text:
Sleep Disorders (PDQ®): Supportive care – Health Professional Information [NCI]
This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER.
Sleep disturbances occur in about 10% to 15% of the general population [1] and are often associated with situational stress, illness, aging, and drug treatment.[2] It is estimated that one-third to one-half of people with cancer experience sleep disturbance.[3,4] Physical illness, pain, hospitalization, drugs and other treatments for cancer, and the psychological impact of a malignant disease may disrupt the sleeping patterns of persons with cancer.[5] Poor sleep adversely affects daytime mood and performance. In the general population, persistent insomnia has been associated with a higher risk of developing clinical anxiety or depression.[6] Sleep disturbances and, ultimately, sleep-wake cycle reversals can be early signs of a developing delirium. (Refer to the PDQ summary on Delirium for more information.) Adequate sleep may increase the cancer patient's pain tolerance.
Sleep consists of two phases: rapid eye movement (REM) sleep and non-REM (NREM) sleep.[7] REM sleep, also known as dream sleep, is the active or paradoxic phase of sleep in which the brain is active. NREM sleep is the quiet or restful phase of sleep. NREM, also referred to as slow wave sleep, is divided into four stages of progressively deepening sleep based on electroencephalogram findings.
The stages of sleep occur in a repeated pattern or cycle of NREM followed by REM, with each cycle lasting approximately 90 minutes. The sleep cycle is repeated four to six times during a 7- to 8-hour sleep period.[7] The sleep-wake cycle is dictated by an inherent biological clock or circadian rhythm. Disruptions in individual sleep patterns can disrupt the circadian rhythm and impair the sleep cycle.[8]
Five major categories of sleep disorders have been defined by the Sleep Disorders Classification Committee of the American Academy of Sleep Medicine:[9]
- Disorders of initiating and maintaining sleep (insomnias).
- Sleep-related breathing disorders (sleep apnea).
- Disorders of excessive somnolence (hypersomnias).
- Disorders of the sleep-wake cycle (circadian rhythm sleep disorders).
- Dysfunctions associated with sleep, sleep stages, or partial arousals (parasomnias).
In this summary, unless otherwise stated, evidence and practice issues as they relate to adults are discussed. The evidence and application to practice related to children may differ significantly from information related to adults. When specific information about the care of children is available, it is summarized under its own heading.
- National Sleep Foundation: Insomnia. Arlington, Va: National Sleep Foundation, 2018. Available online. Last accessed January 5, 2018.
- Sateia MJ, Pigeon WR: Identification and management of insomnia. Med Clin North Am 88 (3): 567-96, vii, 2004.
- Palesh OG, Roscoe JA, Mustian KM, et al.: Prevalence, demographics, and psychological associations of sleep disruption in patients with cancer: University of Rochester Cancer Center-Community Clinical Oncology Program. J Clin Oncol 28 (2): 292-8, 2010.
- Savard J, Morin CM: Insomnia in the context of cancer: a review of a neglected problem. J Clin Oncol 19 (3): 895-908, 2001.
- Berger AM: Update on the state of the science: sleep-wake disturbances in adult patients with cancer. Oncol Nurs Forum 36 (4): E165-77, 2009.
- Ohayon MM, Caulet M, Lemoine P: Comorbidity of mental and insomnia disorders in the general population. Compr Psychiatry 39 (4): 185-97, 1998 Jul-Aug.
- Hirshkowitz M: Normal human sleep: an overview. Med Clin North Am 88 (3): 551-65, vii, 2004.
- Hrushesky WJ, Grutsch J, Wood P, et al.: Circadian clock manipulation for cancer prevention and control and the relief of cancer symptoms. Integr Cancer Ther 8 (4): 387-97, 2009.
- American Academy of Sleep Medicine: The International Classification of Sleep Disorders: Diagnostic & Coding Manual. 2nd ed. Westchester, Ill: American Academy of Sleep Medicine, 2005.
Sleep Disturbance in Cancer Patients
Cancer patients are at great risk of developing insomnia and disorders of the sleep-wake cycle. Insomnia is the most common sleep disturbance in this population and is most often secondary to physical and/or psychological factors related to cancer and/or cancer treatment.[1,2,3,4,5] Anxiety and depression—common psychological responses to the diagnosis of cancer, cancer treatment, and hospitalization—are highly correlated with insomnia.[6,7];[8][Level of evidence: II]
Sleep disturbances may be exacerbated by paraneoplastic syndromes associated with steroid production and by symptoms associated with tumor invasion, such as draining lesions, gastrointestinal (GI) and genitourinary (GU) alterations, pain, fever, cough, dyspnea, pruritus, and fatigue. Medications—including vitamins, corticosteroids, neuroleptics for nausea and vomiting, and sympathomimetics for the treatment of dyspnea—as well as other treatment factors can negatively impact sleep patterns.
Side effects of treatment that may affect the sleep-wake cycle include the following:[9];[8][Level of evidence: II]
- Pain.
- Anxiety.
- Night sweats/hot flashes (refer to the PDQ summary on Hot Flashes and Night Sweats for more information).
- GI disturbances (e.g., incontinence, diarrhea, constipation, or nausea).
- GU disturbances (e.g., incontinence, retention, or GU irritation).
- Respiratory disturbances.
- Fatigue.
Sustained use of the following can cause insomnia:
- Sedatives and hypnotics (e.g., glutethimide, benzodiazepines, pentobarbital, chloral hydrate, secobarbital sodium, and amobarbital sodium).
- Anticonvulsants (e.g., phenytoin).
- Corticosteroids.
- Oral contraceptives.
- Monoamine oxidase inhibitors.
- Methyldopa.
- Propranolol.
- Atenolol.
- Alcohol.
- Thyroid preparations.
In addition, withdrawal from the following substances may cause insomnia:
- Central nervous system depressants (e.g., barbiturates, opioids, glutethimide, chloral hydrate, methaqualone, ethchlorvynol, alcohol, and over-the-counter and prescription antihistamine sedatives).
- Benzodiazepines.
- Major tranquilizers.
- Tricyclic and monamine oxidase inhibitor antidepressants.
- Illicit drugs (e.g., marijuana, cocaine, phencyclidine, and opioids).
Hypnotics can interfere with rapid eye movement (REM) sleep, resulting in increased irritability, apathy, and diminished mental alertness. Abrupt withdrawal of hypnotics and sedatives may lead to symptoms such as nervousness, jitteriness, seizures, and REM rebound. REM rebound has been defined as a marked increase in REM sleep with increased frequency and intensity of dreaming, including nightmares.[10] The increased physiologic arousal that occurs during REM rebound may be dangerous for patients with peptic ulcers or a history of cardiovascular problems. Newer medications for insomnia have reduced adverse effects.[11]
The sleep of hospitalized patients is likely to be frequently interrupted by treatment schedules, hospital routines, and roommates, which singularly or collectively alter the sleep-wake cycle. Other factors influencing sleep-wake cycles in the hospital setting include patient age, comfort, pain, and anxiety; and environmental noise and temperature.[12]
Consequences of sleep disturbances can influence outcomes of therapeutic and supportive care measures.[13] The patient with mild to moderate sleep disturbances may experience irritability and inability to concentrate, which may in turn affect the patient's compliance with treatment protocols, ability to make decisions, and relationships with significant others. Depression and anxiety can also be caused by sleep disturbances. Supportive care measures are directed toward promoting quality of life and adequate rest.
- Savard J, Morin CM: Insomnia in the context of cancer: a review of a neglected problem. J Clin Oncol 19 (3): 895-908, 2001.
- Savard J, Simard S, Blanchet J, et al.: Prevalence, clinical characteristics, and risk factors for insomnia in the context of breast cancer. Sleep 24 (5): 583-90, 2001.
- Savard J, Simard S, Hervouet S, et al.: Insomnia in men treated with radical prostatectomy for prostate cancer. Psychooncology 14 (2): 147-56, 2005.
- Otte JL, Carpenter JS, Russell KM, et al.: Prevalence, severity, and correlates of sleep-wake disturbances in long-term breast cancer survivors. J Pain Symptom Manage 39 (3): 535-47, 2010.
- Lee ES, Lee MK, Kim SH, et al.: Health-related quality of life in survivors with breast cancer 1 year after diagnosis compared with the general population: a prospective cohort study. Ann Surg 253 (1): 101-8, 2011.
- Bardwell WA, Profant J, Casden DR, et al.: The relative importance of specific risk factors for insomnia in women treated for early-stage breast cancer. Psychooncology 17 (1): 9-18, 2008.
- Palesh OG, Roscoe JA, Mustian KM, et al.: Prevalence, demographics, and psychological associations of sleep disruption in patients with cancer: University of Rochester Cancer Center-Community Clinical Oncology Program. J Clin Oncol 28 (2): 292-8, 2010.
- Van Onselen C, Cooper BA, Lee K, et al.: Identification of distinct subgroups of breast cancer patients based on self-reported changes in sleep disturbance. Support Care Cancer 20 (10): 2611-9, 2012.
- Vena C, Parker K, Cunningham M, et al.: Sleep-wake disturbances in people with cancer part I: an overview of sleep, sleep regulation, and effects of disease and treatment. Oncol Nurs Forum 31 (4): 735-46, 2004.
- Chouinard G: Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound. J Clin Psychiatry 65 (Suppl 5): 7-12, 2004.
- Barbera J, Shapiro C: Benefit-risk assessment of zaleplon in the treatment of insomnia. Drug Saf 28 (4): 301-18, 2005.
- Boonstra L, Harden K, Jarvis S, et al.: Sleep disturbance in hospitalized recipients of stem cell transplantation. Clin J Oncol Nurs 15 (3): 271-6, 2011.
- Sateia MJ, Doghramji K, Hauri PJ, et al.: Evaluation of chronic insomnia. An American Academy of Sleep Medicine review. Sleep 23 (2): 243-308, 2000.
