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1.  Adiposity, serum lipid levels, and allergic sensitization in Chinese men and women 
Background
Obesity and allergic diseases have increased dramatically in recent decades. While adiposity has been associated with asthma, associations with allergic sensitization have been inconsistent.
Objective
To examine the association of adiposity and lipid profiles with allergic sensitization.
Methods
This study included 1,187 rural Chinese twins (653 men) aged 18-39 years, with skin prick tests (SPT), anthropometric and DEXA-assessed adiposity measures, and lipid assessments. Allergic sensitization was defined as positive SPT to ≥1 allergen (9 foods and 5 aeroallergens tested). We applied gender-stratified generalized estimating equations to assess the association of adiposity and serum lipids with allergic sensitization, and structural equation models to estimate the genetic/environmental influences on any observed associations.
Results
Males had lower percent body fat (%BF) (13.9% vs. 28.8%) but higher rates of allergic sensitization (56.2% vs. 36.7%) than females. Males in the highest %BF quartile were 2.1 times more likely sensitized than the lowest quartile (95%CI 1.3-3.5, P-trend=0.003). In males, the risk of allergic sensitization increased with HDL<40 mg/dl (OR=4.0, 95%CI 1.8-9.2) and higher LDL quartiles (P-trend=0.007). This appeared to be partially explained by shared genetic factors between serum lipid levels and allergic sensitization. In females, lower HDL was associated with increased risk of allergic sensitization.
Conclusions
In this relatively lean Chinese population, higher %BF, lower HDL and higher LDL were associated with greater risk of allergic sensitization, most notable in males. The observed associations between adiposity, serum lipids and allergic sensitization in males appear to be partially explained by common genetic influences on these traits.
doi:10.1016/j.jaci.2008.11.032
PMCID: PMC2697621  PMID: 19135238
DEXA; Body mass index; Adiposity; Serum lipids; Sensitization
2.  Gender-Specific Association of Sleep Duration with Blood Pressure in Rural Chinese Adults 
Sleep medicine  2011;12(7):693-699.
Background
There are limited data about the role of gender on the relationship between sleep duration and blood pressure (BP) from rural populations.
Methods
We conducted a cross-sectional rural population-based study. This report includes 1,033 men and 783 women aged 18–65 years from a cohort of twins enrolled in Anhui, China, between 2005 and 2008. Sleep duration was derived from typical bedtime, wake-up time, and sleep latency as reported on a standard sleep questionnaire. Primary outcomes included measured systolic blood pressure (SBP) and diastolic blood pressure (DBP). High blood pressure (HBP) was defined as SBP≥130 mmHg, DBP ≥85 mmHg, or physician diagnosed hypertension. Linear and logistic regression models were used to assess gender-specific associations between sleep duration and BP or HBP, respectively, with adjustment for known risk factors including adiposity and sleep-related disorder risk from the questionnaires. Generalized estimating equations were used to account for intra-twin pair correlations.
Results
Compared with those sleeping 7 to less than 9 hours, women sleeping <7 hours had a higher risk of HBP (odds ratios [ORs] 3.0, 95% confidence interval [CI], 1.4–6.6); men sleeping ≥9 hours had a higher risk of HBP (ORs=1.5, 95%CI: 1.1–2.2).
Conclusions
Among rural Chinese adults, a gender-specific association of sleep duration with BP exists such that HBP is associated with short sleep duration in women and long sleep duration in men. Longitudinal studies are needed to further examine the temporal relationship and biological mechanisms underlying sleep duration and BP in this population. Our findings underscore the potential importance of appropriate sleep duration for optimal blood pressure.
doi:10.1016/j.sleep.2010.12.019
PMCID: PMC3755492  PMID: 21764369
sleep duration; high blood pressure; gender difference; rural Chinese
3.  Dietary nutrients associated with short and long sleep duration. Data from a nationally representative sample☆ 
Appetite  2013;64:71-80.
Short sleep duration is associated with weight gain and obesity, diabetes, cardiovascular disease, psychiatric illness, and performance deficits. Likewise, long sleep duration is also associated with poor physical and mental health. The role of a healthy diet in habitual sleep duration represents a largely unexplored pathway linking sleep and health. This study evaluated associations between habitual sleep parameters and dietary/nutritional variables obtained via the National Health and Nutrition Examination Survey (NHANES), 2007–2008. We hypothesized that habitual very short (<5 h) short (5–6 h) and long (9+ h) sleep durations are associated with intake of a number of dietary nutrient variables. Overall, energy intake varied across very short (2036 kcal), short (2201 kcal), and long (1926 kcal) sleep duration, relative to normal (2151 kcal) sleep duration (p = 0.001). Normal sleep duration was associated with the greatest food variety (17.8), compared to very short (14.0), short (16.5) and long (16.3) sleep duration (p < 0.001). Associations between sleep duration were found across nutrient categories, with significant associations between habitual sleep duration and proteins, carbohydrates, vitamins and minerals. In stepwise analyses, significant contributors of unique variance included theobromine (long sleep RR = 0.910, p < 0.05), vitamin C (short sleep RR = 0.890, p < 0.05), tap water (short sleep RR = 0.952, p < 0.001; very short (<5 h) sleep RR = 0.941, p < 0.05), lutein + zeaxanthin (short sleep RR = 1.123, p < 0.05), dodecanoic acid (long sleep RR = 0.812, p < 0.05), choline (long sleep RR = 0.450, p = 0.001), lycopene (very short (<5 h) sleep RR = 0.950, p <0.05), total carbohydrate (very short (<5 h) sleep RR = 0.494, p <0.05; long sleep RR = 0.509, p <0.05), selenium (short sleep RR = 0.670, p <0.01) and alcohol (long sleep RR = 1.172, p < 0.01). Overall, many nutrient variables were associated with short and/or long sleep duration, which may be explained by differences in food variety. Future studies should assess whether these associations are due to appetite dysregulation, due to short/long sleep and/or whether these nutrients have physiologic effects on sleep regulation. In addition, these data may help us better understand the complex relationship between diet and sleep and the potential role of diet in the relationship between sleep and obesity and other cardiometabolic risks.
doi:10.1016/j.appet.2013.01.004
PMCID: PMC3703747  PMID: 23339991
Sleep; Sleep duration; Diet; Nutrition; Epidemiology
4.  Risk Factors Associated with the Development of Atopic Sensitization in Indonesia 
PLoS ONE  2013;8(6):e67064.
Background
The prevalence of allergic diseases has increased not only in high income but also in low-to-middle income countries. However, risk factors for their development are still not well established, particularly in the latter.
Objective
To assess prevalence and identify risk factors for sensitization to two major inhalant allergens among children from semi-urban and rural areas in Indonesia.
Method
A cross-sectional survey was performed among 1,674 school children aged 5–15 years old. Information on potential risk factors and reported allergic symptoms were obtained by questionnaire. Helminth infections were assessed. Skin prick tests (SPT) were performed, total IgE as well as allergen-specific IgE for house dust mite (HDM) and cockroach were measured.
Result
The prevalence of allergic skin sensitization to both aeroallergens was significantly higher in the semi-urban than in the rural area. However, serum IgE against HDM and cockroach as well as total IgE were significantly lower in semi-urban than in rural children. In the semi-urban area, there was a significant positive association between SPT to HDM and higher paternal education but a negative one with hookworm infection. The risk factors linked to cockroach sensitization were different: being of a farmer offspring and lacking access to piped water were associated with an increased risk for a positive SPT to cockroach. No significant associations between measured risk factors and having a positive SPT were found in the rural area.
