1. Current guidelines may not provide adequate guidance for prescribing anticoagulation in patients with atrial fibrillation
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Current guidelines based on the CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes, stroke, and vascular disease) score threshold for anticoagulation may not provide adequate guidance for determining the benefits and risks of anticoagulation therapy in patients with atrial fibrillation. The findings are published in Annals of Internal Medicine.
Oral anticoagulation dramatically reduces risk for ischemic stroke in patients with atrial fibrillation but increases the risk for major hemorrhage. The decision to recommend anticoagulation to a patient with atrial fibrillation should be based on the expected net clinical benefit, or the difference between the reduction in ischemic stroke risk and increase in bleeding risk weighted by the severity of each of these outcomes. Current guidelines recommend using anticogulation in a patient with a CHA2DS2-VASc score of 2 or greater. However, because stroke rates in patients with nonvalvular atrial fibrillation who are not receiving anticoagulant therapy vary widely across published studies, the net clinical benefit may not be as clear as the guidelines suggest.
Researchers from the University of California, San Francisco used a computer model to determine the effect of variation in published atrial fibrilation stroke rates on the net clinical benefit of anticoagulation for more than 33,000 patients. They found that the net clinical benefit of warfarin anticoagulation varied close to 4-fold when variation in stroke rates published in different studies was accounted for. These finding suggest that current guidelines based on CHA2DS2-VASc score may need to be revised in favor of more accurate, individualized assessments of risk for both ischemic stroke and major bleeding. The authors say that until such time, guidelines should better reflect the uncertainty of the current approach in which a patient's CHA2DS2-VASc score is used as the primary basis for recommending anticoagulation therapy.
2. Patient with multiple cancers with common genetic origin successfully treated with pembrolizumab
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A single immunotherapeutic agent can successfully treat more than one type of cancer in the same patient when the cancer has a common genetic cause. A brief case report is published in Annals of Internal Medicine.
Patients with Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer) are at increased risk for several types of cancer, including colorectal, uterine, gastric, pancreatic, ovarian, and bile duct. Clinicians from Baylor College of Medicine's Dan L Duncan Comprehensive Cancer Center evaluated a 55-year-old woman with a family history of colon, uterine, and gastric cancer who presented with abdominal pain, fatigue, and weight loss. Evaluation revealed two types of cancer - localized colon cancer and a metastatic bile duct cancer - both of which were deficient in mismatch repair. Genetic testing confirmed a diagnosis of Lynch syndrome.
The clinicians discussed with the patient the options of standard chemotherapy, which usually provides only modest and short term benefit in advanced bile duct cancer, or checkpoint inhibitor therapy, which interferes with the ability of cancer to suppress the immune system's attack on cancer cells. The patient preferred the latter so she received pembrolizumab, a humanized antibody that blocks the programmed cell death 1 receptor on lymphocytes, intravenously every 3 weeks. The tumor's response to therapy was dramatic and progressive. Sixteen months after initiation of pembrolizumab therapy, colonoscopy and positron emission tomography-computed tomography showed complete regression of all previously documented sites of disease.
According to the authors, these findings suggest that checkpoint inhibition is an attractive and potentially effective treatment for cancers caused by Lynch syndrome.
Also in this issue:
Oversight of Patient-Centered Outcomes Research: Recommendations
From a Delphi Panel
Luke Gelinas, PhD; Joel S. Weissman, MD; Holly Fernandez Lynch, JD; Avni Gupta, BDS, MPH; Ronen Rozenblum, PhD; Emily A. Largent, JD, PhD, RN; and I. Glenn Cohen, JD; for the Delphi Working Group Participants*
Dying Healthy: Public Health Priorities for Fixed Population
George J. Annas, JD, MPH, and Sandro Galea, MD, DrPH
Ideas and Opinions