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Transdermal treatment options for neurological disorders: impact on the elderly.

As people grow old, their need for medications increases dramatically because of the higher incidence of chronic pain, diabetes mellitus, cardiovascular and neurological diseases in the elderly population. Furthermore, the elderly require special consideration with respect to drug delivery, drug interactions and adherence. In particular, patients with chronic neurological diseases often require multiple administration of drugs during the day to maintain constant plasma medication levels, which in turn increases the likelihood of poor adherence. Consequently, several attempts have been made to develop pharmacological preparations that can achieve a constant rate of drug delivery. For example, transdermal lisuride and apomorphine have been shown to reduce motor fluctuations and duration of 'off' periods in advanced Parkinson's disease, while rotigotine allows significant down-titration of levodopa without severe adverse effects. Thus, parkinsonian patients with long-term levodopa syndrome or motor disorders during sleep could benefit from use of transdermal lisuride and apomorphine. Moreover, transdermal dopaminergic drugs, particularly rotigotine, seem the ideal treatment for patients experiencing restless legs syndrome or periodic limb movement disorder during sleep, disorders that are quite common in elderly people or in association with neurodegenerative diseases. Unlike dopaminergic drugs, transdermal treatments for the management of cognitive and behavioural dysfunction in patients with Parkinson's disease and Alzheimer's disease have inconsistent effects and no clearly established role. Nevertheless, because of their favourable pharmacological profile and bioavailability, the cholinesterase inhibitors tacrine and rivastigmine are expected to show at least the same benefits as oral formulations of these drugs, but with fewer severe adverse effects. Transdermal delivery systems play an important role in the management of neuropathic pain. The transdermal lidocaine (lignocaine) patch is recommended as first-line therapy for the treatment of postherpetic neuralgia. Furthermore, in patients with severe persistent pain, transdermal delivery systems using the opioids fentanyl and buprenorphine are able to achieve satisfactory analgesia with good tolerability, comparable to the benefits seen with oral formulations. Transdermal administration is the ideal therapeutic approach for chronic neurological disorders in elderly people because it provides sustained therapeutic plasma levels of drugs, is simple to use, and may reduce systemic adverse effects. Several transdermal delivery systems are currently under investigation for the treatment of Parkinson's disease, Alzheimer's disease and neuropathic pain. Although most transdermal delivery systems treatments cannot be considered as first-line therapy at present, some of them provide clear advantages compared with other routes of administration and may become the preferred treatment in selected patients. In general, however, most transdermal treatments still require long-term evaluation in large patient groups in order to optimise dosages and evaluate the actual incidence of local and systemic adverse effects.

Administration, Cutaneous↗

CNS-related side-effects with metoprolol and atenolol.

Vivid and bizarre dreams, hallucinations, sleep disturbance and psychosis have all been described following treatment with beta-blockers. It has been suggested that these central nervous system (CNS) side-effects are related to the degree of lipophilicity of the beta-blocker. A randomized double-blind crossover study was performed to compare the incidence of CNS side-effects with atenolol and metoprolol in hypertensive patients who had reported CNS side-effects with lipophilic beta-blockers. Eleven women and six men completed the study, in which a 30-item psychiatric questionnaire was used to detect changes in psychological status and possible CNS side-effects. Discontinuation of the original lipophilic beta-blocker produced a significant improvement in quality of sleep, dreams, concentration, memory, energy, and anxiety. No significant CNS side-effects were reported with atenolol, but introduction of metoprolol caused a significant increase in the incidence of sleep disturbance (p less than 0.01) and restless nights (p less than 0.05), as well as failure to achieve satisfactory sexual intercourse (p less than 0.05). When compared with atenolol, metoprolol was associated with a significantly higher incidence of restless disturbed nights (p less than 0.05). Blood pressure control was identical for both beta-blockers. This study appears to confirm the association between CNS-related side-effects and the lipophilicity of beta-blockers.

Adult↗

Sleep symptoms and clinical markers of illness in patients with heart failure.

