Endotypic traits of supine position and supine-predominant obstructive sleep apnoea in Asian patients.

BACKGROUND: Over half of all cases of obstructive sleep apnoea (OSA) are classified as supine-related OSA; however, the pathological endotype during supine position is not fully understood. This study aims to investigate the endotypic traits of supine-predominant OSA and explore the variations in endotypic traits between the supine and lateral positions. METHODS: We prospectively recruited 689 adult patients with OSA from a single sleep centre between April 2020 and December 2022. Endotypic traits, namely arousal threshold, collapsibility, loop gain and upper airway muscle compensation, were retrieved from polysomnographic signals. We identified spOSA by a supine to non-supine apnoea-hypopnoea index (AHI) ratio >2. We cross-sectionally compared demographic and endotypic traits between supine-predominant OSA and non-positional OSA and examined the associations between supine-predominant OSA and endotypic traits. Additionally, we compared the changes in endotypic traits between supine and lateral positions in patients with supine-predominant OSA and non-positional OSA. RESULTS: In our study sample, 75.8% of patients were identified as having supine-predominant OSA. Compared to non-positional OSA, supine-predominant OSA was associated with low collapsibility (ß= -3.46 %eupnoea, 95% CI -5.93- -1.00 %eupnoea) and reduced compensation (ß= -6.79 %eupnoea, 95% CI -10.60- -2.99 %eupnoea). When transitioning from the lateral to supine position, patients with supine-predominant OSA had a substantial decrease in compensation compared to those with non-positional OSA (-11.98 versus -6.28 %eupnoea). CONCLUSIONS: Supine-predominant OSA is the prevalent phenotype of OSA in Asian patients. Inadequate upper airway compensation appears to be a crucial underlying pathology in patients with supine-predominant OSA.

Continuous positive airway pressure and adherence in patients with different endotypes of obstructive sleep apnea.

Determining the endotypes of obstructive sleep apnea (OSA) has potential implications for precision interventions. Here we assessed whether continuous positive airway pressure (CPAP) treatment outcomes differ across endotypic subgroups. We conducted a retrospective analysis of data obtained from 225 patients with moderate-to-severe OSA from a single sleep centre. Polysomnographic and CPAP titration study data were collected between May 2020 and January 2022. One-month CPAP treatment adherence was followed. Obstructive sleep apnea endotypes, namely arousal threshold, collapsibility, loop gain, and upper airway gain were estimated from polysomnography and dichotomised as high versus low. We examined associations between endotypic subgroups and (1) optimal CPAP titration pressure, (2) CPAP-related improvements in sleep architecture (proportions of slow-wave and rapid eye movement (REM) sleep), and (3) CPAP adherence. We observed that patients with high collapsibility required a higher CPAP pressure than those with low collapsibility (∆ = 0.4 cmH2 O, 95% confidence interval [CI] = 0.3-1.7). A larger increase in slow-wave sleep and in REM sleep proportions after CPAP treatment were observed in patients with a high arousal threshold, high collapsibility, high loop gain, or high upper airway gain than in those with low levels of endotypes. High loop gain and high collapsibility were independently associated with longer CPAP use hours per night (∆ = 0.6 h, 95% CI = 0.2-1.5 and ∆ = 0.3 h, 95% CI = 0.03-1.5, respectively). In conclusion, different endotypic subgroups of OSA exhibit a difference in outcomes of CPAP treatment. Knowledge of endotypes may help clinicians to understand which patients are expected to benefit most from CPAP therapy prior to its administration.

EfficientNet-based machine learning architecture for sleep apnea identification in clinical single-lead ECG signal data sets.

