Melatonin in elderly patients with insomnia.– A systematic review

Summary Background Melatonin is a hormone and antioxidant produced by the pineal gland of which four neurobiological roles have been claimed in the aged population: anti-ageing agent; free-radical scavenger; regulator of circadian rhythm; endogeneous sleep-inducer. The „melatonin replacement” hypothesis states that 1) the well-evidenced age-related decline contributes to insomnia and that 2) replacement with physiological doses of melatonin improves sleep. The aim of this review was to determine the evidence for the efficacy of melatonin in elderly insomniacs. Methods MEDLINE‘s database from 1990–2000 was searched with „melatonin”, „geriatrics” and „(frail)-elderly” as major subheadings. This resulted in 78 articles: only studies with empirical treatment data were reviewed (N=12). Results Six reports (abstract, research letter, retrospective case study, 3 open label studies) showed a trend towards efficacy of melatonin: sleep quality improved and in patients with Alzheimer‘s disease sundowning was reduced.?   In 6 double blind, randomised crossover trials, a total number of 95 patients (mean ages: 65–79yrs) were treated. Melatonin doses ranged from 0.5mg to 6mg; most took a single dose 30–120min before bedtime. In 3 studies a slow release form was used. Sleep quality was objectively measured by wrist actigraphy (n=4) and polysomnography (n=2), and additionally subjective sleep quality was assessed (n=2). Sleep latency decreased significantly in 4 studies. In 3 studies other measures of sleep quality (sleep efficiency, total sleep time and wake time during sleep) improved. Subjective sleep quality did not improve. No early-morning sleepiness occurred. Comparison of the studies suggests that melatonin is most effective in elderly insomniacs who chronically use benzodiazepines and/or with documented low melatonin levels during sleep. Conclusion There is sufficient evidence that low doses of melatonin improve initial sleep quality in selected elderly insomniacs. However, larger randomized controlled trials, with less strict inclusion criteria are necessary to yield evidence of effectiveness (i.e. clinical and subjective relevance) in geriatric patients who suffer from insomnia, before wide-spread use can be advocated. Received: 26 June 2001/Accepted: 10 July 2001     

Sleep disturbances in aspartylglucosaminuria (AGU): A questionnaire study

Summary Sleep disturbances are common in many progressive metabolic encephalopathies. The possible presence of disturbed sleep–wake behaviour in the lysosomal storage disorder aspartylglucosaminuria, has not been previously studied, however. The sleep–wake behaviour of 81 patients with aspartylglucosaminuria (AGU, age 3–55 years, median 22 years; 42 female and 39 male) and 49 controls (age 2–57 years, median 18 years; 25 female and 24 male) was assessed through a postal survey. A slightly modified version of the validated Basic Nordic Sleep Questionnaire was used. Fifty-eight per cent of the AGU patients were reported to suffer daily from a sleep-related problem (controls 31%, p < 0.01). In AGU adults (age >17 years) and children (age ≤17 years), the corresponding figures were 52% and 61%, respectively (control children 22%, p < 0.05 and control adults 38%, p = 0.06). In AGU children, settling difficulties were reported to occur significantly more commonly than in control children. Children with AGU were also reported to snore more often than were the controls. Adults with this disorder were found to suffer from severely fragmented night-time sleep, which was experienced as highly distressing by the parents and other caregivers. A long night sleep period was reported to be common in the ageing AGU patients (AGU 9.5 ± 1.7 vs controls 7.2 ± 1.0 h, mean ± SD, p < 0.001). Parents and caregivers also often complained about disturbing movements during sleep in AGU patients. In conclusion, both children and adults with aspartylglucosaminuria were reported to display several types of sleep disturbances significantly more commonly than healthy controls. Competing interests: None declared     

Automated detection of sleep disordered breathing using a nasal pressure monitoring device

