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PubMed2000

Which derivative from overnight oximetry best predicts symptomatic response to nasal continuous positive airway pressure in patients with obstructive sleep apnoea?

The cost and inconvenience of polysomnography for the investigation of obstructive sleep apnoea (OSA) has led to the search for simpler and cheaper alternatives. These are usually compared to an apnoea/hypopnoea index (AHI) derived from oro-nasal airflow and ribcage/abdominal effort sensors. However, AHI is not a proven gold standard for the identification of clinically important OSA. Recent work has shown that correctly analysed oximetry indices not only mimic AHI with considerable accuracy, but also predict the symptomatic response to nasal continuous positive airway pressure (nCPAP) at least as well as conventional polysomnographic indices. This current study looks at 10 different derivatives of all-night oximeter tracings in 81 patients with OSA, and compares their ability to predict the improvement in subjective sleepiness after 6 months of nCPAP therapy. Sleep apnoea in this study was defined as a > 4% SaO2 dip rate of > 10 h(-1), and an Epworth sleepiness score (ESS) of > 10 on presentation. Subjects took part in a placebo-controlled trial of nCPAP for 1 month and thereafter were all supplied with nCPAP set at an effective pressure. All night SaO2 was sampled every 2 sec and later analysed for mean, median, mean nadir of SaO2 dip, time below 90%, 2 and 12 sec delta index (an average measure of SaO2 change across these two time periods), rapid resaturation index (rises in SaO2 > 3% within 10 sec per hour), and > 4, > 3, and > 2% dips per hour. These indices were then correlated with the change in ESS seen after 6 months on nCPAP. Median compliance for the group was 5.8 (5/95% range, 1.5-8.0) h night(-1). The two best correlates of improvement in ESS were the > 4% SaO2 dips h(-1) (Spearman's r = -0.33 P=0.002) and the delta 12 sec index (r = -0.33, P = 0.003). Cumulative time below 90% SaO2 was almost as good (r = -0.29, P = 0.009). The worst correlate was the > 2% SaO2 dips h(-1) (r = 0.01, not significant). This study has identified which of several analyses of overnight oximeter recordings best identify nCPAP responsive OSA. Both > 4% SaO2 dips and 12 sec delta index are equally predictive and presumably the most appropriate derivatives to calculate from overnight records of SaO2.

Adult↗
PubMed2005

Comparison of three ways to determine and deliver pressure during nasal CPAP therapy for obstructive sleep apnoea.

BACKGROUND: The simplest method of initiating and maintaining therapeutic continuous positive airways pressure (CPAP) therapy for obstructive sleep apnoea (OSA) has not been established. METHODS: Ninety eight subjects with OSA requiring CPAP treatment (more than 10 dips in oxygen desaturation of >4% per hour of sleep study and Epworth Sleepiness Score (ESS) >9) were randomised prospectively to three different methods of CPAP delivery for 6 months: (1) autotitration pressure throughout; (2) autotitration pressure for 1 week followed by fixed pressure (95th centile) thereafter; and (3) fixed pressure determined by algorithm (based on neck size and dip rate). Patients and investigators were blind to group allocation. One week after initiation the patients were routinely reviewed by sleep nurses. Study assessments took place before starting CPAP treatment and 1 and 6 months after to assess ESS, maintenance of wakefulness test, 24 hour blood pressure, general health (SF-36), and sleep apnoea related quality of life. CPAP internal monitoring data were also collected. RESULTS: There were no significant differences in any of the outcome measures or CPAP monitoring data between the three groups. The 95th centile CPAP pressures delivered in the 6 month and 1 week autotitration groups were higher than in the algorithm group, but the median pressures were lowest in the 6 month autotitration group. CONCLUSIONS: The method of determining CPAP pressure for treatment of moderate to severe OSA makes no significant difference to clinical outcome measures. The autotitration CPAP machine used has no advantage in this setting over simpler methods of pressure determination.

