ObjectiveTo investigate the association between metabolic associated fatty liver disease （MAFLD） and the risk of atherosclerotic cardiovascular disease （ASCVD）， and to provide data support for the prevention and treatment of such metabolic-associated diseases in clinical practice. MethodsAn observation cohort was established for the workers of Kailuan who underwent physical examination for the first time from June 2006 to October 2007 and had complete liver assessment data， without the history of malignant tumor， MAFLD or ASCVD. According to the presence or absence of MAFLD， the patients were divided into non-MAFLD group with 67 565 patients and MAFLD group with 29 004 patients， and according to the presence or absence of ASCVD， the patients were divided into non-ASCVD group with 69 141 patients and ASCVD group with 481 patients. The group t-test or the Wilcoxon rank-sum test was used for comparison of continuous data between the two groups. The χ² test was used for comparison of categorical data between the two groups. The life-table method was used to calculate the cumulative incidence rates of new-onset ASCVD and MAFLD； the Kaplan-Meier method was used to plot the survival curves of the cumulative incidence rates of ASCVD in the MAFLD group and the non-MAFLD group and the cumulative incidence rates of MAFLD in the ASCVD group and the non-ASCVD group， and the log-rank test was used for comparison of cumulative incidence rates between two groups. A multivariate Cox proportional-hazards regression model analysis was used to investigate the impact of MAFLD on the risk of ASCVD and the impact of ASCVD on the risk of MAFLD. ResultsCompared with the non-MAFLD group， the MAFLD group had significantly higher levels of body mass index （BMI）， waist circumference， systolic blood pressure （SBP）， diastolic blood pressure （DBP）， resting heart rate， alanine aminotransferase， uric acid （UA）， fasting blood glucose （FBG）， triglyceride （TG）， total cholesterol， low-density lipoprotein cholesterol， and high sensitivity C-reactive protein （hs-CRP）， as well as significanty lower levels of estimated glomerular filtration rate （eGFR） and high-density lipoprotein cholesterol （all P <0.05）. Compared with the non-ASCVD group， the ASCVD group had significantly higher levels of BMI， waist circumference， SBP， DBP， UA， FBG， TG， and hs-CRP and a significantly lower level of eGFR （all P<0.05）. The incidence rate of new-onset ASCVD continued to increase over time in the MAFLD group and the non-MAFLD group， while the incidence rate of new-onset MAFLD firstly increased and then remained stable over time in the ASCVD group and the non-ASCVD group. There were 4 263 cases （14.70%） of new-osnet ASCVD in the MAFLD group， with an incidence density of 12.90 per 1 000 person-years， while there were 6 529 cases （9.66%） of new-osnet ASCVD in the non-MAFLD group， with an incidence density of 8.24 per 1 000 person-years， and there were significant differences in the incidence density and cumulative incidence rate of ASCVD between the two groups （χ²=519.09 and 531.80， both P<0.05）. There were 148 cases （30.77%） of new-onset MAFLD in the ASCVD group， with an incidence density of 40.10 per 1 000 person-years， while there were 32 194 cases （46.56%） of new-onset MAFLD in the non-ASCVD group， with an incidence density of 57.59 per 1 000 person-years， and there were significant differences in the incidence density and cumulative incidence rate of MAFLD between the two groups （χ²=19.29 and 30.78， both P<0.05）. The corrected multivariate Cox proportional-hazards regression model analysis showed that MAFLD was a risk factor for new-onset ASCVD （hazard ratio ［HR］=1.11， 95% confidence interval ［CI］： 1.06 — 1.16， P<0.001）， while ASCVD was a protective factor against new-onset MAFLD （HR=0.72， 95%CI： 0.61 — 0.85， P<0.001）. ConclusionThere is a significant association between MAFLD and ASCVD， with an increase in the risk of ASCVD in the MAFLD population and a reduction in the risk of MAFLD in the ASCVD population.

