Body mass index influences the response to infliximab in ankylosing spondylitis

INTRODUCTION: The excess of adipose tissue in obese individuals may have immunomodulating properties and pharmacokinetic consequences. The aim of this study was to determine whether body mass index (BMI) affects response to infliximab (IFX) in ankylosing spondylitis (AS) patients. METHODS: In 155 patients retrospectively included with active AS, the BMI was calculated before initiation of IFX treatment (5 mg/kg intravenously). After 6 months of treatment, changes from baseline in BASDAI, Visual Analogue Scale (VAS) pain, C-reactive protein (CRP) level, and total dose of nonsteroidal antiinflammatory drug (NSAID) were dichotomized with a threshold corresponding to a decrease of 50% of initial level of the measure, into binary variables assessing response to IFX (BASDAI50, VAS50, CRP50, NSAID50). Whether the BMI was predictive of the response to IFX therapy according to these definitions was assessed with logistic regression. RESULTS: Multivariate analysis found that a higher BMI was associated with a lower response for BASDAI50 (P = 0.0003; OR, 0.87; 95% CI (0.81 to 0.94)), VAS50 (P < 0.0001; OR, 0.87; 95% CI (0.80 to 0.93)); CRP50 (P = 0.0279; OR, 0.93; 95% CI (0.88 to 0.99)), and NSAID50 (P = 0.0077; OR, 0.91; 95% CI (0.85 to 0.97)), criteria. According to the three WHO BMI categories, similar results were found for BASDAI50 (77.6%, 48.9%, and 26.5%; P < 0.0001), VAS50 (72.6%, 40.4%, and 16.7%; P < 0.0001); CRP50 (87.5%, 65.7%, and 38.5%; P = 0.0001), and NSAID50 (63.2%, 51.5%, and 34.6%; P = 0.06). CONCLUSIONS: This study provides the first evidence that a high BMI negatively influences the response to IFX in AS. Further prospective studies, including assessment of the fat mass, pharmacokinetics, and adipokines dosages are mandatory to elucidate the role of obesity in AS IFX response

Independent Behavior of Commensal Flora for Carriage of Fluoroquinolone-Resistant Bacteria in Patients at Admission▿

The important role of commensal flora as a natural reservoir of bacterial resistance is now well established. However, whether the behavior of each commensal flora is similar to that of other floras in terms of rates of carriage and risk factors for bacterial resistance is unknown. During a 6-month period, we prospectively investigated colonization with fluoroquinolone-resistant bacteria in the three main commensal floras from hospitalized patients at admission, targeting Escherichia coli in the fecal flora, coagulase-negative Staphylococcus (CNS) in the nasal flora, and α-hemolytic streptococci in the pharyngeal flora. Resistant strains were detected on quinolone-containing selective agar. Clinical and epidemiological data were collected. A total of 555 patients were included. Carriage rates of resistance were 8.0% in E. coli, 30.3% in CNS for ciprofloxacin, and 27.2% in streptococci for levofloxacin; 56% of the patients carried resistance in at least one flora but only 0.9% simultaneously in all floras, which is no more than random. Risk factors associated with the carriage of fluoroquinolone-resistant strains differed between fecal E. coli (i.e., colonization by multidrug-resistant bacteria) and nasal CNS (i.e., age, coming from a health care facility, and previous antibiotic treatment with a fluoroquinolone) while no risk factors were identified for pharyngeal streptococci. Despite high rates of colonization with fluoroquinolone-resistant bacteria, each commensal flora behaved independently since simultaneous carriage of resistance in the three distinct floras was uncommon, and risk factors differed. Consequences of environmental selective pressures vary in each commensal flora according to its local specificities (clinical trial NCT00520715 [http://clinicaltrials.gov/ct2/show/NCT00520715])

Increased arterial stiffness in systemic lupus erythematosus (SLE) patients at low risk for cardiovascular disease: a cross-sectional controlled study.

