Pharmacotherapy of fibromyalgia

There have been substantial advances in the pharmacotherapy of fibromyalgia (FM), which have occurred in parallel with advances in our understanding of the pathophysiology of FM in the past several years. Consortia of researchers have established a core set of symptom domains, which constitute the condition of FM, including pain, fatigue, sleep and mood disturbance and cognitive dysfunction, which significantly impact a patient's overall well-being and ability to function. Outcome measures, which assess these domains, both singly and in composite format, are showing increasing reliability to discriminate between the treatment and placebo arms in clinical trials of emerging therapies, which are targeting the pathophysiologic mechanisms of FM. Several different medications, including the serotonin and norepinephrine reuptake inhibitors, duloxetine and milnacipran, and the α(2)δ modulator, pregabalin, have been approved by the Food and Drug Administration (FDA) for the management of FM, based on their clinically meaningful and durable effect on pain in monotherapy trials. They also have been shown to beneficially effect patient global impression of change, function and variably other key symptom domains, such as fatigue, sleep disturbance and cognition. Other medicines, although they have not gone through the formal approval process, have also shown efficacy in multiple domains of FM. Although combination trials have generally not yet been performed, the combined use of medicines with complementary mechanisms of action is rational, and, when done with appropriate caution, will likely be shown to be safe and well tolerated. Adjunctive therapy with medicines targeted at specific symptom domains, such as sleep, as well as treatments aimed at common co-morbid conditions, such as irritable bowel syndrome, or disease states, such as rheumatoid arthritis, should be considered for the purpose of reducing the patient's overall symptom burden. Current therapies neither completely treat FM symptoms nor benefit all patients; thus, further research on new therapies with different mechanisms and side-effect profiles is needed.     

Gastroesophageal reflux disease and sleep disturbances

Nighttime reflux during sleep plays a crucial role in several conditions associated with gastroesophageal reflux disease (GERD). Reflux patterns during arousal and sleep are different because of delayed gastric emptying, reduced esophageal peristalsis, decreases in swallowing and salivary secretion, and prolonged esophageal clearance during sleep. Clinical evidence strongly suggests that GERD is associated with sleep disturbances such as shorter sleep duration, difficulty falling asleep, arousals during sleep, poor sleep quality, and awakening early in the morning. New mechanisms on how GERD affects sleep have been recently identified by using actigraphy, and sleep deprivation was found to induce esophageal hyperalgesia to acid perfusion. Thus, the relationship between GERD and sleep disturbances is bidirectional. Among lifestyle modifications, avoidance of a late night meal plays a role in prevention of nighttime reflux. Treatment with a proton pump inhibitor (PPI) improves both nighttime symptoms and subjective sleep parameters, but its effects on objective sleep parameters remain unclear. Better control of nighttime acid secretion by administering a PPI at different times or by providing a double-dose PPI, adding H(2) receptor antagonists, or other new agents is proposed. The effects of such treatments on sleep disturbances remain to be elucidated. GERD patients with sleep disturbances report more severe symptoms and poorer quality of life as compared to those without sleep disturbances. Consequently, GERD should also be classified as GERD with sleep disturbance and GERD without sleep disturbance.     

Nightly variation in sleep-related respiratory disturbance in older adults

This study investigated variation in respiratory disturbance during sleep. Sixty-six healthy elderly subjects (mean age = 67.2) underwent two consecutive nights of polysomnography. Respiratory disturbance was assessed by Respiratory Disturbance Index (RDI), the number of events per hour of sleep. Results indicated an increase in RDI from Night 1 to Night 2. Fourteen subjects increased their RDI by over 2.5, and eight by over 5.0, events per hour on Night 2. The increase was not a function of increased REM on Night 2. Age was positively related to RDI on individual lab nights but unrelated to nightly variation in RDI. Subjects without complaints of insomnia were more likely to show increases in RDI, perhaps reflecting the sounder sleep of this group on the second laboratory night. This study suggests that a single night of polysomnography is likely to underestimate the absolute level of respiratory disturbance seen in a subsequent recording night. Studies placing prevalence of such disturbance in the elderly at approximately 30% are thus likely to be underestimates. Whether this "error" is important will depend ultimately upon the meaning of various absolute levels of respiratory disturbance in healthy older persons.     

