Mepolizumab versus benralizumab for eosinophilic granulomatosis with polyangiitis (EGPA): A European real-life retrospective comparative study

Background: Following the results of the MANDARA trial, this real-life study aimed at comparing the effectiveness and safety profile of mepolizumab versus benralizumab in a European EGPA cohort. Methods: We conducted a retrospective observational comparative study including EGPA patients, who received mepolizumab or benralizumab at the asthma dose. Patients were matched 1:1 by sex, age, BVAS and oral corticosteroid (OCS) dosage at the treatment initiation (T0). Complete response (CR) and partial response (PR), disease activity, OCS, pulmonary parameters, eosinophil count, relapses, and safety outcomes were also compared at 3, 6 and 12 months. Results: Patients treated with mepolizumab or benralizumab (n = 88 each) were matched: 57 % were females, median age was 54 years (IQR 45–60), median OCS dose 10 (7.5–12.5) and 10 (7–13) mg/day, median BVAS 4 (2–7) and 3 (2–8), respectively. 45.4 % of patients in the mepolizumab group and 51.1 % in the benralizumab group achieved CR or PR at T3, with CR steadily increasing during follow-up for both treatments. At T12, a higher CR rate was found in the benralizumab group (48.1 % vs 32.4 %, p = 0.005). No differences in BVAS, OCS, and respiratory parameters were observed between groups at the different timepoints. Throughout the follow-up, both treatments reduced eosinophil count, although a deeper reduction was found in the benralizumab group at all timepoints (p < 0.0001). Safety profile was comparable between patient groups. Conclusion: Mepolizumab and benralizumab showed comparable overall effectiveness and safety in EGPA. However, benralizumab achieved a higher CR rate at T12, and a deeper peripheral eosinophil reduction

Testing of a model for risk factors for eating disorders and higher weight among emerging adults: Baseline evaluation

Although a range of risk factors have been identified for disordered eating and weight status, the breadth of risk factors have been rarely considered within a single, comprehensive model. The robustness of these findings across countries also remains an open question. The present study sampled 6272 participants aged 18–30 years from eight countries in an attempt to evaluate combined and unique predictors for these two conditions, and to explore possible cross-country differences in these models. Participants completed a range of demographic, biological, behavioral, psychological, and sociocultural measures to test a comprehensive model of the contributions of these predictors for disordered eating and weight-related constructs (binge eating, body mass index, compensatory behaviors, dietary restraint, drive for muscularity, and drive for leanness). Structural invariance testing within a multigroup path analysis framework revealed that a single model across the eight countries provided poor model fit. Freeing of 22% of parameters across countries provided excellent fit and a satisfactory compromise for country-invariant and country-variant parameters in the model. Overall, predictors accounted for between 15% and 60% of variance in the outcome measures, with lowest explained variance for the disordered eating outcomes. Significant unique contributions to prediction were observed for each of the five risk factor variable types and across the eight countries. Thus, the findings show strong support for this model as an explanatory framework of both disordered eating and weight status.</p

The basal to total insulin ratio in outpatients with diabetes on basal-bolus regimen