Conclusion
Sensitization to HDM and cockroach is common in Indonesia, more often translating into a positive SPT in the semi-urban than in the rural setting. Whereas high paternal education and low hookworm infection were associated with increased risk of SPT to HDM, we were surprised to find parameters of lower SES were identified as risk factor for cockroach SPT.
doi:10.1371/journal.pone.0067064
PMCID: PMC3686782  PMID: 23840583
5.  Peruvians’ sleep duration: analysis of a population-based survey on adolescents and adults 
PeerJ  2014;2:e345.
Background. Sleep duration, either short or long, has been associated with diseases such as obesity, type-2 diabetes and cardiovascular diseases. Characterizing the prevalence and patterns of sleep duration at the population-level, especially in resource-constrained settings, will provide informative evidence on a potentially modifiable risk factor. The aim of this study was to explore the patterns of sleep duration in the Peruvian adult and adolescent population, together with its socio-demographic profile.
Material and Methods. A total of 12,424 subjects, mean age 35.8 years (SD ±17.7), 50.6% males, were included in the analysis. This is a cross-sectional study, secondary analysis of the Use of Time National Survey conducted in 2010. We used weighted means and proportions to describe sleep duration according to socio-demographic variables (area and region; sex; age; education attainment; asset index; martial and job status). We used Poisson regressions, taking into account the multistage sampling design of the survey, to calculate crude and adjusted prevalence ratios (PR) and 95% confidence intervals (95% CI). Main outcomes were short- (<6 h) and long-sleep duration (≥ 9 h).
Results. On average, Peruvians slept 7.7 h (95% CI [7.4–8.0]) on weekdays and 8.0 h (95% CI [7.8–8.1]) during weekends. The proportions of short- and long-sleep, during weekdays, were 4.3% (95% CI [2.9%–6.3%]) and 22.4% (95% CI [14.9%–32.1%]), respectively. Regarding urban and rural areas, a much higher proportion of short-sleep was observed in the former (92.0% vs. 8.0%); both for weekdays and weekends. On the multivariable analysis, compared to regular-sleepers (≥ 6 to <9 h), short-sleepers were twice more likely to be older and to have higher educational status, and 50% more likely to be currently employed. Similarly, relative to regular-sleep, long-sleepers were more likely to have a lower socioeconomic status as per educational attainment.
Conclusions. In this nationally representative sample, the sociodemographic profile of short-sleep contrasts the long-sleep. These scenarios in Peru, as depicted by sleeping duration, differ from patterns reported in other high-income settings and could serve as the basis to inform and to improve sleep habits in the population. Moreover, it seems important to address the higher frequency of short-sleep duration found in urban versus rural settings.
doi:10.7717/peerj.345
PMCID: PMC3994633  PMID: 24765579
Sleep; Peru; Cross-sectional studies; Sleep deprivation; Sleep duration; Time-use studies; Socioeconomic factors
6.  Dissociation between the Prevalence of Atopy and Allergic Disease in Rural China among Children and Adults 
Background
The prevalence of allergic diseases is increasing worldwide, but the reasons are not well understood. Previous studies suggest that this trend may be associated with lifestyle and urbanization.
Objective
To describe patterns of sensitization and allergic disease in an unselected agricultural Chinese population.
Methods
The data was derived from a community-based twin study in Anqing, China. Skin prick testing was performed to foods and aeroallergens. Atopy was defined as sensitization to ≥1 allergen. Allergic disease was ascertained by self-report. The analysis was stratified by sex and age (children [11-17 years] and adults [≥18 years]) and included 1059 same-sex twin pairs.
Results
Of 2118 subjects, 57.6% were male (n=1220). Ages ranged from 11-71 years; 43.3% were children (n=918). Atopy was observed in 47.2% (n=999) of participants. The most common sensitizing foods were shellfish (16.7%) and peanut (12.3%). The most common sensitizing aeroallergens were dust mite (30.6%) and cockroach (25.2%). Birth order and zygosity had no effect on sensitization rates. Multivariate logistic regression models revealed risk factors for sensitization include age for foods and sex for aeroallergens. The rates of food allergy and asthma were estimated to be <1%.
Conclusions
Atopic sensitization was common in this rural farming Chinese population, particularly to shellfish, peanut, dust mite, and cockroach. The prevalence of allergic disease, in contrast, was quite low.
Clinical Implications
Allergen sensitization was far more common than the rate of self-reported allergic disease in this community. Evidence of sensitization is an inadequate marker of allergic disease and better correlates with clinical disease are needed.
Capsule summary
Among this large unselected Chinese rural farming community, atopy was observed in nearly half of the study subjects, but the rate of allergic disease was comparatively very low.
doi:10.1016/j.jaci.2008.08.009
PMCID: PMC2747487  PMID: 18805578
aeroallergens; rural; farming community; Chinese; food allergens; prevalence; sensitization; skin prick tests
7.  Genetic and Environmental Contributions to Allergen Sensitization in a Chinese Twin Study 
Background:
Allergic disease is on the rise worldwide. Effective prevention of allergic disease requires comprehensive understanding of the factors that contribute to its intermediate phenotypes, such as sensitization to common allergens.
Objective:
To estimate the degree of genetic and environmental contributions to sensitization to food or aeroallergens.
Methods:
Sensitization was defined as a positive skin prick test to an allergen. We calculated the zygosity-specific concordance rates and odds ratios (ORs) for sensitization to food and aeroallergens in 826 Chinese twin pairs (472 MZ and 354 DZ) aged 12 to 28 years. We also applied structural equation modeling procedures to estimate genetic and environmental influences on sensitization.
Results:
The concordance rates and risk of sensitization in one twin given the presence vs. the absence of sensitization in the other twin were higher in MZ twins than those in DZ twins. However, a large number of MZ twins were discordant in sensitization to common allergens. These observations suggest both genetic and environmental factors influence sensitization. Consistently, the estimated heritability and individual environmental components of the liability to sensitization ranged from 0.51 to 0.68 and 0.32 to 0.49, respectively, based on the best-fitted structural equation model. We also observed high phenotypic correlations between sensitization to two aeroallergens (cockroach and dust mite: 0.83) and two food allergens (peanut and shellfish: 0.58), but only moderate correlations for the pairs between sensitization to a food and an aeroallergen (0.31-0.46). The shared genetic and environmental factors between paired sensitizations contribute to the observed correlations.
Conclusion:
We demonstrated that sensitization to common food and aeroallergens were influenced by both genetic and environmental factors. Moreover, we found that paired allergen sensitizations might share some common sets of genes and environmental factors. This study underscores the need to further delineate unique and/or pleiotropic genetic and environmental factors for allergen sensitization.
doi:10.1111/j.1365-2222.2009.03228.x
PMCID: PMC2756049  PMID: 19302247
Twin; sensitization; positive SPT; structural equation modeling; heritability; environmental factors
8.  Sleep disorders in children 
Clinical Evidence  2010;2010:2304.
Introduction
Sleep disorders may affect between 20% and 30% of young children, and include problems getting to sleep (dyssomnias), or undesirable phenomena during sleep (parasomnias), such as sleep terrors and sleepwalking. Children with physical or learning disabilities are at increased risk of sleep disorders.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for dyssomnias in children? What are the effects of treatments for parasomnias in children? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 28 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antihistamines; behavioural therapy plus antihistamines, plus benzodiazepines, or plus chloral and derivatives; benzodiazepines alone; exercise; extinction and graduated extinction; 5-hydroxytryptophan; light therapy; melatonin; safety/protective interventions for parasomnias; scheduled waking (for parasomnias); sleep hygiene; and sleep restriction.
