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Background: Admission to the hospital is a major risk factor for the development of venous thromboembolism (VTE). Whether thromboprophylaxis with low-molecular-weight heparin prevents symptomatic VTE in medically ill, hospitalized older adults remains debated. Methods: In a prospective, randomized, placebo-controlled, double-blind, multicenter trial, older adults (>70 years of age) hospitalized for acute medical conditions were randomly assigned to receive 40 mg a day of low-molecular-weight heparin (enoxaparin) or placebo for 6 to 14 days. The primary efficacy outcome was the cumulative incidence of symptomatic VTE (distal or proximal deep vein thrombosis, fatal or nonfatal pulmonary embolism) at 30 days. The primary safety outcome was major bleeding. Secondary outcomes included efficacy and safety outcomes at 90 days. Results: The trial was prematurely discontinued in September 2020, 5 years after enrollment began, because of drug supply issues. By the time of trial discontinuation, 2559 patients had been randomly assigned at 47 centers. Median age was 82 years and 60% of patients were female. In the intention-to-treat population, the primary efficacy outcome occurred in 22 out of 1278 (cumulative incidence, 1.8%) patients in the enoxaparin group and in 27 out of 1263 (cumulative incidence, 2.2%) patients in the placebo group (cumulative incidence difference, -0.4 percentage points; 95% confidence interval, -1.5 to 0.7), with no significant difference in time to VTE (P=0.46). The incidence of major bleeding was 0.9% in the enoxaparin group and 1.0% in the placebo group. At 90 days there were 14 symptomatic pulmonary emboli in the enoxaparin group and 25 in the placebo group; all 39 pulmonary embolism events resulted in hospital readmission and/or death, with 5 deaths from pulmonary embolism in the enoxaparin group and 11 deaths in the placebo group. Conclusions: This trial of thromboprophylaxis in medically ill, hospitalized older adults did not demonstrate that enoxaparin reduced the risk of symptomatic VTE after 1 month. Because the trial was prematurely discontinued, larger trials are needed to definitively address this question. (Funded by the French Ministry of Health Programme Hospitalier de Recherche Clinique, grant number PHRC-N-13-0283; ClinicalTrials.gov number, NCT02379806.) [ABSTRACT FROM AUTHOR]

BACKGROUND: Acetaminophen is the most widely used analgesic today. A recent systematic review found increased adverse events and mortality at therapeutic dosage. Our aim was to challenge these results in a large sample of older adults living in nursing homes (NHs). DESIGN: Prospective study using data from the Impact of Educational and Professional Supportive Interventions on Nursing Home Quality Indicators project (IQUARE), a multicenter, individually tailored, nonrandomized controlled trial in NHs across southwestern France. SETTING/PARTICIPANTS: We studied data from 5429 participants living in 175 NHs (average age, 86.1 ± 8.1 years; 73.9% women). MEASUREMENTS: All prescriptions obtained at baseline were analyzed by a pharmacist for acetaminophen use as stand‐alone or associated. Myocardial infarction (MI) and strokes were reported from participants' medical records at 18‐month follow‐up. Dates of death were obtained. Data collection was done through an online questionnaire at baseline and at 18 months by NH staff. Analyses were realized in our total population and a population matched on propensity score of acetaminophen intake. Six models were run for each outcome. RESULTS: A total of 2239 participants were taking, on average, 2352 ± 993 mg of acetaminophen daily. Results for mortality were: hazard ratio (HR) = 0.97 (95% confidence interval [CI] = 0.86‐1.10). No associations between acetaminophen intake and the risk of mortality or MI were found. In one of our models, acetaminophen intake was associated with a significant increased risk of stroke in diabetic subjects (OR = 3.19; 95% CI = 1.25‐8.18; P = .0157). [Correction added March 16, 2019, after first publication online. In the previous sentence, "HR" was mistakenly used instead of "OR".] CONCLUSION: Despite old age, polypharmacy, and polymorbidity, acetaminophen was found safe for most, but not all, of our NH study population. Pain management in NHs is a health priority, and acetaminophen remains a good therapeutic choice as a first‐line analgesic. More studies are needed on older diabetic patients. [ABSTRACT FROM AUTHOR]

The article discusses Joseph Bunel and his wife Marie Bunel, an interracial couple who lived during the late eighteenth and early nineteenth-centuries in France, Saint-Domingue (modern Haiti), and Philadelphia, Pennsylvania. Both Joseph and Marie were merchants and Joseph served as a diplomat to the U.S. during the administration of U.S. President John Adams for the newly independent Saint-Domingue with a goal to resume commercial relations between the two nations despite the ongoing Quasi French War. Some of the subjects explored include 19th century commerce, race, slavery, freedmen, social status and nationalism.