Adolescent↗
PubMed2001

Sleep-wake schedule disorder disability: a lifelong untreatable pathology of the circadian time structure.

Certain sleep-wake schedule disorders (SWSDs) cannot be successfully managed clinically using conventional methods of sleep therapy. We describe two cases of SWSD, the first following head trauma and the second originating during childhood, that had been misdiagnosed by physicians for many years. After conventional treatment for SWSD with light therapy and melatonin failed to bring about substantial improvement, it was determined that they were suffering from an incurable disability. Hence, we propose new medical terminology for such cases--SWSD disability. SWSD disability is an untreatable pathology of the circadian time structure. Patients suffering from SWSD disability should be encouraged to accept the fact that they suffer from a permanent disability, and that their quality of life can only be improved if they are willing to undergo rehabilitation. It is imperative that physicians recognize the medical condition of SWSD disability in their patients and bring it to the notice of the public institutions responsible for vocational and social rehabilitation.

Adult↗
PubMed2000

The art and science of continuous positive airway pressure therapy in obstructive sleep apnea.

Despite the high prevalence of obstructive sleep apnea (OSA) syndrome, no ideal therapy has emerged to date. Based on recent randomized trials, continuous positive airway pressure (CPAP) therapy is the treatment of choice. Although CPAP can prevent pharyngeal collapse in virtually all patients who choose to wear it, poor patient adherence with treatment limits its effectiveness. Although convincing data exist that treatment with CPAP can alleviate the neurocognitive sequelae of OSA, data on cardiovascular complications are more limited. Several recent reports support a lowering of nocturnal and daytime blood pressure with CPAP, but data on the prevention of myocardial infarction and cerebrovascular events are currently lacking. Patient adherence with CPAP can be improved with optimization of mask comfort, heated humidification, and intensive support and education. For those who remain poorly compliant, alternative therapies such as autotitrating devices and oral positive airway pressure can be considered. Further research into the basic mechanisms underlying OSA will be required for new therapeutic targets to develop.

Humans↗
PubMed1999

Mandibular advancement oral appliance therapy for obstructive sleep apnoea: effect on awake calibre of the velopharynx.

BACKGROUND: The mechanisms of action of oral appliance therapy in obstructive sleep apnoea are poorly understood. Videoendoscopy of the upper airway was used during wakefulness to examine whether the changes in pharyngeal dimensions produced by a mandibular advancement oral appliance are related to the improvement in the severity of obstructive sleep apnoea. METHODS: Fifteen patients with mild to moderate obstructive sleep apnoea (median (range) apnoea index (AI) 4(0-38)/h, apnoea-hypopnoea index (AHI) 28(9-45)/h) underwent overnight polysomnography and imaging of the upper airway before and after insertion of the oral appliance. Images were obtained in the hypopharynx, oropharynx, and velopharynx at end tidal expiration during quiet nasal breathing in the supine position. The cross sectional area and diameters of the upper airway were measured using image processing software with an intraluminal catheter as a linear calibration. RESULTS: AI decreased to a median (range) value of 0 (0-6)/h (p<0.01) and AHI to 8 (1-28)/h (p<0.001) following insertion of the oral appliance. The median (95% confidence interval) cross sectional area of the upper airway increased by 18% (3 to 35) (p<0.02) in the hypopharynx and by 25% (11 to 69) (p<0.005) in the velopharynx, but not significantly in the oropharynx. Although in general the shape of the pharynx did not change following insertion of the oral appliance, the lateral diameter of the velopharynx increased to a greater extent than the anteroposterior diameter. Following insertion of the oral appliance the reduction in AHI was related to the increase in cross sectional area of the velopharynx (p = 0.01). CONCLUSIONS: A mandibular advancement oral appliance increases the cross sectional area of the upper airway during wakefulness, particularly in the velopharynx. Assuming this effect on upper airway calibre is not eliminated by sleep, mandibular advancement oral appliances may reduce the severity of obstructive sleep apnoea by maintaining patency of the velopharynx, particularly in its lateral dimension.

