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Abstract Background PARP inhibitors (PARPi) are used in the treatment of ovarian, breast, pancreatic, and prostate cancers. Pneumonitis has been identified as a potential side effect, with a higher meta-analysis-assessed risk for olaparib versus other PARPi. Olaparib-induced interstitial lung disease (O-ILD) was first described within the Japanese population, with few information available for Caucasian patients. Methods We performed a retrospective study by pooling data from the French and Belgian pharmacovigilance databases from 2018 to 2022. Patients with O-ILD were included following a central review by: 1) pharmacologists using the French drug causality assessment method; 2) senior pneumologists or radiologists, using the Fleischner Society’s recommendations. Results Five patients were identified and analysed. All were females, with ovarian or breast cancer. Median age at O-ILD diagnosis was 71 (38–72) years old, with no smoking history. Median delay between treatment initiation and symptom occurrence was 12 (6–33) weeks. Pneumonitis severity assessed using the Common Terminology Criteria for Adverse Events V5 was Grade 3 (n = 4) or 2 (n = 1). CT-scan review (n = 3) described hypersensitivity pneumonitis reaction as a common pattern. Bronchioalveolar lavage (n = 4) revealed lymphocytic alveolitis. Treatments relied on olaparib discontinuation (n = 5) and glucocorticoid intake (n = 4), with no fatal issue. Safe re-challenge with PARPi occurred in two patients. Forty additional O-ILD cases were identified in the WHO VigiBase database, including one fatal case. Conclusions PARPi-ILD is a rare but potentially life-threatening disease, presenting as a hypersensitivity pneumonitis pattern within 3 months of PARPi initiation. Treatment primarily relies on medication discontinuation. Re-challenging with another PARPi could be considered. Clinical trial number CEPRO #2023–010.

Abstract Using a combination of short- and long-reads sequencing, we were able to sequence the complete mitochondrial genome of the invasive ‘New Zealand flatworm’ Arthurdendyus triangulatus (Geoplanidae, Rhynchodeminae, Caenoplanini) and its two complete paralogous nuclear rRNA gene clusters. The mitogenome has a total length of 20,309 bp and contains repetitions that includes two types of tandem-repeats that could not be solved by short-reads sequencing. We also sequenced for the first time the mitogenomes of four species of Caenoplana (Caenoplanini). A maximum likelihood phylogeny associated A. triangulatus with the other Caenoplanini but Parakontikia ventrolineata and Australopacifica atrata were rejected from the Caenoplanini and associated instead with the Rhynchodemini, with Platydemus manokwari. It was found that the mitogenomes of all species of the subfamily Rhynchodeminae share several unusual structural features, including a very long cox2 gene. This is the first time that the complete paralogous rRNA clusters, which differ in length, sequence and seemingly number of copies, were obtained for a Geoplanidae.

We introduce an approach to sampling equilibrium solvent water molecule configurations within proteins that leverages analog quantum computing. We present a complete end-to-end study from the molecular biology application to the development of the quantum algorithm to the implementation on a neutral atom quantum processing unit (QPU). To do so, we combine a quantum placement strategy to the 3D Reference Interaction Site Model, an approach capable of predicting continuous solvent distributions. The intrinsic quantum nature of such coupling guarantees molecules not to be placed too close to each other, a constraint usually imposed by hand in classical approaches. We present first a full quantum adiabatic evolution model that uses a local Rydberg Hamiltonian to cast the general problem into an antiferromagnetic Ising model. Its solution is embodied into a Rydberg atom array QPU. Following a classical emulator implementation, a QPU portage allows to experimentally validate the algorithm performances on an actual quantum computer. As a perspective of use on next generation devices, we emulate a second hybrid quantum-classical version of the algorithm. Such a variational quantum approach uses a classical Bayesian minimization routine to find the optimal laser parameters. Overall, these Quantum-3D-RISM algorithms open a route towards the application of analog quantum computing in molecular modeling and drug design.

