Trials of patent foramen ovale (PFO) closure to prevent recurrent stroke have been inconclusive. We investigated whether patients with cryptogenic stroke and echocardiographic features representing ...risk of stroke would benefit from PFO closure or anticoagulation, as compared with antiplatelet therapy.
In a multicenter, randomized, open-label trial, we assigned, in a 1:1:1 ratio, patients 16 to 60 years of age who had had a recent stroke attributed to PFO, with an associated atrial septal aneurysm or large interatrial shunt, to transcatheter PFO closure plus long-term antiplatelet therapy (PFO closure group), antiplatelet therapy alone (antiplatelet-only group), or oral anticoagulation (anticoagulation group) (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization groups 2 and 3). The primary outcome was occurrence of stroke. The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 2, and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 3.
A total of 663 patients underwent randomization and were followed for a mean (±SD) of 5.3±2.0 years. In the analysis of randomization groups 1 and 2, no stroke occurred among the 238 patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet-only group (hazard ratio, 0.03; 95% confidence interval, 0 to 0.26; P<0.001). Procedural complications from PFO closure occurred in 14 patients (5.9%). The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet-only group (4.6% vs. 0.9%, P=0.02). The number of serious adverse events did not differ significantly between the treatment groups (P=0.56). In the analysis of randomization groups 1 and 3, stroke occurred in 3 of 187 patients assigned to oral anticoagulants and in 7 of 174 patients assigned to antiplatelet therapy alone.
Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation. (Funded by the French Ministry of Health; CLOSE ClinicalTrials.gov number, NCT00562289 .).
Increased rates of sexually transmitted infections (STIs) have been reported among men who have sex with men. We aimed to assess whether post-exposure prophylaxis (PEP) with doxycycline could reduce ...the incidence of STIs.
All participants attending their scheduled visit in the open-label extension of the ANRS IPERGAY trial in France (men aged 18 years or older having condomless sex with men and using pre-exposure prophylaxis for HIV with tenofovir disoproxil fumarate plus emtricitabine) were eligible for inclusion in this open-label randomised study. Participants were randomly assigned (1:1) at a central site to take a single oral dose of 200 mg doxycycline PEP within 24 h after sex or no prophylaxis. The primary endpoint was the occurrence of a first STI (gonorrhoea, chlamydia, or syphilis) during the 10-month follow-up. The cumulative probability of occurrence of the primary endpoint was estimated in each group with the Kaplan-Meier method and compared with the log-rank test. The primary efficacy analysis was done on the intention-to-treat population, comprising all randomised participants. All participants received risk-reduction counselling and condoms, and were tested regularly for HIV. This trial is registered with ClinicalTrials.gov number, NCT01473472.
Between July 20, 2015, and Jan 21, 2016, we randomly assigned 232 participants (n=116 in the doxycycline PEP group and n=116 in the no-PEP group) who were followed up for a median of 8·7 months (IQR 7·8–9·7). Participants in the PEP group used a median of 680 mg doxycycline per month (IQR 280–1450). 73 participants presented with a new STI during follow-up, 28 in the PEP group (9-month probability 22%, 95% CI 15–32) and 45 in the no-PEP group (42%, 33–53; log-rank test p=0·007). The occurrence of a first STI in participants taking PEP was lower than in those not taking PEP (hazard ratio HR 0·53; 95% CI 0·33–0·85; p=0·008). Similar results were observed for the occurrence of a first episode of chlamydia (HR 0·30; 95% CI 0·13–0·70; p=0·006) and of syphilis (0·27; 0·07–0·98; p=0·047); for a first episode of gonorrhoea the results did not differ significantly (HR 0·83; 0·47–1·47; p=0·52). No HIV seroconversion was observed, and 72 (71%) of all 102 STIs were asymptomatic. Rates of serious adverse events were similar in the two study groups. Gastrointestinal adverse events were reported in 62 (53%) participants in the PEP group and 47 (41%) in the no-PEP group (p=0·05).
