[Study of the relationship between arousal parameters and daytime sleepiness in patients with obstructive sleep apnea syndrome].

OBJECTIVE: To explore the effect of arousal parameters on excessive daytime sleepiness(EDS) in patients with obstructive sleep apnea syndrome(OSAS). METHODS: A total of 205 patients who underwent polysomnography (PSG) from June 2012 to September 2013 in our hospital were enrolled. They were divided into 3 groups:85 patients in the OSAS sleepiness group (AHI ≥ 5/h, ESS ≥ 9), 86 patients in the OSAS non-sleepiness group (AHI ≥ 5/h, ESS<9), and 34 healthy subjects in the control group (AHI<5 times/h, ESS<9). Patient characteristics and PSG parameters of the 3 groups were analyzed. RESULTS: The difference of age, BMI, ESS, N1+ N2%, N3%, AHI, oxygen desaturation index (ODI), mean oxygen saturation (MSaO2), lowest oxygen saturation (LSaO2), oxygen below 90% of the time (T90%), total arousal index (ARtotI), respiratory arousal index/ARtotI (RAI/ARtotI), spontaneous arousal index/ARtotI (SAI/ARtotI), sleep pressure score (SPS) were statistically different among the 3 groups (P < 0.05). But except for REM% [(15 ± 5)%, (16 ± 6)%, (17 ± 7)%, P > 0.05], the difference of age and BMI between OSAS sleepiness group and OSAS non-sleepiness group were not significant (P > 0.016 7), but the difference of other indices between any 2 groups were significant (P < 0.016 7). ARtotI and SPS were positively correlated with ESS (r = 0.383 and 0.244, P < 0.001). Logistic regression analysis showed that only awakening and SPS were the risk factors for OSAS [OR = 1.070 (95% CI: 1.038 - 1.102) and 0.158 (95% CI: 0.026 - 0.984), respectively]. CONCLUSIONS: Arousal at night is closely associated with EDS in OSAS. ARtotI and SPS can be evaluated as an objective indicator of EDS in OSAS patients.

The Association of High Arousal Threshold with Hypertension and Diabetes in Obstructive Sleep Apnea.

Objective: Compared to low arousal threshold (AT), high AT is an easily overlooked characteristic for obstructive sleep apnea (OSA) severity estimation. This study aims to evaluate the relationship between high AT, hypertension and diabetes in OSA, compared to those with apnea-hypopnea index (AHI). Methods: A total of 3400 adults diagnosed with OSA were retrospectively recruited. Propensity score matching (PSM) was conducted to further categorize these patients into the low and high AT groups based on the strategy established by previous literature. The different degrees of AHI and quantified AT (AT score) were subsequently measured. The correlation of AT and AHI with the occurrence of various comorbidities in OSA was estimated by logistic regression analysis with odds ratio (OR). Results: After PSM, 938 pairs of patients arose. The median AT score of high and low AT group was 21.7 and 12.2 scores, and the adjusted OR of high AT for hypertension and diabetes was 1.31 (95% CI = 1.07-1.62, P < 0.01) and 1.45 (95% CI = 1.01-2.08, P < 0.05), respectively. Compared to low AT score group, the OR significantly increased in patients with very high AT score (30 ≤ AT score), especially for diabetes (OR = 1.79, 95% CI = 1.02-3.13, P < 0.05). The significant association was not observed in AHI with increasing prevalent diabetes. Conclusion: Higher AT is significantly associated with increased prevalence of hypertension and diabetes in patients with OSA. Compared with AHI, AT score is a potentially comprehensive indicator for better evaluating the relationship between OSA and related comorbidities.

The Causal Association Between Obstructive Sleep Apnea and Child-Onset Asthma Come to Light: A Mendelian Randomization Study.