Objective: To evaluate the basal/total ratio of daily insulin dose (b/T) in outpatients with diabetes type 1 (DM1) and type 2 (DM2) on basal-bolus regimen, by investigating whether there is a relationship with HbA1c and episodes of hypoglycemia. Methods: Multicentric, observational, cross-sectional study in Italy. Adult DM1 (n = 476) and DM2 (n = 541) outpatients, with eGFR &gt;30&nbsp;mL/min/1.73&nbsp;m 2 , on a basal-bolus regimen for at least six months, were recruited from 31 Italian Diabetes services between March and September 2016. Clinicaltrials.govID: NCT03489031. Results: Total daily insulin dose was significantly higher in DM2 patients (52.3 ± 22.5 vs. 46 ± 20.9&nbsp;U/day), but this difference disappeared when insulin doses were normalized for body weight. The b/T ratio was lower than 0.50 in both groups: 0.46 ± 0.14 in DM1 and 0.43 ± 0.15 in DM2 patients (p = 0.0011). The b/T was significantly higher in the patients taking metformin in both groups, and significantly different according to the type of basal insulin (Degludec, 0.48 in DM1 and 0.44 in DM2; Glargine, 0.44 in DM1 and 0.43 in DM2; Detemir, 0.45 in DM1 and 0.39 in DM2). The b/T ratio was not correlated in either group to HbA1c or incidence of hypoglycemia (&lt;40&nbsp;mg/dL, or requiring caregiver intervention, in the last three months). In the multivariate analysis, metformin use and age were independent predictors of the b/T ratio in both DM1 and DM2 patients, while the type of basal insulin was an independent predictor only in DM1. Conclusion: The b/T ratio was independent of glycemic control and incidence of hypoglycemia

Relationship between carotid intima-media thickness and non valvular atrial fibrillation type.

OBJECTIVE:Carotid intima-media thickness (cIMT) is a surrogate marker of subclinical atherosclerosis and it is able to predict both coronary and cerebral vascular events. No data exist on the association between cIMT and non valvular atrial fibrillation (NVAF) type. We conduct this study with the aim to analyze the association between abnormal cIMT and NVAF type.METHODS:A cross-sectional study of the "Atrial fibrillation Registry for Ankle-brachial index Prevalence Assessment-Collaborative Italian Study (ARAPACIS)" has been performed. Among 2027 patients enrolled in the ARAPACIS, 673 patients, who underwent carotid ultrasound examination to assess cIMT, were included in the study.RESULTS:Among the entire population, 478 patients (71%) had cIMT > 0.90 mm. Patients with an abnormal cIMT (>0.90 mm) were significantly older and more likely hypertensive, diabetic and with a previous history of stroke than those with normal cIMT ( 640.90 mm). These patients had more permanent/persistent NVAF and CHA2DS2-VASc score 65 2 (p < 0.0001) compared to those with cIMT <0.90 mm. Excluding all patients affected by previous cardiovascular disease, logistic regression analysis showed that independent predictors of abnormal cIMT were: age class 65-74 yrs. (p < 0.001), age class 6575 yrs. (p < 0.001), arterial hypertension (p < 0.001), calcium-channel blockers use (p < 0.001) and persistent/permanent NVAF (p = 0.001).CONCLUSION:Our findings show a high prevalence of abnormal cIMT in NVAF patients, reinforcing the concept that NVAF and systemic atherosclerosis are closely associated. Abnormal cIMT was particularly evident in persistent/permanent NVAF suggesting a more elevated atherosclerotic burden in patients with long-standing NVAF

Relationship between carotid intima-media thickness and non valvular atrial fibrillation type

Objective: Carotid intima-media thickness (cIMT) is a surrogate marker of subclinical atherosclerosis and it is able to predict both coronary and cerebral vascular events. No data exist on the association between cIMT and non valvular atrial fibrillation (NVAF) type. We conduct this study with the aim to analyze the association between abnormal cIMT and NVAF type. Methods: A cross-sectional study of the "Atrial fibrillation Registry for Ankle-brachial index Prevalence Assessment-Collaborative Italian Study (ARAPACIS)" has been performed. Among 2027 patients enrolled in the ARAPACIS, 673 patients, who underwent carotid ultrasound examination to assess cIMT, were included in the study. Results: Among the entire population, 478 patients (71%) had cIMT>0.90mm. Patients with an abnormal cIMT (>0.90mm) were significantly older and more likely hypertensive, diabetic and with a previous history of stroke than those with normal cIMT (≤0.90mm). These patients had more permanent/persistent NVAF and CHA2DS2-VASc score ≥ 2 (p<0.0001) compared to those with cIMT <0.90mm. Excluding all patients affected by previous cardiovascular disease, logistic regression analysis showed that independent predictors of abnormal cIMT were: age class 65-74 yrs. (p<0.001), age class ≥75 yrs. (p<0.001), arterial hypertension (p<0.001), calcium-channel blockers use (p<0.001) and persistent/permanent NVAF (p=0.001). Conclusion: Our findings show a high prevalence of abnormal cIMT in NVAF patients, reinforcing the concept that NVAF and systemic atherosclerosis are closely associated. Abnormal cIMT was particularly evident in persistent/permanent NVAF suggesting a more elevated atherosclerotic burden in patients with long-standing NVAF