To assess the accuracy of a single channel portable monitoring device (RUSleeping™ RTS, Respironics, Murrysville, PA) that measures nasal pressure (a surrogate for airflow) to detect sleep disordered breathing (SDB). Twenty-five adult patients referred to a community sleep laboratory with suspected obstructive sleep apnea (OSA) participated in this investigation. The portable monitoring device was used in the sleep laboratory to acquire data concurrently with a standard multi-channel polysomnogram (PSG) to assess SDB. Respiratory events were scored manually on the PSG using standard criteria for clinical research to quantify an apnea–hypopnea index (AHI) based on events during sleep. The portable monitoring device automatically calculated an unedited respiratory event index (REI) based on recording time. These data were then compared using the Pearson product–moment correlation coefficient, Bland–Altman analysis, receiver operating characteristic (ROC) curves, and likelihood ratios. All 25 subjects completed the study. Mean age of subjects was 42.4 ± 12.9 years and mean body mass index was 31.0 ± 7.4 kg m⁻². There was good agreement between the REI and the AHI (R = 0.77, p < 0.001, mean difference 2.6 events per hour [2 SD: 39.8] using a Bland–Altman plot). The area under the ROC curve for detecting SDB (PSG AHI greater than or equal to five events per hour) with the REI was 0.94 (95% CI 0.84–1.0). For an REI >11.9 events per hour, the sensitivity was 0.89 (95% CI 0.65–0.99) and the specificity was 0.86 (95% CI 0.42–1.0) with a likelihood ratio of 6.2 for a positive test (LR+) and 0.13 for a negative test (LR−). Similar results were observed for detecting moderate–severe SDB (PSG AHI ≥ 15 events h⁻¹) using REI >15.2 events h⁻¹. In a population of subjects with suspected OSA, this portable monitoring device can automatically quantify an REI that compares well to the AHI scored manually on a concurrent PSG. Such a device may prove useful to assess SDB in high risk populations with self-administered testing in ambulatory settings such as the home. This study was performed at the Sleep Center of Greater Pittsburgh Sleep Laboratory.     

Spontaneous pneumomediastinum secondary to refractory dermatomyositis successfully treated with rituximab

Spontaneous pneumomediastinum has been described in patients with dermatomyositis (DM) and polymyositis (Korkmaz et al., Rheumatology 40:476–478, 2001; Maruoka et al., Mod Rheumatol 16:55–57, 2006; Kono et al., Ann Rheum Dis 59:372–376, 2000; Neves et al., Clin Rheumatol 26:105–107, 2007). Literature reviews suggest that this complication has a mortality of between 27% and 41% ( Kono et al., Ann Rheum Dis 59:372–376, 2000; Neves et al., Clin Rheumatol 26:105–107, 2007; Goff et al., Arthritis Rheum 61:108–118, 2009). This is the first report of rituximab being used successfully as part of the treatment for DM complicated by pneumomediastinum.     

Noonan syndrome and related disorders: Alterations in growth and puberty

Noonan syndrome is a relatively common multiple malformation syndrome with characteristic facies, short stature and congenital heart disease, most commonly pulmonary stenosis (Noonan, Clin Pediatr, 33:548–555, 1994). Recently, a mutation in the PTPN11 gene (Tartaglia, Mehler, Goldberg, Zampino, Brunner, Kremer et al., Nat Genet, 29:465–468, 2001) was found to be present in about 50% of individuals with Noonan syndrome. The phenotype noted in Noonan syndrome is also found in a number of other syndromes which include LEOPARD (Gorlin, Anderson, Blaw, Am J Dis Child, 17:652–662, 1969), Cardio-facio-cutaneous syndrome (Reynolds, Neri, Hermann, Blumberg, Coldwell, Miles et al., Am J Med Genet, 28:413–427, 1986) and Costello syndrome (Hennekam, Am J Med Genet, 117C(1):42–48, 2003). All three of these syndromes share similar cardiac defects and all have postnatal short stature. Very recently, HRAS mutations (Aoki, Niihori, Kawame, Kurosawa, Ohashi, Tanaka et al., Nat Genet, 37:1038–1040, 2005) have been found in the Costello syndrome and germline mutations in KRAS and BRAF genes (Rodriguez-Viciana, Tetsu, Tidyman, Estep, Conger, Santa Cruz et al., Nat Genet, 2006; Niihori, Aoki, Narumi, Neri, Cave, Verloes et al., Nat Genet, 38:294–296, 2006) in the Cardio-facio-cutaneous syndrome. Phenotypic overlap between these genetic disorders can now be explained since each is caused by germline mutations that are major components of the RAS-MAPK pathway. This pathway plays an important role in growth factor and cytokine signaling as well as cancer pathogenesis.     