Assessment is the initial step in management strategies. Assessment data should include documentation of predisposing factors, sleep patterns, emotional status, exercise and activity levels, diet, symptoms, medications, and caregiver routines.[1] The sections below outline recommendations for a sleep history and physical examination. Data can be retrieved from multiple sources: the patient's subjective report of sleep difficulty, objective observations of behavioral and physiologic manifestations of sleep disturbances, and reports from the patient's significant others regarding the patient's quality of sleep.[2] Use of the Insomnia Severity Index is suggested to screen for insomnia in clinical settings.[3,4]
The diagnosis of insomnia is primarily based on a careful, detailed medical and psychiatric history. The American Academy of Sleep Medicine has produced guidelines for the use of polysomnography as an objective tool in evaluating insomnia. The routine polysomnogram includes the monitoring of electroencephalography, electro-oculography, electromyography, effort of breathing and air flow, oxygen saturation, electrocardiography, and body position. Polysomnography is the major diagnostic tool in sleep disorders and is indicated in the evaluation of suspected sleep-related breathing disorders and periodic limb movement disorder, and when the cause of insomnia is uncertain or when behavioral or pharmacologic therapy is unsuccessful.[5][Level of evidence: IV]
Sleep disturbance has been shown to change throughout the cancer trajectory, which supports the need to assess sleep throughout the patient's cancer experience. One descriptive study [6][Level of evidence: II] involving 398 women with breast cancer used the General Sleep Disturbance Scale (GSDS) to identify three different sleep trajectories when self-reported sleep was evaluated beginning before surgery and continuing for 6 months. One group (55% of the sample) had a high level of sleep disturbance throughout the study, defined as scores on the GSDS of around 58 to 60 at all data points. A second group (40% of the sample) was considered to have a low level of sleep disturbance throughout, defined as scores on the GSDS in the low 30s at each data point. The final group (5% of the sample) started out high with scores around 62, but their scores decreased to below 30 over the first 4 months and remained there through month 6. Women in the group who were identified as having a more severe sleep disorder were significantly younger, had more comorbidities, had a lower performance status, and experienced hot flashes.
Risk Factors for Sleep Disorders
- Disease factors, including paraneoplastic syndromes with increased steroid production; and symptoms associated with tumor invasion (e.g., obstruction, pain, fever, shortness of breath, pruritus, and fatigue).
- Treatment factors, including symptoms related to surgery (e.g., pain, frequent monitoring, and use of opioids); chemotherapy (e.g., exogenous corticosteroids); and symptoms related to chemotherapy.
- Medications such as opioids; sedatives/hypnotics; steroids; caffeine/nicotine; some antidepressants; and dietary supplements, including some vitamins, diet pills, and other products promoting weight loss and appetite suppression.
- Environmental factors.
- Physical and/or psychological stressors.
- Depression (refer to the PDQ summary on Depression for more information).
- Anxiety (refer to the Anxiety Disorders: Description and Etiology section in the PDQ summary on Adjustment to Cancer: Anxiety and Distress for more information).
- Delirium (refer to the PDQ summary on Delirium for more information).
- Daytime seizures, snoring, and headaches.
Characterization of Sleep
- Usual patterns of sleep, including usual bedtime, routine before retiring (e.g., food, bath, and medications), length of time before onset of sleep, and duration of sleep (awaking episodes during night, ability to resume sleep, and usual time of awakening).
- Characteristics of disturbed sleep (changes after diagnosis, treatment, and/or hospitalization).
- Perception of significant others as to the quantity and quality of patient's sleep.
- Family history of sleep disorders.
- American Academy of Sleep Medicine: The International Classification of Sleep Disorders: Diagnostic & Coding Manual. 2nd ed. Westchester, Ill: American Academy of Sleep Medicine, 2005.
- Perlis ML, Jungquist C, Smith MT, et al.: Cognitive Behavioral Treatment of Insomnia: A Session-by-Session Guide. New York, NY: Springer Science+Business Media LLC, 2008.
- Bastien CH, Vallières A, Morin CM: Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Med 2 (4): 297-307, 2001.
- Savard MH, Savard J, Simard S, et al.: Empirical validation of the Insomnia Severity Index in cancer patients. Psychooncology 14 (6): 429-41, 2005.
- Littner M, Hirshkowitz M, Kramer M, et al.: Practice parameters for using polysomnography to evaluate insomnia: an update. Sleep 26 (6): 754-60, 2003.
- Van Onselen C, Cooper BA, Lee K, et al.: Identification of distinct subgroups of breast cancer patients based on self-reported changes in sleep disturbance. Support Care Cancer 20 (10): 2611-9, 2012.
Management of sleep disturbances should focus on treatment of problems with falling asleep, staying asleep, or early morning awakenings. Other areas to manage include symptoms from cancer and its treatment, and the identification and management of environmental and psychological factors. When sleep disturbances are caused by symptoms of cancer or treatment, measures that control or alleviate symptoms are often the key to resolving sleep disturbances. Management of sleep disturbances combines nonpharmacologic and pharmacologic approaches individualized for the patient.
Nonpharmacologic Management of Sleep Disturbances
Many people who experience insomnia have been found to practice poor sleep hygiene (such as smoking and drinking excessive alcohol just before bedtime), which can exacerbate or perpetuate insomnia.[1][Level of evidence: III] Therefore, a complete assessment of sleep hygiene (i.e., time in bed; napping during the day; intake of caffeine, alcohol, or foods that are heavy, spicy, or sugary; exercise; and sleep environment) and use of behavioral management strategies (i.e., fixed bedtime; restrictions on smoking, diet, and excessive alcohol 4–6 hours before bedtime; and increased exercise) may prove effective in reducing sleep disturbance.
Sleep hygiene in an inpatient setting involves modifying the sleep environment to decrease sleep disruption. Minimizing noise, dimming or turning off lights, adjusting room temperature, and consolidating patient care tasks to reduce the number of interruptions can increase the amount of uninterrupted sleep.[2][Level of evidence: IV]
Cognitive strategies include restructuring negative thoughts, beliefs, and attitudes related to sleep and preventing excessive monitoring or worrying about getting enough sleep.[3] Behavioral strategies include stimulus control and sleep restriction. Both of these strategies seek to limit the time spent in bed that does not involve sleeping.[3,4,5] Several large, randomized trials and meta-analyses provide the evidence base for the efficacy of cognitive behavioral therapy (CBT) for insomnia (CBT-I).[3,6,7] Most of these trials have been in populations of patients without cancer. Components of CBT-I include the following:
- Cognitive restructuring.
- Behavioral strategies.
- Relaxation training.[4]
- Basic sleep hygiene education.
Relaxation therapy can be used to achieve both behavioral and cognitive outcomes, particularly when it is combined with imagery. Educational objectives around sleep hygiene are also used to treat insomnia and include content on the following:[4]
- Sleeping and waking up at regular times.
- Relaxing before bedtime.
- Creating a dark, comfortable sleep environment.
- Avoiding watching television or working in the bedroom.
- Getting ample daylight during nonsleep hours.
- Avoiding naps.
- Limiting caffeine.
- Getting regular exercise but no closer than 3 hours before bedtime.
Practice guidelines from the American Academy of Sleep Medicine clearly state that multicomponent therapy is recommended over single therapies. Because of insufficient evidence about its efficacy, sleep hygiene education should not be recommended as a single-modality management approach; other reviews state that sleep hygiene by itself is not effective.[6,8] Information about sleep hygiene, although not sufficient alone to combat sleep disturbances, should be included as a foundation of education related to sleep issues.
Several trials and meta-analyses have shown CBT-I to be at least as effective as conventional pharmacological therapies in treating primary chronic insomnia but without side effects.[6,7,9,10,11]
A four-arm study (conducted in patients with primary chronic insomnia) that evaluated zolpidem versus CBT versus zolpidem and CBT versus placebo reported a greater effect (P = .05) on sleep-onset latency for both groups involving CBT (change of 44%) versus the group receiving zolpidem alone (change of 29%).[12] Another study, also conducted in patients with primary chronic insomnia, evaluated CBT with temazepam alone versus a combination of CBT and temazepam versus placebo and found that all active treatments were significantly better than placebo and that there was a trend for the most improvement in the combined arm of CBT and temazepam.[13] Both arms with CBT demonstrated greater reductions in time to sleep onset than did the pharmacotherapy-alone arm (64% combined arm, 55% CBT arm, and 47% temazepam arm). A meta-analysis examining pharmacologic and behavioral studies for persistent insomnia found that pharmacologic and behavioral treatments did not differ in magnitude of benefit except for latency to sleep onset, in which greater reductions were found with behavioral therapy.[7]
There are limited data evaluating elements of CBT-I in cancer survivors, and most of the data that exist are about women with breast cancer. However, there have been at least four randomized controlled trials of CBT-I in cancer survivors.[14,15,16,17] The intervention was typically delivered over 5 to 8 weekly, small-group, in-person sessions. One of these trials included patients with cancer diagnoses other than breast cancer,[16] and results did not differ by cancer diagnosis. All studies showed improvements in numerous sleep parameters over time in the groups receiving CBT-I and demonstrated continued benefits 6 and 12 months later. Two of the four trials did not use active control arms.[14,16]
Studies using active control arms were in breast cancer survivors. One study compared CBT-I with sleep education and hygiene in 72 women,[15] while the other study used a healthy-eating education control group.[17] In the study comparing CBT-I with sleep education and hygiene, both groups significantly improved over time, with some significant differences between groups favoring CBT-I for time to fall asleep, time awake after sleep, total sleep time, and overall sleep quality. For example, the group receiving CBT-I improved by 30 minutes in time to fall asleep, compared with 11 minutes in the sleep education and hygiene group.[15]
In the study utilizing the healthy-eating education control, 219 women were randomly assigned to a behavioral therapy group consisting of stimulus control, general sleep hygiene (limiting naps, going to bed and rising at consistent times), and relaxation or to a healthy-eating education control group. The interventions were delivered by trained nurses in person, 2 days before the initiation of chemotherapy and before each chemotherapy treatment and 30 days after the last chemotherapy treatment. The nurses worked with women assigned to behavioral therapy to individualize and reinforce the behaviors. The Pittsburgh Sleep Quality Index (PSQI) was used to measure subjective sleep quality but was complemented by use of a sleep diary and wrist actigraph. Sleep quality significantly improved in the group receiving behavioral therapy, compared with the control group. These differences were also seen in data from the sleep diary and actigraph, with both showing significantly fewer awakenings in the behavioral therapy group.[18] Sleep quality was significantly better at 90 days and at 1 year in the behavioral therapy group, as measured by the PSQI but not the diary or actigraph.[17]
