Head-to-head comparison of the diagnostic performances of Rubidium-PET and SPECT with CZT camera for the detection of myocardial ischemia in a population of women and overweight individuals.

BACKGROUND: The aim of this study was to compare the diagnostic performances for the detection of myocardial ischemia of 82-Rb-PET-MPS and 99m-Tc-SPECT-MPS in overweight individuals and women. METHODS AND RESULTS: Men with BMI ≥ 25 and women referred for MPS were considered for inclusion. All individuals underwent 99m-Tc-SPECT-MPS with CZT cameras and 82-Rb-PET-MPS in 3D-mode. Individuals with at least one positive MPS were referred for coronary angiography (CA) with FFR measurements. A criterion for positivity was a composite endpoint including significant stenosis on CA or, in the absence of CA, the occurrence of acute coronary event during the following year. 313 patients (46% women) with mean BMI of 31.8 ± 6.5 were included. Sensitivity for the detection of myocardial ischemia was higher with 82-Rb-PET-MPS compared with 99m-Tc-SPECT-MPS (85% vs. 57%, P < .05); specificity was equally high with both imaging techniques (93% vs. 94%, P > .05). 82-Rb-PET allowed for a more accurate detection of patients with a high-risk coronary artery disease (HR-CAD) than 99m-Tc-SPECT-MPS (AUC = 0.86 vs. 0.75, respectively; P = .04). CONCLUSIONS: In women and overweight individuals, 82-Rb-PET-MPS provides higher sensitivity for the detection of myocardial ischemia than 99m-Tc-SPECT-MPS thanks to a better image quality and an improved detection of HR-CAD.

The impact of having a baby with cleft lip and palate on parents and on parent-baby relationship: the first French prospective multicentre study.

BACKGROUND: The objective of this prospective, multidisciplinary and multicenter study was to explore the effect of a cleft lip, associated or not with a cleft palate, on parents, on parent-infant relationship, and on the baby's relational development. It also highlighted how the type of cleft and the timing of the surgery could impact this effect. METHOD: 158 infants, with Cleft lip with or without Palate, and their parents participated in this multicenter prospective cohort. Clinical evaluations were performed at 4 and 12 months postpartum. The impact on the parents and on the parent-infant relationship was evaluated by the Parenting Stress Index (PSI), the Edinburgh Post-partum Depression Scale (EPDS) and the Impact-on-Family Scale (IOFS). The relational development of the infant was assessed using the Alarm Distress Baby Scale (ADBB). The main criteria used to compare the infants were the severity of cleft and the time of surgery. RESULTS: The timing of surgery, the type of malformation or the care structure had no effect on social withdrawal behaviors of the child at 4 and 12 months postpartum (ADBB). Furthermore, early intervention significantly decreased maternal stress assessed with the PSI at 4 months. Parents for whom it had been possible to give a prenatal diagnosis were much better prepared to accept the waiting time between birth and the first surgical intervention (IOFS). Higher postpartum depression scores (EPDS) were found for both parents compared to the general population. CONCLUSION: A joint assessment of the mental health of both infants and parents is required in the follow-up of cleft lip and palate. Even if most families are remarkably resilient faced with this major cause of stress, a significant proportion of them could require help to deal with the situation, especially during this first year of follow-up. An assessment of the child's social withdrawal behaviour and of the parental stress and depression appears useful, in order to adapt care to infant and parent's needs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00993993. Registered 10/14/2009 <.

Increased rate of lumbar spondylolisthesis in rheumatoid arthritis: A case-control study.

