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Aim:To compare the microbial communities inside hemodialysis catheters from symptomatic and asymptomatic patients to determine their differences.Materials & methods:Catheters (n = 41) were removed from patients in the Saskatchewan Health Authority over an 18-month period. The catheter section inside the body was flushed and the contents were evaluated using culture-dependent and culture-independent analysis.Results:All catheters were colonized by bacteria, with considerable overlap between groups based on microbial communities and the individual species detected. More Gram-negative species were detected by sequencing, whereas predominantly Gram-positive strains were cultured. Antibiotic resistance and biofilm formation was widespread and not correlated with either catheter group.Conclusion:Common pathogens were detected in each set of catheters, therefore predicting infections based on the microbiology is difficult.

AbstractWe report a case of Vandammella animalimorsusin an adult female patient following a cat scratch/bite. Animal bite/scratches may lead to zoonotic transmission of bacteria that subsequently lead to infection. Wound management and antimicrobial therapy is often necessary. The organism was initially misidentified as Neisseria animaloris/zoodegmatisand highlights the difficulty of correctly identifying some bacteria in clinical microbiology laboratories.

In this paper, we will propose a way to accurately model certain naturally occurring collections of data. Through this proposed model, the proportion of das leading digit, $$d\in \llbracket 1,9\rrbracket $$d∈〚1,9〛, in data is more likely to follow a law whose probability distribution is determined by a specific upper bound, rather than Benford’s Law, as one might have expected. These probability distributions fluctuate nevertheless around Benford’s values. These peculiar fluctuations have often been observed in the literature in such data sets (where the physical, biological or economical quantities considered are upper bounded). Knowing beforehand the value of this upper bound enables to find, through the developed model, a better adjusted law than Benford’s one.

Résumé:Les personnes âgées atteintes de troubles neurocognitifs (démences) vivant en centre d’hébergement adoptent fréquemment des comportements réactifs qui limitent leur engagement dans des occupations. La présente étude vise à identifier des moyens d’intervention centrés sur l’engagement des personnes âgées ayant un trouble neurocognitif avec l’environnement humain et non humain en centre d’hébergement afin de diminuer leurs comportements réactifs, en particulier les comportements d’errance, d’apathie et d’agitation. Cette revue de la portée est basée sur la méthode proposée par Levac et ses collaborateurs (2010). Parmi les 21 études retenues, la plupart s’intéressent à des interventions ciblant l’environnement non humain (n=9) ou ciblant simultanément l’environnement humain et non humain (n=9). Plusieurs de ces interventions sont efficaces pour diminuer les comportements réactifs et permettent aux personnes âgées de s’engager avec leur environnement. Le support de l’environnement humain semble toutefois nécessaire à l’utilisation optimale de plusieurs interventions.Abstract:Background. Older adults with neurocognitive disorder (dementia) living in nursing homes frequently exhibit reactive behaviours that limit their engagement in occupations.Objectives. To identify interventions in terms of engagement with the human and nonhuman environment in nursing homes that help reduce reactive behaviours, in particular wandering, apathy and agitation.Methods. This scoping review is based on the methodology of Levac et al. (2010).Results. Of the 21 included studies, the majority focuses on interventions targeting the nonhuman environment (n=9) or simultaneously the human and nonhuman environments (n=9).Conclusions. Several interventions on the human and nonhuman environments have been deemed effective to reduce reactive behaviours and to enable older adults to engage with their environment. However, the support of the human environment seems to be necessary for the optimal use of several interventions.

RésuméLes personnes âgées atteintes de troubles neurocognitifs (démences) vivant en centre d’hébergement adoptent fréquemment des comportements réactifs qui limitent leur engagement dans des occupations. La présente étude vise à identifier des moyens d’intervention centrés sur l’engagement des personnes âgées ayant un trouble neurocognitif avec l’environnement humain et non humain en centre d’hébergement afin de diminuer leurs comportements réactifs, en particulier les comportements d’errance, d’apathie et d’agitation. Cette revue de la portée est basée sur la méthode proposée par Levac et ses collaborateurs (2010). Parmi les 21 études retenues, la plupart s’intéressent à des interventions ciblant l’environnement non humain (n=9) ou ciblant simultanément l’environnement humain et non humain (n=9). Plusieurs de ces interventions sont efficaces pour diminuer les comportements réactifs et permettent aux personnes âgées de s’engager avec leur environnement. Le support de l’environnement humain semble toutefois nécessaire à l’utilisation optimale de plusieurs interventions.

