Risk stratification for predicting recurrent venous thromboembolism after discontinuation of anticoagulation: a post hoc analysis of a French prospective multicentre study.

BACKGROUND: We aimed to validate and to refine current recurrent venous thromboembolism (VTE) risk classification. METHODS: We performed a post hoc analysis of a multicentre cohort including 1881 patients with a first symptomatic VTE prospectively followed after anticoagulation discontinuation. The primary objective was to validate the International Society of Thrombosis and Haemostasis (ISTH) risk classification in predicting recurrence risk. The secondary objective was to evaluate a refined ISTH classification based on the recurrence risk estimate for each individual risk factor. RESULTS: During a 4.8-year median follow-up after anticoagulation discontinuation, symptomatic recurrent VTE occurred in 230 patients (12.2%). Based on the ISTH classification, patients with unprovoked VTE or VTE with minor or major persistent risk factors had a 2-fold increased recurrence risk compared with those with VTE and major transient risk factors. Recurrence risk was not increased in patients with minor transient factors (hazard ratio (HR) 1.31, 95% CI 0.84-2.06). Individual risk factors analysis identified hormone-related VTE (pregnancy: HR 0.26, 95% CI 0.08-0.82; oestrogens: HR 0.25, 95% CI 0.14-0.47) and amyotrophic lateral sclerosis (HR 5.84, 95% CI 1.82-18.70). After reclassification of these factors as major transient for the former and major persistent for the latter, the modified ISTH classification allowed us to accurately discriminate between patients at low risk of recurrence (i.e. with major transient risk factors) and those at high risk of recurrence (i.e. without major transient risk factors). CONCLUSIONS: Among patients who stopped anticoagulation after a first VTE, a refined ISTH classification based on recurrence risk intensity of individual factors allowed discrimination between patients at low recurrence risk, including hormonal exposure in women, and patients at high recurrence risk.

Association between obstructive sleep apnea and venous thromboembolism recurrence: results from a French cohort.

BACKGROUND: Growing evidence suggests the relationship between obstructive sleep apnea (OSA) and venous thromboembolism (VTE). Few studies focused on VTE recurrence risk associated with OSA after anticoagulation cessation. METHODS: In a prospective cohort study, patients with documented VTE, were followed for an indefinite length of time and VTE recurrence were documented and adjudicated. The primary outcome was recurrent VTE after anticoagulation discontinuation. Secondary outcomes included all-cause mortality and the clinical presentation of VTE. Univariable and multivariable analyses were performed to identify risk factors for recurrence and mortality. RESULTS: Among the 2109 patients with documented VTE included, 74 patients had moderate to severe OSA diagnosis confirmed by home sleep test or polysomnography. During a median follow-up of 4.8 (interquartile range 2.5-8.0) years recurrent VTE occurred in 252 patients (9 with OSA and 243 without OSA). The recurrence risk in the univariable and multivariable analysis was not increased in patients with OSA, regardless of the time of diagnosis (before or after index VTE or pooled). VTE phenotype was significantly more often PE with or without associated deep vein thrombosis in the first event and recurrence for OSA patients compared to non-OSA patients. The risk of death was not increased in the OSA population compared to non-OSA patients in multivariable analysis. CONCLUSIONS: In patients with OSA and VTE, the risk of all-cause mortality and VTE recurrence after anticoagulation discontinuation was not increased compared to non-OSA patients.

Risk of recurrent venous thromboembolism and bleeding in patients with interstitial lung disease: a cohort study.