Cardiovascular disease (CVD) is a major cause of death in systemic lupus erythematosus (SLE) patients. Although the risk for cardiovascular events in patients with SLE is significant, the absolute number of events per year in any given cohort remains small. Thus, CVD risks stratification in patients with SLE focuses on surrogate markers for atherosclerosis at an early stage, such as reduced elasticity of arteries. Our study was designed to determine whether arterial stiffness is increased in SLE patients at low risk for CVD and analyze the role for traditional and non-traditional CVD risk factors on arterial stiffness in SLE. Carotid-femoral pulse wave velocity (PWV) was prospectively assessed as a measure of arterial stiffness in 41 SLE patients and 35 controls (CTL). Adjustment on age or Framingham score was performed using a logistic regression model. Factors associated with PWV were identified separately in SLE patients and in controls using Pearson's correlation coefficient for univariate analysis and multiple linear regression for multivariate analysis. SLE patients and controls displayed a low 10-year risk for CVD according to Framingham score (1.8±3.6% in SLE vs 1.6±2.8% in CTL, p = 0.46). Pulse wave velocity was, however, higher in SLE patients (7.1±1.6 m/s) as compared to controls (6.3±0.8 m/s; p = 0.01, after Framingham score adjustment) and correlated with internal carotid wall thickness (p = 0.0017). In multivariable analysis, only systolic blood pressure (p = 0.0005) and cumulative dose of glucocorticoids (p = 0.01) were associated with PWV in SLE patients. Interestingly, the link between systolic blood pressure (SBP) and arterial stiffness was also confirmed in SLE patients with normal systolic blood pressure. In conclusion, arterial stiffness is increased in SLE patients despite a low risk for CVD according to Framingham score and is associated with systolic blood pressure and glucocorticoid therapy

Predictors of Study Attrition in a Randomized Controlled Trial Evaluating a Perinatal Home-Visiting Program with Mothers with Psychosocial Vulnerabilities.

Randomised controlled trials evaluating perinatal home-visiting programs are frequently confronted with the problem of high attrition rates. The aim of the present study is to identify predictors of study attrition in a trial evaluating a perinatal home-visiting program in France.CAPEDP is a French randomized trial comparing a perinatal home-visiting program using psychologists versus usual care (N = 440). The first assessment was at inclusion into the trial at the 27th week of pregnancy and the final assessment when the child reached the age of two. Attrition rates were calculated at 3 and 24 months postpartum. Stepwise logistic regression was used to identify predictors of early (between inclusion and 3 months postpartum) and later (between 3 and 24 months postpartum) attrition among social, psychological and parenting factors.Attrition rates were 17% and 63% at 3 and 24 months respectively. At 24 months, there was significantly more attrition in the control arm (70.6%) compared to the intervention arm (55.2%). Five independent predictors of early attrition were identified: having already had an abortion; having greater attachment insecurity as measured with the Vulnerable Attachment Style Questionnaire (VASQ); having lower global severity of psychiatric symptoms as assessed with the Symptom Check-List (SCL-90) at inclusion, being neither currently employed nor studying; and declaring no tobacco consumption during pregnancy. Being randomized into the control arm, having undergone early parental loss before age 11 and having lower global severity of psychiatric symptoms (SCL-90) at 3 months postpartum were the only variables associated with later attrition.This study provides key information for identifying mothers who may require specific support to avoid study attrition in trials evaluating a home-visiting program

Patient-important outcomes in randomized controlled trials in critically ill patients: a systematic review

