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Importance: The optimal transfusion strategy in patients with acute myocardial infarction and anemia is unclear.Objective: To determine whether a restrictive transfusion strategy would be clinically noninferior to a liberal strategy.Design, Setting, and Participants: Open-label, noninferiority, randomized trial conducted in 35 hospitals in France and Spain including 668 patients with myocardial infarction and hemoglobin level between 7 and 10 g/dL. Enrollment could be considered at any time during the index admission for myocardial infarction. The first participant was enrolled in March 2016 and the last was enrolled in September 2019. The final 30-day follow-up was accrued in November 2019.Interventions: Patients were randomly assigned to undergo a restrictive (transfusion triggered by hemoglobin ≤8; n = 342) or a liberal (transfusion triggered by hemoglobin ≤10 g/dL; n = 324) transfusion strategy.Main Outcomes and Measures: The primary clinical outcome was major adverse cardiovascular events (MACE; composite of all-cause death, stroke, recurrent myocardial infarction, or emergency revascularization prompted by ischemia) at 30 days. Noninferiority required that the upper bound of the 1-sided 97.5% CI for the relative risk of the primary outcome be less than 1.25. The secondary outcomes included the individual components of the primary outcome.Results: Among 668 patients who were randomized, 666 patients (median [interquartile range] age, 77 [69-84] years; 281 [42.2%] women) completed the 30-day follow-up, including 342 in the restrictive transfusion group (122 [35.7%] received transfusion; 342 total units of packed red blood cells transfused) and 324 in the liberal transfusion group (323 [99.7%] received transfusion; 758 total units transfused). At 30 days, MACE occurred in 36 patients (11.0% [95% CI, 7.5%-14.6%]) in the restrictive group and in 45 patients (14.0% [95% CI, 10.0%-17.9%]) in the liberal group (difference, -3.0% [95% CI, -8.4% to 2.4%]). The relative risk of the primary outcome was 0.79 (1-sided 97.5% CI, 0.00-1.19), meeting the prespecified noninferiority criterion. In the restrictive vs liberal group, all-cause death occurred in 5.6% vs 7.7% of patients, recurrent myocardial infarction occurred in 2.1% vs 3.1%, emergency revascularization prompted by ischemia occurred in 1.5% vs 1.9%, and nonfatal ischemic stroke occurred in 0.6% of patients in both groups.Conclusions and Relevance: Among patients with acute myocardial infarction and anemia, a restrictive compared with a liberal transfusion strategy resulted in a noninferior rate of MACE after 30 days. However, the CI included what may be a clinically important harm.Trial Registration: ClinicalTrials.gov Identifier: NCT02648113. [ABSTRACT FROM AUTHOR]

Importance: Clinical guidelines for the early management of acute heart failure in the emergency department (ED) setting are based on only moderate levels of evidence, with subsequent low adherence to these guidelines.Objective: To test the effect of an early guideline-recommended care bundle on short-term prognosis in older patients with acute heart failure in the ED.Design, Setting, and Participants: Stepped-wedge cluster randomized trial in 15 EDs in France of 503 patients 75 years and older with a diagnosis of acute heart failure in the ED from December 2018 to September 2019 and followed up for 30 days until October 2019.Interventions: A care bundle that included early intravenous nitrate boluses; management of precipitating factors, such as acute coronary syndrome, infection, or atrial fibrillation; and moderate dose of intravenous diuretics (n = 200). In the control group, patient care was left to the discretion of the treating emergency physician (n = 303). Each center was randomized to the order in which they switched to the "intervention period." After the initial 4-week control period for all centers, 1 center entered in the intervention period every 2 weeks.Main Outcomes and Measures: The primary end point was the number of days alive and out of hospital at 30 days. Secondary outcomes included 30-day all-cause mortality, 30-day cardiovascular mortality, unscheduled readmission, length of hospital stay, and kidney impairment.Results: Among 503 patients who were randomized (median age, 87 years; 298 [59%] women), 502 were analyzed. In the intervention group, patients received a median (interquartile range) of 27.0 (9-54) mg of intravenous nitrates in the first 4 hours vs 4.0 (2.0-6.0) mg in the control group (adjusted difference, 23.8 [95% CI, 13.5-34.1]). There was a significantly higher percentage of patients in the intervention group treated for their precipitating factors than in the control group (58.8% vs 31.9%; adjusted difference, 31.1% [95% CI, 14.3%-47.9%]). There was no statistically significant difference in the primary end point of the number of days alive and out of hospital at 30 days (median [interquartile range], 19 [0- 24] d in both groups; adjusted difference, -1.9 [95% CI, -6.6 to 2.8]; adjusted ratio, 0.88 [95% CI, 0.64-1.21]). At 30 days, there was no significant difference between the intervention and control groups in mortality (8.0% vs 9.7%; adjusted difference, 4.1% [95% CI, -17.2% to 25.3%]), cardiovascular mortality (5.0% vs 7.4%; adjusted difference, 2.1% [95% CI, -15.5% to 19.8%]), unscheduled readmission (14.3% vs 15.7%; adjusted difference, -1.3% [95% CI, -26.3% to 23.7%]), median length of hospital stay (8 d in both groups; adjusted difference, 2.5 [95% CI, -0.9 to 5.8]), and kidney impairment (1% in both groups).Conclusions and Relevance: Among older patients with acute heart failure, use of a guideline-based comprehensive care bundle in the ED compared with usual care did not result in a statistically significant difference in the number of days alive and out of the hospital at 30 days. Further research is needed to identify effective treatments for acute heart failure in older patients.Trial Registration: ClinicalTrials.gov Identifier: NCT03683212. [ABSTRACT FROM AUTHOR]

Aims: Few studies describe recent changes in the prevalence, management, and outcomes of cardiogenic shock (CS) patients complicating acute myocardial infarction (AMI) in the era of widespread use of invasive strategies. The aim of the present study was to analyse trends observed in CS complicating AMI over the past 10 years, focusing on the timing of CS occurrence (i.e. primary CS, CS on admission vs. secondary CS, CS developed subsequently during hospitalization).Methods and Results: Three nationwide French registries conducted and designed to evaluate AMI management and outcomes in 'real-life' practice included consecutive AMI patients (n = 9951) admitted to intensive cardiovascular care units (ICCUs) over a 1-month period, 5 years apart. The prevalence of CS complicating AMI decreased from 2005 to 2015: 5.9%, mean age 74.1 ± 12.7 in 2005; 4.0%, mean age 73.9 ± 12.7 in 2010, 2.8%, mean age 71.1 ± 15.0 in 2015 (P < 0.001). It decreased for both primary (1.8% to 1.0%) and secondary CS (4.1% to 1.8%). The profile of CS patients also changed over time with more patients presenting out-of-hospital cardiac arrest. In both primary and secondary CS, the use of percutaneous coronary intervention increased markedly over time, as did the use of mechanical ventilation and cardiac assist devices. Over the 10-year period, in-hospital mortality remained unchanged for both primary CS (41.8% to 37.8%) or secondary CS (57.3% to 58.8%). However, 1-year mortality decreased in patients with primary CS (from 60% to 37.8%, P = 0.038), and remained unchanged in patients developing secondary CS (from 64.5% to 69.1%, P = 0.731).Conclusion: Cardiogenic shock complicating AMI has become less frequent but, if present, CS, and particularly secondary CS, carries a very high mortality, which has not substantially improved over the past 10 years, in spite of the more frequent use of invasive strategies. [ABSTRACT FROM AUTHOR]

Importance: The safety of the pulmonary embolism rule-out criteria (PERC), an 8-item block of clinical criteria aimed at ruling out pulmonary embolism (PE), has not been assessed in a randomized clinical trial.Objective: To prospectively validate the safety of a PERC-based strategy to rule out PE.Design, Setting, and Patients: A crossover cluster-randomized clinical noninferiority trial in 14 emergency departments in France. Patients with a low gestalt clinical probability of PE were included from August 2015 to September 2016, and followed up until December 2016.Interventions: Each center was randomized for the sequence of intervention periods. In the PERC period, the diagnosis of PE was excluded with no further testing if all 8 items of the PERC rule were negative.Main Outcomes and Measures: The primary end point was the occurrence of a thromboembolic event during the 3-month follow-up period that was not initially diagnosed. The noninferiority margin was set at 1.5%. Secondary end points included the rate of computed tomographic pulmonary angiography (CTPA), median length of stay in the emergency department, and rate of hospital admission.Results: Among 1916 patients who were cluster-randomized (mean age 44 years, 980 [51%] women), 962 were assigned to the PERC group and 954 were assigned to the control group. A total of 1749 patients completed the trial. A PE was diagnosed at initial presentation in 26 patients in the control group (2.7%) vs 14 (1.5%) in the PERC group (difference, 1.3% [95% CI, -0.1% to 2.7%]; P = .052). One PE (0.1%) was diagnosed during follow-up in the PERC group vs none in the control group (difference, 0.1% [95% CI, -∞ to 0.8%]). The proportion of patients undergoing CTPA in the PERC group vs control group was 13% vs 23% (difference, -10% [95% CI, -13% to -6%]; P < .001). In the PERC group, rates were significantly reduced for the median length of emergency department stay (mean reduction, 36 minutes [95% CI, 4 to 68]) and hospital admission (difference, 3.3% [95% CI, 0.1% to 6.6%]).Conclusions and Relevance: Among very low-risk patients with suspected PE, randomization to a PERC strategy vs conventional strategy did not result in an inferior rate of thromboembolic events over 3 months. These findings support the safety of PERC for very low-risk patients presenting to the emergency department.Trial Registration: clinicaltrials.gov Identifier: NCT02375919. [ABSTRACT FROM AUTHOR]

