Explore the vast range of titles available.

Background. Multidrug-resistant Enterobacteriaceae (MRE) are widespread in the community, especially in tropical regions. Travelers are at risk of acquiring MRE in these regions, but the precise extent of the problem is not known. Methods. From February 2012 to April 2013, travelers attending 6 international vaccination centers in the Paris area prior to traveling to tropical regions were asked to provide a fecal sample before and after their trip. Those found to have acquired MRE were asked to send fecal samples 1, 2, 3, 6, and 12 months after their return, or until MRE was no longer detected. The fecal relative abundance of MRE among all Enterobacteriaceae was determined in each carrier. Results. Among 824 participating travelers, 574 provided fecal samples before and after travel and were not MRE carriers before departure. Of these, 292 (50.9%) acquired an average of 1.8 MRE. Three travelers (0.5%) acquired carbapenemase-producing Enterobacteriaceae. The acquisition rate was higher in Asia (142/196 [72.4%]) than in sub-Saharan Africa (93/195 [47.7%]) or Latin America (57/183 [31.1%]). MRE acquisition was associated with the type of travel, diarrhea, and exposure to β-lactams during the travel. Three months after return, 4.7% of the travelers carried MRE. Carriage lasted longer in travelers returning from Asia and in travelers with a high relative abundance of MRE at return. Conclusions. MRE acquisition is very frequent among travelers to tropical regions. Travel to these regions should be considered a risk factor of MRE carriage during the first 3 months after return, but not beyond. Clinical Trials Registration. NCT01526187.

Escherichia coli is an important cause of bloodstream infections (BSI), which is of concern given its high mortality and increasing worldwide prevalence. Finding bacterial genetic variants that might contribute to patient death is of interest to better understand infection progression and implement diagnostic methods that specifically look for those factors. E . coli samples isolated from patients with BSI are an ideal dataset to systematically search for those variants, as long as the influence of host factors such as comorbidities are taken into account. Here we performed a genome-wide association study (GWAS) using data from 912 patients with E . coli BSI from hospitals in Paris, France. We looked for associations between bacterial genetic variants and three patient outcomes (death at 28 days, septic shock and admission to intensive care unit), as well as two portals of entry (urinary and digestive tract), using various clinical variables from each patient to account for host factors. We did not find any association between genetic variants and patient outcomes, potentially confirming the strong influence of host factors in influencing the course of BSI; we however found a strong association between the papGII operon and entrance of E . coli through the urinary tract, which demonstrates the power of bacterial GWAS when applied to actual clinical data. Despite the lack of associations between E . coli genetic variants and patient outcomes, we estimate that increasing the sample size by one order of magnitude could lead to the discovery of some putative causal variants. Given the wide adoption of bacterial genome sequencing of clinical isolates, such sample sizes may be soon available.

Travelers are at high risk of acquiring multi-drug resistant Enterobacteriaceae (MRE) while traveling abroad. Acquisition of extended spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) while traveling has been extensively described, but not that of plasmid-mediated cephalosporinase producing Enterobacteriaceae (pAmpC-E). Here, we characterized the pAmpC-E acquired in 574 French travelers to tropical areas enrolled in the VOYAG-R study. Among the 526 MRE isolated at return, 57 (10.8%) from 49 travelers were pAmpC-E. The acquisition rate of pAmpC-E was 8.5% (49/574) ranging from 12.8% (25/195) in Asia, 7.6% (14/184) in Latin America to 5.1% (10/195) in Africa. The highest acquisition rates were observed in Peru (21.9%), India (21.4%) and Vietnam (20%). The carriage of pAmpC-E decreased quickly after return with 92.5% of colonized travelers being negative at one month. Most enzymes were CMY types (96.5%, n = 55, only met in Escherichia coli), including 40 CMY-2 (70.2%), 12 CMY-42 (21.1%), 1 CMY-6 and two new CMY-2 variants. The remaining were two DHA observed in Klebsiella pneumoniae. CMY-2 producing strains were acquired worldwide whereas CMY-42, except for one, were all acquired in Asia. BlaCMY-2 genes were associated with different plasmid types, including IncI1 (45. 2%), IncF (10%), IncF-IncI (7.5%), IncA/C (5%) and IncR (2.5%) whereas blaCMY-42 were all associated with IncI1 plasmids. Even though the pAmpC-E acquisition rate was much lower than that of ESBL-E, it was significant, especially in Asia, showing that pAmpC-E, especially CMY-type producing E. coli have spread in the community settings of tropical regions.

