CT features of community-acquired pneumonia at the emergency department.

BACKGROUND: Chest computed tomography (CT) was reported to improve the diagnosis of community-acquired pneumonia (CAP) as compared to chest X-ray (CXR). The aim of this study is to describe the CT-patterns of CAP in a large population visiting the emergency department and to see if some of them are more frequently missed on CXR. MATERIALS AND METHODS: This is an ancillary analysis of the prospective multicenter ESCAPED study including 319 patients. We selected the 163 definite or probable CAP based on adjudication committee classification; 147 available chest CT scans were reinterpreted by 3 chest radiologists to identify CAP patterns. These CT-patterns were correlated to epidemiological, biological and microbiological data, and compared between false negative and true positive CXR CAP. RESULTS: Six patterns were identified: lobar pneumonia (51/147, 35%), including 35 with plurifocal involvement; lobular pneumonia (43/147, 29%); unilobar infra-segmental consolidation (24/147, 16%); bronchiolitis (16/147, 11%), including 4 unilobar bronchiolitis; atelectasis and bronchial abnormalities (8/147, 5.5%); interstitial pneumonia (5/147, 3.5%). Bacteria were isolated in 41% of patients with lobar pneumonia-pattern (mostly Streptococcus pneumoniae and Mycoplasma pneumonia) versus 19% in other patients (p = 0.01). Respiratory viruses were equally distributed within all patterns. CXR was falsely negative in 46/147 (31%) patients. Lobar pneumonia was significantly less missed on CXR than other patterns (p = 0.003), especially lobular pneumonia and unilobar infra-segmental consolidation, missed in 35% and 58% of cases, respectively. CONCLUSION: Lobar and lobular pneumonias are the most frequent CT-patterns. Lobar pneumonia is appropriately detected on CXR and mainly due to Streptococcus pneumoniae or Mycoplasma pneumoniae. Chest CT is very useful to identify CAP in other CT-patterns. Prior the COVID pandemic, CAP was rarely responsible for interstitial opacities on CT.

Effects of Long-term Norfloxacin Therapy in Patients With Advanced Cirrhosis.

BACKGROUND & AIMS: There is debate over the effects of long-term oral fluoroquinolone therapy in patients with advanced cirrhosis. We performed a randomized controlled trial to evaluate the effects of long-term treatment with the fluoroquinolone norfloxacin on survival of patients with cirrhosis. METHODS: We performed a double-blind trial of 291 patients with Child-Pugh class C cirrhosis who had not received recent fluoroquinolone therapy. The study was performed at 18 clinical sites in France from April 2010 through November 2014. Patients were randomly assigned to groups given 400 mg norfloxacin (n = 144) or placebo (n = 147) once daily for 6 months. Patients were evaluated monthly for the first 6 months and at 9 months and 12 months thereafter. The primary outcome was 6-month mortality, estimated by the Kaplan-Meier method, censoring spontaneous bacterial peritonitis, liver transplantation, or loss during follow-up. RESULTS: The Kaplan-Meier estimate for 6-month mortality was 14.8% for patients receiving norfloxacin and 19.7% for patients receiving placebo (P = .21). In competing risk analysis that took liver transplantation into account, the cumulative incidence of death at 6 months was significantly lower in the norfloxacin group than in the placebo group (subdistribution hazard ratio, 0.59; 95% confidence interval, 0.35-0.99). The subdistribution hazard ratio for death at 6 months with norfloxacin vs placebo was 0.35 (95% confidence interval, 0.13-0.93) in patients with ascites fluid protein concentrations <15 g/L and 1.39 (95% confidence interval, 0.42-4.57) in patients with ascites fluid protein concentrations ≥15 g/L. Norfloxacin significantly decreased the incidence of any and Gram-negative bacterial infections without increasing infections caused by Clostridium difficile or multiresistant bacteria. CONCLUSIONS: In a randomized controlled trial of patients with advanced cirrhosis without recent fluoroquinolone therapy, norfloxacin did not reduce 6-month mortality, estimated by the Kaplan-Meier method. Norfloxacin, however, appears to increase survival of patients with low ascites fluid protein concentrations. ClinicalTrials.gov ID: NCT01037959.

Hepatocyte microvesicle levels improve prediction of mortality in patients with cirrhosis.