Relationship between carotid intima-media thickness and non valvular atrial fibrillation type

OBJECTIVE: Carotid intima-media thickness (cIMT) is a surrogate marker of subclinical atherosclerosis and it is able to predict both coronary and cerebral vascular events. No data exist on the association between cIMT and non valvular atrial fibrillation (NVAF) type. We conduct this study with the aim to analyze the association between abnormal cIMT and NVAF type. METHODS: A cross-sectional study of the "Atrial fibrillation Registry for Ankle-brachial index Prevalence Assessment-Collaborative Italian Study (ARAPACIS)" has been performed. Among 2027 patients enrolled in the ARAPACIS, 673 patients, who underwent carotid ultrasound examination to assess cIMT, were included in the study. RESULTS: Among the entire population, 478 patients (71%) had cIMT > 0.90 mm. Patients with an abnormal cIMT (>0.90 mm) were significantly older and more likely hypertensive, diabetic and with a previous history of stroke than those with normal cIMT ( 640.90 mm). These patients had more permanent/persistent NVAF and CHA2DS2-VASc score 65 2 (p < 0.0001) compared to those with cIMT <0.90 mm. Excluding all patients affected by previous cardiovascular disease, logistic regression analysis showed that independent predictors of abnormal cIMT were: age class 65-74 yrs. (p < 0.001), age class 6575 yrs. (p < 0.001), arterial hypertension (p < 0.001), calcium-channel blockers use (p < 0.001) and persistent/permanent NVAF (p = 0.001). CONCLUSION: Our findings show a high prevalence of abnormal cIMT in NVAF patients, reinforcing the concept that NVAF and systemic atherosclerosis are closely associated. Abnormal cIMT was particularly evident in persistent/permanent NVAF suggesting a more elevated atherosclerotic burden in patients with long-standing NVAF. TRIAL REGISTRATION: http://clinicaltrials.gov/ct2/show/NCT01161251

Prevalence of peripheral artery disease by abnormal ankle-brachial index in atrial fibrillation: implications for risk and therapy.

