This article about hemorrhagic complications of anticoagulant and thrombolytic treatment is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based ...Clinical Practice Guidelines (8th Edition). Bleeding is the major complication of anticoagulant and fibrinolytic therapy. The criteria for defining the severity of bleeding vary considerably between studies, accounting in part for the variation in the rates of bleeding reported. The major determinants of vitamin K antagonist (VKA)-induced bleeding are the intensity of the anticoagulant effect, underlying patient characteristics, and the length of therapy. There is good evidence that VKA therapy, targeted international normalized ratio (INR) of 2.5 (range, 2.0-3.0), is associated with a lower risk of bleeding than therapy targeted at an INR > 3.0. The risk of bleeding associated with IV unfractionated heparin (UFH) in patients with acute venous thromboembolism is < 3% in recent trials. This bleeding risk may increase with increasing heparin dosages and age (> 70 years). Low-molecular-weight heparin (LMWH) is associated with less major bleeding compared with UFH in acute venous thromboembolism. Higher doses of UFH and LMWH are associated with important increases in major bleeding in ischemic stroke. In ST-segment elevation myocardial infarction, addition of LMWH, hirudin, or its derivatives to thrombolytic therapy is associated with a small increase in the risk of major bleeding, whereas treatment with fondaparinux or UFH is associated with a lower risk of bleeding. Thrombolytic therapy increases the risk of major bleeding 1.5-fold to threefold in patients with acute venous thromboembolism, ischemic stroke, or ST-elevation myocardial infarction.
In August 2022, these guidelines were reviewed by an expert work group convened by ASH. Review included limited searches for new evidence and discussion of the search results. Following this review, ...the ASH Committee on Quality agreed to continue monitoring the supporting evidence rather than revise or retire these guidelines at this time. Limited searches and expert review will be repeated annually going forward until these guidelines are revised or retired.
Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), occurs in ∼1 to 2 individuals per 1000 each year, corresponding to ∼300 000 to 600 000 events in the United States annually.
Objective: These evidence-based guidelines from the American Society of Hematology (ASH) intend to support patients, clinicians, and others in decisions about treatment of VTE.
Methods: ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and adult patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment.
Results: The panel agreed on 28 recommendations for the initial management of VTE, primary treatment, secondary prevention, and treatment of recurrent VTE events.
Conclusions: Strong recommendations include the use of thrombolytic therapy for patients with PE and hemodynamic compromise, use of an international normalized ratio (INR) range of 2.0 to 3.0 over a lower INR range for patients with VTE who use a vitamin K antagonist (VKA) for secondary prevention, and use of indefinite anticoagulation for patients with recurrent unprovoked VTE. Conditional recommendations include the preference for home treatment over hospital-based treatment for uncomplicated DVT and PE at low risk for complications and a preference for direct oral anticoagulants over VKA for primary treatment of VTE.
Objective To examine the evidence on the benefits and harms of screening for prostate cancer.Design Systematic review and meta-analysis of randomised controlled trials.Data sources Electronic ...databases including Medline, Embase, CENTRAL, abstract proceedings, and reference lists up to July 2010.Review methods Included studies were randomised controlled trials comparing screening by prostate specific antigen with or without digital rectal examination versus no screening. Data abstraction and assessment of methodological quality with the GRADE approach was assessed by two independent reviewers and verified by the primary investigator. Mantel-Haenszel and inverse variance estimates were calculated and pooled under a random effects model expressing data as relative risks and 95% confidence intervals.Results Six randomised controlled trials with a total of 387 286 participants that met inclusion criteria were analysed. Screening was associated with an increased probability of receiving a diagnosis of prostate cancer (relative risk 1.46, 95% confidence interval 1.21 to 1.77; P<0.001) and stage I prostate cancer (1.95, 1.22 to 3.13; P=0.005). There was no significant effect of screening on death from prostate cancer (0.88, 0.71 to 1.09; P=0.25) or overall mortality (0.99, 0.97 to 1.01; P=0.44). All trials had one or more substantial methodological limitations. None provided data on the effects of screening on participants’ quality of life. Little information was provided about potential harms associated with screening.Conclusions The existing evidence from randomised controlled trials does not support the routine use of screening for prostate cancer with prostate specific antigen with or without digital rectal examination.
This article about hemorrhagic complications of anticoagulant and thrombolytic treatment is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based ...Clinical Practice Guidelines (8th Edition). Bleeding is the major complication of anticoagulant and fibrinolytic therapy. The criteria for defining the severity of bleeding vary considerably between studies, accounting in part for the variation in the rates of bleeding reported. The major determinants of vitamin K antagonist (VKA)-induced bleeding are the intensity of the anticoagulant effect, underlying patient characteristics, and the length of therapy. There is good evidence that VKA therapy, targeted international normalized ratio (INR) of 2.5 (range, 2.0-3.0), is associated with a lower risk of bleeding than therapy targeted at an INR > 3.0.
