Is the duration of dual antiplatelet therapy (DAPT) excessive in post-angioplasty in chronic coronary syndrome? Data from the France-PCI registry (2014-2019).

Background: while the duration of dual antiplatelet therapy (DAPT) following coronary angioplasty for chronic coronary syndrome (CCS) recommended by the European Society of Cardiology has decreased over the last decade, little is known about the adherence to those guidelines in clinical practice in France. Aim: To analyze the real duration of DAPT post coronary angioplasty in CCS, as well as the factors affecting this duration. Methods: Between 2014 and 2019, 8.836 percutaneous coronary interventions for CCS from the France-PCI registry were evaluated, with 1 year follow up, after exclusion of patients receiving oral anticoagulants, procedures performed within one year of an acute coronary syndrome, and repeat angioplasty. Results: Post-percutaneous coronary intervention (PCI) DAPT duration was > 12 months for 53.1% of patients treated for CCS; 30.5% had a DAPT between 7 and 12 months, and 16.4% a DAPT ≤ 6 months. Patients with L-DAPT (>12 months) were at higher ischemic risk [25.0% of DAPT score ≥2 vs. 18.8% DAPT score ≥2 in S&I-DAPT group (≤12 months)]. The most commonly used P2Y12 inhibitor was clopidogrel (82.2%). The prescription of ticagrelor increased over the period. Conclusions: post-PCI DAPT duration in CCS was higher than international recommendations in the France PCI registry between 2014 and 2019. More than half of the angioplasty performed for CCS are followed by a DAPT > 12 months. Ischemic risk assessment influences the duration of DAPT. This risk is probably overestimated nowadays, leading to a prolongation of DAPT beyond the recommended durations, thus increasing the bleeding risk.

[Aortic stenosis: An update]. / Rétrécissement aortique : mise au point.

Aortic stenosis remains one of the most frequent valvulopathy worldwide, burdened with great mortality and morbidity, and for which there is not yet an effective preventive approach, although the pathophysiological mechanisms involved in its development are better understood nowadays. Its cure, however, has been revolutionized in the last decade by the advent of transcatheter aortic valve implantation, or TAVI (also named transcatheter aortic valve replacement or TAVR). The technique of TAVI has been refined and its indications has been extended, following the publication of large randomized controlled trials where it was compared to surgical aortic valve replacement with favorable results. Consequently, transfemoral TAVR has become the first line of treatment in case of symptomatic severe aortic valve stenosis. In this review, we describe the pathophysiological mechanisms leading to severe aortic stenosis and the main ongoing randomized controlled trials targeting them. We describe the indication for surgical or percutaneous aortic valve replacement and the main complications following the procedure.

[COVID-19 and mechanical circulatory support]. / COVID-19 et assistance circulatoire.

Extracorporeal membrane oxygenation (ECMO) is mainly used as a rescue therapy in COVID-19 patients with severe acute respiratory distress syndrome (ARDS). More rarely, COVID-19 can be complicated by hemodynamic failure due to fulminant myocarditis or massive pulmonary embolism necessitating the implantation of venous-arterial ECMO. The management of ECMO during the COVID-19 pandemic is challenging due to some specificities related to the disease characteristics, such as the management of anticoagulation in patients with a hypercoagulable state and an increased risk of venous thromboembolism. In large retrospective cohorts, survival of ECMO-rescued COVID-19 patients with ADRS was reported to be similar to that reported in previous studies on ECMO support for severe ARDS. Full consideration of ECMO candidacy is crucial for appropriate allocation of resources.

[Older people with complex, combined care needs: the need for tailored collaborative care]. / Ouderen met complexe, gecombineerde problemen: noodzaak tot samenwerken op maat.

Older patients with combined psychiatric, physical and cognitive health problems - patients who need double care - benefit from integrated medical and psychiatric care. The characteristics of these patients, as well as the problems that may exist in offering them adequate integrated care, are illustrated on the basis of a case description. Improvement of existing regional arrangements, premised on a collaborative care model, and involving hospital care, mental health services, nursing home care and community care services, is recommended. In settings that offer 24 hour long-term residential care and treatment, the expertise of mental health services and nursing homes must be structurally combined.

Risk factors for cerebrospinal fluid shunt infections during an outbreak: a case-control study.