AbstractStaphylococcus pseudintermediusis increasingly recognized as a human pathogen. We report the first case of an urinary tract infection in a male patient with this organism.

In this study, we investigated how IBD patterns shared between individuals of the same breed could be informative of its admixture level, with the underlying assumption that the most admixed breeds, i.e. the least genetically isolated, should have a much more fragmented genome. We considered 111 goat breeds (i.e. 2501 individuals) and 156 sheep breeds (i.e. 3304 individuals) from Europe, Africa and Asia, for which beadchip SNP genotypes had been performed. We inferred the breed’s level of admixture from: (i) the proportion of the genome shared by breed’s members (i.e. “genetic integrity level” assessed from ADMIXTURE software analyses), and (ii) the “AV index” (calculated from Reynolds’ genetic distances), used as a proxy for the “genetic distinctiveness”. In both goat and sheep datasets, the statistical analyses (comparison of means, Spearman correlations, LM and GAM models) revealed that the most genetically isolated breeds, also showed IBD profiles made up of more shared IBD segments, which were also longer. These results pave the way for further research that could lead to the development of admixture indicators, based on the characterization of intra-breed shared IBD segments, particularly effective as they would be independent of the knowledge of the whole genetic landscape in which the breeds evolve. Finally, by highlighting the fragmentation experienced by the genomes subjected to crossbreeding carried out over the last few generations, the study reminds us of the need to preserve local breeds and the integrity of their adaptive architectures that have been shaped over the centuries.

The resistance of cancer cells to therapy is responsible for the death of most patients with cancer1. Epithelial-to-mesenchymal transition (EMT) has been associated with resistance to therapy in different cancer cells2,3. However, the mechanisms by which EMT mediates resistance to therapy remain poorly understood. Here, using a mouse model of skin squamous cell carcinoma undergoing spontaneous EMT during tumorigenesis, we found that EMT tumour cells are highly resistant to a wide range of anti-cancer therapies both in vivo and in vitro. Using gain and loss of function studies in vitro and in vivo, we found that RHOJ—a small GTPase that is preferentially expressed in EMT cancer cells—controls resistance to therapy. Using genome-wide transcriptomic and proteomic profiling, we found that RHOJ regulates EMT-associated resistance to chemotherapy by enhancing the response to replicative stress and activating the DNA-damage response, enabling tumour cells to rapidly repair DNA lesions induced by chemotherapy. RHOJ interacts with proteins that regulate nuclear actin, and inhibition of actin polymerization sensitizes EMT tumour cells to chemotherapy-induced cell death in a RHOJ-dependent manner. Together, our study uncovers the role and the mechanisms through which RHOJ acts as a key regulator of EMT-associated resistance to chemotherapy.

•Treatment options for carbapenem-resistant A. baumanniiare limited.•The ATLAS program collects antimicrobial activity data against A. baumanniiworldwide.•Regional tigecycline and colistin MIC90s were 1 or 2 mg/L against A. baumannii.•1.6%–10.2% of meropenem-resistant A. baumanniiin each region were colistin-resistant.•Rates of meropenem resistance were highest in Africa/Middle East and Latin America.