Interstitial lung disease (ILD) encompasses various parenchymal lung disorders, which has the potential to increase the risk of venous thromboembolism (VTE). To evaluate, in patients with ILD and VTE, the risk of recurrent VTE during follow-up after stopping anticoagulation. This was a cohort of patients with a first VTE recruited between 1997 and 2015. The primary outcome was adjudicated fatal or nonfatal recurrent VTE after stopping anticoagulation. Main secondary outcomes were major or clinically relevant non-major bleeding under anticoagulation. Among 4314 patients with VTE, 50 had ILD diagnosed before VTE. Of these, anticoagulation was stopped in 30 patients after a median duration of 180 days and continued indefinitely in 20 patients. During a median follow-up of 27.8 months after anticoagulation discontinuation, recurrent VTE occurred in 15 on 30 patients (annual incidence of 19.2 events per 100-person-years [95%CI 12.0-29.3], case-fatality rate of 6.7% [95%CI 1.21-29.8]). The risk of recurrence was threefold higher when VTE was unprovoked and case-fatality rate of recurrence was increased by 3 when VTE index was PE. During the anticoagulant period, (median duration of 8.6 months), 6 patients had a major or clinically relevant bleeding (annual incidence of 7.3 events per 100-person-years [95%CI 3.4-15.1], case-fatality rate of 16.7% [95%CI 3.0-56.4]). In patients with ILD, the risk of recurrent VTE after stopping anticoagulation and the risk of bleeding under anticoagulation were very high. Our results suggest that anticoagulation should not be prolonged beyond 3-6 months of anticoagulation in most of cases.

Prevalence of Pulmonary Embolism Among Patients With COPD Hospitalized With Acutely Worsening Respiratory Symptoms.

IMPORTANCE: The prevalence of pulmonary embolism in patients with chronic obstructive pulmonary disease (COPD) and acutely worsening respiratory symptoms remains uncertain. OBJECTIVE: To determine the prevalence of pulmonary embolism in patients with COPD admitted to the hospital for acutely worsening respiratory symptoms. DESIGN, SETTING, AND PARTICIPANTS: Multicenter cross-sectional study with prospective follow-up conducted in 7 French hospitals. A predefined pulmonary embolism diagnostic algorithm based on Geneva score, D-dimer levels, and spiral computed tomographic pulmonary angiography plus leg compression ultrasound was applied within 48 hours of admission; all patients had 3-month follow-up. Patients were recruited from January 2014 to May 2017 and the final date of follow-up was August 22, 2017. EXPOSURES: Acutely worsening respiratory symptoms in patients with COPD. MAIN OUTCOMES AND MEASURES: The primary outcome was pulmonary embolism diagnosed within 48 hours of admission. Key secondary outcome was pulmonary embolism during a 3-month follow-up among patients deemed not to have venous thromboembolism at admission and who did not receive anticoagulant treatment. Other outcomes were venous thromboembolism (pulmonary embolism and/or deep vein thrombosis) at admission and during follow-up, and 3-month mortality, whether venous thromboembolism was clinically suspected or not. RESULTS: Among 740 included patients (mean age, 68.2 years [SD, 10.9 years]; 274 women [37.0%]), pulmonary embolism was confirmed within 48 hours of admission in 44 patients (5.9%; 95% CI, 4.5%-7.9%). Among the 670 patients deemed not to have venous thromboembolism at admission and who did not receive anticoagulation, pulmonary embolism occurred in 5 patients (0.7%; 95% CI, 0.3%-1.7%) during follow-up, including 3 deaths related to pulmonary embolism. The overall 3-month mortality rate was 6.8% (50 of 740; 95% CI, 5.2%-8.8%). The proportion of patients who died during follow-up was higher among those with venous thromboembolism at admission than the proportion of those without it at admission (14 [25.9%] of 54 patients vs 36 [5.2%] of 686; risk difference, 20.7%, 95% CI, 10.7%-33.8%; P < .001). The prevalence of venous thromboembolism was 11.7% (95% CI, 8.6%-15.9%) among patients in whom pulmonary embolism was suspected (n = 299) and was 4.3% (95% CI, 2.8%-6.6%) among those in whom pulmonary embolism was not suspected (n = 441). CONCLUSIONS AND RELEVANCE: Among patients with chronic obstructive pulmonary disease admitted to the hospital with an acute worsening of respiratory symptoms, pulmonary embolism was detected in 5.9% of patients using a predefined diagnostic algorithm. Further research is needed to understand the possible role of systematic screening for pulmonary embolism in this patient population.

