Sleep Disorder Cohort Research Articles

Elucidating sleep disorders: a comprehensive bioinformatics analysis of functional gene sets and hub genes.

Sleep disorders (SD) are known to have a profound impact on human health and quality of life although their exact pathogenic mechanisms remain poorly understood. The study first accessed SD datasets from the GEO and identified DEGs. These DEGs were then subjected to gene set enrichment analysis. Several advanced techniques, including the RF, SVM-RFE, PPI networks, and LASSO methodologies, were utilized to identify hub genes closely associated with SD. Additionally, the ssGSEA approach was employed to analyze immune cell infiltration and functional gene set scores in SD. DEGs were also scrutinized in relation to miRNA, and the DGIdb database was used to explore potential pharmacological treatments for SD. Furthermore, in an SD murine model, the expression levels of these hub genes were confirmed through RT-qPCR and Western Blot analyses. The findings of the study indicate that DEGs are significantly enriched in functions and pathways related to immune cell activity, stress response, and neural system regulation. The analysis of immunoinfiltration demonstrated a marked elevation in the levels of Activated CD4+ T cells and CD8+ T cells in the SD cohort, accompanied by a notable rise in Central memory CD4 T cells, Central memory CD8 T cells, and Natural killer T cells. Using machine learning algorithms, the study also identified hub genes closely associated with SD, including IPO9, RAP2A, DDX17, MBNL2, PIK3AP1, and ZNF385A. Based on these genes, an SD diagnostic model was constructed and its efficacy validated across multiple datasets. In the SD murine model, the mRNA and protein expressions of these 6 hub genes were found to be consistent with the results of the bioinformatics analysis. In conclusion, this study identified 6 genes closely linked to SD, which may play pivotal roles in neural system development, the immune microenvironment, and inflammatory responses. Additionally, the key gene-based SD diagnostic model constructed in this study, validated on multiple datasets showed a high degree of reliability and accuracy, predicting its wide potential for clinical applications. However, limited by the range of data sources and sample size, this may affect the generalizability of the results.

The Effects of Different Types of Sleep Disorder on Colorectal Cancer: A Nationwide Population-Based Cohort Study.

The impact of sleep disorders (SDs), particularly sleep apnea (SA), on the development of colorectal cancer (CRC) has been the subject of significant research. However, the potential contribution of other SDs to the incidence of CRC remains unexplored. The objective of this study was to examine the effects of SDs on the risk of developing CRC. This study assessed CRC risk among individuals diagnosed with SDs compared with age- and sex-matched unaffected individuals. A longitudinal, nationwide, population-based cohort study was conducted using data from the Taiwan National Health Insurance Research Database (NHIRD) encompassing 177,707 individuals diagnosed with SDs and 177,707 matched controls. Cox proportional hazard regression analysis was used to determine the relative increased risk of CRC in individuals with SDs and specific subgroups of SDs. The CRC incidences were 1.32-fold higher (95% CI 1.23-1.42) in the overall SD cohort, 1.17-fold higher (95% CI 0.82-1.68) in the SA cohort, 1.42-fold higher (95% CI 1.31-1.55) in the insomnia cohort, 1.27-fold higher (95% CI 1.17-1.38) in the sleep disturbance cohort, and 1.00-fold higher (95% CI 0.77-1.29) in the other SD cohort, after adjusting for age, sex, and comorbidities.

P032 Adequate health literacy predicts adherence to continuous positive airway pressure in adults with Obstructive Sleep Apnoea