The purpose of this study was to survey patients with heart failure (HF) for sleep symptoms using a standardized questionnaire and correlate symptoms with conventional markers of clinical status. A self-report paper questionnaire was offered to patients presenting to a tertiary care HF clinic. Symptoms were grouped according to "risk" categories and correlated with routine clinical information. One hundred six (52.7% of 201 with all data) respondents had a high pretest probability for sleep apnea syndrome. Sixty three (31.3%) reported symptoms suggesting the presence of chronic insomnia; seven (3.5%) and eight (4%) reported symptoms of narcolepsy and restless legs syndrome, respectively. High-risk respondents for sleep apnea had a higher body mass index (p<0.001), were younger (p<0.05), and had a higher ejection fraction (p<0.05). The odds ratio (confidence interval) for paroxysmal nocturnal dyspnea (PND) to a complaint of sleepiness was 1.99 (1.1-3.6) and to a complaint of insomnia was 3.5 (1.8-6.5). In men, complaints of sleepiness in patients with PND were correlated, 4.47 (1.9-10.3), as was a correlation to high pretest probability for sleep apnea, 2.47 (1.1-5.5). There were no correlation of New York Heart Association status classification to high risk for sleep apnea, but a complaint of insomnia tended to occur with worsening functional status (p<0.05). There was only modest correlation of self-reported symptoms as elicited by a questionnaire and risk for sleep disorders with common clinical assessments for HF. Such collection of symptoms might be useful in establishing guidelines for routine sleep testing or as an adjunct to clinical trials.

Adolescent↗

Symptoms of sleep disorders, inattention, and hyperactivity in children.

Children with sleep disorders are often inattentive or hyperactive, and some carry a diagnosis of attention deficit/hyperactivity disorder (ADHD) until their sleep disorder is detected. However, the potential behavioral impact of undiagnosed sleep disorders is not known. We sought to determine whether children with higher levels of inattention and hyperactivity more frequently have symptoms of sleep-related breathing disorders (SRBDs) or periodic limb movement disorder (PLMD). We surveyed parents of 2-18-year-old patients at a child psychiatry clinic (n = 70) and a general pediatrics clinic (n = 73) to assess the children's behavior, snoring, complaints of restless legs at night, and daytime sleepiness. A validated pediatric sleep questionnaire provided the explanatory variables, and a scale for inattention and hyperactivity, derived from the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), provided the dependent variable. Habitual snoring was more frequent (33%) among children who carried a diagnosis of ADHD than among the other children at the psychiatry or general pediatric clinics (11 and 9%, respectively, chi-square test, p = 0.01). Snoring scores, derived from six snoring- and SRBD-related question items, were associated with higher levels of inattention and hyperactivity. The complaint of restless legs and a composite score for daytime sleepiness showed some evidence, though less consistent, of an association with inattention and hyperactivity. The association of snoring with inattention and hyperactivity suggests that SRBDs and perhaps other sleep disorders could be a cause of inattention and hyperactivity in some children. If a causal effect is present, our data suggest that 81% of habitually snoring children who have ADHD--25% of all children with ADHD--could have their ADHD eliminated if their habitual snoring and any associated SRBD were effectively treated.

Adolescent↗

Alcohol use and periodic limb movements of sleep.

Alcohol causes significant sleep disturbance but the causes are not well understood. We investigated the relationship between alcohol use and periodic limb movements in a large population of patients at a sleep disorders center. The likelihood of having a clinically significant number of periodic leg movements (more than 20 per hour of sleep) was increased 3-fold in women who consumed two or more alcoholic drinks per day compared with those who did not (25% versus 8%). A similar relation was found among men (22% versus 13%). In addition, women who consumed two or more drinks per day were more likely to report symptoms of restless legs and to be diagnosed with restless legs syndrome. These findings suggest that periodic leg movements contribute to sleep disturbance in a significant proportion of alcohol users. Alcohol use may increase the frequency of periodic leg movements in susceptible individuals. On the other hand, subjects with symptoms related to periodic leg movements may be using alcohol to relieve symptoms, or the movements may be secondary to alcohol-induced sleep disturbance.

Adult↗

Sleep-wake cycle in human African trypanosomiasis.

Sleeping sickness patients are classically described as sleepy by day and restless by night. Prior to this study, we had objectively confirmed this description by recording 24-h sleep patterns in a patient with human African trypanosomiasis. We report 24-h polysomnographic recordings (EEG, electrooculogram, electromyogram, electrocardiogram, and nasal, buccal, and thoracic respiratory traces) performed on two eight-channel electroencephalographs in eight patients with untreated sleeping sickness at an early stage of meningoencephalitis. As in our previously reported patient, there was no hypersomnia. The patients presented mainly a disorganization of the circadian alternation of sleeping and waking, with no or little alteration in the states of vigilance at this early stage of the disease. The disorganization was proportional to the degree of severity of the clinical symptoms. It may be due to an alteration in biological clock mechanisms.