Objectives:To investigate the correlation between resting heart rate(RHR)and atherosclerotic cardiovascular disease(ASCVD)and all-cause death in young and middle-aged people.Methods:A prospective cohort study was conducted enrolling 72 642 young and middle-aged participants(aged<60 years),who participated in the medical examination of the Kailuan Study from June 2006 to October 2007.According to the quartile of the RHR level,the participants were divided into Q1 group(<67 beats/min,n=14 381),Q2 group(67-70 beats/min,n=15 815),Q3 group(71-75 beats/min,n=15 876),Q4 group(76-80 beats/min,n=13 933)and Q5 group(>80 beats/min,n=12 637).Cox proportional hazard regression model was used to analyze the effect of RHR on ASCVD and all-cause death.The dose-response relationship between RHR and the risk of ASCVD and all-cause death was investigated using a restricted cubic spline regression model.Results:During a mean follow-up of(10.0±4.85)years,2 898 patients(3.99%)developed ASCVD.Multivariate Cox regression analysis showed that after adjusting for confounding factors,the risk of RHR and ASCVD in group Q5 increased by 20%compared with group Q1(HR=1.20,95%CI:1.06-1.35,P<0.05).There was no significant risk in groups Q2 to Q4 compared to Q1 group(all P>0.05).In addition,the risk of ASCVD increased by 4%for every 10 beats/min increase in RHR(HR=1.04,95%CI:1.01-1.07,P=0.009).During the follow-up period of(10.2±4.82)years,all-cause death occurred in 2 175 participants(2.99%).The results showed that compared with Q1 group,the risk of all-cause death in Q3 to Q5 groups increased by 33%(HR=1.33,95%CI:1.15-1.54,P<0.001),33%(HR=1.33,95%CI:1.14-1.54,P<0.001),and 78%(HR=1.78,95%CI:1.54-2.05,P<0.001)respectively,and there was no statistical significance between group Q2 and group Q1.The risk of all-cause death increased by 15%for every 10 beats/min increase in RHR(HR=1.15,95%CI:1.11-1.19,P<0.001).Restricted cubic spline analysis showed that RHR was linearly correlated with risk of ASCVD(Poverall=0.022,Pnon-linear=0.617),and the risk of ASCVD increased significantly with RHR>72 beats/min.RHR was linearly associated with the risk of all-cause death(Poverall<0.001,Pnon-linear=0.212),and the risk of all-cause death was significantly increased with RHR>72 betas/min.Conclusions:Higher RHR is associated with an increased risk of ASCVD and all-cause mortality in young and middle-aged individuals.

Objectives:To investigate the association between the triglyceride-glucose(TyG)index and risk of non-alcoholic fatty liver disease(NAFLD)in young and middle-aged(<60 years)adults.Methods:From June 2006 to October 2007,47 675 employees of Kailuan Group with no liver disease were selected as the study objects.Based on the TyG index quartile,participants were divided into Q1 group(TyG index≤8.08,n=11 924),Q2 group(8.0836.46,n=11 919),the association between TyG index,cum-TyG and cumulative exposure time and the risk of NAFLD was analyzed.Results:The average age of the study population was(44.3±8.7)years,36 345 participants were males(76.23%).During a median follow-up period of 11.55(7.28,13.89)years,4 635(9.72%)participants developed new-onset NAFLD.After adjusting for confounders,cox regression analysis showed that compared with the Q1 group,the HR(95%CI)for NAFLD in the Q2 to Q4 groups were 1.328(1.191-1.480),1.591(1.430-1.770),and 2.106(1.861-2.384),respectively,Ptrend<0.001.Compared with the cum-Q1 group,the HR(95%CI)for NAFLD in the cum-Q2 to cum-Q4 groups were 1.571(1.426-1.730),2.123(1.935-2.330)and 2.593(2.367-2.840),respectively,Ptrend<0.001.Compared with the TyG index for 0 year,the HR(95%CI)of NAFLD for 2,4 and 6 years was 1.333(1.196-1.486),1.879(1.690-2.088)and 3.184(2.860-3.545),respectively,Ptrend<0.001.Conclusions:Increased TyG index is an independent risk factor for the new-onset NAFLD in young and middle-aged population.