Nightly variation in sleep-related respiratory disturbance in older adults

This study investigated variation in respiratory disturbance during sleep. Sixty-six healthy elderly subjects (mean age = 67.2) underwent two consecutive nights of polysomnography. Respiratory disturbance was assessed by Respiratory Disturbance Index (RDI), the number of events per hour of sleep. Results indicated an increase in RDI from Night 1 to Night 2. Fourteen subjects increased their RDI by over 2.5, and eight by over 5.0, events per hour on Night 2. The increase was not a function of increased REM on Night 2. Age was positively related to RDI on individual lab nights but unrelated to nightly variation in RDI. Subjects without complaints of insomnia were more likely to show increases in RDI, perhaps reflecting the sounder sleep of this group on the second laboratory night. This study suggests that a single night of polysomnography is likely to underestimate the absolute level of respiratory disturbance seen in a subsequent recording night. Studies placing prevalence of such disturbance in the elderly at approximately 30% are thus likely to be underestimates. Whether this “error” is important will depend ultimately upon the meaning of various absolute levels of respiratory disturbance in healthy older persons.     

A comparison of sleep in rheumatic and non-rheumatic patients

The St. Mary's Hospital Sleep Questionnaire was used to investigate sleep in 439 hospitalized rheumatic and non-rheumatic patients. This questionnaire enabled an evaluation of both the level of sleep disturbance and the causes of such disturbance. The findings from this study indicated that there was little difference in the level of sleep disturbance between rheumatic and non-rheumatic patients. The sleep problem most frequently cited by rheumatic patients was pain. Noise appeared to be the worst environmental sleep problem in these patients. The only significant difference in the sleep problems reported by rheumatic and non-rheumatic patients, was that pain was cited more frequently in the rheumatic group. In order to determine whether sleep varied according to type of rheumatic disease, the rheumatic patients were divided into four diagnostic groups (rheumatoid arthritis; seronegative spondarthritis; osteoarthritis; other conditions). There were no significant differences between these groups in sleep disturbance or reported sleep problems.     

Sleep in bipolar patients

Background  Sleep disturbance has been described in bipolar disorder (BPD). Specific complaints may include frequent nighttime awakenings, poor quality of sleep, reduction in total sleep time, and nightmares. Most patients with BPD also report insomnia when in depression, but a significant percentage of patients report hypersomnia symptoms with prolonged nighttime sleep, difficulty in wakening, and excessive daytime sleepiness. Objectives  The present study aims to investigate whether bipolar patients with sleep disorders presented impairment in quality of life, disability, and global function. Methods  One hundred ninety bipolar patients type-I diagnosed by application of Structured Clinician Interview for DSM-IV Disorders (SCID), were distributed in two groups based on absence or presence of sleep disorders. Quality of life, disability, and global dysfunction were evaluated using the Health Organization’s Quality of Life instrument (WHOQOL-Brief), the Sheehan Disability Scale, and the Global Assessment of Functioning (GAF), respectively. Results  Sleep complaints have negative influence on general quality of life, observed by decreased scores in WHOQOL and GAF domains and increased Sheehan scores, indicating the importance of maintenance of normal sleep in bipolar patients. Conclusion  Our results suggest that sleep complains impair quality of life and global function. Collectively, further studies are warranted to investigate the impairment of sleep disturbance on others neurotrophic factors and neurochemical pathways.     

Sleep disturbance and HIV disease

HIV-associated sleep disturbance may be easy to overlook, underdiagnose, and undertreat, due to the many medical and psychosocial problems faced by people with HIV disease. Identifying the cause of the disturbance and distinguishing between sleep disturbance and fatigue are critical for effective treatment. A thorough patient history can help clinicians provide accurate diagnosis and therapy. To date, there is no known remedy to correct HIV-associated sleep disturbance. Clinicians should consider behavior modification techniques, such as relaxation training, habit training, and reversal of negative conditioning, before administering sleep medications.     

Sleep,immunity and inflammation in gastrointestinal disorders

Sleep disorders have become a global issue,and discovering their causes and consequences are the focus of many research endeavors.An estimated 70 million Americans suffer from some form of sleep disorder.Certain sleep disorders have been shown to cause neurocognitive impairment such as decreased cognitive ability,slower response times and performance detriments.Recent research suggests that individuals with sleep abnormalities are also at greater risk of serious adverse health,economic consequences,and most importantly increased all-cause mortality.Several research studies support the associations among sleep,immune function and inflammation.Here,we review the current research linking sleep,immune function,and gastrointestinal diseases and discuss the interdependent relationship between sleep and these gastrointestinal disorders.Different physiologic processes including immune system and inflammatory cytokines help regulate the sleep.The inflammatory cytokines such as tumor necrosis factor,interleukin-1(IL-1),and IL-6 have been shown to be a significant contributor of sleep disturbances.On the other hand,sleep disturbances such as sleep deprivation have been shown to up regulate these inflammatory cytokines.Alterations in these cytokine levels have been demonstrated in certain gastrointestinal diseases such as inflammatory bowel disease,gastro-esophageal reflux,liver disorders and colorectal cancer.In turn,abnormal sleep brought on by these diseases is shown to contribute to the severity of these same gastrointestinal diseases.Knowledge of these relationships will allow gastroenterologists a great opportunity to enhance the care of their patients.     