Evidence for only two independent pathways for decreasing senescence in <Emphasis Type="Italic">Caenorhabditis elegans</Emphasis>

Cold temperature, dietary restriction, reduced insulin/insulin-like growth factor signaling, and mutations in mitochondrial genes have all been shown to extend the lifespan of Caenorhabditis elegans (Kenyon et al., Nature 366:461–464, 1993; Klass, Mech Ageing Dev 6:413–429, 1977; Lakowski and Hekimi, Science 272:1010–1013, 1996). Additionally, all of them extend the lifespan of mice (Bluher et al., Science 299:572–574, 2003; Conti et al., Science 314:825–828, 2006; Holzenberger et al., Nature 421:182–187, 2003; Liu et al., Genes Dev 19:2424–2434, 2005; Weindruch and Walford, Science 215:1415–1418, 1982). The mechanism by which these treatments extend lifespan is currently unknown, but our study uses an epistatic approach to show that these four manipulations are mainly additive in terms of lifespan. Classical interpretation of this data suggests that these manipulations are independent of each other. However, using a Gompertz mortality rate analysis, the maximum mortality rate doubling time can be achieved through the use of only dietary restriction and cold temperature, suggesting that the mechanisms by which cold temperature and caloric restriction extend lifespan are the only independent mechanisms.     

Simultaneous deep vein thrombosis and transverse myelitis with negative serology as a first sign of antiphospholipid syndrome: a case report and review of the literature

Transverse myelitis is a rare manifestation of antiphospholipid syndrome, usually secondary to systemic lupus erythematosus (Rheum Dis Clin North Am 20:129–158, 1994). Only about 110 reports of this complication have been reported (Lupus 10:851–856, 2001). A connection has been demonstrated between positive serology for antiphospholipid and transverse myelitis (Lupus 8:109–115, 1999). Herein, we report of a young patient admitted with deep vein thrombosis and neurological manifestations of transverse myelitis with negative serology for systemic lupus erythematosus and antiphospholipid, who developed positive anticardiolipin antibody during pulse therapy with cyclophosphamide and methylprednisolone.     

Gender differences in Saudi patients with obstructive sleep apnea

Obstructive sleep apnea (OSA) remains under-recognized in women possibly due to differences in clinical presentation, difference in tolerance to symptoms, and rate of usage and referral to sleep services. No reports have addressed OSA in women in the Middle Eastern (Arab) population. Therefore, we conducted this study to assess the differences in demographics, clinical presentation, and polysomnographic (PSG) findings between Saudi women and men diagnosed to have (OSA). The study group comprised 191 consecutive Saudi women and 193 consecutive men who were referred to the Sleep Disorders Centre and were found by in-laboratory PSG to have OSA. Demographic and clinical data were obtained by personal interviews. Women were significantly older than men (53.9 and 43.0 years, respectively; p < 0.001). Similarly, their body mass index was significantly higher than men (p < 0.001). Insomnia was more common among women (39.8%) compared to men (25.9%; p = 0.005). Other sleep symptoms including witnessed apnea, and excessive daytime sleepiness did not show any statistical difference between the two groups. Women were more likely than men to be diagnosed with hypothyroidism, diabetes, hypertension, cardiac disease, and asthma. Apnea–hypopnea index (AHI) was statistically higher in men compared to women; however, most of apnea/hypopnea events in women occurred during rapid eye movement sleep, and the mean duration of hypopnea and apnea was significantly lower in women (p = 0.004). Sleep efficiency was lower in women (71.5% vs. 77.7%) in men (p < 0.001). The desaturation index was higher in men (p = 0.01), but no difference was found in lowest SaO₂ or time with SaO₂ less than 90%. The present study showed important clinical and PSG differences between Saudi women and men with OSA. Clinicians need to be aware of these differences when assessing women for the possibility of OSA as they may be symptomatic at a lower AHI and have significant comorbid conditions that can be adversely affected if their OSA was not timely managed.     