Objectives:To investigate the association between the triglyceride-glucose(TyG)index and risk of non-alcoholic fatty liver disease(NAFLD)in young and middle-aged(<60 years)adults.Methods:From June 2006 to October 2007,47 675 employees of Kailuan Group with no liver disease were selected as the study objects.Based on the TyG index quartile,participants were divided into Q1 group(TyG index≤8.08,n=11 924),Q2 group(8.0836.46,n=11 919),the association between TyG index,cum-TyG and cumulative exposure time and the risk of NAFLD was analyzed.Results:The average age of the study population was(44.3±8.7)years,36 345 participants were males(76.23%).During a median follow-up period of 11.55(7.28,13.89)years,4 635(9.72%)participants developed new-onset NAFLD.After adjusting for confounders,cox regression analysis showed that compared with the Q1 group,the HR(95%CI)for NAFLD in the Q2 to Q4 groups were 1.328(1.191-1.480),1.591(1.430-1.770),and 2.106(1.861-2.384),respectively,Ptrend<0.001.Compared with the cum-Q1 group,the HR(95%CI)for NAFLD in the cum-Q2 to cum-Q4 groups were 1.571(1.426-1.730),2.123(1.935-2.330)and 2.593(2.367-2.840),respectively,Ptrend<0.001.Compared with the TyG index for 0 year,the HR(95%CI)of NAFLD for 2,4 and 6 years was 1.333(1.196-1.486),1.879(1.690-2.088)and 3.184(2.860-3.545),respectively,Ptrend<0.001.Conclusions:Increased TyG index is an independent risk factor for the new-onset NAFLD in young and middle-aged population.

Objectives:To investigate the correlation between resting heart rate(RHR)and atherosclerotic cardiovascular disease(ASCVD)and all-cause death in young and middle-aged people.Methods:A prospective cohort study was conducted enrolling 72 642 young and middle-aged participants(aged<60 years),who participated in the medical examination of the Kailuan Study from June 2006 to October 2007.According to the quartile of the RHR level,the participants were divided into Q1 group(<67 beats/min,n=14 381),Q2 group(67-70 beats/min,n=15 815),Q3 group(71-75 beats/min,n=15 876),Q4 group(76-80 beats/min,n=13 933)and Q5 group(>80 beats/min,n=12 637).Cox proportional hazard regression model was used to analyze the effect of RHR on ASCVD and all-cause death.The dose-response relationship between RHR and the risk of ASCVD and all-cause death was investigated using a restricted cubic spline regression model.Results:During a mean follow-up of(10.0±4.85)years,2 898 patients(3.99%)developed ASCVD.Multivariate Cox regression analysis showed that after adjusting for confounding factors,the risk of RHR and ASCVD in group Q5 increased by 20%compared with group Q1(HR=1.20,95%CI:1.06-1.35,P<0.05).There was no significant risk in groups Q2 to Q4 compared to Q1 group(all P>0.05).In addition,the risk of ASCVD increased by 4%for every 10 beats/min increase in RHR(HR=1.04,95%CI:1.01-1.07,P=0.009).During the follow-up period of(10.2±4.82)years,all-cause death occurred in 2 175 participants(2.99%).The results showed that compared with Q1 group,the risk of all-cause death in Q3 to Q5 groups increased by 33%(HR=1.33,95%CI:1.15-1.54,P<0.001),33%(HR=1.33,95%CI:1.14-1.54,P<0.001),and 78%(HR=1.78,95%CI:1.54-2.05,P<0.001)respectively,and there was no statistical significance between group Q2 and group Q1.The risk of all-cause death increased by 15%for every 10 beats/min increase in RHR(HR=1.15,95%CI:1.11-1.19,P<0.001).Restricted cubic spline analysis showed that RHR was linearly correlated with risk of ASCVD(Poverall=0.022,Pnon-linear=0.617),and the risk of ASCVD increased significantly with RHR>72 beats/min.RHR was linearly associated with the risk of all-cause death(Poverall<0.001,Pnon-linear=0.212),and the risk of all-cause death was significantly increased with RHR>72 betas/min.Conclusions:Higher RHR is associated with an increased risk of ASCVD and all-cause mortality in young and middle-aged individuals.

