刘中勇从“气血瘀滞”论治不寐的临证经验

不寐,现代医学称睡眠障碍,是一种临床常见病和多发病,本病发病原因尚不明确,通常不伴明显器质性病变,病人自觉症状重,西医尚无明确的治愈方法。祖国医学很早就认识到本病,积累了丰富的经验。刘中勇教授在古人的基础上提出从"气血瘀滞"的角度论治不寐,临床取得较好疗效,本文将从病因病机、理论探析、辨证论治三个方面介绍其相关经验,供同行参考。     

The challenges in scoring hypopneas in children: is pulse wave amplitude drop the answer?

BackgroundIdentifying electroencephalogram (EEG) cortical arousals are crucial in scoring hypopneas and respiratory efforts related arousals (RERAs) during a polysomnogram. As children have high arousal threshold, many of the flow limited breaths or hypopneas may not be associated with visual EEG arousals, hence this may lead to potential underestimation of the degree of sleep disordered breathing. Pulse wave amplitude (PWA) is a signal obtained from finger photoplethysmography which correlates directly to finger blood flow. The drop in PWA has been shown to be a sensitive marker for subcortical/autonomic and cortical arousals. Our aim was to use the drop in PWA as a surrogate for arousals to guide scoring of respiratory events in pediatric patients.MethodsTen polysomnograms for patients between the ages of 5–15 years who had obstructive apnea-hypopnea indices between 1 and 5 events/hour were identified. Patients with syndromes were excluded. A drop in PWA signal of at least 30% that lasted for 3 s was needed to identify subcortical/autonomic arousals. Arousals were rescored based on this criteria and subsequently respiratory events were rescored. Paired t-tests were employed to compare PSG indices scored with or without PWA incorporation.ResultsThe sample of 10 children included 2 females, and the average age was 9.8 ± 3.1 years. Overall, polysomnography revealed an average total sleep time of 464.1 ± 25 min, sleep efficiency of 92% +/−4.2, sleep latency of 19.6 ± 17.0 min, rapid eye movement (REM) latency 143 ± 66 min, N1 3.9% +/−2.0, N2 50.3% +/−12.0, N3 28.2% +/−9.1, REM 16.7% +/−4.0, and wakefulness after sleep onset (WASO) 18.1 ± 7.5 min. Including arousals from PWA changes, respiratory indices significantly increased including total AHI (2.3 ± 0.7 vs 5.7 ± 2.1, p < 0.001), obstructive AHI (1.45 ± 0.7 vs 4.8 ± 1.8, p < 0.001), and RDI (2.36 ± 0.7 vs 7.6 ± 2.0, p < 0.001). Likewise, total arousal index was significantly higher (8.7 ± 2.3 vs 29.4 ± 6.5, p < 0.001).ConclusionsThe drop in pulse wave amplitude signal is a useful marker to guide scoring arousals that are not otherwise easily identified in pediatric polysomnography and subsequently helped in scoring respiratory events that otherwise would not be scored. Further studies are needed to delineate if such methodology would affect clinical outcome.     

Analysis of arterial hypertension pharmacotherapy in patients with obstructive sleep apnea syndrome

IntroductionObstructive sleep apnea (OSA) is often connected with arterial hypertension and it could also be a cause of secondary hypertension. Treatment of arterial hypertension and optimal blood pressure level are important for prevention of cardiovascular complications. It is not well known how to treat patients with OSA and arterial hypertension. Also many patients with OSA suffer from metabolic syndrome which worsen their prognosis.AimThe aim of our study was to assess arterial hypertension compensation in patients with metabolic syndrome and moderate to severe OSA and to analyze used pharmacotherapy.Materials and methods85 hypertensive patients (75 men) with metabolic syndrome, average age 53.6 ± 9.3 years, were evaluated using overnight sleep study with diagnosis of OSA, average apnea–hypopnea index (AHI) 56.3 ± 23. Patients underwent 24 h ambulatory blood pressure monitoring (ABPM) and their current pharmacotherapy data were obtained. Appropriate combinations of antihypertensive drugs (patients with metabolic syndrome) were derived from ESH/ESC 2013 guidelines.ResultsArterial hypertension was well compensated in only 11.8% of the patients. 24.7% patients were treated according to current guidelines. Fisher's exact test with analysis of adjusted residues has found higher rate of blood pressure subcompensation in patients treated with triple+ combination of drugs (p = 0.035, 51.4% vs 10%).ConclusionOnly a small number of patients had optimal blood pressure level and were treated according to current ESH/ESC guidelines. We have to constantly appeal to all physicians to perform ABPM in patients with OSA.     

Absence of FGFR3–TACC3 rearrangement in hematological malignancies with numerical chromosomal alteration

FGFR–TACC, found in different tumor types, is characterized by the fusion of a member of fibroblast grown factor receptor (FGFR) tyrosine kinase (TK) family to a member of the transforming acidic coiled-coil (TACC) proteins. Because chromosome numerical alterations, hallmarks of FGFR–TACC fusions are present in many hematological disorders and there are no data on the prevalence, we studied a series of patients with acute myeloid leukemia and myelodysplastic syndrome who presented numerical alterations using cytogenetic traditional analysis. None of the analyzed samples showed FGFR3–TACC3 gene fusion, so screening for this mutation at diagnosis is not recommended.     