International audienceBackground: Intensivists’ clinical decision making pursues two main goals for patients: to decrease mortality and to improve quality of life and functional status in survivors. Patient-important outcomes are gaining wide acceptance in most fields of clinical research. We sought to systematically review how well patient-important outcomes are reported in published randomized controlled trials (RCTs) in critically ill patients.Methods: Literature search was conducted to identify eligible trials indexed from January to December 2013. Articles were eligible if they reported an RCT involving critically ill adult patients. We excluded phase II, pilot and physiological crossover studies. We assessed study characteristics. All primary and secondary outcomes were collected, described and classified using six categories of outcomes including patient-important outcomes (involving mortality at any time on the one hand and quality of life, functional/cognitive/neurological outcomes assessed after ICU discharge on the other).Results: Of the 716 articles retrieved in 2013, 112 RCTs met the inclusion criteria. Most common topics were mechanical ventilation (27%), sepsis (19%) and nutrition (17%). Among the 112 primary outcomes, 27 (24%) were patient-important outcomes (mainly mortality, 21/27) but only six (5%) were patient-important outcomes besides mortality assessed after ICU discharge (functional disability = 4; quality of life = 2). Among the 598 secondary outcomes, 133 (22%) were patient-important outcomes (mainly mortality, 92/133) but only 41 (7%) were patient-important outcomes besides mortality assessed after ICU discharge (quality of life = 20, functional disability = 14; neurological/cognitive performance = 5; handicap = 1; post-traumatic stress = 1). Seventy-three RCTs (65%) reported at least one patient-important outcome but only 11 (10%) reported at least one patient-important outcome besides mortality assessed after ICU discharge.Conclusion: Patient-important outcomes are rarely primary outcomes in RCTs in critically ill patients published in 2013. Among them, mortality accounted for the majority. We promote the use of patient-important outcomes in critical care trials

IMPACT OF A RANDOMIZED HOME-VISITING TRIAL ON INFANT SOCIAL WITHDRAWAL IN THE CAPEDP PREVENTION STUDY

International audienc

Prospective Evaluation of In-hospital Mortality with the P-POSSUM Scoring System in Patients Undergoing Major Digestive Surgery

Background The P-POSSUM score, the most well known of predictive scores for postoperative mortality, requires validation for population and setting. Methods Validation methods included discrimination (C-index statistic), observed: expected (O:E) ratio, calibration with the Hosmer-Lemeshow test, and subgroup analysis (emergency surgery, cancer, age, organs). The study included 3,881 multisite patients undergoing major digestive surgery in France. Results Discrimination via the receiver operating characteristic curve was good (C-index = 0.87). The overall O: E ratio was 1 (95% confidence interval ([95 % CI]: 0.88-1.13), and therefore the quality of the surgical performance is within normal ranges. The O: E ratio, calculated by risk ranges, showed overestimation in the low risk range, especially in the 3 % to 6 % and 6 % to 10 % ranges. Calibration was poor (p &lt; 0.001). The model deviated from the normal pattern of calibration, with mortality lower than expected in the high-risk range. Subgroup analysis found reasonable to good discrimination of populations (C-index ranging from 0.78 to 0.93 except for liver surgery [0.67]) while calibration of individuals remained poor (p &lt; 0.001 to 0.02). Conclusions Good discrimination, as well as nonsignificant overall O: E values, makes P-POSSUM a valuable tool when it is used for surgical audit to compare mortality between populations for major digestive surgery. Conversely, poor calibration (goodness-of-fit), especially in subgroup analysis, and underestimation or overestimation of O: E ratios considerably limits the value of P-POSSUM for prediction of mortality in individuals. Therefore P-POSSUM should not be used to predict outcomes for one particular patient

Can we improve transthoracic echocardiography training in non-cardiologist residents? Experience of two training programs in the intensive care unit

