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Journal of Thrombosis and Haemostasis :... Jul 2017Advances in the management of patients with suspected pulmonary embolism (PE) have improved diagnostic accuracy and made management algorithms safer, easier to use, and... (Review)
Review
Advances in the management of patients with suspected pulmonary embolism (PE) have improved diagnostic accuracy and made management algorithms safer, easier to use, and well standardized. These diagnostic algorithms are mainly based on the assessment of clinical pretest probability, D-dimer measurement, and imaging tests-predominantly computed tomography pulmonary angiography. These diagnostic algorithms allow safe and cost-effective diagnosis for most patients with suspected PE. In this review, we summarize signs and symptoms of PE, current existing evidence for PE diagnosis, and focus on the challenge of diagnosing PE in special patient populations, such as pregnant women, or patients with a prior VTE. We also discuss novel imaging tests for PE diagnosis and highlight some of the additional challenges that might require adjustments to current diagnostic strategies, such as the reduced clinical suspicion threshold, resulting in a lower proportion of PE among suspected patients as well as the overdiagnosis of subsegmental PE.
Topics: Acute Disease; Algorithms; Computed Tomography Angiography; Cost-Benefit Analysis; Dyspnea; Female; Fibrin Fibrinogen Degradation Products; Hematology; Hemorrhage; Humans; Lung; Magnetic Resonance Angiography; Male; Pregnancy; Probability; Pulmonary Alveoli; Pulmonary Embolism; Radionuclide Imaging; Reproducibility of Results; Tomography, X-Ray Computed
PubMed: 28671347
DOI: 10.1111/jth.13694 -
Oncology Research and Treatment 2015
Topics: Congresses as Topic; Health Care Costs; Hematology; Humans; Medical Oncology
PubMed: 25676571
DOI: 10.1159/000369567 -
Health Technology Assessment... Sep 2015While it is accepted practice to remove extradural (EDH) and subdural haematomas (SDH) following traumatic brain injury, the role of surgery in parenchymal traumatic... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
While it is accepted practice to remove extradural (EDH) and subdural haematomas (SDH) following traumatic brain injury, the role of surgery in parenchymal traumatic intracerebral haemorrhage (TICH) is controversial. There is no evidence to support Early Surgery in this condition.
OBJECTIVES
There have been a number of trials investigating surgery for spontaneous intracerebral haemorrhage but none for TICH. This study aimed to establish whether or not a policy of Early Surgery for TICH improves outcome compared with a policy of Initial Conservative Treatment.
DESIGN
This was an international multicentre pragmatic parallel group trial. Patients were randomised via an independent telephone/web-based randomisation service.
SETTING
Neurosurgical units in 59 hospitals in 20 countries registered to take part in the study.
PARTICIPANTS
The study planned to recruit 840 adult patients. Patients had to be within 48 hours of head injury with no more than two intracerebral haematomas greater than 10 ml. They did not have a SDH or EDH that required evacuation or any severe comorbidity that would mean they could not achieve a favourable outcome if they made a complete recovery from their head injury.
INTERVENTIONS
Patients were randomised to Early Surgery within 12 hours or to Initial Conservative Treatment with delayed evacuation if it became clinically appropriate.
MAIN OUTCOME MEASURES
The Extended Glasgow Outcome Scale (GOSE) was measured at 6 months via a postal questionnaire. The primary outcome was the traditional dichotomised split into favourable outcome (good recovery or moderate disability) and unfavourable outcome (severe disability, vegetative, dead). Secondary outcomes included mortality and an ordinal assessment of Glasgow Outcome Scale and Rankin Scale.
RESULTS
Patient recruitment began in December 2009 but was halted by the funding body because of low UK recruitment in September 2012. In total, 170 patients were randomised from 31 centres in 13 countries: 83 to Early Surgery and 87 to Initial Conservative Treatment. Six-month outcomes were obtained for 99% of 168 eligible patients (82 Early Surgery and 85 Initial Conservative Treatment patients). Patients in the Early Surgery group were 10.5% more likely to have a favourable outcome (absolute benefit), but this difference did not quite reach statistical significance because of the reduced sample size. Fifty-two (63%) had a favourable outcome with Early Surgery, compared with 45 (53%) with Initial Conservative Treatment [odds ratio 0.65; 95% confidence interval (CI) 0.35 to 1.21; p = 0.17]. Mortality was significantly higher in the Initial Conservative Treatment group (33% vs. 15%; absolute difference 18.3%; 95% CI 5.7% to 30.9%; p = 0.006). The Rankin Scale and GOSE were significantly improved with Early Surgery using a trend analysis (p = 0.047 and p = 0.043 respectively).