Abstract Study Objectives Obstructive sleep apnoea (OSA) is a chronic disease with significant health implications and adequate adherence to continuous positive airway pressure (CPAP) is essential for effective treatment. In many chronic diseases, health literacy has been found to predict treatment adherence and outcomes. In this study, the aim was to determine the health literacy of a sleep clinic population and evaluate the association between health literacy and CPAP adherence. Methods A prospective cohort study was undertaken, recruiting 104 consecutive patients with a variety of sleep diagnoses attending the clinic. The Short Form Rapid Estimate of Adult Literacy in Medicine (REALM-SF), a validated questionnaire was administered to measure health literacy. In a sub-group of 91 patients prescribed CPAP for OSA, CPAP usage was measured, with adequate usage defined as greater than 4hrs/night CPAP therapy. Results 71% of the sleep clinic cohort was found to have adequate health literacy as measured by the REALM-SF. In those prescribed CPAP for OSA, inadequate health literacy was associated with a two fold increase risk for inadequate CPAP usage (adjusted odds ratio 2.75, 95% CI: 1.00 - 7.6, p = 0.05). There was a 1.7hr/night difference in median CPAP usage comparing those with adequate to inadequate health literacy (4.6hrs versus 6.3hrs/night). Conclusions The majority of this sleep disorders cohort had adequate health literacy as measured by the REALM-SF questionnaire. However inadequate health literacy appears to be an independent predictor of treatment adherence, and may represent a potentially modifiable risk factor of poor treatment outcomes in OSA.

Adequate health literacy is associated with adherence to continuous positive airway pressure in adults with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a chronic disease with significant health implications and adequate adherence to continuous positive airway pressure (CPAP) is essential for effective treatment. In many chronic diseases, health literacy has been found to predict treatment adherence and outcomes. In this study, the aim was to determine the health literacy of a sleep clinic population and evaluate the association between health literacy and CPAP adherence. A prospective cohort study was undertaken, recruiting 104 consecutive patients with a variety of sleep diagnoses. The Short Form Rapid Estimate of Adult Literacy in Medicine (REALM-SF), a validated questionnaire, was administered to measure health literacy. In a sub-group of 91 patients prescribed CPAP for OSA, CPAP usage was measured, with adequate usage defined as greater than 4 h/night CPAP therapy. Seventy-one percent of the sleep clinic cohort was found to have adequate health literacy, as measured by the REALM-SF. In those prescribed CPAP for OSA, inadequate health literacy was associated with a twofold increased risk for inadequate CPAP usage (adjusted odds ratio [OR] 2.9, 95% CI: 1.1 to 8.22, p = 0.045). There was a 1.7 h/night difference in median CPAP usage comparing those with adequate to inadequate health literacy (4.6 h vs. 6.3 h/night). The majority of this sleep disorders cohort had adequate health literacy as measured by the REALM-SF questionnaire. However, inadequate health literacy appears to be an independent predictor of treatment adherence and may represent a modifiable risk factor of poor treatment outcomes in OSA.

Sleep disorders associated with risk of prostate cancer: a population-based cohort study

BackgroundDisrupted sleep rhythms may lead to cancer development. We conducted a population-based cohort study to evaluate the incidence and risk of prostate cancer in patients with sleep disorders (SDs).MethodsPatients newly diagnosed with SDs between 2000 and 2010 were enrolled from the Taiwan Longitudinal Health Insurance Database. A non-SD cohort age-matched (5-y intervals), comorbidities, and medications was randomly sampled from the general population at a 1:1 ratio. The follow-up period extended from the index date of SDs to the diagnosis of prostate cancer, censoring, or the end of 2013. We used Cox proportional hazards models to calculate the risk of prostate cancer.ResultsIn total, 41,444 patients were enrolled in each cohort. The mean age of the SD cohort was 48.0 years and that of the non-SD cohort was 47.8 years, with 58.2% of both cohorts aged younger than 50 years. The incidence of prostate cancer increased with age. The overall incidence of prostate cancer was higher in the SD cohort than in the non-SD cohort (9.56 vs 6.36 per 10,000 person-y), with an adjusted hazard ratio of 1.42 (95% CI = 1.20–1.69). Age-specific analysis revealed a 1.35-fold increased risk of prostate cancer in the patients aged ≥65 years in the SD cohort compared with the non-SD counterparts (95% CI = 1.10–1.65).ConclusionsPatients with SDs are associated with increased risk of prostate cancer.

Association between sleep disorders and subsequent chronic spontaneous urticaria development: A population-based cohort study.