Key Points
Sleep disorders may affect between 20% and 30% of young children, and include problems getting to sleep (dyssomnias) or undesirable phenomena during sleep (parasomnias), such as sleep terrors and sleepwalking. Children with physical or learning disabilities are at increased risk of sleep disorders. Other risk factors include the child being the first born, having a difficult temperament or having had colic, and increased maternal responsiveness.
There is a paucity of evidence about effective treatments for sleep disorders in children, especially parasomnias, but behavioural interventions may be the best first-line approach.
Extinction and graduated extinction in otherwise healthy children with dyssomnia may improve sleep quality and settling, and reduce the number of tantrums and wakenings compared with no treatment. Extinction and graduated extinction in children with physical disabilities, learning disabilities, epilepsy, or attention-deficit disorder with dyssomnia may be more effective at improving settling, reducing the frequency and duration of night wakings, and improving parental sleep compared with no treatment; however, we don't know whether it is more effective in improving sleep duration.Graduated extinction may be less distressing for parents, and therefore may have better compliance.
Sleep hygiene for dyssomnia in otherwise healthy children may be more effective in reducing the number and duration of bedtime tantrums compared with placebo, but we don’t know if it is more effective at reducing night wakenings, improving sleep latency, improving total sleep duration, or improving maternal mood. Sleep hygiene and graduated extinction seem to be equally effective at reducing bedtime tantrums in otherwise healthy children with dyssomnia.We don't know whether sleep hygiene for dyssomnia in children with physical disabilities, learning disabilities, epilepsy, or attention-deficit disorder is effective.
Melatonin for dyssomnia in otherwise healthy children may be more effective at improving sleep-onset time, total sleep time, and general health compared with placebo. Evidence of improvements in dyssomnia with melatonin is slightly stronger in children with physical disabilities, learning disabilities, epilepsy, or attention-deficit disorder.
Little is known about the long-term effects of melatonin, and the quality of the product purchased could be variable as melatonin is classified as a food supplement.
Antihistamines for dyssomnia may be more effective than placebo at reducing night wakenings and decreasing sleep latency, but we don’t know if they are more effective at increasing sleep duration. The evidence for antihistamines in dyssomnia comes from only one small, short-term study.
We don’t know whether behavioural therapy plus antihistamines, plus benzodiazepines, or plus chloral and derivatives, exercise, light therapy, or sleep restriction are effective in children with dyssomnia.
We don’t know whether antihistamines, behavioural therapy plus benzodiazepines or plus chloral and derivatives, benzodiazepines, 5-hydroxytryptophan, melatonin, safety/protective interventions, scheduled waking, sleep hygiene, or sleep restriction are effective in children with parasomnia.
PMCID: PMC3217667  PMID: 21418676
9.  Sleep and use of electronic devices in adolescence: results from a large population-based study 
BMJ Open  2015;5(1):e006748.
Objectives
Adolescents spend increasingly more time on electronic devices, and sleep deficiency rising in adolescents constitutes a major public health concern. The aim of the present study was to investigate daytime screen use and use of electronic devices before bedtime in relation to sleep.
Design
A large cross-sectional population-based survey study from 2012, the youth@hordaland study, in Hordaland County in Norway.
Setting
Cross-sectional general community-based study.
Participants
9846 adolescents from three age cohorts aged 16–19. The main independent variables were type and frequency of electronic devices at bedtime and hours of screen-time during leisure time.
Outcomes
Sleep variables calculated based on self-report including bedtime, rise time, time in bed, sleep duration, sleep onset latency and wake after sleep onset.
Results
Adolescents spent a large amount of time during the day and at bedtime using electronic devices. Daytime and bedtime use of electronic devices were both related to sleep measures, with an increased risk of short sleep duration, long sleep onset latency and increased sleep deficiency. A dose–response relationship emerged between sleep duration and use of electronic devices, exemplified by the association between PC use and risk of less than 5 h of sleep (OR=2.70, 95% CI 2.14 to 3.39), and comparable lower odds for 7–8 h of sleep (OR=1.64, 95% CI 1.38 to 1.96).
Conclusions
Use of electronic devices is frequent in adolescence, during the day as well as at bedtime. The results demonstrate a negative relation between use of technology and sleep, suggesting that recommendations on healthy media use could include restrictions on electronic devices.
doi:10.1136/bmjopen-2014-006748
PMCID: PMC4316480  PMID: 25643702
sleep; media use; EPIDEMIOLOGY; adolescents
10.  Predicting Allergic Disease at Age Four Using an Atopy Predisposition Score at Age Two: The Application of Item Response Theory 
Pediatric Allergy and Immunology  2011;23(2):195-201.
When defining allergic outcomes in epidemiology studies results of the skin prick test (SPT) panel is often dichotomized as positive/negative or categorized based on the number of positive responses. Item Response Theory (IRT) models, however, may prove to be a better alternative with the ability to generate scores that account for both type and number of positive SPTs. IRT was applied to SPT responses administered to 537 children at age two in order to determine predictability of allergic disease at age four. The children received SPTs to 15 aeroallergens and two foods. Atopy predisposition scores were obtained from the IRT model using the posterior distribution of the latent trait, atopy. These scores were used to predict persistent wheeze, rhino-conjunctivitis, and eczema at age four. Results were compared to the dichotomized and categorical (positive to ≥ 2, positive to one, versus negative to all allergens) SPT variables. At age two, 39% of children had at least one positive SPT. All three allergic disease outcomes were significantly associated with IRT atopy scores: persistent wheeze odds ratio (OR)=1.7 (95% confidence interval (CI): 1.2, 2.3); rhino-conjunctivitis OR=1.7 (95% CI:1.2, 2.3); eczema OR=1.6 (95% CI: 1.2, 2.3). In contrast, rhino-conjunctivitis was the only outcome significantly associated with the dichotomized SPT variable with an OR=1.9 (95% CI:1.2, 3.0). For the categorical SPT variable, all three allergic symptoms were significantly associated with positive to ≥ 2 allergens compared to negative to all, but no difference was observed between those with positive to one compared to negative to all. The IRT model proved to be an informative methodology to assess the predictability of early SPT responses and identify the allergens most associated with atopy predisposition.
doi:10.1111/j.1399-3038.2011.01251.x
PMCID: PMC3310291  PMID: 22192382
Item Response Theory; Skin Prick Test; Allergy; Atopy; Asthma; Wheeze; Rhino-conjunctivitis; Eczema; Predicting allergies
11.  235 Frequency of Patients With Clinical Manifestations of Allergic Rhinitis without Evidence of Systemic Atopy and Specific ige Sensitization 
Background
The diagnosis of allergic rhinitis (AR) is based on clinical manifestations and supported by a positive result for skin prick test (SPT) or serum specific immunoglobulin E (sIgE) antibodies to aeroallergens. Our objective was to investigate the frequency of patients with clinical manifestations of AR without evidence of specific IgE sensitization.
Methods
We evaluated patients with clinical manifestations suggestive of AR, other causes of rhinitis excluded, aged >5 years and who had total serum IgE and SPT or sIgE to aeroallergens measured. Skin tests were performed with extracts of Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia tropicalis and Aspergillus fumigatus (FDA Allergenic) and total serum IgE and sIgE, for the same allergens, by ImmunoCAP (Phadia). Patients were subdivided into groups according to the results profile, and comparatively analyzed for association with asthma, severity of rhinitis and age.