BACKGROUND: There are few published reports of cerebrospinal fluid (CSF) shunt infection outbreaks. In 2017-2018, British Columbia Children's Hospital (BCCH) experienced an increase in CSF shunt infections co-incident with a move to new operating rooms and a change in shunt catheters used. AIMS: To describe how an outbreak was detected, investigations were undertaken to determine the cause, risk factors associated with CSF shunt infection during the outbreak, and changes implemented to attempt to control the outbreak. METHODS: Retrospective case-control study. Population included patients who underwent new shunt insertion or revision. Univariate logistic regression models were fitted for each of the variables. Associations with P-values <0.2 were considered of potential interest for further investigation. FINDINGS: There were six cases of CSF shunt infection and 19 controls. The causative organism was different in each case. The only risk factors that met the criteria for further investigation were being a neonate at the time of surgery [odds ratio (OR) 9.0, 95% confidence interval (CI) 0.7-125.3, P=0.10] and the presence of gastrointestinal disease (OR 3.8, 95% CI 0.5-26.2, P=0.18). No association was found with the operating room used or the surgical staff. In response to the outbreak, human traffic through the operating rooms was limited, rigid adherence to the wearing of surgical masks was enforced, and return to the previous CSF shunt catheters used was implemented. CONCLUSION: No modifiable risk factors were associated with CSF shunt infection. After implementation of surgical protocol changes, no further cases of CSF shunt infection linked to the outbreak were identified.

[What antithrombotic treatment should we prescribe after transvalvular aortic valve implantation?] / Quel traitement antithrombotique après un remplacement valvulaire aortique percutané ?

The performance and indications of transvalvular aortic valve implantation or TAVI has considerably expanded and is now the first therapeutic line option in the management of severe aortic stenosis. The targeted population shares both high risk of ischemic complications, particularly stroke or subclinical leaflet thrombosis of the bioprothesis, as well as hemorrhagic complications, strongly correlated to death. Based on previous experience with intracoronary stents, a dual antiplatelet therapy has been recommended by experts' consensus. This paradigm is now challenged by the observed increased risk of hemorrhagic complications without a reduction of ischemic events. Moreover, the role of non-vitamin K oral anticoagulant in patients undergoing TAVI remains to be determined. Several large ongoing randomized controlled trials will likely change our practice within the next coming year.

Long-term effectiveness and side effects of mandibular advancement devices on dental and skeletal parameters.

INTRODUCTION: Continuous positive airways pressure, generally used to treat obstructive sleep apnea-hypopnea syndrome (OSAHS), is not tolerated well by many patients. An alternative is to treat OSAHS with mandibular advancement devices (MAD). This research assesses the long term (> 2 years) effectiveness and the side effects on dental and skeletal parameters of these devices. MATERIAL AND METHODS: We selected 24 patients with moderate to severe OSAHS. All were treated with MADs for at least 2 years. We gathered cephalometric teleradiographs in centric relation and sleep recordings before and after the patients were treated. We evaluated the patients' apnea-hypopnea indexes (AHI) as well as their Epworth sleepiness scale (ESS) scores. We measured the inclination of the central incisors and the positions of the upper and lower jaws. RESULTS: Mandibular advancement devices were used for more than 2 years (3.9 ± 1.9 years). We observed a statistically significant decrease of the patients' AHI and their ESS scores. We also observed a modification of the inclination of the lower central incisors (+0.521; P = 0.047) and of the position of the maxilla (-0.287; P = 0.039). DISCUSSION: We demonstrated the clinical effectiveness of mandibular advancement devices for treating OSAHS, with a very low rate of side effects on dental and skeletal positions.

Management of antiplatelet therapy for non elective invasive procedures of bleeding complications: proposals from the French working group on perioperative haemostasis (GIHP), in collaboration with the French Society of Anaesthesia and Intensive Care Medicine (SFAR).