Purpose: Obstructive sleep apnea (OSA) had been associated with asthma in observational studies, but the effect of OSA on the onset of asthma in childhood or adulthood remains unclear, and the causal inferences have not been confirmed. This study aims to investigate the potential causal association between OSA with asthma, including different age-of-onset subtypes, providing reliable basis for the clinical treatment of OSA and asthma. Patients and Methods: Causality between OSA and asthma was assessed using a two-sample bi-directional Mendelian randomization (MR) analysis. OSA data were obtained from the FinnGen consortium R9, while asthma and its subtypes (adult-onset asthma, child-onset asthma, and moderate-to-severe asthma) were sourced from the IEU OpenGWAS project. The inverse-variance weighted (IVW) method was chosen as the primary analysis and was complemented by various sensitivity analyses. The MR-PRESSO outlier test was employed to systematically identify and remove outlier variants, mitigating heterogeneity and potential effects of horizontal pleiotropy. Results: The MR analyses provided evidence of genetically predicted OSA having a promoting effect on child-onset asthma (OR,1.49; 95% CI, 1.05-2.11; P=0.025) and moderate-to-severe asthma (OR,1.03; 95% CI, 1.00-1.06; P=0.046). However, no causal association between OSA with asthma and adult-onset asthma was observed. Conclusion: Our study revealed a causal association between OSA and child asthma, but not in adults. Moderate-to-severe asthma may have a potential promoting effect on OSA. These findings underscore the importance of age-specific considerations in managing asthma and suggests the need for personalized approaches in clinical practice.

Application Value of Cardiometabolic Index for the Screening of Obstructive Sleep Apnea with or Without Metabolic Syndrome.

Background: Obstructive sleep apnea (OSA) is a common chronic disease with various comorbidities. The cardiometabolic index (CMI) reflects visceral fat tissue distribution and function, assessing the risk of obesity-related conditions such as metabolic syndrome (MetS) and stroke, which are strongly connected to OSA. The relationship between CMI with OSA and OSA combined with MetS (OMS) remains unclear. This study aims to evaluate the screening value of CMI for OSA and OMS, compared to the lipid accumulation product (LAP). Methods: A total of 280 participants who underwent polysomnography were finally included, with the measurements of metabolic-related laboratory test results such as total cholesterol and triglyceride. Receiver operating curve (ROC) analysis and calculation of the area under the curve (AUC) were conducted to assess the screening potential of CMI, LAP, and the logistic regression models established based on them for OSA and OMS. The Youden index, sensitivity, and specificity were used to determine the optimal cutoff points. Results: ROC curve analysis revealed that the AUCs for CMI in screening OSA and OMS were 0.808 and 0.797, and the optimal cutoff values were 0.71 (sensitivity 0.797, specificity 0.776) and 0.89 (sensitivity 0.830, specificity 0.662), respectively, showing higher Youden index than LAP. The AUCs of screening models based on CMI for OSA and OMS were 0.887 and 0.824, respectively. Conclusion: CMI and LAP can effectively screen for OSA and OMS, while CMI has more practical cutoff values for identifying the diseased states. Screening models based on CMI demonstrate a high discriminatory ability for OSA and OMS, which needs verification in a large-scale population.

Establishment and Application Evaluation of an Improved Obstructive Sleep Apnea Screening Questionnaire for Chinese Community: The CNCQ-OSA.

Objective: Obstructive sleep apnea (OSA) is a common sleep-disordered breathing disease. We aimed to establish an improved screening questionnaire without physical examinations for OSA named the CNCQ-OSA (Chinese community questionnaire for OSA). Methods: A total of 2585 participants who visited sleep medicine center and underwent overnight polysomnography were grouped into two independent cohorts: derivation (n = 2180) and validation (n = 405). The CNCQ-OSA was designed according to the baseline of patients in derivation cohort. We comprehensively analyzed the data to evaluate the predictive value of the CNCQ-OSA, compared to the GOAL questionnaire, STOP-Bang questionnaire (SBQ) and NoSAS questionnaire. Results: The CNCQ-OSA included seven variables: loud snoring, BMI ≥ 25 kg/m2, male gender, apnea, sleepiness, hypertension and age ≥30, with a total score ranging from 7 to 16.7 points (≥13.5 points indicating high risk of OSA, ≥14.5 points indicating extremely high risk). In the derivation and validation cohorts, the areas under the curve of the CNCQ-OSA were 0.761 and 0.767, respectively. In the validation cohort, the sensitivity and specificity of a CNCQ-OSA score ≥13.5 points for the apnea-hypopnea index (AHI) ≥5/h were 0.821 and 0.559, respectively (Youden index, 0.380), and the score ≥14.5 points were 0.494 and 0.887, respectively (Youden index, 0.375). The CNCQ-OSA had a better predictive value for AHI ≥ 5/h, AHI > 15/h and AHI > 30/h, with the highest Youden index, compared to the other questionnaires. Conclusion: The CNCQ-OSA can effectively identify the risk of OSA, which is appropriate for self-screening at home without physical examinations.

