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91.

Background and aims

Since accelerated atherosclerosis has been reported in systemic lupus erythematosus (SLE), predictive biomarkers of cardiovascular disease (CVD) are needed. Among non-traditional risk factors, bone mineral density (BMD) has been related to CVD. However, its role in SLE remains controversial. This study aims to analyze the associations of subclinical atherosclerosis with traditional and non-traditional CV risk factors.

Methods and results

In a cross-sectional study, atherosclerosis burden was compared between 112 female SLE patients and 31 controls. Plaque number and carotid intima-media wall thickness (cIMT) were assessed by ultrasonography. In a retrospective study, BMD determinations obtained 5-years before the ultrasonography assessment were analyzed in a subgroup of 62 patients. Plaque frequency was increased in SLE, even in patients without CV events or carotid wall thickening. cIMT was increased in patients with CVD, positively correlated with body mass index (BMI). Interestingly, a paradoxical effect of BMI on carotid parameters was observed. Whereas underweight patients (BMI < 20) showed increased prevalence of carotid plaques with low cIMT, those with BMI > 30 showed higher cIMT and plaque burden. Overweight patients (25 < BMI<30) exhibited both elevated cIMT and plaque number. BMI was an independent predictor of BMD. In our retrospective study, patients with either clinical or subclinical CVD exhibited lower BMD levels than their CV-free counterparts. A low lumbar spine BMD independently predicted CVD development after adjusting for confounders.

Conclusion

SLE was associated with a higher subclinical atherosclerosis burden, a bimodal effect being observed for BMI. Decreased BMD can be a CV risk biomarker in SLE.  相似文献   
92.

Background

Scientific guidelines consider atrial fibrillation (AF) complicating degenerative mitral regurgitation (DMR) a debated indication for surgery.

Objectives

This study analyzed the prognostic/therapeutic implications of AF at DMR diagnosis and long-term.

Methods

Patients were enrolled in the MIDA (Mitral Regurgitation International Database) registry, which reported the consecutive, multicenter, international experience with DMR due to flail leaflets echocardiographically diagnosed.

Results

Among 2,425 patients (age 67 ± 13 years; 71% male, 67% asymptomatic, ejection fraction 64 ± 10%), 1,646 presented at diagnosis with sinus rhythm (SR), 317 with paroxysmal AD, and 462 with persistent AF. Underlying clinical/instrumental characteristics progressively worsened from SR to paroxysmal to persistent AF. During follow-up, paroxysmal and persistent AF were associated with excess mortality (10-year survival in SR and in paroxysmal and persistent AF was 74 ± 1%, 59 ± 3%, and 46 ± 2%, respectively; p < 0.0001), that persisted 20 years post-diagnosis and independently of all baseline characteristics (p values <0.0001). Surgery (n = 1,889, repair 88%) was associated with better survival versus medical management, regardless of all baseline characteristics and rhythm (adjusted hazard ratio: 0.26; 95% confidence interval: 0.23 to 0.30; p < 0.0001) but post-surgical outcome remained affected by AF (10-year post-surgical survival in SR and in paroxysmal and persistent AF was 82 ± 1%, 70 ± 4%, and 57 ± 3%, respectively; p < 0.0001).

Conclusions

AF is a frequent occurrence at DMR diagnosis. Although AF is associated with older age and more severe presentation of DMR, it is independently associated with excess mortality long-term after diagnosis. Surgery is followed by improved survival in each cardiac rhythm subset, but persistence of excess risk is observed for each type of AF. Our study indicates that detection of AF, even paroxysmal, should trigger prompt consideration for surgery.  相似文献   
93.

Background

There are conflicting data regarding the relative effectiveness of renal sympathetic denervation (RSD) in patients with hypertension.

Objectives

The purpose of this study was to evaluate the blood pressure (BP) response after RSD in sham-controlled randomized trials.

Methods

Databases were searched through June 30, 2018. Randomized trials (RCTs) with ≥50 patients comparing catheter-based RSD with a sham control were included. The authors calculated summary treatment estimates as weighted mean differences (WMD) with 95% confidence intervals (CIs) using random-effects meta-analysis.

