Diagnosing pulmonary thromboembolism: Concerns and controversies

Pulmonary thromboembolism (PTE) is an important cause of mortality/morbidity even today despite advancement in clinical understanding as well as diagnostic facilities. Clinical diagnosis of PTE is often challenging because of nonspecific sign/symptoms. Adherence to clinical decision-making protocols and appropriate use of diagnostic modalities like computed tomography pulmonary angiography can resolve the diagnostic dilemma in most cases and help in the overall management of PTE. This article deals with various concerns as well as controversies surrounding accurate diagnosis of PTE as on date.     

Thrombosis and thromboembolism: Brighton collaboration case definition and guidelines for data collection,analysis, and presentation of immunization safety data

This is a Brighton Collaboration case definition of thrombosis and thromboembolism to be used in the evaluation of adverse events following immunization, and for epidemiologic studies for the assessment of background incidence or hypothesis testing. The case definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of SARS-CoV-2 vaccines. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected expert reviewers prior to submission.     

Utilization of and Outcomes Associated with Intravascular Ultrasound during Deep Venous Stent Placement among Medicare Beneficiaries

PurposeTo evaluate temporal trends, practice variation, and associated outcomes with the use of intravascular ultrasound (US) during deep venous stent placement among Medicare beneficiaries.Materials and MethodsAll lower extremity deep venous stent placement procedures performed between January 1, 2017, and December 31, 2019 among Medicare beneficiaries were included. Temporal trends in intravascular US use were stratified by procedural setting and physician specialty. The primary outcome was a composite of 12-month all-cause mortality, all-cause hospitalization, or repeat target vessel intervention. The secondary outcome was a composite of 12-month stent thrombosis, embolization, or restenosis.ResultsAmong the 20,984 deep venous interventions performed during the study period, 15,184 (72.4%) utilized intravascular US. Moderate growth in intravascular US use was observed during the study period in all clinical settings. There was a variation in the use of intravascular US among all operators (median, 77.3% of cases; interquartile range, 20.0%–99.2%). In weighted analyses, intravascular US use during deep venous stent placement was associated with a lower risk of both the primary (adjusted hazard ratio, 0.72; 95% confidence interval [CI], 0.69–0.76; P < .001) and secondary (adjusted hazard ratio, 0.32; 95% CI, 0.27–0.39; P < .001) composite end points.ConclusionsIntravascular US is frequently used during deep venous stent placement among Medicare beneficiaries, with further increase in use from 2017 to 2019. The utilization of intravascular US as part of a procedural strategy was associated with a lower cumulative incidence of adverse outcomes after the procedure, including venous stent thrombosis and embolization.     

Impact of anticoagulation status on recanalization and outcome of cerebral venous thrombosis

Effective anticoagulation status may determine the recanalization and outcome of cerebral venous thrombosis (CVT). We report impact of anticoagulation status on recanalization and outcome of CVT. This is a retrospective study on 126 patients with CVT diagnosed on magnetic resonance venography (MRV). Their clinical features and risk factors were noted. The data were retrieved from a prospectively maintained registry, and international normalized ratio (INR) was noted after discharge till 3 months. All the patients were on acenocoumarol. Based on INR value, patients were categorized as Group A (effective anticoagulation INR within the therapeutic range or above) and Group B (ineffective anticoagulation INR > 50% below the therapeutic range). A repeat MRV at 3 months was done for recanalization. Outcome at 3 months was evaluated using modified Rankin Scale (mRS), and categorized as good (mRS ≤ 2) and poor (mRS 2 or more) 101(80.2%) patients were in group A and 25(19.8%) in group B. Their demographic, risk factors, magnetic resonance imaging (MRI) and MRV findings were comparable. On repeat MRV, recanalization occurred in 22/24(91.7%); 15(88%) in group A and 7(100%) in group B. Recanalization was independent of coagulation status. Seven (5.6%) patients died and 107(84.9%) had good outcome; 85(84.2%) in group A and 22(88%) in group B. Kaplan Meier analysis also did not reveal survival or good outcome benefits between the groups. In CVT, outcome and recanalization at 3 months are not dependent on coagulation status. Further prospective studies are needed regarding duration of anticoagulant and its impact on recanalization and outcome.     

Evaluation of timolol maleate gel for management of hard-to-heal chronic venous leg ulcers. Phase II randomised-controlled study

BackgroundVenous leg ulcers (VLUs) often take a very long time to heal. Timolol maleate has been reported as displaying efficacy in healing of VLUs.ObjectivesTo evaluate the efficacy of timolol maleate gel in the management of hard-to-heal VLUs and to assess its safety as a topical agent during 12 weeks of use in combination with conventional treatment.MethodsA prospective, phase-II randomised-controlled trial with a sample size based on Fleming's one-stage design (P0 = 0.25, P1 = 0.45, alpha = 0.1, beta = 0.2) was planned. Patients with VLUs present for ≥ 24 weeks and with ≥ 50% granulation tissue were included. One drop of sustained-release timolol gel (Timoptol® LP 0.5%, Santen, Tampere, Finland) per 6 cm² VLU area was applied every 2 days for 12 weeks in timolol-treated patients, as adjuvant therapy to the standard care protocol (interface dressing and multilayer venous compression). Controls received standard care alone. The primary endpoint was to obtain ≥ 40% reduction in ulcer area at week 12 (W12).ResultsForty-three patients were randomised to the study, with 40 receiving at least one treatment and included in the analysis: 21 timolol-treated patients and 19 controls (females: 70%; median age: 72.5 [range 35–93] years). At W12, ≥ 40% ulcer-area reduction was achieved in 14/21 (67%) timolol-treated patients vs. 6/19 (32%) controls. No serious adverse events occurred. Local wound infections not requiring systemic antibiotics occurred in 5 cases in the timolol group and in one case in the controls.ConclusionsThese results support the benefit and safety of using timolol maleate to manage hard-to-heal VLUs, but confirmation is required in a larger multicentre randomised phase-III study.     