Background Identifying factors that predict the course of persistent symptoms that occurred during the COVID-19 pandemic is a public health issue. Modifiable factors could be targeted in therapeutic interventions.Objective This prospective study based on the population-based CONSTANCES cohort examined whether the psychological burden associated with incident persistent symptoms (ie, that first occurred from March 2020) would predict having ≥1 persistent symptom 6–10 months later.Methods A total of 8424 participants (mean age=54.6 years (SD=12.6), 57.2% women) having ≥1 incident persistent symptom at baseline (ie, between December 2020 and February 2021) were included. The psychological burden associated with these persistent symptoms was assessed with the Somatic Symptom Disorder-B Criteria Scale (SSD-12). The outcome was having ≥1 persistent symptom at follow-up. Adjusted binary logistic regression models examined the association between the SSD-12 score and the outcome.Findings At follow-up, 1124 participants (13.3%) still had ≥1 persistent symptom. The SSD-12 score at baseline was associated with persistent symptoms at follow-up in both participants with (OR (95% CI) for one IQR increase: 1.42 (1.09 to 1.84)) and without SARS-CoV-2 infection prior to baseline (1.39 (1.25 to 1.55)). Female gender, older age, poorer self-rated health and infection prior to baseline were also associated with persistent symptoms at follow-up.Conclusions The psychological burden associated with persistent symptoms at baseline predicted the presence of ≥1 persistent symptom at follow-up regardless of infection prior to baseline.Clinical implications Intervention studies should test whether reducing the psychological burden associated with persistent symptoms could improve the course of these symptoms.

The potential of chitosans to control grapevine trunk diseases (GTDs) has been studied in a public-private partnership. In vitro tests, vineyard efficacy trials and laboratory analyses were carried out to understand their mode of action. In vitro, low molecular weight (MW) chitosans, the most soluble, were often the most effective. In the vineyard, the most effective were those with a medium MW, in particular chitosan hydrochlorides which form a protective film. They could be used to dress wounds caused by pruning, re-trunking or curettage.

Acute exercise induces transient modifications in the tumor microenvironment and has been linked to reduced tumor growth along with increased infiltration of immune cells within the tumor in mouse models. In this study, we aimed to evaluate the impact of acute exercise before treatment administration on tumor growth in a mice model of MC38 colorectal cancer receiving an immune checkpoint inhibitor (ICI) and chemotherapy. Six-week-old mice injected with colorectal cancer cells (MC38) were randomized in 4 groups: control (CTRL), immuno-chemotherapy (TRT), exercise (EXE) and combined intervention (TRT/EXE). Both TRT and TRT-EXE received ICI: anti-PD1-1 (1 injection/week) and capecitabine + oxaliplatin (5 times a week) for 1 week (experimentation 1), 3 weeks (experimentation 2). TRT-EXE and EXE groups were submitted to 50 minutes of treadmill exercise before each treatment administration. Over the protocol duration, tumor size has been monitored daily. Tumor growth and microenvironment parameters were measured after the intervention on Day 7 (D7) and Day 16 (D16). From day 4 to day 7, tumor volumes decreased in the EXE/TRT group while remaining stable in the TRT group (p=0.0213). From day 7 until day 16 tumor volume decreased with no significant difference between TRT and TRT/EXE. At D7 the TRT/EXE group exhibited a higher total infiltrate T cell (p=0.0118) and CD8+ cytotoxic T cell (p=0.0031). At D16, tumor marker of apoptosis, vascular integrity and inflammation were not significantly different between TRT and TRT/EXE. Our main result was that acute exercise before immuno-chemotherapy administration significantly decreased early-phase tumor growth (D0 to D4). Additionally, exercise led to immune cell infiltration changes during the first week after exercise, while no significant molecular alterations in the tumor were observed 3 weeks after exercise.

The foundations of the Curiosithèque project are presented here: the aim is to map and inventory the written production that accompanied collections of curiosities by bringing together for the first time in a digital library the scattered volumes and fragments of a library of curiosities (1565–1750). The possible applications of the project are demonstrated using a case study drawn from the printed works in the Gaignières collection.