OBJECTIVE: The aim of this study was to compare the prevalence of lumbar spondylolisthesis (SPL) in patients suffering from low back pain (LBP) with or without rheumatoid arthritis (RA) and to identify potential factors associated with SPL in patients with RA. METHODS: We performed a case-control study. Cases and control patients had chronic LBP (more than 4 weeks). Patient with RA fulfilled the 2010 ACR/EULAR criteria. The main outcome was the presence of lumbar SPL on lumbar X-ray. The prevalence of SPL between RA and control patients was compared using chi-squared test. Potential factors associated with SPL in patients with RA were investigated by univariate and multivariate analysis, estimating odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: A total of 67 cases and 83 controls were included. Median [interquartile range] age of patients with RA was 60.0 years [51.0-72.0]; 80.6% were females; and 92.5% and 83.6% were positive for anti-citrullinated protein antibodies (ACPAs) or rheumatoid factor, respectively. Mean RA disease duration was 11.2 ± 8.7 years. SPL was more frequent in patients with RA than controls (41.8% versus 18.1%, P = 0.001). Adjusted to gender, RA was associated with increased prevalence of SPL (OR 3.15 [95% CI 1.48-6.70], P = 0.003). Among patients with RA, SPL was mainly Grade 1 (85.7%). Multivariate analysis revealed SPL is associated with increased age in patients with RA (OR 1.06 [1.02-1.11], P = 0.004). CONCLUSION: In a population of patients with chronic LBP, the prevalence of lumbar SPL was higher with than without RA. SPL might be explained by synovitis of lumbar facet joints.

Association between maternal social deprivation and prenatal care utilization: the PreCARE cohort study.

BACKGROUND: Maternal social deprivation is associated with an increased risk of adverse maternal and perinatal outcomes. Inadequate prenatal care utilization (PCU) is likely to be an important intermediate factor. The health care system in France provides essential health services to all pregnant women irrespective of their socioeconomic status. Our aim was to assess the association between maternal social deprivation and PCU. METHODS: The analysis was performed in the database of the multicenter prospective PreCARE cohort study. The population source consisted in all parturient women registered for delivery in 4 university hospital maternity units, Paris, France, from October 2010 to November 2011 (N = 10,419). This analysis selected women with singleton pregnancies that ended after 22 weeks of gestation (N = 9770). The associations between maternal deprivation (four variables first considered separately and then combined as a social deprivation index: social isolation, poor or insecure housing conditions, no work-related household income, and absence of standard health insurance) and inadequate PCU were tested through multivariate logistic regressions also adjusted for immigration characteristics and education level. RESULTS: Attendance at prenatal care was poor for 23.3% of the study population. Crude relative risks and confidence intervals for inadequate PCU were 1.6 [1.5-1.8], 2.3 [2.1-2.6], and 3.1 [2.8-3.4], for women with a deprivation index of 1, 2, and 3, respectively, compared to women with deprivation index of 0. Each of the four deprivation variables was significantly associated with an increased risk of inadequate PCU. Because of the interaction observed between inadequate PCU and mother's country of birth, we stratified for the latter before the multivariate analysis. After adjustment for the potential confounders, this social gradient remained for women born in France and North Africa. The prevalence of inadequate PCU among women born in sub-Saharan Africa was 34.7%; the social gradient in this group was attenuated and no longer significant. Other factors independently associated with inadequate PCU were maternal age, recent immigration, and unplanned or unwanted pregnancy. CONCLUSION: Social deprivation is independently associated with an increased risk of inadequate PCU. Recognition of risk factors is an important step in identifying barriers to PCU and developing measures to overcome them.

Step-down strategy of spacing TNF-blocker injections for established rheumatoid arthritis in remission: results of the multicentre non-inferiority randomised open-label controlled trial (STRASS: Spacing of TNF-blocker injections in Rheumatoid ArthritiS Study).