Microvesicles (MVs) are extracellular vesicles released by cells following activation or apoptosis. Some MV subpopulations augment with cirrhosis severity and contribute to portal hypertension. This study aimed at determining if plasma MV levels can estimate the presence of hepatic venous pressure gradient (HVPG) ≥10 mm Hg and predict mortality in patients with advanced chronic liver disease. All patients with severe fibrosis or cirrhosis undergoing liver catheterization between 2013 and 2015 at two centers were prospectively included. We measured circulating levels of annexin V+ , platelet, leukocyte, endothelial, and hepatocyte MVs. The test cohort included 139 patients. Hepatocyte MV levels were 4.0-fold and 2.2-fold higher in patients with Child-Pugh C than in those with Child-Pugh A or B liver disease, respectively. Levels of other MV subpopulations were not influenced by liver disease severity. Hepatocyte MV levels correlated with HVPG but could not identify patients with HVPG ≥10 mm Hg. Hepatocyte MV level >65 U/L predicted 6-month mortality independently of Child-Pugh score and of Model for End-Stage Liver Disease (MELD). Patients with hepatocyte MV levels >65 U/L and MELD >15 had a higher 6-month mortality than other patients (23% versus 3%; P = 0.001). These findings were confirmed in a validation cohort including 103 patients. CONCLUSION: Circulating MV levels cannot identify patients with HVPG ≥10 mm Hg; by contrast, hepatocyte MV levels strongly improve prediction of 6-month mortality in patients with advanced chronic liver disease; therapies associated with decreased levels of circulating hepatocyte MV might be attractive strategies in patients with severe cirrhosis. (Hepatology 2018).

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

BACKGROUND: 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.

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

BACKGROUND: To 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. METHODS: This 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. RESULTS: Group 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. CONCLUSIONS: Although 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.

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

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: This study provides key information for identifying mothers who may require specific support to avoid study attrition in trials evaluating a home-visiting program.

Standardized approach to valve repair using an expansible aortic ring versus mechanical Bentall: early outcomes of the CAVIAAR multicentric prospective cohort study.

OBJECTIVE: The study objective was to compare the 30-day outcomes of a standardized aortic valve repair technique (REPAIR group) associating root remodeling with an expansible aortic ring annuloplasty versus mechanical composite valve and graft (CVG group) replacement in treating aortic root aneurysms. METHODS: A total of 261 consecutive patients with aortic root aneurysm were enrolled in this multicentric prospective cohort (131 in the CVG group, 130 in the REPAIR group) in 20 centers. The main end point is a composite criterion including mortality; reoperation; thromboembolic, hemorrhagic, or infectious events; and heart failure. Secondary end points were major adverse valve-related events. Crude and propensity score adjusted estimates are provided. RESULTS: The mean age was 56.1 years, and the valve was bicuspid in 115 patients (44.7%). The median (interquartile range) preoperative aortic insufficiency grade was 2.0 (1.0-3.0) in the REPAIR group and 3.0 (2.0-3.0) in the CVG group (P = .0002). Thirty-day mortality was 3.8% (n = 5) in both groups (P = 1.00). Despite a learning curve and longer crossclamp times for valve repair (147.7 vs 99.8 minutes, P < .0001), the 2 groups did not differ significantly for the main criterion (odds ratio, 1.31; 95% confidence interval, 0.72-2.40; P = .38) or 30-day mortality (odds ratio, 0.99; 95% confidence interval, 0.28-3053; P = .99), with a trend toward more frequent major adverse valve-related events in the CVG group (odds ratio, 2.52; 95% confidence interval, 0.86-7.40; P = .09). At discharge, 121 patients (96.8%) in the REPAIR group had grade 0 or 1 aortic insufficiency. CONCLUSIONS: A new standardized approach to valve repair, combining an expansible aortic annuloplasty ring with the remodeling technique, presented similar 30-day results to mechanical CVG with a trend toward reducing major adverse valve-related events. Analysis of late outcomes is in process for 3- and 10-year follow-ups.

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.

Timing of intermittent seminal HIV-1 RNA shedding in patients with undetectable plasma viral load under combination antiretroviral therapy.

It was demonstrated that combination antiretroviral therapy (cART) reduces the HIV-1 viral load (VL) in the blood and the seminal compartment. Some studies have reported that the seminal HIV-1 VL is undetectable in individuals with an undetectable blood plasma viral load (bpVL) under cART. However, some recent studies have demonstrated that seminal HIV-1 RNA may still be detected, and potentially infectious, even in the case of an undetectable bpVL. The aim of this retrospective study was to determine the detection rate of a seminal VL and whether shedding could be intermittent over a very short time. From January 2006 to December 2011, 88 HIV-1 infected men, enrolled in an Assisted Reproduction program, provided 306 semen samples, corresponding to 177 frozen sperm samples (two samples delivered at a one-hour interval (n = 129) or one sample (n = 48)). All enrolled men were under cART, with an undetectable bpVL for more than 6 months. HIV-1 RNA was quantified in seminal plasma using a Roche COBAS Ampliprep COBAS TaqMan HIV-1 test. Seminal HIV-1 RNA was detected in 23 samples (7.5%) from 17 patients (19.3%). This detection rate was stable over years. With regards to the freezing of two samples delivered at a one-hour interval, the proportion of discordance between the first and second samples was 9.3% (12/129). Our results confirm the intermittent shedding of HIV-1 in semen. While this finding has been shown by studies examining longer time intervals, to our knowledge, this has never been demonstrated over such a short time interval.