A Surveillance Report of HIV Status and High Risk Behaviors Among Rapid Testing Participants in Tallinn,Estonia

Estonia has the second highest adult HIV prevalence in Europe of 1.3%. The primary transmission is among injecting drug users (IDU), who account for 56–90% of HIV infections (Report on the Global AIDS Epidemic: UNAIDS/WHO, July 2008 and Platt et al. AIDS 20(16):2120–2123, 2006). Of those persons newly diagnosed, 50.4% reported injecting drugs in the last 12 months, 16.3% of these reported IDU as the sole risk factor and 31.2% reported IDU among other risk factors. In this sample (n = 790) 170 persons reported a high risk behavior and 51 persons received a positive result through rapid testing. The largest proportion (35.29%) was among persons reporting high risk heterosexual intercourse and second (33.33%) among persons sharing injecting equipment. Covariates in a logistic regression model indicate that male sex (OR = 2.57, 95% CI 1.00–6.59), non-Estonian ethnicity (OR = 2.68, 95% CI 1.46–4.93), higher education (OR = 0.56, 95% CI 0.40–0.80), and high risk heterosexual intercourse (OR = 2.68, 95% CI 1.19–6.02) are statistically significant in predicting a positive HIV status.     

The thrifty phenotype hypothesis revisited

Twenty years ago, Hales and Barker along with their co-workers published some of their pioneering papers proposing the ‘thrifty phenotype hypothesis’ in Diabetologia (4;35:595–601 and 3;36:62–67). Their postulate that fetal programming could represent an important player in the origin of type 2 diabetes, the metabolic syndrome and cardiovascular disease (CVD) was met with great scepticism.     

Higher comorbidity, poor functional status and higher health care utilization in veterans with prevalent total knee arthroplasty or total hip arthroplasty

The objective of this study was to compare comorbidity, functional ability, and health care utilization in veterans with total knee arthroplasty (TKA) or total hip arthroplasty (THA) versus matched control populations. A cohort of veterans using Veterans Affairs (VA) healthcare system reported limitations in six activities of daily living (ADLs; bathing, dressing, eating, walking, transferring, and using the toilet), demographics, and physician-diagnosed comorbidity. VA databases provided healthcare utilization and International Classification of Diseases-9/Common procedure terminology codes for TKA/THA. Patients were classified as: (1) primary TKA; (2) primary THA; (3) combination group (≥1 procedure); and (4) control veteran population (no THA/TKA). Multivariable regression analyses compared the risk or counts of ADL limitation and in-/out-patient visits. After multivariable adjustment, TKA, THA or combination groups had significantly higher prevalence of the following compared to veteran controls: arthritis, diabetes, or heart disease (p < 0.0001 each), severe (≥3) ADL limitation (33%, 42%, 42% vs. 24%; p < 0.0001), and annual hospitalization rate (24%, 19%, 26% vs. 16%, p < 0.0001). Annual outpatient surgery visits were more (2.5, 2.3, 2.3 vs. 2, p = 0.01) and risk of any mental health outpatient visit was lower (12%, 11%, 12% vs. 18%, p = 0.0039). All ADLs, except eating, were significantly more limited in arthroplasty groups (p ≤ 0.0009). Severe ADL limitation was more prevalent in veterans with arthroplasty than in two age-matched US cohorts: 13.4 times in ≥65 years; and 1.2-, 1.6-, and 4-fold in ≥85, 75–84, and 65–74 years. Poorer function and higher comorbidity and utilization in veterans with TKA/THA suggest that this group is appropriate for interventions targeted at improving function and decreasing utilization. Supported by NIH CTSA Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research) The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs.     