OBJECTIVE: Our objective was to create a machine learning architecture capable of identifying obstructive sleep apnea (OSA) patterns in single-lead electrocardiography (ECG) signals, exhibiting exceptional performance when utilized in clinical data sets. METHODS: We conducted our research using a data set consisting of 1656 patients, representing a diverse demographic, from the sleep center of China Medical University Hospital. To detect apnea ECG segments and extract apnea features, we utilized the EfficientNet and some of its layers, respectively. Furthermore, we compared various training and data preprocessing techniques to enhance the model's prediction, such as setting class and sample weights or employing overlapping and regular slicing. Finally, we tested our approach against other literature on the Apnea-ECG database. RESULTS: Our research found that the EfficientNet model achieved the best apnea segment detection using overlapping slicing and sample-weight settings, with an AUC of 0.917 and an accuracy of 0.855. For patient screening with AHI > 30, we combined the trained model with XGBoost, leading to an AUC of 0.975 and an accuracy of 0.928. Additional tests using PhysioNet data showed that our model is comparable in performance to existing models regarding its ability to screen OSA levels. CONCLUSIONS: Our suggested architecture, coupled with training and preprocessing techniques, showed admirable performance with a diverse demographic dataset, bringing us closer to practical implementation in OSA diagnosis. Trial registration The data for this study were collected retrospectively from the China Medical University Hospital in Taiwan with approval from the institutional review board CMUH109-REC3-018.

Recommended assessment and management of sleep disordered breathing in patients with atrial fibrillation, hypertension and heart failure: Taiwan Society of Cardiology/Taiwan Society of sleep Medicine/Taiwan Society of pulmonary and Critical Care Medicine joint consensus statement.

Sleep disordered breathing (SDB) is highly prevalent and may be linked to cardiovascular disease in a bidirectional manner. The Taiwan Society of Cardiology, Taiwan Society of Sleep Medicine and Taiwan Society of Pulmonary and Critical Care Medicine established a task force of experts to evaluate the evidence regarding the assessment and management of SDB in patients with atrial fibrillation (AF), hypertension and heart failure with reduced ejection fraction (HFrEF). The GRADE process was used to assess the evidence associated with 15 formulated questions. The task force developed recommendations and determined strength (Strong, Weak) and direction (For, Against) based on the quality of evidence, balance of benefits and harms, patient values and preferences, and resource use. The resulting 11 recommendations are intended to guide clinicians in determining which the specific patient-care strategy should be utilized by clinicians based on the needs of individual patients.

Clinical characteristics of Asian patients with sleep apnea with low arousal threshold and sleep structure change with continuous positive airway pressure.

PURPOSE: Low respiratory arousal threshold (ArTH) has been observed to be prevalent in patients with obstructive sleep apnea (OSA), and is associated with poor adherence to continuous positive airway pressure (CPAP) treatment. This study aimed to examine the associations between low ArTH and clinical characteristics. The second aim was to examine sleep structure changes between diagnostic polysomnography (PSG) and CPAP titration studies. METHODS: PSG data for 3718 adults who had an apnea-hypopnea index (AHI) ≥ 5 were reviewed retrospectively, as well as 206 CPAP titration studies among these participants. Participants were dichotomized into low- and high-ArTH groups according to their PSG parameters. The associations between low ArTH and clinical characteristics were examined by multivariate logistic regressions. The sleep structure changes between PSG and CPAP titration studies were examined by repeated measures ANOVA. RESULTS: Fifty percent of patients with OSA had low ArTH. Compared with high-ArTH patients, low-ArTH patients were less obese and composed of a higher percentage of women. In logistic regression models, low ArTH was associated with bruxism and nocturia, but not with illnesses after adjusting for AHI and body mass index. Compared with diagnostic PSG studies, low-ArTH patients had significantly decreased stage changes and increased percentage of rapid eye movement sleep during CPAP titration studies. CONCLUSION: Low ArTH was prevalent in this large sample of patients with OSA. Arousal threshold was not associated with an increased risk of physical illnesses but was with certain clinical complaints. Low-ArTH patients benefited from CPAP titration study for improved sleep structure.

Comparison between COPD Assessment Test (CAT) and modified Medical Research Council (mMRC) dyspnea scores for evaluation of clinical symptoms, comorbidities and medical resources utilization in COPD patients.