The risk of bleeding associated with IV unfractionated heparin (UFH) in patients with acute venous thromboembolism is < 3% in recent trials. This bleeding risk may increase with increasing heparin dosages and age (> 70 years). Low-molecular-weight heparin (LMWH) is associated with less major bleeding compared with UFH in acute venous thromboembolism. Higher doses of UFH and LMWH are associated with important increases in major bleeding in ischemic stroke. In ST-segment elevation myocardial infarction, addition of LMWH, hirudin, or its derivatives to thrombolytic therapy is associated with a small increase in the risk of major bleeding, whereas treatment with fondaparinux or UFH is associated with a lower risk of bleeding.
Thrombolytic therapy increases the risk of major bleeding 1.5-fold to threefold in patients with acute venous thromboembolism, ischemic stroke, or ST-elevation myocardial infarction.
This chapter about hemorrhagic complications of anticoagulant treatment is part of the seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Bleeding is the ...major complication of anticoagulant therapy. The criteria for defining the severity of bleeding varies considerably between studies, accounting in part for the variation in the rates of bleeding reported. The major determinants of vitamin K antagonist-induced bleeding are the intensity of the anticoagulant effect, underlying patient characteristics, and the length of therapy. There is good evidence that vitamin K antagonist therapy, targeted international normalized ratio (INR) of 2.5 (range, 2.0 to 3.0), is associated with a lower risk of bleeding than therapy targeted at an INR > 3.0. The risk of bleeding associated with IV unfractionated heparin (UFH) in patients with acute venous thromboembolism (VTE) is < 3% in recent trials. This bleeding risk may increase with increasing heparin dosages and age (> 70 years). Low molecular weight heparin (LMWH) is associated with less major bleeding compared with UFH in acute VTE. UFH and LMWH are not associated with an increase in major bleeding in ischemic coronary syndromes, but are associated with an increase in major bleeding in ischemic stroke. Information on bleeding associated with the newer generation of antithrombotic agents has begun to emerge. In terms of treatment decision making for anticoagulant therapy, bleeding risk cannot be considered alone, ie, the potential decrease in thromboembolism must be balanced against the potential increased bleeding risk.
This chapter about hemorrhagic complications of anticoagulant treatment is part of the seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Bleeding is the ...major complication of anticoagulant therapy. The criteria for defining the severity of bleeding varies considerably between studies, accounting in part for the variation in the rates of bleeding reported. The major determinants of vitamin K antagonist-induced bleeding are the intensity of the anticoagulant effect, underlying patient characteristics, and the length of therapy. There is good evidence that vitamin K antagonist therapy, targeted international normalized ratio (INR) of 2.5 (range, 2.0 to 3.0), is associated with a lower risk of bleeding than therapy targeted at an INR > 3.0. The risk of bleeding associated with IV unfractionated heparin (UFH) in patients with acute venous thromboembolism (VTE) is < 3% in recent trials. This bleeding risk may increase with increasing heparin dosages and age (> 70 years). Low molecular weight heparin (LMWH) is associated with less major bleeding compared with UFH in acute VTE. UFH and LMWH are not associated with an increase in major bleeding in ischemic coronary syndromes, but are associated with an increase in major bleeding in ischemic stroke. Information on bleeding associated with the newer generation of antithrombotic agents has begun to emerge. In terms of treatment decision making for anticoagulant therapy, bleeding risk cannot be considered alone, ie, the potential decrease in thromboembolism must be balanced against the potential increased bleeding risk.
Abstract Background Osteoporotic fractures are associated with high morbidity, mortality, and cost. Methods We performed a post hoc analysis of the Women’s Health Initiative (WHI) clinical trials ...(CT) data to assess osteoporosis treatment and identify participant characteristics associated with utilization of osteoporosis medication(s) after new diagnoses of osteoporosis and/or fracture. Information from visits prior to and immediately subsequent to the first fracture event or osteoporosis diagnosis were evaluated for medication use. A full logistic regression model was used to identify factors predictive of osteoporosis medication use after a fracture and/or a diagnosis of osteoporosis. Results The median length of follow-up from enrollment to the last WHI clinic visit for the study cohort was 13.9 years. Among the 13,990 women who reported new diagnoses of osteoporosis and/or fracture between enrollment and their final WHI visit, and also had medication data available, 21.6% reported taking an osteoporosis medication other than estrogen. Higher daily calcium intake, diagnosis of osteoporosis alone or both osteoporosis and fracture (compared to diagnosis of fracture alone), Asian or Pacific Islander race/ethnicity (compared to white/Caucasian), higher income, and hormone therapy use (past or present) were associated with significantly higher likelihood of osteoporosis pharmacotherapy. Women with black/African-American race/ethnicity (compared to white/Caucasian), BMI > 30 (compared to BMI of 18.5-24.9), current tobacco use (compared to past use or lifetime nonusers), and history of arthritis were less likely to use osteoporosis treatment. Conclusion Despite well-established treatment guidelines in postmenopausal women with osteoporosis and/or history of fractures, pharmacotherapy use was suboptimal in this study. Initiation of osteoporosis treatment after fragility fracture may represent an opportunity to improve later outcomes in these high-risk women. Specific attention needs to be paid to increasing treatment among women with fragility fractures, obesity, current tobacco use, history of arthritis or of black race/ethnicity.