Adolescent↗

Sleep and dialysis: a research-based review of the literature.

Textbook descriptions of dialysis patients have long included features of insomnia, day-night reversal, and disturbed sleep. Moore recently, a very high prevalence of subjective sleep complaints and specific primary sleep disorders such as sleep apnea syndrome, periodic leg movement disorder, and restless legs syndrome have been documented in the population. These problems may in part be responsible for the low rehabilitation rate seen in ESRD patients. The purpose of this article is to assist dialysis nurses in their efforts to better understand the sleep alterations experienced by their patients by presenting a succinct review of the research literature. The major topics of discussion include: the prevalence and importance of sleep complaints in dialysis patients; subjective features and related factors; polysomnographic features; and contributing factors.

Humans↗

[Restless legs syndrome and psychiatric diseases].

Restless legs syndrome (RLS) is a common sleep disorder characterized by dysesthesias and paresthesias in the legs, occurring at rest, worsening at evening and night and alleviated by movements. Apart from idiopathic cases, RLS and psychiatric diseases share a common association and recent studies have shown a strong association between RLS and antidepressants. The effects of antidepressants such as selective serotonin reuptake inhibitors and venlafaxine on worsening RLS have been widely studied and their use should be avoided. The clinical spectrum of RLS and the physiopathological link with antidepressant will be discussed in this review in order to provide new preventive strategy in clinical practice to improve diagnosis, orientating therapeutic decision and evaluating efficacy of treatment.

Antidepressive Agents↗

Sleep-disordered breathing and hypotension.

We investigated the presence of low blood pressure (BP) in 4,409 subjects referred for overnight polysomnography. A low resting arterial BP (systolic BP < 105 mm Hg, diastolic BP < 65 mm Hg) was present in 101 subjects (2.3%). Low BP was more prevalent in subjects with upper airway resistance syndrome (UARS) (23%) than in subjects with obstructive sleep apnea syndrome (OSAS) (0.06%), parasomnia (0.7%), restless leg syndrome (0.9%), or psychological insomnia (0.9%). In order to investigate BP homeostasis, we conducted polysomnography followed by tilt-table testing on 15 subjects with orthostatic intolerance (OI) and UARS, five normotensive subjects with UARS, five subjects with insomnia and low BP, 15 subjects with OSAS, and 15 healthy control subjects. Fifteen subjects with UARS and OI and 15 healthy controls also underwent 24-h ambulatory BP monitoring. Subjects with OI and UARS had lower mean daytime systolic (119 +/- 28 mm Hg) and diastolic (75 +/- 18 mm Hg) BP than did control subjects (131 +/- 35 mm Hg and 86 +/- 19 mm Hg, respectively) (p < 0.05). During tilt-table testing, subjects with UARS and a history of OI had a greater decrease in systolic BP (27 +/- 3 mm Hg) than did control subjects (7.5 +/- 1.6 mm Hg), subjects with OSAS (6.8 +/- 1.2 mm Hg), normotensive subjects with UARS (7.2 +/- 0.84 mm Hg), or hypotensive insomniacs (7.4 +/- 1.1 mm Hg) (p < 0.01). We conclude that approximately one fifth of subjects with UARS have low BP and complain of OI. Tilt-table testing may be indicated to confirm orthostatic intolerance in subjects with UARS.

Adult↗

[Restless legs syndrome in childhood].

The diagnostic criteria of restless legs syndrome were defined in 1995 by the International Restless Legs Syndrome Study Group (IRLSSG). In light of the latest scientific evidence and increasing clinical experience, the diagnostic criteria were revised in a consensus workshop. Participants of the workshop considered the development of new diagnostic criteria especially important for the following subgroups: (1) for children and (2) for the cognitively impaired elderly. The common characteristic of both groups lies in their difficulty in expressing subjective symptoms adequately. This considerably impedes the diagnosis of restless legs syndrome. In 2002, a proposal for diagnostic criteria of restless legs syndrome in childhood was formulated by members of the study groups "Movement Disorders and Sleep" and "Paediatrics" of the German Sleep Society. The proposal was partially incorporated into the diagnostic criteria for restless legs syndrome in childhood suggested by the IRLSSG. The current criteria are recommendations to enhance further research and must be validated by clinical studies. The following article gives an overview of published studies on restless legs syndrome in childhood, reviews the proposals for diagnostic criteria, and summarizes the peculiarities to be considered in diagnosing restless legs syndrome in children.