Objective To investigate whether suffering from atrial fibrillation in different ages of people increasing the onset risk of new-onset acute myocardial infarction(AMI).Methods A prospective cohort study was conducted to select 96 624 Kailuan Group employees undergoing the health examination from June 2006 to October 2007 for including the study.The participants were followed up once a year,and the last fol-low-up date was December 31,2020,with a median follow-up of 14.01 years,and the endpoint event was new-onset AMI.The participants were divided into two age groups according to the age ≥60 years and the age＜60 years old,and divided into the atrial fibrillation group and non-atrial fibrillation group according to whether they had atrial fibrillation.The epidemiological investigation and anthropometric measurements were carried out on the participates.Whether atrial fibrillation was correlated to the onset of new-onset AMI in different age groups conducted the statistical analysis.Results Among the total participants,there were 411 cases in the atrial fibrillation group and 96 213 cases in the non-atrial fibrillation group.Among the participants＜60 years old,there were 121 cases in the atrial fibrillation group and 75 151 cases in the non-atrial fibrillation group.Among the participants ≥60 years old,there were 290 cases in the atrial fibrillation group and 21 062 cases in the non-atrial fibrillation group.In the total participants,the cumulative incidence rate of AMI in the atrial fibrillation group was higher than that in the non-atrial fibrillation group(5.68％vs.1.92％),and the difference was statistically significant(P＜0.05).In the participants＜60 years old,the cumulative incidence rate of AMI in the atrial fibrillation group was higher than that in the non-atrial fibrillation group(7.40％vs.1.43％),and the difference was statistically significant(P＜0.05).In the participants 60 year old,the cu-mulative incidence rate of AMI had no statistical difference between the atrial fibrillation group and non-atrial fibrillation group(4.54％vs.3.87％,P=0.547).In the whole participants,atrial fibrillation was a risk factor for new-onset AMI(HR=1.877,95％CI:1.177-2.991,P=0.008),and there was an interaction between age and atrial fibrillation(P=0.016).In the age stratification analysis,atrial fibrillation was a risk factor for new-onset AMI in＜60-year-old population(HR=3.029,95％CI:1.508-6.082,P=0.002).Conclusion Atrial fibrillation is an independent risk factor for new-onset AMI,especially to young and middle-aged people(＜60 years old).

Objective:To investigate the effects of ultrasound-guided serratus anterior plane block (SAPB) on hemodynamics in children with microtia undergoing auricular reconstruction.Methods:This research was a prospective randomized control study. Patients were prospectively recruited from March 2022 to July 2022 at the Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Children with microtia undergoing auricular reconstruction with costal cartilage were randomly included in either a SAPB-pre group(SAPB pre-rib harvest group) or a SAPB-post group(SAPB post-rib harvest group). Both groups of children were anesthetized with combined intravenous and inhalation anesthesia. Anesthesia maintenance was provided with i. v. propofol 4-6 mg·kg -1·h -1 and remifentanil 0.1-0.3 μg·kg -1·min -1, sevoflurane at 1% concentration, and a flow rate of 2.5 L/min. During the operation, bispectral index(BIS) was maintained between 40-60, and alterations in mean arterial pressure (MAP) and heart rate (HR) were <20%, compared to the basic values. During the operation, 1% sevoflurane was inhaled to maintain anesthesia. The fluctuation of BIS, MAP, and HR was adjusted by the intraoperative infusion of remifentanil and propofol. Ultrasound-guided SAPB in the SAPB-pre group was performed by an anesthesiologist after tracheal intubation of general anesthesia. In the SAPB-post group, ultrasound-guided SAPB was performed by the same anesthesiologist before the tracheal catheter was removed at the end of the operation, and the concentration of ropivacaine was 0.25% (3 mg/kg). MAP, HR, and BIS were recorded at each time point of admission, pre-rib harvest, during-rib harvest, post-rib harvest, anesthesia extubation, leaving the room. The consumptions of propofol and remifentanil during the operation were also recorded. Continuous data were presented as Mean±SD. Non-repeated measurement parametric variables were compared using the independent samples t-test. Repeated measurement parametric variables were assessed using repeated measures analysis of variance. The same data at varying time points were compared using Dunnett- t test of multiple comparison procedures. Categorical data were compared using the Chi-square test. Results:Sixty children were randomized to SAPB-pre group and SAPB-post group and 30 in each group. The data of gender (boy 22/ girl 8 vs. boy 23/ girl 7), age[(8.03±1.07)years vs. (8.33±1.16)years], body mass index [(17.46±2.79)kg/m 2 vs. (17.23±2.11)kg/m 2], operation time[(185.33±16.29)min vs. (190.00±16.50)min] and length of costocartilage[(23.13±1.46)cm vs. (23.63±1.27)cm] between the two groups showed no significant differences ( P>0.05). There was no significant difference in MAP, HR and BIS values at the time of pre-rib harvest, during-rib harvest, and post-rib harvest in the SAPB-pre group ( P>0.05). In the SAPB-post group, the fluctuations of MAP, HR and BIS values at the time of pre-rib harvest, during-rib harvest and post-rib harvest were obvious ( P<0.01). The consumptions of propofol and remifentanil during the operation in the SAPB-pre group were significantly less than that in the SAPB-post group[(555.67±150.90)mg vs. (788.50±191.02)mg, P<0.01; (745.33±183.56)μg vs. (1 080.00±247.26)μg, P<0.01]. Conclusion:Ultrasound-guided serratus anterior plane block can stabilize the hemodynamics during auricular reconstruction using costal cartilage and reduce the consumption of general anesthetic.