Adult↗
PubMed2005

Patients' perspectives on how idiopathic pulmonary fibrosis affects the quality of their lives.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a debilitating lung disease with a survival of only three to five years from the time of diagnosis. Due to a paucity of studies, large gaps remain in our understanding of how IPF affects the quality of patients' lives. In only one other study did investigators ask patients directly for their perspectives on this topic. Further, currently there is no disease-specific instrument to measure health-related quality of life (HRQL) in patients with IPF. A carefully constructed measurement instrument, sensitive to underlying change, is needed for use in clinical trials and longitudinal studies of patients with IPF. Before developing such an instrument, researchers must improve their understanding of the relevant effects of IPF on patients' lives. On a broader scale, to provide the best care for people with IPF, clinicians must appreciate--from patients' perspectives--how this disease affects various aspects of their lives. METHODS: We used focus groups and individual in-depth interviews with 20 IPF patients to collect their perspectives on how IPF affects their lives (with a focus on the quality of their lives). We then analyzed these perspectives and organized them into a conceptual framework for describing HRQL in patients with IPF. Next, we examined how well certain existing measurement instruments--which have been administered to IPF patients in prior studies--covered the domains and topics our patients identified. RESULTS: In our framework, we identified 12 primary domains: symptoms, IPF therapy, sleep, exhaustion, forethought, employment and finances, dependence, family, sexual relations, social participation, mental and spiritual well-being, mortality. Each domain is composed of several topics, which describe how IPF affects patients' lives. When we compared the content of our conceptual framework with the existing instruments, we found the coverage of the existing instruments to be inadequate for several reasons, including they may tap general areas of QOL or HRQL but not some areas that appear to be most directly affected by IPF, and they include items that are relevant to symptoms and effects of other respiratory diseases but not IPF. CONCLUSION: Collecting patients' perspectives and developing an organized inventory of the relevant effects of IPF on patients' lives provides valuable information for improving our understanding of the impact of this disease on patients and their loved ones. We believe our findings will help alert clinicians and researchers to IPF patients' experiences and concerns. Based on the comparison or our conceptual framework with the content of four existing instruments, it would appear that developing an IPF-specific measurement instrument is justified. Our conceptual framework for describing health-related quality of life in patients with IPF lays a solid foundation for constructing such an instrument.

Adult↗
PubMed1982

Neurotransmitter precursors and brain function.

Brain function can be affected by the availability of dietary precursors of neurotransmitters. This occurs because the rate-limiting synthetic enzymes are not "saturated" with substrate under normal circumstances. Tyrosine affects catecholaminergic neurons that fire rapidly, whether in the brain stem to decrease blood pressure in hypertension or in the adrenal gland to increase blood pressure in hypotension, and has been used in the treatment of Parkinson's disease and depression. Choline forms acetylcholine and has been used successfully in the treatment of tardive dyskinesia and memory disorders. Tryptophan, which forms serotonin, has been used for chronic pain therapy, sleep disorders, depression, and appetite control. Although these substances may lack the potency of traditionally used agonists, they offer an increase in specificity because the enzymes necessary to convert them to neurotransmitters are found only in neurons. Precursors are also "physiological"; they are consumed as foods and, therefore, should be relatively safe therapeutic agents.

Animals↗
PubMed2000

[Artifact detection and signal reconstruction in the pupillogram].

Just as the EEG reflects different wake and sleep stages, changes in pupil dynamics reflecting different levels of vigilance are also to be found. The literature contains numerous reports on experimental set-ups for the recording of the pupillogram. Interesting methods of signal processing are to be found in [7] and [5]. Currently, such recordings are being used to check the success of sleep therapy. A problem that still needs solving is the optimal handling of artifacts caused by blinking. The present article proposes a procedure for artifact detection by back-propagation networks, and subsequent reconstruction of the signal by an AR model. Estimation of the signal is first demonstrated by a test signal, and then by a corrupted pupillogram.