UNLABELLED: Tumour necrosis factor (TNF)-blocker tapering has been proposed for patients with rheumatoid arthritis (RA) in remission. OBJECTIVE: The trial aims to compare the effect of progressive spacing of TNF-blocker injections (S-arm) to their maintenance (M-arm) for established patients with RA in remission. METHODS: The study was an 18-month equivalence trial which included patients receiving etanercept or adalimumab at stable dose for ≥1 year, patients in remission on 28-joint Disease Activity Score (DAS28) for ≥6 months and patients with stable joint damage. Patients were randomised into two arms: maintenance or injections spacing by 50% every 3 months up to complete stop. Spacing was reversed to the previous interval in case of relapse, and eventually reattempted after remission was reachieved. The primary outcome was the standardised difference of DAS28 slopes, based on a linear mixed-effects model (equivalence interval set at ±30%). RESULTS: 64 and 73 patients were included in the S-arm and M-arm, respectively, which was less than planned. In the S-arm, TNF blockers were stopped for 39.1%, only tapered for 35.9% and maintained full dose for 20.3%. The equivalence was not demonstrated with a standardised difference of 19% (95% CI -5% to 46%). Relapse was more common in the S-arm (76.6% vs 46.5%, p=0.0004). However, there was no difference in structural damage progression. CONCLUSIONS: Tapering was not equivalent to maintenance strategy, resulting in more relapses without impacting structural damage progression. Further studies are needed to identify patients who could benefit from such a strategy associated with substantial cost savings. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT00780793; EudraCT identifier: 2007-004483-41.

Ventilator-associated pneumonia due to carbapenem-resistant Gram-negative bacilli in an intensive care unit without carbapenemase-producing Enterobacteriaceae or epidemic Acinetobacter baumannii.

Risk factors for ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Gram-negative bacilli (CR-GNB) have rarely been evaluated in intensive care units (ICU) without epidemic carbapenemase-producing Acinetobacter baumannii or Enterobacteriaceae. We addressed this issue in a cohort of 141 patients (previous antimicrobial exposure, n = 131) with a first episode of VAP in a medico-surgical ICU. Twenty-six VAP (18.4%) involved a CR-GNB (Pseudomonas aeruginosa, n = 14, Stenotrophomonas maltophilia, n = 11, and A. baumannii, n = 1), without previous carbapenem exposure in 12 (46.1%) cases. GNB resistant to all ß-lactams except carbapenems were equally isolated in CR-GNB VAP (co-infections, 23%) and other episodes (30%). Previous exposure to aminoglycosides (odds ratio (OR) 1.14 per day, 95% confidence interval (CI) 1.02-1.30, p = 0.02) and the number of antimicrobial classes used before VAP (OR 1.38 per class, 95% CI 1.10-1.73, p = 0.006) were the only independent predictors of CR-GNB. These results suggest that the empirical use of a carbapenem-colistin combination should be evaluated in late-onset VAP following broad-spectrum antimicrobial exposure.

Breastfeeding duration and cognitive development at 2 and 3 years of age in the EDEN mother-child cohort.

OBJECTIVE: To investigate the dose-response relationship between breastfeeding duration and cognitive development in French preschool children. STUDY DESIGN: In the French EDEN Mother-Child Cohort Study, we evaluated language ability with the Communicative Development Inventory (CDI) in 1387 2-year-old children and overall development with the Ages and Stages Questionnaire (ASQ) in 1199 3-year-old children. Assessments were compared between breastfed and non-breastfed children and also according to breastfeeding duration in multivariable linear models, controlling for a wide range of potential confounders. We tested departure from linearity. RESULTS: After adjustments, ever-breastfed children scored 3.7 ± 1.8 (P = .038) points higher than never-breastfed children on the CDI and 6.2 ± 1.9 (P = .001) points higher on the ASQ. Among breastfed children, exclusive and any-breastfeeding durations were positively associated with both CDI and ASQ scores. The fine motor domain of ASQ was associated with any-breastfeeding duration, and the problem solving domain with exclusive-breastfeeding duration. We did not observe significant departures from linearity. No interactions were found between the child's sex, parental education or socioeconomic status, and breastfeeding duration. CONCLUSION: Longer breastfeeding duration was associated with better cognitive and motor development in 2- and 3-year-old children and a dose-response relationship was suggested.

Multicentre medicoeconomic evaluation of cardiac magnetic resonance imaging for predicting coronary artery disease in left ventricular dysfunction: The CAMAREC study design.