Abstract Background Carotid atherosclerotic plaques remain silent until their rupture, which may lead to detrimental ischemic events such as strokes. This is due, in part, to intraplaque hemorrhages (IPH) and the resulting inflammatory processes, which may promote carotid plaque vulnerability. Currently, the benefits of carotid endarterectomy remain unclear for asymptomatic patients. Interestingly, the completion of physical activity (PA) may have beneficial effects; however, the paucity of current data warrants robust longitudinal interventions. We therefore aim to study the effects of a 6-month longitudinal personalized home-based PA program on IPH, biological, and inflammatory markers in asymptomatic stroke patients. Methods Eighty patients (≥ 18 years old) will be recruited for the Physical Activity and Carotid Atherosclerotic Plaque Hemorrhage (PACAPh) clinical trial from the Hospices Civils de Lyon. Patients will be eligible if they present with carotid stenosis ≥ 50% and are asymptomatic from any ischemic events for at least 6 months. Recruited patients will be randomized into either a PA or a control group, and assessed at baseline and after 6 months. At both time points, all patients will be assessed using magnetic resonance imaging to assess IPH, blood sampling to measure inflammatory markers and monocytic phenotyping, PA and sedentary behavior questionnaires, 6-min walking test, and maximal isometric quadricep contraction test. The randomized PA intervention will consist of reaching a daily walking step goal individually tailored to each patient. Steps will be collected using a wirelessly connected wristband. The number of steps completed by individuals in the PA group will be re-evaluated bimonthly to encourage walking habits. Discussion The PACAPh study is the first of its kind representing a feasible, easily accessible therapeutic strategy for asymptomatic stroke patients. We hypothesize that the personalized home-based PA program will reduce IPH and modulate inflammatory and biological parameters in patients presenting with carotid plaques. If the results of the PACAPh study prove to be beneficial on such health parameters, the implementation of such kind of intervention in the daily treatment of these patients would be an advantageous and cost-effective practice to adopt globally. Trial registration This study has been approved by the National Ethics Committee (IDRCB:2019-A01543-54/SI:19.06.21.40640). ClinicalTrials.gov NCT04053166

Objective To evaluate the impact of conducting all possible pooled analyses across different combinations of randomised controlled trials and endpoints.Design Multiverse analysis, consisting of numerous pooled analyses of individual participant data.Setting Individual patient data from 12 randomised controlled trials comparing canagliflozin treatment with placebo, shared on the Yale University Open Data Access project (https://yoda.yale.edu/) platform, up to 16 April 2021.Participants 15 094 people with type 2 diabetes mellitus.Main outcome measures Pooled analyses estimated changes in serum glycated haemoglobin (HbA1c), major adverse cardiovascular events, and serious adverse events at weeks 12, 18, 26, and 52. The distribution of effect estimates was calculated for all possible combinations, and the direction and magnitude of the first and 99th centiles of effect estimates were compared.Results Across 16 332 distinct pooled analyses comparing canagliflozin with placebo for changes in HbA1c, standardised effect estimates were in favour of canagliflozin treatment at both the first centile (−0.75%) and 99th centile (−0.48%); 15 994 (97.93%) analyses showed significant results (P

Introduction: The clinical presentation of the behavioral variant of frontotemporal dementia (bvFTD) differs from that of Alzheimer disease (AD), with major impairments in behavioral functions in bvFTD and cognitive impairment in AD. Both behavioral disturbances in bvFTD and cognitive impairment in AD contribute to caregiver burden. Objective: To investigate the impact of home confinement during the COVID-19 crisis on the burden of caregivers of bvFTD or AD patients. Methods: During the COVID-19 lockdown in France, neurologists and neuropsychologists from the Memory Center of Nantes Hospital conducted teleconsultations for 38 AD patients and 38 bvFTD patients as well as for their caregivers. During these consultations, caregivers were invited to rate the change in their burden during home confinement. They were also invited to rate behavioral or emotional changes in the patients during, compared with before, the confinement. Results: Twenty-two bvFTD caregivers and 14 AD caregivers experienced an increase in burden. For bvFTD caregivers, this increased burden occurred regardless of behavioral changes, while AD caregivers experienced an increased burden related to changes in patients’ neuropsychiatric symptoms. Among the whole cohort, 2 factors were associated with increased caregiver burden: behavioral change and bvFTD. Conclusion: The results demonstrate that during home confinement in the COVID-19 crisis, neuropsychiatric symptoms were the core factor that impacted caregiver burden in different ways depending on the disease.