Effectiveness and safety of dupilumab for the treatment of severe asthma in a real-life French multi-centre adult cohort.

BACKGROUND: Dupilumab is a monoclonal anti-IL-4Rα antibody developed for the treatment of severe asthma (SA). An early access programme for dupilumab was opened in France in SA patients experiencing unacceptable steroids side-effects and/or life-threatening exacerbations. OBJECTIVE: To assess changes in asthma control between baseline and 12 months of treatment. METHODS: Multi-centre (n = 13) retrospective real-life cohort study. This study is registered on ClinicalTrials.gov (NCT04022447). RESULTS: Overall, 64 patients with SA (median age 51, interquartile range [44-61]; 53% females) received dupilumab as add-on therapy to maximal standard of care; and 76% were on oral daily steroids at baseline. After 12 months, median asthma control test score improved from 14 [7-16] to 22 [17-24] (P < .001); median forced expiratory volume in 1 seconds increased from 58% [47-75] to 68% [58-88] (P = .001); and daily prednisone dose was reduced from 20 [10-30] to 5 [0-7] mg/d (P < .001). Annual exacerbations decreased from 4 [2-7] to 1 [0-2] (P < .001). Hypereosinophilia ≥1500/mm3 was observed at least once during follow-up in 16 patients (25%), persisting after 6 months in 8 (14%) of them. Increase in blood eosinophil count did not modify the clinical response during the study period. Injection-site reaction was the most common side effect (14%). Three deaths were observed, none related to treatment by investigators. CONCLUSION & CLINICAL RELEVANCE: In this first real-life cohort study of predominantly steroid-dependent SA, dupilumab significantly improved asthma control and lung function and reduced oral steroids use and exacerbations rate. Despite limitations due to the retrospective study, these results are consistent with controlled trials efficacy data. Further studies are required to assess the clinical significance and long-term prognosis of sustained dupilumab-induced hypereosinophilia.

Patent Foramen Ovale and Ischemic Stroke in Patients With Pulmonary Embolism: A Prospective Cohort Study.

Background: Pulmonary embolism (PE) is associated with increased risk for ischemic stroke, but the underlying mechanism remains unclear. The authors hypothesized that paradoxical embolism through patent foramen ovale (PFO) should be the main mechanism. Objective: To determine the frequency of recent ischemic stroke in patients with symptomatic PE according to whether PFO was detected. Design: Prospective cohort study with masked assessment of stroke outcomes. (ClinicalTrials.gov: NCT01216423). Setting: 4 French hospital centers. Participants: 361 consecutive patients with symptomatic acute PE from 13 November 2009 through 21 December 2015. Intervention: Systematic contrast transthoracic echocardiography (TTE) and cerebral magnetic resonance imaging (MRI) within 7 days after enrollment. Measurements: Recent symptomatic or silent ischemic stroke was diagnosed on the basis of clinical examination and cerebral MRI showing a hypersignal on the trace diffusion-weighted image with reduction or pseudonormalization of apparent diffusion coefficient. Results: Contrast TTE was conclusive in 324 of 361 patients and showed PFO in 43 patients (13%). The median age was 66 years (interquartile range, 54 to 77 years). In total, 51% of patients (145/284) had associated deep venous thrombosis, 91% (279/306) had cardiovascular risk factors, and 10% (16/151) presented with arrhythmia (no difference between PFO and non-PFO groups). Cerebral MRI was conclusive in 315 patients. Recent ischemic stroke was more frequent in the PFO group than in the non-PFO group (9 of 42 patients [21.4%] vs. 15 of 273 patients [5.5%]; difference in proportions, 15.9 percentage points [95% CI, 4.7 to 30.7 percentage points]). Limitation: Because of inconclusive contrast TTE or MRI, 46 patients were excluded from analysis. Conclusion: Frequency of recent ischemic stroke in patients with symptomatic PE was higher in patients with PFO than in those without PFO. This finding supports the hypothesis that paradoxical embolism is an important mechanism of ischemic stroke in patients with PFO. Primary Funding Source: French Ministry of Health.