BACKGROUND: The 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) proposed a new severity assessment system for emphasizing clinical symptom evaluation by COPD Assessment Test (CAT) or modified Medical Research Council (mMRC) dyspnea scores. The aim of the study was to evaluate the effectiveness of two scoring systems in evaluating COPD patients. METHODS: A population based cross-sectional study employing computer-assisted telephone interviewing system (CATI) for surveying the epidemiology of COPD in Taiwan. Among 6600 subjects recruited (age > 40), 404 subjects (6.1%) were diagnosed as COPD. The comorbidities, COPD-related symptoms, health care resources utilization were compared between CAT and mMRC. RESULTS: There were significant differences in all co-morbidities, symptom severity in favor of CAT as compared to mMRC. When comparing health care resources utilization, CAT and mMRC have equal effectiveness in evaluating patients with regular medical treatment. There were significant differences in emergency room visit and hospitalization in favor of mMRC. However, CAT was more effective in evaluating patients with ICU admission (P = 0.005). CONCLUSION: Compared with CAT and mMRC, there are individual benefits in the evaluation of clinical symptoms, co-morbidities and medical resources utilization for ER, hospitalization and ICU admission in COPD patients.

The association between continuous positive airway pressure therapy and liver disease development in obstructive sleep apnea/hypopnea syndrome patients: a nationwide population-based cohort study in Taiwan.

PURPOSE: Studies on the association between continuous positive airway pressure (CPAP) treatment and liver diseases such as non-alcoholic fatty liver disease (NAFLD) and cirrhosis in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) are limited. To the best of our knowledge, none exists that makes use of a national database in an Asian population. This study aims to evaluate the effects of CPAP treatment on patients with these two disorders in a retrospective, population-based study in Taiwan. METHODS: Using the Taiwan National Health Insurance claims database, this study collected the data of OSAHS patients diagnosed between 2000 and 2008 and divided them into CPAP treatment and non-CPAP treatment groups. All subjects were followed up until 2010. Liver disease incidence and risk were calculated. RESULTS: The CPAP group had a lower cumulative incidence rate of developing liver disease than the non-CPAP group within the observation periods (p < 0.001). After adjusting for age, gender, urbanization level, and comorbidities, the CPAP treatment group showed a lower risk of developing liver disease compared with the non-CPAP treatment group (sub-aHR of 0.66 (95% CI 0.55-0.80), p < 0.001). CONCLUSIONS: Our observations suggest that CPAP treatment may play an important role to delay the progression of liver disease in OSAHS patients and decreases the incidence of liver disease among OSAHS patients. Thus, CPAP therapy may be a feasible way to decrease the risk of liver disease among patients with OSAHS.

A psychometric assessment of the St. George's respiratory questionnaire in patients with COPD using Rasch model analysis.

BACKGROUND: The St. George's Respiratory Questionnaire (SGRQ) was a widely used tool to assess disease impact on patients with obstructive airways disease. Although traditional methods have generally supported construct validity and internal consistency reliability of SGRQ, such methods cannot facilitate the evaluation of whether items are equivalent to different individuals. The purpose of this study is to rigorously examine the psychometric properties of the SGRQ in patients with chronic obstructive pulmonary disease (COPD) using Rasch model analysis. METHODS: A methodological research was conducted on SGRQ in a sample of 240 male patients with COPD recruited from the outpatient services in Central Taiwan. The psychometric properties of the SGRQ were examined using Rasch model analysis with a mixed rating scale and partial credit mode by Winsteps software. The level of matching between the item's difficulty and person's ability was analyzed by item-person targeting as well as ceiling and floor effects. Item-person maps were also examined for checking the location of the item's difficulty and person's measures along the same scale. Finally, the differential item functioning (DIF) was examined to measure group equivalence associated with age and disease's severity. RESULTS: Each of the three domains (Symptom, Activity, Impact) of the SGRQ was found to be unidimensionality. The person separation index ranged from 1.21 (Symptom domain) to 2.50 (Activity domain). There was a good targeting for the SGRQ domains, except the Impact domain (1.36). The percentage of ceiling and floor effects were below 10%, except the ceiling effect in the Impact domain (26.25%). From item-person maps, gaps of location of item corresponded to patient's ability were identified. The results have also showed that many items in SGRQ revealed age or severity related DIF. CONCLUSIONS: Except the Symptom domain of SGRQ, the others have a reliabile internal consistency and a good hierarchical structure. The results of Rasch model analysis can highlight aspects for scale improvement, such as gap, duplicate items or scale responses. There was some age or severity related DIF indicating somewhat unstable across different characteristics of group. IRB No.: DMR94-IRB-179.