En tant qu'usager et gestionnaire d'eaux de surface, EDF contribue pleinement à l'atteinte du bon état écologique défini par la directive cadre européenne sur l'eau. La direction « Recherche et Développement » d'EDF (EDF R&D) s'est donc mobilisée pour fournir une expertise sur les bioindicateurs retenus, notamment pour les poissons. L'objectif était d'évaluer leur réponse aux pressions à proximité des aménagements de production d'électricité. L'analyse des résultats de l'IPR obtenus dans deux contextes piscicoles a été réalisée par EDF R&D, en collaboration avec l'Office Français de la Biodiversité : (i) peuplement plurispécifique d'un grand cours d'eau et (ii) peuplement salmonicole dominé par la truite. L'indice poissons européen a également été appliqué dans ces mêmes contextes. Ces analyses ont mis en évidence les limites d'application et la robustesse de ces indicateurs. Elles ont notamment contribué à la notice d'utilisation de l'IPR publiée en 2006 par l'OFB. Les indices poissons développés pour l'évaluation de l'état écologique fournissent une évaluation synthétique de l'état des peuplements piscicoles. Seul un diagnostic fin permet l'évaluation de l'impact d'une perturbation donnée, comme la présence et l'exploitation des aménagements de production d'électricité.

Background: Persistent physical symptoms are common after a coronavirus disease 2019 (COVID-19) episode, but their pathophysiological mechanisms remain poorly understood. In this study, we aimed to explore the association between anxiety and depression at 1-month after acute infection and the presence of fatigue, dyspnea, and pain complaints at 3-month follow-up.Methods: We conducted a prospective study in patients previously hospitalized for COVID-19 followed up for 3 months. The Hospital Anxiety and Depression Scale (HAD-S) was administered by physicians at 1-month follow-up, and the presence of fatigue, dyspnea, and pain complaints was assessed at both 1 month and 3 months. Multivariable logistic regressions explored the association between anxiety and depression subscores and the persistence of each of the physical symptom at 3 months.Results: A total of 84 patients were included in this study (Median age: 60 years, interquartile range: 50.5–67.5 years, 23 women). We did not find any significant interaction between anxiety and the presence of fatigue, dyspnea, or pain complaints at 1 month in predicting the persistence of these symptoms at 3 months (all p ≥ 0.36). In contrast, depression significantly interacted with the presence of pain at 1 month in predicting the persistence of pain at 3 months (OR: 1.60, 95% CI: 1.02–2.51, p = 0.039), with a similar trend for dyspnea (OR: 1.51, 95% CI: 0.99–2.28, p = 0.052).Discussion and Conclusion: Contrary to anxiety, depression after an acute COVID-19 episode may be associated with and increased risk of some persistent physical symptoms, including pain and dyspnea.