Results

The analysis included 977 patients from 6 trials. The reduction in 24-h ambulatory systolic blood pressure (ASBP) was significantly greater for patients treated with RSD than sham procedure (WMD ?3.65 mm Hg, 95% CI: ?5.33 to ?1.98; p < 0.001). Compared with sham, RSD was also associated with a significant decrease in daytime ASBP (WMD ?4.07 mm Hg, 95% CI: ?6.46 to ?1.68; p < 0.001), office systolic BP (WMD ?5.53 mm Hg, 95% CI: ?8.18 to ?2.87; p < 0.001), 24-h ambulatory diastolic BP (WMD ?1.71 mm Hg, 95% CI: ?3.06 to ?0.35; p = 0.01), daytime ambulatory diastolic BP (WMD ?1.57 mm Hg, 95% CI: ?2.73 to ?0.42; p = 0.008), and office diastolic BP (WMD ?3.37 mm Hg, 95% CI: ?4.86 to ?1.88; p < 0.001). Compared with first-generation trials, a significantly greater reduction in daytime ASBP was observed with RSD in second-generation trials (6.12 mm Hg vs. 2.14 mm Hg; p interaction = 0.04); however, this interaction was not significant for 24-h ASBP (4.85 mm Hg vs. 2.23 mm Hg; p interaction = 0.13).

Conclusions

RSD significantly reduced blood pressure compared with sham control. Results of this meta-analysis should inform the design of larger, pivotal trials to evaluate the long-term efficacy and safety of RSD in patients with hypertension.  相似文献   
94.

Background

Physicians treating nonvalvular atrial fibrillation (AF) assess stroke and bleeding risks when deciding on anticoagulation. The agreement between empirical and physician-estimated risks is unclear. Furthermore, the association between patient and physician sex and anticoagulation decision-making is uncertain.

Methods

We pooled data from 2 national primary care physician chart audit databases of patients with AF (Facilitating Review and Education to Optimize Stroke Prevention in Atrial Fibrillation and Coordinated National Network to Engage Physicians in the Care and Treatment of Patients with Atrial Fibrillation Chart Audit) with a combined 1035 physicians (133 female, 902 male) and 10,927 patients (4567 female and 6360 male).

Results

Male physicians underestimated stroke risk in female patients and overestimated risk in male patients. Female physicians estimated stroke risk well in female patients but underestimated the risk in male patients. Risk of bleeding was underestimated in all. Despite differences in risk assessment by physician and patient sex, > 90% of patients received anticoagulation across all subgroups. There was modest agreement between physician estimated and calculated (ie, CHADS2 score) stroke risk: Kappa scores were 0.41 (0.35-0.47) for female physicians and 0.34 (0.32-0.36) for male physicians.

Conclusions

Our study is the first to examine the association between patient and physician sex influences and stroke and bleeding risk estimation in AF. Although there were differences in agreement between physician estimated stroke risk and calculated CHADS2 scores, these differences were small and unlikely to affect clinical practice; further, despite any perceived differences in the accuracy of risk assessment by sex, most patients received anticoagulation.  相似文献   
95.

Background and aims

It is not known whether non alcoholic fatty liver disease (NAFLD) is a risk factor for diabetes in non obese, non centrally-obese subjects. Our aim was to investigate relationships between fatty liver, insulin resistance and a biomarker score for liver fibrosis with incident diabetes at follow up, in subjects who were neither obese nor centrally-obese.