Effectiveness and safety of acupuncture in treating sleep disturbance in dementia patients: A PRISMA-compliant systematic review and limitations of current evidence

Background:Dementia is of increasing importance, as it is a major public health problem worldwide. Sleep disturbance is common in dementia patients and may be associated with worse cognitive symptoms or behavioral and psychological symptoms of dementia. Non-pharmacological approaches, such as acupuncture, for treating this clinical condition are gaining importance. This study aimed to comprehensively search and analyze randomized controlled clinical trials (RCTs) of acupuncture in treating sleep disturbance or sleep disorders in dementia patientsMethods:A comprehensive search was conducted from 12 electronic databases on December 2, 2020. We included RCTs reporting the effectiveness and safety of acupuncture in treating sleep disorders or disturbance in dementia patients. The methodological quality of the included studies was assessed using the Cochrane Collaboration''s risk-of-bias tool.Results:Five articles with four original RCTs met the inclusion criteria. These studies reported clinical data suggesting that adjuvant acupuncture for hypnotics, and ear acupressure in dementia patients with sleep disorders or sleep disturbance may have clinical benefits in certain sleep-related parameters and total effective rate (TER). Only 1 study reported the safety profile of the intervention, and no acupuncture-related adverse reactions were reported. Some studies compared 2 kinds of acupuncture methods, and found that specific acupuncture methods were superior to conventional acupuncture in improving sleep-related parameters, cognitive function and TER. The methodological quality of the included clinical studies was not high.Conclusions:There were limited acupuncture studies on this topic. Given the number of studies included and their sample size, methodological quality, and heterogeneities, clinically relevant conclusions could not be drawn. Further clinical studies are needed in this field considering its urgency and importance.     

Sleep disturbance and obesity: changes following surgically induced weight loss

BACKGROUND: Obesity causes sleep disturbance and is the most significant risk factor for sleep apnea. Only surgical methods provide substantial sustained weight loss for most severely obese subjects. OBJECTIVE: To study sleep disturbance in patients undergoing laparoscopic adjustable gastric banding with a commercially available product (Lap-Band). METHODS: In this study, 313 consecutive patients with severe obesity (body mass index [calculated as weight in kilograms divided by the square of height in meters] >35) completed a preoperative sleep questionnaire and clinical assessment. One hundred twenty-three patients completed the same assessment 12 months after surgery. The characteristics of sleep disturbance and changes in responses to weight loss have been assessed. RESULTS: There was a high prevalence of significantly disturbed sleep in men (59%) and women (45%), with women less likely to have had their sleep disturbance investigated. Observed sleep apnea was more common in men, but daytime sleepiness was not affected by sex. Waist circumference was the best clinical measure predicting observed sleep apnea (R = 0.36; P<.001). The group lost an average of 48% (SD, 16%) of excess weight by 12 months. There was a significant improvement in the responses to all questions at follow-up, with habitual snoring reduced to 14% (preoperative value, 82%), observed sleep apnea to 2% (preoperative value, 33%), abnormal daytime sleepiness to 4% (preoperative value, 39%), and poor sleep quality to 2% (preoperative value, 39%) (P<.001 for all). CONCLUSIONS: Obesity-related sleep disorders improve markedly with weight loss. Sustainable weight loss should be a primary aim in the management of severely obese patients with significant sleep disturbance, including sleep apnea. Low-risk laparoscopic obesity surgery should be considered for selected patients with this important comorbidity.     

Sleep, health, and aging. Bridging the gap between science and clinical practice

Problems with sleep are common with advancing years and occur in over half of adults age 65 and older. It has been estimated that insomnia affects about a third of the older population in this country. This inability to have restful sleep at night results in excessive daytime sleepiness, attention and memory problems, depressed mood, falls, and lowered quality of life. Other factors associated with aging, such as disease, changes in environment, or concurrent age-related processes also may contribute to problems of sleep. Data indicate that age by itself does not predict incident complaints of insomnia, even in the presence of lowered sleep efficiency and decreased proportion of slow-wave sleep. Rather, the prevalence of insomnia and other sleep disorders is high in the geriatric population due to the associated comorbidities common in late life. It is now evident that disturbance in sleep can also lead to adverse changes in functioning of a number of body systems.     