Patients with chronic spontaneous urticaria (CSU) often have sleep disorders (SDs) because of pruritus. However, SDs might also contribute to the development of CSU. Here, we present the first population-based cohort study on the association between SDs and subsequent CSU development.This study investigated whether SDs increase the risk of CSU by using a population-based database in Taiwan.This retrospective matched-cohort study included 105,892 patients with new-onset SDs (SD cohort) and 105,892 randomly selected controls (control cohort). Each patient was monitored for 10 years to individually identify patients who were subsequently diagnosed as having CSU during the follow-up period. A Cox proportional hazard regression analysis was conducted to determine the risk of CSU in patients with SDs compared with the controls.All relevant comorbidities were more prevalent in the SD cohort than in the control cohort (P < .001). During the follow-up period, the incidence rates of CSU among the patients with SDs and controls were 53.4 and 28.3 per 10,000 person-years, respectively. After adjustment for age, sex, and comorbidities, the adjusted hazard ratio for CSU in the SD cohort was 1.83 (95% confidence interval = 1.73–1.93, P < .001).The risk of CSU was higher in the patients with SDs than in the controls.

Sleep disorders associated with risk of rheumatoid arthritis.

Immune disorders impair sleep quality and sleep disorders (SDs) may derange immune function. The study evaluated the incidence and risk of rheumatoid arthritis (RA) in patients with SDs using a nationwide cohort. We recognized the patients with SDs from 1998 to 2002 by using the Taiwan National Health Insurance Research Database. One control patient for each SD patient was randomly selected and matched based on the proportion of age, sex, and index year. We calculated the person years of follow-up for each participant from the index date to RA diagnosis, censoring, or until December 31, 2011. The risk of RA was estimated by using Cox models incorporating demographics and comorbidities. We enrolled 65,754 patients with SDs and 65,753 controls and followed for 637,906 and 662,514 person-years, respectively. The patients with SDs exhibited a 1.49-fold greater risk of RA development compared with the comparison cohort when we adjusted for covariates. The patients with sleep apnea (SA) showed the greatest incidence density rate of RA, followed by those with non-apnea SDs and the non-SD cohort (4.11, 3.29, and 2.15 per 10,000 person-years, respectively). The SA cohort had a 2.56-fold adjusted hazard ratio (aHR) of RA (95% confidence interval [CI] = 1.11-5.91) and the non-apnea SD cohort had a 1.47-fold aHR of RA (95% CI = 1.18-1.84) compared with the non-SD cohort. Women with SDs presented a considerable risk of developing RA. This nationwide cohort study indicates that SDs are associated with the risk of RA development.

The Incidence and Risk of Herpes Zoster in Patients With Sleep Disorders: A Population-Based Cohort Study.

Lack of sleep can compromise the immune system, which may reactivate latent varicella-zoster virus. Studies on sleep disorders and the risk of herpes zoster (HZ) are scant.We conducted a population-based cohort study to evaluate the risk of HZ in patients with sleep disorders and potential risk factors for HZ development.We identified patients with sleep disorders without apnea from 2002 to 2005 by using the Taiwan Longitudinal Health Insurance Database. The patients without sleep disorders were randomly selected and frequency matched with patients with sleep disorders according to age, sex, and index year. We estimated the follow-up time in person-years for the patients from the entry date until HZ diagnosis, loss to follow-up, or the end of 2010. We used Cox proportional hazards regression models and a sensitivity analysis to estimate the risk of HZ while controlling for demographic characteristics and comorbidities.A total of 131,001 study participants (follow-up, 948,177 person-years; mean age, 51.2 ± 16.5 years; 62.2% women) were included in the study. Patients with sleep disorders exhibited a higher incidence of HZ compared with a comparison cohort when stratified by age, sex, and comorbidities. After adjustment for covariates, the sleep disorder cohort exhibited a 1.23-fold greater risk of HZ compared with the comparison cohort (95% confidence interval [CI] = 1.17–1.30). The incidence of HZ increased with age. Adults ages 65 years and older exhibited a 6.11-fold greater risk of HZ development compared with their younger counterparts (95% CI = 5.34–7.00). Cancers and autoimmune diseases were independent risk factors of HZ development.The patients with sleep disorders may carry an increased risk of developing HZ.