IMPORTANCE: Alzheimer disease (AD), a neurodegenerative disease characterized by β-amyloid plaques and τ tangles in the brain, represents an unmet medical need with no fully approved therapeutics to modify disease progression. OBJECTIVE: To investigate the safety and efficacy of crenezumab, a humanized monoclonal immunoglobulin G4 antibody targeting β-amyloid oligomers, in participants with prodromal to mild (early) AD. DESIGN, SETTING, AND PARTICIPANTS: Two phase 3 multicenter randomized double-blind placebo-controlled parallel-group efficacy and safety studies of crenezumab in participants with early AD, CREAD and CREAD2, were initiated in 2016 and 2017, respectively, and were designed to evaluate the efficacy and safety of crenezumab in participants with early AD. CREAD (194 sites in 30 countries) and CREAD2 (209 sites in 27 countries) were global multicenter studies. A total of 3736 and 3664 participants were screened in CREAD and CREAD2, respectively. A total of 3736 and 3664 participants were screened in CREAD and CREAD2, respectively. Both trials enrolled individuals aged 50 to 85 years with early AD. Participants with some comorbidities and evidence of cerebral infarction or more than 4 microbleeds or areas of leptomeningeal hemosiderosis on magnetic resonance imaging were excluded. After 2923 and 2858 were excluded, respectively, 813 participants in CREAD and 806 in CREAD2 were randomly assigned in a 1:1 ratio to either placebo or crenezumab. In the final analysis, there were 409 participants in the placebo group and 404 in the crenezumab group in CREAD and 399 in the placebo group and 407 in the crenezumab group in CREAD2. Data were analyzed up until January 2019 and August 2019, respectively. INTERVENTIONS: Participants received placebo or 60 mg/kg crenezumab intravenously every 4 weeks for up to 100 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was change from baseline to week 105 in Clinical Dementia Rating–Sum of Boxes (CDR-SB) score. RESULTS: There were 813 participants in CREAD (mean [SD] age, 70.7 [8.2] years; 483 female and 330 male) and 806 in CREAD2 (mean [SD] age, 70.9 [7.7] years; 456 female and 350 male). Baseline characteristics were balanced between both groups. The between-group difference in mean change from baseline in CDR-SB score (placebo minus crenezumab) was −0.17 (95% CI, −0.86 to 0.53; P = .63) at week 105 in the CREAD study (88 placebo; 86 crenezumab). Compared with previous trials, no new safety signals were identified, and amyloid-related imaging abnormalities with edema were rare, mild, and transient. No meaningful changes in AD biomarkers were observed. Both studies were discontinued following a preplanned interim analysis indicating that CREAD was unlikely to meet the primary end point. CONCLUSIONS AND RELEVANCE: Crenezumab was well tolerated but did not reduce clinical decline in participants with early AD. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: CREAD, NCT02670083; CREAD2, NCT03114657

We report a case of borderline oxacillin-resistant S. pseudintermedius(BORSP) in a rheumatoid arthritis patient with severe osteoporosis. The organism is also resistant to erythromycin and clindamycin. We also present clear evidence on transmission from the family dog.

Operando and in situ techniques are becoming mandatory to study Li-ion, post Li-ion, and solid-state batteries. They are essential for monitoring the (electro)chemical and dynamic processes in the battery environment and for providing understanding at different spatial and temporal scales. While operando measurements are becoming more and more routine, scientists have to keep in mind that such experiments are not always harmless for the battery operation, especially when using synchrotron techniques. This is the case in the example described herein with Mg batteries. We show that the electrode reactivity in a InSb/organohaluminate electrolyte/Mg cell is strongly retarded during operando synchrotron X-ray absorption acquisition. Through comparison of ex situ, operando, and in situ data, we demonstrate that this effect occurred only on the samples’ volumes exposed to the X-ray radiation. This study illustrates how incorrect conclusions might be drawn from operando measurements, especially when looking at new battery chemistries, and calls for extreme caution when designing and interpreting operando data.

AbstractThis article examines the rise of vernacular consequence marker ça-fait-que (CFQ),often realized as [fɛk] or [fak], at the expense of its standard counterparts doncand alorsin Montreal French. The apparent-time analysis is based on a 2012 corpus of semi-directed interviews collected in Montreal. Previous studies treated the CFQ/donc/alorsalternation as a purely lexical sociolinguistic variable. Our analysis shows how a vernacular variant (CFQ), initially associated with the working class and stigmatized, comes to compete, develop as a default form, and eventually crowd out forms at the other end of the social prestige scale (alorsand donc). We rely on new socio-phonetic considerations to unveil a reconfiguration of the variable. The integration of the sociophonetic dimension sheds light on a complex process of diffusion, where a change from below is propelled by an additional change, but from above. Our article shows the key role played by women in both changes.