Importance: The high mortality rate in critically ill elderly patients has led to questioning of the beneficial effect of intensive care unit (ICU) admission and to a variable ICU use among this population.Objective: To determine whether a recommendation for systematic ICU admission in critically ill elderly patients reduces 6-month mortality compared with usual practice.Design, Setting, and Participants: Multicenter, cluster-randomized clinical trial of 3037 critically ill patients aged 75 years or older, free of cancer, with preserved functional status (Index of Independence in Activities of Daily Living ≥4) and nutritional status (absence of cachexia) who arrived at the emergency department of one of 24 hospitals in France between January 2012 and April 2015 and were followed up until November 2015.Interventions: Centers were randomly assigned either to use a program to promote systematic ICU admission of patients (n=1519 participants) or to follow standard practice (n=1518 participants).Main Outcomes and Measures: The primary outcome was death at 6 months. Secondary outcomes included ICU admission rate, in-hospital death, functional status, and quality of life (12-Item Short Form Health Survey, ranging from 0 to 100, with higher score representing better self-reported health) at 6 months.Results: One patient withdrew consent, leaving 3036 patients included in the trial (median age, 85 [interquartile range, 81-89] years; 1361 [45%] men). Patients in the systematic strategy group had an increased risk of death at 6 months (45% vs 39%; relative risk [RR], 1.16; 95% CI, 1.07-1.26) despite an increased ICU admission rate (61% vs 34%; RR, 1.80; 95% CI, 1.66-1.95). After adjustments for baseline characteristics, patients in the systematic strategy group were more likely to be admitted to an ICU (RR, 1.68; 95% CI, 1.54-1.82) and had a higher risk of in-hospital death (RR, 1.18; 95% CI, 1.03-1.33) but had no significant increase in risk of death at 6 months (RR, 1.05; 95% CI, 0.96-1.14). Functional status and physical quality of life at 6 months were not significantly different between groups.Conclusions and Relevance: Among critically ill elderly patients in France, a program to promote systematic ICU admission increased ICU use but did not reduce 6-month mortality. Additional research is needed to understand the decision to admit elderly patients to the ICU.Trial Registration: clinicaltrials.gov Identifier: NCT01508819. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to prospectively evaluate the combined use of The Memorial Sloan Kettering Cancer Center nomogram and Tenon score to select, in patients with metastatic sentinel lymph node (SN), those at low risk of metastatic non-SN for whom additional axillary lymph node dissection (ALND) could be avoided.Methods: From January 2011 to July 2012, a prospective non-interventional nationwide study was conducted (NCT01509963). We sought to identify the false reassurance rate (FRR, a negative test result is false) in patients with both a ⩽10% probability of metastatic non-SN with the MSKCC nomogram and a Tenon score ⩽3.5 (low risk): the proportion of patients with metastatic non-SN at additional ALND. Our hypothesis was that these patients would have a FRR⩽5%.Results: Data on 2822 patients with breast cancer from 53 institutions were prospectively recorded. At least one SN was metastatic (isolated tumour cells, micro- or macrometastases) in 696 patients (24.7%). Among patients with ALND and complete data to calculate combined risk (n=504), 67 and 437 patients had low and high combined risk, respectively. Patients at low risk had less ALND (47%) compared to patients at high risk (P<0.001). This study did not meet its primary objective because the FRR in patients with low risk was 16.4% (11 out of 67) (95% confidence interval (CI): 9.7-23.1%). In the high-risk group, 33.9% (148 out of 437) (95% CI: 29.6-38.4%) had non-SN metastases (P=0.004).Conclusions: In this controlled prospective study, metastatic SN patients with both a ⩽10% probability of metastatic non-SN with the MSKCC nomogram and a Tenon score ⩽3.5 failed to identify patients at low risk of metastatic non-SN when completion ALND was not systematic. [ABSTRACT FROM AUTHOR]