Effect of Early Initiation of Varenicline on Smoking Cessation in COPD Patients Admitted for Exacerbation: The Save Randomized Clinical Trial.

Our main objective was to demonstrate that, in smoker patients hospitalised for Chronic Obstructive Pulmonary Disease (COPD) exacerbation, early initiation of varenicline during 12 weeks, combined with an intensive counselling, is associated with a higher continuous abstainers rate (CAR) at one year as compared to intensive counselling alone. In this multicenter, prospective, double-blind, randomised study, 81 smoking COPD patients hospitalised for an acute exacerbation for at least 24 h were allocated to receive either varenicline (n = 42) or placebo (n = 39) for 12 weeks, in association with an intensive counselling in the 2 groups, and followed up for 40 weeks. The primary outcome was CAR at week 52. Secondary outcomes included CAR at week 12 and 26, partial abstinence rate (PAR) at week 12, 26 and 52, nicotinic substitute consumption and adverse events. At week 52, CAR was not different in placebo and varenicline groups (25.6%). At week 12, CAR was significantly higher in the varenicline group (50%) as compared to placebo group (27%) (p = 0.041). Nicotine consumption was significantly higher at week 52 in the placebo group (55.3%) as compared to the varenicline group (24.4%) (p = 0.005). There was no significant difference in PAR at week 12, 26 and 52; the frequency of adverse events was similar between the two groups. Among active smoker COPD patients with exacerbation, 12-week varenicline associated with intensive counselling for smoking cessation increased the rate of continuous abstainers as compared to placebo. However, benefit was not maintained after varenicline discontinuation.Clinical Trials Registration: URL: http://www.controlled-trials.com. Unique identifier: NCT01694732.

Computed tomography pulmonary angiography versus ventilation-perfusion lung scanning for diagnosing pulmonary embolism during pregnancy: a systematic review and meta-analysis.

Differences between computed tomography pulmonary angiography and ventilation-perfusion lung scanning in pregnant patients with suspected acute pulmonary embolism are not well-known, leading to ongoing debate on which test to choose. We searched in PubMed, EMBASE, Web of Science and the Cochrane Library databases and identified all relevant articles and abstracts published up to October 1, 2017. We assessed diagnostic efficiency, frequency of non-diagnostic results and maternal and fetal exposure to radiation exposure. We included 13 studies for the diagnostic efficiency analysis, 30 for the analysis of non-diagnostic results and 22 for the radiation exposure analysis. The pooled rate of false negative test results was 0% for both imaging strategies with overlapping confidence intervals. The pooled rates of non-diagnostic results with computed tomography pulmonary angiography and ventilation-perfusion lung scans were 12% (95% confidence interval: 8-17) and 14% (95% confidence interval: 10-18), respectively. Reported maternal and fetal radiation exposure doses were well below the safety threshold, but could not be compared between the two diagnostic methods given the lack of high quality data. Both imaging tests seem equally safe to rule out pulmonary embolism in pregnancy. We found no significant differences in efficiency and radiation exposures between computed tomography pulmonary angiography and ventilation-perfusion lung scanning although direct comparisons were not possible.

Six months versus two years of oral anticoagulation after a first episode of unprovoked deep-vein thrombosis. The PADIS-DVT randomized clinical trial.

