Does REM Sleep-Dependent Obstructive Sleep Apnea Have Clinical Significance?

(1) Background: The clinical significance of rapid eye movement (REM) sleep-dependent obstructive sleep apnea (OSA) remains controversial because various criteria have been used to describe it. This study determined the clinical significance of REM-OSA in Koreans using data from patients with sufficient total sleep time (TST) and REM sleep duration. (2) Methods: We investigated 1824 patients with OSA who were diagnosed by polysomnography (PSG). REM-OSA was defined as an overall apnea-hypopnea index (AHI) ≥ 5, NREM-AHI < 15, and REM-AHI/NREM-AHI ≥ 2. Demographic and medical data were collected from digital medical records and sleep questionnaires. We compared clinical and PSG data between REM-OSA and REM sleep-nondependent OSA (nREM-OSA). (3) Results: In total, 140 patients (20.2%) were categorized as REM-OSA. Those patients were predominantly female (53.6% vs. 21.7% of the overall cohort, p < 0.001). REM-OSA is frequent in the mild (69.3% vs. 18.8%) to moderate (30% vs. 27.9%) range of OSA (p < 0.001). (4) Conclusions: The prevalence of REM-OSA was similar to that in previous study findings: frequent in mild to moderate OSA and females, which is consistent with results in Western populations. Our findings suggest that REM-OSA does not have clinical significance as a subtype of OSA.

Cognitive behavioral therapy for insomnia in restless legs syndrome patients.

OBJECTIVES: The purpose of this study was to investigate the effects of cognitive behavioral therapy for insomnia (CBTI) in patients with Restless Legs Syndrome (RLS). METHODS: This is a randomized controlled study. The patients were sequentially selected and randomly assigned to either a CBTI group or a non-CBTI group. A total of 25 RLS patients with comorbid insomnia were recruited from a tertiary university hospital sleep center. Twelve were assigned to the CBTI group, and 13 were assigned to the non-CBTI group. The CBTI group received 4 sessions of behavioral therapy, while the non-CBTI group received one informative session on sleep hygiene. All patients completed sleep and psychiatric-related questionnaires. In addition, each individual completed a one-week sleep log for collecting subjective sleep data and actigraphy for objective sleep data. RESULTS: After conducting the CBTI, there were significant improvements in severity of insomnia symptoms, subjective sleep efficiency, total sleep time, latency to sleep onset, wake after sleep onset, objective latency to sleep onset, and anxiety in the CBTI group as compared to the non-CBTI group. The effect of CBTI on sleep-related data was maintained for up to three months. CONCLUSIONS: CBTI was effective in RLS patients by improving sleep quality and anxiety symptoms. CBTI may be considered in clinical practice for RLS patients with comorbid insomnia.

miRNA biogenesis-associated RNase III nucleases Drosha and Dicer are upregulated in colorectal adenocarcinoma.

Drosha and Dicer are important regulators of microRNA (miRNA) biogenesis, and it has been suggested that their aberrant regulation may cause colorectal cancer (CRC). The aim of the present study was to evaluate the mRNA expression levels of these two important RNase III nucleases and their association with clinical features in CRC specimens from South Korean patients. The expression levels of Drosha and Dicer mRNA were investigated in 77 CRC tissues and adjacent histologically non-neoplastic tissues using the quantitative polymerase chain reaction. The expression levels of Drosha and Dicer mRNA were identified to be upregulated in CRC. Neither the Drosha nor the Dicer mRNA expression level was associated with any clinical parameter, including sex, age, TNM stage, body mass index and carcinoembryonic antigen titer in patients with CRC. Furthermore, the expression levels of Drosha and Dicer mRNA were not associated with each other. The miRNA biogenesis-associated RNase III nucleases Drosha and Dicer are significantly upregulated in CRC, suggesting their importance in the pathobiology of colorectal carcinogenesis.