Doxycycline PEP reduced the occurrence of a first episode of bacterial STI in high-risk men who have sex with men.
France Recherche Nord & Sud Sida-HIV Hépatites (ANRS) and Bill & Melinda Gates Foundation.
The full data set of the NEMO-3 experiment has been used to measure the half-life of the two-neutrino double beta decay of Formula omittedMo to the ground state of Formula omittedRu, Formula omitted ...year. The two-electron energy sum, single electron energy spectra and distribution of the angle between the electrons are presented with an unprecedented statistics of Formula omitted events and a signal-to-background ratio of Formula omitted 80. Clear evidence for the Single State Dominance model is found for this nuclear transition. Limits on Majoron emitting neutrinoless double beta decay modes with spectral indices of Formula omitted, as well as constraints on Lorentz invariance violation and on the bosonic neutrino contribution to the two-neutrino double beta decay mode are obtained.
Mycoplasma genitalium (MG) is an emerging pathogen among men who have sex with men (MSM) with raising rates of antibiotic resistance. This study assessed the prevalence and incidence of MG infection ...in MSM enrolled in the open-label phase of the ANRS IPERGAY trial with on-demand tenofovir disoproxil fumarate/emtricitabine for human immunodeficiency virus prevention and the impact of doxycycline post-exposure prophylaxis (PEP).
210 subjects were tested at baseline and at 6 months by real-time PCR assays for MG detection in urine samples and oropharyngeal and anal swabs. Resistance to azithromycin (AZM), to fluoroquinolones (FQs), and to doxycycline was investigated in the French National Reference Center of Bacterial Sexually Transmitted Infections (STIs).
The all-site prevalence of MG at baseline was 10.5% (6.3% in urine samples, 4.3% in anal swabs, 0.5% in throat swabs) and remained unchanged at 6 months whether or not PEP was used: 9.9% overall, 10.2% with PEP, 9.6% without. The overall rate of MG resistance (prevalent and incident cases) to AZM and FQs was 67.6% and 9.1%, respectively, with no difference between arms. An in vivo mutation of the MG 16S rRNA, which could be associated with tetracycline resistance, was observed in 12.5% of specimens tested.
The prevalence of MG infection among MSM on pre-exposure prophylaxis was high and its incidence was not decreased by doxycycline prophylaxis with a similar high rate of AZM and FQ resistance, raising challenging issues for the treatment of this STI and supporting current recommendations to avoid testing or treatment of asymptomatic MG infection.
Following the 2010–2014 French national stroke action plan, the number of stroke center (SC) has gradually increased in France, allowing a homogeneous coverage and access to neurovascular care in ...organized and territorially defined structures. However, operational difficulties within SCs have been progressively reported over the last few years. The objective of this study was to identify the medical staff shortages in SC that may contribute to these difficulties.
A survey on the medical staffing level as of January 1, 2021 was sent to all French SC managers. Specific questions related on vacancies, need of interim medical staff, and participation in out-of-hour healthcare services.
Among the 139 SC managers contacted, 122 (88%) filled in the questionnaire. Analysis of the data showed that over 879 physician positions opened, 163 (18.5%) remained vacant for a mean of two years, and that in 51 SCs (41.9%), more than two positions were unfilled. In 13 of these 51 SCs, the out-of-hour healthcare services relied on less than four practitioners, defining a critical situation, and three other SCs had to close temporarily (2) or permanently (1). Moreover, 39.2% of SCs with at least one vacancy used interim physicians, for a median period of 12.5 weeks/year (IQR 5–18).
This study highlights the significant medical staff shortage in French SCs. In the absence of urgent measures, more SCs will close, jeopardizing the regional network and access to care for stroke patients.
Background and purpose
Asymptomatic intracranial hemorrhage (aICH) is a common occurrence after endovascular treatment (EVT) for acute ischemic stroke (AIS). The aims of this study were to address ...its impact on 3‐month functional outcome and to identify risk factors for aICH after EVT.