Higher risk of developing a subsequent migraine in adults with nonapnea sleep disorders: A nationwide population-based cohort study

ObjectiveThis nationwide population-based cohort study evaluated the effect of nonapnea sleep disorders (NSDs) on the subsequent development of a migraine. MethodsWe identified 46,777 patients aged 20years and older who were diagnosed with an NSD (ICD-9-CM: 307.4 or 780.5) and without coding for apnea-sleep disorders (ICD-9-CM: 780.51, 780.53, or 780.57) between 2000 and 2002 as the sleep disorder (SD) cohort. A comparison cohort of 93,552 people was enrolled. We calculated the adjusted hazard ratio (aHR) for developing a migraine (ICD-9-CM: 346) after adjusting for age, sex, comorbidity, and drug use. A Kaplan–Meier analysis was used to measure the cumulative incidence of a migraine between 2 curves until the end of 2011. ResultsThe cumulative incidence of a migraine was significantly higher in the SD cohort. The aHR for developing a migraine in the SD cohort was 3.52 (95% CI=3.28–3.79). The risk of developing a migraine with an NSD was higher in men (aHR=4.31) than in women (aHR=3.35). The age-stratified effect of an NSD on developing a migraine was highest among patients aged 55years and younger. Higher risks of developing a migraine were observed among the participants without any comorbidity and without any drug treatment for their insomnia. ConclusionThe findings of this population-based cohort study indicate a higher risk of developing a subsequent migraine in patients with an NSD, which could be considered an independent, predisposing factor for developing subsequent a migraine in adulthood.

Increased risk of erectile dysfunction among patients with sleep disorders: a nationwide population-based cohort study.

Few studies have investigated the relationship between sleep disorders (SD) and erectile dysfunction (ED). Therefore, this study explored whether patients with SD in an Asian population are at an increased risk of developing ED. This longitudinal nationwide population-based cohort study investigated the incidence and risk of developing ED in 34,548 men newly diagnosed with SD between 2002 and 2008 from the National Health Insurance Research Database. A total of 138,192 controls without SD were randomly recruited from the general population and frequency matched according to age and sex. The follow-up period began from the date of entering the study cohort until the date of an ED event, censoring, or 31 December 2010. We conducted Cox proportional hazard regression analyses to estimate the effects of SD on the risk of ED. The SD cohort had a 2.11-fold adjusted hazard ratio (HR) of subsequent ED development compared with the non-SD cohort [95% confidence interval (CI)=1.89-2.37]. The incidence of ED increased with age for both cohorts and was higher for the patients in the SD cohort. Compared with the participants without SD or comorbidities, the patients without SD with any comorbidity exhibited a 1.79-fold risk of developing ED (95% CI=1.54-2.09); the highest risk was for those with both SD and any comorbidity (HR=3.34, 95% CI=2.82-3.95). Furthermore, SD patients who had a particular number of comorbidities showed the dose-response effect of developing ED. This nationwide cohort study determined that ED risk evidently increased in SD patients compared with the general population.

Interactive Cohort Identification of Sleep Disorder Patients Using Natural Language Processing and i2b2.

Nationwide Children's Hospital established an i2b2 (Informatics for Integrating Biology & the Bedside) application for sleep disorder cohort identification. Discrete data were gleaned from semistructured sleep study reports. The system showed to work more efficiently than the traditional manual chart review method, and it also enabled searching capabilities that were previously not possible. We report on the development and implementation of the sleep disorder i2b2 cohort identification system using natural language processing of semi-structured documents. We developed a natural language processing approach to automatically parse concepts and their values from semi-structured sleep study documents. Two parsers were developed: a regular expression parser for extracting numeric concepts and a NLP based tree parser for extracting textual concepts. Concepts were further organized into i2b2 ontologies based on document structures and in-domain knowledge. 26,550 concepts were extracted with 99% being textual concepts. 1.01 million facts were extracted from sleep study documents such as demographic information, sleep study lab results, medications, procedures, diagnoses, among others. The average accuracy of terminology parsing was over 83% when comparing against those by experts. The system is capable of capturing both standard and non-standard terminologies. The time for cohort identification has been reduced significantly from a few weeks to a few seconds. Natural language processing was shown to be powerful for quickly converting large amount of semi-structured or unstructured clinical data into discrete concepts, which in combination of intuitive domain specific ontologies, allows fast and effective interactive cohort identification through the i2b2 platform for research and clinical use.