BACKGROUND: Cardiac magnetic resonance imaging may provide a non-invasive alternative to coronary angiography for differentiating between ischaemic and non-ischaemic cardiomyopathy in cases of unexplained reduced left ventricular ejection fraction. AIM: The CAMAREC study aims to evaluate the diagnostic accuracy of cardiac magnetic resonance imaging in predicting significant coronary artery disease in patients with reduced left ventricular ejection fraction, using coronary angiography as the gold standard for comparison. METHODS: CAMAREC is a prospective cohort study of 406 patients in 10 centres with newly diagnosed, unexplained left ventricular ejection fraction ≤ 45%. Cardiac magnetic resonance imaging and coronary angiography will be conducted within a 2-week interval, starting with cardiac magnetic resonance imaging; independent committees will review the results blindly. Primary outcome is sensitivity of detecting ischaemic scar on cardiac magnetic resonance imaging for predicting significant coronary artery disease on coronary angiography according to Felker's criteria. Secondary outcomes include specificity and positive and negative predictive values (with 95% confidence intervals) of cardiac magnetic resonance imaging for predicting significant coronary artery disease in patients with reduced left ventricular ejection fraction, kappa concordance coefficient between cardiac magnetic resonance imaging and coronary angiography for diagnosing the affected myocardial territory, and the impact of cardiac magnetic resonance imaging on revascularization decisions. Two ancillary studies will evaluate the incremental cost-effectiveness of using cardiac magnetic resonance imaging first versus coronary angiography first, and the sensitivity of pre- and postcontrast T1-mapping for predicting significant coronary artery disease in patients with reduced left ventricular ejection fraction. CONCLUSION: Our study protocol is designed to rigorously evaluate cardiac magnetic resonance imaging as a non-invasive alternative to coronary angiography in patients with unexplained reduced left ventricular ejection fraction. The results will have significant implications for patient management, and may support growing evidence for the clinical utility of cardiac magnetic resonance imaging.

[ 18 F]FDG Positron Emission Tomography for Initial Staging and Healing Assessment at the End of Therapy in Lymph Nodes and Bone Tuberculosis.

Objective: In extra-pulmonary tuberculosis, therapeutic management is difficult in the absence of reliable tool to affirm healing at the end of treatment. In this prospective multicenter study, we evaluated [18F]FDG-PET for this purpose. Methods: Forty-two patients out of 55 included patients could be analyzed. Additionally to usual biological, histological and morphological explorations, [18F]FDG-PET was performed at diagnosis (PET1), at the end of treatment (PET2), indeed 6 months later. Then patients were followed until 12 months after end of prescribed treatment. Results: PET1 was positive in 97.6% of patients and discovered unknown injured sites in 52.7% of cases. PET2 was positive in 83.3% of uncured patients, and in 82.3% of cured patients. The sum and mean value of SUVmax measured in PET/CT lesions decreased between PET1 and PET2 in all patients. Mean value of SUVmax (MSUV) and sum value of SUVmax on PET2 showed the highest AUC on ROC curves for the diagnosis of healing at the end of prescribed treatment; MSUV 3.5 on PET2 had a sensitivity of 76.5% and a specificity of 80.0% to affirm healing at the end of prescribed treatment. Conclusions: [18F]FDG-PET/CT was useful at diagnosis, discovering unknown lesions in 52.7% of cases. MSUV on PET2 was the best criteria to affirm healing at the end of prescribed treatment.

An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-ß-1a and hydroxychloroquine in hospitalized patients with COVID-19.