The decarbonisation of the building heating sector requires a shift from decentralised fossil fuel heating appliances to systems converting energy carriers with low greenhouse gas (GHG) emissions. However, for certain energy carriers, a considerable portion of GHG emissions arises upstream during production, processing and transportation, rather than during energy conversion. Accurately quantifying these indirect GHG emissions typically requires life cycle assessments, which are often resource-intensive and impractical during the early stages of energy system design. This study introduces operational GHG emissions as a pragmatic metric for the preliminary assessment of energy carrier environmental impact in building heating applications. These operational GHG emissions include both direct CO2emissions and indirect CO2, CH4and N2O emissions. Based on a comprehensive literature analysis, average estimates are proposed for the operational GHG emissions of various energy carriers within a European context, including natural gas, oil, coal and wood, as well as the average European and Belgian electricity grid, and hydrogen from various production methods. The findings underscore the significant contribution of indirect GHG emissions, as the selection of the energy carrier with the lowest environmental impact hinges on whether direct emissions alone or the broader operational GHG emissions are considered. By integrating operational GHG emissions into the early design stages of energy systems, stakeholders can make more informed decisions about which energy systems warrant further investigation, thereby facilitating more sustainable energy system development from the outset.

Residential building heating stands as a significant energy consumer with substantial environmental implications. To facilitate a sustainable transition, it is essential to assess the emissions and costs associated with current heating practices. This study investigates the economical and environmental aspects of residential building heating in the Brussels-Capital Region (BCR), Belgium. Employing a bottom-up methodology that integrates Energy Performance of Buildings (EPB) certificates with specific emissions and cost data, the analysis evaluates the emissions (including direct and indirect greenhouse gases (GHG), NOx, SO2and PM2.5) and the levelized cost of heat (LCOH) of the existing array of heating appliances in the BCR. The analysis reveals notable variations in emissions intensity and LCOH across diverse heating technologies, highlighting the intricate interplay between environmental sustainability and economic viability. Wood and electric-powered appliances demonstrate relatively low GHG emissions compared to fossil fuel appliances. Nonetheless, individual wood-fueled appliances exhibit elevated NOxand PM2.5emissions compared to the current weighted average emissions intensity of the BCR. Furthermore, sensitivity analysis underscores the substantial influence of fuel price scenario on the most cost-effective heating technology. This study provides a balanced framework for informed decision-making on residential building heating, offering benchmarks for transitioning to a more sustainable urban heating infrastructure.

Staphylococcus pseudintermediusis a well known commensal organism of dogs but also a canine opportunistic pathogen. Reports of this organism being recovered from specimens from humans might suggest an increase prevalence in human infections and/or improved diagnostic leading to more accurate identification. Here we report a case of persistent S. pseudintermediusinfection in an adult female oncology patient including colonization of the tip of an indwelling catheter. Diligence by laboratories in correctly isolating and identifying this pathogen (including susceptibility testing) is essential for optimal patient care.

Graphical abstract:

Portal vein thrombosis (PVT) is no longer a contraindication for liver transplantation (LT). While therapeutic anticoagulation (tAC) is recommended during the waiting period, there is no evidence for its usefulness in the prevention of PVT recurrence after LT.

Portal vein thrombosis (PVT) is no longer a contraindication for liver transplantation (LT). While therapeutic anticoagulation (tAC) is recommended during the waiting period, there is no evidence for its usefulness in the prevention of PVT recurrence after LT. The aim of our study was to evaluate the role of tAC post‐LT in the prevention of PVT recurrence. All adult LTs performed in two high‐volume centers between 2003 and 2018 were retrospectively analysed. Only patients with PVT classified as Yerdel grade I or II and with standard portal reconstruction were included. PVT recurrence and tAC‐associated morbidity within 1 year were compared between patients receiving tAC or not. During the study period, of 2612 LTs performed, 235 (9%) patients with PVT were included; 113 patients (48.1%) received post‐LT tAC (tAC group) while 122 (51.9%) did not (non‐tAC group). The incidence of bleeding events was significantly higher in the tAC group (26 [23%] vs. 5 [4.1%], P< .01) and the initial hospitalization duration was longer (21 vs. 17.5 days, P< .01). Within the first year, PVT recurrence was observed for 9 (3.8%) patients without any difference between the tAC and non‐tAC groups (6 [5.1%] vs. 3 [2.5%], P= .39). The only identified risk factor for PVT recurrence was the recipients’ age (odds ratio= 0.94, P= .03). Graft (P= .11) and patient (P= .44) survival were similar between the two groups. Therapeutic anticoagulation is not necessary in the prevention of grade I/II PVT recurrence and is associated with higher morbidity and longer hospital stay.