Background: In 2010, to reduce late HIV diagnosis, the French national health agency endorsed non-targeted HIV screening in health care settings. Despite these recommendations, non-targeted screening has not been implemented and only physician-directed diagnostic testing is currently performed. A survey conducted in 2010 in 29 French Emergency Departments (EDs) showed that non-targeted nurse-driven screening was feasible though only a few new HIV diagnoses were identified, predominantly among high-risk groups. A strategy targeting high-risk groups combined with current practice could be shown to be feasible, more efficient and cost-effective than current practice alone.Methods/design: DICI-VIH (acronym for nurse-driven targeted HIV screening) is a multicentre, cluster-randomized, two-period crossover trial. The primary objective is to compare the effectiveness of 2 strategies for diagnosing HIV among adult patients visiting EDs: nurse-driven targeted HIV screening combined with current practice (physician-directed diagnostic testing) versus current practice alone. Main secondary objectives are to compare access to specialist consultation and how early HIV diagnosis occurs in the course of the disease between the 2 groups, and to evaluate the implementation, acceptability and cost-effectiveness of nurse-driven targeted screening. The 2 strategies take place during 2 randomly assigned periods in 8 EDs of metropolitan Paris, where 42 % of France's new HIV patients are diagnosed every year. All patients aged 18 to 64, not presenting secondary to HIV exposure are included. During the intervention period, patients are invited to fill a 7-item questionnaire (country of birth, sexual partners and injection drug use) in order to select individuals who are offered a rapid test. If the rapid test is reactive, a follow-up visit with an infectious disease specialist is scheduled within 72 h. Assuming an 80 % statistical power and a 5 % type 1 error, with 1.04 and 3.38 new diagnoses per 10,000 patients in the control and targeted groups respectively, a sample size of 140,000 patients was estimated corresponding to 8,750 patients per ED and per period. Inclusions started in June 2014. Results are expected by mid-2016.Discussion: The DICI-VIH study is the first large randomized controlled trial designed to assess nurse-driven targeted HIV screening. This study can provide valuable information on HIV screening in health care settings.Trial Registration: ClinicalTrials.gov: NCT02127424 (29 April 2014). [ABSTRACT FROM AUTHOR]

Background: The incidence of biliary complications following liver transplantation (LT) remains high, ranging from 10 to 50 % of patients, especially when the diameter of the bile duct is smaller than 7 mm. Biliary reconstruction is most often performed by duct-to-duct anastomosis. In a preliminary study (n = 20), we previously reported a technique of biliary reconstruction using an intraductal stent tube followed by its endoscopic removal and showed both the feasibility and safety of this innovative procedure. The next step is to validate the potential benefit of this procedure in a randomized controlled trial.Design: This is a multicenter randomized controlled trial in France comparing the efficacy of biliary reconstruction with or without a removable intraductal stent on reducing biliary complications. Inclusion and randomization are performed during LT when a duct-to-duct biliary anastomosis smaller than 7 mm in diameter is envisioned. In the intraductal stent group, a custom-made segment of a T-tube is placed into the bile duct and removed endoscopically 4 to 6 months later. The surgical technique is described in a video during randomization and is available on the secure website used for inclusion and randomization. The primary endpoint is the occurrence of biliary complications, including biliary fistulae and strictures, during the 6 months of follow-up. Secondary evaluation criteria are the incidence of complications related to the stent placement and its extraction by endoscopy. The inclusion of 248 patients in total has been determined based on an expected incidence of biliary complications of 25% in the non-IST group and a 60% reduction of biliary complications (10%) in the IST group.Discussion: Biliary complications following LT are significant causes of morbidity, retransplantation, and mortality. Although controversial, the use of a T-tube has been proven to be useless and even responsible for specific complications related to the external part of the tube in many studies, including several randomized trials. However, several studies have identified a small bile duct diameter as a risk factor for biliary stenosis. A threshold of 7 mm was found to be significantly associated with biliary stenosis. Our team published a preliminary study that included 20 patients using a new technique of intraductal stenting. Only four complications were reported in the overall study population, whereas no biliary complication occurred in the subgroup of patients who received a whole graft LT. Moreover, no technical failures and no procedure-related complications were noted before and during the drain removal. Although an intraductal stent tube in duct-to duct biliary anastomosis seems feasible and safe, a multicenter randomized controlled trial is needed to validate its benefit as a protective tool against the occurrence of biliary complications. One original aspect of this protocol is the video demonstration of the surgical procedure, which is available on the web to standardize and homogenize the technique. The surgical community may be inspired by this type of tool in the future to minimize technical bias related to technical issues.Trial Registration: NCT02356939, date of registration 2 February 2015. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of Pulmonary Embolism (PE) in the emergency department (ED) is crucial. As emergency physicians fear missing this potential life-threatening condition, PE tends to be over-investigated, exposing patients to unnecessary risks and uncertain benefit in terms of outcome. The Pulmonary Embolism Rule-out Criteria (PERC) is an eight-item block of clinical criteria that can identify patients who can safely be discharged from the ED without further investigation for PE. The endorsement of this rule could markedly reduce the number of irradiative imaging studies, ED length of stay, and rate of adverse events resulting from both diagnostic and therapeutic interventions. Several retrospective and prospective studies have shown the safety and benefits of the PERC rule for PE diagnosis in low-risk patients, but the validity of this rule is still controversial. We hypothesize that in European patients with a low gestalt clinical probability and who are PERC-negative, PE can be safely ruled out and the patient discharged without further testing.Methods/design: This is a controlled, cluster randomized trial, in 15 centers in France. Each center will be randomized for the sequence of intervention periods: a 6-month intervention period (PERC-based strategy) followed by a 6-month control period (usual care), or in reverse order, with 2 months of "wash-out" between the 2 periods. Adult patients presenting to the ED with a suspicion of PE and a low pre test probability estimated by clinical gestalt will be eligible. The primary outcome is the percentage of failure resulting from the diagnostic strategy, defined as diagnosed venous thromboembolic events at 3-month follow-up, among patients for whom PE has been initially ruled out.Discussion: The PERC rule has the potential to decrease the number of irradiative imaging studies in the ED, and is reported to be safe. However, no randomized study has ever validated the safety of PERC. Furthermore, some studies have challenged the safety of a PERC-based strategy to rule-out PE, especially in Europe where the prevalence of PE diagnosed in the ED is high. The PROPER study should provide high-quality evidence to settle this issue. If it confirms the safety of the PERC rule, physicians will be able to reduce the number of investigations, associated subsequent adverse events, costs, and ED length of stay for patients with a low clinical probability of PE.Trial Registration: NCT02375919 . [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant radiochemotherapy (RCT) is now part of the armamentarium of cancer of the lower and middle rectum. It is recommended in current clinical practice prior to surgical excision if the lesion is classified T3/T4 or N+. Histological complete response, defined by the absence of persistent tumor cell invasion and lymph node (ypT0N0) after pathological examination of surgical specimen has been shown to be an independent prognostic factor of overall survival and disease-free survival. Surgical excision is usually performed between 6 and 8 weeks after completion of CRT and pathological complete response rate ranges around 12%. In retrospective studies, a lengthening of the interval after RCT beyond 10 weeks was found as an independent factor increasing the rate of pathological complete response (between 26% and 31%), with a longer disease-free survival and without increasing the operative morbidity. The aim of the present study is to evaluate in 264 patients the rate of pathological complete response rate of rectal cancer after RCT by lengthening the time between RCT and surgery.Methods/design: The current study is a multicenter randomized trial in two parallel groups comparing 7 and 11 weeks of delay between the end of RCT and cancer surgery of rectal tumors. At the end of the RCT, surgery is planified and randomization is performed after patient's written consent for participation. The histological complete response (ypT0N0) will be determined with analysis of the complete residual tumor and double reading by two pathologists blinded of the group of inclusion. Patients will be followed in clinics for 5 years after surgery. Participation in this trial does not change patient's management in terms of treatment, investigations or visits. Secondary endpoints will include overall and disease free survival, rate of sphincter conservation and quality of mesorectal excision. The number of patients needed is 264.Trial Registration: ClinicalTrial.gov: NCT01648894. [ABSTRACT FROM AUTHOR]