Objective:To investigate the effects of ultrasound-guided serratus anterior plane block (SAPB) on hemodynamics in children with microtia undergoing auricular reconstruction.Methods:This research was a prospective randomized control study. Patients were prospectively recruited from March 2022 to July 2022 at the Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Children with microtia undergoing auricular reconstruction with costal cartilage were randomly included in either a SAPB-pre group(SAPB pre-rib harvest group) or a SAPB-post group(SAPB post-rib harvest group). Both groups of children were anesthetized with combined intravenous and inhalation anesthesia. Anesthesia maintenance was provided with i. v. propofol 4-6 mg·kg -1·h -1 and remifentanil 0.1-0.3 μg·kg -1·min -1, sevoflurane at 1% concentration, and a flow rate of 2.5 L/min. During the operation, bispectral index(BIS) was maintained between 40-60, and alterations in mean arterial pressure (MAP) and heart rate (HR) were <20%, compared to the basic values. During the operation, 1% sevoflurane was inhaled to maintain anesthesia. The fluctuation of BIS, MAP, and HR was adjusted by the intraoperative infusion of remifentanil and propofol. Ultrasound-guided SAPB in the SAPB-pre group was performed by an anesthesiologist after tracheal intubation of general anesthesia. In the SAPB-post group, ultrasound-guided SAPB was performed by the same anesthesiologist before the tracheal catheter was removed at the end of the operation, and the concentration of ropivacaine was 0.25% (3 mg/kg). MAP, HR, and BIS were recorded at each time point of admission, pre-rib harvest, during-rib harvest, post-rib harvest, anesthesia extubation, leaving the room. The consumptions of propofol and remifentanil during the operation were also recorded. Continuous data were presented as Mean±SD. Non-repeated measurement parametric variables were compared using the independent samples t-test. Repeated measurement parametric variables were assessed using repeated measures analysis of variance. The same data at varying time points were compared using Dunnett- t test of multiple comparison procedures. Categorical data were compared using the Chi-square test. Results:Sixty children were randomized to SAPB-pre group and SAPB-post group and 30 in each group. The data of gender (boy 22/ girl 8 vs. boy 23/ girl 7), age[(8.03±1.07)years vs. (8.33±1.16)years], body mass index [(17.46±2.79)kg/m 2 vs. (17.23±2.11)kg/m 2], operation time[(185.33±16.29)min vs. (190.00±16.50)min] and length of costocartilage[(23.13±1.46)cm vs. (23.63±1.27)cm] between the two groups showed no significant differences ( P>0.05). There was no significant difference in MAP, HR and BIS values at the time of pre-rib harvest, during-rib harvest, and post-rib harvest in the SAPB-pre group ( P>0.05). In the SAPB-post group, the fluctuations of MAP, HR and BIS values at the time of pre-rib harvest, during-rib harvest and post-rib harvest were obvious ( P<0.01). The consumptions of propofol and remifentanil during the operation in the SAPB-pre group were significantly less than that in the SAPB-post group[(555.67±150.90)mg vs. (788.50±191.02)mg, P<0.01; (745.33±183.56)μg vs. (1 080.00±247.26)μg, P<0.01]. Conclusion:Ultrasound-guided serratus anterior plane block can stabilize the hemodynamics during auricular reconstruction using costal cartilage and reduce the consumption of general anesthetic.