The relationship between obstructive sleep apnea and asthma severity and vice versa: a systematic review and meta-analysis.

BACKGROUND: There is a great association between the prevalence of obstructive sleep apnea (OSA) and asthma. Nonetheless, whether OSA impacts lung function, symptoms, and control in asthma and whether asthma increases the respiratory events in OSA are unknown. This meta-analysis aimed to examine the relationship between obstructive sleep apnea and asthma severity and vice versa. METHODS: We carried out a systematic search of PubMed, EMBASE, and Scopus from inception to September 2022. Primary outcomes were lung function, parameters of polysomnography, the risk of OSA in more severe or difficult-to-control asthmatic patients, and the risk of asthma in patients with more severe OSA. Heterogeneity was examined with the Q test and I2 statistics. We also performed subgroup analysis, Meta-regression, and Egger's test for bias analysis. RESULTS: 34 studies with 27,912 subjects were totally included. The results showed that the comorbidity of OSA aggravated lung function in asthmatic patients with a consequent decreased forced expiratory volume in one second %predicted (%FEV1) and the effect was particularly evident in children. %FEV1 tended to decrease in adult asthma patients complicated with OSA, but did not reach statistical significance. Interestingly, the risk of asthma seemed to be slightly lower in patients with more severe OSA (OR = 0.87, 95%CI 0.763-0.998). Asthma had no significant effect on polysomnography, but increased daytime sleepiness assessed by the Epworth Sleepiness Scale in OSA patients (WMD = 0.60, 95%CI 0.16-1.04). More severe asthma or difficult-to-control asthma was independently associated with OSA (odds ratio (OR) = 4.36, 95%CI 2.49-7.64). CONCLUSION: OSA was associated with more severe or difficult-to-control asthma with decreased %FEV1 in children. The effect of OSA on lung function in adult patients should be further confirmed. Asthma increased daytime sleepiness in OSA patients. More studies are warranted to investigate the effect of asthma on OSA severity and the impact of different OSA severity on the prevalence of asthma. It is strongly recommended that people with moderate-to-severe or difficult-to-control asthma screen for OSA and get the appropriate treatment.

Application value of joint NoSAS score and Epworth Sleepiness Scale for assessment of obstructive sleep apnea hypopnea syndrome.

OBJECTIVE: By comparing the predictive value of the NoSAS (Neck circumference, Obesity, Snoring, Age and Sex) score combined with the Epworth Sleepiness Scale (ESS), STOP-Bang Questionnaire (STOP-Bang), STOP Questionnaire (STOP) and Berlin Questionnaire (Berlin), the application value of the NoSAS score combined with ESS in screening Obstructive sleep apnea hypopnea syndrome (OSAHS) in the population is evaluated. METHOD: 2560 suspected OSAHS patients visited the Sleep Medical Center of the First Hospital of Guangzhou Medical University between September 1, 2016 and October 31, 2020, and were monitored with a polysomnogram (PSG) after completing the NoSAS score, ESS, STOP-Bang, STOP and Berlin. The sensitivity, specificity, positive predictive value, negative predictive value and receiver operating characteristic (ROC) curve of each scale were calculated, and the accuracy in predicting OSAHS of the NoSAS score combined with ESS and each scale was analyzed. RESULTS: The areas under the ROC curve scored by Berlin were higher than those of the other four questionnaires with Apnea Hypopnea Index (AHI) cutoffs of ≥5 and ≥ 10 events/h, while the area under the ROC curve scored by the NoSAS score was the highest with AHI cutoffs of ≥15, ≥20, ≥25 and ≥ 30 events/h. Among the five scales, the diagnostic odds ratio (DOR) of the NoSAS score was the highest. When a NoSAS score of ≥7 was used as the cutoff point for diagnostic NoSAS, it had higher sensitivity and specificity with a NoSAS score of ≥8 as the cutoff point for diagnostic NoSAS. A NoSAS score of ≥7 combined with ESS significantly improved its specificity for predicted OSAHS patients. CONCLUSION: The NoSAS score is a simple and effective new tool for screening patients for OSAHS, while a NoSAS score of ≥7 combined with ESS can further improve its specificity. Thus, we suggest further screening with ESS after a NoSAS score of ≥7 in suspected populations.