Sleep disorders increase the risk of venous thromboembolism in individuals without sleep apnea: a nationwide population-based cohort study in Taiwan

ObjectiveStudies investigating the relationship between sleep disorders (SDs) and the risk of venous thromboembolism (VTE) are scarce. The present study from Taiwan evaluated whether the risk of VTE was associated with SDs other than sleep apnea. MethodsThe present study investigated the incidence and risk of VTE in 46,371 people with SDs, compared with 92,742 controls without SDs. The follow-up period began from the date of entering the study cohort to the date of a VTE event, censoring, or December 31, 2011. A Cox proportional hazards regression analysis was conducted to estimate the effects of SDs on the risk of VTE. ResultsThe SD cohort had a 1.79-fold adjusted hazard ratio (HR) of subsequent VTE, compared with the non-SD cohort (95% CI 1.49–2.16). The incidence of VTE increased with age for both cohorts but was higher for those in the SD cohort. However, the adjusted HRs for VTE were significantly higher for the people with SDs aged ≦49 years (HR 3.29, 95% CI 2.12–5.12) and 50–64 years (HR 2.43, 95% CI 1.76–3.35), but were not significant for the oldest group (HR 1.11, 95% CI 0.84–1.47), compared with the controls. The multiplicative increased risk of VTE was significant for the people with SDs with any comorbidity. ConclusionThis nationwide cohort study determined that the VTE risk significantly increased in people with SDs compared with those of the general population.

Sleep Disorders and Increased Risk of Subsequent Acute Coronary Syndrome in Individuals without Sleep Apnea: A Nationwide Population-Based Cohort Study

Studies investigating the relationship between nonapnea sleep disorders and the risk of acute coronary syndrome (ACS) are scant. This study evaluated whether the risk of ACS is associated with sleep disorders other than sleep apnea in Taiwan. This longitudinal nationwide population-based cohort study investigated the incidence and risk of ACS in 49,099 cases of nonapnea sleep disorders newly diagnosed from January 1997 to December 2001. In total, 98,198 control participants without sleep disorders were randomly selected, frequency matched by age and sex from the general population. The follow-up period started from the date of entering the study cohort to the date of an ACS event, censoring, or December 31, 2010. We conducted Cox proportional hazard regression analysis to estimate the effects of nonapnea sleep disorders on ACS risk. The nonapnea sleep disorder cohort had an adjusted hazard ratio (HR; 95% confidence interval [CI] = 1.29-1.60) of subsequent ACS 1.43-fold higher than that of the cohort without sleep disorders. The highest crude effect of nonapnea sleep disorders on ACS incidence was detected among young adults. However, by adjusting for probable risk factors, the HR of ACS increased with age. Compared with women, men had an adjusted HR of 1.57 (95% CI = 1.42-1.75). Hypertension, diabetes mellitus (DM), and hyperlipidemia were also significant factors associated with the increased risk of ACS. This nationwide population-based cohort study provides evidence that patients with nonapnea sleep disorders are at higher risk of developing acute coronary syndrome, which increases with age.

Population-based cohort study on the increase in the risk for type 2 diabetes mellitus development from nonapnea sleep disorders