Validation of overnight oximetry to diagnose patients with moderate to severe obstructive sleep apnea.

BACKGROUND: Polysomnography (PSG) is treated as the gold standard for diagnosing obstructive sleep apnea (OSA). However, it is labor-intensive, time-consuming, and expensive. This study evaluates validity of overnight pulse oximetry as a diagnostic tool for moderate to severe OSA patients. METHODS: A total of 699 patients with possible OSA were recruited for overnight oximetry and PSG examination at the Sleep Center of a University Hospital from Jan. 2004 to Dec. 2005. By excluding 23 patients with poor oximetry recording, poor EEG signals, or respiratory artifacts resulting in a total recording time less than 3 hours; 12 patients with total sleeping time (TST) less than 1 hour, possibly because of insomnia; and 48 patients whose ages less than 20 or more than 85 years old, data of 616 patients were used for further study. By further considering 76 patients with TST < 4 h, a group of 540 patients with TST ≥ 4 h was used to study the effect of insufficient sleeping time. Alice 4 PSG recorder (Respironics Inc., USA) was used to monitor patients with suspected OSA and to record their PSG data. After statistical analysis and feature selection, models built based on support vector machine (SVM) were then used to diagnose moderate and moderate to severe OSA patients with a threshold of AHI = 30 and AHI = 15, respectively. RESULTS: The SVM models designed based on the oxyhemoglobin desaturation index (ODI) derived from oximetry measurements provided an accuracy of 90.42-90.55%, a sensitivity of 89.36-89.87%, a specificity of 91.08-93.05%, and an area under ROC curve (AUC) of 0.953-0.957 for the diagnosis of severe OSA patients; as well as achieved an accuracy of 87.33-87.77%, a sensitivity of 87.71-88.53%, a specificity of 86.38-86.56%, and an AUC of 0.921-0.924 for the diagnosis of moderate to severe OSA patients. The predictive outcome of ODI to diagnose severe OSA patients is better than to diagnose moderate to severe OSA patients. CONCLUSIONS: Overnight pulse oximetry provides satisfactory diagnostic performance in detecting severe OSA patients. Home-styled oximetry may be a tool for severe OSA diagnosis.

Development and preliminary validation of a questionnaire on regular exercise beliefs among patients with chronic obstructive pulmonary disease.

AIMS AND OBJECTIVES: To develop a Regular Exercise Belief Questionnaire and test its psychometric properties for patients with chronic obstructive pulmonary disease. BACKGROUND: Regular exercise has been shown to significantly improve physical capacity and the quality of life of patients with chronic obstructive pulmonary disease. However, their adherence to long-term exercise is low. To develop an effective strategy for promoting good exercise behaviours, it is important to have a validated instrument to evaluate factors related to engaging in exercise. DESIGN AND METHODS: A cross-sectional design was used for the study. Construction of the Regular Exercise Belief Questionnaire was based on the Theory of Planned Behaviour Reliability and validity were assessed using a sample of 136 male patients with chronic obstructive pulmonary disease. The construct validity of the questionnaire was confirmed through exploratory factor analysis and known group technique. RESULTS: Exploratory factor analysis resulted in an eight-factor solution that explained 70·4% of the total variance. The internal consistency of the Regular Exercise Belief Questionnaire was 0·83-0·93. The Regular Exercise Belief Questionnaire was preliminarily found to be reliable and exhibited satisfactory validity for patients with chronic obstructive pulmonary disease. CONCLUSION: The Regular Exercise Belief Questionnaire is the first theory-based measure of exercise beliefs among patients with chronic obstructive pulmonary disease. The questionnaire provides an effective method to examine behaviour beliefs, normative beliefs and control beliefs about regular exercise. CLINICAL RELEVANCE: The measure can be used to periodically evaluate the exercise beliefs in clinics and to examine the effectiveness of exercise programmes in patients with chronic obstructive pulmonary disease. The result of the evaluation could also apply to identify strategies related to promoting exercise behaviours.