Background: Cognitive complaints are frequent after COVID-19 but their clinical determinants are poorly understood. This study aimed to explore the associations of objective cognitive performances and psychological distress with cognitive complaints in COVID-19 survivors.Materials and Methods: Patients previously hospitalized for COVID-19 in a university hospital during the first wave of COVID-19 pandemic in France were followed-up at 1 month after their admission. Cognitive complaints were self-reported and standardized instruments were used to assess neuropsychological status (Digit Symbol Substitution Test, Semantic Verbal Fluency Test, Mini Mental Status Examination) and psychological distress (Hospital Anxiety and Depression Scale, HADS). Multivariable analyses were adjusted for age, sex, admission in intensive care unit (ICU) and need for oxygen and C-reactive protein.Results: One hundred patients (34% women, median age: 60 years [interquartile range: 49–72)] completed the neuropsychological assessment at follow-up. In multivariable analyses, cognitive complaints at 1-month were associated with greater HADS score (OR for one interquartile range: OR: 1.96, 95% CI: 1.08–3.57) and older age (OR: 1.05, 95% CI: 1.01–1.09) and, negatively, with admission in ICU (OR: 0.22, 95% CI: 0.05–0.90). In contrast, none of the objective neuropsychological test scores was significantly associated with cognitive complaints. Exploratory analysis showed that cognitive complaints were associated with both anxiety and depressive symptoms.Discussion: These preliminary results suggest that cognitive complaints at 1 month after a hospitalization for COVID-19 are associated with psychological distress, independently of objective neuropsychological status. Anxiety and depression symptoms should be systematically screened in patients presenting with cognitive complaints after a severe COVID-19 episode.

Objectives To determine whether the terrorist attacks occurring in Paris on November 2015 have changed benzodiazepine use in the French population.Design Interrupted time series analysis.Setting National population-based cohort.Participants 90 258 individuals included in the population-based CONSTANCES cohort from 2012 to 2017.Outcome measures Benzodiazepine use was evaluated according to two different indicators using objective data from administrative registries: weekly number of individuals with a benzodiazepine delivered prescriptions (BDP) and weekly number of defined daily dose (DDD). Two sets of analyses were performed according to sex and age (≤50 vs >50). Education, income and area of residence were additional stratification variables to search for at-risk subgroups.Results Among women, those with younger age (incidence rate ratios (IRR)=1.18; 95% CI=1.05 to 1.32 for BDP; IRR=1.14; 95% CI=1.03 to 1.27 for DDD), higher education (IRR=1.23; 95% CI=1.03 to 1.46 for BDP; IRR=1.23; 95% CI=1.01 to 1.51 for DDD) and living in Paris (IRR=1.27; 95% CI=1.05 to 1.54 for BDP) presented increased risks for benzodiazepine use. Among participants under 50, an overall increase in benzodiazepine use was identified (IRR=1.14; 95% CI=1.02 to 1.28 for BDP and IRR=1.12; 95% CI=1.01 to 1.25 for DDD) and in several strata. In addition to women, those with higher education (IRR=1.22; 95% CI=1.02 to 1.47 for BDP), lower income (IRR=1.17; 95% CI=1.02 to 1.35 for BDP) and not Paris residents (IRR=1.13; 95% CI=1.02 to 1.26 for BDP and IRR=1.13; 95% CI=1.03 to 1.26 for DDD) presented increased risks for benzodiazepine use.Conclusion Terrorist attacks might increase benzodiazepine use at a population level, with at-risk subgroups being particularly concerned. Information and prevention strategies are needed to provide appropriate care after such events.

We conducted a retrospective study on all cases of pneumococcal septic arthritis (SA) in patients >18 years of age reported to the Picardie Regional Pneumococcal Network in France during 2005–2016. Among 1,062 cases of invasive pneumococcal disease, we observed 16 (1.5%) SA cases. Although SA is uncommon in adult patients, the prevalence of pneumococcal SA in the Picardie region increased from 0.69% during 2005–2010 to 2.47% during 2011–2016 after introduction of the pneumococcal 13-valent conjugate vaccine. We highlight the emergence of SA cases caused by the 23B serotype, which is not covered in the vaccine.