Arousal↗
PubMed2003

GABA(C) receptors as drug targets.

GABA(C) receptors are the least studied of the three major classes of GABA receptors. The physiological roles of GABA(C) receptors are still being unravelled and the pharmacology of these receptors is being developed. A range of agents has been described that act on GABA(C) receptors with varying degrees of specificity as agonists, partial agonists, antagonists and allosteric modulators. Pharmacological differences are known to exist between subtypes of cloned GABA(C) receptors that have been cloned from mammalian sources. There is evidence for functional GABA(C) receptors in the retina, spinal cord, superior colliculus, pituitary and gastrointestinal tract. Given the lower abundance and less widespread distribution of GABA(C) receptors in the CNS compared to GABA(A) receptors, GABA(C) receptors may be a more selective drug target than GABA(A) receptors. The major indications for drugs acting on GABA(C) receptors are in the treatment of visual, sleep and cognitive disorders. The most promising leads are THIP, a GABA(C) receptor antagonist in addition to its well known activity as a GABA(A) receptor partial agonist, which is being evaluated for sleep therapy, and CGP36742, an orally active GABA(B) and GABA(C) receptor antagonist, which enhances cognition. Analogues of THIP and CGP36742, such as aza-THIP, that are selective for GABA(C) receptors are being developed. TPMPA and related compounds such as P4MPA, PPA and SEPI are also important leads for the development of systemically active selective GABA(C) receptor antagonists.

Allosteric Regulation↗
PubMed2002

Atypical benign partial epilepsy of childhood (pseudo-Lennox syndrome): report of two brothers.

Two brothers (3 and 2 year old) with characteristic findings of atypical benign partial epilepsy of childhood (pseudo-Lennox syndrome) are reported, to emphasize the presence of a possibility of a genetic basis of this disorder and the importance of intravenous immune globulin (IVIG), vigabatrin (VGB) and lamotrigine (LTG) therapy. Sleep EEGs of both the patients showed typical features of Lennox-Gastaut syndrome. On follow-up, the convulsions were found to be resistant to numerous antiepileptic agents in one patient while they were easily controlled with LTG monotherapy in the other patient. In the elder brother, who was diagnosed as intractable epilepsy, the convulsions disappeared with IVIG and VGB. During the long term follow-up, they were seizure free for five and two years respectively, and their mental motor development was excellent.

Anticonvulsants↗
PubMedDate not supplied

[A trial of the clinical use of a new method of electrosleep].

A novel device and technique of interference electric sleep therapy have been developed and tried in 125 children and 324 adults with different diseases. The highest clinical response, especially in children, was achieved on Elson unit.

Adolescent↗
PubMed1998

Antidepressant drugs: disturbing and potentially dangerous adverse effects.

Adverse effects associated with antidepressant drug therapy rarely cause significant morbidity or mortality. Nevertheless, the successful management of patients with depression requires recognition of potential adverse effects that have serious consequences, which include the discontinuation of otherwise effective therapy. The aim of this overview is to highlight the more common and potentially deleterious adverse effects of both older and newer classes of antidepressant drugs. Major adverse effects attributed to the tricyclic antidepressant drugs (TCAs) include conduction defects and lethal overdose. Most worrisome with the selective serotonin reuptake inhibitor drugs (SSRIs) is the serotonin syndrome. Although rare, this syndrome can be insidious and lethal. Recent trends toward the use of medication combinations and augmentation therapies significantly enhance the risk of serotonin syndrome. Cognitive impairment also may occur, especially with the TCAs. Apathy is occasionally a problem with SSRI therapy. The syndrome of inappropriate antidiuretic hormone (SIADH) has been reported with most antidepressant drugs but appears to be more common with serotonergic agents and in elderly patients. Although seizures are uncommon in patients receiving antidepressant therapy, the risk must be understood by both the patient and the clinician. Adverse effects related to sexual function are common, especially with TCAs, SSRIs, and venlafaxine. Sexual dysfunction often leads to noncompliance and self-discontinuation of therapy. Sleep disturbances are common in patients with depression, and recent data illustrate how crucial sleep regulation is to mood. Antidepressant drugs vary in their sleep effects. Although antidepressant drugs can cause a variety of adverse effects, these drugs save lives and their benefits far exceed their risks.