The effect of non-benzodiazepine sedative hypnotics on CPAP adherence in patients with OSA: a systematic review and meta-analysis.

STUDY OBJECTIVES: This meta-analysis aimed to explore the effect of non-benzodiazepine sedative hypnotics (NBSH) on continuous positive airway pressure (CPAP) adherence in patients with obstructive sleep apnea (OSA). METHODS: We conducted a systematic search through PubMed, Medline, the Cochrane Library, EMBASE, Scopus and ClinicalTrials (all searched from inception to August 15, 2020). Publications were limited to articles, clinical conferences and letters, including randomized controlled trials and retrospective studies. We used a random-effects model to calculate the odds ratio (OR) and mean difference (MD) with corresponding confidence interval (CI). Subgroup analyses were conducted to analyze the sources of heterogeneity. RESULTS: Eight studies fulfilled the inclusion and exclusion criteria for patients newly diagnosed with obstructive sleep apnea. Overall, the use of NBSH was associated with increased use of CPAP per night (MD = 0.62 h; 95% CI = 0.26-0.98) and use for more nights (MD = 12.08%; 95% CI = 5.27-18.88). When a study seriously affecting heterogeneity was removed, more patients adhered well with CPAP use (pooled OR = 2.48; 95% CI = 1.75-3.52) with good adherence defined as CPAP use for >4 h/night on >70% of nights. Among prescribed NBSHs, eszopiclone showed the most significant effect on CPAP adherence. CONCLUSION: CPAP adherence may increase in OSA patients treated with non-benzodiazepine sedative hypnotics especially eszopiclone. The effect of zolpidem and zaleplon on CPAP adherence requires further investigation by larger scale, randomized, controlled trials.

Epidemiological and clinical characteristics of suspected COVID-19 patients in the isolation ward in Guangzhou, China: a cohort study.

BACKGROUND: Since there are reports of cases of 2019-coronavirus disease (COVID-19) asymptomatic carriers in China recently and fever is one of the main symptoms, we aimed to distinguish COVID-19 cases from other febrile patients with clinical examinations in this study. METHODS: A total of 134 suspected COVID-19 patients in the isolation ward of the First Affiliated Hospital of Guangzhou Medical University were recruited from January 23 to May 23, 2020. We analyze the pathogenic form and clinical characteristics. RESULTS: Among them, pathogens were identified in only 84 patients (62.7%), including 23 (17.1%) with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), 30 (22.3%) with other viruses, 31 (25.0%) with other pathogens and 3 (3.5%) with mixed infections. The commonly observed symptoms of COVID-19 patients were cough, fever, fatigue, and muscle aches, which were significantly different than the symptoms of nonviral infections (P<0.05) but from those of other viral infections (P>0.05). Furthermore, lactate dehydrogenase and the neutrophil/lymphocyte were found significantly high in COVID-19 patients compared to non-COVID-19 patients (P<0.05). The most common manifestations of COVID-19 patients were ground-glass opacities (100%) with or without lung consolidation, however, they also often showed involvement of several lobes of both lungs (P<0.05). Due to the clear differential diagnosis, the overall antibiotic use rate was 35.8% (31/87). CONCLUSIONS: When diagnosing COVID-19, infections with other pathogens should not be ignored. Successful pathogen identification will support accurate treatment.