In some places, patients may not have access to in-person, professionally delivered CBT-I because of limited resources. A randomized controlled trial conducted with breast cancer survivors demonstrated that CBT-I delivered via digital media can also produce meaningful clinical improvements, although improvements are not as robust as those produced with professionally delivered CBT-I. This three-armed trial compared video-based CBT-I (VCBT-I) and professionally delivered CBT-I (PCBT-I) with a no-treatment control group in 242 breast cancer survivors. Both the VCBT-I and PCBT-I groups were associated with significantly greater improvements in diary-measured sleep variables, compared with the control group. The patients in the PCBT-I group reported greater improvements in some sleep outcomes and in fatigue and depression levels than did the VCBT-I group.[19]
Reference | Cancer Type | Sample Size and Design | Control and CBT-I Intervention | Measures | Outcomes |
ISI = Insomnia Severity Index; PCBT-I = professionally administered CBT-I; PSQI = Pittsburgh Sleep Quality Index; QOL = quality of life; RCT = randomized controlled trial; VCBT-I = video-based CBT-I. | |||||
a Actigraphy: A technique that uses a small instrument called an actigraph (a watch-like sensory unit) worn on the wrist or ankle to measure body gross motor activity. It is helpful in determining sleep patterns and daytime activity. | |||||
b Polysomnography: A test used to diagnose sleep disorders on the basis of sleep-related biophysiological changes. | |||||
Berger et al., 2009[17] | Breast (stages I–III) during chemotherapy | N = 219; RCT | Control: Healthy-eating group (sessions with equal time, attention) | PSQI, sleep diary, actigraphya, fatigue assessment | Significant improvement in sleep quality and nighttime awakenings for CBT group, compared with control group |
CBT-I: Individualized plan before chemotherapy, stimulus control, modified sleep restriction, relaxation therapy, sleep hygiene | |||||
Epstein et al., 2007[15] | Breast (stages I–III) | N = 72; RCT | Control: Sleep education and hygiene | Sleep diary, actigraphy, ISI | Both groups improved over time; significant improvement between groups favored CBT-I group in time to fall asleep, time awake after sleep onset, total sleep time, sleep quality (as measured by ISI) |
CBT-I: 6 sessions, stimulus control, sleep restriction, sleep education and hygiene | |||||
Espie et al., 2008[16] | Mixed | N = 150; RCT | Control: Sleep education and hygiene | Sleep diary; actigraphy; fatigue, depression/anxiety, and QOL assessments | Significant improvement in time to fall asleep, time awake after sleep onset, sleep efficiency, fatigue, specific QOL outcomes for CBT-I group, compared with control group |
CBT-I: 5 weekly sessions, stimulus control, sleep restriction, cognitive restructuring | |||||
Savard et al., 2005[14] | Breast (stages I–III) | N = 57; RCT | Control: Wait list | Sleep diary; polysomnographyb; ISI; fatigue, depression/anxiety, and QOL assessments | Significant improvement in time to fall asleep, time awake after sleep onset, sleep efficiency, depression/anxiety, and QOL outcomes for CBT group, compared with control group |
CBT-I: 8 weekly sessions, stimulus control, sleep restriction, sleep education and hygiene, cognitive restructuring, fatigue management | |||||
Savard et al., 2014[19] | Breast (stages I–III) | N = 242; RCT | Control: No treatment (n = 81) | Sleep diary; ISI; actigraphy; fatigue, depression/anxiety, and QOL assessments | Compared with control group, PCBT-I and VCBT-I groups associated with significant improvement in sleep diary–measured sleep variables; compared with VCBT-I group, PCBT-I group had more improvement in sleep, fatigue, and depression/anxiety outcomes and had higher remission rates for insomnia |
PCBT-I (n = 81): 6 weekly sessions | |||||
VCBT-I (n = 80): 60-min animated video, 6 booklets | |||||
CBT-I content: Similar for both groups (stimulus control, sleep restriction, sleep education and hygiene, cognitive restructuring) |
Inpatient nonpharmacologic management
CBT delivered by psychologists has shown promise for the treatment of insomnia in patients with cancer.[14][Level of evidence: I] A randomized controlled study investigated the effectiveness of a protocol-driven cognitive behavioral intervention for insomnia delivered by oncology nurses.[16][Level of evidence: I] This group intervention consisted of standard CBT components such as stimulus control and sleep restriction. Participants included patients with heterogeneous cancers randomly assigned to receive the intervention (n = 100) or treatment as usual (n = 50). Primary outcomes were sleep diary measures at baseline, posttreatment, and at 6-month follow-up. CBT was associated with significant and sustained improvements in several sleep aspects. These improvements were seen for both subjective (sleep diary) and objective (actigraphy) assessments. Additionally, CBT patients showed significant improvements in fatigue, anxiety, and depressive symptoms and reported improved quality of life, compared with patients who received treatment as usual.[16][Level of evidence: I]
A study conducted in cancer survivors demonstrated the benefits of a specialized yoga program to improve sleep quality and reduce medication use. A total of 410 cancer survivors with moderate to severe sleep disturbances were randomly assigned to receive standard care or standard care plus a 4-week yoga intervention delivered in two weekly sessions by trained yoga instructors. The yoga participants showed significant improvement in sleep quality, daytime dysfunction, nighttime awakening, and sleep efficiency, compared with standard-care participants. Two major limitations of this study were its limited population generalizability, as most study participants were female, white, married, and well-educated breast cancer survivors; and the lack of an adequate control group with respect to nonspecific effects such as group support and attention.[20]
Other actions or interventions that may promote rest in the hospital or extended-care setting include the following:[21,22]
- Keeping the patient's skin clean and dry.
- Giving back rubs and/or massaging areas of the body to bring comfort to the patient (e.g., bony prominences, head and scalp, shoulders, hands, and feet).
- Keeping bedding and/or surfaces of support devices (chairs and pillows) clean, dry, and wrinkle-free.
- Ensuring adequate bedcovers for warmth.
- Regulating fluid intake to avoid frequent awakening for elimination.
- Encouraging bowel and bladder elimination before sleep.
- Promoting optimal bowel function (increased fluids, dietary fiber, and use of stool softeners and laxatives).
- Using a condom catheter for nocturnal incontinence.
- Providing a high-protein snack 2 hours before bedtime (e.g., milk, turkey, or other foods high in tryptophan).
- Avoiding beverages with caffeine and other stimulants, including dietary supplements that promote metabolism changes and appetite suppression.
- Encouraging the patient to dress in loose, soft clothing.
- Facilitating comfort through repositioning and support with pillows as needed.
- Encouraging activity and being out of the bed as much as possible during waking hours.
- Encouraging the patient to keep regular bedtime and awakening hours and avoid napping during the day.
- Minimizing and coordinating necessary bedside contacts.
Psychological interventions are directed toward facilitating the patient's coping processes through education, support, and reassurance. As the patient learns to cope with the stresses of illness, hospitalization, and treatment, sleep may improve.[23][Level of evidence: IV] Communication, verbalization of concerns, and openness between the patient, family, and health care team should be encouraged. Relaxation exercises and self-hypnosis performed at bedtime can help promote calm and sleep. Cognitive-behavioral interventions that diminish the distress associated with early insomnia and change the goal from "need to sleep" to "just relax" can diminish anxiety and promote sleep.[24]
Pharmacologic Management of Sleep-Wake Cycle Disturbances
When cancer survivors experience sleep-wake disturbances, cognitive behavioral intervention counseling should be the first consideration for management. (Refer to the Nonpharmacologic Management of Sleep Disturbances section of this summary for more information.) It is acknowledged that resources for education and training in CBT may not be readily available in many cancer centers, and therefore community resources need to be investigated. In areas where CBT is not available or has been utilized but has not been successful, pharmacologic management can be considered. In addition, when patients have comorbidities contributing to sleep-wake cycle disturbances (such as hot flashes, uncontrolled pain, anxiety, depression, or other mood disturbances),[25,26] then pharmacologic management will probably be necessary. While many pharmacologic agents are approved for primary insomnia and many other agents are used off-label to manage sleep and related symptoms, most of the approved sleep aids have not been studied in cancer populations; therefore, the risk/benefit profiles of these drugs are not delineated in this setting.
Despite the lack of evidence in cancer populations, pharmacologic interventions are widely used by clinicians. Therefore, the following discussion of pharmacologic agents and recommendations for use is based on evidence from studies conducted in patients with primary insomnia and clinical experience.[4,27,28]
Several classes of medications are used to treat sleep-wake cycle disturbances:
- Nonbenzodiazepine benzodiazepine receptor agonists (e.g., zolpidem).
- Benzodiazepines (e.g., lorazepam).
- Melatonin receptor agonists (e.g., ramelteon).
- Antihistamines (e.g., hydroxyzine).
- Antidepressants (e.g., trazodone) and antipsychotics (e.g., quetiapine) that have sedative effects.
Drug characteristics that should be taken into account before a drug is chosen to treat an individual patient include the following:
- Absorption.
- Time to reach maximum concentration.
- Elimination half-life.
- Receptor activity.
- Ability to cross the blood-brain barrier.
- Dose and frequency.
- Formulation (short-acting versus long-acting).
These pharmacokinetic principles are important for the matching of agents to the type of sleep disturbance (e.g., problems falling asleep versus problems staying asleep). There are also safety issues to be considered, such as potentials for tolerance, abuse, dependence, withdrawal (including risk of rebound insomnia), and drug-drug and drug-disease interactions. Medications for sleep-wake cycle disturbances should be used short-term and/or as needed.
General considerations for the use of hypnotics
Medications used to induce sleep are intended for the short-term management of sleep disorders. The use of these medications for longer periods is poorly studied. They are usually combined with lifestyle changes that will reinforce good sleep habits and negate the need for chronic hypnotic medications.
Most research studies of current and historic hypnotic medications rarely exceed a duration of 12 to 16 weeks of study. Additionally, none of the current hypnotics re-create normal sleep architecture, and variations from normal periods of rapid eye movement (REM) sleep and non-REM sleep are common. It is important to taper hypnotic medications slowly, or the variations in normal sleep patterns can become even more pronounced, with the majority of time spent in REM sleep in a condition known as REM rebound.[29,30]
Table 2 lists the drug categories and specific medications, including doses, commonly used within those categories.