Sex-specific Age-Related Worsening of Pathological Endotypic Traits in Patients with Obstructive Sleep Apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is more prevalent in men and older adults. Few studies have explored variations in pathological endotypic traits by age and sex using a large patient sample, offering insights into the development of the disease. Our study aims to examine how endotype characteristics of obstructive sleep apnea vary across age in different sex. METHODS: A cross-sectional study was conducted, enrolling 2296 adult patients referred for in-laboratory diagnostic polysomnography at a single sleep center in Taiwan. Among them, 1374 had an apnea-hypopnea index ≥ 5. Using the "Phenotyping Using Polysomnography" method, we estimated four endotypic traits-arousal threshold, upper airway collapsibility, loop gain, and upper airway muscle compensation. Demographic and polysomnographic characteristics were compared between sexes and age groups. Generalized linear regression and generalized additive models were employed to explore the associations of sex and age with endotypic traits. RESULTS: Men with OSA exhibited higher collapsibility and lower compensation than women (difference: 4.32 %eupnea and 4.49 %eupnea, respectively). Younger patients with OSA had a higher prevalence of obesity, more snoring symptoms, and lower loop gain compared to older patients. For men, age was correlated with increased collapsibility, increased loop gain, and decreased arousal threshold after 37 years old. Whereas in women, endotypic traits were not associated with age, except for an increase in loop gain with advancing age. CONCLUSIONS: Personalized treatment options for OSA should take into consideration age and sex. Reducing loop gain could be a treatment objective for older patients with OSA.

Dose of selective serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding in older adults.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have been associated with an increased risk of upper gastrointestinal bleeding (UGIB) in older patients but little is known about the risk associated with individual SSRI drugs and doses. AIMS: To quantify the risk of UGIB in relation to individual SSRI use in older adults. METHODS: We conducted a nested case-control study within a cohort of 9565 patients aged ⩾65 years prescribed SSRIs from 2000 to 2013 using claims data of universal health insurance in Taiwan. Incident cases of UGIB during the follow-up period were identified and matched with three control subjects. Conditional logistic regression was used to estimate the odds ratio (OR) of UGIB associated with individual SSRI use and cumulative dose. RESULTS: UGIB risk increased with the increasing cumulative doses of SSRIs (adjusted OR: 1.28, 95% confidence interval (CI): 1.02-1.62 for the highest vs. the lowest tertile). Compared with users of other SSRIs, fluoxetine users were at an increased risk of UGIB (adjusted OR: 1.25, 95% CI: 1.03-1.50) with a dose-response manner, whereas paroxetine users had 29% decreased odds (95% CI: 0.56-0.91). The increased risk was only observed among current fluoxetine users. CONCLUSIONS: Fluoxetine therapy was associated with an increased risk of UGIB in a dose-response manner among older adults.

Integrative traditional Chinese medicine treatment for children with obstructive sleep apnea.

Purpose: Obstructive sleep apnea (OSA) is a chronic disease that affects 1%-6% of children. Our study aims to explore the effectiveness and clinical characteristics of integrative Traditional Chinese Medicine (ITCM) for pediatric OSA. Materials and methods: In this retrospective cohort study, we assessed differences of polysomnography (PSG) parameters and clinical characteristics between 2009 and 2020. Children <12 years old diagnosed with OSA (n = 508) were included and were categorized into ITCM cohort, western medicine (WM) cohort ,and surgery cohort. Outcomes were apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and body mass index (BMI). Results: There were 56 (11%), 324 (63.8%), and 128 (25.2%) patients in the ITCM, WM, and surgery cohorts. Among 17, 26, and 33 patients in the ITCM, WM, and surgery cohorts underwent follow-up PSG studies, respectively. In the ITCM follow-up cohort, AHI were significantly reduced (9.59 to 5.71, p < 0.05). BMI significantly increased in the WM follow-up cohort (19.46 to 20.50, p < 0.05) and the surgery follow-up cohort (18.04 to 18.85, p < 0.01). Comparing ITCM to WM cohort, a significant difference was found between the changes in RDI (ITCM: -6.78, WM: 0.51, p < 0.05) after treatment. Among ITCM follow-up cohort, the most prescribed TCM formula was Forsythia and Laminaria Combination. The most prescribed TCM herb was Ephedrae Herba. Conclusions: ITCM therapy can significantly reduce RDI and control BMI. We identified potential TCM treatments for pediatric OSA. Further study of the pharmacological mechanisms and clinical efficacy is warranted.