Longitudinal virological changes and underlying pathogenesis in hospitalized COVID-19 patients in Guangzhou, China.

Prolonged viral RNA shedding and recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in coronavirus disease 2019 (COVID-19) patients have been reported. However, the clinical outcome and pathogenesis remain unclear. In this study, we recruited 43 laboratory-confirmed COVID-19 patients. We found that prolonged viral RNA shedding or recurrence mainly occurred in severe/critical patients (P<0.05). The average viral shedding time in severe/critical patients was more than 50 days, and up to 100 days in some patients, after symptom onset. However, chest computed tomography gradually improved and complete absorption occurred when SARS-CoV-2 RT-PCR was still positive, but specific antibodies appeared. Furthermore, the viral shedding time significantly decreased when the A1,430G or C12,473T mutation occurred (P<0.01 and FDR<0.01) and increased when G227A occurred (P<0.05 and FDR<0.05). High IL1R1, IL1R2, and TNFRSF21 expression in the host positively correlated with viral shedding time (P<0.05 and false discovery rate <0.05). Prolonged viral RNA shedding often occurs but may not increase disease damage. Prolonged viral RNA shedding is associated with viral mutations and host factors.

Serum Amyloid A in Stable COPD Patients is Associated with the Frequent Exacerbator Phenotype.

Background: We sought to determine whether circulating inflammatory biomarkers were associated with the frequent exacerbator phenotype in stable COPD patients ie, those with two or more exacerbations in the previous year. Methods: Eighty-eight stable, severe, COPD patients (4 females) were assessed for exacerbation frequency, pulmonary function, fraction of expired nitric oxide (FENO); inflammatory variables were measured in venous blood. Logistic regression assessed associations between the frequent exacerbator phenotype and systemic inflammation. Results: Compared with infrequent exacerbators, frequent exacerbators (n=10; 11.4%) had greater serum concentration (median (25th-75th quartile)) of serum amyloid A (SAA; 134 (84-178) vs 71 (38-116) ng/mL; P=0.024), surfactant protein D (SP-D; 15.6 (9.0-19.3) vs 8.5 (3.6-14.9) ng/mL; P=0.049) and interleukin-4 (IL-4; 0.12 (0.08-1.44) vs 0.03 (0.01-0.10) pg/mL; P=0.001). SAA, SP-D and IL-4 were not significantly correlated with FEV1%predicted or FVC %predicted. After adjusting for sex, age, BMI, FEV1/FVC and smoking pack-years, only SAA remained independently associated with the frequent exacerbator phenotype (OR 1.49[1.09-2.04]; P=0.012). The odds of being a frequent exacerbator was 18-times greater in the highest SAA quartile (≥124.1 ng/mL) than the lowest SAA quartile (≤44.1 ng/mL) (OR 18.34[1.30-258.81]; P=0.031), and there was a significant positive trend of increasing OR with increasing SAA quartile (P=0.008). For SAA, the area under the receiver operating characteristic curve was 0.721 for identification of frequent exacerbators; an SAA cut-off of 87.0 ng/mL yielded an 80% sensitivity and 61.5% specificity. Conclusion: In stable COPD patients, SAA was independently associated with the frequent exacerbator phenotype, suggesting that SAA may be a useful serum biomarker to inform progression or management in COPD.

Improved night shift schedule related to the mortality of critically ill patients with Corona Virus Disease 2019.

PURPOSE: To determine the relationship between the improved night shift schedule and the mortality of critically ill patients with Corona Virus Disease 2019 (COVID-19). METHODS: According to the time of the implementation of the new night shift schedule, we divided all patients into two groups: initial period group and recent period group. The clinical electronic medical records, nursing records, laboratory findings, and radiological examinations for all patients with laboratory confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection were reviewed. Cox proportional hazard ratio (HR) models were used to determine the risk factors associated with in hospital death. RESULTS: A total of 75 patients were included in this study. Initial period group includes 45 patients and recent period group includes 30 patients. The difference in mortality between the two groups was significant, 77.8% and 36.7%, respectively. Leukocytosis at admission and admitted to hospital before the new night shift schedule were associated with increased odds of death. CONCLUSIONS: Shift arrangement of medical staff are associated with the mortality of critically ill patients with COVID-19. The new night shift schedule might improve the continuity of treatment, thereby improving the overall quality of medical work and reducing the mortality of critically ill patients.