Results
We evaluated 116 patients (64% female) aged between 5 and 79 years, including 34 children (29%) and 63 (54%) with bronchial asthma. The observed profiles and frequencies were: high IgE levels and positivity in the SPT or sIgE –55%; normal IgE levels and SPT or sIgE positivity –9%; high IgE levels and SPT and sIgE negativity –3 %; normal IgE levels and negativity in the SPT and sIgE –23%. Among patients with normal levels of total serum IgE and no evidence of specific IgE sensitization, 14% had asthma, while in the remainder the prevalence of asthma was 34% (P = 0.0009). There was no statistical significance in the influence of the rhinitis severity and age in the absence of markers of atopy and allergen sensitization.
Conclusions
We observed a significant number of patients with clinical manifestations of AR, without evidence of systemic atopy and specific IgE sensitization, indicating the importance of careful research of local allergic rhinitis, as well as other causes of chronic rhinitis. Local allergic rhinitis appears to be less frequent in patients with rhinitis and asthma. The observation of 13% of patients with elevated levels of total IgE without specific sensitization implies the possibility of sensitization to aeroallergens which were not investigated, such as occupational allergens.
doi:10.1097/01.WOX.0000411992.25922.6b
PMCID: PMC3513054
12.  Short Sleep Duration Is Associated with Insulin Resistance Independent of Adiposity in Chinese Adult Twins 
Sleep medicine  2011;12(9):914-919.
Objective
To investigate the association between sleep duration and insulin resistance in rural Chinese adults and examine whether any such associations are independent of adiposity.
Methods
This is a cross-sectional analysis of 854 men and 640 women aged 20 to 70 years from the Anqing Twin Cohort. The following measures were obtained for each subject: Body mass index (BMI) and percentage of trunk fat (%TF), fasting plasma glucose, homeostatic model assessment of insulin resistance index (HOMA-IR), self-reported sleep duration, and measures of snoring and sleep disturbance from the Pittsburgh Sleep Quality Indices (PSQI) questionnaire modified for a Chinese population. Multivariate linear regressions were applied to examine the association of sleep duration with HOMA-IR, with and without adjustment for adiposity variables, along with other relevant covariates.
Results
In this sample of relatively lean rural Chinese adults, short sleep duration was associated with HOMA-IR in women but not in men. In women, short (≤7 hrs/night) sleep duration was associated with a higher HOMA-IR (p=0.003) compared with normal sleep duration (>7 to ≤8 hrs/night) after adjustment for all the covariates except adiposity. Further adjustment for BMI or %TF attenuated the sleep-HOMA-IR association, but the association remained significant upon adjustment for BMI (p=0.013); and upon adjustment for %TF (p=0.026). Long sleep duration (>8 hrs/night) was not significantly associated with HOMA-IR.
Conclusion
In this rural Chinese cohort, short sleep duration is independently associated with increased insulin resistance among women only, even after adjusting for adiposity and other potential confounders.
doi:10.1016/j.sleep.2011.04.006
PMCID: PMC3210935  PMID: 21940204
sleep duration; insulin resistance; adiposity; gender; rural; adults
13.  Inverse relationship of food and alcohol intake to sleep measures in obesity 
Nutrition & Diabetes  2013;3(1):e58-.
Background:
Short sleep and weight gain are inversely related. Sleep deprivation acutely increases food intake but little is known about eating behavior in chronically sleep-deprived, obese individuals.
Objective:
To characterize the relationship between sleep, food intake and alcohol consumption under free-living conditions in obese, chronically sleep-deprived individuals.
Design:
Cross-sectional study of a cohort of obese men and premenopausal women.
Subjects:
A total of 118 obese subjects (age: 40.3±6.7 years; 91 females/27 males; body mass index 38.7±6.4 kg m−2).
Measurements:
Energy, macronutrient, alcohol and caffeine intake assessed by 3-day food records. Sleep duration estimated by actigraphy. Respiratory disturbance index assessed by a portable device.
Results:
Subjects slept 360.7±50.2 min per night and had a total energy intake of 2279.1±689 kcal per day. Sleep duration and energy intake were inversely related (r=−0.230, P=0.015). By extrapolation, each 30-min deficit per day in sleep duration would translate to an ∼83 kcal per day increase in energy intake. In addition, sleep apnea was associated with a shift from carbohydrate to fat intake. Alcohol intake in subjects consuming >3.5 g of alcohol per day (N=41) was inversely related to sleep duration (r=−0.472, P=0.002).
Conclusions:
Shorter sleep duration and obstructive sleep apnea are associated with higher energy, fat and alcohol intakes in obese individuals. The importance of this study relies on the population studied, obese subjects with chronic sleep deprivation. These novel findings apply to the large segment of the US population who are obese and sleep-deprived.
doi:10.1038/nutd.2012.33
PMCID: PMC3557370  PMID: 23357877
sleep apnea; public health; CPAP; epidemic
14.  The Association of Short and Long Sleep Durations with Insulin Sensitivity In Adolescents 
The Journal of pediatrics  2010;158(4):617-623.
Objective
To characterize the relationship between insulin sensitivity, assessed by the homeostasis model of insulin (HOMA), and objective measurements of sleep duration in adolescents.
Study design
Cross-sectional analysis from two examinations conducted in the Cleveland Children’s Sleep and Health Cohort (n=387; 43% minorities). Biochemical and anthropometry measurements made in a Clinical Research Unit. Sleep duration measured by actigraphy.
Results
Decreased sleep duration was associated with increased adiposity and minority race. Sleep duration had a quadratic “u-shape” association with HOMA. When adjusted for age, sex, race, preterm status and activity, adolescents who slept 7.75 hours had the lowest predicted HOMA (1.96 [95% CI: 1.82, 2.10]), and adolescents who slept 5.0 hours or 10.5 hours had HOMA indices that were about 20% higher (2.36 [95% CI: 1.94, 2.86] and 2.41 [95% CI: 1.93, 3.01], respectively). After adjusting for adiposity, the association between shorter sleep and HOMA was appreciably attenuated, but the association with longer sleep persisted.
Conclusions
Shorter and longer sleep durations are associated with decreased insulin sensitivity in adolescents. Whereas the association between shorter sleep duration with insulin sensitivity is likely explained by the association between short sleep and obesity, association between longer sleep and insulin sensitivity is independent of obesity.
doi:10.1016/j.jpeds.2010.09.080
PMCID: PMC3076647  PMID: 21146189
Sleep; insulin resistance; obesity
15.  Sleep duration and its correlates in middle-aged and elderly Chinese women: the Shanghai Women’s Health Study 
Sleep medicine  2012;13(9):1138-1145.
Background
Abnormal sleep duration, either long or short, is associated with disease risk and mortality. Little information is available on sleep duration and its correlates among Chinese women.
Methods
Using information collected from 68,832 women who participated in the Shanghai Women’s Health Study (SWHS), we evaluated sleep duration and its correlations with sociodemographic and lifestyle factors, health status, and anthropometric measurements and their indexes using polynomial logistic regression.
Results
The mean age of the study population was 59.6 years (SD=9.0; range: 44.6–79.9 years) at time of sleep duration assessment. Approximately 80% of women reported sleeping 6–8 hours per day, 11.5% slept five hours or less, and 8.7% slept nine hours or more. As expected, age was the strongest predictor for sleep duration and was negatively correlated with sleep duration. In general, sleep duration was positively associated with energy intake, intakes of total meat and fruits, body mass index (BMI), waist-hip ratio (WHR), and waist circumference (WC) after adjustment for age and other factors. Both short and long sleep duration were negatively associated with education level, family income, and leisure-time physical activity and positively associated with number of live births, history of night shift work, and certain chronic diseases, compared to sleep duration around seven hours/day (6.5–7.4 hours/day). Short sleep duration was related to tea consumption and passive smoking. Long sleep duration was related to menopausal status and marital status.