The optimal duration of anticoagulation after a first episode of unprovoked deep-vein thrombosis is uncertain. We aimed to assess the benefits and risks of an additional 18 months of treatment with warfarin versus placebo, after an initial 6 months of anticoagulation for a first unprovoked proximal deep-vein thrombosis. We conducted a multicenter, randomized, double-blind, controlled trial comparing an additional 18 months of warfarin with placebo in patients with a unprovoked proximal deep-vein thrombosis initially treated for 6 months (treatment period: 18 months; follow up after treatment period: 24 months). The primary outcome was the composite of recurrent venous thromboembolism or major bleeding at 18 months. Secondary outcomes were the composite at 42 months, as well as each component of the composite, and death unrelated to pulmonary embolism or major bleeding, at 18 and 42 months. All outcomes were centrally adjudicated. A total of 104 patients, enrolled between July 2007 and October 2013 were analyzed on an intention-to-treat basis; no patient was lost to follow-up. During the 18-month treatment period, the primary outcome occurred in none of the 50 patients in the warfarin group and in 16 out of 54 patients (cumulative risk, 29.6%) in the placebo group (hazard ratio, 0.03; 95% confidence interval: 0.01 to 0.09; P<0.001). During the entire 42-month study period, the composite outcome occurred in 14 patients (cumulative risk, 36.8%) in the warfarin group and 17 patients (cumulative risk, 31.5%) in the placebo group (hazard ratio, 0.72; 95% confidence interval: 0.35-1.46). In conclusion, after a first unprovoked proximal deep-vein thrombosis initially treated for 6 months, an additional 18 months of warfarin therapy reduced the composite of recurrent venous thrombosis and major bleeding compared to placebo. However, this benefit was not maintained after stopping anticoagulation. Clinical registration: this trial was registered at www.clinicaltrials.gov as #NCT00740493.

Risk factors for recurrent venous thromboembolism after unprovoked pulmonary embolism: the PADIS-PE randomised trial.

We aimed to identify risk factors for recurrent venous thromboembolism (VTE) after unprovoked pulmonary embolism.Analyses were based on the double-blind randomised PADIS-PE trial, which included 371 patients with a first unprovoked pulmonary embolism initially treated during 6 months who were randomised to receive an additional 18 months of warfarin or placebo and followed up for 2 years after study treatment discontinuation. All patients had ventilation/perfusion lung scan at inclusion (i.e. at 6 months of anticoagulation).During a median follow-up of 41 months, recurrent VTE occurred in 67 out of 371 patients (6.8 events per 100 person-years). In main multivariate analysis, the hazard ratio for recurrence was 3.65 (95% CI 1.33-9.99) for age 50-65 years, 4.70 (95% CI 1.78-12.40) for age >65 years, 2.06 (95% CI 1.14-3.72) for patients with pulmonary vascular obstruction index (PVOI) ≥5% at 6 months and 2.38 (95% CI 1.15-4.89) for patients with antiphospholipid antibodies. When considering that PVOI at 6 months would not be available in practice, PVOI ≥40% at pulmonary embolism diagnosis (present in 40% of patients) was also associated with a 2-fold increased risk of recurrence.After a first unprovoked pulmonary embolism, age, PVOI at pulmonary embolism diagnosis or after 6 months of anticoagulation and antiphospholipid antibodies were found to be independent predictors for recurrence.

Risk of recurrent venous thromboembolism in COPD patients: results from a prospective cohort study.

We aimed to assess the risk of recurrent venous thromboembolism (VTE) in patients with chronic obstructive pulmonary disease (COPD) following cessation of anticoagulation therapy.In a prospective cohort of 1468 patients with a documented episode of VTE, followed for up to 5 years after cessation of anticoagulation therapy, the diagnosis of COPD was confirmed in 136. The main outcome was recurrent VTE. The secondary outcome was overall mortality. Univariate and multivariate analyses were performed to identify the risk factors of recurrence.Of the 1468 patients included, recurrent VTE was observed in 306 (34 with COPD and 272 without) during a median follow-up period of 36.5 months. The incidence rate of recurrent VTE was 9.1% (95% CI 6.5-12.8) for COPD patients and 7.0% (95% CI 6.2-7.9) for non-COPD patients. COPD was not associated with an increased risk of VTE recurrence on univariate or multivariate analyses (hazard ratio: 1.0 (95% CI 0.7-1.4)). The risk of death, adjusted for demographic and clinical characteristics, showed no increase in COPD patients, as compared to non-COPD patients.In patients with COPD who had an acute episode of VTE, the risk of recurrent VTE was not any higher than that in non-COPD patients.