OBJECTIVES: We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-ß-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in coronavirus 2019 disease (COVID-19) inpatients requiring oxygen and/or ventilatory support. METHODS: We conducted a phase III multicentre, open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), an add-on to the Solidarity trial (NCT04315948, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO seven-point ordinal scale. Secondary outcomes included quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory specimens and pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, trials of which were stopped prematurely. RESULTS: The intention-to-treat population included 583 participants-lopinavir/ritonavir (n = 145), lopinavir/ritonavir-IFN-ß-1a (n = 145), hydroxychloroquine (n = 145), control (n = 148)-among whom 418 (71.7%) were male, the median age was 63 years (IQR 54-71), and 211 (36.2%) had a severe disease. The day-15 clinical status was not improved with the investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.83, (95% confidence interval (CI) 0.55-1.26, p 0.39), lopinavir/ritonavir-IFN-ß-1a versus control, aOR 0.69 (95%CI 0.45-1.04, p 0.08), and hydroxychloroquine versus control, aOR 0.93 (95%CI 0.62-1.41, p 0.75). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of serious adverse events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms. CONCLUSION: In adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir-IFN-ß-1a and hydroxychloroquine improved neither the clinical status at day 15 nor SARS-CoV-2 clearance in respiratory tract specimens.

Patient-perceived flares in rheumatoid arthritis: A sub-analysis of the STRASS treatment tapering strategy trial.

OBJECTIVES: Patient's and physician's perspective can differ in rheumatoid arthritis (RA). The aim was to define the concept of patient-reported flares. METHODS: Post-hoc analysis of a randomized controlled trial of a step-down strategy in RA patients treated with anti-TNF, in DAS28-remission for ≥6 months, randomized to either "spacing" or "maintaining" anti-TNF. The occurrence of patient-reported flares (PRF) was evaluated every 3 months for 18 months by: "Over the last 3 months, did you experience symptoms suggestive of disease exacerbation?". Visits with and without PRF were compared, using a linear mixed effects model, in terms of symptoms, disability based on the Health Assessment Questionnaire, quality of life based on Short Form 36 Health Survey and DAS28-based relapses (DBR), defined as an increase of DAS28>0.6 and an absolute value of DAS28>2.6. The agreement between PRF and DBR was measured by the kappa coefficient on repeated data. RESULTS: In all, 137 patients were analyzed: mean age 55±11 years, females 78%, mean RA duration 9.5±8.0 years. Over the 18 months, PRF concerned 27.2% of the 940 available visits. DBR and PRF were observed in 24% and 16% of 940 visits for 137 patients respectively. All the items were associated with PRF with standardized effect size between -0.58 (SF36 PCS) and 0.87 (DAS28). The agreement between PRF and DBR was moderate (κ=0.44). CONCLUSION: The concept of flare refers to more than just RA disease activity.

Effect of rapid desensitization on platelet inhibition and basophil activation in patients with aspirin hypersensitivity and coronary disease.

Aims: To determine antiplatelet efficacy after desensitization in patients with a history of aspirin hypersensitivity. Methods and results: We conducted a case-control study to evaluate the efficacy of aspirin 1 day (D1) and 6-8 weeks (W6-8) after desensitization. We also assessed ex vivo basophil reactivity to aspirin after desensitization. Cases were patients with coronary artery disease (CAD) and documented history of aspirin hypersensitivity who underwent rapid successful oral desensitization to aspirin. Controls were patients with stable CAD without hypersensitivity and receiving aspirin. Among 56 cases, 27 received aspirin for acute coronary syndromes and 29 were treated for stable CAD. Aspirin was effective (defined as light transmission aggregometry induced by arachidonic acid ≤20%) at D1 in 86% of cases (P = 0.045 vs. controls) and in 95% at W6-8, vs. 100% of controls (P = 0.39). Urinary excretion of thromboxane B2 diminished substantially in cases (P < 0.0001, D0 vs. W6-8) but remained higher than in controls (P = 0.03). Platelet reactivity (defined by platelet P-selectin expression, activated glycoprotein IIb/IIIa inhibitors, and platelet-monocyte aggregates) was similar in cases between D0 and D1 but decreased at W6-8. Basophil activation (quantified by upregulation of CD203c in response to aspirin) was higher in cases at W6-8 than in controls (P = 0.0002). Conclusion: Thus, following rapid desensitization, aspirin achieves rapid biological efficacy, which is slightly lower at D1, but becomes indistinguishable from chronically treated patients at W6-8. Persistent basophil activation several weeks after desensitization suggests infraclinical hypersensitivity and the need to continue aspirin to maintain desensitization.