Drug Category | Medication | Dose | Comments | Reference |
CR = controlled-release; FDA = U.S. Food and Drug Administration; REM = rapid eye movement. | ||||
Nonbenzodiazepine benzodiazepine receptor agonist | zaleplon (Sonata) | 5–20 mg | Useful for problems falling asleep only. | [31][Level of evidence: I] |
zolpidem tartrate (Ambien) | 5–10 mg | Useful for problems falling asleep only. Maximum suggested dose for women: 5 mg. | [31][Level of evidence: I] | |
zolpidem tartrate extended-release (Ambien CR) | 6.25–12.5 mg | Biphasic release; useful for problems both falling asleep and staying asleep. Do not crush or split tablets. Maximum suggested dose for women: 6.25 mg. | [31][Level of evidence: I] | |
eszopiclone (Lunesta) | 1–3 mg | Useful for problems both falling asleep and staying asleep. Do not take with or right after meal. | [31][Level of evidence: I] | |
Benzodiazepine | clonazepam (Klonopin) | 0.25–2 mg | Used for REM sleep disorder (not FDA approved). | [31][Level of evidence: III] |
lorazepam (Ativan) | 0.5–4 mg; dose >2 mg rare | Risk of loss of motor coordination, falls, and cognitive impairment. | [31][Level of evidence: I] | |
temazepam (Restoril) | 7.5–30 mg | Risk of loss of motor coordination, falls, and cognitive impairment. | [31][Level of evidence: II] | |
Melatonin receptor agonist | ramelteon (Rozerem) | 8 mg | Useful for problems falling asleep only. Little negative effect on cognition, somnolence, motor coordination, or nausea. | [31][Level of evidence: I] |
Antihistamine | diphenhydramine (Benadryl) | 25–100 mg | Useful for problems falling asleep only. Anticholinergic side effects; increases delirium risk in elderly patients. | [31][Level of evidence: I] |
hydroxyzine (Vistaril, Atarax) | 10–100 mg | Useful for problems falling asleep only. Anticholinergic side effects; increases delirium risk in elderly patients. | [32][Level of evidence: II] | |
Tricyclic antidepressant | doxepin (Silenor) | 3–6 mg | Lower doses used for treatment of primary insomnia when antidepressant effect not needed. Risk of anticholinergic side effects and weight gain. | [31][Level of evidence: I] |
amitriptyline (Elavil) | 10–25 mg | Lower doses used for treatment of primary insomnia when antidepressant effect not needed. Risk of anticholinergic side effects and weight gain. | [33][Level of evidence: II] | |
nortriptyline (Pamelor) | 10–50 mg | Risk of anticholinergic side effects and weight gain. | [34][Level of evidence: III] | |
Second-generation antidepressant | trazodone (Desyrel) | 25–100 mg | Risk of orthostatic hypotension and falls. | [35] |
mirtazapine (Remeron) | 7.5–45 mg | If depression not a concern, 7.5–15 mg best for sleep, hot flashes, increased appetite, and less morning sedation. Risk of falls. | [33][Level of evidence: III] | |
Antipsychotic | quetiapine (Seroquel) | 25–100 mg | Risk of weight gain, metabolic syndrome, abnormal/involuntary movements; possible cardiovascular effects (e.g., prolonged QT interval). Generally not a preferred agent due to side effects. | [36][Level of evidence: III] |
Chloral derivative | chloral hydrate | 500–1,000 mg | Used mainly for sleep maintenance. Risk of gastric irritation, dependence, and withdrawal. Lethal in overdose. | [31][Level of evidence: I] |
Nonbenzodiazepine benzodiazepine receptor agonists
All agents in this class are FDA approved for primary insomnia. These agents promote sleep by enhancing the effects of gamma-aminobutyric acid (GABA) at the GABA type A (GABAA) receptor. Unlike traditional benzodiazepines (e.g., lorazepam), these agents preferentially target specific GABAA receptor subtypes. Zolpidem and zaleplon bind predominantly to the alpha-1 subtype of GABAA, and eszopiclone preferentially targets the alpha-3 receptor subtype. This selective receptor subtype targeting has both advantages and disadvantages. These agents have mainly hypnotic/sedative effects and lack the anxiolytic, anticonvulsant, and myorelaxant effects seen with benzodiazepines. Conversely, because of the selective receptor subtype targeting, these agents have fewer effects on cognitive, psychomotor function and carry less risk of tolerance, dependence, and withdrawal (especially physical withdrawal) than do benzodiazepines.[4,27,28]
These agents may be preferred for use in patients with cancer, when only hypnotic effects are desired, and should be taken just before bedtime (or even in bed) because they enter the brain very quickly; some of these agents (e.g., zaleplon) have a short elimination half-life. Because of their longer-lasting effects, zolpidem extended-release and eszopiclone are preferred in the treatment of difficulties in staying asleep. However, these agents carry a higher risk of residual morning sedation and cognitive/motor impairments than do agents with shorter elimination half-lives (e.g., zaleplon and immediate-release zolpidem).
Benzodiazepines target several GABAA receptor subtypes, including alpha-1, -2, -3, and -5, and work by enhancing GABA effects at these receptors. In addition to hypnotic/sedative effects, these agents also have anxiolytic, anticonvulsant, and myorelaxant effects. Benzodiazepines are preferred when other effects (such as antianxiety or muscle relaxant effects) are desirable with or without the hypnotic effects.[4,27,28]
Benzodiazepines carry a much higher risk of tolerance, dependence, and withdrawal than do the nonbenzodiazepine receptor agonists. Benzodiazepine withdrawal has been associated with the risk of seizures, delirium tremens, autonomic instability, and death. These agents should be used with extreme caution and with close monitoring in patients with histories of significant substance use because these patients are vulnerable to tolerance and dependence issues. Benzodiazepines have also been associated with cognitive impairment and difficulties with motor coordination.
Generally, benzodiazepines with longer half-lives (e.g., clonazepam) are associated with a higher risk of residual morning sedation and cognitive/motor impairments. Agents with shorter elimination half-lives (e.g., lorazepam) are generally preferred for short-term anxiolytic effects and difficulties falling asleep and in elderly patients. Agents with longer half-lives (e.g., clonazepam) are preferred for the treatment of persistent anxiety and difficulties falling and staying asleep. All benzodiazepines are associated with risk of respiratory depression and should be used with caution in patients with preexisting respiratory disorders.
Melatonin receptor agonists: Ramelteon and tasimelteon
Ramelteon and tasimelteon work by binding to the melatonin receptor types MT1 and MT2. Ramelteon is useful only for the treatment of difficulties falling asleep and does not have any other effects, such as anxiolytic or myorelaxant effects, while tasimelteon is indicated for use in circadian sleep disorder. These agents do not treat difficulties staying asleep but also carry much less risk of cognitive/motor impairments and dependence issues.[27,28,37]
Diphenhydramine and hydroxyzine decrease arousal by blockading histamine receptors. Antihistamines are sold over the counter and are useful for treating difficulties in falling asleep only. There is limited evidence for the use of antihistamines to treat insomnia; these agents are used when traditional hypnotics or benzodiazepines are less suitable because of the risk of cross-dependence or other issues, such as vulnerability of a patient to addictions. The anticholinergic properties of antihistamines may also be beneficial in the treatment of nausea and vomiting. The sedative and anticholinergic properties of these agents increase the risk of delirium, especially in older patients.[27,28]
Sedating antidepressants are considered first-line agents when insomnia is comorbid with depression/anxiety symptomatology. (Refer to the Pharmacologic Intervention section in the PDQ summary on Depression for more information.) These drugs include tricyclic antidepressants (e.g., amitriptyline) and second-generation antidepressants (e.g., mirtazapine). The sedating effects of tricyclic antidepressants are caused mainly by histamine receptor blockading and partially by blockading of 5-HT2 and muscarinic receptors. The sedating effects of mirtazapine are caused by its blocking of 5-HT2 and histamine receptors, while those of trazodone are caused by its blocking actions at the at histamine, 5-HT, and noradrenaline receptors.[4,27,28]
Tricyclic antidepressants have a small therapeutic window and can be lethal in overdose, compared with second-generation antidepressants such as mirtazapine. Additionally, tricyclics carry other risks, such as risk of weight gain, anticholinergic side effects, and cardiovascular side effects and should be used under close supervision. These agents sometimes are used in low doses (see Table 2) as adjuncts to other antidepressants in the treatment of insomnia comorbid with depression/anxiety. This helps to avoid the side effects associated with higher doses while delivering the needed sedating effects. Tricyclics can also boost appetite and may be the treatment of choice for insomnia in patients with comorbid cachexia. Certain tricyclics (amitriptyline and nortriptyline) can also be beneficial in the treatment of pain syndromes (e.g., neuropathic pain) and headaches when these issues are comorbid with insomnia. Low doses of antidepressants (subtherapeutic for depression) are frequently used to treat insomnia without any comorbidities.
Mirtazapine, a second-generation antidepressant, also has appetite-stimulating and antiemetic properties in addition to sedating effects. It is frequently used in insomniac patients with depression (therapeutic dose for depression, 15–45 mg) or without depression (subtherapeutic doses for depression, 7.5–15 mg) with comorbid nausea or loss of appetite. In low doses, trazodone (50–100 mg) can promote sleep and is often combined with other antidepressants (e.g., fluoxetine 20 mg in the morning) in depressed patients with insomnia.