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Soil microbial biomass C and N, microbial diversities and enzyme activity in 0-10 cm and 10-20 cm soil layers of different degraded grasslands (non-degradation, ND; light degradation, LD; moderate degradation, MD; sever degradation, SD; and black soil beach, ED) were measured by Biolog and other methods. The results showed that: 1) There were significant diffe-rences between 0-10 cm and 10-20 cm soil layers in soil microbial biomass, diversities and inver-tase activities in all grasslands. 2) The ratio of soil microbial biomass C to N decreased significantly with the grassland degradation. In the 0-10 cm soil layer, microbial biomass C and N in ND and LD were significantly higher than that in MD, SD and ED. Among the latter three kinds of grasslands, there was no difference for microbial biomass C, but microbial biomass N was lower in MD than in the other grasslands. The average color change rate (AWCD) and McIntosh Index (U) also decreased with grassland degradation, but only the reduction from ND to MD was significant. There were no differences among all grasslands for Shannon index (H) and Simpson Index (D). The urease activity was highest in MD and SD, and the activity of phosphatase and invertase was lowest in ED. In the 10-20 cm soil layer, microbial biomass C in ND and LD were significantly higher than that in the other grasslands. Microbial biomass N in LD and ED were significantly higher than that in the other grasslands. Carbon metabolism index in MD was significantly lower than that in LD and SD. AWCD and U index in ND and LD were significantly higher than that in ED. H index and D index showed no difference among different grasslands. The urease activity in ND and MD was significantly higher than that in the other grasslands. The phosphatase activity was highest in MD, and the invertase activity was lowest in MD. 3) The belowground biomass was significantly positively correlated with microbial biomass, carbon metabolic index and phosphatase activity, and the urease activity was negatively correlated with microbial biomass N, H index and D index.

The Effect of Seed-Borne Fungi and Epichloë Endophyte on Seed Germination and Biomass of Elymus sibiricus.

The interactive effects of asexual Epichloë (formerly known as Neotyphodium) endophytes isolated from Hordeum brevisubulatum, Elymus tangutorum and Achnatherum inebrians, and seed-borne fungi on Elymus sibiricus seeds, were determined by an in vitro study using supernatants from liquid cultures of the endophyte strains. In an 8 week greenhouse study, the effects on the seedlings growth was measured. The in vitro study was carried out with the seed-borne fungi Alternaria alternata, Bipolaris sorokiniana, Fusarium avenaceum, and a Fusarium sp. isolated from E. sibiricus. Different concentrations and combinations of the liquid cultures of endophytic fungi enhanced the interim germination, germination rate, length of coleoptile and radicle, and seedling dry weight of E. sibiricus under stress from seed-borne fungi. In the greenhouse study, different concentrations of the supernatant of the endophytes from H. brevisubulatum and E. tangutorum but not A. inebrians, signficantly (P < 0.05) enhanced E. sibiricus seed germination. There was no significant (P > 0.05) increase of the tiller numbers after 2 weeks. However, later on, there were significant (P < 0.05) increases in tiller number (4-8 weeks), seedling height (2-8 weeks) and dry weight (2-8 weeks). The application of Epichloë endophyte culture supernatants was an effective strategy to improve seed germination and growth under greenhouse conditions.

Mood Symptoms and Restless Legs Syndrome Without Periodic Limb Movements During Sleep: Is it a Clinical Subtype?

Frequently co-occurring restless legs syndrome (RLS) and periodic limb movements during sleep (PLMS) are postulated to share common pathophysiology. The authors compared clinical characteristics and polysomnography (PSG) parameters among 155 idiopathic, untreated RLS patients who were stratified into three groups based on periodic limb movement index (PLMI). The authors found that RLS patients without PLMS (PLMI <5) had higher depression and anxiety scores, a lower total arousal index, longer latency to REM, and a higher spontaneous arousal frequency on PSG than RLS patients with PLMS. RLS severity was associated with PLMI in RLS patients with PLMS but not without PLMS. RLS without PLMS seems to be a phenotypically distinct clinical subtype of RLS. Future study should examine whether RLS without PLMS has a different clinical course, treatment response, and pathophysiology than RLS with PLMS.

Two subtypes of positional obstructive sleep apnea: Supine-predominant and supine-isolated.

OBJECTIVES: The body position has a strong influence on obstructive sleep apnea (OSA). The purpose of this study is to compare the clinical features of two subtypes of positional OSA (POSA), namely supine-predominant OSA (spOSA) and supine-isolated OSA (siOSA), so as to discuss whether the two groups can be classified separately. METHODS: A total of 279 consecutive patients with OSA were enrolled. The POSA was defined as having an overall apnea-hypopnea index (AHI) ⩾ 5 with supine AHI > 2 times the non-supine AHI. Only those with ⩾ 30 min spent in the supine and non-supine sleeping positions were included, and split night studies were excluded from the study. Patients were considered spOSA unless their non-supine AHI was negligible (<5) (siOSA). The clinical and polysomnographic characteristics of both groups were compared. RESULTS: Two hundred and sixteen subjects (77.4%) met the criteria for POSA, with 158 (73.1%) of them classified as spOSA, and 58 (26.9%) as siOSA. The siOSA patients had lower arousal indices, but poorer quality of sleep, and were more depressed and anxious compared with the spOSA subjects. CONCLUSIONS: Those with siOSA and spOSA show different clinical features. SIGNIFICANCE: These findings suggest that a more detailed sub-classification of POSA is needed.