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Background: Ventilator-associated pneumonia (VAP) accounts for 25% of infections in intensive care units. Compared to a long duration (LD) of antibiotic therapy, a short duration (SD) has a comparable clinical efficacy with less antibiotic use and less multidrug-resistant (MDR) pathogen emergence, with the exception of documented VAP of non-fermenting Gram-negative bacilli (NF-GNB), including Pseudomonas aeruginosa (PA). These results have led the American Thoracic Society to recommend SD therapy for VAP, except for PA-VAP. Thus the beneficial effect of SD therapy in PA-VAP is still a matter of debate. We aimed to assess the non-inferiority of a short duration of antibiotics (8 days) versus prolonged antibiotic therapy (15 days) in PA-VAP.Methods/design: The impact of the duration of antibiotics on clinical events in patients with Pseudomonas aeruginosa ventilator-associated pneumonia (iDIAPASON) trial is a randomized, open-labeled non-inferiority controlled trial, conducted in 34 French intensive care units (ICUs), comparing two groups of patients with PA-VAP according to the duration (8 days or 15 days) of effective antibiotic therapy against PA. The primary outcome is a composite endpoint combining day 90 mortality and PA-VAP recurrence rate during hospitalization in the ICU. Furthermore, durations of mechanical ventilation and hospitalization, as well as number and types of extrapulmonary infections or acquisition of MDR pathogens during the hospitalization in the ICU will be recorded. Recurrence with predefined criteria (clinical suspicion of VAP associated with a positive quantitative culture of a respiratory sample) will be evaluated by two independent experts.Discussion: Demonstrating that an SD (8 days) versus LD (15 days) therapy strategy in PA-VAP treatment is safe and not associated with an increased mortality or recurrence rate could lead to a change in practices and guidelines in the management of antibiotic therapy of this frequent ICU complication. This strategy could lead to decreased antibiotic exposure during hospitalization in the ICU and in turn reduce the acquisition and the spread of MDR pathogens.Trial Registration: ClinicalTrials.gov: NCT02634411 . Registered on 19 November 2015. [ABSTRACT FROM AUTHOR]

Background: The optimal management of patients with ST-segment elevation myocardial infarction (STEMI) presenting late->12 hours following symptom onset-is still under debate.Objectives: The purpose of this study was to describe characteristics, temporal trends, and impact of revascularization in a large population of latecomer STEMI patients.Methods: The authors analyzed the data of 3 nationwide observational studies from the FAST-MI (French Registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction) program, conducted over a 1-month period in 2005, 2010, and 2015. Patients presenting between 12 and 48 hours after symptom onset were classified as latecomers.Results: A total of 6,273 STEMI patients were included in the 3 cohorts, 1,169 (18.6%) of whom were latecomers. After exclusion of patients treated with fibrinolysis and patients deceased within 2 days after admission, 1,077 patients were analyzed, of whom 729 (67.7%) were revascularized within 48 hours after hospital admission. At 30-day follow-up, all-cause death rate was significantly lower among revascularized latecomers (2.1% vs 7.2%; P < 0.001). After a median follow-up of 58 months, the rate of all-cause death was 30.4 (95% CI: 25.7-35.9) per 1,000 patient-years in the revascularized latecomers group vs 78.7 (95% CI: 67.2-92.3) per 1,000 patient-years in the nonrevascularized latecomers group (P < 0.001). In multivariate analysis, revascularization of latecomer STEMI patients was independently associated with a significant reduction of mortality occurrence during follow-up (HR: 0.65 [95% CI: 0.50-0.84]; P = 0.001).Conclusions: Coronary revascularization of latecomer STEMI patients is associated with better short and long-term clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor.Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population).Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8-3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74-0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, pinteraction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78-1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75-1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48-2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36-3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74-1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75-0·95, p=0·005, in contrast to patients without PCI where it did not, pinteraction=0·012. Benefit was present irrespective of time from most recent PCI.Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk.Funding: AstraZeneca. [ABSTRACT FROM AUTHOR]