Antidepressive Agents↗
PubMed2000

In vivo efficacy of heated and non-heated humidifiers during nasal continuous positive airway pressure (nCPAP)-therapy for obstructive sleep apnoea.

Upper airway dryness is a frequent side-effect of nasal continuous positive airway pressure therapy (nCPAP) in obstructive sleep apnoea (OSA). In this situation, heated or non-heated passover humidifiers are often added to the nCPAP-therapy. The efficacy of these two modes in terms of increasing the absolute humidity of the inspired air in vivo has so far not been established. The present investigation was therefore designed to compare various heated and non-heated passover humidifiers in terms of the their ability to increase the absolute humidity in the inspired air during nCPAP. In six healthy test individuals, nCPAP-therapy at pressures of 5 mbar and 10 mbar was simulated, and the relative humidity and temperature of the air within the tube at the junction between CPAP tube and mask were measured. In each test person, measurements were carried out both with and without the two heated (HC 100, Fischer&Paykel Inc., New Zealand and HumidAire, ResMed Ltd., Australia) and two non-heated (Oasis and Humidifier, both from Respironics Inc., U.S.A.) passover humidifiers under steady-state conditions. The absolute humidity was calculated from the relative humidity and temperature measurements. The mean (SD) absolute humidity (gm(-3)) in the steady-state was significantly (P<0.05 higher with each of the humidifiers than that calculated when no humidifier was used. The relevant figures were as follows: no humidifier: 10(-2) (1.8) gm(-3) (at 5 mbar)/9.8 (1.8) gm(-3) (at 10 mbar); Humidifier: 16.4 (0.97)/15.6 (1.26); Oasis: 17.3 (0.97)/ 16.7 (0.93); HC100: 26.5 (1.40)/26.2 (1.23); HumidAire: 31.8 (2.50)/30.9 (2.64). The mean increase in absolute humidity (in gm(-3)) with the aid of the heated humidifiers was 16.3 (5 mbar) gm(-3)/16.4 (10 mbar) gm(-3) with HC100 and 21.6/21.1 with HumidAire, and in both cases was clearly and significantly (P=0.028) higher in comparison with the non-heated humidifiers--6.2/5.8 with Humidifier and 7.2/6.9 with Oasis. In terms of the absolute humidity achieved within the CPAP tube system, the heated humidifiers were clearly superior to the non-heated humidifiers. These results were, however, obtained under laboratory conditions, and therefore cannot be translated unreservedly to the situation represented by long-term CPAP-treatment. Furthermore, it is possible that the smaller humidification capacity of the non-heated humidifiers may still suffice to meet the requirements of clinical use in terms of effectively preventing dry airways under CPAP treatment. This point, however, needs further investigation on the basis of long-term clinical studies.

Adult↗
PubMed1980

Partial sleep deprivation as therapy for depression.

We investigated the influence of partial sleep deprivation on depressive symptoms in 30 patients with endogenous depression. The patients were awakened during the second half of the night and remained awake until the following evening. Antidepressant pharmacotherapy was not interrupted. Partial sleep deprivation significantly reduced the depression symptoms (mean value, 30.1%). The interindividual variations were considerable; deterioration was rare, and in 75% of the cases improvement occurred. Execution is simple, less stressful for the patient than total sleep deprivation, and can be carried out at home. Partial sleep deprivation has no contraindications except in the case of severe physical illness. The duration of the therapeutic effect is varied; repetition is possible. We discuss chronobiological hypothesis to explain the effect of sleep deprivation.