Background We aimed to investigate the association of intracranial complications diagnosed on neuroimaging with neurological outcomes of adults with severe pneumococcal meningitis. Methods We performed a retrospective multicenter study on consecutive adults diagnosed with pneumococcal meningitis requiring at least 48 h of stay in the intensive care unit (ICU) and undergoing neuroimaging, between 2005 and 2021. All neuroimaging were reanalyzed to look for intracranial complications which were categorized as (1) ischemic lesion, (2) intracranial hemorrhage (3) abscess/empyema, (4) ventriculitis, (5) cerebral venous thrombosis, (6) hydrocephalus, (7) diffuse cerebral oedema. The primary outcome was unfavorable outcome at 90 days after ICU admission, defined by a modified Rankin Scale (mRS) score > 2. Results Among the 237 patients included, intracranial complications were diagnosed in 68/220 patients (31%, 95%CI 0.25–0.37) who underwent neuroimaging at ICU admission and in 75/110 patients (68%, 95%CI 0.59–0.77) who underwent neuroimaging during ICU stay. At 90 days, 103 patients (44%, 95%CI 37–50) had unfavorable outcome, including 71 (30%) deaths. The most frequent intracranial complications were ischemic lesion (69/237 patients, 29%), diffuse cerebral oedema (43/237, 18%) and ventriculitis (36/237, 15%). Through multivariable analysis, we found that intracranial complications (adjusted odds ratio (aOR) 2.88, 95%CI 1.37–6.21) were associated with unfavorable outcome, along with chronic alcohol consumption (aOR 3.10, 95%CI 1.27–7.90), chronic vascular disease (aOR 4.41, 95%CI 1.58–13.63), focal neurological sign(s) (aOR 2.38, 95%CI 1.11–5.23), and cerebrospinal fluid leukocyte count < 1000 cell/microL (aOR 4.24, 95%CI 2.11–8.83). Competing risk analysis, with persistent disability (mRS score 3–5) as the primary risk and ICU-death as the competing risk, revealed that chronic alcohol consumption was the sole significant variable associated with persistent disability at 90 days (cause-specific hazard ratio 4.26, 95%CI 1.83–9.91), whereas the remaining variables were associated with mortality. Conclusions In adults with severe pneumococcal meninigitis, intracranial complications were independently associated with a higher risk of poor functional outcome, in the form of persistent disability or death. This study highlights the value of neuroimaging studies in this population, and provides relevant information for prognostication.

Case-only designs have been used since late 1980's. In these, as opposed to case-control or cohort studies for instance, only cases are required and are self-controlled, eliminating selection biases and confounding related to control subjects, and time-invariant characteristics. The objectives of this systematic review were to analyze how the two main case-only designs - case-crossover (CC) and self-controlled case series (SCCS) - have been applied and reported in pharmacoepidemiology literature, in terms of applicability assumptions and specificities of these designs. We systematically selected all reports in this field involving case-only designs from MEDLINE and EMBASE up to September 15, 2010. Data were extracted using a standardized form. The analysis included 93 reports 50 (54%) of CC and 45 (48%) SCCS, 2 reports combined both designs. In 12 (24%) CC and 18 (40%) SCCS articles, all applicable validity assumptions of the designs were fulfilled, respectively. Fifty (54%) articles (15 CC (30%) and 35 (78%) SCCS) adequately addressed the specificities of the case-only analyses in the way they reported results. Our systematic review underlines that implementation of CC and SCCS designs needs to be more rigorous with regard to validity assumptions, as well as improvement in results reporting.

IntroductionPostoperative delirium (POD) is one of the most frequent complication after surgery in elderly patients, and is associated with increased morbidity and mortality, prolonged length of stay, cognitive and functional decline leading to loss of autonomy, and important additional healthcare costs. Perioperative inflammatory stress is a key element in POD genesis. Melatonin exhibits antioxidative and immune-modulatory proprieties that are promising concerning delirium prevention, but in perioperative context literature are scarce and conflicting. We hypothesise that perioperative melatonin can reduce the incidence of POD.Methods and analysisThe DELIRLESS trial is a prospective, national multicentric, phase III, superiority, comparative randomised (1:1) double-blind clinical trial. Among patients aged 70 or older, hospitalised and scheduled for surgery of a severe fracture of a lower limb, 718 will be randomly allocated to receive either melatonin 4 mg per os or placebo, every night from anaesthesiologist preoperative consultation and up to 5 days after surgery. The primary outcome is POD incidence measured by either the French validated translation of the Confusion Assessment Method (CAM) score for patients hospitalised in surgery, or CAM-ICU score for patients hospitalised in ICU (Intensive Care Unit). Daily delirium assessment will take place during 10 days after surgery, or until the end of hospital stay if it is shorter. POD cumulative incidence function will be compared at day 10 between the two randomised arms in a competing risks framework, using the Fine and Grey model with death as a competing risk of delirium.Ethics and disseminationThe DELIRLESS trial has been approved by an independent ethics committee the Comité de Protection des Personnes (CPP) Sud-Est (ref CPP2020-18-99 2019-003210-14) for all study centres. Participant recruitment begins in December 2020. Results will be published in international peer-reviewed medical journals.Trial registration numberNCT04335968, first posted 7 April 2020.Protocol version identifierN°3–0, 3 May 2021.