This interview was conducted by Atiya Henry, Commissioning Editor of Future Microbiology.Joseph M Blondeau, MSc, PhD, RSM(CCM), SM(AAM), SM(ASCP), FCCP is a Clinical Microbiologist and Head of Clinical Microbiology at Royal University Hospital (Saskatoon Health Region) and the University of Saskatchewan in Saskatoon, Canada. He is also the Provincial Clinical Lead for Microbiology in Saskatchewan, Canada. He holds a Masters of Sciences in Microbiology from Dalhousie University (1985) and a Doctor of Philosophy in Medical Microbiology from the University of Manitoba (1989). Following completion of his PhD, he completed an 1-month post-doctoral training in an infectious diseases research laboratory at Dalhousie University and following which he completed a 2-year post-doctoral residency training program in Clinical Microbiology, also at Dalhousie University. He holds appointments as a Clinical Associate Professor of Pathology, Adjunct Professor of Microbiology and Immunology and Clinical Associate Professor of Ophthalmology. He teaches to undergraduate and graduate students in the areas of microbiology, infectious diseases, antimicrobial agents and pharmacology. Dr Blondeau’s main research interests are in the area of antimicrobial agents and antimicrobial resistance, clinical microbiology and clinical outcomes associated with antimicrobial therapy in both human and veterinary medicine.

A In-Pb solid solution is investigated as negative electrode for Mg-ion battery and shows reversible alloying, with upon magnesiation the formation of crystalline Mg2Pb and an electrochemically-driven amorphization of MgIn.

FAT1, which encodes a protocadherin, is one of the most frequently mutated genes in human cancers1–5. However, the role and the molecular mechanisms by which FAT1mutations control tumour initiation and progression are poorly understood. Here, using mouse models of skin squamous cell carcinoma and lung tumours, we found that deletion of Fat1accelerates tumour initiation and malignant progression and promotes a hybrid epithelial-to-mesenchymal transition (EMT) phenotype. We also found this hybrid EMT state in FAT1-mutated human squamous cell carcinomas. Skin squamous cell carcinomas in which Fat1was deleted presented increased tumour stemness and spontaneous metastasis. We performed transcriptional and chromatin profiling combined with proteomic analyses and mechanistic studies, which revealed that loss of function of FAT1activates a CAMK2–CD44–SRC axis that promotes YAP1 nuclear translocation and ZEB1expression that stimulates the mesenchymal state. This loss of function also inactivates EZH2, promoting SOX2expression, which sustains the epithelial state. Our comprehensive analysis identified drug resistance and vulnerabilities in FAT1-deficient tumours, which have important implications for cancer therapy. Our studies reveal that, in mouse and human squamous cell carcinoma, loss of function of FAT1promotes tumour initiation, progression, invasiveness, stemness and metastasis through the induction of a hybrid EMT state.

A critical review of the current state of knowledge of chemical emissions from indoor sources, partitioning among indoor compartments, and the ensuing indoor exposure leads to a proposal for a modular mechanistic framework for predicting human exposure to semivolatile organic compounds (SVOCs). Mechanistically consistent source emission categories include solid, soft, frequent contact, applied, sprayed, and high temperature sources. Environmental compartments are the gas phase, airborne particles, settled dust, indoor surfaces, and clothing. Identified research needs are the development of dynamic emission models for several of the source emission categories and of estimation strategies for critical model parameters. The modular structure of the framework facilitates subsequent inclusion of new knowledge, other chemical classes of indoor pollutants, and additional mechanistic processes relevant to human exposure indoors. The framework may serve as the foundation for developing an open-source community model to better support collaborative research and improve access for application by stakeholders. Combining exposure estimates derived using this framework with toxicity data for different end points and toxicokinetic mechanisms will accelerate chemical risk prioritization, advance effective chemical management decisions, and protect public health.