Impact of a manualized multifocal perinatal home-visiting program using psychologists on postnatal depression: the CAPEDP randomized controlled trial.

CONTEXT: Postnatal maternal depression (PND) is a significant risk factor for infant mental health. Although often targeted alongside other factors in perinatal home-visiting programs with vulnerable families, little impact on PND has been observed. OBJECTIVE: This study evaluates the impact on PND symptomatology of a multifocal perinatal home-visiting intervention using psychologists in a sample of women presenting risk factors associated with infant mental health difficulties. METHODS: 440 primiparous women were recruited at their seventh month of pregnancy. All were future first-time mothers, under 26, with at least one of three additional psychosocial risk factors: low educational level, low income, or planning to raise the child without the father. The intervention consisted of intensive multifocal home visits through to the child's second birthday. The control group received care as usual. PND symptomatology was assessed at baseline and three months after birth using the Edinburgh Postnatal Depression Scale (EPDS). RESULTS: At three months postpartum, mean (SD) EPDS scores were 9.4 (5.4) for the control group and 8.6 (5.4) for the intervention group (p = 0.18). The difference between the mean EPDS scores was 0.85 (95% CI: 0.35; 1.34). The intervention group had significantly lower EPDS scores than controls in certain subgroups: women with few depressive symptoms at inclusion (EPDS <8): difference = 1.66 (95%CI: 0.17; 3.15), p = 0.05, adjusted for baseline EPDS score), women who were planning to raise the child with the child's father: difference = 1.45 (95%CI: 0.27; 2.62), p = 0.04 (adjusted); women with a higher educational level: difference = 1.59 (95%CI: 0.50; 2.68) p = 0.05 (adjusted). CONCLUSION: CAPEDP failed to demonstrate an overall impact on PND. However, post-hoc analysis reveals the intervention was effective in terms of primary prevention and in subgroups of women without certain risk factors. Effective overall reduction of PND symptomatology for young, first-time mothers presenting additional psychosocial risk factors may require more tailored interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT00392847 Promoting Parental Skills and Enhancing Attachment in Early Childhood (CAPEDP).

Central or peripheral catheters for initial venous access of ICU patients: a randomized controlled trial.

OBJECTIVES: The vast majority of ICU patients require some form of venous access. There are no evidenced-based guidelines concerning the use of either central or peripheral venous catheters, despite very different complications. It remains unknown which to insert in ICU patients. We investigated the rate of catheter-related insertion or maintenance complications in two strategies: one favoring the central venous catheters and the other peripheral venous catheters. DESIGN: Multicenter, controlled, parallel-group, open-label randomized trial. SETTING: Three French ICUs. PATIENTS: Adult ICU patients with equal central or peripheral venous access requirement. INTERVENTION: Patients were randomized to receive central venous catheters or peripheral venous catheters as initial venous access. MEASUREMENTS AND RESULTS: The primary endpoint was the rate of major catheter-related complications within 28 days. Secondary endpoints were the rate of minor catheter-related complications and a composite score-assessing staff utilization and time spent to manage catheter insertions. Analysis was intention to treat. We randomly assigned 135 patients to receive a central venous catheter and 128 patients to receive a peripheral venous catheter. Major catheter-related complications were greater in the peripheral venous catheter than in the central venous catheter group (133 vs 87, respectively, p=0.02) although none of those was life threatening. Minor catheter-related complications were 201 with central venous catheters and 248 with peripheral venous catheters (p=0.06). 46% (60/128) patients were managed throughout their ICU stay with peripheral venous catheters only. There were significantly more peripheral venous catheter-related complications per patient in patients managed solely with peripheral venous catheter than in patients that received peripheral venous catheter and at least one central venous catheter: 1.92 (121/63) versus 1.13 (226/200), p<0.005. There was no difference in central venous catheter-related complications per patient between patients initially randomized to peripheral venous catheters but subsequently crossed-over to central venous catheter and patients randomized to the central venous catheter group. Kaplan-Meier estimates of survival probability did not differ between the two groups. CONCLUSION: In ICU patients with equal central or peripheral venous access requirement, central venous catheters should preferably be inserted: a strategy associated with less major complications.