International audienceBackgroundTo evaluate the diagnostic performances of two training programs for residents with no prior ultrasound experience to reach competences in extended basic critical care transthoracic echocardiography (CCE) including Doppler capabilities.MethodsThis is a prospective observational study in two intensive care units of teaching hospitals. Group I (five residents) completed a short training program (4-h theory; 3-h practical); group II (six residents) completed a longer training program (6-h theory; 12-h practical). The residents and an expert examined all patients who required a transthoracic echocardiography. Their agreement studied by Cohen’s κ coefficient, concordance coefficient correlation (CCC) and Bland–Altman plots was used as an indicator of program effectiveness.ResultsGroup I performed 136 CCEs (mean/resident 27; range 22–32; 65 in ventilated patients) in 115 patients (62 men; 64 ± 18 years; Simplified Acute Physiologic Score [SAPS] II 37 ± 18). Group II performed 158 CCEs (mean/resident 26; range 21–31; 65 in ventilated patients) in 108 patients (64 men; 58 ± 17 years; SAPS II 42 ± 22). Both groups adequately assessed left ventricular (LV) systolic function (κ 0.75, 95 % confidence interval [CI] 0.64–0.86; κ 0.77, 95 % CI 0.66–0.88, respectively) and pericardial effusion (κ 0.83, 95 % CI 0.67–0.99; κ 0.76, 95 % CI 0.60–0.93, respectively). Group II appraised severe right ventricular dilatation and significant left-sided valve disease with good to very good agreement (κ 0.80, 95 % CI 0.56–0.96; κ 0.79, 95 % CI 0.66–0.93, respectively). Regarding left ventricular ejection fraction, E/A ratio, E/e′ ratio and aortic peak velocity assessed by group II, CCCs were all >0.70 and the bias (mean difference) ±SD on Bland–Altman analysis was 1.3 ± 8.8 %, 0 ± 0.3, 0.4 ± 2.2 and 0.1 ± 0.4 m/s, respectively. Detection of paradoxical septum (κ 0.65, 95 % CI 0.37–0.93), of heterogeneous LV contraction (κ 0.49, 95 % CI 0.33–0.65) and of respiratory variation of the inferior vena cava (κ 0.27, 95 % CI 0.09–0.45), as well as stroke volume measurement (CCC 0.65, 95 % CI 0.54–0.74; bias ± SD −1.4 ± 4.7 cm), was appraised by group II with moderate agreement requiring probably more comprehensive training.ConclusionsAlthough a training program blending 6-h theory and 12-h practical may be adapted to achieve some essential competences, it seems to be insufficiently to perform a complete extended basic critical care transthoracic echocardiography including Doppler capabilities

Carotid plaque and intima-media thickness and the incidence of ischemic events in patients with atherosclerotic vascular disease

We aimed to evaluate whether carotid intima-media thickness (CIMT) or the presence of plaque can confer additional predictive value of future cardiovascular (CV) ischemic events in patients with pre-existing atherosclerotic vascular disease. We identified 2317 patients enrolled in the REduction of Atherothrombosis for Continued Health (REACH) registry who had atherosclerotic vascular disease and baseline CIMT measurements. The entire range of CIMT was divided into quartiles and the fourth quartile (? 1.5 mm) was defined as carotid plaque. Mean ± standard deviation baseline CIMT was 1.31 ± 0.65 mm. Associated CV ischemic events and vascular-related hospitalizations were evaluated over a 2-year follow-up. There was a positive increase in adjusted hazard ratios (HRs) for all-cause mortality (p = 0.04 for trend) and the quadruple endpoint (CV death, myocardial infarction (MI), stroke, hospitalization for CV events) with increasing quartiles of CIMT (p = 0.0008 for trend), which was mainly driven by the fourth quartile (carotid plaque). HRs for all-cause mortality, CV death, CV death/MI/stroke and the quadruple endpoint comparing the highest (carotid plaque) with the lowest CIMT quartile were 2.09 (95% CI, 1.07-4.10; p = 0.03); 2.49 (1.10-5.67; p = 0.03); 1.71 (1.10-2.67; p = 0.02); and 1.73 (1.31-2.27; p = 0.0001). In conclusion, our analyses suggest that the presence of carotid plaque, rather than the thickness of intima-media, appears to be associated with increased risk of CV morbidity and mortality, but confirmation of these findings in other population and prospective studies is required