AbstractStaphylococcus pseudintermediuscolonizes and is a pathogen of dogs and is being increasingly recognized from specimens from humans with various infections. We describe a case of S. pseudintermediusbacteremia in a 4 month old pediatric oncology patient with clear evidence of transmission from the family pet.

Three mono-CN ligated anionic cobalt A3-triarylcorroles were synthesized and investigated as to their spectroscopic and electrochemical properties in CH2Cl2, pyridine (Py), and dimethyl sulfoxide (DMSO). The newly synthesized corroles provide the first examples of air-stable cobalt corroles with an anionic axial ligand and are represented as [(Ar)3CorCoIII(CN)]−TBA+, where Cor is the trivalent corrole macrocycle, Ar is p-(CN)Ph, p-(CF3)Ph, or p-(OMe)Ph, and TBA+is the tetra-n-butylammonium (TBA) cation. Multiple redox reactions are observed for each mono-CN derivative with a key feature being a more facile first oxidation and a more difficult first reduction in all three solvents as compared to all previously examined corroles with similar meso-and β-pyrrole substituents. Formation constants (log K) for conversion of the five-coordinate mono-CN complex to its six-coordinate bis-CN form ranged from 102.8for Ar = p-(OMe)Ph to 104.7for Ar = p-(CN)Ph in DMSO as determined by spectroscopic methodologies. The in situ generated bis-CN complexes, represented as [(Ar)3CorCoIII(CN)2]2–(TBA+)2, and the mixed ligand complexes, represented as [(Ar)3CorCoIII(CN)(Py)]−TBA+, were also investigated as to their electrochemical and spectroscopic properties. UV–visible spectra and electrode reactions of the synthesized mono-CN derivatives are compared with the neutral mono-DMSO cobalt corrole complexes and the in situ generated bis-CN and bis-Py complexes, and the noninnocent (or innocent) nature of each cobalt corrole system is addressed. The data demonstrate the ability of the CN–axial ligand(s) to stabilize the high-valent forms of the metallocorrole, leading to systems with innocent macrocyclic ligands. Although a number of six-coordinate cobalt(III) corroles with N-donor ligands were characterized in the solid state, a dissociation of one axial ligand readily occurs in nonaqueous solvents, and this behavior contrasts with the high stability of the currently studied bis-CN adducts in CH2Cl2, pyridine, or DMSO. Linear free energy relationships were elucidated between the meso-phenyl Hammett substituent constants (Σσ) and the measured binding constants, the redox potentials, and the energy of the band positions in the mono-CN and bis-CN complexes in their neutral or singly oxidized forms, revealing highly predictable trends in the physicochemical properties of the anionic corroles.

Methicillin-resistant Staphylococcus aureus(MRSA) has unfortunately become a common pathogen in many healthcare facilities. In many institutions, vancomycin remains the preferred agent for treating serious MRSA infections including bacteraemia with or without endocarditis. The mutant prevention concentration (MPC) testing ≥109colony forming units of bacteria, describes the antimicrobial drug concentration blocking the growth of the least susceptible cell from high density bacterial populations. With blood culture isolates of MRSA, we discovered strains with MPC values ≥32 µg/ml and viable cells could be readily recovered from agar plates containing 32 µg/ml of vancomycin. To investigate MRSA strains surviving in high concentrations of vancomycin on drug containing agar plates, we utilized electron microscopy to measure cell wall thickness as this has been previously reported as a potential mechanism of resistance1along with septum thickening. Our data shows MRSA replication from high density bacterial populations in the presence of ≥32 µg/ml of vancomycin. Such observations may explain vancomycin failure in some patients and/or persistent bacteraemia and could potentially question the use of this drug in some critically ill patients in favour of an alternative agent.

