI = 1.3–1.5). The use of sleep medication increased with age. When comparing reasons for placement in RC, medication use was particularly low among unaccompanied minor asylum seekers (2%). About half of the youths used concomitant psychotropic medication, with clear gender differences; girls used about twice as much antidepressants, anxiolytics, and antipsychotics, whereas boys used 1.3 times more psychostimulants. Conclusion: Youths in RC used more sleep medication and concomitant psychotropic medication than the GenPop, most likely reflecting the increased psychosocial strain and mental disorders reported in this population. Further studies of prevalence, assessment, and treatment of sleep problems in RC populations are warranted.

Purpose To identify and analyze postmarketing cases of complex sleep behaviors (CSBs) resulting in serious injuries, including death, associated with eszopiclone, zaleplon, or zolpidem (Z-drugs). Methods Retrospective analysis of the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from 16 December 1992 through 27 February 2018 and medical literature using PubMed and EMBASE. We used random sampling and descriptive statistics. Results We identified 66 cases that met inclusion and exclusion criteria, four of which were identified in the medical literature. Twenty cases reported death and 46 cases reported serious injuries in association with CSBs occurring after the use of a Z-drug. Fatal cases described events, such as carbon monoxide poisoning, drowning, falls, hypothermia, motor vehicle collisions, and apparent completed suicide. Nonfatal cases resulting in serious injuries described events, such as accidental overdoses, falls, gunshot wounds, hypothermia, third-degree burns, and self-injuries or suicide attempts. Twenty-two cases reported a previous episode of a CSB while taking a Z-drug prior to the event reported in this case series. Conclusions The FAERS and medical literature cases support the need for increased awareness of the consequences that may occur because of CSBs associated with the use of Z-drugs. Therefore, to protect public health, regulatory actions were taken, including adding a Boxed Warning, a Contraindication in patients who have experienced a prior episode of a CSB with a Z-drug, and updating the existing Warnings and Precautions. An FDA Drug Safety Communication was also disseminated to alert healthcare professionals and the public of this potential risk.

Sleep plays an important role in the recovery of critically ill patients. However, patients in the intensive care unit (ICU) often suffer sleep disturbances and abnormal circadian rhythms, which may increase delirium and lengthen ICU stay. Nonpharmacologic strategies for preventing and treating sleep disturbances and delirium, such as overnight eye masks and ear plugs, are usually employed first, given the lack of adverse effects. However, a multimodal approach to care including pharmacotherapy may be necessary. Despite the limited available data supporting their use, medications such as melatonin, ramelteon, suvorexant, and dexmedetomidine may promote sleep and improve a variety of patient-centric outcomes such as delirium. This narrative review focuses on these nonbenzodiazepine agents used for sleep in the ICU. Practical application of each of these agents is described for when providers choose to utilize one of these pharmacotherapies to promote sleep or prevent delirium.

We investigated the effects of sleep-inducing agents with different mechanisms of action on the loss of the righting reflex induced by isoflurane or a mixture of medetomidine, midazolam, and butorphanol (MMB), followed by atipamezole reversal. Chlorpromazine and brotizolam delayed recovery from both types of anesthesia, whereas the melatonin receptor agonist ramelteon had no effect. The orexin receptor antagonist suvorexant delayed recovery from anesthesia only in the case of MMB, while the sleep-promoting supplement glycine only delayed recovery in the case of isoflurane. These results suggest that the simple comparison method is applicable for testing substances expected to exert sleep-inducing effects. Keywords: Hypnotics, Anesthesia, Method

Introduction We evaluated the clinical profile of the orexin receptor antagonist suvorexant for treating insomnia in patients with mild‐to‐moderate probable Alzheimer's disease (AD) dementia. Methods Randomized, double‐blind, 4‐week trial of suvorexant 10 mg (could be increased to 20 mg based on clinical response) or placebo in patients who met clinical diagnostic criteria for both probable AD dementia and insomnia. Sleep was assessed by overnight polysomnography in a sleep laboratory. The primary endpoint was change‐from‐baseline in polysomnography‐derived total sleep time (TST) at week 4. Results Of 285 participants randomized (suvorexant, N = 142; placebo, N = 143), 277 (97%) completed the trial (suvorexant, N = 136; placebo, N = 141). At week 4, the model‐based least squares mean improvement‐from‐baseline in TST was 73 minutes for suvorexant and 45 minutes for placebo; (difference = 28 minutes [95% confidence interval 11‐45], p < 0.01). Somnolence was reported in 4.2% of suvorexant‐treated patients and 1.4% of placebo‐treated patients. Discussion Suvorexant improved TST in patients with probable AD dementia and insomnia.