Gastroesophageal Reflux Disease as an Etiology of Sleep Disturbance in Subjects with Insomnia and Minimal Reflux Symptoms: A Pilot Study of Prevalence and Response to Therapy

Background Gastroesophageal reflux disease (GERD) is a well-recognized cause of impaired sleep in patients with frequent GERD symptoms, as well as those with sleep apnea. GERD’s role in sleep disturbance of minimally symptomatic patients with poor sleep quality is less clear. Aim We aimed to define the prevalence of GERD-related sleep disturbance in minimally-symptomatic subjects with demonstrated insomnia, and to assess the changes in sleep efficiency in these subjects after vigorous acid suppression. Methods We recruited subjects aged 18–75 years reporting at least 6 months of insomnia, and sleep difficulty at least three nights per week. Subjects with a BMI > 30, a history of snoring or ongoing use of proton pump inhibitor or H2 receptor antagonist were excluded. Subjects underwent concurrent sleep study with dual channel 24-h pH study. Sleep efficiency, defined as the percentage of time after sleep initiation that the subject actually slept, and spontaneous arousal index, defined as the number of arousals per hour, were calculated. Those with a sleep study demonstrating poor sleep quality (sleep efficiency of <83%, and >10 arousals/h for those aged <45, and >15 for those who were 45 or older) and no obstructive sleep apnea were treated with rabeprazole 20 mg PO BID × 14 days. After 14 days, the subjects underwent repeat sleep study with pH monitoring. The GERD Symptom Assessment Scale (GSAS), the Epworth Sleepiness Scale (ESS) and the Functional Outcomes of Sleep Questionnaire (FOSQ) were administered to subjects at study inception and after 2 weeks of therapy. Results Twenty-four subjects reporting insomnia were enrolled, and 20 met criteria for disordered sleep and no OSA. Seventeen completed both the first and second studies, and 16 were adequate for analysis. Baseline GSAS demonstrated trivial or no reflux symptoms in the cohort (no subject scored >8 out of 45 on GSAS, corresponding to a median rating of reflux symptoms of “not at all”). Four of 16 subjects (25%) demonstrated abnormal pH studies at baseline. All four had normalization of acid exposures on PPI. After 2 weeks of treatment, three of these four subjects had normalization of sleep efficiency, compared to 4 of 12 of the subjects with normal Johnson-DeMeester scores. Repeated measures analysis showed significant improvement in spontaneous arousal index between the first and second study for the whole group (P < 0.0035). Pre- and post-therapy ESS and FOSQ scores were not significantly different. Conclusions Despite the lack of GERD symptoms, a significant minority of subjects with sleep disturbance have abnormal acid exposures. These preliminary data suggest that aggressive treatment of GERD in such patients may result in improvement in sleep efficiency. This work was presented in abstract form at the Annual Meeting of the Associated Professional Sleep Societies (SLEEP 2007), Minneapolis, MN, June 9–14, 2007.     

Therapeutic Endoscopic Ultrasound for Biliary and Pancreatic Disorders

The role of endoscopic ultrasound (EUS) has greatly expanded since the first clinical examination performed nearly 30 years ago. The introduction of linear instruments allowed tissue sampling (Kulesza and Eltoum Clin Gastroenterol Hepatol 5:1248–1254, 2007; Levy and Wiersema Gastrointest Endosc 62:417–426, 2005) and therapeutic interventions applications, including celiac plexus and ganglia blockade and neurolysis (Wiersema and Wiersema Gastrointest Endosc 44:656–662, 1996; Levy and Wiersema Gastroenterol Clin North Am, 35:153–165, 2006; Levy et al. Am J Gastroenterol 103:98–103, 2008), pancreatic fluid drainage (Lopes et al. Arq Gastroenterol 45:17–21, 2008; Norton et al. Mayo Clin Proc 76:794–798, 2001; Kruger et al. Gastrointest Endosc 63:409–416, 2006; Seifert et al.: Endoscopy 32:255–259, 2000), cholecystenterostomy (Kwan et al. Gastrointest Endosc 66:582–586, 2007), and delivery of cytotoxic agents (eg, chemotherapy, radioactive seeds, and gene therapy) (Chang et al.: Cancer 88:1325–1335, 2000; Chang Endoscopy 38(Suppl 1):S88–S93, 2006). The continued need to develop less invasive alternatives to surgical and interventional radiologic therapies drove the development of EUS-guided methods for biliary and pancreatic intervention. This article reviews existing data and focuses on established and emerging EUS techniques for accessing and draining the bile and pancreatic ducts.     