Artificially engineered twisted van der Waals (vdW) heterostructures have unlocked new pathways for exploring emergent quantum phenomena and strongly correlated electronic states. Many of these phenomena are highly sensitive to the twist angle, which can be deliberately tuned to tailor the interlayer interactions. This makes the twist angle a critical tunable parameter, emphasizing the need for precise control and accurate characterization during device fabrication. In particular, twisted cuprate heterostructures based on Bi2Sr2CaCu2O8 + x (BSCCO) have demonstrated angle‐dependent superconducting properties, positioning the twist angle as a key tunable parameter. However, the twisted interface is highly unstable under ambient conditions and vulnerable to damage from conventional characterization tools such as electron microscopy or scanning probe techniques. In this work, a fully non‐invasive, polarization‐resolved Raman spectroscopy approach is introduced for determining twist angles in artificially stacked BSCCO heterostructures. By analyzing twist‐dependent anisotropic vibrational Raman modes, particularly utilizing the out‐of‐plane A1g vibrational mode of Bi/Sr at ≈116 cm−1, clear optical fingerprints of the rotational misalignment between cuprate layers are identified. The high‐resolution confocal Raman setup, equipped with polarization control and RayShield filtering down to 10 cm−1, allows for reliable and reproducible measurements without compromising the material's structural integrity. A fully non‐invasive polarization‐resolved Raman spectroscopy technique is demonstrated for quantifying twist angles in Bi2Sr2CaCu2O8+X cuprate heterostructures. By analyzing anisotropic vibrational modes, particularly the A1g mode at ~116 cm−1, distinct optical fingerprints of interlayer misalignment are identified, enabling precise and reliable twist‐angle metrology for fragile, superconducting van der Waals quantum materials.

PurposeShortening the duration of antibiotic therapy (ABT) is a key measure in antimicrobial stewardship. The optimal duration of ABT for treatment of postoperative intra-abdominal infections (PIAI) in critically ill patients is unknown.MethodsA multicentre prospective randomised trial conducted in 21 French intensive care units (ICU) between May 2011 and February 2015 compared the efficacy and safety of 8-day versus 15-day antibiotic therapy in critically ill patients with PIAI. Among 410 eligible patients (adequate source control and ABT on day 0), 249 patients were randomly assigned on day 8 to either stop ABT immediately (n = 126) or to continue ABT until day 15 (n = 123). The primary endpoint was the number of antibiotic-free days between randomisation (day 8) and day 28. Secondary outcomes were death, ICU and hospital length of stay, emergence of multidrug-resistant (MDR) bacteria and reoperation rate, with 45-day follow-up.ResultsPatients treated for 8 days had a higher median number of antibiotic-free days than those treated for 15 days (15 [6–20] vs 12 [6–13] days, respectively; P < 0.0001) (Wilcoxon rank difference 4.99 days [95% CI 2.99–6.00; P < 0.0001). Equivalence was established in terms of 45-day mortality (rate difference 0.038, 95% CI − 0.013 to 0.061). Treatments did not differ in terms of ICU and hospital length of stay, emergence of MDR bacteria or reoperation rate, while subsequent drainages between day 8 and day 45 were observed following short-course ABT (P = 0.041).ConclusionShort-course antibiotic therapy in critically ill ICU patients with PIAI reduces antibiotic exposure. Continuation of treatment until day 15 is not associated with any clinical benefit.Clinicaltrials.gov identifierNCT01311765.

Patients with inflammatory rheumatisms, such as rheumatoid arthritis, are more prone to develop skin cancers than the general population, with an additional increased incidence when receiving TNF blockers. There is therefore a need that physicians treating patients affected with inflammatory rheumatisms with TNF blockers recognize malignant skin lesions, requiring an urgent referral to the dermatologist and a potential withdrawal or modification of the immunomodulatory treatment. We aimed to demonstrate that an online training dedicated to skin tumors increase the abilities of rheumatologists to discriminate skin cancers from benign skin tumors. A nationwide randomized web-based survey involving 141 French rheumatologists was conducted. The baseline evaluation included short cases with skin lesion pictures and multiple choice questions assessing basic knowledge on skin cancers. For each case, rheumatologists had to indicate the nature of skin lesion (benign; premalignant/malignant), their level of confidence in this diagnosis (10-points Likert scale), and the precise dermatological diagnosis among 5 propositions. Different scores were established. After randomization, only one group had access to the online formation consisting in 4 e-learning modules on skin tumors, of 15 minutes each (online training group). After reevaluation, the trained and the non-trained group (control group) were compared. The primary end-point was the number of adequate diagnoses of the nature of the skin lesions. The mean number of adequate diagnosis for the benign versus premalignant/malignant nature of the lesions was higher in the online training group (13.4 vs. 11.2 points; p value <0.0001). While the other knowledge scores were also significantly higher, no statistical difference was observed on the level of self-confidence between the 2 groups. In conclusion, the online formation was effective to improve the rheumatologists' ability to diagnose skin cancer.