Abstract Background Heterogeneity and lack of targeted therapies represent the two main impediments to precision treatment of triple-negative breast cancer (TNBC), and therefore, molecular subtyping and identification of therapeutic pathways are required to optimize medical care. The aim of the present study was to define robust TNBC subtypes with clinical relevance. Methods Gene expression profiling by means of DNA chips was conducted in an internal TNBC cohort composed of 238 patients. In addition, external data (n = 257), obtained by using the same DNA chip, were used for validation. Fuzzy clustering was followed by functional annotation of the clusters. Immunohistochemistry was used to confirm transcriptomics results: CD138 and CD20 were used to test for plasma cell and B lymphocyte infiltrations, respectively; MECA79 and CD31 for tertiary lymphoid structures; and UCHL1/PGP9.5 and S100 for neurogenesis. Results We identified three molecular clusters within TNBC: one molecular apocrine (C1) and two basal-like-enriched (C2 and C3). C2 presented pro-tumorigenic immune response (immune suppressive), high neurogenesis (nerve infiltration), and high biological aggressiveness. In contrast, C3 exhibited adaptive immune response associated with complete B cell differentiation that occurs in tertiary lymphoid structures, and immune checkpoint upregulation. External cohort subtyping by means of the same approach proved the robustness of these results. Furthermore, plasma cell and B lymphocyte infiltrates, tertiary lymphoid structures, and neurogenesis were validated at the protein levels by means of histological evaluation and immunohistochemistry. Conclusion Our work showed that TNBC can be subcategorized in three different subtypes characterized by marked biological features, some of which could be targeted by specific therapies.

Cet article étudie le récit des pratiques d’un enseignant responsable d’un lycée Nouveau Départ accueillant des élèves qui, après avoir décroché, retournent aux études L’approche paradoxale systémique (Barel, 1989) permet de souligner une des caractéristiques de ces structures atypiques: celle d’être hors des normes scolaires habituelles tout en préparant à une épreuve de certification du système scolaire, ce qui implique l’acquisition d’un contenu en référence à un diplôme de l’éducation nationale et l’intériorisation des exigences impersonnelles de sa passation. Décryptant les justifications des pratiques du responsable face à l’absentéisme — principale expression de l’indiscipline dans un Lycée Nouveau Départ — notre étude montre que c’est en ayant la conduite paradoxale de «viser l’impossible» que, lui et son équipe, remplissent leur mission.

Pre-term birth is a major health concern that occurs in approximately 10% of births worldwide. Despite high incidence rate, long-term consequences of pre-term birth remain unclear. Recent evidence suggests that elevated oxidative stress observed in pre-term born infants could persist into adulthood. Given that oxidative stress is known to play an important role in response to physical activity and hypoxia, we investigated whether oxidative stress responses to acute exercise in normoxia and hypoxia may be differently modulated in pre-term vs. full-term born adults. Twenty-two pre-term born and fifteen age-matched full-term born controls performed maximal incremental cycling tests in both normoxia (FiO2: 0.21) and normobaric hypoxia (FiO2: 0.13; simulated altitude of 3800 m) in blinded and randomized manner. Plasma levels of oxidative stress (advanced oxidation protein products [AOPP] and malondialdehyde), antioxidant (ferric reducing antioxidant power, glutathione peroxidase, catalase [CAT] and superoxide dismutase [SOD]) and nitrosative stress markers (nitrotyrosine, nitrite and total nitrite and nitrate [NOx]) were measured before and immediately after each test. AOPP (+24%, P

Abstract Innovative approaches combining regulatory networks (RN) and genomic data are needed to extract biological information for a better understanding of diseases, such as cancer, by improving the identification of entities and thereby leading to potential new therapeutic avenues. In this study, we confronted an automatically generated RN with gene expression profiles (GEP) from a cohort of multiple myeloma (MM) patients and normal individuals using global reasoning on the RN causality to identify key-nodes. We modeled each patient by his or her GEP, the RN and the possible automatically detected repairs needed to establish a coherent flow of the information that explains the logic of the GEP. These repairs could represent cancer mutations leading to GEP variability. With this reasoning, unmeasured protein states can be inferred, and we can simulate the impact of a protein perturbation on the RN behavior to identify therapeutic targets. We showed that JUN/FOS and FOXM1 activities are altered in almost all MM patients and identified two survival markers for MM patients. Our results suggest that JUN/FOS-activation has a strong impact on the RN in view of the whole GEP, whereas FOXM1-activation could be an interesting way to perturb an MM subgroup identified by our method.

