Melatonin supplementation for the treatment of infantile spasms: protocol for a randomised placebo-controlled triple-blind trial.

INTRODUCTION: Infantile spasms (IS) is a type of severe epileptic encephalopathy that occurs in infancy and early childhood. IS is characterised clinically by epileptic spasms, often accompanied by sleep disorder and abnormal circadian rhythm. The endogenous circadian rhythm disorder, in turn, can make spasms worse. Melatonin has also been found to have anticonvulsant and neuroprotective properties by adjusting the circadian rhythm. However, there are lack of relevant studies on controlling IS by using melatonin. This study aims to analyse the therapeutic effect of melatonin supplementation for the treatment of IS. METHODS AND ANALYSIS: This is a triple-blinded (trial participant, outcome assessor and the data analyst), prospective, randomised controlled trial to be conducted in the Department of Paediatrics, The First Medical Center of Chinese PLA General Hospital, Beijing, China from November 2020. Patients (n=70) aged 3 months to 2 years with IS will be recruited in this study after receiving written consent from their parents or guardians. Patients will be randomly divided into two equal groups and treated with a combination of adrenocorticotropic hormone, magnesium sulfate and either melatonin or placebo. Clinical data from the patients in the two groups before and after the treatment will be collected and compared. The primary outcome will be assessed 2 weeks later by seizure diaries and reported as the average reduced rate of spasms frequency. Secondary outcomes include the response rate (the rate of spasms-free), electroencephalogram hypsarrhythmia assessment and the psychomotor development assessment (Denver Developmental Screening Test). Sleep quality and safety will also be assessed. ETHICS AND DISSEMINATION: The protocol for this study was approved by the Ethics Committee of Chinese PLA General Hospital (reference number S2020-337-01) and was reported according to the Standard Protocol Items: Recommendations for Interventional Trials statement. Findings of this research will be disseminated through national and international meetings, conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2000036208.

Shift Workers at Risk for Metabolic Syndrome.

In this highly digitalized era, sleep disorders are becoming more common and are associated with an increased burden of chronic disease. Shift workers are at an increased risk for both sleep disorders and metabolic syndrome. In this article, the authors outline the connection between circadian discordance, hormonal imbalance, and the development of metabolic syndrome in shift workers. Based on a literature review of animal model studies, observational studies, and clinical trials conducted between August and October of 2018, the authors offer several clinical interventions, including work schedules, light therapy, medications, and dietary habits to improve the circadian synchronicity of shift workers and reduce their risk of morbidity and mortality. It is important for physicians to be familiar with the consequences of shift work and ways to mitigate the risks for this patient population.

Optimized Sleep After Brain Injury (OSABI): A Pilot Study of a Sleep Hygiene Intervention for Individuals With Moderate to Severe Traumatic Brain Injury.

Background. Disrupted sleep is common after traumatic brain injury (TBI) particularly in the inpatient rehabilitation setting where it may affect participation in therapy and outcomes. Treatment of sleep disruption in this setting is varied and largely unexamined. Objective. To study the feasibility of instituting a sleep hygiene intervention on a rehabilitation unit. Methods. Twenty-two individuals admitted to a brain injury unit were enrolled and allocated, using minimization, to either a sleep hygiene protocol (SHP) or standard of care (SOC). All participants wore actigraphs, underwent serial cognitive testing, and had light monitors placed in their hospital rooms for 4 weeks. Additionally, participants in the SHP received 30 minutes of blue-light therapy each morning, had restricted caffeine intake after noon, and were limited to 30-minute naps during the day. SHP participants had their lights out time set according to preinjury sleep time preference. Both groups were treated with the same restricted formulary of centrally acting medications. Results. Of 258 patients screened, 27 met all study inclusion criteria of whom 22 were enrolled. Nine participants in each group who had at least 21 days of treatment were retained for analysis. The protocol was rated favorably by participants, families, and staff. Actigraph sleep metrics improved in both groups during the 4-week intervention; however, only in the SHP was the change significant. Conclusions. Sleep hygiene is a feasible, nonpharmacologic intervention to treat disrupted sleep in a TBI inpatient rehabilitation setting. A larger study is warranted to examine treatment efficacy. ClinicalTrials.gov Identifier: NCT02838082.