Symptomless multi-variable apnea prediction index assesses adverse outcomes in patients with Corona Virus Disease 2019.

PURPOSE: To explore the relationship between symptomless multi-Variable apnea prediction (sMVAP) index and adverse outcomes of patients with Corona Virus Disease 2019 (COVID-19). METHODS: According to the sMVAP quartiles, we divided all patients into four groups. The clinical electronic medical records, nursing records, laboratory findings, and radiological examinations for all patients with laboratory confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection were reviewed. Cox proportional hazard ratio (HR) models were used to determine the risk factors associated with in hospital death. RESULTS: A total of 97 patients were included in this study. The "Quartile 4" group 's ICU transfer rate was significantly higher than the "Quartile 1" group. Coronary heart disease, high d-dimer and sMVAP at admission were associated with increased odds of death. CONCLUSIONS: Using the sMVAP index for obstructive sleep apnea hypopnea syndrome (OSAHS) risk assessment, and then predicting the adverse outcomes of COVID-19 patients, is an effective method. Therefore, the use of sMVAP index for OSAHS screening for inpatients with COVID-19 should be vigorously promoted, and high-risk patients should be effectively managed.

Validation of the NoSAS Score for the Screening of Sleep-Disordered Breathing: A Hospital-Based Retrospective Study in China.

STUDY OBJECTIVES: This study was conducted to validate the NoSAS score in clinical populations and to compare it with the Berlin, STOP, and STOP-Bang questionnaires, as well as the Epworth Sleepiness Scale (ESS), in screening for sleep-disordered breathing (SDB). METHODS: A retrospective analysis was conducted of all patients aged 18 to 80 years who had completed a full-night polysomnography (PSG) at the sleep center of the First Affiliated Hospital of Guangzhou Medical University from October 2012 to November 2016. Patients who had incomplete or unanswered questionnaires were excluded. The data for the NoSAS score, ESS, STOP, STOP-Bang, and Berlin questionnaires were collected, after which the NoSAS score was compared against the other questionnaires for SDB screening. RESULTS: A total of 2,208 participants were enrolled in this study. The NoSAS scores, which ranged from 0 to 17 and allocated a threshold of 8 points, identified individuals at risk of clinically significant SDB (defined as an apnea-hypopnea index [AHI] cutoff of ≥ 20 events/h), with an area under the curve (AUC) of 0.707. The NoSAS score performed significantly better than the STOP (AUC 0.655) and STOP-Bang (AUC 0.704) questionnaires and the ESS (AUC 0.642), and it was at par with the Berlin (AUC 0.697) scores for SDB screening. A significant correlation was found between the AHI and NoSAS score (r = .386, P < .001). CONCLUSIONS: The NoSAS score is a simple, efficient, and easy method for screening SDB in the clinical setting, especially in moderate to severe SDB. It demonstrates a moderately high level of sensitivity for SDB.

Antioxidant Carbocysteine Treatment in Obstructive Sleep Apnea Syndrome: A Randomized Clinical Trial.