Objective: Severe preeclampsia may require the delivery of the placenta to avoid life-threatening complications for the mother. Before 26 weeks of gestation, this often results in perinatal death. A decrease in soluble fms-like tyrosine kinase 1 (sFlt1), an anti-angiogenic factor central to the pathophysiology of the maternal syndrome, has been reported after LDL- apheresis. The present study tested whether LDL-apheresis could be used to allow women with early and severe preeclampsia to reach a gestational age where the baby had a viable chance of survival.Study Design: A phase II prospective study. Adult women were included if they had very early (<26 weeks of gestation) preeclampsia without severe (<5th percentile) intra-uterine growth retardation. Treatment consisted of two weekly sessions (90 min each) of LDL-apheresis of whole blood. The primary endpoint was the status of the baby (dead or living) at 6 months post-delivery. Sample size and stopping rules were calculated assuming a desired success rate of at least 90%.Results: The study was interrupted for safety reasons after the inclusion of two patients: both developed secondary uncontrolled hypertension and blurred vision during the first week of treatment. The first neonate, born at 25 + 3 weeks of gestation, died of sepsis at day 5; the second, born at 26 + 2 weeks of gestation, is still alive and well. In these two patients, the impact of apheresis sessions on sFlt1 concentrations was inconsistent.Conclusion: LDL-apheresis did not result in the prolongation of pregnancy in this phase II trial. Further studies will be needed to delineate the appropriate contours of this therapeutic strategy. [ABSTRACT FROM AUTHOR]

Background: Elderly patients are underrepresented in acute myocardial infarction trials. Our aim was to determine whether, in elderly patients, changes in management in the past 15 years are associated with improved 1-year mortality after hospital admission for myocardial infarction.Methods: We used data from 4 1-month French registries, conducted 5 years apart from 1995 to 2010, including 3389 elderly patients (≥75 years of age).Results: From 1995 to 2010, mean age remained stable (82.1 years), similar in ST- and non-ST-elevation myocardial infarction patients. Obesity, diabetes, hypertension, and hypercholesterolemia increased. History of prior myocardial infarction, stroke, and peripheral artery disease remained stable, while history of heart failure decreased. Major changes in management were noted: early percutaneous coronary intervention, early treatment with antiplatelet agents, low-molecular-weight heparin, beta-blockers, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and statins all increased. Early mortality after hospital admission decreased from 25.0% to 8.4%. One-year mortality decreased from 36.2% to 20.0% (adjusted hazard ratio 2010 vs 1995: 0.47, 0.39-0.57), both for ST-elevation myocardial infarction (36.8% to 21.1%) and non-ST-elevation myocardial infarction (34.8% to 19.1%). Mortality reduction was observed in all age groups, including those ≥85 years of age (from 46.2% to 31.4%). The study period, however, was no longer associated with decreased mortality when variables reflecting management changes were taken into account.Conclusions: Early and 1-year mortality after hospital admission of elderly patients with acute myocardial infarction has substantially decreased over the past 15 years. This improvement is likely mediated by increasing use of recommended management strategies. These data support the application of guidelines derived from trials mostly including younger patients to elderly populations as well. [ABSTRACT FROM AUTHOR]

Abstract: Background: There are limited data on the safety and efficacy of low molecular weight heparin (LMWH) in elderly patients with acute myocardial infarction (AMI). Methods: We aimed to compare LMWH with unfractioned heparin (UFH) in the management of AMI in elderly patients. FAST-MI is a nationwide registry carried out over a 1-month period in 2005, including consecutive patients with AMI admitted to intensive care unit <48h from symptom onset in 223 participating centers. We assessed the impact of LMWH on bleeding, the need for blood transfusion and one-year survival in elderly patients (≥75years). Results: 963 patients treated with heparin were included (mean age 82±5years; 51% women; 42.5% ST-elevation myocardial infarction). Major bleeding (2.4% vs. 6.1%, P=0.004) and blood transfusions (4.6% vs. 9.7%, P=0.002) were significantly less frequent with LMWH compared with the UFH, a difference that persisted after multivariate adjustment (OR=0.41, 95% CI: 0.20–0.83 and OR=0.49, 95% CI: 0.28–0.85, respectively). One-year survival and stroke and reinfarction-free survival were also significantly higher with LMWH compared with UFH (OR=0.66, 95% CI: 0.50–0.85 and OR=0.71, 95% CI: 0.56–0.91, respectively). In two cohorts of patients matched on a propensity score for getting LMWH and with similar baseline characteristics (328 patients per group), major bleeding and transfusion were significantly lower while one-year survival was significantly higher in patients receiving LMWH. Conclusions: The present data show that in elderly patients admitted for AMI, use of LMWH is associated with less bleeding, less need for transfusion, and higher survival, compared with the use of UFH. [Copyright &y& Elsevier]