Control treatments in biologics trials of rheumatoid arthritis were often not deemed acceptable in the context of care.

OBJECTIVES: Control treatments in randomized controlled trials (RCTs) should not deliberately disadvantage patients. The objectives of the study were to compare (1) willingness to include vs. (2) willingness to prescribe control treatment among physicians randomized to assess, respectively, either (1) enrollment in a trial or (2) appropriateness of control treatment in a care context for the same fictional patient. STUDY DESIGN AND SETTING: Physicians were authors of articles about rheumatoid arthritis (RA), involved in RA patient care, and used to enrolling patients in trials. The outcomes were willingness to give control treatment: trial enrollment or control-treatment appropriateness in care context. We derived three case vignettes of fictional standard eligible patients for each of 30 RCTs assessing biologics in RA. Physicians were randomly allocated to the "trial" or "care" arm. For each of the 90 fictional patients, physicians assigned to the trial arm were asked if they would enroll the patient in the RCT the patient was derived from. For the same 90 fictional patients, physicians assigned to the care arm were asked if the control treatment of the RCT was appropriate in a context of usual care. RESULTS: Of the 1,779 physicians invited to participate, 151 were randomized. Half of the fictional patients {41/90; 45% [95% confidence interval (CI): 37%, 53%]} would be enrolled in the RCT although the control-arm treatment of the RCT was not considered appropriate for them in the context of care. This rate differed by type of comparator [55% for non-head-to-head RCTs vs. 6% for head-to-head RCTs; adjusted odds ratio (aOR), 23.9 (95% CI: 5.5, 92.7)] and duration of trial control treatment [56% for ≤24 weeks and 15% for >24 weeks; aOR, 10.7 (95% CI: 2.8, 63.9)] but not patient RA activity [aOR, 2.5 (95% CI: 1.0, 6.6)]. The limitation of this study was that physicians gave their opinion on fictional patients with only RA. CONCLUSIONS: Control treatments in RCTs of biologics in RA are often deemed not acceptable in the context of usual care, especially those for non-head-to-head RCTs. These findings raise ethical concerns and challenge the choice of the comparator in RCTs.

Liver steatosis assessed by preoperative MRI: An independent risk factor for severe complications after major hepatic resection.

BACKGROUND: Steatosis assessed by histology is commonly considered to be a significant risk factor for liver surgery. MRI is considered as the new gold standard for noninvasive liver fat quantification. The purpose was to assess whether liver steatosis determined by preoperative MRI is an independent risk factor of complications after major liver resection. METHODS: All patients who underwent liver MRI before major liver resection in our institution between January 2001 and December 2011 were included in this retrospective study. The liver fat fraction (LFF) was assessed on in- and opposed-phase T1-weighted dual echo gradient echo MRI and steatosis was defined as a MRI LFF of ≥ 5%. The association between steatosis and postoperative complications (Clavien-Dindo classification, ascites > 500 mL at day 5, 50-50 criteria, fistula/collection, blood liver test alterations, pulmonary complications, nonpulmonary complications, >1 complication, duration of stay in the intensive care unit, duration of hospital stay, and death) was assessed by multivariate analysis using the appropriate model. RESULTS: A MRI LFF of ≥ 5% was associated with severe postoperative complications (Clavien-Dindo score ≥ IIIa; P = .04), more pulmonary complications (P = .02), and longer duration of hospital stay (P = .02) on the multivariate model adjusted for confounding factors. The postoperative aminotransferase levels were higher in patients with a MRI LFF of ≥ 5%, than in other patients (P = .0008). CONCLUSION: Liver steatosis assessed by routine preoperative MRI is shown to be an independent risk factor of severe postoperative complications after major liver resection.