Development and application of health outcome descriptors facilitated decision-making in the production of practice guidelines.

OBJECTIVE: Stakeholders involved in developing recommendations need to have a common understanding of health outcomes and the perspective of affected individuals. In this paper we report on the development and application of health outcome descriptors (HODs) to inform decision-making by panels developing guideline recommendations. STUDY DESIGN AND SETTING: Ten American Society of Hematology guideline panels addressing the management of venous thromboembolism developed HODs, rated their importance and health utility, applied them to prioritize outcomes, and to balance potential benefits and harms to formulate recommendations. RESULTS: It was feasible to involve 18 panelists in developing 127 HODs. There was high agreement (82%) across the ten panels about outcomes perceived as critical or important for decision-making. Panelists' utility ratings of the outcomes were strongly correlated with panelists' outcome importance ratings (Pearson's r=-0.88). HODs were incorporated into Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence-to-decision (EtD) frameworks to support a shared understanding of health outcomes in panel deliberations. CONCLUSION: HODs serve as a valuable tool to promote an explicit, common understanding of health outcomes during clinical guideline development and across different stakeholders. They are helpful across multiple steps of guideline development to facilitate panels' judgements, aiming to avoid variable implicit interpretations of health outcomes.

Pulmonary Embolism in the Intensive Care Unit: Therapy in Subpopulations.

The optimal management of a submassive or massive pulmonary embolism (PE) during pregnancy is unclear because of a lack of large clinical trials. Evaluation of the patient who may be a candidate for more aggressive therapy includes the use of biomarkers and echocardiogram for risk stratification. PE Response teams (PERTs) have gained increasing acceptance by the medical community and are being implemented in hospitals in the United States and worldwide. PERTs bring together a team of specialists from different disciplines to enhance decision-making in the patient with acute submassive and massive PE.

Management of Right Ventricular Failure in Pulmonary Embolism.

Acute right ventricular failure remains the leading cause of mortality associated with acute pulmonary embolism (PE). This article reviews the pathophysiology behind acute right ventricular failure and strategies for managing right ventricular failure in acute PE. Immediate clot reduction via systemic thrombolytics, catheter based procedures, or surgery is always advocated for unstable patients. While waiting to mobilize these resources, it often becomes necessary to support the RV with vasoactive medications. Clinicians should carefully assess volume status and use caution with volume resuscitation. Right ventricular assist devices may have an expanding role in the future.

Is intravenous thrombolysis safe for acute ischemic stroke patients taking warfarin with INR 1.9?: A case report.

INTRODUCTION: Intravenous thrombolysis is not suitable for patients undergoing oral anticoagulants therapy, with INR > 1.7 or PT > 15 s. We described a case of intravenous thrombolysis in a patient with INR 1.9. PATIENT CONCERNS: A 66-year-old female patient was diagnosed with acute appendicitis complicated with atrial fibrillation. Seven days after admission, the patient suffered mixed aphasia with right limb asthenia. The NIHSS score was 11 points. and early infarction and hemorrhagic manifestations were not found in the emergency head CT. Thirty minutes after the onset of symptoms, NIHSS of patient increased from 11 to 14, but the INR was 1.92. DIAGNOSIS: Acute ischemic stroke. INTERVENTIONS: The IT therapy was recommended and all the therapy related risks were explained to the patient's parents. Briefly, the patient was given rTPA 38.5 mg. In addition to intravenous thrombolysis, VitK1 40 mg was simultaneously administered. OUTCOME: The patient's symptoms of drowsiness were improved. After 24 hours, all symptoms were stabilized with NIHSS of 2 points, there was a slight language obstruction, and no hemorrhagic transformation in head CT. Three months later, the review showed MRS score of 0, and the patient could take care of herself in daily life. CONCLUSION: The clinical guidelines are still the main reference for guiding clinical practice, and the main thrombolytic standards and contraindications for treatment still need to be conformed. On this basis, for individualized patients, clinicians must accurately judge the cause of acute stroke, to make optimal choice, reduce disability and mortality, and improve quality of life of patients.

Clinical Practice and Guidelines for Managing Antithrombotics before and after Endoscopy: A National Survey Study.