Methods and results

As many as 70,303 subjects with a body mass index (BMI) < 25 kg/m2 and without diabetes were followed up for a maximum of 7.9 years. At baseline, fatty liver was identified by liver ultrasound, insulin resistance (IR) by homeostatic model assessment of insulin resistance (HOMA-IR) ≥2.0, and central obesity by waist circumference (waist circumference ≥90 cm (men) and ≥85 cm (women). The Fibrosis-4 (FIB-4 score) was used to estimate extent of liver fibrosis. Cox proportional hazards models adjusted for confounders were used to estimate hazard ratios (aHRs) for incident diabetes. As many as 852 incident cases of diabetes occurred during follow up (median [IQR] 3.71 [2.03] years). Mean ± SD BMI was 22.8 ± 1.8 and 21.7 ± 2.0 kg/m2 in subjects with and without diabetes at follow up. In subjects without central obesity and with fatty liver, aHRs (95% CI) for incident diabetes at follow up were 2.17 (1.56, 3.03) for men, and 2.86 (1.50,5.46) for women. Similar aHRs for incident diabetes occurred with fatty liver, IR and the highest quartile of FIB-4 combined, in men; and there was a non significant trend toward increased risk in women.

Conclusions

In normal weight, non-centrally obese subjects NAFLD is an independent risk factor for incident diabetes.  相似文献   
96.

Background

Nutrition specialists are considered key members of multicomponent pediatric weight management intervention teams, but to date, their contribution has not been quantified.

Objective

The purpose of this systematic review was to estimate the effectiveness of interventions provided by treatment teams that include a nutrition specialist on pediatric weight management outcomes, including body mass index (BMI), BMI z score, and waist circumference when compared with treatment teams that do not include a nutrition specialist.

Methods

The results of a comprehensive literature search and a systematic and more targeted update of that search were included in the meta-analyses: a search of controlled trials published between July 2005 and April 2012, conducted during the 2015 Pediatric Weight Management Update Project of the Academy of Nutrition and Dietetics Evidence Analysis Library, and an update search of controlled trials published between May 2012 and December 2015 focusing on a more specific topic within the previous search. Studies included overweight and/or obese patients aged 6 to 18 years receiving outpatient weight management treatment. Data extraction of all studies identified was performed using a standardized tool. The resulting data from the search and the systematic update were merged. Ninety-nine studies and 209 study arms were included in the analysis. An exploratory meta-analysis using alternative meta-analytic methods designed for complex, heterogenous interventions was conducted to identify relative contributions by intervention provider category at selected time points. Meta-regression analyses were used to evaluate significant differences from the reference category for each provider category.

Results

The nutrition specialist-only condition resulted in increased reductions in BMI z score compared with behavioralist-only, combined nutrition specialist and behavioralist, and neither nutrition specialist or behavioralist category (reference) throughout the analysis. Meta-regression analysis indicated that the difference in BMI z score between the nutrition specialist-only category and the reference category was significant at 3 to <6 months, 6 months to <1 year, and 1-year to 2-year time points (P=0.01, P=0.05, and P=0.01, respectively). There were smaller increases in BMI over time for the nutrition specialist-only provider category compared with reference categories, and this difference was significant at the 3 to <6 months and 1-year to 2-years time points (P=0.001 and P=0.05, respectively). There were no significant differences among provider categories for waist circumference at any time point.

Conclusions

Indirect evidence indicated that pediatric weight management outcomes for BMI z score and BMI at selected time points appeared to be better when a nutrition specialist was involved in delivering care.  相似文献   
97.
BackgroundThe efficacy of ticagrelor in the long-term post–ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain.ObjectivesThe purpose of this study was to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy.MethodsThis international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age <75 years) with STEMI receiving fibrinolytic therapy. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). The key outcomes were cardiovascular mortality, myocardial infarction, or stroke, and the same composite outcome with the addition of severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events at 12 months.ResultsThe combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups.ConclusionAmong patients age <75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel. (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis [TREAT]; NCT02298088)  相似文献   
98.

Introduction

There is an urgent need for new anti-tuberculosis (TB) drugs and optimization of current TB treatment. Moxifloxacin and linezolid are valuable options for the treatment of drug-resistant TB; however, it is crucial to find a dose at which these drugs not only show high efficacy but also suppress the development of further drug resistance.