Relationship between Symptom Profiles and Endotypes among Patients with Obstructive Sleep Apnea: A Latent Class Analysis.

Rationale: Obstructive sleep apnea (OSA) is a heterogeneous syndrome with various endotypic traits and symptoms. A link among symptoms, endotypes, and disease prognosis has been proposed but remains unsupported by empirical data. Objectives: To link symptom profiles and endotypes by clustering endotypic traits estimated using polysomnographic signals. Methods: We recruited 509 patients with moderate to severe OSA from a single sleep center. Polysomnographic data were collected between May 2020 and January 2022. Endotypic traits, namely arousal threshold, upper airway collapsibility, loop gain, and upper airway muscle compensation, were retrieved using polysomnographic signals during non-rapid eye movement periods. We used latent class analysis to group participants into endotype clusters. Demographic and polysomnographic parameter differences were compared between clusters, and associations between endotype clusters and symptom profiles were examined using logistic regression analyses. Results: Three endotype clusters were identified, characterized by high collapsibility/loop gain, low arousal threshold, and low compensation, respectively. Patients in each cluster exhibited similar demographic characteristics, but those in the high collapsibility/loop gain cluster had the highest proportion of obesity and severe oxygen desaturation observed in polysomnographic studies. The low compensation cluster was characterized by fewer sleepy symptoms and exhibited a lower rate of diabetes mellitus. Compared with the excessively sleepy group, disturbed sleep symptoms were associated with the low arousal threshold cluster (odds ratio, 1.89; 95% confidence interval, 1.16-3.10). Excessively sleepy symptoms were associated with the high collapsibility/loop gain cluster (odds ratio, 2.16; 95% confidence interval, 1.39-3.37) compared with the minimally symptomatic group. Conclusions: Three pathological endotype clusters were identified among patients with moderate to severe OSA, each exhibiting distinct polysomnographic characteristics and clinical symptom profiles.

Rest-activity rhythm associated with depressive symptom severity and attention among patients with major depressive disorder: a 12-month follow-up study.

Introduction: Patients with depressive disorder demonstrate rest-activity rhythm disturbances and cognitive function impairment. This study examined the association of individual rest-activity rhythm changes over time with mood symptoms and attention. Methods: We recruited 15 adult outpatients with a diagnosis of major depressive disorder from a single medical center and observed them for 12 months. Weekly rest-activity parameters, including rhythm characteristics generated from nonparametric circadian rhythm analysis, were retrieved from actigraphy data. Attention was evaluated weekly with a smartphone-based psychomotor vigilance test upon awakening. Depressive symptom severity was evaluated using the Beck Depression Inventory (BDI) fortnightly. The association of rest-activity parameters with BDI score and attention was examined using generalized linear mixed regression. A fixed-effects analysis was used to examine the association between rest-activity parameters and depressive episodes. Results: An advanced bedtime and most active continuous 10 h starting time were associated with depressive symptom severity but also associated with higher vigilance test performance. A longer sleep duration, mainly due to an earlier bedtime, was associated with depressive symptom severity. Compared to remission, sleep duration was 27.8 min longer during depressive episodes, and bed time was 24 min earlier. A shorter sleep duration and increased activity during sleep were associated with poorer attention. Discussion: Rest-activity rhythms change with mood symptoms among patients with depressive disorder. The circadian rhythms of rest-activity among patients with depressive disorder should be distinguished during various mood states in future studies.

Efficacy and safety of indacaterol 150 and 300 µg in chronic obstructive pulmonary disease patients from six Asian areas including Japan: a 12-week, placebo-controlled study.

