Supplementary Table 9, column 'Edoxaban', row 'eGFR category', '95 mL/min' (page 15). The cell should be coloured green instead of yellow. It should also read "60 mg"instead of "60 mg (use with caution in 'supranormal' renal function)."In the above-indicated cell, a footnote has also been added to state: "Edoxaban should be used in patients with high creatinine clearance only after a careful evaluation of the individual thromboembolic and bleeding risk."Supplementary Table 9, column 'Edoxaban', row 'Dose reduction in selected patients' (page 16). The cell should read "Edoxaban 60 mg reduced to 30 mg once daily if any of the following: creatinine clearance 15-50 mL/min, body weight <60 kg, concomitant use of dronedarone, erythromycin, ciclosporine or ketokonazole"instead of "Edoxaban 60 mg reduced to 30 mg once daily, and edoxaban 30 mg reduced to 15mg once daily, if any of the following: creatinine clearance of 30-50 mL/min, body weight <60 kg, concomitant us of verapamil or quinidine or dronedarone."

/pdf/2020-esc-guidelines-for-the-diagnosis-and-management-of-38dpic1xu8.pdf

2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS).

https://www.healthcare.uiowa.edu/familymedicine/fpinfo/Docs/Chest%20Rx%20VTE%20Feb%202016.pdf

Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report

America's health care system has become too complex and costly to continue business as usual. Best Care at Lower Cost explains that inefficiencies, an overwhelming amount of data, and other economic and quality barriers hinder progress in improving health and threaten the nation's economic stability and global competitiveness. According to this report, the knowledge and tools exist to put the health system on the right course to achieve continuous improvement and better quality care at a lower cost.The costs of the system's current inefficiency underscore the urgent need for a systemwide transformation. About 30 percent of health spending in 2009--roughly $750 billion--was wasted on unnecessary services, excessive administrative costs, fraud, and other problems. Moreover, inefficiencies cause needless suffering. By one estimate, roughly 75,000 deaths might have been averted in 2005 if every state had delivered care at the quality level of the best performing state. This report states that the way health care providers currently train, practice, and learn new information cannot keep pace with the flood of research discoveries and technological advances.About 75 million Americans have more than one chronic condition, requiring coordination among multiple specialists and therapies, which can increase the potential for miscommunication, misdiagnosis, potentially conflicting interventions, and dangerous drug interactions. Best Care at Lower Cost emphasizes that a better use of data is a critical element of a continuously improving health system, such as mobile technologies and electronic health records that offer significant potential to capture and share health data better. In order for this to occur, the National Coordinator for Health Information Technology, IT developers, and standard-setting organizations should ensure that these systems are robust and interoperable. Clinicians and care organizations should fully adopt these technologies, and patients should be encouraged to use tools, such as personal health information portals, to actively engage in their care.This book is a call to action that will guide health care providers; administrators; caregivers; policy makers; health professionals; federal, state, and local government agencies; private and public health organizations; and educational institutions.

Best Care at Lower Cost: The Path to Continuously Learning Health Care in America

There is increasing concern that most current published research findings are false. The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientific field. In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance. Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true. Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias. In this essay, I discuss the implications of these problems for the conduct and interpretation of research.

Why most published research findings are false

Importance Prostate cancer is the most common cancer diagnosis made in men with more than 160 000 new cases each year in the United States. Although it often has an indolent course, prostate cancer remains the third-leading cause of cancer death in men. Observations When prostate cancer is suspected, tissue biopsy remains the standard of care for diagnosis. However, the identification and characterization of the disease have become increasingly precise through improved risk stratification and advances in magnetic resonance and functional imaging, as well as from the emergence of biomarkers. Multiple management options now exist for men diagnosed with prostate cancer. Active surveillance (the serial monitoring for disease progression with the intent to cure) appears to be safe and has become the preferred approach for men with less-aggressive prostate cancer, particularly those with a prostate-specific antigen level of less than 10 ng/mL and Gleason score 3 + 3 tumors. Surgery and radiation continue to be curative treatments for localized disease but have adverse effects such as urinary symptoms and sexual dysfunction that can negatively affect quality of life. For metastatic disease, chemotherapy as initial treatment now appears to extend survival compared with androgen deprivation therapy alone. New vaccines, hormonal therapeutics, and bone-targeting agents have demonstrated efficacy in men with metastatic prostate cancer resistant to traditional hormonal therapy. Conclusions and Relevance Advances in the diagnosis and treatment of prostate cancer have improved the ability to stratify patients by risk and allowed clinicians to recommend therapy based on cancer prognosis and patient preference. Initial treatment with chemotherapy can improve survival compared with androgen deprivation therapy. Abiraterone, enzalutamide, and other agents can improve outcomes in men with metastatic prostate cancer resistant to traditional hormonal therapy.