Insomnia

Effective management of insomnia begins with recognition and adequate assessment. Family doctors and other health care providers such as practice nurses and psychologists should routinely enquire about sleep habits as a component of overall health assessment. Identification and treatment of primary psychiatric disorders, medical conditions, circadian disorders, or specific physiological sleep disorders--eg, sleep apnoea and periodic limb movement disorder--are essential steps in management of insomnia. Conditioned aspects of insomnia can be primary (psychophysiological insomnia) or may complicate sleep disturbance owing to other causes. Approved hypnotic drugs have clearly been shown to improve subjective and objective sleep measures in various short-term situations. Despite widespread use of standard hypnotics and sedating antidepressants for chronic insomnia, their role for this indication still remains to be further defined by research evidence. Non-pharmacological treatments, particularly stimulus control and sleep restriction, are effective for conditioned aspects of insomnia and are associated with durable long-term improvement in sleep.     

Sleep-Disordered Breathing—Do We Have to Change Gears in Heart Failure?

The majority of patients with heart failure have sleep-disordered breathing (SDB)—with central (rather than obstructive) sleep apnoea becoming the predominant form in those with more severe disease. Cyclical apnoeas and hypopnoeas are associated with sleep disturbance, hypoxaemia, haemodynamic changes, and sympathetic activation. Such patients have a worse prognosis than those without SDB. Mask-based therapies of positive airway pressure targeted at SDB can improve measures of sleep quality and partially normalise the sleep and respiratory physiology, but recent randomised trials of cardiovascular outcomes in central sleep apnoea have been neutral or suggested the possibility of harm, likely from increased sudden death. Further randomised outcome studies (with cardiovascular mortality and hospitalisation endpoints) are required to determine whether mask-based treatment for SDB is appropriate for patients with chronic systolic heart failure and obstructive sleep apnoea, for those with heart failure with preserved ejection fraction, and for those with decompensated heart failure. New therapies for sleep apnoea—such as implantable phrenic nerve stimulators—also require robust assessment. No longer can the surrogate endpoints of improvement in respiratory and sleep metrics be taken as adequate therapeutic outcome measures in patients with heart failure and sleep apnoea.     

阻塞性睡眠呼吸暂停低通气综合征与哮喘

最近研究表明阻塞性睡眠呼吸暂停低通气综合征(OSAHS)是支气管哮喘急性加重的独立危险因素。OSAHS常涉及睡眠时上气道吸气气流受限及气道塌陷,常与日间症状如嗜睡、抑郁、精力难以集中等相关。支气管哮喘常表现为气道慢性炎症、气道高反应、可逆性气道气流受限等。现已有大量学者对其相关性作出研究,但未达成统一共识。目前认为神经反射因素、胃食管反流、气道及全身炎症反应、睡眠结构紊乱、肥胖、心血管疾病、激素治疗及鼻部疾病等可能是OSAHS与哮喘相互影响及作用的机制。本文就OSAHS与哮喘的相关性及其机制作一综述。     

Sleep and circadian rhythm disorders in fibromyalgia

Fibromyalgia (FM) is a syndrome of generalized muscle pain that is also associated with equally distressing symptoms of sleep disturbance and fatigue. FM shows clinical overlap with other stress-associated disorders, including chronic fatigue syndrome (CFS) and depression. All of these conditions have the features of disrupted sleep patterns and dysregulated biologic circadian rhythms, such as stress hormone secretion. This review focuses on the role of sleep and circadian rhythm disorders in FM and, in the absence of any specific treatment for FM, presents a pragmatic therapeutic approach aimed at identifying and treating comorbid sleep and depressive disorders, optimizing sleep habits, and judicious use of pharmacologic agents.     

Sleep disturbance in early HIV infection

Immune proteins may have a role in HIV-related sleep disturbance. Observations of two notable sleep changes, increase in slow wave sleep and the need for too much sleep, during early stage HIV infection prompted researchers to investigate the neurological changes occurring with sleep structure alterations. When psychiatric, psychological, medical, and pharmacological variables are excluded, researchers begin to examine the effect of HIV infection on the brain itself. While reasons for sleep structure distortion remain unknown, new data suggests that irregular levels of peptides may be involved. Upcoming clinical trials will evaluate medications for efficacy in treating HIV-related sleep disturbance. This could lead to therapies that restore sleep and improve quality of life.     