BACKGROUND AND OBJECTIVE: The efficacy and safety of indacaterol, a novel inhaled once daily ultra long-acting ß(2) -agonist was evaluated in COPD patients in six Asian countries/areas. This study was primarily designed to obtain the regulatory approval of indacaterol in Japan. METHODS: Moderate-to-severe COPD patients were randomized to indacaterol 150 µg, indacaterol 300 µg or placebo once daily. Efficacy variables: trough FEV(1) (average of 23 h 10 min and 23 h 45 min post-dose values), health status (St. George's Respiratory Questionnaire) and transition dyspnoea index at week 12. Safety/tolerability was evaluated. RESULTS: A total of 347 patients were randomized (96.5% male, mean (SD) age 66.7 (8.38) years, post-bronchodilator FEV(1) % predicted: 53.7 (12.50)); 88.8% completed. The least squares means (LSM) trough FEV(1) at week 12 for indacaterol 150 µg, indacaterol 300 µg and placebo were 1.34 L, 1.37 L and 1.17 L, respectively, with differences versus placebo exceeding the prespecified minimal clinically important difference of 0.12 L (0.17 L and 0.20 L for indacaterol 150 µg and 300 µg, respectively, both P < 0.001). The week 12 LSM transition dyspnoea index score was statistically superior for both indacaterol doses versus placebo (differences of 1.30 and 1.26, P < 0.001; both exceeding the minimal clinically important difference of 1). At week 12, both indacaterol doses provided statistically significant (P ≤ 0.005) and clinically meaningful (≥4 units) improvements in LSM St. George's Respiratory Questionnaire total score versus placebo (differences: -4.8 and -5.7 units). Adverse events for indacaterol (49.1%, both doses) were lower than placebo (59.0%) and were mostly mild/moderate in severity; no deaths were reported. CONCLUSIONS: Indacaterol provided clinically significant bronchodilation and improvements in dyspnoea and health status in Asian COPD patients.

The Effectiveness and Tolerability of Glycopyrronium for Patients with Chronic Obstructive Pulmonary Disease in a Clinical Setting: GLARE-Taiwan.

Glycopyrronium (GLY) is a pharmacological maintenance treatment for chronic obstructive pulmonary disease (COPD). However, its effectiveness and tolerability for COPD patients in routine clinical practice have not been well-investigated. This study aimed to assess the effectiveness of GLY on health-related quality of life and its safety in patients with COPD in a routine clinical care setting. This multi-center, prospective, six-month observational study recruited patients diagnosed with COPD and treated with GLY at three medical centers in central Taiwan. The full analysis set (n = 102) had a significant improvement in the Clinical COPD Questionnaire total (mean ± SD = −0.39 ± 0.90, p = 0.002), symptoms (mean ± SD = −0.61 ± 0.90, p < 0.001) and mental state scores (mean ± SD = −0.54 ± 1.72, p = 0.021) but not the functional state score (mean ± SD = −0.10 ± 1.15, p = 0.529). During the observational period, 58 patients (52.73%) experienced adverse events; only one adverse event (dizziness) was suspected to be related to the study drug. Three patients (2.73%) discontinued the study and GLY treatment because of an adverse event. One patient (0.91%) died during the study period because of a cerebral infarction, which was judged to be not associated with GLY treatment. In conclusion, GLY could be effective in improving the health status and is safe for patients with COPD in a real-life setting.

Impact of sleep timing on attention, sleepiness, and sleep quality among real-life night shift workers with shift work disorder: a cross-over clinical trial.

STUDY OBJECTIVES: To examine the effect of sleep timing intervention on sleep quality, attention, and sleepiness at work among night shift workers with shift work disorder. METHODS: We recruited 60 real-life night shift workers through advertisements to participate this cross-over clinical trial. Shift work disorder was confirmed with interview and sleep log. Participants were designated to follow evening sleep (15:00-23:00) and morning sleep (09:00-17:00) schedules in a randomized order. Chronotype was confirmed by the Munich Chronotype Questionnaire. Sleep behaviors and light exposure were recorded using actigraphy. Outcome measures were sleepiness evaluated by the Karolinska Sleepiness Scale, sleep quality evaluated by the Pittsburgh Sleep Quality Index, and attention performance assessed with psychomotor vigilance test. Differences in outcome between the morning and evening sleep schedules were compared using repeated measures ANOVA. RESULTS: The participants slept for longer durations during evening sleep schedules compared with morning sleep schedules. Lower sleepiness scores, higher sleep quality, and shorter reaction times and less lapse numbers in the psychomotor vigilance test were observed for participants during evening sleep schedules than morning sleep schedules after adjustment for light exposure and sleep duration. Significant interaction effects were observed for reaction time and lapse number between chronotype and sleep schedule, where the differences between sleep schedules were most prominent among those with late chronotypes. CONCLUSIONS: It is recommended that night shift workers with shift work disorder arrange to sleep in the evening instead of the morning for better sleep and attention performance, especially those with late chronotypes. TRIAL REGISTRATION: Sleep Schedule Intervention Study Among Night Shift Workers, https://clinicaltrials.gov/ct2/show/NCT04160572, ClinicalTrials.gov Identifier: NTC04160572.