The French Working Group on Perioperative Haemostasis (GIHP) and the French Study Group on Haemostasis and Thrombosis (GFHT) in collaboration with the French Society of Anaesthesia and Intensive Care Medicine (SFAR) drafted up-to-date proposals on the management of antiplatelet therapy for non-elective invasive procedures or bleeding complications. The proposals were discussed and validated by a vote; all proposals could be assigned with a high strength. Emergency management of oral antiplatelet agents (APA) requires knowledge on their pharmacokinetic/pharmacodynamics parameters, evaluation of the degree of the alteration of haemostatic competence and the associated bleeding risk. Platelet function testing may be considered. When APA-induced bleeding risk may worsen the prognosis, measures should be taken to neutralise antiplatelet therapy by considering not only the efficacy of available means (which can be limited for prasugrel and even more for ticagrelor) but also the risks that these means expose the patient to. The measures include platelet transfusion at the appropriate dose and haemostatic agents (tranexamic acid; rFVIIa for ticagrelor). When possible, postponing non-elective invasive procedures at least for a few hours until the elimination of the active compound (which could compromise the effect of transfused platelets) or if possible a few days (reduction of the effect of APA) should be considered.

Use of radar detectors to track attendance of albatrosses at fishing vessels.

Despite international waters covering over 60% of the world's oceans, understanding of how fisheries in these regions shape ecosystem processes is surprisingly poor. Seabirds forage at fishing vessels, which has potentially deleterious effects for their population, but the extent of overlap and behavior in relation to ships is poorly known. Using novel biologging devices, which detect radar emissions and record the position of boats and seabirds, we measured the true extent of the overlap between seabirds and fishing vessels and generated estimates of the intensity of fishing and distribution of vessels in international waters. During breeding, wandering albatrosses (Diomedea exulans) from the Crozet Islands patrolled an area of over 10 million km2 at distances up to 2500 km from the colony. Up to 79.5% of loggers attached to birds detected vessels. The extent of overlap between albatrosses and fisheries has widespread implications for bycatch risk in seabirds and reveals the areas of intense fishing throughout the ocean. We suggest that seabirds equipped with radar detectors are excellent monitors of the presence of vessels in the Southern Ocean and offer a new way to monitor the presence of illegal fisheries and to better understand the impact of fisheries on seabirds.

Well-being of nursing staff on specialized units for older patients with combined care needs.

WHAT IS ALREADY KNOWN ABOUT THE SUBJECT: Working in long-term care is seen as a stressful, physically and mentally demanding occupation, and thus, nursing staff are at risk for work and stress-related diseases. In older patients, psychiatric illnesses often occur in combination with physical illnesses, requiring nursing care that is specific to these combined care needs. The impact of caring for these patients on the mental well-being of nurses is unknown. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE: Nursing staff working on specialized units for patients with combined care needs experience high levels of self-efficacy in combination with strong feelings of self-rated competence. Although levels of burnout are relatively low, mental healthcare nursing staff is more at risk for burnout when working in specialized settings for patients with combined care needs than nursing home staff working in specialized settings for these patients. Nursing staff characteristics, such as years of working experience and age, seem more important in relation to staff well-being than patient characteristics in specialized settings for combined care needs. WHAT ARE THE IMPLICATIONS FOR PRACTICE: Staff well-being might benefit from specializing care, so that patients with similar care needs are placed together and care is focused. The presence of specialized care units for older patients with combined care needs can allow for both targeted and focused allocation of nursing staff to these units and provision of specific training. ABSTRACT: Introduction In older patients, psychiatric illnesses frequently exist in tandem with physical illnesses, requiring nursing care that is specific to these combined care needs. The impact of caring for these patients on the mental well-being of nursing staff is unknown. AIM: To investigate whether care characteristics of patients with combined care needs are related to the mental well-being of nursing staff. METHOD: Well-being of nursing staff was studied within a larger exploratory observational cross-sectional study that examined the differences and similarities of specialized combined care units in Dutch mental healthcare and nursing home settings. RESULTS: Nursing staff across settings, with more than 5 years of work experience, felt competent in caring for patients with combined care needs. No significant effects of care characteristics of patients with combined care needs on the work-related well-being of nursing staff were shown. Both mental health nursing staff and older employees, however, were found to be more at risk for burnout. IMPLICATIONS/CONCLUSION: Staff well-being might benefit from placing patients with combined care needs together, so care is focused. The presence of specialized care units can allow for both targeted and focused allocation of nursing staff to these units and provision of specific training.

[Coronary thrombosis: Physiopathology and treatment in the era of tailored medicine]. / Thrombose coronaire : physiopathologie et traitement à l'ère de la médecine personnalisée.