Focuses on the explanation of the French leaders in justifying a war whose main goal, the restoration of slavery, conflicted with their revolutionary ideals. Background on the expeditionary force sent by Napoléon Bonaparte from 1802 to 1803 to the French colony of Saint-Domingue for the restoration of French authority on the place; Information on the way the soldiers made sense of the disparity between their own political beliefs and the mission Bonaparte has entrusted to them; Discussion of the slaves' revolutionary ideals.

Background: Even after resection of early-stage non-small-cell lung cancer (NSCLC), patients have a high risk of developing recurrence and second primary lung cancer. We aimed to assess efficacy of a follow-up approach including clinic visits, chest x-rays, chest CT scans, and fibre-optic bronchoscopy versus clinical visits and chest x-rays after surgery for resectable NSCLC.Methods: In this multicentre, open-label, randomised, phase 3 trial (IFCT-0302), patients aged 18 years or older and after complete resection of pathological stage I-IIIA NSCLC according to the sixth edition of the TNM classification were enrolled within 8 weeks of resection from 122 hospitals and tertiary centres in France. Patients were randomly assigned (1:1) to CT-based follow-up (clinic visits, chest x-rays, thoraco-abdominal CT scans, and fibre-optic bronchoscopy for non-adenocarcinoma histology) or minimal follow-up (visits and chest x-rays) after surgery for NSCLC, by means of a computer-generated sequence using the minimisation method. Procedures were repeated every 6 months for the first 2 years and yearly until 5 years. The primary endpoint was overall survival analysed in the intention-to-treat population. Secondary endpoints, also analysed in the intention-to-treat population, included disease-free survival. This trial is registered with ClinicalTrials.gov, NCT00198341, and is active, but not enrolling.Findings: Between Jan 3, 2005, and Nov 30, 2012, 1775 patients were enrolled and randomly assigned to a follow-up group (888 patients to the minimal follow-up group; 887 patients to the CT-based follow-up group). Median overall survival was not significantly different between follow-up groups (8·5 years [95% CI 7·4-9·6] in the minimal follow-up group vs 10·3 years [8·1-not reached] in the CT-based follow-up group; adjusted hazard ratio [HR] 0·95, 95% CI 0·83-1·10; log-rank p=0·49). Disease-free survival was not significantly different between follow-up groups (median not reached [95% CI not estimable-not estimable] in the minimal follow-up group vs 4·9 [4·3-not reached] in the CT-based follow-up group; adjusted HR 1·14, 95% CI 0·99-1·30; log-rank p=0·063). Recurrence was detected in 246 (27·7%) of 888 patients in the minimal follow-up group and in 289 (32·6%) patients of 887 in the CT-based follow-up group. Second primary lung cancer was diagnosed in 27 (3·0%) patients in the minimal follow-up group and 40 patients (4·5%) in the CT-based follow-up group. No serious adverse events related to the trial procedures were reported.Interpretation: The addition of thoracic CT scans during follow-up, which included clinic visits and chest x-rays after surgery, did not result in longer survival among patients with NSCLC. However, it did enable the detection of more cases of early recurrence and second primary lung cancer, which are more amenable to curative-intent treatment, supporting the use of CT-based follow-up, especially in countries where lung cancer screening is already implemented, alongside with other supportive measures.Funding: French Health Ministry, French National Cancer Institute, Weisbrem-Benenson Foundation, La Ligue Nationale Contre Le Cancer, and Lilly Oncology.Translation: For the French translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Introduction: Recurrent venous thromboembolism (VTE) despite curative anticoagulation is frequent in patients with cancer. Identifying patients with a high risk of recurrence could have therapeutic implications. A prospective study was designed to validate the Ottawa risk score of recurrent