Conclusions
In this large, population-based study, we found that sleep duration among middle-aged and elderly Chinese women was associated with several sociodemographic and lifestyle factors and with disease status. The main limitation of the study is the cross-sectional design that does not allow us to draw any causal inference. However, this study provides information for future investigation into the nature of these associations so that recommendations can be developed to reduce sleep problems in middle-aged and elderly Chinese women. It also provides important information on potential confounders for investigation of sleep duration on health outcomes in this population.
doi:10.1016/j.sleep.2012.06.014
PMCID: PMC3474879  PMID: 22938861
Sleep duration; socio-economic factor; lifestyle; health status; BMI; correlation; Chinese
16.  House dust bioactivities predict skin prick test reactivity for children with high risk of allergy 
Background
Although evidence suggests that ambient exposures to endotoxin and other immunostimulants during early life influence allergic risk, efforts to understand this host-environment relationship have been hampered by a paucity of relevant assays.
Objectives
These investigations determined whether parameters of house dust extract (HDE) bioactivity were predictive of allergen skin prick test (SPT) reactivity for infants at high risk of allergy participating in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS).
Methods
We conducted a nested case-control study, selecting 99 CCAAPS children who had positive SPT results to at least 1 aeroallergen at age 3 years and 101 subjects with negative SPT results. HDEs were prepared from dust samples collected from the subjects' homes at age 1 year. Murine splenocytes and bone marrow–derived dendritic cells were incubated with HDEs, and supernatant cytokine concentrations were determined by means of ELISA. Alternatively, bone marrow–derived dendritic cells were preincubated with HDEs, and then LPS-induced IL-6 responses were assessed. HDE endotoxin levels were determined by using the limulus amebocyte lysate assay.
Results
HDEs derived from the homes of children with positive (cases) and negative (control subjects) SPT results had similar bioactivities. However, when cases were considered in isolation, HDEs with higher levels of bioactivity were significantly associated with children who had lower numbers of positive SPT results. Analogous statistical analyses did not identify any association between HDE endotoxin levels and the aeroallergen sensitization profiles of children included in this study.
Conclusion
HDE immunostimulatory activities predicted the aeroallergen sensitization status of CCAAPS subjects better than HDE endotoxin levels. These results provide the first published evidence that HDE bioassays have clinical relevance in predicting atopic risk.
doi:10.1016/j.jaci.2012.01.051
PMCID: PMC3582404  PMID: 22385634
House dust extract; aeroallergen sensitization; tolerance; allergy; skin prick test; human; innate immunity
17.  Polysomnography in Patients With Obstructive Sleep Apnea 
Executive Summary
Objective
The objective of this health technology policy assessment was to evaluate the clinical utility and cost-effectiveness of sleep studies in Ontario.
Clinical Need: Target Population and Condition
Sleep disorders are common and obstructive sleep apnea (OSA) is the predominant type. Obstructive sleep apnea is the repetitive complete obstruction (apnea) or partial obstruction (hypopnea) of the collapsible part of the upper airway during sleep. The syndrome is associated with excessive daytime sleepiness or chronic fatigue. Several studies have shown that OSA is associated with hypertension, stroke, and other cardiovascular disorders; many researchers believe that these cardiovascular disorders are consequences of OSA. This has generated increasing interest in recent years in sleep studies.
The Technology Being Reviewed
There is no ‘gold standard’ for the diagnosis of OSA, which makes it difficult to calibrate any test for diagnosis. Traditionally, polysomnography (PSG) in an attended setting (sleep laboratory) has been used as a reference standard for the diagnosis of OSA. Polysomnography measures several sleep variables, one of which is the apnea-hypopnea index (AHI) or respiratory disturbance index (RDI). The AHI is defined as the sum of apneas and hypopneas per hour of sleep; apnea is defined as the absence of airflow for ≥ 10 seconds; and hypopnea is defined as reduction in respiratory effort with ≥ 4% oxygen desaturation. The RDI is defined as the sum of apneas, hypopneas, and abnormal respiratory events per hour of sleep. Often the two terms are used interchangeably. The AHI has been widely used to diagnose OSA, although with different cut-off levels, the basis for which are often unclear or arbitrarily determined. Generally, an AHI of more than five events per hour of sleep is considered abnormal and the patient is considered to have a sleep disorder. An abnormal AHI accompanied by excessive daytime sleepiness is the hallmark for OSA diagnosis. For patients diagnosed with OSA, continuous positive airway pressure (CPAP) therapy is the treatment of choice. Polysomnography may also used for titrating CPAP to individual needs.
In January 2005, the College of Physicians and Surgeons of Ontario published the second edition of Independent Health Facilities: Clinical Practice Parameters and Facility Standards: Sleep Medicine, commonly known as “The Sleep Book.” The Sleep Book states that OSA is the most common primary respiratory sleep disorder and a full overnight sleep study is considered the current standard test for individuals in whom OSA is suspected (based on clinical signs and symptoms), particularly if CPAP or surgical therapy is being considered.
Polysomnography in a sleep laboratory is time-consuming and expensive. With the evolution of technology, portable devices have emerged that measure more or less the same sleep variables in sleep laboratories as in the home. Newer CPAP devices also have auto-titration features and can record sleep variables including AHI. These devices, if equally accurate, may reduce the dependency on sleep laboratories for the diagnosis of OSA and the titration of CPAP, and thus may be more cost-effective.
Difficulties arise, however, when trying to assess and compare the diagnostic efficacy of in-home PSG versus in-lab. The AHI measured from portable devices in-home is the sum of apneas and hypopneas per hour of time in bed, rather than of sleep, and the absolute diagnostic efficacy of in-lab PSG is unknown. To compare in-home PSG with in-lab PSG, several researchers have used correlation coefficients or sensitivity and specificity, while others have used Bland-Altman plots or receiver operating characteristics (ROC) curves. All these approaches, however, have potential pitfalls. Correlation coefficients do not measure agreement; sensitivity and specificity are not helpful when the true disease status is unknown; and Bland-Altman plots measure agreement (but are helpful when the range of clinical equivalence is known). Lastly, receiver operating characteristics curves are generated using logistic regression with the true disease status as the dependent variable and test values as the independent variable. Thus, each value of the test is used as a cut-point to measure sensitivity and specificity, which are then plotted on an x-y plane. The cut-point that maximizes both sensitivity and specificity is chosen as the cut-off level to discriminate between disease and no-disease states. In the absence of a gold standard to determine the true disease status, ROC curves are of minimal value.
At the request of the Ontario Health Technology Advisory Committee (OHTAC), MAS has thus reviewed the literature on PSG published over the last two years to examine new developments.
Methods
Review Strategy
There is a large body of literature on sleep studies and several reviews have been conducted. Two large cohort studies, the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study, are the main sources of evidence on sleep literature.
To examine new developments on PSG published in the past two years, MEDLINE, EMBASE, MEDLINE In-Process & Other Non-Indexed Citations, the Cochrane Database of Systematic Reviews and Cochrane CENTRAL, INAHTA, and websites of other health technology assessment agencies were searched. Any study that reported results of in-home or in-lab PSG was included. All articles that reported findings from the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study were also reviewed.