To the Editor: Nonvalvular atrial fibrillation (NVAF) is the most common sustained arrhythmia encountered in clinical practice and is associated with a 5-fold increased risk for stroke (1). Moreover, patients with NVAF often suffer from atherosclerotic complications such as acute myocardial infarction (AMI) (2). Peripheral artery disease (PAD) is an established marker of systemic atherosclerosis but its prevalence in NVAF is still unclear. We reasoned that inclusion of ankle-brachial index (ABI), which is an established tool for diagnosis of PAD (3), in the CHA2DS2-VASc (4) score would better define the prevalence of vascular disease. To address this issue, the Italian Society of Internal Medicine (SIMI) established an Italian registry documenting ABI in NVAF patients. The Atrial Fibrillation Registry for the ARAPACIS (Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study) study is an independent research project involving all Regional Councils of SIMI. The first objective of the study was to estimate the prevalence of ABI 640.90 in NVAF patients. Consecutive patients with NVAF referred to internal medicine wards were eligible for the enrollment. Enrollment started in October 2010 and continued until October 30, 2012. Patients were enrolled if they were 18 years or older and had a diagnosis of NVAF, recording during the qualifying admission/consultation or in the preceding 12 months, and if it was possible to obtain the ABI measurement. Exclusion criteria included the following: acquired or congenital valvular AF, active cancer, disease with life expectancy <3 years, hyperthyroidism and pregnancy. We initially planned to include 3,000 patients. The Data and Safety Monitoring Board (Online Appendix) decided to perform an interim analysis to assess the prevalence of ABI in the enrolled populations\u2014as a higher than expected prevalence of low ABI was detected\u2014and decided to interrupt the patients' enrollment. The sample size was amended as follows: a sample of 2,027 patients leads to the expected prevalence of 21% with a 95% confidence interval width of 3.5% (StataCorp LP, College Station, Texas). Among the 2,027 NVAF patients included in the study, hypertension was detected in 83%, diabetes mellitus in 23%, dyslipidemia in 39%, metabolic syndrome in 29%, and smoking in 15%. At least 1 atherosclerotic risk factor was detected in 90% of patients. The NVAF population was at high risk for stroke, with only 18% having a CHA2DS2-VASc score of 0 to 1, while 82% had a risk 652. Despite this, 16% were untreated with any antithrombotic drug, 19% were treated with antiplatelet drugs (APs), and 61% with oral anticoagulants (OAC); 4% of patients were treated with both APs and OAC. Among the AF population, 428 patients (21%) had ABI 640.90 compared with 1,381 patients, who had an ABI of 0.91 to 1.39 (69%); 204 patients (10%) had ABI 651.40 (Fig. 1). ABI recorded only in 1 leg was excluded from the analysis (n = 14). ABI 640.90 progressively increased from paroxysmal to permanent NVAF (18%, 21%, 24%; p = 0.0315). Figure 1. ABI Distribution of Any Category and CHA2DS2-VASc Score Including ABI 640.90 C = congestive heart failure (or left ventricular systolic dysfunction) (Points: 1), H = hypertension (Points: 1), A2 = Age 6575 years (Points: 2), D = diabetes mellitus (Points: 1), S2 = prior stroke or transient ischemic attack or thromboembolism (Points: 2); V = vascular disease (previous acute myocardial infarction, peripheral arterial disease, or aortic plaque) (Points: 1); A = age 65 to 74 years (Points: 1); Sc = sex category (female) (Points: 1). ABI = ankle brachial index. Figure optionsDownload full-size imageDownload high-quality image (447 K)Download as PowerPoint slide NVAF patients with ABI 640.90 were more likely to be hypertensive (88% vs. 82%; p = 0.032), diabetic (34% vs. 20%; p 0.90 (93% vs. 82%; p < 0.0001). Logistic regression analysis demonstrated that ABI 640.90 was significantly associated with a smoking habit (odds ratio [OR]: 1.99; 95% confidence interval [CI]: 1.48 to 2.66; p < 0.0001), diabetes (OR: 1.93; 95% CI: 1.51 to 2.46; p < 0.0001), age class 65 to 74 years (OR: 2.05; 95% CI: 1.40 to 3.07; p < 0.0001), age class 6575 years (OR: 3.12; 95% CI: 2.16 to 4.61; p < 0.0001), and history of previous transient ischemic attack/stroke (OR: 1.64; 95% CI: 1.20 to 2.24; p = 0.002). Vascular disease, as assessed by the history elements of CHA2DS2VASc score, was recorded in 17.3% of patients; inclusion of ABI 640.90 in the definition of vascular disease yielded a total prevalence of 33%. A higher prevalence of vascular disease was detected if ABI 640.90 was included in the CHA2DS2VASc score (Fig. 1). CHA2DS2VASc including ABI 640.90 was more associated with previous stroke (43%; OR: 1.85; 95% CI: 1.41 to 2.44; p < 0.0001) compared to CHA2DS2VASc with ABI 0.91 to 1.39 (23%; OR: 1.52; 95% CI: 1.10 to 2.11; p = 0.0117). To the best of our knowledge, there is no large-scale study that specifically examined the prevalence of ABI 640.90 in NVAF. In our population, 21% had ABI 640.90 indicating that NVAF is often associated with systemic atherosclerosis. The CHADS2 has been recently refined with the CHA2DS2-VASc score, which includes vascular disease as documented by a history of AMI, symptomatic PAD, or detection of atherosclerotic plaque in the aortic arch (4). Comparison of vascular prevalence as assessed by CHA2DS2-VASc score and/or ABI 640.90 is of interest to define the potentially positive impact of measuring ABI in the management of NVAF patients. Inclusion of ABI 640.90 in the definition of vascular disease greatly increased the prevalence of vascular disease, which increased from 17.3% (based on history alone) to 33% (based on ABI) in the entire population. If ABI 640.90 was encompassed in the definition of vascular disease of CHA2DS2-VASc score the prevalence of vascular disease increased in every risk class. Inclusion of ABI 640.90 in the CHA2DS2-VASc score allowed us to better define the risk profile of NVAF patients with an up-grading of the risk score in each CHA2DS2-VASc score category. This may have important therapeutic implications if the new score could be tested prospectively, as a higher number of NVAF patients would potentially be candidates for an anticoagulant treatment by measuring ABI. A prospective study is, therefore, necessary to validate the risk score of this new definition of vascular disease. In conclusion, this study provides the first evidence that one-fifth of NVAF patients had an ABI 640.90, indicating that it may represent a simple and cheap method to better define the prevalence of vascular disease in NVAF