Adolescent↗

[Sleep disorders in patients treated with continuous ambulatory peritoneal dialysis].

BACKGROUND: A lot of patients with end stage renal disease with the necessity of renal replacement therapy have some sleep problems. The aim of this study was to get basic information about the sleep of patients treated with continuous ambulatory peritoneal dialysis (CAPD), mainly their subjective view on their sleep, including comparison with hemodialyzed patients (HD). METHODS: All patients treated with continuous ambulatory peritoneal dialysis in two dialysis centres were given a simple questionnary containing 20 questions concerning sleep. It was filled in by all these patients--25 patients (mean age 58.1 years)--12 men and 13 women. Data obtained from 103 hemodialyzed patients from the same two-dialysis centres were used for comparison (mean age 60.4 years)--61 men and 42 women (the same questionnary). RESULTS: 40% of CAPD patients regard their sleep as bad. Thirty six percent of patients have problems with falling asleep, 32% awake three times or more during the night and 28% snore or have some breath problems. CAPD patients feel more frequently tired after the night (32% vs. 18.4% HD), more patients sleep during the day (64% vs. 5.15% HD) and fewer patients feel restlessness of legs (36% vs. 45.6% HD). These differences are not statistically significant. CONCLUSION: Occurrence of sleep disorders and their characteristics in patients on CAPD is similar to that in hemodialyzed patients.

Adult↗

Restless legs syndrome: a clinical study of 55 patients.

BACKGROUND: Restless legs syndrome (RLS) is a common sleep disorder. In 1995, clinical criteria for the diagnosis of RLS were defined. OBJECTIVE: To describe the clinical spectrum in a series of unselected RLS patients meeting the new diagnostic criteria. METHODS: We prospectively assessed by questionnaire and clinical assessment the characteristics of 55 consecutive RLS patients (35 women, 20 men; mean age = 62 +/- 16 years). RESULTS: In 27% of the patients, RLS started before the age of 20 years (early-onset RLS). Sensory disturbances were painful in 56% of patients and felt in legs (98%), arms (35%), and 'internally' (45%). Motor disturbances included 'dyskinesias while awake' (36%). Insomnia (58%) was commoner than hypersomnia (24%). In 67% of the patients, no etiology of RLS was found (idiopathic RLS). Early-onset RLS was more commonly familial (p = 0.01) and associated with 'growing pains' (p = 0.005) than late-onset RLS. Patients with RLS and hypersomnia were younger (p = 0.01) and less commonly had painful sensations (p = 0.04) than patients with RLS and insomnia. Patients with idiopathic RLS were younger (p = 0.004), and less commonly had insomnia (p = 0.01) than patients with symptomatic RLS. CONCLUSIONS: RLS is a clinically pleomorphic syndrome, reflecting the contribution of multiple genetic and acquired factors in the pathogenesis of RLS.

Adult↗

Releasing restraints: providing safe care for the elderly.

To examine the behavioral effects of releasing restraints and the feasibility of caring for patients considered at risk if unrestrained, two patients were continuously videotaped using surveillance cameras for 1 week with and 1 week without restraints. The videotapes were coded and analyzed using nonparametric and parametric statistics. In Patient #1, motor behavioral changes with a decrease of restless behaviors, as well as changes in sleeping position, were observed. There were no changes in verbal behavior. For Patient #2, no changes in motor or verbal behavior were observed. Nursing care showed a non-significant decrease in nursing care time and an increase in the number of nursing contacts. The implications of the findings and the use of videotapes as a method for collecting observational data in the clinical area are discussed.

Aged↗

Periodic limb movement disorders and spells of profound muscle weakness due to airborne and dietary factors in humans.