[Hypothalamic intravascular B-cell lymphoma in an immunocompetent patient]. / Linfoma B intravascular hipotalamico en una paciente inmunocompetente.

TITLE: Linfoma B intravascular hipotalamico en una paciente inmunocompetente.

Sleep coaching: non-pharmacological treatment of non-restorative sleep in Austrian railway shift workers.

Sleep coaching by Holzinger & Klösch™ is a new, Gestalt therapy-based holistic approach to non-pharmacological treatment of non-restorative sleep. It includes psychotherapeutic aspects which enable participants to improve their sleep quality by developing their own coping strategies as a daily routine. Dream work and relaxation techniques are also part of the programme. The aim of this study was to measure the effectiveness of a two-day sleep coaching seminar on sleep quality, daytime sleepiness, and work and life quality in shift workers employed in an Austrian railway company (Österreichische Bundesbahnen, ÖBB). Thirty shift workers (28 male; mean age=24±45.90, age range 24-56 years) answered the same survey before and six months after the seminar (baseline and follow-up) containing items of the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS), their chronotype, personality factors, and burnout risk factors. The baseline findings in this group were compared with those of non-completers (who did not take the follow-up survey) (N=154) to see if the two groups differed significantly enough to create a bias among completers (who took the follow-up survey as well). Groups differed significantly in burnout levels as well as sleep duration, but not in the distribution of critical PSQI and ESS values. The two-day sleep coaching seminar resulted in a significant improvement in total PSQI score and subjective sleep quality and in a significant reduction in diurnal fatigue, sleep latency, and daytime sleepiness. Nevertheless, more research with a larger sample and a longitudinal design is needed to establish the long-term effects of sleep coaching.

Clinical chronobiology: a timely consideration in critical care medicine.

A fundamental aspect of human physiology is its cyclical nature over a 24-h period, a feature conserved across most life on Earth. Organisms compartmentalise processes with respect to time in order to promote survival, in a manner that mirrors the rotation of the planet and accompanying diurnal cycles of light and darkness. The influence of circadian rhythms can no longer be overlooked in clinical settings; this review provides intensivists with an up-to-date understanding of the burgeoning field of chronobiology, and suggests ways to incorporate these concepts into daily practice to improve patient outcomes. We outline the function of molecular clocks in remote tissues, which adjust cellular and global physiological function according to the time of day, and the potential clinical advantages to keeping in time with them. We highlight the consequences of "chronopathology", when this harmony is lost, and the risk factors for this condition in critically ill patients. We introduce the concept of "chronofitness" as a new target in the treatment of critical illness: preserving the internal synchronisation of clocks in different tissues, as well as external synchronisation with the environment. We describe methods for monitoring circadian rhythms in a clinical setting, and how this technology may be used for identifying optimal time windows for interventions, or to alert the physician to a critical deterioration of circadian rhythmicity. We suggest a chronobiological approach to critical illness, involving multicomponent strategies to promote chronofitness (chronobundles), and further investment in the development of personalised, time-based treatment for critically ill patients.

Factors related to quality of life among older adults in Bangladesh: A cross sectional survey.

This cross-sectional design study aimed to describe quality of life and examine factors related to quality of life among older adults in Bangladesh. Convenience sampling was used to recruit 280 older adults from ten villages in two southern districts. The results demonstrate that the majority of the participants reported an overall moderate score of quality of life. Moreover, participants' sleep problems, depression, religiosity, and activities of daily living were negatively correlated with quality of life whereas social support and health service availability were positively correlated with quality of life. Implementing intervention programs upon the significant related factors to improve older adults' quality of life is recommended.

Circadian Disruption Associated with Alzheimer's Disease.

Alzheimer's disease (AD) is increasing in prevalence and has a significant impact on caregivers and the healthcare system. One of the many physiologic process affected by AD is the circadian system, with disruption reflected in abnormalities of the sleep-wake cycle. This interaction is bidirectional, with circadian and sleep disruption influencing disease progression. Understanding the bidirectional relationship between AD and circadian disruption may allow for earlier recognition of the potential to develop dementia as well as improved targeted approaches for therapy. Therapies including melatonin and bright light therapy may be advantageous in improving sleep and circadian rhythms and preventing the progression of disease. However, unfortunately, these modalities are not curative, and additional research is needed to improve treatment options for these individuals.