Transcranial Electrical Stimulation targeting limbic cortex increases the duration of human deep sleep

BackgroundResearchers have proposed that impaired sleep may be a causal link in the progression from Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD). Several recent findings suggest that enhancing deep sleep (N3) may improve neurological health in persons with MCI, and buffer the risk for AD. Specifically, Transcranial Electrical Stimulation (TES) of frontal brain areas, the inferred source of the Slow Oscillations (SOs) of N3 sleep, can extend N3 sleep duration and improve declarative memory for recently learned information. Recent work in our laboratory using dense array Electroencephalography (dEEG) localized the sources of SOs to anterior limbic sites – suggesting that targeting these sites with TES may be more effective for enhancing N3.MethodsFor the present study, we recruited 13 healthy adults (M = 42 years) to participate in three all-night sleep EEG recordings where they received low level (0.5 mA) TES designed to target anterior limbic areas and a sham stimulation (placebo). We used a convolutional neural network, trained and tested on professionally scored EEG sleep staging, to predict sleep stages for each recording.ResultsWhen compared to the sham session, limbic-targeted TES significantly increased the duration of N3 sleep. TES also significantly increased spectral power in the 0.5–1 Hz frequency band (relative to pre-TES epochs) in left temporoparietal and left occipital scalp regions compared to sham.ConclusionThese results suggest that even low-level TES, when specifically targeting anterior limbic sites, can increase deep (N3) sleep and thereby contribute to healthy sleep quality.     

Does Outcome/Survival of Patients With Myelodysplastic Syndromes Should Be Predicted by Reduced Levels of ADAMTS-13? Results From a Pilot Study

IntroductionVon Willebrand factor (vWF) cleaving protease ADAMTS-13 has a key role for maintaining normal size of vWF. A deficiency or dysfunction of vWF cleaving protease is associated with ultra large vWF multimers and thrombotic microangiopathy. Patients with cancers have reduced levels of vWF cleaving protease. In this pilot study, we have evaluated whether or not deficiencies of ADAMTS-13 were present in myelodysplastic syndromes (MDS). Moreover, we assessed if a reduction in basal levels of ADAMTS-13 may play a role in the prognosis of MDS.Patients and MethodsWe measured and compared the levels of vWF cleaving protease ADAMTS-13 in 100 patients with MDS and 35 healthy controls. Patients were divided into 2 groups according to the International Prognostic Scoring System: group I consisting of 44 patients with low-risk MDS and group II of 56 patients with high-risk MDS. Patients with high-risk and low-risk MDS presented significantly lower levels of ADAMTS-13 than controls (P < .001 and P = .0177, respectively). High-risk patients had significantly lower levels of ADAMTS-13 when compared with the low-risk group (P < .001).ResultsWe found that reduced levels of ADAMTS-13 have a relationship with overall survival (P < .001). Statistical analysis showed that ADAMTS-13 correlates with cytogenetics (P < .001) and a tendency of slight correlation with platelet count and basal levels of ADAMTS-13 (R, 0.35; P value, 0.001). Moreover, we found that levels of ADAMTS-13 have correlation with response to treatment (P < .001).ConclusionsADAMTS-13 in MDS might represent a surrogate marker of prognosis, response to therapy, or disease progression. Further studies are needed.     

Using recreational cannabis to treat insomnia: Evidence from over-the-counter sleep aid sales in Colorado

This study seeks to understand whether people substitute between recreational cannabis and conventional over-the-counter (OTC) sleep medications. UPC-level grocery store scanner data in a multivariable panel regression design were used to compare the change in the monthly market share of sleep aids with varying dispensary-based recreational cannabis access (existence, sales, and count) in Colorado counties between 12/2013 and 12/2014. We measured annually-differenced market shares for sleep aids as a portion of the overall OTC medication market, thus accounting for store-level demand shifts in OTC medication markets and seasonality, and used the monthly changes in stores’ sleep aid market share to control for short-term trends. Relative to the overall OTC medication market, sleep aid market shares were growing prior to recreational cannabis availability. The trend reverses (a 236% decrease) with dispensary entry (−0.33 percentage points, 95% CI −0.43 to −0.24, p < 0.01) from a mean market share growth of 0.14 ± 0.97. The magnitude of the market share decline increases as more dispensaries enter a county and with higher county-level cannabis sales. The negative associations are driven by diphenhydramine- and doxylamine-based sleep aids rather than herbal sleep aids and melatonin. These findings support survey evidence that many individuals use cannabis to treat insomnia, although sleep disturbances are not a specific qualifying condition under any U.S. state-level medical cannabis law. Investigations designed to measure the relative effectiveness and side effect profiles of conventional OTC sleep aids and cannabis-based products are urgently needed to improve treatment of sleep disturbances while minimizing potentially serious negative side effects.     

The effect of short or long sleep duration on quality of life and depression: an internet-based survey in Japan

BackgroundTo date, no previous studies have evaluated the relationship between sleep duration and quality of life (QOL) or depression in the general population after controlling for daytime sleepiness and sleep disturbances.MethodsA web-based cross-sectional survey was conducted with 8698 subjects aged 20–69 years. We examined the relationships between weekday sleep duration and daytime sleepiness, sleep disturbance, QOL and depression, using the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (without the item for sleep duration), 8-item Short Form and Center for Epidemiological Studies Depression Scale (CES-D).ResultsDaytime sleepiness tended to increase in proportion to shorter weekday sleep durations. Sleep disturbances, physical and mental QOL, and CES-D scores were worse in both the shorter and longer sleep groups compared with the group with 7–8 h of sleep. Hierarchical logistic regression analyses revealed that short sleep duration but not long sleep duration was significantly associated with reduction of both physical and mental QOL, even after controlling for the presence of daytime sleepiness and sleep disturbance. Both short and long sleep duration were independently and significantly correlated with depression after controlling for daytime sleepiness; however, there was no statistically significant association after adjusting for the effects of sleep disturbance.ConclusionsThe results suggested adverse effects of short sleep but not long sleep on both physical and mental QOL. In addition, the negative impact of specific types of sleep disturbance on depression may be greater than the impact of shortening of sleep duration.