Sleep disturbance and its correlates among elderly Japanese

Although sleep disturbance is a major public health problem in the elderly, few studies have examined the association between sleep disturbance and other related factors in Japan. We examined correlates of sleep disturbance among Japanese elderly. Participants in this cross-sectional study (255 men and 263 women) were those enrolled in a population-based health examination for 65 year-old residents in N City, Japan in 1996 and 1997. Epidemiological data were collected by a self-administered questionnaire. Sleep disturbances were assessed by three common symptoms: difficulty in falling asleep, frequent awakening at night and not feeling rested in the morning. The mean sleep duration was longer in men than in women (7.2 vs 6.8 h, P<0.01), and women reported difficulty in falling asleep more frequently than men (22.4 vs 15.3%, P<0.05). Sleep disturbances were associated with low educational attainment, retirement from work, higher body mass index (BMI), irregular bedtime, history of cardiovascular disease, arthritis or joint pain and prostatic hypertrophy, and lower subjective well-being in men, and the use of sleeping pills and depression in both genders, but not with marital status, residential status, smoking habits, exercise, limited instrumental activity of daily living, and past episode of such chronic diseases as hypertension and stroke. Our study suggests a close association of sleep disturbances among elderly Japanese with several medical/psychiatric health problems that are usually more prevalent in such an age group. Our findings emphasize the realistic need for clinicians to take underlying health problems into consideration when their patients complain of sleep-related symptoms.     

Sleep disturbance in Parkinson disease

Sleep disturbance is common in patients with Parkinson disease (PD), but it is often undetected due to inadequate history taking and poor self-reporting. Impaired sleep can have a severe impact on health, general well being, and quality of life. Sleep problems in PD have many potential causes, including the direct effect of PD itself, adverse events of anti-Parkinsonian medications, daytime sleep disturbance, age related causes, and other comorbidities. Patients with PD and their sleep partners should be asked about sleep disturbances and other night-time symptoms. Treatment strategies rely on identifying causal factors and need to be tailored to the individual and reviewed regularly.     

Sleep quality,sleep duration and sexual health among older people: Findings from the English Longitudinal Study of Ageing

ContextHow sleep quality and sexual health are associated among community-dwelling individuals remains largely unknown.ObjectiveWe examined the association of sleep disturbance and sleep duration with a range of measures assessing sexual activities, functioning and concerns in a representative sample of older people.MethodsParticipants were community-dwelling adults aged 50-90+ years from wave 6 (2012/2013) of the English Longitudinal Study of Ageing (ELSA) who reported any sexual activity in the last year. Sleep disturbance, sleep duration and sexual health were measured by self-report at wave 6. Retrospective reports of restless sleep (waves 1–6 [2002–2013]) were also examined. The association between sleep measures and sexual health was assessed using logistic regressions stratified by gender and adjusted for demographic, health and lifestyle factors with results expressed as odds ratios (OR) and 95% confidence intervals (CI).ResultsAmong both men and women disturbed sleep was associated with reported declines in sexual activity and function over the last year, and increased concern about their sexual desire, frequency of sexual activity and sexual functioning. Robust associations between high sleep disturbance and vaginal pain (OR = 1.67, 95% CI = 1.21, 2.31) and vaginal dryness (OR = 1.69, 95% CI = 1.24, 2.30) were also observed among women. Retrospective reports of restless sleep showed a dose-response relationship with reported declines in sexual health over the last year, and increased concerns about sexual expression and functioning.ConclusionsSelf-reported sleep disturbance and retrospective restless sleep were mainly associated with subjective assessments of recent declines in sexual activity and functioning, and higher levels of sexual concerns.     

强直性脊柱炎患者睡眠状态问卷研究

目的研究强直性脊柱炎(AS)患者睡眠状态,探讨睡眠障碍、疼痛之间的性别差异。方法57例男性和23例女性AS患者,进行睡眠状态问卷调查,并与临床资料进行比较。结果74%的女性和46%的男性AS患者有睡眠障碍(P<0.05),造成睡眠障碍的主要原因是疼痛。睡眠障碍和疼痛、晨僵及BathAS活动指数(BASDAI)评分之间存在相关性。结论睡眠障碍是AS的常见问题,与疼痛、病情活动相关,男性女性AS患者之间主观睡眠障碍、疼痛差异存在统计学意义。