Background
End-of-life decisions are frequently made by patients’ surrogates. Race and ethnicity may affect such decision making. Few studies have described how different racial/ethnic groups ...experience end-of-life surrogate decision making.
Objectives
To describe the self-reported experience the self-reported experience of African-American, Caucasian, and Hispanic surrogate decision makers of seriously ill patients and to examine the relationship of race, ethnicity, and culture to that experience.
Design
Purposive sample to include racial/ethnic minorities in a qualitative study using focus group interviews.
Participants
The participants of the study were 44 experienced, mostly female, surrogate decision makers for older veterans.
Approach
Transcripts were qualitatively analyzed to identify major themes, with particular attention to themes that might be unique to each of the three groups.
Results
The experience of burden of end-of-life decision making was similar in all three groups. This burden in its medical, personal, and familial dimensions is compounded by uncertainty about prognosis and the patient’s preferences. Racial/ethnic variations of responses to this burden concerned the physician–family relationship, religion and faith, and past experiences with race/ethnicity concordant versus non-concordant physicians.
Conclusions
Regardless of race/ethnicity, surrogates for seriously ill patients appeared to experience increased significant, multidimensional burdens of decision making under conditions of uncertainty about a patient’s preferences. This aspect of the burden of surrogate decision making may not be fully appreciated by physicians. Physicians should identify and be especially attentive to strategies used by surrogates, which may vary by race/ethnicity, to reduce the uncertainty about a patient’s preferences and thus the burden of surrogate decision making to assist them in this difficult process.
Abstract Objective To describe self-reported decision-making styles and associated pathways through end-of-life (EOL) decision-making for African-American, Caucasian, and Hispanic seriously ill male ...Veterans, and to examine potential relationships of race/ethnicity on these styles. Methods Forty-four African American, White, and Hispanic male Veterans with advanced serious illnesses participated in 8 racially/ethnically homogenous focus groups. Transcripts were qualitatively analyzed to identify major themes, with particular attention to themes that might be unique to each of the racial/ethnic groups. Results Patients described two main decision-making styles, deciding for oneself and letting others decide, leading to five variants that we labeled Autonomists, Altruists, Authorizers, Absolute Trusters, and Avoiders. These variants, with exception of avoiders (not found among White patients), were found across all racial/ethnic groups. The variants suggested different ‘implementation strategies’, i.e., how clear patients made decisions and whether or not they then effectively communicated them. Conclusion These identified decision-making styles and variants generate strategies for clinicians to better address individualized advance care planning. Practice implications Physicians should elicit seriously ill patients’ decision-making styles and consider potential implementation strategies these styles may generate, thus tailoring individualized recommendations to assist patients in their advance care planning. Patient-centered EOL decision-making can ensure that patient preferences are upheld.
Clock gene dysregulation has been shown to underlie various sleep disorders and may lead to negative cardio-metabolic outcomes. However, the association between sleep apnea (SA) and core clock gene ...expression is unclear. We performed a cross-sectional analysis of 49 Veterans enrolled in a study of SA outcomes in veterans with chronic kidney disease, not selected for SA or sleep complaints. All participants underwent full polysomnography and next morning whole blood collection for clock gene expression. We defined SA as an apnea-hypopnea index ≥15 events/h; nocturnal hypoxemia(NH) was defined as ≥10% of total sleep time spent at <90% oxygen saturation. We used quantitative real-time PCR to compare the relative gene expression of clock genes between those with and without SA or NH. Clock genes studied were Bmal1, Ck1δ, Ck1ε, Clock, Cry1, Cry2, NPAS2, Per1, Per2, Per3, Rev-Erb-α, RORα, and Timeless. Our cohort was 90% male, mean age was 71 yr (SD 11), mean body mass index was 30 kg/m
(SD 5); 41% had SA, and 27% had NH. Compared with those without SA, Per3 expression was reduced by 35% in SA ( P = 0.027). Compared with those without NH, NPAS2, Per1, and Rev-Erb-α expression was reduced in NH (50.4%, P = 0.027; 28.7%, P = 0.014; 31%, P = 0.040, respectively). There was no statistical difference in expression of the remaining clock genes by SA or NH status. Our findings suggest that SA or related NH and clock gene expression may be interrelated. Future study of 24 h clock gene expression in SA is needed to establish the role of clock gene regulation on the pathway between SA and cardio-metabolic outcomes.
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