Thiazolidinedione use is not associated with worse cardiovascular outcomes: a study in 28,332 high risk patients with diabetes in routine clinical practice: brief title: thiazolidinedione use and mortality.

OBJECTIVE: Assess the cardiovascular safety of Thiazolidinediones (TZD) in routine clinical practice. BACKGROUND: TZD are insulin-sensitizing antidiabetic drugs commonly used in type 2 diabetes, but their cardiovascular safety has been questioned. We examined the association between TZD use and major cardiovascular outcomes. METHODS: We examined 2-year mortality, non-fatal myocardial infarction (MI), and congestive heart failure (CHF) rates among outpatients with high cardiovascular risk and diabetes according to TZD use in the REACH Registry. Multivariable adjustment and propensity scores were used in the analyses. RESULTS: A total of 4997 out of 28,332 patients took TZDs at baseline. During follow-up, 1532 patients died. The mortality rates (95% confidence interval [CI]) were 6.5% (5.5-7.6) with TZD and 7.2% (6.33-8.06) without; adjusted hazard ratio (HR) was 1.06 (0.89-1.26, P=0.54). The lack of association with mortality was consistent across subgroups regardless of history of atherothrombosis or CHF. Rates of non-fatal MI (HR 1.10, 95% CI 0.83-1.45, P=0.50) and non-fatal CHF (HR 0.90, CI 0.75-1.09, P=0.27) were similar in users and non-users. TZD use was associated with an increased risk of CHF in patients aged >80 years (HR 1.59, CI 1.06-2.40, P=0.03). CONCLUSIONS: Use of TZD was not associated with increased incidence of major cardiovascular events in patients with diabetes from this large registry. Older patients experienced an increased risk of CHF over the study interval. Limitations of this study include its observational design, and thus unmeasured confounders cannot be excluded.

Factors associated with 2009 monovalent H1N1 vaccine coverage: a cross sectional study of 1,308 patients with psoriasis in France.

BACKGROUND: Patients with immune-mediated inflammatory diseases like psoriasis are at increased risk of infection. Specific recommendations are available regarding vaccinations however the vaccination coverage in patients with chronic inflammatory diseases has received limited attention and studies are not available in patients with psoriasis. OBJECTIVES: To assess the coverage of 2009 monovalent H1N1 vaccination and to identify factors associated with vaccination among patients with psoriasis. METHODS: Patients member of the French psoriasis patients association were sent a self administrated anonymous questionnaire. It consisted in socio-demographic data, history of psoriasis, seasonal and vaccination status. Factors associated with vaccination for A/H1N1 influenza were identified and adjusted odds ratios (ORa) and prevalence ratios (PRa) were estimated with their 95% confidence intervals (95% CIs) using logistic regression models. RESULTS: 1308 psoriasis patients with a mean age of 58.2 years completed the study between September and December 2010. A total of 240 (19%) patients received the 2009 monovalent H1N1 vaccine. 25 out of 75 patients treated with biologics (33%) received the vaccine. Previous influenza seasonal (ORa (PRa)=10.2 (6.6) [6.1 (4.1)-16.9 (10.7)]), pneumococcal (ORa (PRa)=2.0 (1.6) [1.2 (1.1)-3.3 (2.3)]) and hepatitis B (ORa (PRa)=2.2 (1.7) [1.4 (1.1)-3.5 (2.5)]) vaccinations were independently associated with being vaccinated for influenza A(H1N1). CONCLUSION: This is the largest study conducted to assess the coverage of 2009 monovalent H1N1 vaccine among patients with psoriasis, a highly prevalent chronic inflammatory disease. This vaccination coverage is more than twice the one in the French general population, but still remained low for patients receiving immunosuppressants. The limited impact of specific recommendations, free vaccines and the massive national campaign warrant alternative strategies in case of future pandemics.

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 < 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 < 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.

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.

A new multimodal geriatric discharge-planning intervention to prevent emergency visits and rehospitalizations of older adults: the optimization of medication in AGEd multicenter randomized controlled trial.