Factors that predict thrombosis in relatives of patients with venous thromboembolism.

When counseling first-degree relatives of patients with venous thromboembolism (VTE), it is important to know whether factors other than thrombophilia influence their risk for thrombosis. We assessed the risk for VTE in 915 first-degree relatives of patients with provoked VTE, compared this with the risk in 1752 first-degree relatives of patients with unprovoked VTE, and then combined data from the 2 groups of relatives to identify predictors of thrombosis. There had been 123 VTEs in 2617 first-degree relatives (0.12 per 100 person-years). The risk for VTE in first-degree relatives was higher if the index cases had an unprovoked compared with a provoked VTE (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.43-3.85), if the index case was younger (OR, 0.97 per year older; 95% CI, 0.96-0.99), and if an additional family member had VTE (OR, 2.71; 95% CI, 2.22-3.31). Among first-degree relatives of an index case with factor V Leiden or the prothrombin 20210A gene variant, the presence of these abnormalities also predicted thrombosis (OR, 4.42; 95% CI, 1.35-14.38). We conclude that thrombosis at a young age and unprovoked VTE predict VTE in first-degree relatives, and that the influence of these 2 factors is additive.

Six Months vs Extended Oral Anticoagulation After a First Episode of Pulmonary Embolism: The PADIS-PE Randomized Clinical Trial.

IMPORTANCE: The optimal duration of anticoagulation after a first episode of unprovoked pulmonary embolism is uncertain. OBJECTIVES: To determine the benefits and harms of an additional 18-month treatment with warfarin vs placebo, after an initial 6-month nonrandomized treatment period on a vitamin K antagonist. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind trial (treatment period, 18 months; median follow-up, 24 months); 371 adult patients who had experienced a first episode of symptomatic unprovoked pulmonary embolism (ie, with no major risk factor for thrombosis) and had been treated initially for 6 uninterrupted months with a vitamin K antagonist were randomized and followed up between July 2007 and September 2014 in 14 French centers. INTERVENTIONS: Warfarin or placebo for 18 months. MAIN OUTCOMES AND MEASURES: The primary outcome was the composite of recurrent venous thromboembolism or major bleeding at 18 months after randomization. Secondary outcomes were the composite at 42 months (treatment period plus 24-month follow-up), as well as each component of the composite, and death unrelated to pulmonary embolism or major bleeding, at 18 and 42 months. RESULTS: After randomization, 4 patients were lost to follow-up, all after month 18, and 1 withdrew due to an adverse event. During the 18-month treatment period, the primary outcome occurred in 6 of 184 patients (3.3%) in the warfarin group and in 25 of 187 (13.5%) in the placebo group (hazard ratio [HR], 0.22; 95% CI, 0.09-0.55; P = .001). Recurrent venous thromboembolism occurred in 3 patients in the warfarin group and 25 patients in the placebo group (HR, 0.15; 95% CI, 0.05-0.43); major bleeding occurred in 4 patients in the warfarin group and in 1 patient in the placebo group (HR, 3.96; 95% CI, 0.44 to 35.89). During the 42-month entire study period (including the study treatment and follow-up periods), the composite outcome occurred in 33 patients (20.8%) in the warfarin group and in 42 (24.0%) in the placebo group (HR, 0.75; 95% CI, 0.47-1.18). Rates of recurrent venous thromboembolism, major bleeding, and unrelated death did not differ between groups. CONCLUSIONS AND RELEVANCE: Among patients with a first episode of unprovoked pulmonary embolism who received 6 months of anticoagulant treatment, an additional 18 months of treatment with warfarin reduced the composite outcome of recurrent venous thrombosis and major bleeding compared with placebo. However, benefit was not maintained after discontinuation of anticoagulation therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00740883.