Coronary thrombosis remains the leading cause for cardiovascular death in France. Great advances have been made in the knowledge of the basic mechanism involved in coronary thrombogenesis and in antithrombotic treatments. They have led to substantial survival benefit after myocardial infarction and enabled development of tailored therapeutic strategies, especially for high-risk patients. Direct oral anticoagulants have now entered the game for secondary prevention after coronary thrombosis.

Respective role of surface electrocardiogram and His bundle recordings to assess the risk of atrioventricular block after transcatheter aortic valve replacement.

BACKGROUND: Atrioventricular block (AVB) is common after transcatheter aortic valve replacement (TAVR) and permanent pacemaker (PPM) implantation is needed in up to 30% of patients. Main predictors of long term AVB are electrocardiographic. The purpose of this study is to assess the prognostic value of serial HV intervals measured before and after TAVR to shorten the timing of PPM implantation. METHODS: His bundle recordings were performed before (HV1), immediately after TAVR (HV2) and at day 2 for Edwards Sapien (ES) and 5 for Medtronic CoreValve (CV) (HV3). PPM indications were high degree AVB before day 5 or prolonged HV interval ≥80ms at the last recording. High degree AVB after discharge was evaluated from the pacemaker memories and ECG at 1 and 6months. RESULTS: Data were obtained in 84 patients (33% CV and 67% ES). HV values were not associated with early or late AVB. PPM were implanted in 27 patients (34%) for documented AVB (n=17, 24%), prolonged HV interval (n=9) or sick sinus syndrome (n=1). Persistent complete AVB during the procedure and postoperative high degree AVB were the only perioperative factors associated with further long term occurrence of high degree AVB (p=0.001 and p<0.001). On multivariate analysis, only postoperative high degree AVB was significant (p=0.001). CONCLUSION: Pre- and post-operative HV measurements were not correlated with late AVB after TAVR. Perioperative persistent complete AVB and postoperative high degree AVB are the only factors to predict late AVB and should be considered for the decision of PPM implantation.

The Journey of Lipoproteins Through the Cell: One Birthplace, Multiple Destinations.

Bacterial lipoproteins are a very diverse group of proteins characterized by the presence of an N-terminal lipid moiety that serves as a membrane anchor. Lipoproteins have a wide variety of crucial functions, ranging from envelope biogenesis to stress response. In Gram-negative bacteria, lipoproteins can be targeted to various destinations in the cell, including the periplasmic side of the cytoplasmic or outer membrane, the cell surface or the external milieu. The sorting mechanisms have been studied in detail in Escherichia coli, but exceptions to the rules established in this model bacterium exist in other bacteria. In this chapter, we will present the current knowledge on lipoprotein sorting in the cell. Our particular focus will be on the surface-exposed lipoproteins that appear to be much more common than previously assumed. We will discuss the different targeting strategies, provide numerous examples of surface-exposed lipoproteins and discuss the techniques used to assess their surface exposure.

Exome sequencing of extreme clopidogrel response phenotypes identifies B4GALT2 as a determinant of on-treatment platelet reactivity.

Interindividual variability in platelet aggregation is common among patients treated with clopidogrel and both high on-treatment platelet reactivity (HTPR) and low on-treatment platelet reactivity (LTPR) increase risks for adverse clinical outcomes. CYP2C19 influences clopidogrel response but only accounts for ∼12% of the variability in platelet reactivity. To identify novel variants implicated in on-treatment platelet reactivity, patients with coronary artery disease (CAD) with extreme pharmacodynamic responses to clopidogrel and wild-type CYP2C19 were subjected to exome sequencing. Candidate variants that clustered in the LTPR subgroup subsequently were genotyped across the discovery cohort (n = 636). Importantly, carriers of B4GALT2 c.909C>T had lower on-treatment P2Y12 reaction units (PRUs; P = 0.0077) and residual platelet aggregation (P = 0.0008) compared with noncarriers, which remained significant after adjusting for CYP2C19 and other clinical variables in both the discovery (P = 0.0298) and replication (n = 160; PRU: P = 0.0001) cohorts. B4GALT2 is a platelet-expressed galactosyltransferase, indicating that B4GALT2 c.909C>T may influence clopidogrel sensitivity through atypical cell-surface glycoprotein processing and platelet adhesion.

Female mate choice predicts paternity success in the absence of additive genetic variance for other female paternity bias mechanisms in Drosophila serrata.

