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BACKGROUND Few data are available on the long-term course and predictors of quality of life (QoL) following acute pulmonary embolism (PE). RESEARCH QUESTION What are the kinetics and determinants of disease-specific and generic health-related QoL 3 and 12 months following an acute PE? STUDY DESIGN AND METHODS The Follow-up after Acute Pulmonary Embolism (FOCUS) study prospectively followed up consecutive adult patients with objectively diagnosed PE. Patients were considered for study who completed the Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire at predefined visits 3 and 12 months following PE. The course of disease-specific QoL as assessed using the PEmb-QoL and the impact of baseline characteristics using multivariable mixed effects linear regression were studied; also assessed was the course of generic QoL as evaluated by using the EuroQoL Group 5-Dimension 5-Level utility index and the EuroQoL Visual Analog Scale. RESULTS In 620 patients (44% women; median age, 62 years), overall disease-specific QoL improved from 3 to 12 months, with a decrease in the median PEmb-QoL score from 19.4% to 13.0% and a mean individual change of -4.3% (95% CI, -3.2 to -5.5). Female sex, cardiopulmonary disease, and higher BMI were associated with worse QoL at both 3 and 12 months. Over time, the association with BMI became weaker, whereas older age and previous VTE were associated with worsening QoL. Generic QoL also improved: the mean ± SD EuroQoL Group 5-Dimension 5-Level utility index increased from 0.85 ± 0.22 to 0.87 ± 0.20 and the visual analog scale from 72.9 ± 18.8 to 74.4 ± 19.1. INTERPRETATION In a large cohort of survivors of acute PE, the change of QoL was quantified between months 3 and 12 following diagnosis, and factors independently associated with lower QoL and slower recovery of QoL were identified. This information may facilitate the planning and interpretation of clinical trials assessing QoL and help guide patient management. CLINICAL TRIAL REGISTRATION German Clinical Trials Registry (Deutsches Register Klinischer Studien: www.drks.de); No.: DRKS00005939.

Recombinant interleukin-2 (rIL-2) is indicated for metastatic renal cell carcinoma and melanoma. Over recent years low-dose rIL-2 has been studied for the treatment of autoimmune diseases and acute coronary syndrome because of its ability to expand and activate T regulatory (Treg) cells. However, several medical conditions potentially benefiting from rIL-2 administrations are characterized by an intrinsic prothrombotic risk, thus requiring concurrent anticoagulation. In our systematic review of the literature, we investigated the potential for drug interactions between oral anticoagulants and rIL-2 by assessing the influence of rIL-2 administration on transporters and cytochromes determining the pharmacokinetics of (direct) oral anticoagulants. We extracted data from 12 studies, consisting of 11 animal studies and one study in humans. Eight studies investigated the pharmacokinetics of P-glycoprotein (P-gp) substrates and reported that the intraperitoneal rIL-2 administration may inhibit intestinal P-gp. Four studies on hepatic cytochrome P450 yielded conflicting results. The only human study included in this systematic review concluded that rIL-2 suppresses the hepatic cytochrome P450, but only if given at higher doses. Based on the results from animal studies, the co-administration of rIL-2 and dabigatran etexilate, a substrate of intestinal P-gp, may lead to higher dabigatran plasma concentrations and bioavailability. Human studies should confirm whether this potential interaction is clinically relevant.

Background Few data are available on the long-term course and predictors of quality of life (QoL) after acute pulmonary embolism (PE). Aims To evaluate the kinetics and determinants of QoL at 3 and 12 months after acute PE. Methods The Follow-Up after acute pulmonary embolism (FOCUS) study prospectively followed consecutive adult patients with objectively diagnosed PE. For this analysis, we considered patients who completed the Pulmonary Embolism QoL (PEmb-QoL) Questionnaire at two predefined visits 3 and 12 months after PE. PEmb-QoL, studied as total score and in its six dimensions, ranges from 0% (best QoL) to 100% (worst QoL). We studied the course of PEmb-QoL and the impact of baseline characteristics using multivariable linear regression. Results In 617 included patients (44% women, median age 62 years), overall QoL improved from 3 to 12 months, with a decrease of the mean PEmb-QoL score from 25.3% to 21.5% (p-value Conclusions In a large cohort of patients with pulmonary embolism, we quantified the improvement of QoL between 3 and 12 months after diagnosis. We identified factors independently associated with lower QoL and slower recovery of QoL that may reflect special patient needs. These estimates may facilitate the planning and interpretation of clinical trials with QoL as a study outcome. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): University Medical Center of the Johannes Gutenberg University, Mainz, Germany; German Federal Ministry of Education and Research

Background It is unclear to which extent persistence of symptoms and/or residual haemodynamic impairment clinical course of pulmonary embolism are associated with worse quality of life (QoL). Aims To study the correlation between symptoms and haemodynamic impairment with QoL during the first year after acute pulmonary embolism (PE). Methods The Follow-Up after acute pulmonary embolism (FOCUS) study prospectively enrolled and followed consecutive adult patients diagnosed with acute symptomatic objectively diagnosed PE. In the present analysis, we considered patients who completed the Pulmonary Embolism QoL (PEmb-QoL) Questionnaire at predefined visits 3 and 12 months after acute PE. The PEmb-QoL score ranges from 0% (best QoL) to 100% (worst QoL). We evaluated at these two time points the correlation between persisting symptoms (group: symptoms), elevation of natriuretic peptides or residual right ventricular dysfunction (group: RVD), or their combination (group: symptoms + RVD) and QoL. Results A total of 617 patients were included; their median age was 62 years, 44% were women; 8% had active cancer, and 21% previous venous thromboembolism. At 3 months, patients with neither symptoms nor RVD (n=302) had the highest quality of life (median score 18%, 25th–75th percentile: 8%–34%), followed by those without symptoms but with RVD (n=255; median score 19%, 25th–75th percentile: 7%–34%), and by those with symptoms only (n=131; median PEmb-QoL 31%, 25th–75th percentile: 18%–49%). Patients with both symptoms and RVD (n=170) had the worst quality of life (median score 38%, 25th–75th percentile: 19%–53%); Figure 1A. At 12 months, we found an overall improvement of PEmb-QoL score. The degree of this QoL improvement varied across groups, being largest for patients who recovered from having symptoms + RVD at 3 months to normalization of at least one at 12 months. The change in QoL from 3 to 12 months was smaller both in patients who had neither symptoms nor RVD and in patients who had no recovery in either symptoms or RVD; Figure 1B. Conclusions Persistent symptoms after PE, especially in patients with elevated biomarkers or residual echocardiographic dysfunction, were the main drivers of QoL at 3 months as well as of the course of QoL over time. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): University Medical Center of the Johannes Gutenberg University, Mainz, Germany; German Federal Ministry of Education and Research

Standard-dose intravenous recombinant interleukin-2 (rIL-2) is indicated for the treatment of some subtypes of cancer; however, severe adverse events, including venous thromboembolism (VTE), may complicate its administration. Low-dose subcutaneous rIL-2 is being studied for the management of immune-mediated diseases, since it can modulate the immunological response by specifically targeting T regulatory (Treg) cells; importantly, it is supposed to cause fewer or no complications. In this systematic review and meta-analysis of phase II-III randomized controlled trials (RCTs), we investigated the safety of low-dose (