Eschscholtzia californicaCham. and Valeriana officinalisL. have long been used for the management of sleep disorders and anxiety. Use of a fixed combination of these two plant extracts (Phytostandard® d’Eschscholtzia et de Valériane, PiLeJe Laboratoire, France) was investigated in an observational study. Adults with adjustment insomnia according to the criteria of the International Classification of Sleep Disorders and with an insomnia severity index (ISI) score >7 enrolled by GPs took a maximum of four tablets of the eschscholtzia and valerian combination every night for four weeks. Within one month, ISI score decreased by approximately 30% (from 16.09 ± 3.67 at inclusion (V1) to 11.32 ± 4.78 at 4 weeks (V2); p < 0.0001). Night sleep duration significantly increased between the first and the fourth week of supplement intake, sleep efficiency increasing from 78.4% ± 12.5 to 84.6% ± 10.2 (p = 0.002). There was no improvement in sleep latency. The number of awakenings decreased by approximately 25% and their total duration by approximately 25 min. Anxiety score significantly decreased by 50% from 13.9 ± 7.3 at V1 to 6.7 ± 6.3 at V2 (p < 0.0001). The supplement was well tolerated. These results suggest that the tested combination of eschscholtzia and valerian extracts could be beneficial for the management of insomnia in adults and deserves further investigation.

IMPORTANCE: Among patients with ST-segment elevation myocardial infarction (STEMI) referred for primary percutaneous coronary intervention (PCI), a survival benefit associated with radial access compared with femoral access remains controversial. OBJECTIVE: To assess whether there is a survival benefit when radial access is used instead of femoral access among patients with STEMI referred for primary PCI. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, open-label, randomized clinical trial was conducted at 5 PCI centers in Canada. In total, 2292 patients with STEMI referred for primary PCI were enrolled between July 2011 and December 2018, with a 30-day follow-up. The primary analyses were conducted based on the intention-to-treat population. INTERVENTIONS: Patients were randomized to radial access (n = 1136) or to femoral access (n = 1156) for PCI. MAIN OUTCOMES AND MEASURES: Initially, the primary outcome was bleeding, but this outcome was modified to 30-day all-cause mortality following the recommendation of the granting agency. Secondary outcomes included recurrent myocardial infarction, stroke, and Thrombolysis in Myocardial Infarction–defined major or minor bleeding. RESULTS: Among the 2292 patients enrolled, the mean (SD) age of the patients randomized to radial access was 61.6 (12.3) years and to femoral access was 62.0 (12.1) years, with 883 male patients in the radial access and 901 male patients in the femoral access group. The trial was stopped early following a futility analysis. Primary PCI was performed in 1082 of 1136 patients (95.2%) in the radial access group and 1109 of 1156 patients (95.9%) in the femoral access group. Bivalirudin was administered to 1001 patients (88.1%) in the radial access group and to 1068 patients (92.4%) in the femoral access group, whereas glycoprotein IIb/IIIa inhibitors were administered in only 69 patients (6.1%) in the radial access group and 68 patients (5.9%) in the femoral access group. A vascular closure device was used in 789 patients (68.3%) in the femoral group. The primary outcome, 30-day all-cause mortality, occurred in 17 patients (1.5%) assigned to radial access and in 15 patients (1.3%) assigned to femoral access (relative risk [RR], 1.15; 95% CI, 0.58-2.30; P = .69). There were no significant differences between patients assigned to radial and femoral access in the rates of reinfarction (1.8% vs 1.6%; RR, 1.07; 95% CI, 0.57-2.00; P = .83), stroke (1.0% vs 0.4%; RR, 2.24; 95% CI, 0.78-6.42; P = .12), and bleeding (1.4% vs 2.0%; RR, 0.71; 95% CI, 0.38-1.33; P = .28). CONCLUSIONS AND RELEVANCE: No significant differences were found for survival or other clinical end points at 30 days after the use of radial access vs femoral access in patients with STEMI referred for primary PCI. However, small absolute differences in end points cannot be definitively refuted given the premature termination of the trial. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01398254