CONCLUSIONS
This is the first ever trial of surgery for TICH and indicates that Early Surgery may be a valuable tool in the treatment of TICH, especially if the Glasgow Coma Score is between 9 and 12, as was also found in Surgical Trial In spontaneous intraCerebral Haemorrhage (STICH) and Surgical Trial In spontaneous lobar intraCerebral Haemorrhage (STICH II). Further research is clearly warranted.
TRIAL REGISTRATION
Current Controlled Trials ISRCTN 19321911.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 70. See the NIHR Journals Library website for further project information.
Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Cerebral Hemorrhage, Traumatic; Female; Hematoma; Humans; Male; Middle Aged; Patient Selection; Sample Size; Time-to-Treatment; Treatment Outcome; Young Adult
PubMed: 26346805
DOI: 10.3310/hta19700 -
Hematology. American Society of... Dec 2016Immune thrombocytopenia (ITP) is a rare, acquired autoimmune condition characterized by a low platelet count and an increased risk of bleeding. Although many children... (Review)
Review
Immune thrombocytopenia (ITP) is a rare, acquired autoimmune condition characterized by a low platelet count and an increased risk of bleeding. Although many children and adults with ITP will not need therapy beyond historic first-line treatments of observation, steroids, intravenous immunoglobulin (IVIG), and anti-D globulin, others will have an indication for second-line treatment. Selecting a second-line therapy depends on the reason for treatment, which can vary from bleeding to implications for health-related quality of life (HRQoL) to likelihood of remission and patient preference with regard to adverse effects, route of administration, and cost. Published studies of these treatments are limited by lack of comparative trials, in addition to inconsistent outcome measures, definitions, and efficacy endpoints. This article provides an up-to-date comparison of the second-line treatments, highlighting important outcome measures including bleeding, HRQoL, fatigue, and platelet counts, which influence treatment selection in a shared decision-making model.
Topics: Adult; Costs and Cost Analysis; Hemorrhage; Humans; Immunoglobulins, Intravenous; Purpura, Thrombocytopenic, Idiopathic; Quality of Life; Rho(D) Immune Globulin; Risk Factors
PubMed: 27913549
DOI: 10.1182/asheducation-2016.1.698 -
Journal of Thrombosis and Haemostasis :... Nov 2016Historically, the bleeding episodes in subjects with coagulation disorders were treated with substitution therapy, initially with whole blood and fresh frozen plasma,... (Review)
Review
Historically, the bleeding episodes in subjects with coagulation disorders were treated with substitution therapy, initially with whole blood and fresh frozen plasma, and more recently with specific factor concentrate. Currently, patients with hemophilia have the possibility of choosing different effective and safe treatments, including novel extended half-life and alternative hemostatic drugs. The availability of novel extended half-life products could probably overcome current prophylaxis limitations, particularly in hemophilia B patients, by reducing the frequency of injections, achieving a higher trough level, and improving the quality of life of the patients. In addition, subcutaneous administration of alternative therapeutics would simplify prophylaxis in patients with hemophilia A and B with and without inhibitors. Regarding von Willebrand disease, a recombinant von Willebrand factor was recently developed to control bleeding episodes in patients with this disease, in addition to available von Willebrand factor/factor VIII concentrates. The management of patients affected by rare bleeding disorders (RBDs) is still a challenge, owing to the limited number of specific products, which are mainly available only in countries with high resources. Some improvements have recently been achieved by the production of new recombinant factor (F) XIII A subunit-derived and FX plasma-derived products for the treatment of patients affected by FXIII and FX deficiency. In addition, the development of novel alternative therapeutics, such as anti-tissue factor pathway inhibitor, ALN-AT3, and ACE910, for patients with hemophilia might also have a role in the treatment of patients affected by RBDs.