Methods

Activity of moxifloxacin and linezolid against Mycobacterium tuberculosis was studied in the hollow-fiber infection model system in log-phase growth under neutral pH and slow growth in an acidic environment. Doses that achieved maximum bacterial kill while suppressing the emergence of drug resistance were determined. Through Monte Carlo simulations the quantitative output of this in vitro study was bridged to the human patient population to inform optimal dosage regimens while accounting for clinical minimum inhibitory concentration (MIC) distributions.

Results and Discussion

Moxifloxacin activity was significantly decreased in an acidified environment. The loss of activity was compensated by accumulation of the drug in TB lung lesions; therefore, moderate efficacy can be expected. Moxifloxacin 800 mg/day is the dose that most likely leads to resistance suppression while exerting maximum bacterial kill. Linezolid demonstrated very good activity even at a reduced pH. Linezolid 900 mg once-daily (QD) is likely to achieve a maximum killing effect and prevent the emergence of drug resistance; 600 mg QD in a robust drug regimen may have similar potential.  相似文献   
99.

Purpose

To qualitatively and quantitatively compare unenhanced ultra-low-dose chest computed tomography (ULD-CT) acquired at 80 kVp and 135 kVp.

Materials and methods

Fifty-one patients referred for unenhanced chest CT were prospectively included. There were 29 men and 22 women, with a mean age of 64.7 ± 11.6 (SD) years (range: 35–91 years) and a mean body mass index of 26.2 ± 6.3 (SD) (range: 17–54.9). All patients underwent two different ULD-CT protocols (80 kVp-40 mA and 135 kVp-10 mA). Image quality of both ULD-CT examinations using a 5-level scale as well as assessability of 6 predetermined lung parenchyma lesions were blindly evaluated by three radiologists and compared using a logistic regression model. Image noise of the two protocols was compared with Wilcoxon signed-rank test.

Results

The mean dose-length product at 80 kVp and at 135 kVp were 14.7 ± 1.8 (SD) mGy.cm and 15.6 ± 1.9 (SD) mGy.cm, respectively (P < 0.001). Image noise was significantly lower at 135 kVp (58.9 ± 12.4) than at 80 kVp (74.7 ± 14.5) (P < 0.001). For all readers and for all examinations, the 135 kVp protocol yielded better image quality than 80 kVp protocol, with a mean qualitative score of 4.5 ± 0.7 versus 3.9 ± 0.8 (P < 0.001). The 135 kVp protocol was significantly more often of diagnostic quality than the 80 kvp protocol (92.3% versus 77.8%, respectively) (P < 0.001) and was less prone to image quality deterioration in obese patients. Parenchymal lesions were never better depicted on the 80 kVp protocol than with the 135 kVp protocol.

Conclusion

Unenhanced chest ULD-CT should be acquired at a high kilovoltage and low current, such as 135 kVp-10 mA, over a low kilovoltage and high current protocol.  相似文献   
100.
Background and purpose — No difference in outcome has been demonstrated comparing cemented taper-slip and composite beam designs in short-term randomised trials; we assessed outcome differences using a registry analysis.

Patients and methods — All cemented stems with > 100 implantations were identified in the National Joint Registry of England and Wales from April 1, 2003 to September 31, 2013 and categorised as taper-slip or composite beam. Survival analyses using Kaplan–Meier and Cox regression were performed.

Results — We identified 292,987 cemented arthroplasties, of which 16% (47,586) were composite beam stems, with taper-slip stems making up the remainder (n = 245,401). There was a statistically significant increased chance of revision in the composite beam group compared with the taper-slip group (1.7% vs 1.3%, p < 0.001) but statistically no significant differences of survival estimates (p = 0.06). When the 2 groups were segregated to delineate the most implanted model in each category, the differences became more profound with the most implanted taper-slip stem (Exeter V40) showing statistically and clinically significant superior 8-year survival: 97.9% compared with 97.6% for all other taper-slip; 97.5% for the most implanted composite beam (Charnley cemented stem); and 97.7% for all other composite beam.

Interpretation — There was an increased incidence of revision for composite beam stems. The most implanted taper-slip stem demonstrated significant survival advantage vs. all other stems.  相似文献   

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