Venous thromboembolism and amyotrophic lateral sclerosis: the Venous Thrombo-Embolism and Sclerosis Lateral Amyotrophic study.

Background: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease. Given the inflammatory nature of ALS and the high number of ALS-related clinical circumstances (eg, prolonged immobilization and infections), patients with ALS may have a high risk of venous thromboembolism (VTE). Objectives: To determine the annual incidence rate of VTE and the predictors of VTE in patients with ALS. Methods: We analyzed a prospective cohort of patients with ALS diagnosed between 2009 and 2019 followed in the Brest University Hospital ALS Centre. Results: Among 227 patients with ALS, VTE occurred in 19 patients during a median follow-up period of 717 days (IQR, 488-1308), yielding an annual incidence rate of 2.93% (95% CI, 1.88%-4.53%). Predictors for VTE were a family history of VTE (hazard ratio [HR], 15.24; 95% CI, 1.72-134.84; P = .01), the presence of noninvasive ventilation at ALS diagnosis (HR, 6.98; 95% CI, 1.09-44.59; P = .04) and a short time (ie, <213 days) between first symptoms and ALS diagnosis (HR, 5.48; 95% CI, 1.57-19.11; P = .01). Recurrent VTE occurred within 3 months after stopping anticoagulation in 5 patients (26.3%). Conclusion: The annual incidence of VTE in patients with ALS is high. Predictive factors of VTE were a VTE history, noninvasive ventilation, and a short time between first symptoms of ALS and ALS diagnosis.

Venous Thromboembolism Associated with Assisted Reproductive Technology: A Systematic Review and Meta-analysis.

BACKGROUND: Hormonal exposure leads to an increased risk of venous thromboembolism (VTE) but the risk of VTE associated with assisted reproductive technology (ART) is not clearly determined. METHODS: We searched in PubMed, EMBASE, Web of Science, and the Cochrane Library databases and identified all relevant articles published up to February 1, 2021. The primary objective was to determine the frequency of VTE associated with ART. Secondary objectives were to determine (1) the risk of VTE associated with ART as compared to pregnancy without ART; (2) the risk of VTE associated with ovarian hyperstimulation syndrome (OHSS); and (3) to determine potential risk factors of VTE related to ART. RESULTS: Fourteen studies were included. The overall frequency of VTE associated with ART was 0.23% (95% confidence interval [CI]: 0.07-0.46). Women undergoing ART had a two- to threefold increased risk of VTE as compared to spontaneous pregnancy (relative risk [RR]: 2.66; 95% CI: 1.60-4.43). The overall frequency of VTE specifically related to OHSS was <0.001%. The risk of VTE after ART complicated by OHSS, as compared to ART without OHSS, was higher but not statistically significant (RR: 14.83; 95% CI: 0.86-255.62). Risk factors of VTE associated with ART were in vitro fertilization procedure (RR, odds ratio [OR], and hazard ratio varying from 1.77, 95% CI: 1.41-2.23 to 4.99, 95% CI: 1.24-20.05), hyperhomocysteinemia (OR: 15.2; 95% CI: 2.0-115.0), polycystic ovarian syndrome (PCOS) (RR: 4.8; 95% CI: 1.7-13.4), successful ART leading to pregnancy (OR: 13.94; 95% CI: 1.41-137.45). CONCLUSION: Further large prospective studies on risk factors of VTE in women undergoing ART are needed in order to optimize thromboprophylaxis in this context.

Pulmonary embolism diagnostic strategies in patients with COPD exacerbation: Post-hoc analysis of the PEP trial.