COVID-19 and venous thromboembolism: Known and unknown for imaging decisions

As we continue to fight against the current coronavirus disease-2019 (COVID-19) pandemic, healthcare professionals across the globe are trying to answer questions surrounding how to best help patients with the up-to-date available science while awaiting the development of new therapies and mass vaccination. Since early in the pandemic, studies indicated a heightened risk of venous thromboembolism (VTE) in COVID-19 infected patients. There have been differing expert opinions about how to assess pretest probability of VTE in this patient population. This has been partly due to the high prevalence of respiratory failure in this patient population and the use of D-dimer as a prognostic test which is also frequently elevated in patients with COVID-19 in absence of VTE. Some experts have argued for an approach similar to usual care with testing if clinical suspicion is high enough. Some have argued for more routine screening at different points of care. Others have even suggested empiric therapeutic anti-coagulation in moderate to severely ill COVID-19 patients. In the following article, we review and summarize the most current literature in hopes of assisting clinicians in decision making and guidance for when to be concerned for VTE in COVID-19 patients. We also discuss research gaps and share pathways currently being used within our institution.     

Development of a core outcome set for venous leg ulceration (CoreVen) research evaluations (protocol)

BackgroundA venous leg ulcer is a chronic leg wound caused by poor venous blood circulation in the lower limbs. It is a recurring condition causing pain, malodour, reduced mobility, and depression. Randomised controlled trials evaluating treatments for venous leg ulcers provide important evidence to inform clinical decision-making. However, for findings to be useful, outcomes need to be clinically meaningful, consistently reported across trials, and fully reported. Research has identified the large number of outcomes reported in venous leg ulcer trials, impacting both synthesis of results, and clinical decision-making. To address this, a core outcome set will be developed. A core outcome set is an agreed standardised set of outcomes which should be, as a minimum, measured and reported in all trials which evaluate treatment effectiveness for a given indication. A core outcome set has the potential to reduce research waste, improve the utility of RCTs, reduce reporting bias, facilitate treatment comparisons across different sources of evidence and expedite the production of systematic reviews, meta-analyses and evidence-based clinical guidelines.AimThe aim of this project is to develop a core outcome set for research evaluating the effectiveness of interventions for treating venous leg ulceration.MethodsThrough a scoping review of the literature on venous leg ulceration, we will firstly identify a list of candidate outcome domains (broad categories in relation to what is being measured) from randomised controlled trials and qualitative research, and outcomes (specific methods in relation to what is being measured). In two further stages, we will use the resulting lists of outcome domains and outcomes to design two online surveys. A range of stakeholders will be invited to participate in the surveys and they will be asked to indicate which outcome domains and outcomes are most important and should be considered as core in future research reports.     

SARS-CoV-2 infection and venous thromboembolism after surgery: an international prospective cohort study

SARS-CoV-2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri-operative or prior SARS-CoV-2 were at further increased risk of venous thromboembolism. We conducted a planned sub-study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 days of surgery. SARS-CoV-2 diagnosis was defined as peri-operative (7 days before to 30 days after surgery); recent (1–6 weeks before surgery); previous (≥7 weeks before surgery); or none. Information on prophylaxis regimens or pre-operative anti-coagulation for baseline comorbidities was not available. Postoperative venous thromboembolism rate was 0.5% (666/123,591) in patients without SARS-CoV-2; 2.2% (50/2317) in patients with peri-operative SARS-CoV-2; 1.6% (15/953) in patients with recent SARS-CoV-2; and 1.0% (11/1148) in patients with previous SARS-CoV-2. After adjustment for confounding factors, patients with peri-operative (adjusted odds ratio 1.5 (95%CI 1.1–2.0)) and recent SARS-CoV-2 (1.9 (95%CI 1.2–3.3)) remained at higher risk of venous thromboembolism, with a borderline finding in previous SARS-CoV-2 (1.7 (95%CI 0.9–3.0)). Overall, venous thromboembolism was independently associated with 30-day mortality (5.4 (95%CI 4.3–6.7)). In patients with SARS-CoV-2, mortality without venous thromboembolism was 7.4% (319/4342) and with venous thromboembolism was 40.8% (31/76). Patients undergoing surgery with peri-operative or recent SARS-CoV-2 appear to be at increased risk of postoperative venous thromboembolism compared with patients with no history of SARS-CoV-2 infection. Optimal venous thromboembolism prophylaxis and treatment are unknown in this cohort of patients, and these data should be interpreted accordingly.