Comparison of impact of insomnia on depression and quality of life in restless legs syndrome/Willis-Ekbom disease and primary insomnia patients.

BACKGROUND: Although insomnia is common among people with restless legs syndrome (RLS), its impact on the daily suffering of those with RLS remains unclear. This study aimed to compare the differential impact of clinical insomnia on depression and quality of life (QoL) among people with RLS, primary insomnia, and healthy controls. METHODS: A total of 148 people with RLS, 115 with primary insomnia, and 117 healthy controls were enrolled into this cross-sectional study. Participants completed sleep, depression, and QoL questionnaires. Clinical insomnia was defined as Korean version of the Insomnia Severity Index (K-ISI) ≥ 15. Correlation coefficients between sleep measures and both depression and QoL were calculated. Multivariate regression was used to identify the clinical factors that were most closely associated with depression and QoL among people with RLS and primary insomnia. RESULTS: Participants with RLS had insomnia and sleep quality at intermediate levels between the healthy controls and primary insomnia subjects, but those with clinical insomnia had equivalent depression and QoL scores regardless of RLS diagnosis. Insomnia severity correlated with depression and QoL in RLS and primary insomnia. Multivariate regression, however, revealed that RLS severity was the most overall predictive factor for depression and QoL among those with RLS. Insomnia severity was the strongest predictor in primary insomnia. CONCLUSION: Insomnia was more closely associated with depression and QoL among people with primary insomnia than those with RLS, but clinical insomnia may have a significant impact in RLS as well. Future RLS studies should account for sleep quality in addition to RLS symptom severity when investigating mood and QoL.

Clinical Characteristics of Primary Insomniacs with Sleep-State Misperception.

BACKGROUND AND PURPOSE: The aims of this study were to determine the prevalence of sleep-state misperception and to identify any differences in the clinical characteristics of primary insomniacs with and without misperception. METHODS: In total, 250 adult primary insomniacs were enrolled whose objective total sleep time (TST) was more than 120 min, as assessed by full-night polysomnography. Sleep state misperception was defined objectively as a TST of at least 6.5 h and an objective sleep efficiency (SE) of at least 85%. RESULTS: The prevalence of sleep-state misperception in primary insomniacs was 26.4%. The (low) quality of sleep and psychiatric parameters were similar in the two groups, although the objective sleep architecture was relatively normal for the misperception group. Multivariate analysis revealed that both SE and sleep quality were significant factors associated with subjective TST in the misperception group, while only SE was significant in those without misperception. Subjective TST was a significant effect factor with respect to sleep quality in the misperception group, while the Beck Depression Inventory-2 score and age were significant factors in those without misperception. CONCLUSIONS: The clinical characteristics of patients with sleep-state misperception differed from those without this condition. This suggests that these two groups should be separated and the treatment goals tailored specifically to each.

Prevalence and clinical characteristics of patients with restless legs syndrome with painful symptoms.

BACKGROUND: The complaint of pain has largely been ignored in the diagnostic criteria for restless legs syndrome (RLS). The purpose of this study was to investigate the prevalence of painful symptoms in RLS, and to compare sleep-related characteristics between the patients who experienced the painful symptoms and those who did not. METHODS: The patients with RLS were retrospectively screened from July 2011 to December 2013 at a tertiary-care sleep center. For classifying those with pain and those without pain, more than three specialists separately observed the patients' reports and complaints of symptoms, and the final decision was made through consensus. The demographics and clinical characteristics, including sleep, psychiatric-related scales, and polysomnographic data were reviewed for the study. RESULTS: One hundred and sixty patients with RLS were selected, and 23.8% of them reported painful symptoms of RLS. Patients with RLS who experienced painful sensations were found to have lower ferritin levels, more severe RLS symptoms, anxiety and depressive symptoms, and a lower quality of life. The polysomnography data found that patients with RLS who experienced painful sensations had a longer latency to sleep onset and a lower periodic limb movement index (PLMI) (p <0.05). CONCLUSIONS: Patients who experienced painful sensations had more severe RLS symptoms and a trend toward lower PLMI during sleep. According to these results, an inference can be made that painful sensations may be one important point in determining the severity of RLS.

Augmentation in restless legs syndrome patients in Korea.