BACKGROUND: The prevalence of pulmonary embolism (PE) is approximately 11-17 % in patients with an acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). The optimal diagnostic strategy for PE in these patients remains undetermined. AIMS: To evaluate the safety and efficacy of standard (revised Geneva and Wells PE scores combined with fixed D-dimer cut-off) and computed tomography pulmonary angiogram (CTPA)-sparing diagnostic strategies (ADJUST-PE, YEARS, PEGeD, 4PEPS) in patients with AE-COPD. METHOD: Post-hoc analyses of data from the multicenter prospective PEP study were performed. The primary outcome was the diagnostic failure rate of venous thromboembolism (VTE) during the entire study period. Secondary outcomes included diagnostic failure rate of PE and deep venous thrombosis (DVT), respectively, during the entire study period and the number of CTPA needed per diagnostic strategy. RESULTS: 740 patients were included. The revised Geneva and Wells PE scores combined with fixed D-dimer cut-off had a diagnostic failure rate of VTE of 0.7 % (95%CI 0.3 %-1.7 %), but >70.0 % of the patients needed imaging. All CTPA-sparing diagnostic algorithms reduced the need for CTPAs (-10.1 % to -32.4 %, depending on the algorithm), at the cost of an increased VTE diagnosis failure rate of up to 2.1 % (95%CI 1.2 %-3.4 %). CONCLUSION: Revised Geneva and Wells PE scores combined with fixed D-dimer cut-off were safe, but a high number of CTPA remained needed. CTPA-sparing algorithms would reduce imaging, at the cost of an increased VTE diagnosis failure rate that exceeds the safety threshold. Further studies are needed to improve diagnostic management in this population.

The SQ HDM SLIT-Tablet is safe and well tolerated in patients with House Dust Mite allergic rhinitis with or without asthma: A "real-life" French study.

BACKGROUND: The SQ House Dust Mite (HDM) SubLingual ImmunoTherapy (SLIT)-Tablet (Acarizax) is the only allergen immunotherapy authorized by European regulatory authorities to treat HDM-induced allergic asthma (AA) that is not well-controlled by inhaled corticosteroids and associated with mild-to-severe HDM allergic rhinitis (AR). The aim of this study was to add evidence on the safety of the SQ HDM SLIT-Tablet in patients with AR, alone or with AA, under real-life conditions. METHODS: This was a French "real-life", multicenter, non-comparative, longitudinal, prospective study. It included patients initiating the SQ HDM SLIT-Tablet for either persistent moderate-to-severe HDM AR or AA not well-controlled by inhaled corticosteroids and associated with mild-to-severe HDM AR. Adverse Events (AEs) were collected at the first intake and throughout the study. Logistic regression was used to compare safety according to asthma control before treatment initiation. RESULTS: Between May 09, 2018 and May 29, 2019, 1526 patients were enrolled at 185 sites and 1483 were included in the safety population (SAF). Of them, 33.6% had suspected clinical manifestations of AA. Asthma was uncontrolled for 18.2% of the patients, partially controlled for 27.9% and well-controlled for 53.8%. Overall, 31.9% of the SAF patients experienced at least one AE. The percentage of patients with AEs was 29.9% among patients with AR alone and 35.9% among those with AA (p = 0.0193). No significant difference was observed in the rate of AE or SAE depending on asthma control at inclusion (2.2% of SAEs reported for patients with uncontrolled asthma, 1.4% for partly controlled and 1.1% for well-controlled). CONCLUSIONS: The overall results indicate a good SQ HDM SLIT-Tablet safety profile consistent with that reported in previous studies, regardless of asthma control.

Asthma and smoking: A review.

Asthma occurrence is often associated with cigarette smoking. Surprisingly, active smokers are excluded from most clinical studies. Prevalence of asthma associated with smoking appears to be similar to asthma in the general population. However, in active smokers, asthma tends to be more difficult to manage and more severe. Several studies have demonstrated a poor response to inhaled corticosteroids (ICS) and an accelerated decline of lung function. Smoking decreases exhaled NO rate and down-regulates ICS receptors, which is associated with increased oxidative stress. Data on biologic therapies are scarce. Finally, nicotine dependence seems higher in asthmatic patients and smoking cessation is thus more difficult.