Nasal dilator strip therapy for chronic sleep-maintenance insomnia and symptoms of sleep-disordered breathing: a randomized controlled trial

To test the impact of nasal dilator strips (NDSs) on insomnia severity, sleep-disordered breathing (SDB) symptoms, sleep quality, and quality of life. Randomized, controlled trial of 4 weeks' duration. Community sample of nonobese, adults with a primary sleep complaint of chronic sleep-maintenance insomnia and mild to moderate SDB symptoms (treatment, n=42; control, n=38). Primary outcomes were four validated scales: Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), Functional Outcomes of Sleep Questionnaire (FOSQ), and Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ). Secondary outcomes were sleep indices, nonrestorative sleep ratings, and SDB symptoms, assessed retrospectively and prospectively. Both groups received nonspecific education about sleep disorders. Treatment group also received a brief SDB education and nasal strip instructions. At 4 weeks' follow-up, the treatment group demonstrated significant (p=.0001), large improvements in ISI and PSQI (mean Cohen's d=1.18) and significant (p<.02), medium-sized improvements in FOSQ and QLESQ (mean d=0.51) compared to small, nonsignificant changes in control group (Cohen's d range=0.36–0.09). Treatment group change scores among all four primary variables were significantly correlated (mean r=0.50, p=0.01). Secondary prospective and retrospective outcomes showed medium to large improvements in treatment compared to controls for sleep indices (mean d=0.52 vs 0.28), nonrestorative sleep ratings (mean d=0.69 vs 0.11), and sleep breathing symptoms (mean d=0.47 vs 0.09). Significance was obtained for prospective sleep indices (p=0.01), retrospective, and prospective nonrestorative sleep ratings (p=0.003, <0.05), and retrospective sleep breathing symptoms (p=0.03). SDB education and NDSs demonstrated therapeutic efficacy in a select sample of insomnia patients with SDB symptoms. Replication of results requires placebo controls and objectively confirmed SDB cases.     

Sleep-related breathing in children with mucopolysaccharidosis

Summary   Background: The mucopolysaccharidoses (MPSs), a group of genetic lysosomal storage disorders, are associated with significant morbidity. Secondarily to specific associated anatomical abnormalities, MPS is associated with sleep disordered breathing (SDB), specifically obstructive sleep apnoea (OSA) that may confer additional morbidity. Few studies have examined SDB in children with MPS using full polysomnography (PSG) and thus the exact prevalence and severity of SDB is unknown. Further, successful treatments for SDB in this population have not been explored. Objectives: This study evaluated both SDB and the efficacy of treatments offered to children with MPS using PSG data. Patients and methods: A retrospective chart review was conducted on all children with MPS and a history of suspected OSA who were referred to the Hospital for Sick Children, Toronto. Both baseline and follow up treatment PSG data were analysed. PSG data recorded included obstructive apnoea-hypopnoea index (OAHI) and central apnoea index (CAI). Results: Fourteen patients (10 male) underwent a baseline PSG. Three of 14 children on ERT were excluded from the main analyses. The median (range) baseline parameters of the population (n = 11) were recorded. The age was 5.2 years (0.8–17.8) and the body mass index (BMI) was 19.9 (13.7–22.2). The OAHI was 6.6 (0.0–54.8); the CAI was 0.6 (0.0–2.6). Seven of 11 (64%) had evidence for OSA and 3/7 children were classified as having severe OSA (OAHI > 10). Of these, 5/7 children underwent treatment for OSA with 3/5 children showing a significant reduction in their OAHI. Further, the 2 patients on ERT therapy with OSA were also both successfully treated. Conclusions: Children with MPS have a high prevalence of significant OSA and thus should be carefully screened for OSA using full polysomnography and treated accordingly. Competing interests: None declared     

Reliability of a Holter-based methodology for evaluation of sleep apnoea syndrome