PURPOSE: Augmentation has been known as the major complication of long-term dopaminergic treatment of restless legs syndrome (RLS). However, there have been no reports on the prevalence of augmentation in Korea. Thus, we aimed to assess the rate of augmentation and evaluate related factors in Korean RLS patients. METHODS: Ninety-four idiopathic RLS patients who have been treated over a period of at least 6 months were enrolled. Thirty subjects were treated with a dopamine agonist only, and 64 were treated with a dopamine agonist and alpha two delta ligands. We assessed the clinical characteristics of those RLS subjects and evaluated the rate of augmentation. Augmentation was assessed using the NIH criteria for augmentation by two RLS experts independently. RESULTS: Eleven subjects (11.7%) were classified as having definitive or highly suggestive clinical indication of augmentation. In comparing the augmentation group with the non-augmentation group, there were no significant differences of baseline clinical characteristics. Four (13.3%) of the dopamine agonists monotherapy group and seven (10.9%) of the combination therapy group were categorized as augmentation. There was no significant difference in the augmentation rate between these two groups. CONCLUSIONS: We found an 11.7% augmentation rate in Korean RLS subjects. There was no difference in the rate of RLS augmentation between the dopaminergic monotherapy group and the combined treatment group. It may be related with using a similar dosage of dopaminergic drugs.

Validation of a Korean version of the insomnia severity index.

BACKGROUND AND PURPOSE: The purposes of this study were to standardize and validate a Korean version of the Insomnia Severity Index (ISI-K), and to evaluate its clinical usefulness. METHODS: We translated the ISI into Korean and then translated it back into English to check its accuracy. The 614 patients with sleep disorders who were enrolled in this study comprised 169 with primary insomnia, 133 with comorbid insomnia, and 312 with obstructive sleep apnea. All subjects underwent one night of polysomnography (PSG) and completed the Korean versions of both the Pittsburgh Sleep Quality Index (PSQI-K) and the Epworth Sleepiness Scale, as well as the ISI-K. The ISI-K was compared to these sleep scales and various PSG sleep parameters. RESULTS: The internal consistency the ISI-K total score was confirmed by a Cronbach's alpha of 0.92, and the item-to-total-score correlations (item-total correlations) ranged from 0.65 to 0.84, suggesting adequate reliability. The correlation between the ISI-K total score and PSQI-K was 0.84, which suggested adequate convergent validity. Low-to-moderate correlations were obtained between the ISI-K total score and PSG-defined sleep parameters: 0.22 for sleep onset latency, 0.38 for wake after sleep onset, and 0.46 for sleep efficiency. A cutoff score of 15.5 on the ISI-K was optimal for discriminating patients with insomnia. The test-retest scores over a 4-week interval with 34 subjects yielded a correlation coefficient of 0.86, suggesting excellent temporal stability. CONCLUSIONS: The findings of this study show that the ISI-K is a reliable and valid instrument for assessing the severity of insomnia in a Korean population.

Effects of pregabalin in patients with hypnotic-dependent insomnia.

STUDY OBJECTIVES: Long-term use of hypnotics runs the risk of dependency, and subjects usually experience difficulties in withdrawal. The objective of this study was to investigate the success of withdrawal using pregabalin and its efficacy on sleep in patients with hypnotic-dependent insomnia. METHODS: We enrolled patients with hypnotic-dependent insomnia who were 18 years or older. The starting dosage of pregabalin was 75 mg/day and was increased up to as much as 300 mg/day, depending on the individual patient's condition, while tapering off hypnotics. After 4 weeks of titration, the final dosage amount was maintained for at least another 4 weeks. Sleep and clinical variables were evaluated at baseline and after treatment, using the Korean versions of various sleep questionnaires as well as polysomnography. RESULTS: Forty subjects were enrolled, with a mean age of 52.0 ± 8.5 years, of whom 28 (70.0%) were women. Twenty-one (52.5%) subjects successfully withdrew from hypnotics. The duration of withdrawal was 42.1 ± 16.0 days (range: 27.0∼84.0). The mean pregabalin dose was 121.4 ± 69.0 mg/day (range: 75.0∼300.0). After pregabalin treatment, there was a significant improvement in the total score of the Pittsburgh Sleep Quality Index (15.0 ± 2.1, 8.9 ± 3.0, p < 0.001), and insomnia severity index (20.9 ± 4.3, 9.6 ± 4.4, p < 0.001); however, most of the sleep variables of the PSG showed no differences. The main adverse effects of pregabalin were nausea and dizziness. CONCLUSIONS: Our results showed pregabalin may be a promising candidate for withdrawal from hypnotics and improved sleep in patients with hypnotic-dependent insomnia.