BackgroundThe last international consensus on the management of type 2 diabetes (T2D) recommends SGLT-2 inhibitors or GLP-1 agonists for patients with clinical cardiovascular (CV) disease; metformin remains the first-line glucose lowering medication. Last studies suggested beneficial effects of SGLT-2 inhibitors or GLP-1 agonists compared to DPP-4 inhibitors, in secondary CV prevention. Recently, a potential benefit of SGLT-2 inhibitors in primary CV prevention also has been suggested. However, no comparison of all the new and the old hypoglycemic drugs is available on CV outcomes. We aimed to compare the effects of old and new hypoglycemic drugs in T2D, on major adverse cardiovascular events (MACE) and mortality.Methods and findingsWe conducted a systematic review and network meta-analysis of clinical trials. Randomized trials, blinded or not, assessing contemporary hypoglycemic drugs on mortality or MACE in patients with T2D, were searched for in Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov. References screening and data extraction were done by multiple observers. Each drug was analyzed according to its therapeutic class. A random Bayesian network meta-analysis model was used. The primary outcomes were overall mortality, cardiovascular mortality, and MACE. Severe adverse events and severe hypoglycemia were also recorded. 175,966 patients in 34 trials from 1970 to 2018 were included. No trials evaluating glinides or alpha glucosidase inhibitors were found. 17 trials included a majority of patients with previous cardiovascular history, 16 trials a majority of patients without. Compared to control, SGLT-2 inhibitors were associated with a decreased risk of overall mortality (OR = 0.84 [95% CrI: 0.74; 0.95]), SGLT-2 inhibitors and GLP-1 agonists with a decreased risk of MACE (OR = 0.89 [95% CrI: 0.81; 0.98] and OR = 0.88 [95% CrI: 0.81; 0.95], respectively). Compared to DPP-4 inhibitors, SGLT-2 inhibitors were associated with a decreased risk of overall mortality (OR = 0.82 [95% CrI: 0.69; 0.98]), GLP-1 agonists with a decreased risk of MACE (OR = 0.88 [95% CrI: 0.79; 0.99]). Insulin was also associated with an increased risk of MACE compared to GLP-1 agonists (OR = 1.19 [95% CrI: 1.01; 1.42]). Insulin and sulfonylureas were associated with an increased risk of severe hypoglycemia. In the trials including a majority of patients without previous CV history, the comparisons of SGLT-2 inhibitors, metformin and control did not showed significant differences on primary outcomes. We limited our analysis at the therapeutic class level.ConclusionsSGLT-2 inhibitors and GLP-1 agonists have the most beneficial effects, especially in T2D patients with previous CV diseases. Direct comparisons of SGLT-2 inhibitors, GLP-1 agonists and metformin are needed, notably in primary CV prevention.Trial registrationPROSPERO CRD42016043823.

Whereas bait and pitfall trappings are two of the most commonly used techniques for sampling ant assemblages, they have not been properly compared in temperate open habitats. In this study, taking advantage of a large-scale project of heathland restoration (three sites along the French Atlantic Coast forming a north-south gradient), we evaluated the relative efficiency of these two methods for assessing both taxonomic and functional diversities of ants. Ants were collected and identified to species level, and six traits related to morphology, behavior (diet, dispersal and maximum foraging distance), and social life (colony size and dominance type) were attributed to all 23 species. Both observed and estimated species richness were significantly higher in pitfalls compared to spatially pair-matched bait traps. Functional richness followed the same pattern, with consistent results for both community weighted mean (CWM) and Rao’s quadratic entropy. Taxonomic and functional diversities from pitfall assemblages increased from north to south locations, following a pattern frequently reported at larger spatial scales. Bait trapping can hardly be considered a complementary method to pitfall trapping for sampling ants in open temperate habitats, as it appears basically redundant with the latter sampling method, at least in coastal heathlands of the East-Atlantic coast.