Aims: Sleep apnoea has significant medical implications. A reliablenon-invasive method (as a regular Holter system with a specificsoftware) would be valuable for the screening of this conditionin ambulatory patients. Methods and results: A total of 40 patients were divided into two groups: Group I,20 patients with clinical suspicion of obstructive sleep apnoea(OSA) and Epworth sleepiness score 10 and Group II, 20 controls.In Group I, polysomnography was performed simultaneously withHolter (specific software to detect sleep apnoea). In GroupII, Holter-based detection was utilized. A cutoff value of 10for the apnoea–hypopnoea index (for polysomnography) orfor the respiratory disturbance index (RDI) (for Holter) wasconsidered abnormal. Sleep apnoea was confirmed by polysomnographyin 14 patients (70%) in Group I. Holter recordings correctlyidentified OSA in 11 patients (r = 0.74 with polysomnography;P = 0.0002). Holter showed 78.5% sensitivity, 83.3% specificity,91.6% positive predictive value, and 62.5% negative predictivevalue (with polysomnography as the gold standard). The RDI measuredby Holter was 19.5 ± 20 in Group I and 3.9 ± 4.4in controls (P < 0.005). The measurement between Holter andpolysomnography (Bland and Altman method) showed good correlation(mean 4.7 with 39.4 and –30.1 SD) and a Pearson correlationcoefficient (r) of 0.74 (P = 0.0002, 95% CI: 0.44–0.89). Conclusion: Holter-based software may constitute an accessible tool on initialsuspicion of OSA.     

Comparison between reported and recorded total sleep time and sleep latency in 6- to 11-year-old children: the Tucson Children’s Assessment of Sleep Apnea Study (TuCASA)

Research comparing parental report of sleep times to objectively obtained polysomnographic evidence of sleep times in schoolchildren is lacking. This report compares habitual sleep time and objectively recorded sleep time and sleep latency with parental reports of sleep time immediately after a night of polysomnography in elementary schoolchildren. Unattended home polysomnograms (PSG) were obtained from 480 children. On the night of the PSG, a parent was asked to complete a Sleep Habits Questionnaire, which inquired about the habitual total sleep time (HABTST) and habitual sleep onset latency (HABSOL) of his/her child on both school days and nonschool days. On the morning after the PSG, the parent was asked to estimate the total sleep time (ESTTST) and sleep onset latency (ESTSOL) of his/her child on the night of the recording. Comparisons were made to actual total sleep time (PSGTST) and sleep latency (PSGSOL) on the PSG. The sample was comprised of 50% girls, 42.3% Hispanic, and 53% aged 6–8 years. The mean HABTST, ESTTST, and PSGTST were 578, 547, and 480 min, respectively. HABTST was greater than both ESTST and PSGTST (p < 0.001). Moreover, ESTTST was greater than PSGTST (p < 0.001). The mean HABSOL, ESTSOL, and PSGSOL were 15, 17, and 11 min. ESTSOL was longer than PSGSOL (p < 0.001). There were no gender differences. However, Hispanic parents reported significantly less HABTST in their children than Caucasian parents (566 vs 587 min, p < 0.001). Parents of schoolchildren in this population-based sample substantially overestimated their children’s actual total sleep time and sleep onset latency.     

Incidence of childhood diabetes mellitus in Yorkshire, northern England, is associated with nitrate in drinking water: an ecological analysis

Summary The relationship between the incidence of childhood-onset insulin-dependent diabetes mellitus and levels of nitrate in drinking water in the former Yorkshire Regional Health Authority was investigated by means of an ecological analysis. A population-based register contributed 1797 0–16-year-olds diagnosed with diabetes between 1978 and 1994. Nitrate data were based on 9330 samples of drinking water tested between 1990 and 1995 in 148 water supply zones, for which 1991 census small area statistics were taken on population density, ethnicity and socio-economic status. Diabetes incidence was positively associated with raised mean nitrate levels with a standardised incidence ratio of 115 in zones with greater than 14.85 mg · l^–1 (χ² = 26.81, 1 df, p < 0.001). Significant negative trends were found between standardised incidence ratios and proportion of non-whites in the population (χ² = 33.57, 1 df, p < 0.001), childhood population density (χ² = 30.81, 1 df, p < 0.001) and the Townsend deprivation score (χ² = 33.89, 1 df, p < 0.001). Poisson regression modelling, adjusting for the other factors, showed a significant increase in relative incidence rate ratio from a baseline of 1 at nitrate levels below 3.22 mg · l^–1 to 1.27 (95 % confidence interval 1.09,1.48) for mean nitrate levels above 14.85 mg · l^–1. An association between higher nitrate levels in domestic drinking water and incidence of childhood diabetes has been demonstrated. This was not explained by the ethnic composition of the population, population density or socioeconomic status. Nitrate in drinking water may be a precursor of chemicals which are toxic to the pancreas. [Diabetologia (1997) 40: 550–556] Received: 24 October 1996 and in revised form: 20 December 1996     