Objective:To compare the efficacy and safety of domestic 16-row and imported 8-row mobile CT in clinics.Methods:A total of 1469 patients accepted domestic 16-row mobile CT head scans (1604 times) from March 2017 to August 2018 in Bayi Brain Hospital Affiliated to 7 th Medical Center of General Hospital of People's Liberation Army and Langfang Aidebao Hospital; and 15510 patients accepted imported 8-row mobile CT head scans (24994 times) from January 2016 to August 2018 in Bayi Brain Hospital Affiliated to 7 th Medical Center of General Hospital of People's Liberation Army. All patients underwent horizontal plain and enhanced head scans, cerebral CT angiography (CTA), and helical 3D imaging; and the imaging quality, operating power consumption, computed tomography dose index volume (CTDIvol) and stability within scanning volume ranges under different scanning modes of the two CT scans were compared. Results:(1) Imaging quality: the horizontal scanning of domestic 16-row mobile CT could clearly display low-density tissues such as the eyeball, optic nerve, brain stem, sulcus and cerebral gyrus; the imaging quality of both CT scans in patients with traumatic subdural hematoma and ischemic stroke completely met the clinical diagnosis and treatment standards. (2) Operating power consumption: the per-hour operating power consumption of domestic 16-row mobile CT ([0.286±0.018] kW·h) was obviously lower than that of imported 8-row mobile CT ([0.485±0.028] kW·h). (3) Radiological hazard: the CTDIvol of the horizontal scanning volume range in domestic 16-row mobile CT ([36.270±0.281] mGy) was significantly lower than that in the imported 8-row mobile CT ([82.520±0.441] mGy, P<0.05); the CTDIvol of enhanced axis scan volume range in the domestic 16-row mobile CT ([36.270±0.335] mGy) was significantly lower than that in the imported 8-row mobile CT ([70.728±0.424] mGy, P<0.05); the CTDIvol in the volume of CTA imaging of domestic 16-row mobile CT ([20.600±0.087] mGy) was significantly lower than that in the imported 8-row mobile CT ([29.300±0.335] mGy, P<0.05). The domestic 16-row mobile CT was designed with shock absorbers and guides; domestic 16-row mobile CT had small load, a low center of gravity, and good stability as compared with imported 8-row mobile CT. Conclusion:In terms of head scanning applications, the imaging quality of domestic 16-row mobile CT and imported 8-row mobile CT is in full compliance with clinical diagnostic standards, but the energy consumption and radiation risk of domestic 16-row mobile CT is significantly lower than imported 8-row mobile CT, enjoying good stability as compared with imported 8-row mobile CT.

Objective To investigate the feasibility of the upper- arm electronic sphygmomanometer for evaluating the blood pressure in patients with atrial fibrillation. Methods Consecutive hospitalized patients with atrial fibrillation for coronary angiography were selected, and the application of upper- arm electronic sphygmomanometer and mercury sphygmomanometer of blood pressure were applied and in the process of coronary angiography, the radial artery invasive blood pressure was recorded and the correlation was analyzed. Results Mercury sphygmomanometer and radial artery invasive blood pressure measurement had a good consistency on systolic blood pressure, diastolic blood pressure, pulse pressure, mean arterial pressure in atrial fibrillation patients, the differences were not statistically significant (P>0.05). Upper- arm electronic sphygmomanometer and radial artery invasive blood pressure measurement had some consistency (pulse rate range, pulse rate of 70-90 beats / min) on systolic blood pressure, diastolic blood pressure, pulse pressure, mean arterial pressure in atrial fibrillation patients, the differences were not statistically significant (P>0.05). Upper-arm electronic sphygmomanometer and mercury sphygmomanometer had some consistency (pulse rate range, pulse rate of 70-90 beats / min) on systolic blood pressure, diastolic blood pressure, pulse pressure, mean arterial pressure in atrial fibrillation patients, the differences were not statistically significant (P>0.05). The correlation between mercury sphygmomanometer and radial artery invasive blood pressure measurement were found on systolic blood pressure, diastolic blood pressure, pulse pressure, mean arterial pressure in atrial fibrillation patients (r=0.71-0.78, P<0.05),which were better than those of upper- arm electronic sphygmomanometer and radial artery invasive blood pressure measurement (r=0.53-0.70, P <0.05). Conclusions The upper- arm electronic sphygmomanometer can be used for the assessment of blood pressure in patients with atrial fibrillation.