Background/Aims: The proper handling of antithrombotics is critical, and this study aimed to assess guideline adherence in the management of antithrombotics before and after endoscopy. Methods: A survey questionnaire was developed. The respondents' demographic information was included, and the questionnaire was divided into the first section for forceps biopsy, the second for polypectomy, and the third for endoscopic submucosal dissection (ESD) in which aspirin, clopidogrel, combination therapy (aspirin and clopidogrel), warfarin, and direct oral anticoagulants (apixaban) were prescribed to imaginary patients. Results: A total of 415 endoscopists completed this survey (response rate of 6.2%, 415/6,673). The percentage of respondents who chose to proceed with biopsy for patients taking aspirin, those taking clopidogrel, those under combination therapy, those taking warfarin, and those taking apixaban was 89.4%, 74.2%, 61.0%, 38.6%, and 50.4%, respectively. Most respondents answered that they would discontinue aspirin, clopidogrel, and a combination of both drugs for 5 days before polypectomy or ESD (69.4%/76.9%, 83.6%/83.9%, and 53.3%/65.8%, respectively). The answers indicated that warfarin should be discontinued with heparin bridge therapy in high thromboembolic risk patients (polypectomy 70.1%, ESD 73.5%). Regarding apixaban use in polypectomy and ESD, 63.9% and 58.1% of respondents, respectively, chose answers consistent with the guidelines. Conclusions: The gap between the guidelines and clinical practice in the management of antithrombotics before and after endoscopy is considerable and should be addressed via educational strategies.

Questionnaire-Based Survey on Gastrointestinal Bleeding and Management of Antithrombotic Agents during Endoscopy Among Asian Countries.

OBJECTIVE: Guidelines on the management of antithrombotic therapy for endoscopic procedures vary among countries. Differences in the management of antithrombotic agents for endoscopic procedures between Western and Eastern countries have already been reported. However, no study has investigated the differences among Asian countries. The aim of this study was to examine the differences in the etiology of gastrointestinal bleeding and management of antithrombotic agents during endoscopic procedures between Japan and other Asian countries (OAC). METHODS: Questionnaires regarding gastrointestinal bleeding in clinical practice and management of antithrombotic agents during endoscopy were distributed to members of the International Gastroenterology Consensus Symposium Study Group. We analyzed the questionnaire answers and compared the results between Japan and OAC. RESULTS: The cause of and treatment methods for gastrointestinal bleeding differed between Japan and OAC. In Japan, the trend was to continue drugs at the time of biopsy and endoscopic therapy. Even in cases of discontinuation, the drug withdrawal period was as short as <3 days. Thrombotic complications caused by the withdrawal of antithrombotic agents were observed more frequently in Japan (34.78%) than in OAC (22.46%; p = 0.016). CONCLUSION: Due to differences in guidelines and complications associated with discontinuation of drugs, the antithrombotic withdrawal period in Japan tended to be shorter than that in OAC.

Predictors of symptomatic intracranial haemorrhage in off-label thrombolysis: an analysis of the Safe Implementation of Treatments in Stroke registry.

BACKGROUND AND PURPOSE: Intravenous thrombolysis (IVT) is the only approved pharmacological treatment for acute ischemic stroke. Off-label IVT for ischemic stroke is common. We aimed to analyse its safety in a large database. METHODS: This was a retrospective analysis of the safe implementation of treatments in stroke (SITS) thrombolysis registry with regard to 11 off-label criteria according to the European licence for alteplase. Symptomatic intracranial haemorrhage (SICH) according to SITS was defined as primary safety endpoint and SICH according to the European Cooperative Acute Stroke Study (ECASS II) definition and the National Institute of Neurological Disorders and Stroke definition as secondary safety endpoints. Multivariable logistic regression analyses after replacing missing values using multiple imputations were performed. RESULTS: Patients from 793 centres in 44 countries were included, mainly (95%) in Europe. A total of 56 258 patients who were treated with intravenous alteplase were included. Median age was 71 (IQR 61-78) years and median National Institutes of Health Stroke Scale score was 12 (IQR 7-17). A total of 16 740 (30%) patients received off-label IVT and 1037 (1.8%) patients suffered from SICH according to the SITS definition (SICH SITS). Median percentage of missing values per variable was 0.4%. The only two off-label criteria constituting independent positive and negative predictors for SICH SITS were high blood pressure (odds ratio, 1.39; 95% confidence interval, 1.08-1.80; P = 0.012) and minor stroke (odds ratio, 0.51; 95% confidence interval, 0.33-0.78; P = 0.002). Very severe stroke, previous stroke and diabetes, age and high glucose levels were additional independent predictors of SICH according to the ECASS II and National Institute of Neurological Disorders and Stroke definitions. CONCLUSIONS: Thrombolysis appears to be safe with regard to SICH for most of the off-label criteria, especially for minor stroke, but is risky in patients with high blood pressure. Individual risk-benefit evaluation should be performed.

Prevalence and Clinical Intentions of Antithrombotic Therapy on Discharge to Hospice Care.