Diffusion of Sleep Laboratories
To estimate the diffusion of sleep laboratories, a list of sleep laboratories licensed under the Independent Health Facility Act was obtained. The annual number of sleep studies per 100,000 individuals in Ontario from 2000 to 2004 was also estimated using administrative databases.
Summary of Findings
Literature Review
A total of 315 articles were identified that were published in the past two years; 227 were excluded after reviewing titles and abstracts. A total of 59 articles were identified that reported findings of the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study.
Prevalence
Based on cross-sectional data from the Wisconsin Sleep Cohort Study of 602 men and women aged 30 to 60 years, it is estimated that the prevalence of sleep-disordered breathing is 9% in women and 24% in men, on the basis of more than five AHI events per hour of sleep. Among the women with sleep disorder breathing, 22.6% had daytime sleepiness and among the men, 15.5% had daytime sleepiness. Based on this, the prevalence of OSA in the middle-aged adult population is estimated to be 2% in women and 4% in men.
Snoring is present in 94% of OSA patients, but not all snorers have OSA. Women report daytime sleepiness less often compared with their male counterparts (of similar age, body mass index [BMI], and AHI). Prevalence of OSA tends to be higher in older age groups compared with younger age groups.
Diagnostic Value of Polysomnography
It is believed that PSG in the sleep laboratory is more accurate than in-home PSG. In the absence of a gold standard, however, claims of accuracy cannot be substantiated. In general, there is poor correlation between PSG variables and clinical variables. A variety of cut-off points of AHI (> 5, > 10, and > 15) are arbitrarily used to diagnose and categorize severity of OSA, though the clinical importance of these cut-off points has not been determined.
Recently, a study of the use of a therapeutic trial of CPAP to diagnose OSA was reported. The authors studied habitual snorers with daytime sleepiness in the absence of other medical or psychiatric disorders. Using PSG as the reference standard, the authors calculated the sensitivity of this test to be 80% and its specificity to be 97%. Further, they concluded that PSG could be avoided in 46% of this population.
Obstructive Sleep Apnea and Obesity
Obstructive sleep apnea is strongly associated with obesity. Obese individuals (BMI >30 kg/m2) are at higher risk for OSA compared with non-obese individuals and up to 75% of OSA patients are obese. It is hypothesized that obese individuals have large deposits of fat in the neck that cause the upper airway to collapse in the supine position during sleep. The observations reported from several studies support the hypothesis that AHIs (or RDIs) are significantly reduced with weight loss in obese individuals.
Obstructive Sleep Apnea and Cardiovascular Diseases
Associations have been shown between OSA and comorbidities such as diabetes mellitus and hypertension, which are known risk factors for myocardial infarction and stroke. Patients with more severe forms of OSA (based on AHI) report poorer quality of life and increased health care utilization compared with patients with milder forms of OSA. From animal models, it is hypothesized that sleep fragmentation results in glucose intolerance and hypertension. There is, however, no evidence from prospective studies in humans to establish a causal link between OSA and hypertension or diabetes mellitus. It is also not clear that the associations between OSA and other diseases are independent of obesity; in most of these studies, patients with higher values of AHI had higher values of BMI compared with patients with lower AHI values.
A recent meta-analysis of bariatric surgery has shown that weight loss in obese individuals (mean BMI = 46.8 kg/m2; range = 32.30–68.80) significantly improved their health profile. Diabetes was resolved in 76.8% of patients, hypertension was resolved in 61.7% of patients, hyperlipidemia improved in 70% of patients, and OSA resolved in 85.7% of patients. This suggests that obesity leads to OSA, diabetes, and hypertension, rather than OSA independently causing diabetes and hypertension.
Health Technology Assessments, Guidelines, and Recommendations
In April 2005, the Centers for Medicare and Medicaid Services (CMS) in the United States published its decision and review regarding in-home and in-lab sleep studies for the diagnosis and treatment of OSA with CPAP. In order to cover CPAP, CMS requires that a diagnosis of OSA be established using PSG in a sleep laboratory. After reviewing the literature, CMS concluded that the evidence was not adequate to determine that unattended portable sleep study was reasonable and necessary in the diagnosis of OSA.
In May 2005, the Canadian Coordinating Office of Health Technology Assessment (CCOHTA) published a review of guidelines for referral of patients to sleep laboratories. The review included 37 guidelines and associated reviews that covered 18 applications of sleep laboratory studies. The CCOHTA reported that the level of evidence for many applications was of limited quality, that some cited studies were not relevant to the recommendations made, that many recommendations reflect consensus positions only, and that there was a need for more good quality studies of many sleep laboratory applications.
Diffusion
As of the time of writing, there are 97 licensed sleep laboratories in Ontario. In 2000, the number of sleep studies performed in Ontario was 376/100,000 people. There was a steady rise in sleep studies in the following years such that in 2004, 769 sleep studies per 100,000 people were performed, for a total of 96,134 sleep studies. Based on prevalence estimates of the Wisconsin Sleep Cohort Study, it was estimated that 927,105 people aged 30 to 60 years have sleep-disordered breathing. Thus, there may be a 10-fold rise in the rate of sleep tests in the next few years.
Economic Analysis
In 2004, approximately 96,000 sleep studies were conducted in Ontario at a total cost of ~$47 million (Cdn). Since obesity is associated with sleep disordered breathing, MAS compared the costs of sleep studies to the cost of bariatric surgery. The cost of bariatric surgery is $17,350 per patient. In 2004, Ontario spent $4.7 million per year for 270 patients to undergo bariatric surgery in the province, and $8.2 million for 225 patients to seek out-of-country treatment. Using a Markov model, it was concluded that shifting costs from sleep studies to bariatric surgery would benefit more patients with OSA and may also prevent health consequences related to diabetes, hypertension, and hyperlipidemia. It is estimated that the annual cost of treating comorbid conditions in morbidly obese patients often exceeds $10,000 per patient. Thus, the downstream cost savings could be substantial.
Considerations for Policy Development
Weight loss is associated with a decrease in OSA severity. Treating and preventing obesity would also substantially reduce the economic burden associated with diabetes, hypertension, hyperlipidemia, and OSA. Promotion of healthy weights may be achieved by a multisectorial approach as recommended by the Chief Medical Officer of Health for Ontario. Bariatric surgery has the potential to help morbidly obese individuals (BMI > 35 kg/m2 with an accompanying comorbid condition, or BMI > 40 kg/m2) lose weight. In January 2005, MAS completed an assessment of bariatric surgery, based on which OHTAC recommended an improvement in access to these surgeries for morbidly obese patients in Ontario.
Habitual snorers with excessive daytime sleepiness have a high pretest probability of having OSA. These patients could be offered a therapeutic trial of CPAP to diagnose OSA, rather than a PSG. A majority of these patients are also obese and may benefit from weight loss. Individualized weight loss programs should, therefore, be offered and patients who are morbidly obese should be offered bariatric surgery.
That said, and in view of the still evolving understanding of the causes, consequences and optimal treatment of OSA, further research is warranted to identify which patients should be screened for OSA.
PMCID: PMC3379160  PMID: 23074483
18.  Sleep disturbance and cardiovascular risk in adolescents 
Background:
Evidence suggests that inadequate or disturbed sleep is associated with increased cardiovascular risk in adults. There are limited data on sleep quality and associated cardiovascular risk in children.