ObjectivesThe evidence concerning the relationship between nonapnea sleep disorders and the risk for type 2 diabetes mellitus (DM) is scant and elusive. Our study aimed to examine if nonapnea sleep disorders increase the risk for DM using a population-based retrospective cohort study from 1997 to 2010. MethodsIn the Taiwan’s National Health Insurance Research Database (NHIRD), 45,602 patients with nonapnea sleep disorders were identified as the study cohort. The comparison cohort was formed by 91,204 age- and gender-matched controls. Cox proportional hazards regression model was used to estimate the risk for developing DM. ResultsIn 45,602 patients with nonapnea sleep disorders, 7241 new cases of DM were reported during the follow-up period. The mean follow-up time was 9.04 (standard deviation [SD], 3.33) and 8.96 (SD, 3.47) for the nonapnea sleep disorders cohort and the comparison cohort, respectively. The incidence rate of DM was higher in the nonapnea sleep disorder cohort than in the comparison cohort (17.6 vs 13.3 per 1000 individuals-years). Overall, patients with nonapnea sleep disorders had a higher risk for DM compared to patients without nonapnea sleep disorders (adjusted hazard ratio [HR], 1.05 [95% confidence interval {CI}, 1.02–1.08]). Men with nonapnea sleep disorders had a higher risk for DM than the men in the comparison group (adjusted HR, 1.08 [95% CI, 1.03–1.14]). Among subjects aged less than 40years, patients with nonapnea sleep disorders had a higher risk for DM than the comparison group (adjusted HR, 1.42 [95% CI, 1.27–1.59]). Compared with the comparison cohort, patients with sleep disturbance had an 11% higher risk for DM (adjusted HR, 1.11 [95% CI, 1.07–1.16]). ConclusionCompared to patients without nonapnea sleep disorders, patients with nonapnea sleep disorders had a higher risk for developing DM, especially among those who were less than 40years of age and who had sleep disturbances.

Non-apnea sleep disorders will increase subsequent liver cancer risk – A nationwide population-based cohort study

It is well known that patients with sleep disorders (SD) have an increased risk of cardiovascular disease, diabetes mellitus, obesity, and total mortality. However, little information exists regarding the relationship between non-apnea SD and the risk of cancer. The goal of this study was to determine if any association between SD and malignancy exists in Taiwan. We used data from the National Health Insurance system of Taiwan to assess this issue. The SD cohort contained 42,351 patients, and each patient was randomly frequency-matched by age and sex with two people from the general population without SD. The Cox's proportional hazard regression analysis was conducted to estimate the effects of SD on cancer risk. In patients with SD, the overall risk of developing cancer was significantly higher than in normal healthy subjects (adjusted Hazard ratio [HR]=1.12, 95% confidence interval=1.06-1.18). This held true even when we analyzed males and females separately. In regards to individual types of cancer, the risk for developing liver cancer among patients with SD was significantly higher than in subjects without SD. For breast cancer the risk showed a marginally significant increase. The nationwide population-based cohort study found Taiwanese patients with SD have a higher risk of developing cancer, particularly liver cancer and, possibly, breast cancer.

A descriptive analysis of neck myoclonus during routine polysomnography.

Although episodes of neck myoclonus (head jerks) in REM sleep have a characteristic appearance, they have so far not been described systematically in video-polysomnography. This study assesses the occurrence, frequency, and characteristics of neck myoclonus in REM sleep in a prospective sleep disorder cohort, and investigates clinical correlates and associations with medication. University hospital sleep disorders center. Two-hundred twenty-eight mixed sleep disorder patients. Not applicable. REM sleep was screened visually for short "stripe-shaped" movement-induced artifacts visible vertically over the EEG leads in polysomnographic registration. If such artifact was present, the synchronized video was inspected for the presence of neck myoclonus. Out of 205 patients, 54.6% (n = 112) had neck myoclonus during REM sleep. The mean neck myoclonus index was 1.0 +/- 2.7/h REM sleep. Younger patients had a higher neck myoclonus index than older patients (< 45 years versus 45-60 years versus > 60 years: 1.8 +/- 4.2 versus 0.6 +/- 1.1 versus 0.5 +/- 1.1; P = 0.004). Ninety-five percent of subjects < 45 years had a neck myoclonus index between 0 and 9.4/h; 95% of subjects > 45 years had a neck myoclonus index between 0 and 2.7/h. Patients on benzodiazepine treatment had no neck myoclonus (0/112 vs. 13/93; P < 0.001). In 23 patients, additional surface neck EMG was performed. EMG activation associated with neck myoclonus had a mean duration of 0.6 +/- 0.4 sec. Correlation between duration of neck EMG activation and movement-induced EEG artifact duration was very high (rho = 0.96; P < 0.001). Neck myoclonus is common during REM sleep and more frequent in younger individuals. This could indicate that neck myoclonus during REM sleep is a physiological phenomenon. If there is a cut-off distinguishing normal from excessive has to be investigated in further studies.