Periodic limb movement disorders and the restless legs syndrome, generally considered to be sleep disorders, have a combined prevalence of almost 10% of the general population and are more common in women than in men. Although reduced dopamine activity in central nervous system motor control pathways seems to play a role, little, other than a list of associated risk factors, is known about the conditions that initiate the episodes. We report three patients, two teenage girls and one female teacher, who developed periodic limb movement disorders associated with high mold counts in a classroom and the gymnasium in the girls' school, and in the ventilating system in the teacher's school. Their disorders occurred when they attended their schools and cleared when they did not. These findings, combined with an earlier report of three cases where the disordered movements were triggered by dietary factors, suggest that in some patients, periodic limb movement disorders may be induced by inhalant as well as by dietary factors. Although these 6 patients may represent a subgroup of people with periodic limb movement disorders, potential dietary and environmental triggers should be considered in the clinical evaluation of patients seeking treatment for periodic limb movement disorders.

Adolescent↗

An automatic method for scoring leg movements in polygraphic sleep recordings and its validity in comparison to visual scoring.

STUDY OBJECTIVES: The study presents an automatic method for scoring leg movements in polysomnographic recordings and describes an empirical investigation of its validity. DESIGN: Leg movements measured by means of the surface electromyogram activation of the right and left tibialis anterior muscle contained in 24 digitally recorded all-night polysomnograms were analyzed visually according to the American Sleep Disorders Association guidelines by 2 experienced raters and automatically scored using a newly developed electromyogram-based analytical method. Two visual scorings and the automatic scoring were compared in pairs using descriptive and confirmative statistical methods. SETTING: N/A. PARTICIPANTS: All-night polysomnograms of adaptation nights at the sleep laboratory of 10 patients with idiopathic restless legs syndrome (RLS) according to the International RLS Study Group. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Agreement rates between the 2 well-trained scorers and the automatic method were comparable. Based on the first scorer's results (100%) 92.5% of the movements were detected by the second scorer and 94.3% by the automatic method. When the visual scorings were compared, the rate of false-positive and false-negative errors were 7% and 3%, respectively. Comparing both visual scorings with the results of the automatic scoring yielded false-positive and false-negative rates in the range from 3% to 8%. CONCLUSIONS: The degree of accordance between the 2 visual scorings and between the visual and the automatic scorings were comparable. Therefore, this method is valid and may be used for the automatic detection of leg movements in future studies.

Electromyography↗

Nicotine withdrawal versus other drug withdrawal syndromes: similarities and dissimilarities.

Many of the symptoms of nicotine withdrawal are similar to those of other drug withdrawal syndromes: anxiety, awakening during sleep, depression, difficulty concentrating, impatience, irritability/anger and restlessness. Slowing of the heart rate and weight gain are distinguishing features of tobacco withdrawal. Although nicotine withdrawal may not produce medical consequences, it lasts for several weeks and can be severe in some smokers. Like most other drug withdrawals, nicotine withdrawal is time-limited, occurs in non-humans, is influenced by instructions/expectancy and abates with replacement therapy and gradual reduction. Unlike some other drug withdrawal syndromes, protracted, neonatal or precipitated withdrawal does not occur. Whether nicotine withdrawal is associated with tolerance, acute physical dependence, greater duration and intensity of use, rapid reinstatement, symptom stages, cross-dependence with other nicotine ligands, reduction by non-pharmacological interventions and genetic influences is unclear. Whether nicotine withdrawal plays a major role in relapse to smoking has not been established but this is also true for other drug withdrawal syndromes.

Animals↗

Pain: clinical validation with postoperative heart surgery patients.

PROBLEM: To estimate the content validity of the nursing diagnosis of pain in postoperative heart surgery patients. METHODS: Observation of and interviews with postoperative heart surgery patients (N = 80), 40 experiencing pain and 40 without pain. FINDINGS: The group experiencing pain had statistically different results from the group without pain, with a higher frequency in the following 19 defining characteristics: verbal report of pain, discomfort, fear of reinjury, sleep disturbance, guarding behavior, distraction behavior, irritability, restlessness, facial mask of pain, increased heart rate, immobility, anxiety, loss of appetite, self-focus, withdrawal, impaired thought process, unusual posture, increased blood pressure, and changes in respiratory patterns. CONCLUSIONS: These defining characteristics support the idea that pain is a complex phenomenon of clinical interest to nursing that needs better understanding. Studies using the same defining characteristics in other sample groups of patients with acute and chronic pain might be useful in the refinement of this nursing diagnosis.

Adult↗