A post-2000 literature search reviewed prevalence of health consequences associated with zolpidem, plus two salient case reports. Common zolpidem-related harms encompassed accidents, falls, overdoses, delirium, and infections. Risks to others included assaults, vehicular accidents, various crimes, and civil actions that occurred during zolpidem-induced delirium, withdrawal, and other impediments. Remarkably, much harm occurred while patients were taking therapeutic doses of licitly prescribed zolpidem (10-30 mg). Zolpidem-associated health, behavioral, and social problems comprise an international pandemic of preventable heath misfortunes.

An unconventional and innovative approach for the quantitative determination of 11 ototoxic and narcoleptic drugs in whole blood is described. The multiclass method allows the inclusion of the most widespread drugs on the market (antihistamines, antidepressants, antihypertensives, anxiolytics, opioids, Z-drugs) responsible for 10% of occupational accidents.The developed procedure involved the use of the desorption electrospray ionization (DESI) interface for the direct analysis of dried blood spots (DBS). All the issues strictly connected to the chemical-physical characteristics of DBS and DESI (sample inhomogeneity, DBS support, DESI geometry and solvent) were carefully evaluated and innovative strategies were applied. Haematocrit was managed using a small and measured volume of blood (2 μL) with analysis of the entire DBS.The proposed method was fully validated in terms of limits of detection, limits of quantitation (LOQs; between 60 pg/mmResults showed a surprising sensitivity, demonstrating that this procedure could be suitable for applications in various fields, e.g. forensic analysis. Moreover, as a collateral benefit, it was discovered that the method is able to analyse very light traces left on plastic and glass surfaces by detached dried blood.

COVID-19 has had a substantial national impact in South Korea, causing negative psychological responses including sleep-related problems. Literature indicates sleep problems among the general population have been reported to be as high as around 35.7% during the first 8 months of COVID-19. Therefore, the aim of this study was to investigate the impact of COVID-19 pandemic on sleep problems among the general population using relative search volume (RSV) data, and whether there are any differences by age and time periods spanning before and during the pandemic. RSV data was collected from the most commonly used search engine in South Korea, NAVER. Search terms were grouped into 4 categories: insomnia, other sleep disorders, sleeping pills, and sleeping pill side effects. Time points were divided into 4 periods, each 7 months long: 7 months before COVID-19 (T0), first confirmed COVID-19 case to 7 months after (T1), 7 to 14 months (T2), and 14 to 21 months (T3). A 2x4 factorial Analysis of Variance was conducted to investigate main effects and interactions between age and time periods. Main effects and interaction effects of age and time periods were significant for all search term groups. For all search terms, both age groups showed dramatic increase from T0 to T1. In age group 60 or above, RSV continued to increase for other sleep disorders and sleeping pill. Insomnia and sleeping pill side effects showed decreasing trend at T3. In general, sudden increase in RSV after occurrence of COVID-19 followed by slow decline were observed. However, for age group 60 or above, RSV values of other sleep disorders and sleeping pills continued to increase, suggesting slower recovery of psychological impact with increasing age. Overall, the results underscore the importance of implementing preventive measures for monitoring sleep problems during the pandemic, especially in the elderly.

The aim of this study was to assess the trends and determinants of sleeping pill consumption in the general population.This was a prospective study that included 4329 participants (2379 women, 51.9 ± 10.4 years) living in the city of Lausanne, Switzerland, followed up for an average of 10.9 years. Benzodiazepines and benzodiazepine receptor agonists were considered as sleeping pills.The prevalence (95% confidence interval [CI]) of sleeping pills use was 8.0% (7.2-8.9) at baseline and 8.4 (7.6-9.3) after 10.9 years. Overall, sleeping pills use was higher among women, elderly individuals, and individuals reporting a history of anxiety and depression. During the 10.9-year follow-up, 85.8% of participants never used sleeping pills, 2.7% used the sleeping pills at all assessments, and 11.5% shifted from using to quitting (and vice versa). On multivariate analysis, the factors associated with "always" sleeping pills use were as follows: female gender (relative risk ratio and [95% CI] = 1.80 [1.14-2.85]); older age (7.05 [3.56-14.0] for 65 + vs 45 years); lower educational level (2.06 [1.06-3.99] for mandatory vs university); anxiety (5.61 [3.61-8.71] for yes/no); and depression (3.75 [2.47-5.69] for yes/no). The same factors were also associated with occasional sleeping pills use (ie, shifters): relative risk ratios and 95% CI = 1.56 (1.26-1.94), 2.37 (1.72-3.26), 1.35 (0.98-1.87), 3.40 (2.59-4.45), and 2.50 (1.99-3.15) for female gender, older age, lower educational level, and anxiety and depression, respectively.During a 10.9-year follow-up, one out of seven participants (14.2%) used sleeping pills at least once during the study period. Sleeping pills use is more frequent among individuals with anxiety or depression, elderly individuals, and women.