VTE in cancer patients., Methods: In a prospective multicenter observational cohort, adult cancer patients with a recent diagnosis of symptomatic or incidental lower limb deep vein thrombosis or pulmonary embolism (PE) were treated with tinzaparin for 6 months. The primary endpoint was the recurrence of symptomatic or asymptomatic VTE within the first 6 months of treatment. All clinical events were centrally reviewed and adjudicated. Time-to-event outcomes were estimated by the Kalbfleisch and Prentice method to take into account the competing risk of death. A C-statistic value of > 0.70 was needed to validate the Ottawa score., Results: A total of 409 patients were included and analyzed on an intention-to-treat basis. Median age was 68 years, 60.4% of patients had PE, and VTE was symptomatic in 271 patients (66.3%). The main primary sites were lung (31.3%), lower digestive tract (14.4%), and breast (13.9%) cancers. The Ottawa score was high (≥ 1) in 58% of patients. The 6-month cumulative incidence of recurrent VTE was 7.3% (95% confidence interval [CI]: 4.9-11.1) overall, and 5.0% (95% CI: 2.3-10.8) versus 9.1% (95%CI: 6.1-13.6) in the Ottawa low versus high risk groups, respectively. The C-statistic value was 0.60 (95% CI: 0.55-0.65)., Conclusion: In this prospective cohort of patients with cancer receiving tinzaparin for VTE, the Ottawa score failed to accurately predict recurrent VTE., Competing Interests: All participants have received fees from LEO Pharma for this research, either personally and/or to support the local organization of the research. Anne Lamblin is an employee of LEO Pharma., (Thieme. All rights reserved.)

Background:  We aimed to identify risk factors for residual pulmonary vascular obstruction after a first unprovoked pulmonary embolism (PE)., Methods:  Analyses were based on data from the double-blind randomized "PADIS-PE" trial that included 371 patients with a first unprovoked PE initially treated during 6 uninterrupted months; all patients underwent baseline ventilation-perfusion lung scanning at inclusion (i.e., after 6 months of anticoagulation). Each patient's pulmonary vascular obstruction indexes (PVOIs) at PE diagnosis and at inclusion were centrally assessed., Results:  Among the 371 included patients, residual PVOI was available in 356 patients, and 150 (42.1%) patients had PVOI ≥ 5%. At multivariable analysis, age > 65 years (odds ratio [OR], 2.81, 95% confidence interval [CI], 1.58-5.00), PVOI ≥ 25% at PE diagnosis (OR, 3.53, 95% CI, 1.94-6.41), elevated factor VIII (OR, 3.89, 95% CI, 1.41-10.8), and chronic respiratory disease (OR, 2.18, 95% CI, 1.11-4.26) were independent predictors for residual PVOI ≥ 5%. Patients with ≥ 1 of these factors represented 94.5% (123 patients) of all patients with residual PVOI ≥ 5%., Conclusion:  Six months after a first unprovoked PE, age > 65 years, PVOI ≥ 25% at PE diagnosis, elevated factor VIII, or chronic respiratory disease were found to be independent predictors for residual pulmonary vascular obstruction., Clinical Trials Registration:  URL: http://www.controlled-trials.com. Unique identifier: NCT00740883., Competing Interests: F.C. reports having received research grant support from Pfizer and fees for board memberships or symposia from Bayer, Bristol-Myers Squibb/Pfizer, and Astra Zeneca, and having received travel support from Bayer, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo, Boehringer Ingelheim, Leo Pharma, Intermune, and Actelion. L.R. declares she has no conflict of interest related to this research. P.R. declares he has no conflict of interest related to this research. R.L.-M. declares he has no conflict of interest related to this research. E.P. declares she has no conflict of interest related to this research. C.T. declares she has no conflict of interest related to this research. O.S. reports having received research grant support from Bayer, Daiichi Sankyo, and Portola Pharmaceuticals, and fees or nonfinancial support for consultancy activities from Actelion, GlaxoSmithKline, Boehringer Ingelheim, and Chiesi. G.P. declares he has no conflict of interest related to this research. L.B. declares he has no conflict of interest related to this research. C.A.L. declares she has no conflict of interest related to this research. P.J. reports having received personal fees or nonfinancial support from Sanofi, GlaxoSmithKline, Bayer, Boehringer Ingelheim, and Leo Pharma. A.M. declares she has no conflict of interest related to this research. F.L. declares he has no conflict of interest related to this research. P.