Pulmonary embolism in the elderly: a review on clinical, instrumental and laboratory presentation

OBJECTIVE: Diagnosis of pulmonary embolism (PE) remains difficult and is often missed in the elderly due to nonspecific and atypical presentation. Diagnostic algorithms able to rule out PE and validated in young adult patients may have reduced applicability in elderly patients, which increases the number of diagnostic tools use and costs. The aim of the present study was to analyze the reported clinical presentation of PE in patients aged 65 and more. MATERIALS AND METHODS: Prospective and retrospective English language studies dealing with the clinical, instrumental and laboratory aspects of PE in patients more than 65 and published after January 1987 and indexed in MEDLINE using keywords as pulmonary embolism, elderly, old, venous thromboembolism (VTE) in the title, abstract or text, were reviewed. RESULTS: Dyspnea (range 59%-91.5%), tachypnea (46%-74%), tachycardia (29%-76%), and chest pain (26%-57%) represented the most common clinical symptoms and signs. Bed rest was the most frequent risk factor for VTE (15%-67%); deep vein thrombosis was detected in 15%-50% of cases. Sinus tachycardia, right bundle branch block, and ST-T abnormalities were the most frequent ECG findings. Abnormalities of chest X-ray varied (less than 50% in one-half of the studies and more than 70% in the other one-half). Arterial blood gas analysis revealed severe hypoxemia and mild hypocapnia as the main findings. D-Dimer was higher than cut-off in 100% of patients in 75% of studies. Clinical usefulness of D-Dimer measurement decreases with age, although the strategies based on D-Dimer seem to be cost-effective at least until 80 years. CONCLUSION: Despite limitations due to pooling data of heterogeneous studies, our review could contribute to the knowledge of the presentation of PE in the elderly with its diagnostic difficulties. A diagnostic strategy based on reviewed data is proposed

Protocol for a modelling study to assess the clinical and cost-effectiveness of indefinite anticoagulant therapy for first unprovoked venous thromboembolism.

INTRODUCTION Deciding whether to stop or extend anticoagulant therapy indefinitely after completing at least 3 months of initial treatment for a first unprovoked venous thromboembolism (VTE) remains a challenge for clinicians, patients and policy makers. Guidelines suggest an indefinite duration of anticoagulant therapy in these patients, yet its benefits, harms and costs have not been formally assessed. The aim of this proposed modelling study is to assess the differences in clinical benefits, harms and costs of stopping versus continuing anticoagulant therapy indefinitely for a first unprovoked VTE. METHODS AND ANALYSIS We will develop a probabilistic Markov model, adopting a 1-month cycle length and a lifetime horizon, to estimate life-years, quality-adjusted life-years, costs and the incremental cost-effectiveness ratios for a simulated population of patients with a first unprovoked VTE who will receive indefinite duration of anticoagulant therapy versus a population who will not receive extended treatment after completing 3 months of initial anticoagulant therapy. The economic evaluation will adopt a third-party payer perspective relating to a Canadian publicly funded healthcare system. Estimates for the probability of relevant clinical events will be informed by systematic reviews and meta-analyses, while costs and utility values will be obtained from published Canadian sources. Stratified analyses based on sex, age and site of initial VTE will also be performed to identify subgroups of patients with a first unprovoked VTE in whom continuing anticoagulant therapy indefinitely might prove to be clinically beneficial and cost-effective over stopping treatment. We will also conduct sensitivity and scenario analyses to assess robustness of study findings to changes in individual or groups of key parameters. ETHICS AND DISSEMINATION Ethical approval is not applicable for this study. The results will be disseminated through presentations at relevant conferences and in a manuscript that will be submitted to a peer-reviewed journal

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Defining time in therapeutic range for busy clinicians: frequency of dose changes is a good surrogate marker to identify patients with suboptimal anticoagulation with warfarin.

International audiencePatients on warfarin with sub-optimal time-in-therapeutic-range (TTR) are more likely to have adverse events. Target-specific oral anticoagulants (TSOACs) are approved and can be used as an alternative to warfarin for a number of indications. Further, the efficacy and safety profiles of the TSOACs compared to warfarin are more favourable when the TTR is ≤65% for certain indications. We aimed to determine simple, sensitive and specific diagnostic tools to identify TTR ≤ 65% during the initial three months of warfarin therapy. A cross-sectional study including patients newly initiated on warfarin without any interruption for three months was conducted. TTR was calculated using the Rosendaal method. Patients were stratified by TTR (≤ 65% or >65%). Number of INR measurements, dose changes and INR measurements of ≤ 1.7 or ≥ 4.0 were evaluated as potential diagnostic tools to identify TTR ≤ 65%. 670 patients were included. The most common indication for anticoagulation was venous thromboembolism. The mean TTR in the first three months was 68 ± 21% (Range: 10 to 100%). Three or more dose changes identified TTR ≤ 65% and demonstrated a sensitivity and specificity of 90% (95%CI 86 to 93%) and 56% (95%CI 51 to 61%), respectively. Three or more INR measurements of ≤ 1.7 during the initial three months of anticoagulation showed a sensitivity and specificity of 37% (95%CI 32 to 43%) and 98% (95%CI 96 to 99%), respectively. Three or more dose changes and three or more INR measurements of ≤ 1.7 could identify patients with a TTR ≤ 65% in the first three months of warfarin therapy

Phenotypic but not allelic ABO blood group association with risk of venous thrombosis.

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Major Bleeding during Secondary Prevention of Venous Thromboembolism in Patients who have Completed Anticoagulation: A Systematic Review and Meta-Analysis.

International audienceBACKGROUND: The risk of major bleeding in patients who have completed anticoagulation therapy for unprovoked venous thromboembolism (VTE) is unknown. OBJECTIVE: To report the major bleeding and fatal bleeding rates in patients randomized to placebo or observation (i.e. no anticoagulation therapy) for the secondary prevention of recurrent VTE. PATIENTS/METHODS: We performed a systematic review and meta-analysis of the literature to summarize the rates of major bleeding and fatal bleeding in patients randomized to placebo or observation during the secondary prevention of VTE. Unrestricted searches of Medline (1950 to August 31, 2013), Embase (1980 to August 31, 2013), and the Cochrane Register of Controlled Trials using the OVID interface were conducted. Publications from potentially relevant journals were also searched by hand. We used a random-effects model to pool study results and I(2) testing to assess for heterogeneity. RESULTS: The analysis included 11 studies and 3,965 patients who were followed for a median of 24 months. The overall pooled major bleeding rate was 0.45 per 100 patient-years (95% CI: 0.29 to 0.64; I(2) : 0%), and the overall pooled fatal bleeding rate was 0.14 per 100 patient-years (95% CI: 0.057 to 0.26; I(2) : 0%). CONCLUSIONS: Patients not receiving anticoagulant therapy for the secondary prevention of VTE experience major bleeding events and this may impact recommendations for extended treatment in this patient population. This article is protected by copyright. All rights reserved