To explore the application of Chaihu-Guizhi-Longgu-Muli decoction (CGLM) combined with Liuwei Dihuang Pills in the treatment of menopausal insomnia and its effect on sleep quality. The data of 120 menopausal insomnia patients admitted to our hospital from February 2019 to February 2020 were retrospectively analyzed and they were equally divided into the experimental group (n=60) and the control group (n=60) according to the order of admission. All patients were treated with Liuwei Dihuang Pills, and the experimental group was additionally given CGLM. The Pittsburgh Sleep Quality Index (PSQI), estrogen level, negative emotion score, quality of life score, serum β-endorphin (β-EP) level, serotonin level (5-HT) and treatment effective rate were compared between the two groups of patients. After treatment, the experimental group obtained markedly lower PSQI scores and negative emotion scores than the control group (P0.001). The estrogen levels, β-EP levels and 5-HT levels of the experimental group after treatment were significantly better than those of the control group (P0.001). Higher quality of life scores and treatment effective rates were observed in the experimental group after treatment than the control group (P0.001). CGLM combined with Liuwei Dihuang Pills can regulate the serum hormone levels of patients with menopausal insomnia, reduce negative emotions and improve sleep quality and quality of life, which merits clinical promotion.

INTRODUCTION: Preclinical evidence suggests that melatonin may affect cellular pathways involved in colorectal cancer (CRC). We sought to test whether melatonin use was associated with decreased risk of CRC using population-based data. METHODS: We performed a nationwide cohort study using a new-user study design. We identified a total of 58,657 incident melatonin users aged 50 years and older from the Prescribed Drug Register, and matched them with 175,971 comparisons who did not use melatonin, on the ratio of 1:3. The Cox regression model was used to calculate hazard ratios and 95% confidence intervals. RESULTS: The incidence rate of CRC was 10.40 per 10,000 person-years for melatonin users, whereas the rate was 12.82 per 10,000 person-years in the nonusers. We found a significant negative association between melatonin use and risk of CRC (adjusted hazard ratio, 0.82; 95% confidence interval, 0.72–0.92). A test for trend showed a significant dose-response correlation (P < 0.001). The decrease of CRC risk was independent of tumor location and stage at diagnosis. When stratified by age groups, the inverse association was significant only among individuals aged 60 years and older. DISCUSSION: This population-based cohort study suggests that the use of melatonin was associated with a reduced risk of CRC. Further studies are needed to confirm the observed association and to explore the underlying mechanisms.

To estimate the prevalence of sleep problems and sleeping pill use and associated factors in the Brazilian population.This study was conducted with data from the 2019 Brazilian National Health Survey. Our sample consisted of 94,114 participants and the outcomes analyzed were sleep problems and sleeping pill use. Sociodemographic, lifestyle, and health characteristics were explored in a descriptive and multivariate analysis with Poisson regression, robust variance, and 5% significance.We found a 35.1% (95%CI: 34.5-35.7) and 8.5% (95%CI: 8.2-8.9) prevalence of sleep problems and sleeping pill use, respectively. Sleep problems were associated with women (PR = 1.41; 95%CI: 1.36-1.46), individuals who self-assess their health as regular/poor/very poor (PR = 1.56; 95%CI: 1.51-1.62), those with chronic diseases (PR = 1.70; 95%CI: 1.64-1.78), those who use alcohol excessively (PR = 1.14; 95%CI: 1.09-1.20), and smokers (PR = 1.16; 95%CI: 1.10-1.22). Sleeping pill use was associated with women (PR = 1.57; 95%CI: 1.43-1.73), divorcees (PR = 1.46; 95%CI: 1.30-1.65), urban denizens (PR = 1.32; 95%CI: 1.21-1.45) those who self-assess their health as regular/poor/very poor (PR = 1.79; 95%CI: 1.64-1.95), those with chronic diseases (PR = 4.07; 95%CI: 3.48-4.77), and smokers (PR = 1.49; IC95%: 1.33-1.67).This study found that the prevalence of sleep problems and sleeping pill use in Brazilians indicates the need for attention and sleep care for this population, especially in women and those with lifestyle and health conditions associated with the analyzed outcomes.

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Insomnia afflicts many geriatric patients worldwide and results in both clinical and economic consequences. Prescribing hypnotics to the elderly is particularly challenging due to multitudes of adverse effects and drug interactions. Although benzodiazepines and "Z" drugs such as zolpidem have been popular in the past, they carry a high risk of adverse effects in the elderly, such as devastating falls and injuries as well as potentially an increase in mortality. Newer classes of hypnotics such as dual orexin receptor antagonists are much better tolerated and can be explored as a potential treatment for insomnia in the elderly.