-Y.L.R. declares he has no conflict of interest related to this research. P.-Y.S. declares he has no conflict of interest related to this research. M.N. declares he has no conflict of interest related to this research. B.P. declares he has no conflict of interest related to this research. P.G. reports having received personal fees and nonfinancial support from Bayer and Leo Pharma. K.L. reports having received personal fees from Bayer-Health Care, Bristol-Myers Squibb, and Boehringer Ingelheim. S.M. declares she has no conflict of interest related to this research. P.M. reports having received research grants from Bayer, fees for board memberships from Bayer, Bristol-Myers Squibb/Pfizer, and Daiichi Sankyo, for lectures from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo, and Sanofi, and for development of educational presentations from Bayer and Bristol-Myers Squibb/Pfizer. S.L. reports having received research grant support from Bayer and Sanofi, and fees for board memberships or consultancy from Bayer, Boehringer Ingelheim, Leo Pharma, and Sanofi. G.M. reports having received research grant support from Bayer, Boehringer Ingelheim, Leo Pharma, and Sanofi, having been an uncompensated board member and a consultant for Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Leo Pharma, and Pfizer, and having received travel support from Bayer, Boehringer Ingelheim, Daiichi Sankyo, Leo Pharma, and Sanofi. C.L. reports having received research grant support from Pfizer and fees for board memberships or symposia from Bayer and Astra Zeneca and having received travel support from Bayer, Daiichi Sankyo, Leo Pharma, Intermune, and Actelion. No other potential conflict of interest relevant to this article was reported., (Georg Thieme Verlag KG Stuttgart · New York.)

Aims: The role of extracorporeal membrane oxygenation (ECMO) remains ill defined in pulmonary embolism (PE). We investigated outcomes in patients with high-risk PE undergoing ECMO according to initial therapeutic strategy., Methods and Results: From 01 January 2014 to 31 December 2015, 180 patients from 13 Departments in nine centres with high-risk PE were retrospectively included. Among those undergoing ECMO, we compared characteristics and outcomes according to adjunctive treatment strategy (systemic thrombolysis, surgical embolectomy, or no reperfusion therapy). Primary outcome was all-cause 30-day mortality. Secondary outcome was 90-day major bleeding. One hundred and twenty-eight patients were treated without ECMO; 52 (mean age 47.6 years) underwent ECMO. Overall 30-day mortality was 48.3% [95% confidence interval (CI) 41-56] (87/180); 43% (95% CI 34-52) (55/128) in those treated without ECMO vs. 61.5% (95% CI 52-78) (32/52) in those with ECMO (P = 0.008). In patients undergoing ECMO, 30-day mortality was 76.5% (95% CI 57-97) (13/17) for ECMO + fibrinolysis, 29.4% (95% CI 51-89) (5/17) for ECMO + surgical embolectomy, and 77.7% (95% CI 59-97) (14/18) for ECMO alone (P = 0.004). Among patients with ECMO, 20 (38.5%, 95% CI 25-52) had a major bleeding event in-hospital; without significant difference across groups., Conclusion: In patients with high-risk PE, those with ECMO have a more severe presentation and worse prognosis. Extracorporeal membrane oxygenation in patients with failed fibrinolysis and in those with no reperfusion seems to be associated with particularly unfavourable prognosis compared with ECMO performed in addition to surgical embolectomy. Our findings suggest that ECMO does not appear justified as a stand-alone treatment strategy in PE patients, but shows promise as a complement to surgical embolectomy.