Antipsychotics such as quetiapine have sedating effects caused mainly by the blockade of histamine receptors. However, these agents should be considered as a last resort and as a short-term treatment because of their serious side-effect profile. The use of antipsychotics has been associated with weight gain, metabolic syndrome, diabetes, cardiovascular risks, and the risk of extrapyramidal side effects, including tardive dyskinesia. Antipsychotics can be considered for treatment-refractory insomnia, especially with comorbid anxiety symptomatology.[27]
Chloral derivative: Chloral hydrate
Chloral hydrate has sleep-promoting effects resulting from its effects on GABA systems. It is associated with risk of withdrawal symptoms similar to those of benzodiazepines and is associated with rapid development of tolerance. Additionally, chloral hydrate carries the risk of gastric irritation and multiple drug-drug interactions, and it is lethal in overdose. Like antipsychotics, chloral hydrate is usually considered only in cases of treatment-refractory insomnia because of its serious side-effect profile and the availability of safer alternatives.[27]
Botanical/dietary supplements
Melatonin, a hormone produced by the pineal gland during the hours of darkness, plays a major role in the sleep-wake cycle and has been linked to the circadian rhythm.[38] Adjuvant melatonin may also improve sleep disruption caused by drugs known to alter normal melatonin production (e.g., beta-blockers and benzodiazepines).[39][Level of evidence: IV] Supplementation with melatonin (2–4 mg in the evening) has been shown to improve sleep in children with endocrine tumors that diminish the natural production of the hormone.[40][Level of evidence: II] However, a meta-analysis of 25 studies exploring the efficacy and safety of melatonin in managing secondary sleep disorders or sleep disorders accompanying sleep restriction found that melatonin was not effective in either of these conditions.[41] The review found that short-term use of melatonin appears to be safe. However, these studies were not conducted in the context of cancer therapy.[38]
Evidence suggests that circulating melatonin levels are significantly lower in physically healthy older people and in insomniacs than in age-matched control subjects. In view of these findings, melatonin replacement therapy may be beneficial in the initiation and maintenance of sleep in elderly patients.[42][Level of evidence: II] A slow-release formulation of melatonin is licensed in Europe and is approved as monotherapy for patients aged 55 years or older for the short-term treatment (up to 13 weeks) of primary insomnia characterized by poor-quality sleep. However, melatonin replacement as a treatment for insomnia has not been studied in older people with cancer. Ramelteon and tasimelteon work via the melatonin receptor system: ramelteon to support the initiation of sleep, and tasimelteon to correct circadian sleep disorder.
Melatonin may interact with certain chemotherapeutic regimens via the cytochrome P450 enzyme and other systems.[43] It may augment the effects of some chemotherapeutic agents metabolized via the enzyme CYP1A2 and may exert inhibitory effects on P-glycoprotein–mediated doxorubicin efflux.
Clinical studies in renal, breast, colon, lung, and brain cancer suggest that melatonin exerts anticancer effects in conjunction with chemotherapy and radiation therapy; however, evidence remains inconclusive.[44,45] All of the studies suggesting antitumor effects of melatonin have been conducted by the same group of investigators and were open label. Efforts by independent groups of investigators are under way to investigate these effects in carefully designed, randomized, blinded studies.[44]In vitro and animal studies have demonstrated the anticancer effects of exogenous melatonin, and lower melatonin levels are associated with tumor growth.[46] Human studies have yet to substantiate any causal or associative relationships.
Cannabisand cannabinoids
No studies have been conducted to specifically evaluate the effects of Cannabis inhalation or other Cannabis products in patients with primary or secondary sleep disturbances. Limited data from in vitro studies, animal studies, and small populations of healthy individuals or chronic Cannabis users are beginning to elucidate some of the relationships between various neurotransmitters and the sleep-wake cycle and related effects of Cannabis pharmacology.[47,48]
Cannabis-based medicines are under development as a treatment for chronic pain syndromes, including cancer-related pain. One such medication under investigation is nabiximols (Sativex), an oromucosal formulation (delta-9-tetrahydrocannabinol and cannabidiol mixed in a 1:1 ratio). Studies conducted with nabiximols, primarily focusing on pain syndromes, have shown improvement in subjective sleep quality when sleep was measured as a secondary outcome.[49] Comorbidities such as pain are common reasons for sleep disturbances. Concerns have been raised about the abuse and dependence potential of nabiximols, especially in the subpopulation of patients with histories of Cannabis use.[50] Nabiximols is approved in Canada for the treatment of central neuropathic pain in patients with multiple sclerosis. In the United States, it is only available for investigational use and is currently under investigation for the treatment of intractable cancer pain.
Current Clinical Trials
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
- Jefferson CD, Drake CL, Scofield HM, et al.: Sleep hygiene practices in a population-based sample of insomniacs. Sleep 28 (5): 611-5, 2005.
- Savard J, Morin CM: Insomnia in the context of cancer: a review of a neglected problem. J Clin Oncol 19 (3): 895-908, 2001.
- Morin CM, Bootzin RR, Buysse DJ, et al.: Psychological and behavioral treatment of insomnia:update of the recent evidence (1998-2004). Sleep 29 (11): 1398-414, 2006.
- Becker PM: Pharmacologic and nonpharmacologic treatments of insomnia. Neurol Clin 23 (4): 1149-63, 2005.
- Jacobs GD, Benson H, Friedman R: Home-based central nervous system assessment of a multifactor behavioral intervention for chronic sleep-onset insomnia. Behav Ther 24 (1): 159-74, 1993.
- Morin CM, Culbert JP, Schwartz SM: Nonpharmacological interventions for insomnia: a meta-analysis of treatment efficacy. Am J Psychiatry 151 (8): 1172-80, 1994.
- Smith MT, Perlis ML, Park A, et al.: Comparative meta-analysis of pharmacotherapy and behavior therapy for persistent insomnia. Am J Psychiatry 159 (1): 5-11, 2002.
- Morgenthaler T, Kramer M, Alessi C, et al.: Practice parameters for the psychological and behavioral treatment of insomnia: an update. An american academy of sleep medicine report. Sleep 29 (11): 1415-9, 2006.
- Edinger JD, Wohlgemuth WK, Radtke RA, et al.: Cognitive behavioral therapy for treatment of chronic primary insomnia: a randomized controlled trial. JAMA 285 (14): 1856-64, 2001.
- Berger AM, VonEssen S, Kuhn BR, et al.: Adherence, sleep, and fatigue outcomes after adjuvant breast cancer chemotherapy: results of a feasibility intervention study. Oncol Nurs Forum 30 (3): 513-22, 2003 May-Jun.
- Berger AM, VonEssen S, Khun BR, et al.: Feasibilty of a sleep intervention during adjuvant breast cancer chemotherapy. Oncol Nurs Forum 29 (10): 1431-41, 2002 Nov-Dec.
- Jacobs GD, Pace-Schott EF, Stickgold R, et al.: Cognitive behavior therapy and pharmacotherapy for insomnia: a randomized controlled trial and direct comparison. Arch Intern Med 164 (17): 1888-96, 2004.
- Morin CM, Colecchi C, Stone J, et al.: Behavioral and pharmacological therapies for late-life insomnia: a randomized controlled trial. JAMA 281 (11): 991-9, 1999.
- Savard J, Simard S, Ivers H, et al.: Randomized study on the efficacy of cognitive-behavioral therapy for insomnia secondary to breast cancer, part I: Sleep and psychological effects. J Clin Oncol 23 (25): 6083-96, 2005.
- Epstein DR, Dirksen SR: Randomized trial of a cognitive-behavioral intervention for insomnia in breast cancer survivors. Oncol Nurs Forum 34 (5): E51-9, 2007.
- Espie CA, Fleming L, Cassidy J, et al.: Randomized controlled clinical effectiveness trial of cognitive behavior therapy compared with treatment as usual for persistent insomnia in patients with cancer. J Clin Oncol 26 (28): 4651-8, 2008.
- Berger AM, Kuhn BR, Farr LA, et al.: One-year outcomes of a behavioral therapy intervention trial on sleep quality and cancer-related fatigue. J Clin Oncol 27 (35): 6033-40, 2009.
- Berger AM, Kuhn BR, Farr LA, et al.: Behavioral therapy intervention trial to improve sleep quality and cancer-related fatigue. Psychooncology 18 (6): 634-46, 2009.
- Savard J, Ivers H, Savard MH, et al.: Is a video-based cognitive behavioral therapy for insomnia as efficacious as a professionally administered treatment in breast cancer? Results of a randomized controlled trial. Sleep 37 (8): 1305-14, 2014.
- Mustian KM, Sprod LK, Janelsins M, et al.: Multicenter, randomized controlled trial of yoga for sleep quality among cancer survivors. J Clin Oncol 31 (26): 3233-41, 2013.
- Page M: Sleep pattern disturbance. In: McNally JC, Stair JC, Somerville ET, eds.: Guidelines for Cancer Nursing Practice. Orlando, Fla: Grune and Stratton, Inc., 1985, pp 89-95.
- Kaempfer SH: Insomnia. In: Baird SB, ed.: Decision Making in Oncology Nursing. Philadelphia, Pa: B.C. Decker, Inc., 1988, pp 78-9.
- Berlin RM: Management of insomnia in hospitalized patients. Ann Intern Med 100 (3): 398-404, 1984.
- Horowitz SA, Breitbart W: Relaxation and imagery for symptom control in cancer patients. In: Breitbart W, Holland JC, eds.: Psychiatric Aspects of Symptom Management in Cancer Patients. Washington, DC: American Psychiatric Press, 1993, pp 147-71.
- Jim HS, Small B, Faul LA, et al.: Fatigue, depression, sleep, and activity during chemotherapy: daily and intraday variation and relationships among symptom changes. Ann Behav Med 42 (3): 321-33, 2011.
- Savard MH, Savard J, Trudel-Fitzgerald C, et al.: Changes in self-reported hot flashes and their association with concurrent changes in insomnia symptoms among women with breast cancer. Menopause 18 (9): 985-93, 2011.
- Wilson SJ, Nutt DJ, Alford C, et al.: British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders. J Psychopharmacol 24 (11): 1577-601, 2010.
- Sullivan SS: Insomnia pharmacology. Med Clin North Am 94 (3): 563-80, 2010.
- Ramakrishnan K, Scheid DC: Treatment options for insomnia. Am Fam Physician 76 (4): 517-26, 2007.
- Schutte-Rodin S, Broch L, Buysse D, et al.: Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med 4 (5): 487-504, 2008.
- Lexicomp Online. Hudson, Ohio: Lexi-Comp, Inc., 2019. Available online with subscription. Last accessed April 23, 2019.
- Alford C, Rombaut N, Jones J, et al.: Acute effects of hydroxyzine on nocturnal sleep and sleep tendency the following day: a C-EEG study. Hum Psychopharmacol Clin Exp 7 (1): 25-35, 1992.
- Wilson S, Nutt D: Management of insomnia: treatments and mechanismsi. Br J Psychiatry 191: 195-7, 2007.
- Pagel JF, Parnes BL: Medications for the Treatment of Sleep Disorders: An Overview. Prim Care Companion J Clin Psychiatry 3 (3): 118-125, 2001.
- James SP, Mendelson WB: The use of trazodone as a hypnotic: a critical review. J Clin Psychiatry 65 (6): 752-5, 2004.
- Chakravorty S, Hanlon AL, Kuna ST, et al.: The effects of quetiapine on sleep in recovering alcohol-dependent subjects: a pilot study. J Clin Psychopharmacol 34 (3): 350-4, 2014.