Methods:
We obtained data on adolescents from the 2009/10 cycle of the Healthy Heart Schools’ Program, a population-based cross-sectional study in the Niagara region of Ontario. Participants underwent measurements of cardiometabolic risk factors, including body mass index (BMI), lipid profile and blood pressure, and they completed questionnaires measuring sleeping habits and nutritional status. We assessed sleep disturbance using the sleep disturbance score derived from the Pittsburgh Sleep Quality Index. We explored associations between sleeping habits and cardiovascular risk factors.
Results:
Among 4104 adolescents (51% male), the mean hours of sleep per night (± standard deviation) were 7.9 ± 1.1 on weeknights and 9.4 ± 1.6 on weekends. In total, 19% of participants reported their sleep quality as fairly bad or very bad on weeknights and 10% reported it as fairly bad or very bad on weekends. In the multivariable regression models, a higher sleep disturbance score was associated with increased odds of being at high cardiovascular risk (highest v. lowest tertile odds ratio [OR] 1.43 [95% confidence interval (CI) 1.16–1.77], p < 0.001), increased odds of hypertension (highest v. lowest tertile OR 1.44 [95% CI 1.02–2.05], p = 0.05) and increased odds of elevated non-high density lipoprotein cholesterol (highest v. lowest tertile OR 1.28 [95% CI 1.00–1.64], p = 0.05). The mean duration of sleep was not associated with these outcomes.
Interpretation:
In healthy adolescents, sleep disturbance is associated with cardiovascular risk factor abnormalities. Intervention strategies to optimize sleep hygiene early in life may be important for the prevention of cardiovascular disease.
doi:10.1503/cmaj.111589
PMCID: PMC3503924  PMID: 23027917
19.  Basophil activation test compared to skin prick test and fluorescence enzyme immunoassay for aeroallergen-specific Immunoglobulin-E 
Background
Skin prick test (SPT) and fluorescence enzyme immunoassay (FEIA) are widely used for the diagnosis of Immunoglobulin-E (IgE)-mediated allergic disease. Basophil activation test (BAT) could obviate disadvantages of SPT and FEIA. However, it is not known whether BAT gives similar results as SPT or FEIA for aeroallergens.
Objectives
In this study, we compared the results of SPT, BAT and FEIA for different aeroallergens.
Methods
We performed BAT, SPT and FEIA in 41 atopic subjects (symptomatic and with positive SPT for at least 1 of 9 common aeroallergens) and 31 non-atopic subjects (asymptomatic and with negative SPT).
Results
Correlations between SPT and BAT, SPT and FEIA, and BAT and FEIA results were statistically significant but imperfect. Using SPT as the "gold standard", BAT and FEIA were similar in sensitivity. However, BAT had lower specificity than FEIA. False positive (BATposSPTneg) results were frequent in those atopic subjects who were allergic by SPT to a different allergen and rare in non-atopic subjects. The false positivity in atopic subjects was due in part to high levels of serum Total-IgE (T-IgE) levels in atopic individuals that lead to basophil activation upon staining with fluorochrome-labeled anti-IgE.
Conclusion
As an alternative to SPT in persons allergic to aeroallergens, BAT in its present form is useful for distinguishing atopic from non-atopic persons. However, BAT in its present form is less specific than FEIA when determining the allergen which a patient is allergic to. This is due to IgE staining-induced activation of atopic person's basophils and/or nonspecific hyperreactivity of atopic person's basophils.
doi:10.1186/1710-1492-8-1
PMCID: PMC3398323  PMID: 22264407
Allergic disease; Basophil activation test; Fluorescence enzyme immunoassay; Skin prick test; Aeroallergen; Immunoglobulin-E
20.  Rapid Eye Movement Sleep in Relation to Overweight in Children and Adolescents 
Archives of general psychiatry  2008;65(8):924-932.
Context
Short sleep duration is associated with obesity, but few studies have examined the relationship between obesity and specific physiological stages of sleep.
Objective
To examine specific sleep stages, including rapid eye movement (REM) sleep and stages 1 through 4 of non-REM sleep, in relation to overweight in children and adolescents.
Design, Setting, and Participants
A total of 335 children and adolescents (55.2% male; aged 7-17 years) underwent 3 consecutive nights of standard polysomnography and weight and height assessments as part of a study on the development of internalizing disorders (depression and anxiety).
Main Outcome Measures
Body mass index (calculated as weight in kilograms divided by height in meters squared) z score and weight status (normal, at risk for overweight, overweight) according to the body mass index percentile for age and sex.
Results
The body mass index z score was significantly related to total sleep time (β=-0.174), sleep efficiency (β=-0.027), and REM density (β=-0.256). Compared with normal-weight children, overweight children slept about 22 minutes less and had lower sleep efficiency, shorter REM sleep, lower REM activity and density, and longer latency to the first REM period. After adjustment for demographics, pubertal status, and psychiatric diagnosis, 1 hour less of total sleep was associated with approximately 2-fold increased odds of overweight (odds ratio=1.85), 1 hour less of REM sleep was associated with about 3-fold increased odds (odds ratio=2.91), and REM density and activity below the median increased the odds of overweight by 2-fold (odds ratio=2.18) and 3-fold (odds ratio=3.32), respectively.
Conclusions
Our results confirm previous epidemiological observations that short sleep time is associated with overweight in children and adolescents. A core aspect of the association between short sleep duration and overweight may be attributed to reduced REM sleep. Further studies are needed to investigate possible mechanisms underpinning the association between diminished REM sleep and endocrine and metabolic changes that may contribute to obesity.
doi:10.1001/archpsyc.65.8.924
PMCID: PMC2729137  PMID: 18678797
21.  Sleep Duration, Sleep Regularity, Body Weight, and Metabolic Homeostasis in School-aged Children 
Pediatrics  2011;127(2):e345-e352.
OBJECTIVE:
The goal was to explore the effects of duration and regularity of sleep schedules on BMI and the impact on metabolic regulation in children.
METHODS:
Sleep patterns of 308 community-recruited children 4 to 10 years of age were assessed with wrist actigraphs for 1 week in a cross-sectional study, along with BMI assessment. Fasting morning plasma levels of glucose, insulin, lipids, and high-sensitivity C-reactive protein also were measured for a subsample.
RESULTS:
Children slept 8 hours per night, on average, regardless of their weight categorization. A nonlinear trend between sleep and weight emerged. For obese children, sleep duration was shorter and showed more variability on weekends, compared with school days. For overweight children, a mixed sleep pattern emerged. The presence of high variance in sleep duration or short sleep duration was more likely associated with altered insulin, low-density lipoprotein, and high-sensitivity C-reactive protein plasma levels. Children whose sleep patterns were at the lower end of sleep duration, particularly in the presence of irregular sleep schedules, exhibited the greatest health risk.
CONCLUSIONS:
Obese children were less likely to experience “catch-up” sleep on weekends, and the combination of shorter sleep duration and more-variable sleep patterns was associated with adverse metabolic outcomes. Educational campaigns, aimed at families, regarding longer and more-regular sleep may promote decreases in obesity rates and may improve metabolic dysfunction trends in school-aged children.
doi:10.1542/peds.2010-0497
PMCID: PMC3025425  PMID: 21262888
sleep duration; obesity; children; lipids; insulin resistance; inflammation
22.  Sleep Duration, Schedule and Quality among Urban Chinese Children and Adolescents: Associations with Routine After-School Activities 
PLoS ONE  2015;10(1):e0115326.
Background
With rapid urbanization accompanied by lifestyle changes, children and adolescents living in metropolitan areas are faced with many time use choices that compete with sleep. This study reports on the sleep hygiene of urban Chinese school students, and investigates the relationship between habitual after-school activities and sleep duration, schedule and quality on a regular school day.