The anti-tumour and anti-metastatic properties of heparins have not been tested in patients with early stage cancer. Whether adjuvant low molecular weight heparin (LMWH) tinzaparin impacts the survival of patients with resected non-small cell lung cancer (NSCLC) was investigated.Patients with completely resected stage I, II or IIIA NSCLC were randomly allocated to receive subcutaneous tinzaparin 100 IU·kg -1 once a day for 12 weeks or no treatment in addition to standard of care. The trial was open-label with blinded central adjudication of study outcomes. The primary outcome was overall survival.In 549 patients randomised to tinzaparin (n=269) or control (n=280), mean±sd age was 61.6±8.9 years, 190 (34.6%) patients had stage II-III disease, and 220 (40.1%) patients received adjuvant chemotherapy. Median follow-up was 5.7 years. There was no significant difference in overall survival between groups (hazard ratio (HR) 1.24, 95% CI 0.92-1.68; p=0.17). There was no difference in the cumulative incidence of recurrence between groups (subdistribution HR 0.94, 95% CI 0.68-1.30; p=0.70).Adjuvant tinzaparin had no detectable impact on overall and recurrence-free survival of patients with completely resected stage I-IIIA NSCLC. These results do not support further clinical evaluation of LMWHs as anti-tumour agents., Competing Interests: Conflict of interest: G. Meyer reports grants and non-financial support from Leo Pharma, outside the submitted work. Conflict of interest: B. Besse has nothing to disclose. Conflict of interest: H. Doubre has nothing to disclose. Conflict of interest: A. Charles-Nelson has nothing to disclose. Conflict of interest: S. Aquilanti reports non-financial support from Leo Pharma, outside the submitted work. Conflict of interest: A. Izadifar has nothing to disclose. Conflict of interest: R. Azarian has nothing to disclose. Conflict of interest: I. Monnet has nothing to disclose. Conflict of interest: C. Lamour has nothing to disclose. Conflict of interest: R. Descourt has nothing to disclose. Conflict of interest: G. Oliviero has nothing to disclose. Conflict of interest: L. Taillade has nothing to disclose. Conflict of interest: C. Chouaid has nothing to disclose. Conflict of interest: F. Giraud has nothing to disclose. Conflict of interest: P-E. Falcoz has nothing to disclose. Conflict of interest: M-P. Revel has nothing to disclose. Conflict of interest: V. Westeel has nothing to disclose. Conflict of interest: A. Dixmier has nothing to disclose. Conflict of interest: J. Tredaniel has nothing to disclose. Conflict of interest: S. Dehette has nothing to disclose. Conflict of interest: C. Decroisette has nothing to disclose. Conflict of interest: A. Prevost has nothing to disclose. Conflict of interest: E. Pichon has nothing to disclose. Conflict of interest: E. Fabre has nothing to disclose. Conflict of interest: J-C. Soria has nothing to disclose. Conflict of interest: S. Friard has nothing to disclose. Conflict of interest: J-B. Stern has nothing to disclose. Conflict of interest: L. Jabot has nothing to disclose. Conflict of interest: G. Dennewald has nothing to disclose. Conflict of interest: G. Pavy has nothing to disclose. Conflict of interest: P. Petitpretz has nothing to disclose. Conflict of interest: J-M. Tourani has nothing to disclose. Conflict of interest: M. Alifano has nothing to disclose. Conflict of interest: Dr. Chatellier has nothing to disclose. Conflict of interest: P. Girard reports personal fees and non-financial support from Leo Pharma, outside the submitted work., (Copyright ©ERS 2018.)

Reported experience with video-assisted anatomic pulmonary segmentectomy is still limited. Over a 28-month period, totally thoracoscopic (TT) anatomic segmentectomies, i.e. using only endoscopic instrumentation and video-display without utility incision, were attempted on 50 patients (25 males and 25 females), aged 18-81 years (mean: 57 years). The indication was a clinical N0 non-small cell lung carcinoma in 25 cases, a solitary metastasis in nine cases and a benign lesion in 16 cases. The following segmentectomies were performed: right apicosuperior (9) right superior (6), right basilar (7), lingula sparing left upper lobectomy (7), left apicosuperior (4), lingula (4), left superior (6) and left basilar (7). It was associated with a radical lymphadenectomy in 20 cases. There was one conversion to thoracotomy. The mean operative time was 188±54 min, the mean intraoperative blood loss was 91±82 ml (range: 0-450 ml). There were four minor postoperative complications (11.7%). The median postoperative stay was 5.6±2.4 days. Out of the 25 patients operated on for a cN0 lung carcinoma, two were finally upstaged to N2. TT anatomic pulmonary segmentectomies are feasible and safe.