- Johnsa JD, Neville MW: Tasimelteon: a melatonin receptor agonist for non-24-hour sleep-wake disorder. Ann Pharmacother 48 (12): 1636-41, 2014.
- Buscemi N, Vandermeer B, Hooton N, et al.: Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. BMJ 332 (7538): 385-93, 2006.
- Dawson D, Encel N: Melatonin and sleep in humans. J Pineal Res 15 (1): 1-12, 1993.
- Jan JE, Espezel H, Appleton RE: The treatment of sleep disorders with melatonin. Dev Med Child Neurol 36 (2): 97-107, 1994.
- van Geijlswijk IM, Korzilius HP, Smits MG: The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis. Sleep 33 (12): 1605-14, 2010.
- Haimov I, Lavie P, Laudon M, et al.: Melatonin replacement therapy of elderly insomniacs. Sleep 18 (7): 598-603, 1995.
- Seely D, Stempak D, Baruchel S: A strategy for controlling potential interactions between natural health products and chemotherapy: a review in pediatric oncology. J Pediatr Hematol Oncol 29 (1): 32-47, 2007.
- Lissoni P, Barni S, Mandalà M, et al.: Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 35 (12): 1688-92, 1999.
- Mills E, Wu P, Seely D, et al.: Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis. J Pineal Res 39 (4): 360-6, 2005.
- Mirick DK, Davis S: Melatonin as a biomarker of circadian dysregulation. Cancer Epidemiol Biomarkers Prev 17 (12): 3306-13, 2008.
- Schierenbeck T, Riemann D, Berger M, et al.: Effect of illicit recreational drugs upon sleep: cocaine, ecstasy and marijuana. Sleep Med Rev 12 (5): 381-9, 2008.
- Murillo-Rodriguez E, Poot-Ake A, Arias-Carrion O, et al.: The emerging role of the endocannabinoid system in the sleep-wake cycle modulation. Cent Nerv Syst Agents Med Chem 11 (3): 189-96, 2011.
- Barnes MP: Sativex: clinical efficacy and tolerability in the treatment of symptoms of multiple sclerosis and neuropathic pain. Expert Opin Pharmacother 7 (5): 607-15, 2006.
- Robson P: Abuse potential and psychoactive effects of δ-9-tetrahydrocannabinol and cannabidiol oromucosal spray (Sativex), a new cannabinoid medicine. Expert Opin Drug Saf 10 (5): 675-85, 2011.
Special Considerations
The Patient With Pain
Since enhanced pain control improves sleep, appropriate analgesics or nonpharmacologic pain management should be administered before introducing sleep medications. Tricyclic antidepressants can be particularly useful for the treatment of insomnia in patients with neuropathic pain and depression. Patients on high-dose opioids for pain may be at increased risk for the development of delirium and organic mental disorders. Such patients may benefit from the use of low-dose neuroleptics as sleep agents (e.g., haloperidol 0.5–1 mg).
The Older Patient
Older patients frequently have insomnia due to age-related changes in sleep. The sleep cycle in this population is characterized by lighter sleep, more frequent awakenings, and less total sleep time. Anxiety, depression, loss of social support, and a diagnosis of cancer are contributory factors in sleep disturbances in older patients.[1]
Sleep problems in older adults are so common that nearly half of all hypnotic prescriptions written are for persons older than 65 years. Although normal aging affects sleep, the clinician should evaluate the many factors that cause insomnia, such as medical illness, psychiatric illness, dementia, alcohol and/or polypharmacy, restless legs syndrome, periodic leg movements, and sleep apnea syndrome. Nonpharmacologic treatment of sleep disorders is the preferred initial management, with the use of medication when indicated and referral to a sleep disorder center when specialized care is necessary.[2]
Providing a regular schedule of meals, discouraging daytime naps, and encouraging physical activity may improve sleep. Hypnotic prescriptions for older patients must be adjusted for variations in metabolism, increased fat stores, and increased sensitivity. Dosages should be reduced by 30% to 50%. Problems associated with drug accumulation (especially flurazepam) must be weighed against the risks of more severe withdrawal or rebound effects associated with short-acting benzodiazepines. An alternate drug for older patients is chloral hydrate.[1]
Somnolence Syndrome in Children
Cranial irradiation and intrathecal methotrexate are used to prevent the development of central nervous system leukemia in children with acute lymphocytic leukemia. Somnolence syndrome (SS) is a complication of cranial irradiation occurring in 30% to 50% of patients who receive more than 18 Gy at daily dose fractions of 1.5 Gy to 2 Gy. The syndrome may appear 4 to 6 weeks posttherapy. SS is characterized by mild drowsiness to moderate lethargy and, occasionally, low-grade fever. The pathophysiology is unknown, but electroencephalogram and cerebral spinal fluid abnormalities are detectable in affected children. Although supportive care measures cannot prevent the occurrence of SS, acknowledgment of the existence of this problem may prevent or minimize anxieties for children and parents when symptoms of SS appear.
Sleep Apnea After Mandibulectomy
Anterior mandibulectomy can result in the development of sleep apnea. All patients with head and neck tumors who have had extensive anterior oral cavity resection should be evaluated before decannulation of the tracheostomy tube. Subsequent flap and/or reconstruction of the lower jaw seems to prevent the development of sleep apnea. In contrast, facial sling suspension of the lower lip does not prevent the development of sleep apnea.[3] Assessment for symptoms and preparation for the appearance of symptoms in this population provide indications for interventions related to sleep apnea.
- Berlin RM: Management of insomnia in hospitalized patients. Ann Intern Med 100 (3): 398-404, 1984.
- Johnston JE: Sleep problems in the elderly. J Am Acad Nurse Pract 6 (4): 161-6, 1994.
- Panje WR, Holmes DK: Mandibulectomy without reconstruction can cause sleep apnea. Laryngoscope 94 (12 Pt 1): 1591-4, 1984.
Changes to This Summary (03 / 10 / 2016)
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Added General considerations for the use of hypnotics as a new subsection.
Added Johnsa et al. as reference 37.
This summary is written and maintained by the PDQ Supportive and Palliative Care Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® – NCI's Comprehensive Cancer Database pages.
About This PDQ Summary
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the pathophysiology and treatment of sleep disorders. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Supportive and Palliative Care Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
- be discussed at a meeting,
- be cited with text, or
- replace or update an existing article that is already cited.
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewer for Sleep Disorders is:
- Jayesh Kamath, MD, PhD (University of Connecticut Health Center)
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Supportive and Palliative Care Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."
The preferred citation for this PDQ summary is:
PDQ® Supportive and Palliative Care Editorial Board. PDQ Sleep Disorders. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/treatment/side-effects/sleep-disorders-hp-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389467]
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.
The information in these summaries should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.
Contact Us
More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website's Email Us.
Last Revised: 2016-03-10
This information does not replace the advice of a doctor. Healthwise, Incorporated, disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use. Learn how we develop our content.


text:
Located in the rich fertile Golden Valleys of Munster, Dairygold has a long and proud history of producing quality-assured, sustainable gold standard cheese and dairy ingredients. With three imperative divisions that drive and support our farmers and business, Dairygold are able to offer clients and consumers full traceability, unrivalled quality and product excellence.
The Challenge
The central focus of a new CRM system was to allow Dairygold to improve customer and supplier relationships. The Co-Operative was previously dependent of on field staff returning to the office to file a paper-based records of customer interactions.
The Solution
Designed and delivered by Ergo, the Customer Relationship Management (CRM) components in Microsoft Dynamics 365 were identified as the best way to meet Dairygold's requirements and to garner a better understanding of farmers and their needs. The new CRM system provides Dairygold with relevant information in a timely manner helping to overcome some of the challenges the teams have encountered when working remotely in rural Ireland.
"CRM allows us to improve the service and support we provide to our member owned and controlled supplier base. It has helped to increase customer satisfaction levels and to strengthen our relationships with farmers"
Ergo's CRM solution has allowed Dairygold to record important items of information, enabling a more enhanced service. All the information is uploaded directly by their staff from any location, solving the challenge of working with customers and suppliers in remote areas.
Via: ErgoGroup.ie

subset: commoncrawl


text:
The film Innocence of Muslims, which denigrates Islam and its prophet, Muhammad, has put the spotlight on a little-known community, Coptic Christians.
The Associated Press and other news organizations report that the man who made the film is Nakoula Basseley Nakoula, a Coptic Christian who lives in the Los Angeles area. (Nakoula denies he made the film, but acknowledges working on it. My colleagues Amy Morgan and Scott Neuman have covered that aspect of the story.)
Copts come from Egypt, where they've lived for centuries, and they've been migrating to the U.S. in ever greater numbers since the Arab Spring, which has given rise to an Islamist government in Egypt. Here's what the AP says about them:
"Coptic Christians belong to the Coptic Orthodox Church of Alexandria, the largest Christian church in Egypt. The church belongs to the Oriental Orthodox family of churches, which has been a distinct church body since the Council of Chalcedon in 451. ... Their history dates back 19 centuries and the language used in their liturgy can be traced to the speech of Egypt's pharaohs."Once a majority in Egypt, Coptic Christians now make up about 10 percent of the country's 85 million people. They are the largest Christian community in the Middle East."
The community has been present in the U.S. since at least the 1950s, says S. Michael Saad, chair, Council for Coptic Studies at Claremont Graduate University in Claremont, Calif. There are about 400,000 Copts in the U.S., and they have the second-highest number of churches in the country's Orthodox community after the Greeks.
"They started coming in the 1950s after the Nasser revolution, when they were hit by both land reform and socialism," Saad tells the Two-Way.
Saad says Coptic migration increased after the 1967 war with Israel, and in the 1970s when Anwar Sadat ruled Egypt. The period saw a rise of fundamentalist Islam, culminating in Sadat's assassination in 1981. His successor, Hosni Mubarak, clamped down on Islamists, and Egypt's approximately 8.5 million Copts were relatively safe during the next three decades — though the community did face violence and pressure. But ever since the ouster of Mubarak in 2011, and the subsequent rise of the Islamist Muslim Brotherhood as a political force, there has been a steady increase in Coptic emigration to the U.S. and elsewhere.
"Numbers have greatly increased over the past 18 months since the so-called Arab Spring," Saad said. "We are seeing tens of families in every church every month."