OBJECTIVE: This study aimed to examine the effects of carbocysteine in OSAS patients. METHODS: A total of 40 patients with moderate to severe obstructive sleep apnea syndrome (OSAS) were randomly divided into two groups. One group was treated with 1500 mg carbocysteine daily, and the other was treated with continuous positive airway pressure (CPAP) at night. Before treatment and after 6 weeks of treatment, all patients underwent polysomnography and completed questionnaires. Treatment compliance was compared between the two groups. Plasma was collected for various biochemical analyses. Endothelial function was assessed with ultrasound in the carbocysteine group. RESULTS: The proportion of patients who fulfilled the criteria for good compliance was higher in the carbocysteine group (n = 17) than in the CPAP group (n = 11; 100% vs. 64.7%). Compared with baseline values, the carbocysteine group showed significant improvement in their Epworth Sleepiness Scale score (10.18 ± 4.28 vs. 6.82 ± 3.66; P ≤ 0.01), apnea-hypopnea index (55.34 ± 25.03 vs. 47.56 ± 27.32; P ≤ 0.01), time and percentage of 90% oxygen desaturation (12.66 (2.81; 50.01) vs. 8.9 (1.41; 39.71); P ≤ 0.01), and lowest oxygen saturation level (65.88 ± 14.86 vs. 70.41 ± 14.34; P ≤ 0.01). Similar changes were also observed in the CPAP group. The CPAP group also showed a decreased oxygen desaturation index and a significant increase in the mean oxygen saturation after treatment, but these increases were not observed in the carbocysteine group. Snoring volume parameters, such as the power spectral density, were significantly reduced in both groups after the treatments. The plasma malondialdehyde level decreased and the superoxide dismutase and nitric oxide levels increased in both groups. The endothelin-1 level decreased in the CPAP group but did not significantly change in the carbocysteine group. Ultrasonography showed that the intima-media thickness decreased (0.71 ± 0.15 vs. 0.66 ± 0.15; P ≤ 0.05) but that flow-mediated dilation did not significantly change in the carbocysteine group. CONCLUSIONS: Oral carbocysteine slightly improves sleep disorders by attenuating oxidative stress in patients with moderate to severe OSAS. Carbocysteine may have a role in the treatment of OSAS patients with poor compliance with CPAP treatment. However, the efficiency and feasibility of carbocysteine treatment for OSAS needs further evaluation. TRIAL REGISTRATION: ClinicalTrials.gov NCT02015598.

Comparison of rivaroxaban mono-therapy and standard-therapy adjusted by CYP2C9 and VKORC1 genotypes in symptomatic pulmonary embolism.

RATIONALE: Pulmonary embolism (PE) is a life-threatening manifestation of venous thromboembolism. Rivaroxaban is an oral anticoagulant, which directly inhibits Factor Xa. The objective of the current study was, in comparison to the standard-therapy method, to investigate the potential of rivaroxaban to improve the treatment of patients with PE, and to reduce hemorrhage in the standard-therapy group through adjusting the dose of warfarin by CYP2C9 and VKORC1 genotypes. METHODS: Sixty-two PE patients with or without deep venous thrombosis (DVT) was randomized to rivaroxaban mono-therapy or standard-therapy with enoxaparin followed by vitamin K antagonist (VKA). Concentration of the anticoagulants was adjusted according to the results of CYP2C9 and VKORC1 genotypes in order to stabilize the international normalized rate (INR) at 2.0-3.0 range. Length of hospital stay at initial hospitalization was compared, therapeutic efficacy was examined by computed tomographic pulmonary angiography (CTPA) and ventilation/perfusion (V/Q) scan, and side-effect of anti-coagulants was monitored at 1-month, and 3- or 6-months follow-up check points. RESULTS: We found that, overall, patients who received rivaroxaban mono-therapy had a significantly shorter length of hospital stay compared with patients who received standard-therapy of enoxaparin followed by VKA (9.29±3.70 versus 11.38±3.12days, P=0.021). The therapeutic efficacy was of no marked difference between these two groups. However, after one month treatment, 50% (16/32) of the standard-therapy group had mild hemorrhage, which was significantly higher than that of rivaroxaban mono-therapy group (16.7%, 5/30, P=0.006). Moreover, a significantly higher rate in the standard-therapy group (22.2% versus 3.4%, P=0.032) was found after 3 or 6months therapy. Major bleeding was slightly but not significantly higher in the standard-therapy group than that in the rivaroxaban therapy group. In addition, 2 (6.3%) patients died from Life-threatening bleeding in the standard-therapy group. CONCLUSION: Findings of the current study suggested that rivaroxaban mono-therapy result in shorter hospital stay compared to the standard-therapy. Implication of CYP2C9 and VKORC1 genotypes in determining dose of warfarin, however, remains to be further examined in larger cohort studies.