Topics: Animals; Blood Coagulation; Drug Combinations; Factor VIII; Factor X; Factor X Deficiency; Factor XIII Deficiency; Hematologic Diseases; Hematology; Hemophilia A; Humans; Male; Mice; Recombinant Proteins; Treatment Outcome; von Willebrand Factor
PubMed: 27590165
DOI: 10.1111/jth.13491 -
Methodist DeBakey Cardiovascular Journal 2018Chronic venous insufficiency (CVI) is responsible for significant costs to society in the form of medical and surgical treatment and, importantly, unmeasurable lost work... (Review)
Review
Chronic venous insufficiency (CVI) is responsible for significant costs to society in the form of medical and surgical treatment and, importantly, unmeasurable lost work productivity due to pain and disability. Symptomatic chronic central vein obstruction, a cause of CVI, is potentially treatable using open surgical and endovascular techniques to restore vessel patency. Although upper extremity central vein obstruction often requires an open surgical procedure for durable relief, endovascular stents have proven remarkably useful for iliofemoral disease. Containment of healthcare resources requires accurate diagnosis, durable treatment modalities, and appropriate patient selection so that therapy is targeted to those individuals most likely to benefit. In this regard, identification of appropriate lesions should be based on intravascular ultrasound and 3-dimensional imaging studies. Treatment with dedicated venous stents offers the potential for long-term symptomatic improvement and increased work productivity when used in a well-defined, anatomically appropriate population with significant, symptomatic CVI.
Topics: Absenteeism; Chronic Disease; Cost of Illness; Efficiency; Health Care Costs; Humans; Lower Extremity; Prevalence; Sick Leave; Treatment Outcome; Veins; Venous Insufficiency; Work Capacity Evaluation
PubMed: 30410645
DOI: 10.14797/mdcj-14-3-166 -
Clinical Radiology Nov 2022To quantitatively evaluate blood-brain barrier (BBB) permeability in the perihaematomal region of spontaneous intracerebral haemorrhage (ICH) and investigate the...
AIM
To quantitatively evaluate blood-brain barrier (BBB) permeability in the perihaematomal region of spontaneous intracerebral haemorrhage (ICH) and investigate the association between the alterations in cerebral blood flow and BBB permeability around the haematoma.
MATERIALS AND METHODS
Spontaneous ICH patients underwent unenhanced computed tomography (CT) and CT perfusion (CTP) simultaneously. Haematoma volume was measured on CT. The values of cerebral haemodynamic parameters including cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and permeability-surface area product (PS) were measured in the perihaematomal region and the contralateral mirror region, and then relative values were calculated for statistical analysis. Linear regression was used to evaluate associations between BBB permeability and variables.
RESULTS
A total of 87 ICH patients were included in this study. The focally elevated BBB permeability was observed in the perihaematomal region in ICH patients. Linear regression showed that reduced rCBF (β = -0.379, p=0.001) and increased rCBV (β = 0.412, p=0.000) correlated independently with increased relative PS (rPS) value in deep ICH, while only increased rCBV (β = 0.423, p=0.071) correlated to increased rPS value in patients with lobar ICH.
CONCLUSIONS
BBB permeability is focally elevated in the region around the haematoma. Cerebral haemodynamic alterations are associated with increased BBB permeability. Cerebral hypoperfusion may aggravate BBB compromise, and a compensatory increase in CBV may lead to reperfusion injury on BBB.
Topics: Humans; Blood-Brain Barrier; Cerebral Hemorrhage; Cerebrovascular Circulation; Hematoma
PubMed: 35786315
DOI: 10.1016/j.crad.2022.05.028 -
Current Opinion in Hematology Nov 2022Hemorrhage is a major cause of preventable death in trauma and cancer. Trauma induced coagulopathy and cancer-associated endotheliopathy remain major therapeutic... (Review)
Review
PURPOSE OF REVIEW
Hemorrhage is a major cause of preventable death in trauma and cancer. Trauma induced coagulopathy and cancer-associated endotheliopathy remain major therapeutic challenges. Early, aggressive administration of blood-derived products with hypothesized increased clotting potency has been proposed. A series of early- and late-phase clinical trials testing the safety and/or efficacy of lyophilized plasma and new forms of platelet products in humans have provided light on the future of alternative blood component therapies. This review intends to contextualize and provide a critical review of the information provided by these trials.
RECENT FINDINGS
The beneficial effect of existing freeze-dried plasma products may not be as high as initially anticipated when tested in randomized, multicenter clinical trials. A next-generation freeze dried plasma product has shown safety in an early phase clinical trial and other freeze-dried plasma and spray-dried plasma with promising preclinical profiles are embarking in first-in-human trials. New platelet additive solutions and forms of cryopreservation or lyophilization of platelets with long-term shelf-life have demonstrated feasibility and logistical advantages.