Aim: Modified Suanzaoren Decoction (MSZRD) is obtained by improving Suanzaoren Decoction (SZRT), a traditional Chinese herbal prescription that has been used to treat insomnia for more than thousands of years. Our previous study showed that MSZRD can improve the gastrointestinal discomfort related insomnia by regulating Orexin-A. This study is the first study to evaluate the effects and possible mechanisms of MSZRD in mice with insomnia caused by p-chlorophenylalanine (PCPA) combined with multifactor random stimulation. Methods: After 14 days of multifactor stimulation to ICR mice, a PCPA suspension (30 mg/mL) was injected intraperitoneally for two consecutive days to establish an insomnia model. Three different doses of MSZRD (3.6, 7.2, and 14.4 g/kg/day) were given to ICR mice for 24 days. The food intake and back temperature were measured, and behavioral tests and pentobarbital sodium-induced sleep tests were conducted. The levels of Orexin-A, corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and adrenocortical hormones (CORT) in the serum and 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE) in hypothalamus were measured using enzyme-linked immunosorbent assay (ELISA) kits. The levels of γ-aminobutyric acid (GABA) and glutamic acid (Glu) were measured by high-performance liquid chromatography (HPLC). The expression of 5HT1A receptor (5-HTRIA) and orexin receptor 2 antibody (OX2R) was measured by Western blot (WB) and immunohistochemical staining (ICH). Hematoxylin and eosin (H&E) staining and Nissl staining were used to assess the histological changes in hypothalamus tissue. Results: Of note, MSZRD can shorten the sleep latency of insomnia mice (P

Purpose/background This study was designed as an early assessment of the safety of the orexin receptor antagonist suvorexant, but also included exploratory assessments of balance and psychomotor performance that are the focus of this report. Methods/procedures This was a double-blind, randomized, 3-period, crossover, phase 1 study. Balance and psychomotor performance were evaluated during the night in 12 healthy elderly participants after bedtime administration of suvorexant 30 mg (a supratherapeutic dose), the GABAergic agonist zolpidem 5 mg (the recommended dose in the elderly), or placebo. Balance (body sway measured by platform stability) and psychomotor performance (measured by choice reaction time) were assessed predose and at 1.5, 4, and 8 hours postdose in each period. Memory (measured by word recall) was assessed predose and at 4 hours postdose. Findings/results At 1.5 hours after nighttime administration of each drug (the approximate time of their anticipated maximal plasma concentrations), both zolpidem and suvorexant increased body sway versus placebo, with a greater increase for zolpidem than suvorexant. Suvorexant increased choice reaction time compared with placebo or zolpidem at 1.5 hours. There were no treatment differences on body sway or choice reaction time at 4 or 8 hours, or on word recall at 4 hours. Implications/conclusions These exploratory data suggest that a 30-mg dose of suvorexant (supratherapeutic) and a 5-mg dose of zolpidem (recommended dose in the elderly) impaired balance at 1.5 hours in healthy elderly people, with potentially less impairment for suvorexant relative to zolpidem, but no treatment differences on body sway or psychomotor performance at 4 and 8 hours. Because of their exploratory nature, these findings and their clinical relevance, if any, require confirmation in a prospective study.

The long-anticipated high-resolution structures of the human melatonin G protein-coupled receptors MT(1) and MT(2), involved in establishing and maintaining circadian rhythm, were obtained in complex with two melatonin analogs and two approved anti-insomnia and anti-depression drugs using X-ray free electron laser serial femtosecond crystallography. The structures shed light on the overall conformation and unusual structural features of melatonin receptors, as well as their ligand binding sites and the melatonergic pharmacophore, thereby providing insights into receptor subtype selectivity. The structures revealed an occluded orthosteric ligand binding site with a membrane-buried channel for ligand entry in both receptors, and an additional putative ligand entry path in MT(2) from the extracellular side. This unexpected ligand entry mode contributes to facilitating the high specificity with which melatonin receptors bind their cognate ligand and exclude structurally similar molecules such as serotonin, the biosynthetic precursor of melatonin. Finally, the MT(2) structure allowed accurate mapping of type 2 diabetes-related single-nucleotide polymorphisms, where a clustering of residues in helices I and II on the protein-membrane interface was observed which could potentially influence receptor oligomerization. The role of receptor oligomerization is further discussed in light of the differential interaction of MT(1) and MT(2) with GPR50, a regulatory melatonin co-receptor. The melatonin receptor structures will facilitate design of selective tool compounds to further dissect the specific physiological function of each receptor subtype as well as provide a structural basis for next generation sleeping aids and other drugs targeting these receptors with higher specificity and fewer side effects.