BACKGROUND: There are no guidelines for antithrombotic therapy on admission to hospice care. Antithrombotic therapy may offer some benefit in these patients, but is also associated with well-described risks. OBJECTIVE: We quantified the frequency and characteristics of patients prescribed antithrombotic therapy on discharge from acute care to hospice care. DESIGN: Retrospective cohort study. Settings/Subjects: Adult (age> = 21 years) patients discharged from acute care to hospice care between January 1, 2010 and June 30, 2014. MEASURES: Our primary outcome of interest was receiving an outpatient prescription for antithrombotic therapy on discharge to hospice care. RESULTS: Among 1141 eligible patients, 77 (6.7%) patients received a prescription for antithrombotic therapy on discharge to hospice care, most frequently, aspirin (57.1%), enoxaparin (26.0%), and warfarin (20.8%). Patients actively treated for deep vein thromboembolism or pulmonary embolism, or with a history of atrial fibrillation or aortic/mitral valve replacement were significantly more likely to receive antithrombotic therapy. Patients with a history of cancer, cerebrovascular disease, or liver disease were significantly less likely to receive antithrombotic therapy (p < 0.05 for all). Among patients who received antithrombotic therapy, 22% were not receiving antithrombotic therapy before the index admission. Among patients previously receiving antithrombotic therapy, 55% continued on the same medication, of which 54.5% did not have any documented rationale for continuation. CONCLUSIONS: Prescriptions for antithrombotic therapy were infrequent and often lacked a documented rationale. Further research is needed on the safety and effectiveness of antithrombotic therapy in hospice care and what drives current medication decisions in the absence of these data.

The Prophylaxis of Venous Thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is the third most common cardiovascular condition, after myocardial infarction and stroke. Prophylactic measures in accordance with current guidelines can significantly reduce the risk of VTE and the associated morbidity and mortality. Until now, the German interdisciplinary, evidence- and consensus-based (S3) clinical practice guideline on VTE prophylaxis was based on a complete review of all pertinent literature available in MEDLINE up to January 2008. More recent publications and drug approvals have made a thorough revision necessary. METHODS: A systematic search was carried out in the MEDLINE and Embase databases for publications that appeared from 1 January 2008 to 7 August 2013. Updates of 5 national and international reference guidelines and 2 new Health Technology Assessment (HTA) reports were considered as well. A structured consensus-finding process was carried out with delegates from 27 scientific medical societies and from the Union of Medical Specialist Associations. RESULTS: 46 randomized controlled trials (RCTs) were included for critical appraisal. New findings led to re-evaluation of the value of compression stockings in combination with pharmacological prophylaxis (open recommendation), and suggest equal value of non-vitamin K antagonist oral anticoagulants (NOACs) and low molecular weight heparins (LMWH) or fondaparinux in elective hip and knee replacement (strong recommendation). For patients undergoing hip fracture surgery, we recommend LMWH or fondaparinux. CONCLUSION: Further research is needed to assess the value of NOACs for pharmacological prophylaxis in orthopedic/trauma patients undergoing surgical procedures other than the ones mentioned above, and into the benefit and harm of new devices available for mechanical prophylaxis. The stringent implementation of basic measures such as early mobilization, movement exercises, and patient instruction is a key point to prevent venous thrombo - embolism.

Increased risk of first-ever stroke in younger patients with atrial fibrillation not recommended for antithrombotic therapy by current guidelines: a population-based study in an East Asian cohort of 22 million people.

OBJECTIVE: To assess the risk of first-ever ischemic stroke in younger patients with atrial fibrillation (AF) who have none of the CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, previous stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category [female sex]) risk factors (excluding female sex) by using the National Health Insurance research database in Taiwan. PATIENTS AND METHODS: From 22,842,778 insured people, we identified 24,612 hospitalized patients with newly diagnosed AF between January 1, 2002, and December 31, 2004, as the AF group and randomly selected 98,448 age- and sex-matched persons without AF as the non-AF group. Both groups were followed up until December 31, 2010, to estimate ischemic stroke incidences in relation to other stroke risk factors. RESULTS: During a follow-up period of 89,468 person-years, the stroke rate was higher in patients with AF than in those without AF (5.79 per 100 person-years vs 2.25 per 100 person-years). The higher prevalence of CHA2DS2-VASc comorbidities (heart failure, hypertension, diabetes, coronary artery disease, and peripheral artery disease) in patients with AF further increased the stroke risk. In 790 patients with AF aged 30 to 55 years who had none of the CHA2DS2-VASc comorbidities at baseline and retained a "low risk," that is, those with a CHA2DS2-VASc score of 0 in men and 1 in women during follow-up, the stroke rate remained considerably higher than that in their non-AF counterparts (1.00 per 100 person-years vs 0.25 per 100 person-years), with a sex-adjusted hazard ratio of 4.09 (95% CI, 2.97-5.62). CONCLUSION: This study finds an increased risk of stroke in younger patients with AF who are not recommended for prevention of thromboembolism by current guidelines. Better stroke risk stratification tools are needed to prioritize younger patients with AF for thromboprophylactic therapy in this population.