NICEFIT-A Prospective, Non-Interventional, and Multicentric Study for the Management of Idiopathic Pulmonary Fibrosis with Antifibrotic Therapy in Taiwan.

Idiopathic pulmonary fibrosis (IPF) causes progressive lung fibrosis with subsequent fatality and has limited treatment options. NICEFIT is the first Taiwan-based prospective, observational, and non-interventional registry for IPF progression under routine clinical practice in Taiwan. Data on 101 patients (aged 74.6 ± 9.1 years and 83.2% men) with IPF were collected over 2 years (2018-2020) from medical centers in Taiwan at baseline, 1 month, and subsequent 3-month intervals. Treated patients (n = 88) received the antifibrotics nintedanib or pirfenidone, compared with the untreated group (n = 13). The 2-year assessment revealed overall preserved lung functionality in the treated patients, with insignificant changes from baseline for percent predicted forced vital capacity or FVC (±1.7%). The presence of respiratory comorbidities significantly increased the risk of both AE and death (with or without AE) over the full study duration. Furthermore, the decline of predicted FVC significantly increased with the risk of acute exacerbations (AE) in the second year. Overall, antifibrotic medication was beneficial in stalling IPF progression, reducing AEs, and delaying mortality in the treated cohort, despite their lower baseline lung functions. Further, no new safety concerns over antifibrotic treatments were observed for the Taiwanese population.

Outcome predictors of cirrhotic patients with spontaneous bacterial empyema.

BACKGROUND: Spontaneous bacterial empyema (SBE) is a complication of cirrhotic patients in which a pre-existing pleural effusion becomes infected. This retrospective study was designed to investigate the bacteriology and outcome predictors of SBE in cirrhotic patients. METHODS: Medical records of cirrhotic patients treated in a tertiary care university hospital from December 2004 to December 2008 were retrospectively reviewed. RESULTS: Of 3390 cirrhotic patients seen during the study period, 81 cases of SBE were diagnosed. The incidence of SBE was 2.4% (81/3390) in cirrhotic patients and 16% (81/508) in patients with cirrhosis with hydrothorax. There were 46 monomicrobial infections found in 46 SBE patients. Aerobic Gram-negative organisms were the predominant pathogens (n=29, 63%), and Escherichia coli (n=9, 20%) was the most frequently isolated sole pathogen. The mortality rate of SBE was 38% (31/81). Univariate analysis showed that Child-Pugh score, model for end-stage liver disease (MELD)-Na score, concomitant bacteraemia, concomitant spontaneous bacterial peritonitis, initial intensive care unit (ICU) admission and initial antibiotic treatment failure were predictors of poor outcomes. Multivariate regression analysis demonstrated that the independent factors related to a poor outcome were initial ICU admission [odds ratio (OR): 4.318; 95% confidence interval 1CI) 1.09-17.03; P=0.037], MELD-Na score (OR: 1.267; 95% CI 1.08-1.49; P=0.004) and initial antibiotic treatment failure (OR: 13.10; 95% CI 2.60-66.03). CONCLUSION: Spontaneous bacterial empyema in cirrhotic patients is a high mortality complication. The independent factors related to poor outcome are high MELD-Na score, initial ICU admission and initial antibiotic treatment failure. High MELD-Na score may be a useful mortality predictor of SBE in cirrhotic patients.