Diagnosis, Cause, and Treatment Approaches for Delayed Sleep-Wake Phase Disorder.

Delayed sleep-wake phase disorder (DSWPD) is commonly defined as an inability to fall asleep and wake at societal times resulting in excessive daytime sleepiness. Although the cause is multifaceted, delays in sleep time are largely driven by misalignment between the circadian pacemaker and the desired sleep-wake timing schedule. Current treatment approaches focus on correcting the circadian delay; however, there is a lack of data investigating combined therapies for treatment of DSWPD.

The etiology of delayed sleep phase disorder.

According to classification manuals for sleep disorders, nine disorders are directly related to biological clock timing misalignments. Of all, delayed sleep phase disorder (DSPD) is the most commonly diagnosed, predominantly affecting adolescents, young adults, and insomnia patients. It is a persistent inability to fall asleep at earlier, more desirable and socially conventional times, coupled with extreme difficulty awakening in the morning. Considerable evidence shows a delay in the circadian clock to be associated with DSPD. Therefore, treatments have mainly focused on advancing the biological clock and sleep timing through pharmacotherapy, phototherapy and behavioral therapies. The clinical evidence indicates that these treatments are efficacious, at least in the short term. However, follow up studies show frequent patient relapse, leading researchers to speculate that alternative etiologies may be contributing to sleep and circadian clock delays in DSPD. The aim of the present paper is to review and collate current literature related to DSPD etiology in order to outline gaps in current knowledge and suggest future research.

Chronic decrease in wakefulness and disruption of sleep-wake behavior after experimental traumatic brain injury.

Traumatic brain injury (TBI) can cause sleep-wake disturbances and excessive daytime sleepiness. The pathobiology of sleep disorders in TBI, however, is not well understood, and animal models have been underused in studying such changes and potential underlying mechanisms. We used the rat lateral fluid percussion (LFP) model to analyze sleep-wake patterns as a function of time after injury. Rapid-eye movement (REM) sleep, non-REM (NREM) sleep, and wake bouts during light and dark phases were measured with electroencephalography and electromyography at an early as well as chronic time points after LFP. Moderate TBI caused disturbances in the ability to maintain consolidated wake bouts during the active phase and chronic loss of wakefulness. Further, TBI resulted in cognitive impairments and depressive-like symptoms, and reduced the number of orexin-A-positive neurons in the lateral hypothalamus.

Predictors of shift work disorder among nurses: a longitudinal study.

BACKGROUND: Shift work is associated with sleep problems and impaired health. The main aim of the present study was to explore predictors of developing shift work disorder (SWD) among Norwegian nurses using a longitudinal design. METHODS: A total of 1533 nurses participating in a survey on shift work, sleep and health responded to questionnaires at baseline and at follow-up about two years later. SWD was defined as problems of excessive sleepiness and/or complaints of insomnia related to the work schedule. RESULTS AND CONCLUSIONS: There was a significant reduction (p < 0.001) in the prevalence of SWD from baseline to follow-up, from 35.7% to 28.6%. Logistic regression analyses showed significant risks of having SWD at follow-up and the following variables measured at baseline: number of nights worked the last year (OR = 1.01, 95% CI = 1.01-1.02), having SWD (OR = 5.19, 95% CI = 3.74-7.20), composite score on the Epworth Sleepiness Scale (OR = 1.08, 95% CI = 1.04-1.13), use of melatonin (OR = 4.20, 95% CI = 1.33-13.33), use of bright light therapy (OR = 3.10, 95% CI 1.14-8.39), and symptoms of depression measured by the Hospital Anxiety and Depression Scale (OR = 1.07, 95% CI = 1.00-1.14). In addition, leaving night work between baseline and follow-up was associated with a significantly reduced risk of SWD at follow-up (OR = 0.12, 95% CI = 0.07-0.22).

Embodiment and dementia: exploring critical narratives of selfhood, surveillance, and dementia care.

In the last decade there has been a notable increase in efforts to expand understandings of dementia by incorporating the body and theorizing its interrelationship with the larger social order. This emerging subfield of dementia studies puts the body and embodied practices at the center of explorations of how dementia is represented and/or experienced. This shift towards a greater recognition of the way that humans are embodied has expanded the horizon of dementia studies, providing the intellectual and narrative resources to examine experiences of dementia, and their interconnections with history, culture, power, and discourse. Our aim in this paper is to critically explore and review dimensions of this expanding research and literature, specifically in relation to three key narratives: (1) rethinking selfhood: exploring embodied dimensions; (2) surveillance, discipline, and the body in dementia and dementia care; and (3) embodied innovations in dementia care practice. We argue that this literature collectively destabilizes dementia as a taken-for-granted category and has generated critical texts on the interrelationship between the body and social and political processes in the production and expression of dementia.