After choosing a first mate, polyandrous females have access to a range of opportunities to bias paternity, such as repeating matings with the preferred male, facilitating fertilization from the best sperm or differentially investing in offspring according to their sire. Female ability to bias paternity after a first mating has been demonstrated in a few species, but unambiguous evidence remains limited by the access to complex behaviours, sperm storage organs and fertilization processes within females. Even when found at the phenotypic level, the potential evolution of any mechanism allowing females to bias paternity other than mate choice remains little explored. Using a large population of pedigreed females, we developed a simple test to determine whether there is additive genetic variation in female ability to bias paternity after a first, chosen, mating. We applied this method in the highly polyandrous Drosophila serrata, giving females the opportunity to successively mate with two males ad libitum. We found that despite high levels of polyandry (females mated more than once per day), the first mate choice was a significant predictor of male total reproductive success. Importantly, there was no detectable genetic variance in female ability to bias paternity beyond mate choice. Therefore, whether or not females can bias paternity before or after copulation, their role on the evolution of sexual male traits is likely to be limited to their first mate choice in D. serrata.

Home-based screening for biliary atresia using infant stool colour cards: a large-scale prospective cohort study and cost-effectiveness analysis.

OBJECTIVE: Biliary atresia (BA), a leading cause of paediatric liver failure and liver transplantation, manifests by three weeks of life as jaundice with acholic stools. Poor outcomes due to delayed diagnosis remain a problem worldwide. We evaluated and assessed the cost-effectiveness of methods of introducing a BA Infant Stool Colour Card (ISCC) screening programme in Canada. SETTING AND METHODS: A prospective study at BC Women's Hospital recruited consecutive healthy newborns through six incrementally more intensive screening approaches. Under the baseline "passive" strategy, families received ISCCs at maternity, with instructions to monitor infant stool colour daily and return the ISCC by mail at age 30 days. Additional strategies were: ISCC mailed to family physician; reminder letters or telephone calls to families or physicians. Random telephone surveys of ISCC non-returners assessed total card utilization. Primary outcome was ISCC utilization rate expressed as a composite outcome of the ISCC return rate and non-returned ISCC use. Markov modelling was used to predict incremental costs and life years gained from screening (passive and reminder), compared with no screening, over a 10-year time horizon. RESULTS: 6,187 families were enrolled. Card utilization rates in the passive screening strategy were estimated at 60-94%. For a Canadian population, the increase in cost for passive screening, compared with no screening, is $213,584 and the gain in life years is 9.7 ($22,000 per life-year gained). CONCLUSIONS: A BA ISCC screening programme targeting families of newborns is feasible in Canada. Passive distribution of ISCC at maternity is potentially effective and highly cost-effective.

Identification of poor response to P2Y12 inhibitors in ACS patients with a new ELISA-based vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation assay.

A new ELISA technique has been developed to measure the vasodilator-associated stimulated phosphoprotein (VASP) platelet reactivity index (PRI) in clopidogrel-treated patients. This technique has not been evaluated in acute coronary syndrome (ACS) patients or in prasugrel-treated patients. We assessed the accuracy of ELISA-VASP to identify high on-treatment platelet reactivity (HPR) in ACS patients in comparison with established platelet function tests. Platelet reactivity was measured in 240 ACS patients treated with clopidogrel (75 or 150 mg) or prasugrel (5 or 10 mg) using flow cytometry (FC-VASP) and the ELISA-VASP technique, light transmission aggregometry (LTA) and VerifyNow-P2Y12 assay (VN-P2Y12). When using the ELISA-VASP PRI, the rate of patients with HPR in the overall ACS population was 15.5%, including a 27% rate in clopidogrel-treated patients and a 4% rate in prasugrel-treated patients. There was a strong correlation between ELISA-VASP PRI and FC-VASP PRI (r = 0.83, r2 = 0.68 p < 0.0001) with an area under the receiver-operating characteristics (ROC) curve to identify HPR (VASP-PRI >50% with FC-VASP) of 0.94, p<0.0001. The threshold of 60% for ELISA-VASP PRI provided the best accuracy (likelihood ratio= 23.67) to identify patients with HPR when compared to FC-VASP, LTA or VN-P2Y12 assays. In conclusion, ELISA-VASP is a fast, easy-to-use and specific test to identify HPR in ACS patients on thienopyridines. A 60% threshold value displays the best accuracy to identify HPR in these patients.