Methods
Cross-sectional, school-based survey of school children (Grades 4–8) living in Shanghai, China, conducted in 2011. Self-reported data were collected on students’ sleep duration and timing, sleep quality, habitual after-school activities (i.e. homework, leisure-time physical activity, recreational screen time and school commuting time), and potential correlates.
Results
Mean sleep duration of this sample (mean age: 11.5-years; 48.6% girls) was 9 hours. Nearly 30% of students reported daytime tiredness. On school nights, girls slept less (p<0.001) and went to bed later (p<0.001), a sex difference that was more pronounced in older students. Age by sex interactions were observed for both sleep duration (p=0.005) and bedtime (p=0.002). Prolonged time spent on homework and mobile phone playing was related to shorter sleep duration and later bedtime. Adjusting for all other factors, with each additional hour of mobile phone playing, the odds of daytime tiredness and having difficulty maintaining sleep increased by 30% and 27% among secondary students, respectively.
Conclusion
There are sex differences in sleep duration, schedule and quality. Habitual activities had small but significant associations with sleep hygiene outcomes especially among secondary school students. Intervention strategies such as limiting children’s use of electronic screen devices after school are implicated.
doi:10.1371/journal.pone.0115326
PMCID: PMC4303432  PMID: 25611973
23.  Effects of geohelminth infection and age on the associations between allergen-specific IgE, skin test reactivity and wheeze: a case-control study 
Background
Most childhood asthma in poor populations in Latin America is not associated with aeroallergen sensitization, an observation that could be explained by the attenuation of atopy by chronic helminth infections or effects of age.
Objective
To explore the effects of geohelminth infections and age on atopy, wheeze, and the association between atopy and wheeze.
Methods
A case-control study was done in 376 subjects (149 cases and 227 controls) aged 7–19 years living in rural communities in Ecuador. Wheeze cases, identified from a large cross-sectional survey, had recent wheeze and controls were a random sample of those without wheeze. Atopy was measured by the presence of allergen-specific IgE (asIgE) and skin prick test (SPT) responses to house dust mite and cockroach. Geohelminth infections were measured in stools and anti-Ascaris IgE in plasma.
Results
The fraction of recent wheeze attributable to anti-Ascaris IgE was 45.9%, while those for SPT and asIgE were 10.0% and 10.5% respectively. The association between atopy and wheeze was greater in adolescents than children. Although Anti-Ascaris IgE was strongly associated with wheeze (adj. OR 2.24 (95% CI 1.33–3.78, P = 0.003) and with asIgE (adj. OR 5.34, 95% CI 2.49–11.45, P < 0.001), the association with wheeze was independent of asIgE. There was some evidence that the association between atopy and wheeze was greater in uninfected subjects compared with those with active geohelminth infections.
Conclusions and clinical relevance
Atopy to house dust mite and cockroach explained few wheeze cases in our study population, while the presence of anti-Ascaris IgE was an important risk factor. Our data provided only limited evidence that active geohelminth infections attenuated the association between atopy and wheeze in endemic areas or that age modified this association. The role of allergic sensitization to Ascaris in the development of wheeze, independent of atopy, requires further investigation.
doi:10.1111/cea.12040
PMCID: PMC3563216  PMID: 23278881
allergen skin test reactivity; allergen-specific IgE; atopy; geohelminths; wheeze
24.  Sleep, physical activity and BMI in six to ten-year-old children measured by accelerometry: a cross-sectional study 
Background
The aim of this study is to describe the relationship between objective measures of sleep, physical activity and BMI in Swedish pre-adolescents. The day-to-day association between physical activity and sleep quality as well as week-day and weekend pattern of sleep is also described.
Method
We conducted a cross sectional study consisted of a cohort of 1.231 children aged six to ten years within the Stockholm county area. Sleep and physical activity were measured by accelerometry during seven consecutive days. Outcome measures are total sleep time, sleep efficiency, sleep start and sleep end; physical activity intensity divided into: sedentary (<1.5 METS), light (1.5 to 3 METS) and moderate-to-vigorous (> 3 METS); and Body Mass Index standard deviations score, BMIsds.
Results
Total sleep time decreased with increasing age, and was shorter in boys than girls on both weekdays and weekends. Late bedtime but consistent wake-up time during weekends made total sleep time shorter on weekends than on weekdays. Day-to-day within-subject analysis revealed that moderate-to-vigorous intense physical activity promoted an increased sleep efficiency the following night (CI < 0.001 to 0.047), while total sleep time was not affected (CI -0.003 to 0.043). Neither sleep duration (CI -0.024 to 0.022) nor sleep efficiency (CI -0.019 to 0.028) affected mean physical activity level the subsequent day. The between-subject analysis indicates that the sleep of children characterized by high moderate-to-vigorous physical activity during the day was frequently interrupted (SE = -.23, P < .01). A negative association between BMIsds and sleep duration was found (-.10, p < .01).
Conclusions
Short sleep duration was associated with high BMI in six to ten year old children. This study underscores the importance of consistent bedtimes throughout the week for promoting sleep duration in preadolescents. Furthermore, this study suggests that a large proportion of intensive physical activity during the day might promote good sleep quality.
doi:10.1186/1479-5868-10-82
PMCID: PMC3691618  PMID: 23800204
Pre-school children; Sleep; Physical activity; Sedentary; BMI; Accelerometry; Weekday; Weekend
25.  Do computer use, TV viewing, and the presence of the media in the bedroom predict school-aged children’s sleep habits in a longitudinal study? 
BMC Public Health  2013;13:684.
Background
Electronic media use is becoming an increasingly important part of life for today’s school-aged children. At the same time, concern of children’s sleep habits has arisen, and cross-sectional studies have shown that electronic media use is associated with short sleep duration and sleep disturbances. The purpose of this longitudinal study was to investigate whether baseline electronic media use and media presence in a child’s bedroom predicted sleep habits as well as changes in these sleep habits 18 months later among 10- to 11-year-old children in Finland.
Methods
The school-aged children (n=353, 51% girls) from 27 schools answered a questionnaire in 2006 and again 2008 in the Helsinki region of Finland. Electronic media use was measured by computer use and TV viewing. Media presence in a child’s bedroom means the presence of a TV or a computer in a child’s bedroom. Sleep habits were measured by bedtimes on school days and at the weekend days, sleep duration, discrepancy of bedtimes, and discrepancy of sleep duration between school days and weekends. Linear regression analyses were used to examine whether electronic media use and media presence predicted sleep habits with adjustments for grade, family structure, and baseline sleep. Gender differences were also examined.
Results
The children used a computer for one hour per day and watched TV over one hour a day in 2006. They slept over nine hours on school days and over ten hours at the weekends in 2008. Computer use and television viewing predicted significantly shorter sleep duration (p<0.001, p<0.05 respectively) and later bedtimes (p<0.001, p<0.01, respectively). Computer use also predicted unfavourable changes in sleep duration (p<0.001) and bedtimes on school days (p<0.001) and weekends (p<0.01). Among boys, media presence in the bedroom predicted poorer sleep habits and irregularity of sleep habits.
Conclusions
Computer use, TV viewing, and the presence of media in children’s bedrooms may reduce sleep duration, and delay bedtimes.
doi:10.1186/1471-2458-13-684
PMCID: PMC3727951  PMID: 23886318
Child; Sleep; Television viewing; Computer use; Longitudinal

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