Delayed sleep phase disorder in youth.

PURPOSE OF REVIEW: For over 30 years, delayed sleep phase disorder (DSPD) has been defined as a debilitating sleep condition. Recently, there is more awareness of DSPD in young people, yet considerable information is needed to understand its cause and treatment. This review describes the latest research findings describing the clinical features, cause, and treatment of DSPD. RECENT FINDINGS: The prevalence of DSPD in adolescents and young adults ranges from 1 to 16%. The impact on the individuals is significant, particularly in the domains of school/work performance and mental health. We describe various contributing factors including reduced homeostatic sleep pressure, a lengthened and delayed circadian rhythm, insensitivity to clock-resetting morning light, and heightened cognitive activity. Evening melatonin administration as a sole treatment appears promising, as is a combination of cognitive-behavior therapy and morning bright light. SUMMARY: Recent findings suggest clinicians to be aware of the clinical features (i.e., significant daytime sleepiness, anxiety and depression symptoms, potential for school dropout) of DSPD, as several biological features underpinning this disorder are unseen in clinical settings. We advise clinicians to become familiar with exogenous evening melatonin administration, and cognitive and behavioral techniques to simultaneously treat the delayed circadian rhythm and associated sleep-onset insomnia.

[Alteration of biological rhythms causes metabolic diseases and obesity]. / La alteracion de los ritmos biologicos causa enfermedades metabolicas y obesidad.

The incidence of obesity worldwide has become a serious, constantly growing public health issue that reaches alarming proportions in some countries. To date none of the strategies developed to combat obesity have proved to be decisive, and hence there is an urgent need to address the problem with new approaches. Today, studies in the field of chronobiology have shown that our physiology continually adapts itself to the cyclical changes in the environment, regard-less of whether they are daily or seasonal. This is possible thanks to the existence of a biological clock in our hypothalamus which regulates the expression and/or activity of enzymes and hormones involved in regulating our metabolism, as well as all the homeostatic functions. It has been observed that this clock can be upset as a result of today's modern lifestyle, which involves a drop in physical activity during the day and the abundant ingestion of food during the night, among other factors, which together promote metabolic syndrome and obesity. Hence, the aim of this review is to summarise the recent findings that show the effect that altering the circadian rhythms has on the metabolism and how this can play a part in the development of metabolic diseases.

TITLE: La alteracion de los ritmos biologicos causa enfermedades metabolicas y obesidad.La incidencia de la obesidad a escala mundial se ha convertido en un grave y creciente problema de salud publica, que alcanza en algunos paises proporciones alarmantes, y hasta el momento ninguna de las estrategias desarrolladas para combatir la obesidad se ha demostrado resolutiva, por lo que es urgente abordar el problema con nuevos enfoques. Actualmente, en el estudio de la cronobiologia se ha demostrado que nuestra fisiologia se adapta continuamente a los cambios ciclicos del ambiente, sean estos diarios o estacionales, debido a la presencia de un reloj biologico en nuestro hipotalamo que regula la expresion y actividad de enzimas y hormonas implicadas en la regulacion del metabolismo, asi como de todas las funciones homeostaticas. Se ha observado que este reloj puede alterarse debido al estilo de vida moderno, que implica una baja actividad fisica durante el dia e ingesta abundante de comida durante la noche, entre otros factores, que promueven todos ellos el sindrome metabolico y la obesidad. Por lo tanto, el objetivo de esta revision es resumir los hallazgos recientes que demuestran el efecto de la alteracion circadiana sobre el metabolismo y como esta puede participar en el desarrollo de enfermedades metabolicas.

Effects of shift and night work in the offshore petroleum industry: a systematic review.