SUMMARY
Recent trials have confirmed logistical advantages of modified plasma and platelet products in the treatment or prophylaxis of bleeding. However, their postulated increased potency profile remains unconfirmed.
Topics: Blood Coagulation Disorders; Blood Component Transfusion; Blood Platelets; Hemorrhage; Hemostatics; Humans; Multicenter Studies as Topic
PubMed: 35942861
DOI: 10.1097/MOH.0000000000000737 -
Current Hematologic Malignancy Reports Aug 2020The Choosing Wisely® initiative, led by the American Board of Internal Medicine Foundation in collaboration with national professional medical societies, aims to help... (Review)
Review
PURPOSE OF REVIEW
The Choosing Wisely® initiative, led by the American Board of Internal Medicine Foundation in collaboration with national professional medical societies, aims to help patients choose care that is essential, free from harm, and evidence-based. The American Society of Hematology has advocated practices specific to hematology for physicians and patients to examine carefully. Here, we summarize various barriers to adopting these practices, interventions used to improve adoption, and challenges in measuring the effectiveness of these interventions.
RECENT FINDINGS
The Choosing Wisely® campaign has become an international effort with more than 20 countries worldwide having embraced it. Such widespread interest indicates that the campaign initiated an important dialog between patients and physicians about overutilization of resources. Evidence showing the positive impact of interventions on adopting these practices is accumulating, but their effect on improving clinical outcomes is uncertain. Decreasing overuse of resources is a cultural change in perspective for practitioners and patients alike. We believe that healthcare delivery is transitioning from being volume-based to value-based. As we continue to support the Choosing Wisely® campaign, we need to implement strategies to document and measure the influence of our value-based recommendations on physician practices, patient care and attitudes, and healthcare costs.
Topics: Choice Behavior; Clinical Decision-Making; Cost-Benefit Analysis; Delivery of Health Care, Integrated; Evidence-Based Medicine; Health Care Costs; Health Promotion; Hematology; Humans; Medical Overuse; Patient Participation; Patient Safety; Practice Patterns, Physicians'; Risk Assessment; Risk Factors; Value-Based Health Insurance
PubMed: 32533390
DOI: 10.1007/s11899-020-00593-2 -
Science Immunology Feb 2021Opportunities to interrogate the immune responses in the injured tissue of living patients suffering from acute sterile injuries such as stroke and heart attack are...
Opportunities to interrogate the immune responses in the injured tissue of living patients suffering from acute sterile injuries such as stroke and heart attack are limited. We leveraged a clinical trial of minimally invasive neurosurgery for patients with intracerebral hemorrhage (ICH), a severely disabling subtype of stroke, to investigate the dynamics of inflammation at the site of brain injury over time. Longitudinal transcriptional profiling of CD14 monocytes/macrophages and neutrophils from hematomas of patients with ICH revealed that the myeloid response to ICH within the hematoma is distinct from that in the blood and occurs in stages conserved across the patient cohort. Initially, hematoma myeloid cells expressed a robust anabolic proinflammatory profile characterized by activation of hypoxia-inducible factors (HIFs) and expression of genes encoding immune factors and glycolysis. Subsequently, inflammatory gene expression decreased over time, whereas anti-inflammatory circuits were maintained and phagocytic and antioxidative pathways up-regulated. During this transition to immune resolution, glycolysis gene expression and levels of the potent proresolution lipid mediator prostaglandin E remained elevated in the hematoma, and unexpectedly, these elevations correlated with positive patient outcomes. Ex vivo activation of human macrophages by ICH-associated stimuli highlighted an important role for HIFs in production of both inflammatory and anti-inflammatory factors, including PGE, which, in turn, augmented VEGF production. Our findings define the time course of myeloid activation in the human brain after ICH, revealing a conserved progression of immune responses from proinflammatory to proresolution states in humans after brain injury and identifying transcriptional programs associated with neurological recovery.
Topics: Adult; Aged; Brain; Cells, Cultured; Cerebral Hemorrhage; Female; Healthy Volunteers; Hematoma; Humans; Longitudinal Studies; Macrophages; Male; Middle Aged; Neuroinflammatory Diseases; Neutrophils; Primary Cell Culture; RNA-Seq; Transcriptome
PubMed: 33891558
DOI: 10.1126/sciimmunol.abd6279