Prevalence of peripheral artery disease by abnormal ankle-brachial index in atrial fibrillation: Implications for risk and therapy

To the Editor: Nonvalvular atrial fibrillation (NVAF) is the most common sustained arrhythmia encountered in clinical practice and is associated with a 5-fold increased risk for stroke (1). Moreover, patients with NVAF often suffer from atherosclerotic complications such as acute myocardial infarction (AMI) (2). Peripheral artery disease (PAD) is an established marker of systemic atherosclerosis but its prevalence in NVAF is still unclear. We reasoned that inclusion of ankle-brachial index (ABI), which is an established tool for diagnosis of PAD (3), in the CHA2DS2-VASc (4) score would better define the prevalence of vascular disease. Toaddress this issue, the ItalianSociety of InternalMedicine (SIMI) established an Italian registry documenting ABI inNVAF patients. The Atrial Fibrillation Registry for the ARAPACIS (Ankle- brachial Index Prevalence Assessment: Collaborative Italian Study) study is an independent research project involving all Regional Councils of SIMI. The first objective of the study was to estimate the prevalence of ABI 0.90 in NVAF patients. Consecutive patients with NVAF referred to internal medicine wards were eligible for the enrollment. Enrollment started in October 2010 and continued until October 30, 2012. Patients were enrolled if they were 18 years or older and had a diagnosis of NVAF, recording during the qualifying admission/consultation or in the preceding 12 months, and if it was possible to obtain the ABI measurement. Exclusion criteria included the following: acquired or congenital valvular AF, active cancer, disease with life expectancy &lt;3 years, hyperthyroidism and pregnancy. We initially planned to include 3,000 patients. The Data and Safety Monitoring Board (Online Appendix) decided to perform an interim analysis to assess the prevalence of ABI in the enrolled populationsdas a higher than expected prevalence of low ABI was detecteddand decided to interrupt the patients’ enrollment. The sample size was amended as follows: a sample of 2,027 patients leads to the expected prevalence of 21% with a 95% confidence interval width of 3.5% (StataCorp LP, College Station, Texas). Among the 2,027 NVAF patients included in the study, hyper- tension was detected in 83%, diabetes mellitus in 23%, dyslipidemia in 39%, metabolic syndrome in 29%, and smoking in 15%. At least 1 atherosclerotic risk factor was detected in 90% of patients. The NVAF population was at high risk for stroke, with only 18% having a CHA2DS2-VASc score of 0 to 1, while 82% had a risk 2. Despite this, 16% were untreated with any antith- rombotic drug, 19% were treated with antiplatelet drugs (APs), and 61% with oral anticoagulants (OAC); 4% of patients were treated with both APs and OAC. Among the AF population, 428 patients (21%) had ABI 0.90 (69%); 204 patients (10%) had ABI 1.40 (Fig. 1). ABI recorded only in 1 leg was excluded from the analysis (n 1⁄4 14). ABI 0.90 progressively increased from paroxysmal to permanent NVAF (18%, tensive (88% vs. 82%; p 1⁄4 0.032), diabetic (34% vs. 20%; p &lt; 0.0001), or smokers (20% vs. 14%; p 1⁄4 0.0008), or to have experi- enced transient ischemic attack or stroke (17% vs. 10%; p &lt; 0.001). 21%, 24%; p 1⁄4 0.0315). NVAF patients with ABI 0.90 were more likely to be hyper- NVAF patients with ABI 0.90 had a higher percentage of CHA2DS2-VASc score 2 compared with those with ABI &gt;0.90 (93% vs. 82%; p &lt; 0.0001). significantly associated with a smoking habit (odds ratio [OR]: 1.99; 95% confidence interval [CI]: 1.48 to 2.66; p &lt; 0.0001), diabetes (OR: 1.93; 95% CI: 1.51 to 2.46; p &lt; 0.0001), age class 65 to 74 years (OR: 2.05; 95% CI: 1.40 to 3.07; p &lt; 0.0001), age Logistic regression analysis demonstrated that ABI 0.90 was class 75 years (OR: 3.12; 95% CI: 2.16 to 4.61; p &lt; 0.0001), and history of previous transient ischemic attack/stroke (OR: 1.64; 95% CI: 1.20 to 2.24; p 1⁄4 0.002). Vascular disease, as assessed by the history elements of CHA2DS2VASc score, was recorded in 17.3% of patients; inclu- sion of ABI 0.90 in the definition of vascular disease yielded a total prevalence of 33%. A higher prevalence of vascular disease was detected if ABI 0.90 was included in the CHA2DS2VASc score (Fig. 1). CHA2DS2VASc including ABI 0.90 was more associated with previous stroke (43%; OR: 1.85; 95% CI: 1.41 to 2.44; p &lt; 0.0001) compared to CHA2DS2VASc with ABI 0.91 to 1.39 (23%; OR: 1.52; 95% CI: 1.10 to 2.11; p 1⁄4 0.0117). To the best of our knowledge, there is no large-scale study that specifically examined the prevalence of ABI 0.90 in NVAF. In our population, 21% had ABI 0.90 indicating that NVAF is often associated with systemic atherosclerosis. The CHADS2 has been recently refined with the CHA2DS2- VASc score, which includes vascular disease as documented by a history of AMI, symptomatic PAD, or detection of atheroscle- rotic plaque in the aortic arch (4). Comparison of vascular prevalence as assessed by CHA2DS2- NVAF patients. Inclusion of ABI 0.90 in the definition of vascular disease greatly increased the prevalence of vascular disease, which increased from 17.3% (based on history alone) to 33% (based compared with 1,381 patients, who had an ABI of 0.91 to 1.39 to better define the risk profile ofNVAFpatients with an up-grading of the risk score in each CHA2DS2-VASc score category. This may have important therapeutic implications if the new score could be tested prospectively, as a higher number of NVAF patients would on ABI) in the entire population. If ABI 0.90 was encompassed in the definition of vascular disease of CHA2DS2-VASc score the prevalence of vascular disease increased in every risk class. Inclusion of ABI0.90 in theCHA2DS2-VASc score allowed us VASc score and/or ABI 0.90 is of interest to define the poten- tially positive impact of measuring ABI in the management of potentially be candidates for an anticoagulant treatment by measuring ABI. A prospective study is, therefore, necessary to validate the risk score of this new definition of vascular disease. In conclusion, this study provides the first evidence that one-fifth of NVAF patients had an ABI 0.90, indicating that it may represent a simple and cheap method to better define the prevalence of vascular disease in NVAF