Periprocedural management of antithrombotic therapy in hospitalized patients.

The management of antithrombotic medications in patients requiring invasive procedures is a common problem in hospital medicine, for which there is limited evidence to guide clinical decision making. Existing guidelines do not address many hospital-based procedures and have not kept pace with the introduction of newer antiplatelet and anticoagulant medications. This article provides a conceptual framework for the periprocedural management of antithrombotic therapy, with a focus on the procedures that hospitalists are most likely to perform and the pharmacology of the common and newer antithrombotic medications.

Biological standards for potency assignment to fibrinolytic agents used in thrombolytic therapy.

Thrombolytic drugs are used for the treatment of thrombotic disorders such as acute myocardial infarction, acute ischemic stroke, and pulmonary embolism. Biological standards are used for potency assignment to the range of fibrinolytic proteins used in thrombolytic therapy. The World Health Organization (WHO) International Standards are primary reference materials, calibrated in arbitrary units (international unit), assigned by collaborative study using the range of assay methods available at the time. Provided the standard and test material are equivalent, adhering to the principle of measuring like versus like, the exact nature of the assay method is unimportant. This approach has been applied successfully for several decades since the advent of fibrinolytic treatment, ensuring consistency for potency labeling and the correct dosing of patients. The emergence of generic biosimilar products and new recombinant variants poses a challenge to this system, where functional differences impact on the relative biological activity in different assay systems. A more demanding system of standardization may therefore be required on the basis of international reference materials with associated reference methods. WHO recognizes this, and where possible and practical is seeking to incorporate concepts of traceability, uncertainty, and commutability to International Standards. However, some caution is needed because limitations on the characterization of many complex biologicals remain real, and a flexible approach is required on the basis of real-world needs.

Safety of protocol violations in acute stroke tPA administration.

BACKGROUND: Intravenous (IV) tissue plasminogen activator remains the only approved therapy for acute ischemic stroke (AIS) in the United States; however, less than 10% of patients receive treatment. This is partially because of the large number of contraindications, narrow treatment window, and physician reluctance to deviate from these criteria. METHODS: We retrospectively analyzed consecutive patients who received IV thrombolysis at our stroke center for National Institute of Neurological Disorders and Stroke (NINDS) protocol violations and rates of symptomatic intracerebral hemorrhage (sICH). Other outcome variables included systemic hemorrhage, modified Rankin Scale at discharge, and discharge disposition. RESULTS: A total of 212 patients were identified in our stroke registry between 2009 and 2011 and included in the analysis. Protocol violations occurred in 76 patients (36%). The most common violations were thrombolysis beyond 3 hours (26%), aggressive blood pressure management (15%), elevated prothrombin time (PT) or partial thromboplastin time (PTT) (6.6%), minor or resolving deficits (4.2%), unclear time of onset (3.9%), and stroke within 3 months (3%). There were no significant differences in any of the safety outcomes or discharge disposition between patients with or without protocol violations. Controlling for age, National Institutes of Health Stroke Scale on admission, and glucose on admission, there was no significant increase in sICH (odds ratio: 3.8; 95% confidence interval: .37-38.72) in the patients who had protocol violations. CONCLUSIONS: Despite more than one third of patients receiving thrombolysis with protocol violations, overall rates of hemorrhage remained low and did not differ from those who did not have violations. Our data support the need to expand access to thrombolysis in AIS patients.

Catheter-based treatment of ilio-femoral deep vein thrombosis - an update on current evidence.

Ilio-femoral deep vein thrombosis (DVT) has a high rate of long-term morbidity in the form of the postthrombotic syndrome (PTS). Therefore, management of acute thrombosis should not only focus on the prevention of acute complications such as propagation or embolisation of the initial clot but also on preventing PTS and recurrent thrombosis. Contemporary catheter-based treatments of deep vein thrombosis have proven to be safe and effective in selected patients. Current guidelines recommend medical therapy with anticoagulation alone for all but the most severe, limb-threatening thrombosis. They additionally allow for consideration of catheter-based treatment in patients with acute DVT and low risk of bleeding complications to prevent PTS. Recent studies favoring interventional therapy have not been included in these guidelines. Data on long-term outcome is expected to be published soon, clarifying and very likely strengthening the role of catheter-based treatments in the management of acute ilio-femoral DVT.