Shift and night work are associated with several negative outcomes. The aim of this study was to make a systematic review of all studies which examine effects of shift and night work in the offshore petroleum industry, to synthesize the knowledge of how shift work offshore may affect the workers. Searches for studies concerning effects on health, sleep, adaptation, safety, working conditions, family- and social life and turnover were conducted via the databases Web of Knowledge, PsycINFO and PubMed. Search was also conducted through inspection of reference lists of relevant literature. We identified studies describing effects of shift work in terms of sleep, adaptation and re-adaptation of circadian rhythms, health outcomes, safety and accidents, family and social life, and work perceptions. Twenty-nine studies were included. In conclusion, the longitudinal studies were generally consistent in showing that adaptation to night work was complete within one to two weeks of work, while re-adaptation to a daytime schedule was slower. Shift workers reported more sleep problems than day workers. The data regarding mental and physical health, family and social life, and accidents yielded inconsistent results, and were insufficient as a base for drawing general conclusions. More research in the field is warranted.

Long-term effects of melatonin on quality of life and sleep in haemodialysis patients (Melody study): a randomized controlled trial.

AIM: The disturbed circadian rhythm in haemodialysis patients results in perturbed sleep. Short term melatonin supplementation has alleviated these sleep problems. Our aim was to investigate the effects of long-term melatonin supplementation on quality of life and sleep. METHODS: In this randomized double-blind placebo-controlled trial haemodialysis patients suffering from subjective sleep problems received melatonin 3 mg day(-1) vs. placebo during 12 months. The primary endpoint quality of life parameter 'vitality' was measured with Medical Outcomes Study Short Form-36. Secondary outcomes were improvement of three sleep parameters measured by actigraphy and nighttime salivary melatonin concentrations. RESULTS: Sixty-seven patients were randomized. Forty-two patients completed the trial. With melatonin, no beneficial effect on vitality was seen. Other quality of life parameters showed both advantageous and disadvantageous effects of melatonin. Considering sleep, at 3 months sleep efficiency and actual sleep time had improved with melatonin compared with placebo on haemodialysis days (difference 7.6%, 95% CI 0.77, 14.4 and 49 min, 95% CI 2.1, 95.9, respectively). At 12 months none of the sleep parameters differed significantly from placebo. Melatonin salivary concentrations at 6 months had significantly increased in the melatonin group compared with the placebo group. CONCLUSIONS: The high drop-out rate limits the strength of our conclusions. However, although a previous study reported beneficial short term effects of melatonin on sleep in haemodialysis patients, in this long-term study the positive effects disappeared during follow up (6-12 months). Also the quality of life parameter, vitality, did not improve. Efforts should be made to elucidate the mechanism responsible for the loss of effect with chronic use.

The management of sleep and circadian disturbance in patients with dementia.

Sleep and circadian disturbances are common among patients with dementia. Symptomatic manifestations vary according to dementia subtype, with one commonly shared pattern--the irregular sleep-wake rhythm (ISWR), a circadian disorder characterized by an absence of the sleepwake cycle's circadian synchronization. Hypothesized mechanisms of circadian rhythm disturbance include suprachiasmatic nucleus (SCN) circadian pacemaker damage, pineal gland and melatonin secretion alterations, and reduced zeitbeigers and decreased input to the SCN. Management options include prescribed sleep/wake scheduling, light therapy, melatonin, physical and social activity, and mixed modality. The mixed-modality approach is the most effective method in treating ISWR. Pharmacologic interventions are controversial, with no evidence supporting their effectiveness while associated with multiple side effects. They should be used with caution and only be considered as short-term therapy. All treatment strategies should be individualized to achieve the best outcomes.

Managing the patient with shift-work disorder.

Behavioral measures, eg, exercise and improved sleep hygiene, can enhance sleep quality and combat insomnia and excessive sleepiness (ES) in shift workers and individuals with shift-work disorder (SWD). Napping before a shift followed by consumption of a caffeinated drink and, if appropriate, scheduled naps at work, may improve ES in patients with SWD. Use of bright light therapy to partially re-entrain the circadian clock should be explored for all night-shift workers-particularly those with SWD. The wakefulness-promoting agents armodafinil and modafinil are FDA approved for the treatment of ES in patients with SWD. Alongside nonpharmacologic interventions, they can be included in a comprehensive management plan for SWD. Melatonin or other sleep-promoting agents may help shift workers achieve sleep during required rest periods and when adjusting to night-shift work; studies are needed in patients with SWD to better evaluate the utility of these agents in this population.