A May 2012 report by the Department of Homeland Security's Office of Immigration Statistics says the number of Egyptians granted asylum in fiscal year 2011 — 1,028 — was almost twice the number the previous year. (It did not provide specific numbers for Copts). But a recent Wall Street Journal story looked at Coptic Christians fleeing Egypt. Here's what it said:
"Immigration lawyer David Barnett says most of his New York-based practice is now focused on Coptic Christians. Mr. Barnett is an observant Jew who prays every day. To accommodate his growing clientele, he employs a native Egyptian as a paralegal and works with a team of Egyptian translators.Many of the new arrivals, the attorney says, are young professionals who worked as doctors, pharmacists, businessmen.'If they have money, they are getting out,' Mr. Barnett says."
As NPR has reported in the past, the community has been the target of violence in Egypt. Saad says the community's situation now — after the movie — is more tenuous.
"The reaction in Egypt is going to be terrible," he said. "Without movies, it's been miserable."
Although the community is likely to feel safer in the U.S., Saad, in a paper published in Studies in World Christianity in December 2010, writes that it faces challenges here, too.
Copyright 2016 NPR. To see more, visit http://www.npr.org/.


text:
There are three things that have to happen to successfully change a habit. The first is that you must make the decision to change. When you make a decision, you are affirming to yourself that you are willing to go to any lengths to make your wishes come true. This means that you will need to completely
Read more-
Change Unhealthy Habits
Get Your Sleep
Research suggests that the amount and quality of sleep we achieve has profound effects on wellness. Nightly sleep is critical for the restoration of health. Sleep expert and President of the American Sleep Research Institute Lynn Larson explains that the link between sleep and decreased longevity is
Read more -
Quit Smoking
Smoking throughout the day is akin to living inside a burning building. Smoking degrades the collagen of your skin causing premature aging, destroys the cells inside your lungs, and promotes heart disease, cataracts and cancer because of the oxidizing radicals released into the blood stream. It can contribute
Read more -
Turn off the Television
There are three major trends in the health of both children and adults that have public health workers concerned: an increase in obesity, attention deficit disorder (ADD) and the amount of time spent watching television. Several recently published research studies indicate that television may be the
Read more


text:
Mailing Address:
University of Hawai'i at Mānoa
Department of Mathematics
2565 McCarthy Mall
Keller 419
Honolulu, HI 96822
Tel: (808) 956-7951
Fax: (808) 956-9139
Web: https://math.hawaii.edu/
UH Catalog:
List of Faculty, Program Overview, Degree Requirements
Courses Offered
Application Deadlines
Fall | Spring |
February 1 | October 1 |
Individual graduate programs may have priority consideration deadlines. Applicants are advised to contact the graduate programs for such dates. Any available funding support is limited and often awarded well in advance of the application deadlines.
Applicants who apply after the application deadlines MUST consult with the graduate programs before submitting an application. Application fees are non-refundable and may not be used for an application submitted at a later date.
Admissions Requirements
Ways to Apply
Apply online or download PDF application forms.
Applicants need to meet:
- Graduate Division admissions standard and documentation requirements, and
- program specific admissions criteria and documentation requirements. Send all program specific documentation requirements directly to the graduate program.
Standardized Exams
Refer to program specific admissions criteria and document requirements to determine if the GRE or another standardized exam is required by the graduate program. Official GRE scores must be sent directly to Graduate Division Student Services. All other scores are to be sent to the graduate program.
TOEFL or IELTS is required of most applicants who are non-native speakers of English. Official TOEFL or IELTS scores must be sent directly to Graduate Division Student Services. Minimum scores vary for each graduate program.
Program Overview
- Departmental
Degree Requirements
All graduate students at UHM need to meet degree requirements set by the Graduate Division and their graduate programs. For general Graduate Division requirements, see Degree Requirements. Below is an overview of the degree requirements for this graduate program.
- Departmental
The information provided here is for reference only. Please refer to the department's website for the latest and most accurate information.


text:
Edit Your Post on Posting HOF
This is not a vent board or any other kind of therapy. Before you hit the POST button, ask yourself if your contribution will add to the level of discussion going on.
Important notes on articles:
Message:... sacrificing for the dog may have been a leg up on lifetime experience as well.
HTTP Link (optional):
Poster's E-Mail (optional):


text:
In the first lawsuit of its kind, several nonprofit groups that received federal grants to help people sign up for insurance under the Affordable Care Act are suing the state of Missouri.
The Missouri law requires health insurance helpers called navigators to be licensed by the state, which involves passing an exam and paying a fee.
Plaintiffs in the lawsuit include the , Planned Parenthood of the St. Louis Region and Southwest Missouri, the and .
They claim that various provisions of the state law "prohibit some plaintiffs from performing the duties required of them by the Affordable Care Act (ACA), prohibit other plaintiffs from providing information about health insurance altogether, and prevent plaintiffs and the Missouri public from receiving information about health insurance from the person or source of their choosing."
The plaintiffs say the Missouri law has made their work pretty much impossible. You can read the complaint here.
"Missouri has placed groups like St. Louis Effort for AIDS in an untenable situation: If they comply with Missouri statutes, they can't perform the duties the Affordable Care Act requires them to perform, but if they comply with the ACA and do perform those duties, they violate the Missouri law and are subject to thousands of dollars in penalties for doing so," says Jay Angoff of Mehri and Skalet, who is representing the plaintiffs. Angoff is a former Missouri insurance commissioner and also the former head of the federal office implementing the ACA at the Department of Health and Human Services.
Missouri is one of more than a dozen states where Republican-led governments have passed laws or otherwise taken steps to restrict insurance navigators and other in-person counselors from attempting to help people sign up for health insurance on the new exchanges.
Florida, for example, barred navigators from state offices, while Texas Gov. Rick Perry ordered strict new regulations, on top of the ones imposed by the federal government. Those include additional training and testing, and reporting the names of people enrolled to the state.
Copyright 2020 NPR. To see more, visit https://www.npr.org.


text:
See Perimeter Adhered.
Aluminum Oxide
Added to the urethane finish for increased abrasion resistance of the wear layer.
Vinyl is constructed of several different layers: the wear layer, the printed or
decorative layer, an inner core consisting of a foam and vinyl layer, and a backing.
The type of backing determines how it can be installed.
The bark of a tree commonly known as Cork Oak and native to the Mediterranean region and the bark naturally splits every 9 to 15 years. It can be safely harvested causing
no harm to the tree. Cork is naturally hypoallergenic and resistant to mold and
Decorative Layer
The rotogravure printing process offers a multitude of design possibilities that
are expressed through the decorative layer such as patterns, geometrics, natural
stone designs and more.
A method of vinyl flooring installation in which the flooring is not bonded to the
substrate by any adhesive.
Full Spread
A vinyl flooring installation method in which the adhesive is trowled over the entire
A vinyl manufacturing process that uses solid colored vinyl chips laid on top of
a carrier sheet and then bonded together with heat and pressure. The inlaid process
has been around for years and generally results in geometric type patterns and designs.
Inner Core
Consisting of a foam and vinyl wear layer, the inner core provides durability, insulation
and comfort.
Made of natural ingredients that include linseed oil, cork, limestone, wood flour
and tree resins. The color goes all the way through, making it extremely wearable
and durable.
Perimeter Adhered
A vinyl flooring installation method in which adhesive is only applied to the perimeter
of the flooring and also at the seams.
These floors have some "give" or elasticity when you walk across them.
This category includes linoleum, cork, rubber and specialty resilient.
The most commonly used method for making residential vinyl floors.
This process involves a print cylinder that spins around while the vinyl's core
layer (called the gel coat) passes underneath. The cylinder systematically prints
various colored ink dyes to create the pattern.
Rubber flooring is extremely durable, virtually indestructible, quiet and warm to
walk on. It also resists dents and stains and its waterproof surface has an anti-slip
finish. However, rubber is relatively expensive and must be installed by an experienced
installer for maximum performance.
Since vinyl comes in 6' and 12' widths, seaming may be necessary depending
on the area to be covered. Certain patterns will hide seams better. For example,
tile patterns with grout lines are better able to mask seams.
Seam Sealer
A thin liquid adhesive applied to the cut edges of carpet to lock in the tufts and
prevent edge ravel. Seam sealers may be visible in contrast with different vinyl
textures and finishes.
A rough floor on top of which the vinyl flooring is applied.
The surface on which the vinyl flooring will be laid. If installing over a wood
substrate, an underlayment will generally be necessary. A concrete substrate will
not require an underlayment but will require some floor preparation.
Vinyl Composition Tiles. A resilient floor covering made of vinyl or vinyl composition
materials. VCT has all the advantages of vinyl.
Made from a mixture of polyvinyl chloride and plasticizer, it is usually flexible
and non-porous. Pigments are added for color.
A layer of material applied to the top surface of vinyl flooring. The thickness
of the wearlayer varies with each vinyl product collection, or series, and is generally
measured in mils. The thickness of a mil is about the same as a page in a phone
book. Premium wearlayers offer superior resistance to stains, scuffs and scratches.
How long a vinyl floor will look new and fresh is based on the wearlayer's performance.


text:
Blood London have been providing Teicoplanin Assay on a self-referral basis to patients in Central and Greater London for over 20 years. Simply walk-in weekdays between 9am and 6pm or on weekends between 10am and 2pm, to have your blood taken by a highly experienced professional in our private, Harley Street clinic using some of the best labs in europe.
Please note that when ordering blood tests on a self-request basis, we will forward you the laboratory report without note or comment from our doctors unless you are under their care.
Following the results of your test, if you would like to undergo a consultation, further testing or treatment please feel free to reach out to the clinic and we'll be happy to help.
Select the test that you would like to undergo
Go to the Harley Street clinic for your blood draw and pay for your test in person
As soon as the results are ready, the will be sent to you by your chosen method


text:
Elements Collection Pizza Cutter
This line of gourmet tools has Cuisinart's trademark logo, elegantly embossed in stainless steel, right on every handle. The black nonslip grips have a firm and comfortable hold to make any task, from stirring to mixing to serving, easy. The Nylon tool heads are safe for nonstick cookware and are heat resistant to 400⁰F. Dishwasher Safe.


text:
Join our affiliate program and start earning money for every sale you send our way!Simply create your account, place your linking code into your website and watch your account balance grow as your visitors become our customers.