Abstract: Background: Whether academic hospitals provide better quality of care for patients with acute myocardial infarction is widely debated. The aim of this study was to compare processes of care and mortality between academic and nonacademic hospitals in the contemporary era of acute myocardial infarction management. Methods: We analyzed the original data from a prospective cohort study of 3059 patients, including 1714 with ST-segment elevation and 1345 with non-ST-segment elevation myocardial infarction, enrolled at 39 and 183 academic and nonacademic hospitals, respectively, in France. Results: Unadjusted 1-year mortality for academic and nonacademic hospitals was 10% versus 15% for patients with ST-segment elevation myocardial infarction (P =.01) and 13% versus 14% for patients with non-ST-segment elevation myocardial infarction (P =.75). Patients treated in academic or nonacademic hospitals with percutaneous coronary intervention capability were more likely to receive reperfusion and recommended drug therapies than those treated in nonacademic hospitals without percutaneous coronary intervention capability. After adjusting for baseline characteristics, the hazards of death associated with admission to nonacademic hospitals with and without percutaneous coronary intervention capability relative to academic hospitals were 1.13 (95% confidence interval [CI], 0.79-1.62) and 1.65 (95% CI, 1.09-2.49) for those with ST-segment elevation myocardial infarction and 0.95 (95% CI, 0.66-1.36) and 1.06 (95% CI, 0.72-1.58) for those with non-ST-segment elevation myocardial infarction, respectively. Further adjustment for receipt of acute reperfusion and recommended drug therapies eliminated all differences in mortality between the study groups. Conclusion: Admission to academic hospitals was associated with a more frequent use of recommended therapies, conveying a survival advantage for patients with ST-segment elevation myocardial infarction. [Copyright &y& Elsevier]

Objective: To evaluate the remodeling of large arteries according to age at menopause, duration of menopause, and use of hormone therapy (HT).Design: A cross-sectional study consisting of baseline measurements of a multicentric randomized trial were used to evaluate arterial parameters.Setting: The study was conducted in France, Belgium, and the Netherlands in academic hospitals and private clinics.Patient(s): Postmenopausal women (n = 538) with mild hypercholesterolemia.Intervention(s): None.Main Outcome Measure(s): Common carotid artery intima-media thickness (CCA-IMT), central pulse pressure, and aortic stiffness (carotid-femoral pulse wave velocity) were measured and centrally controlled for quality. Multivariate regression analysis was used to assess the possible covariates associated with arterial parameters.Result(s): Women were 58 ± 6 (mean ± SD) years of age with an age of 50 ± 5 at menopause and a mean duration of menopause of 8 ± 7 years. Lower age at menopause, time since menopause, and absence of HT use were independently associated with worsening of the arterial parameters. After multivariate analysis, HT was associated with a lower CCA-IMT (-40 μm [range -64 to -1]), whereas lower age at menopause and menopause duration were respectively associated with a CCA-IMT increase (25 μm/5 y and 27 μm/5 y). Similarly, values of central pulse pressure and pulse wave velocity were lower in HT users (-3.1 mm Hg [-5.1 to -0.9] and -0.31 m/s [-0.63 to -0.02], respectively) but worsened with age at menopause and menopause duration.Conclusion(s): The age at menopause, the time since menopause, and the use of HT are independently associated with the thickening and stiffening of the large arteries.Clinical Trial Registration Number: NCT00163163. [ABSTRACT FROM AUTHOR]

Objective: To assess the level of circulating endothelial progenitor cells (CEPC) in cycling women compared with men and menopausal women. Design: Controlled clinical study. Setting: Healthy, nonsmoking volunteers. Patient(s): Twelve women, aged 18–40 years, with regular menstrual cycles, 12 menopausal women, and two groups of 12 age-matched men were recruited. Women did not receive any hormone therapy. Intervention(s): Collection of 20 mL of peripheral blood. Main Outcome Measure(s): The number of CEPC, defined as (Lin−/7AAD−/CD34+/CD133+/KDR+) cells per 106 mononuclear cells (MNC), was measured by flow cytometry. Result(s): The number of CEPC was significantly higher in cycling women than in age-matched men and menopausal women (26.5 per 106 MNC vs. 10.5 per 106 MNC vs. 10 per 106 MNC, respectively). The number of CEPC was similar in menopausal women, age-matched, and young men. Conclusion(s): The number of CEPC is influenced by an age–gender interaction. This phenomenon may explain in part the better vascular repair and relative cardiovascular protection in younger women as compared with age-matched men. [Copyright &y& Elsevier]