Methods
Patients with AIS attributable to anterior circulation large vessel occlusion who underwent EVT were enrolled in a multicenter prospective registry. Based on imaging performed 22–36 h post‐EVT, we included patients with no intracranial hemorrhage (ICH) or aICH. Poor outcome defined as a 3‐month modified Rankin Scale (mRS) score 4–6 and overall 3‐month mRS score distribution were compared according to presence/absence of aICH, and aICH subtype using logistic regression. We assessed the risk factors of aICH using a multivariate logistic regression model.
Results
Of the 1526 patients included in the study, 653 (42.7%) had aICH. Patients with aICH had a higher rate of poor outcome: odds ratio (OR) 1.88 (95% confidence interval CI 1.44–2.44). Shift analysis of mRS score found a fully adjusted OR of 1.79 (95% CI 1.47–2.18). Hemorrhagic infarction (OR 1.63 95% CI 1.22–2.18) and parenchymal hematoma (OR 2.99 95% CI 1.77–5.02) were associated with higher risk of poor outcome. Male sex, diabetes, coronary artery disease, baseline National Institutes of Health Stroke Scale score and Alberta Stroke Program Early Computed Tomography Score, number of passes and onset to groin puncture time were independently associated with aICH.
Conclusions
Patients with aICH, irrespective of the radiological pattern, have a worse functional outcome at 3 months compared with those without ICH after EVT for AIS. The number of EVT passes and the time from onset to groin puncture are factors that could be modified to reduce deleterious ICH.
In a prospective multicenter cohort study, asymptomatic intracranial hemorrhages do not seem to be so well named. Patients who suffer asymptomatic intracranial hemorrhages, irrespectively of the radiological pattern, have a worse functional outcome at 3‐months compared with those without intracranial hemorrhage after endovascular treatment for acute ischemic stroke. The number of endovascular treatment passes and the time from onset to groin puncture are factors that could be modified to reduce these deleterious ICH.
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Intravenous alteplase is the only thrombolytic treatment approved for patients with acute ischemic stroke (AIS). Although no randomized controlled trial (RCT) has shown the superiority of ...tenecteplase over alteplase in AIS, tenecteplase is increasingly used off-label in Stroke Units. The purpose of the present work was to provide an up-to-date set of expert consensus statements on the use of tenecteplase in AIS.
Members of the working group were selected by the French Neurovascular Society. RCTs comparing tenecteplase and alteplase in the treatment of AIS were reviewed. Recent meta-analysis and real-life experience data on tenecteplase published until 30th October 2021 were also analyzed. After a description of the available data, we tried to answer the subsequent questions about the use of tenecteplase in AIS: What dosage of tenecteplase should be preferred? How effective is tenecteplase for cerebral artery recanalization? What is the clinical effectiveness of tenecteplase? What is the therapeutic safety of tenecteplase? What are the benefits associated with tenecteplase ease of use? Then expert consensus statements for tenecteplase use were submitted. In October 2021 the working group was asked to review and revise the manuscript. In November 2021, the current version of the manuscript was approved.
A set of three expert consensus statements for the use of tenecteplase within 4.5hours of symptom onset in AIS patients were issued: (1) It is reasonable to use tenecteplase 0.25mg/kg when mechanical thrombectomy (MT) is planned. (2) Tenecteplase 0.25mg/kg can be used as an alternative to alteplase 0.9mg/kg in patients with medium- or small-vessel occlusion not retrievable with MT. (3) Tenecteplase 0.25mg/kg could be considered as an alternative to alteplase 0.9mg/kg in patients without vessel occlusion.
These expert consensus statements could provide a framework to guide the clinical decision-making process for the use of tenecteplase according to admission characteristics of AIS patients. However, existing data are limited, requiring inclusions in ongoing RCTs or real-life registries.
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