- Username must be a minimum of 4 characters.- Username can be alpha-numeric.- Username can contain these characters: _ (underscores only)- Password must be a minimum of 4 characters.- Password can be alpha-numeric.- Password can contain these characters: !@#$%^&*()-_ []{}<>+=
This entry must match the Password entry.


text:
$4.99 Flat Rate Shipping
New look website & great features
Thousands of new & vintage pieces
Tons of collections
🔍Enhanced product search🔍
You have %itemCount% in your cart. Total being %total%
The center of a geometrically layered band is encrusted in a single row of smoky rhinestones for an edgy refinement. Features a stretchy band for a flexible fit.
Sold as one individual ring.
We work hard to bring you a wide selection of jewelry from the extensive Paparazzi jewelry catalog. Pieces may be in stock, out of stock, pre-claim, or pre-order. For pre-claim, please see here. For pre-order, see note below and our New Release collection. Don't see something you're looking for? Please Contact Us.
If a Pre-Order piece (says "PRE-ORDER" in title): then it is a New Release item is still on its way to us from Paparazzi Accessories (the "Manufacturer"). When you purchase a pre-order item, it will be shipped to you as soon as it is received in stock.Pre-Order items in the same paid order as in stock items may delay the shipment of that particular order until the final pre-order item is received. For complete details, please see our Shipping Policy.
Products are shipped within 2 to 6 business days.
Care for your Paparazzi jewelry is simple. For tips, please see this page.
For return policy, see here.


text:
Dinosaur Hoodie Pajamas For Couples
These Dinosaur matching PJs are TOO CUTE to ignore!
Strike off your couple goals with our matching pajama sets for men and women. You've gotta get this Today!!
Buy these adorable and cozy his and hers pajama sets for yourself today!
✔ These soft and furry pajamas are best for your Christmas pajama party!
✔ Material: Made of thick and warm Fleece for fall and winters
✔ Features:
- Full Sleeves and Hooded Shirt with Ears
- Cute Dinosaur with Spikes on the front and back.
✔ Designs Not available in local stores!
✔ One Set Includes:
1 X Hoodie
1 X Trouser
✔ Please measure with a measuring tape and select your size carefully.
P.S. order a size larger for a perfect fit.
✔ Don't waste your time thinking as these might go out of stock pretty soon!
Hurry! LIMITED STOCKS ADD TO CART NOW!!
FREE Shipping
Processing Time: 3-5 days of order
Return & Refund: You can apply for a return within 10 days of receipt of the parcel
Thank you for visiting and shopping at BigBeryl. Following are the terms and conditions that constitute our Shipping Policy.
Shipment Processing Time
All orders are processed within 3-5 business days. Orders are not shipped or delivered on weekends or holidays.
If the product needs customizations then the processing may differ, it will be mentioned on the respective product page.
If we are experiencing a high volume of orders, shipments may be delayed by a few days. Please allow additional days in transit for delivery. If there will be a significant delay in shipment of your order, we will contact you via email or telephone.
Shipping Rates & Delivery Estimates
We don't charge anything, Yes! the shipping is completely FREE!
Countries |
Estimated delivery time |
Shipment cost |
15-25 days |
Free |
EU, Japan, South Korea, Russian Federations, Sweden, Denmark, Norway, AUS |
10-25 days |
Free |
Other |
15-45 days |
Free |
Notes -
1) Delivery delays can occasionally occur due unavoidable factors like extreme weather, pandemic, local factors
2) Please provide correct address at the time of order. In the event of wrong address the local post carriers may destroy the package when they are not able to reach you.
If you have given wrong address contact us immediately on firstname.lastname@example.com to make it right.
Incorrect Address
We know you're excited to receive your order, but did you know that reviewing your shipping address can make all the difference? To avoid any delivery mishaps, it's crucial to double-check your address information before completing your purchase.
Please remember that we cannot update information once your package departs our facility.
This means we are not responsible for lost or damaged packages due to an incorrect address.
To ensure that your package arrives on time and in excellent condition, follow these simple tips:
1) Verify your shipping address before placing your order
2) Use an accurate and complete address
3) Include any necessary apartment or suite numbers
By taking these steps, you can help avoid shipping snafus and ensure a smooth delivery experience.
Shipment confirmation & Order tracking
You will receive a Shipment Confirmation email once your order has shipped containing your tracking number(s). The tracking number will be active within 2-3 days.
Customs, Duties and Taxes
BigBeryl is not responsible for any customs and taxes applied to your order. All fees imposed during or after shipping are the responsibility of the customer (tariffs, taxes, etc.).
BigBeryl is not liable for any products damaged or lost during shipping. If you received your order damaged, please contact the shipment carrier to file a claim.
Please save all packaging materials and damaged goods before filing a claim.
Returns & Refund Policy
Our Return & Refund Policy provides detailed information about options and procedures for returning your order.
Returns & Refunds
Returns & Refunds
We do not accept returns unless there is a defect in the product. Our policy lasts 10 days. If 10 days have gone by since your order delivered, unfortunately, we can't offer you a refund or exchange.
To be eligible for a return, your item must be unused and in the same condition that you received it. It must also be in the original packaging. Do not ship a product unless your return has been approved.
You can apply for full Refund if:
1) Product received is damaged.
2) The product is received too late, that is if 75 days has passed by since your order was shipped.
3) The product is not what you order, for example, color is different.
To complete your return, we require a receipt or proof of purchase.
Please see that the customers are responsible for ALL return shipping costs. Our customer support team is always ready to help you with your concerns. Send us an email at email@example.com and we will get back to you within 24 hours.
There are certain situations where only partial refunds are granted (if applicable)
> Any item not in its original condition is damaged or missing parts for reasons not due to our error.
Note: Partial refunds also means that return shipping will be deducted from your refund.
Refunds (if applicable):
Once your return is received and inspected, we will send you an email to notify you that we have received your returned item. We will also notify you of the approval or rejection of your refund.
If you are approved, then your refund will be processed, and a credit will automatically be applied to your credit card or original method of payment, within a certain amount of days.
Notes -
1) 5% Bank Payment Processing fees will be deducted from the full refund.
2) In event of wrong address/ insufficient address provided by the customer resulting in package returned or discarded by the local post, customer is not eligible for refund.
Late or missing refunds (if applicable):
If you haven't received a refund yet, first check your bank account again.
Then contact your credit card company, it may take some time before your refund is officially posted.
Next, contact your bank. There is often some processing time before a refund is posted.
If you've done all of this and you still have not received your refund yet, please contact us at email@example.com.
Sale items (if applicable)
Only regular priced items may be refunded, unfortunately, sale items cannot be refunded.
Exchanges (if applicable)
If the product is damaged/ broken or the product delivered is different from what you ordered then we will replace a new product in exchange.
Return Shipping:
You will be responsible for paying for your own shipping costs for returning your item. Shipping costs are non-refundable. If you receive a refund, the cost of return shipping will be deducted from your refund.
If you are shipping an item over $75, you should consider using a trackable shipping service or purchasing shipping insurance. We don't guarantee that we will receive your returned item.


text:
8 Ways to Fix: Text SMS App Not Working
Text SMS App Not Working creates a big issue when you urgently need it. However, users of the app often encounter bugs.
Text SMS app users often experience issues such as not being able to load the app or it not working. These problems can arise for many reasons.
This article will provide all information regarding the Text SMS app not functioning and possible solutions.
Why is Text SMS App Not Working?
If Text SMS app not working, It can happen due to several reasons, such as:
- There Might be a glitch or a bug in the Text SMS app.
- Your device is not compatible with Text SMS app
- You have turned on the low data mode in your mobile
- You haven't updated the Text SMS app in a long while
- Your Wi-Fi or mobile data is not working properly
9 Fixes "Text SMS App Not Working"?
1. Check if Wi-Fi or cellular data is working
It is common to get stuck on an app page when you aren't connected to the internet or have poor internet connectivity. Switch off the internet connection and then turn it on again to find a good place.
2. Clear Cache and Data in the Text SMS App
Steps To Clear Cache and Data in the Text SMS App:
Step 1: Click the menu icon on your device from the device's home screen.
Step 2: Make a selection of options.
Step 3: Apps should be chosen.
Step 4: From your app list, find the Text SMS app. Select it by clicking on it.
Step 5: Choose a storage option.
Step 6: Click the "Clear Data" option at the bottom of the screen. This helps to clean the data as well as the cache.
You can Check Here What is Cache?
Note: Available screens, settings, or steps for clearing the cache may vary by software version and phone model.
3. Update Text SMS App
Your smartphone is running an outdated version of Text SMS, which is why it's not working properly.
Apps must be kept up-to-date because bugs can be fixed, and patches and new features are all available as part of in-app upgrades. The Text SMS app can be downloaded from the Google Play Store.
4. Restart Your Phone
If you experience similar problems, you can reset your phone. If your phone is not responding to your commands, you can restart the app and it will work as new.
It is easy to reset your device and fix any technical problems you may have with its functions or features.
Before using the app, ensure your device is connected to the internet. Your application should now be live and available for use.
5. Contact the Text SMS support team
After trying several methods, you can always contact the Text SMS Support team if your issue is not solved. They provide 24*7 customer service. So, you can contact Text SMS Support and ask your query. They will solve the issue as soon as possible.
Thus, these processes can help to solve the Text SMS App not working issue.
6. Reinstall Text SMS App
These issues can usually be fixed by reinstalling the program. First, you need to delete the app from your device. Next, go to Google Play and search for the app. Select the program you wish to install and click the Install button.
7. Try using Text SMS with a different browser or device
Finally, a common way to troubleshoot a computer problem is to see if you can reproduce the same issue elsewhere. If the iPhone Text SMS app isn't working, for example, try using Text SMS in the iPhone's Safari browser — or a browser on your computer. If it isn't working in Chrome on your PC, try opening the site in Firefox.
Final Thought
Today's generation is the Internet generation. And there are hundreds of data stored and cleaned. So there is nothing to worry about. There might be any technical error Text SMS with the application, or this error might be from your side. So, If there is an error from the company side then it will be solved as early as possible by the company.
If Error from your side then you can try the above-mentioned solution to solve your Problem. Hope this guide will help you to solve the problem which you are finding. If Helped then please share it with your friends and social media to help us to reach out more people. Have a good day.