Aged↗
PubMed2001

Estrogen replacement therapy moderates the sleep disruption associated with nocturnal blood sampling.

STUDY OBJECTIVES: To determine whether chronic oral estrogen replacement therapy (ERT) (1) improves the sleep of older, non-symptomatic postmenopausal women; and (2) reduces the sleep disruption associated with a stressor (frequent remote nocturnal blood-sampling through an intravenous catheter). DESIGN: Descriptive, cross-sectional, secondary analysis of a larger study. SETTING: The General Clinical Research Center at the University of Washington Medical Center. PARTICIPANTS: Women aged 57-80 (mean age = 70) at least 5 years past menopause were recruited from the community. Hot flashes and significant sleep difficulties were exclusion criteria. The ERT group (n=37) consisted of women on chronic oral ERT for > or = 2 years. The NERT group (n=56) consisted of women not using estrogen (NERT) for > or = 2 years. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Following an adaptation night, polysomnographic measures were collected for 2 consecutive nights. A blood sample was collected every 20 minutes for the last 24 hours (including Night 2), through an intravenous catheter. The only group difference in sleep on the baseline (non-catheter) night was that NERT women had a shorter sleep latency. Sleep on the catheter night was characterized by increased wakefulness, longer sleep latency, and decreased REM sleep for both groups relative to the baseline. However, the impact of nocturnal blood sampling was much greater for NERT than for ERT women: they experienced significantly greater percent changes in more sleep-wake variables, particularly slow-wave sleep (SWS). CONCLUSIONS: In this cross-sectional study, the use of chronic oral ERT was associated with little effect on the sleep of older postmenopausal women not experiencing hot flashes, except in the presence of a challenge to sleep. ERT ameliorated the disruptive effect of nocturnal blood sampling on both objectively assessed and subjectively assessed sleep.

Aged↗
PubMed1998

Failure of CPAP therapy in obstructive sleep apnoea syndrome: predictive factors and treatment with bilevel-positive airway pressure.

Continuous positive airway pressure (CPAP) is the most widely used therapy for obstructive sleep apnoea (OSA). Despite its general efficacy, oxygen desaturation due to hypoventilation persists in some patients. The present study analysed the factors which are associated with this primary failure and, moreover, examined the effect of a bilevel positive airway pressure (BiPAP) trial. In a 15-month period, 13 patients with OSA (Group A) failed to respond to initial CPAP therapy defined by a remaining apnoea/hypopnoea index (AHI) of > or = 5 or a mean nocturnal SaO2 < 90%. These patients were compared to an age- and AHI-matched control group (Group B) successfully treated by CPAP. A logistic regression analysis was performed to identify factors which are associated with initial failure to CPAP. Patients of the CPAP-failure group were treated with nasal BiPAP in the control mode. These patients were significantly more obese than patients of the control group (mean body mass index 44.2 +/- 7.7 vs 31.2 +/- 6.3 kg m-2; P < 0.001). PaO2 at rest (P < 0.001) and at exercise (P < 0.005) was significantly lower in Group A patients. PaCO2 at rest (P < 0.001) was significantly higher in Group A patients and changed for the worse during exercise, whereas it improved in the control group. Group A patients spent significantly (P < 0.0001) more time with oxygen saturation < 90%. The percentage of time spent at < 90% of SaO2 was the only factor which was independently associated with the initial failure of CPAP (OR 1.13; 95% CI 1.0-1.2). After 3 months of treatment with BiPAP, the patients' blood gas values while awake improved significantly (P < 0.05) for PaO2 as well as for PaCO2. In conclusion, patients with OSA resistant to initial CPAP are morbidly obese with impaired awake blood gas values. The percentage of time spent at < 90% of nocturnal SaO2 is independently associated with initial failure of CPAP. BiPAP in the control mode is adequate for nocturnal ventilation, and improves awake blood gas values.

Adult↗