Sleep and circadian abnormalities in patients with cirrhosis: features of delayed sleep phase syndrome?

Sleep disturbances are common in patients with cirrhosis but their origins are unknown. The aim of this study was to investigate possible involvement of the circadian system. Sleep was monitored for two weeks, in the home environment, using sleep diaries and actigraphy, in 35 patients with cirrhosis (21 men; mean age [±1SD] 58 ± 10 yr) and 12 matched healthy controls (eight men; mean age 56 ± 15 yr); urinary 6-sulphatoxymelatonin (aMT6s), the major metabolite of melatonin, was measured over 56 h, to assess circadian rhythmicity. The patients woke up and got up significantly later than the healthy volunteers and their sleep was significantly more fragmented. Mean 24-hour urinary aMT6s outputs were comparable in the patients and controls (15.5±13.1 vs. 20.3±13.8 μg/24 h) but were significantly lower in the decompensated patients (9.8 ± 11.3 vs. 17.0 ± 13.3 μg/24 h; p = 0.03). Significant 24-hour urinary aMT6s rhythms were observed in 26 (79%) of the 33 patients with complete urine collections; 20 patients had a normally timed (midnight–06:00) urinary aMT6s peak, while it was delayed (≥ 06:00) in the remainder. Significant correlations were observed between abnormalities in the urinary aMT6s profile (delays and/or lack of a 24-hour rhythm) and indices of sleep timing; parallel delays were observed in sleep habits and urinary aMT6s peaks. The association between delayed circadian rhythms and delayed sleep habits observed in approximately one-third of the patients with cirrhosis is reminiscent of ‘delayed sleep phase syndrome’; this condition is managed by attempting to resynchronise the circadian clock by exposure to bright light shortly after morning awakening.     

Sleep architecture in children and adolescents with cystic fibrosis and the association with severity of lung disease

Previous studies have shown that sleep complaints are common in adult patients with cystic fibrosis (CF). However, there is very little data on sleep in children and adolescents with CF and the association with severity of lung disease. A prospective study was conducted in CF children and age-matched controls. All patients completed sleep questionnaire and underwent an overnight polysomnographic study. Thirty-eight children and adolescents met the criteria for entry into the analysis, 24 children and adolescents with CF (S) and 14 controls (C). Sleep complaints were common in children and adolescents with CF; 43.5% reported sleep onset problem, 39.1% reported sleep maintenance problem, 30.4% were noted to snore at night, and 73.9% reported daytime sleepiness. Children and adolescents with CF had a significant decrease in sleep efficiency [SE; 75.2 ± 2.5% (S) vs 85.6 ± 1.7%(C); P < 0.01], prolonged rapid eye movement (REM) latency [150.5 ± 16.6 min (S) vs 85.6 ± 11.0 min (C); P < 0.05], and reduction in percentage of REM sleep [12.7 ± 1.5% (S) vs 18.3 ± 1.3% (C); P < 0.05]. The degree of sleep disruption as indicated by SE was correlated with forced expiratory volume in one second (FEV₁; r = 0.52, P < 0.05). However, there was no significant correlation between SE and minimum oxygen saturation [r = 0.30, P=not significant (NS)] or SE and maximal end-tidal pCO₂ (r = 0.11, P=NS). It is concluded that children and adolescents with CF have frequent sleep complaints and significant alteration in the sleep architecture. The magnitude of sleep disruption is associated with severity of lung disease, but is not directly correlated with the degree of nocturnal hypoxemia or hypoventilation. It is speculated that sleep disruption in children and adolescents with CF may have an impact on quality of life and clinical outcomes in this population.