OBJECTIVES: To determine whether a new multimodal comprehensive discharge-planning intervention would reduce emergency rehospitalizations or emergency department (ED) visits for very old inpatients. DESIGN: Six-month prospective, randomized (Zelen design), parallel-group, open-label trial. SETTING: Six acute geriatric units (AGUs) in Paris and its surroundings. PARTICIPANTS: Six hundred sixty-five consecutive inpatients aged 70 and older (intervention group (IG) n = 317; control group (CG) n = 348). INTERVENTION: Intervention-dedicated geriatricians different from those in the study centers implemented the intervention, which targeted three risk factors for preventable readmissions and consisted of three components: comprehensive chronic medication review, education on self-management of disease, and detailed transition-of-care communication with outpatient health professionals. MEASUREMENTS: Emergency hospitalization or ED visit 3 and 6 months after discharge, as assessed by telephone calls to the participant, the caregiver, and the general practitioner and confirmed with the hospital administrative database. RESULTS: Twenty-three percent of IG participants were readmitted to hospital or had an ED visit 3 months after discharge, compared with 30.5% of CG participants (P = .03); at 6 months, the proportions were 35.3% and 40.8%, respectively (P = .15). Event-free survival was significantly higher in the IG at 3 months (hazard ratio (HR) = 0.72, 95% confidence interval (CI) = 0.53-0.97, P = .03) but not at 6 months (HR = 0.81, 95% CI = 0.64-1.04, P = .10). CONCLUSION: This intervention was effective in reducing rehospitalizations and ED visits for very elderly participants 3 but not 6 months after their discharge from the AGU. Future research should investigate the effect of this intervention of transitional care in a larger population and in usual acute and subacute geriatric care.

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.

Two-year vascular event rates in patients with symptomatic cerebrovascular disease: the REACH registry.

BACKGROUND AND PURPOSE: Few practice-based studies have reported vascular outcome events among patients with cerebrovascular disease (CeVD). We describe 2-year vascular outcomes among symptomatic CeVD patients from the REduction of Atherothrombosis for Continued Health (REACH) Registry. METHODS: Vascular events (stroke; myocardial infarction, MI; cardiovascular death, CV death; hospitalization) were studied among symptomatic CeVD patients from a prospective cohort of stable outpatients with established atherothrombosis or ≥3 atherothrombotic risk factors. RESULTS: Of the 69,055 patients in REACH, 18,992 (28%) had symptomatic CeVD, of which outcome data were available for 18,189 patients. At 2 years, the frequency of non-fatal stroke was 5.93% (95% CI 5.22-6.64), non-fatal MI 2.21% (95% CI 1.65-2.76), CV death 4.45% (95% CI 3.66-5.22), combined vascular endpoint 11.48% (95% CI 10.46-12.49), and all deaths 7.39% (95% CI 6.34-8.42). The frequency of stroke, MI, CV death, or hospitalization for atherothrombotic events was 21.05% (95% CI 20.05-22.03). Event rates were lowest among patients with CeVD alone and highest among patients with CeVD, coronary artery disease, and peripheral artery disease. Other predictors of the primary outcome were increasing age, history of diabetes, current smoking, asymptomatic carotid stenosis, and carotid plaque. Outcomes were similar across geographical regions. CONCLUSIONS: Symptomatic CeVD patients encounter high vascular event rates despite treatment. Recurrent nonfatal stroke is more common than nonfatal MI.

Metformin use and mortality among patients with diabetes and atherothrombosis.

BACKGROUND: Metformin is recommended in type 2 diabetes mellitus because it reduced mortality among overweight participants in the United Kingdom Prospective Diabetes Study when used mainly as a means of primary prevention. However, metformin is often not considered in patients with cardiovascular conditions because of concerns about its safety. METHODS: We assessed whether metformin use was associated with a difference in mortality among patients with atherothrombosis. The study sample comprised 19 691 patients having diabetes with established atherothrombosis participating in the Reduction of Atherothrombosis for Continued Health (REACH) Registry between December 1, 2003, and December 31, 2004, treated with or without metformin. Multivariable adjustment and propensity score were used to account for baseline differences. The main outcome measure was 2-year mortality. RESULTS: The mortality rates were 6.3% (95% confidence interval [CI], 5.2%-7.4%) with metformin and 9.8% 8.4%-11.2%) without metformin; the adjusted hazard ratio (HR) was 0.76 (0.65-0.89; P < .001). Association with lower mortality was consistent among subgroups, noticeably in patients with a history of congestive heart failure (HR, 0.69; 95% CI, 0.54-0.90; P = .006), patients older than 65 years (0.77; 0.62-0.95; P = .02), and patients with an estimated creatinine clearance of 30 to 60 mL/min/1.73 m(2) (0.64; 95% CI, 0.48-0.86; P = .003) (to convert creatinine clearance to mL/s/m(2), multiply by 0.0167). CONCLUSIONS: Metformin use may decrease mortality among patients with diabetes when used as a means of secondary prevention, including subsets of patients in whom metformin use is not now recommended. Metformin use should be tested prospectively in this population to confirm its effect on survival.

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]).