The Diagnosis and Treatment of Prostate Cancer: A Review.

Objective: To identify medical practices that offer no net benefits. Methods: We reviewed all original articles published in 10 years (2001-2010) in one high-impact journal. Articles were classified on the basis of whether they addressed a medical practice, whether they tested a new or existing therapy, and whether results were positive or negative. Articles were then classified as 1 of 4 types: replacement, when a new practice surpasses standard of care; back to the drawing board, when a new practice is no better than current practice; reaffirmation, when an existing practice is found to be better than a lesser standard; and reversal, when an existing practice is found to be no better than a lesser therapy. This study was conducted from August 1, 2011, through October 31, 2012. Results: We reviewed 2044 original articles, 1344 of which concerned a medical practice. Of these, 981 articles (73.0%) examined a new medical practice, whereas 363 (27.0%) tested an established practice. A total of 947 studies (70.5%) had positive findings, whereas 397 (29.5%) reached a negative conclusion. A total of 756 articles addressing a medical practice constituted replacement, 165 were back to the drawing board, 146 were medical reversals, 138 were reaffirmations, and 139 were inconclusive. Of the 363 articles testing standard of care, 146 (40.2%) reversed that practice, whereas 138 (38.0%) reaffirmed it. Conclusion: The reversal of established medical practice is common and occurs across all classes of medical practice. This investigation sheds light on low-value practices and patterns of medical research.

/pdf/a-decade-of-reversal-an-analysis-of-146-contradicted-medical-tsndagq1vf.pdf

A Decade of Reversal: An Analysis of 146 Contradicted Medical Practices

of the Clinical Problem Hypertension is a leading risk factor for mortality and disability. Recent estimates are that 874 million adults worldwide have an SBP of 140 mm Hg or higher.1,2 With its association with CVD, stroke (cerebrovascular accident [CVA]), heart failure, and chronic kidney disease (CKD), hypertension is second only to cigarette smoking as a preventable cause of death in the United States.3 Given demographic trends and the increasing prevalence of hypertension with increasing age (79% of men and 85% of women >75 years old have hypertension), the consequences of hypertension are expected to increase.1,2 Characteristics of the Guideline Source This guideline was developed by the ACC and the AHA in partnership with other professional societies. The ACC/AHA Task Force on Clinical Practice Guidelines selected a writing committee that was notable for its inclusion of people with a breadth of backgrounds, wide scope of practice, and freedom from conflicts of interest. This writing committee reviewed the relevant evidence and commissioned an independent evidence review committee to conduct formal systematic reviews regarding 4 questions of critical importance. The guideline document was reviewed by individuals representing the partner specialty societies and other content reviewers. The writing committee was aware of any conflicts of interest among reviewers (Table). Viewpoint page 2073 and Editorial page 2083

Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults

IDEALLY, GOOD MEDICAL PRACTICES ARE REPLACED BY BETter ones, based on robust comparative trials in which new interventions outperform older ones and establish new standards of care. Often, however, established standards must be abandoned not because a better replacement has been identified but simply because what was thought to be beneficial was not. In these cases, it becomes apparent that clinicians, encouraged by professional societies and guidelines, have been using medications, procedures, or preventive measures in vain. For example, percutaneous coronary intervention performed for stable coronary artery disease and hormone therapy prescribed for postmenopausal women cost billions of dollars and supported the existence of entire specialties for many years. Stable coronary artery disease accounted for 85% of all stenting in the United States at the time of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial. Large, well-designed randomized trials that tested whether these practices improved major patient outcomes revealed that patients were not being helped. Defenders of these therapies and interventions wrote rebuttals and editorials and fought for their specialties, but the reality was that the best that could be done was to abandon ship. How many established standards of medical care are wrong? It is not known. Medical practice has evolved out of centuries of theorizing, personal experiences, bits of evidence, expert consensus, and diverse conflicts and biases. Rigorous questioning of long-established practices is difficult. There are thousands of clinical trials, but most deal with trivialities or efforts to buttress the sales of specific products. Given this conundrum, it is possible that some entire medical subspecialties are based on little evidence. Their disappearance probably would not harm patients and might help salvage derailed health budgets. However, it is unlikely that specialists would support trials testing practices that constitute their main source of income. Instead, the research community performs studies of modest incremental value without even knowing whether the basic standards of care are appropriate. Rarely, some investigators find the courage to test established “truths” with large, rigorous randomized trials. When this happens, empirical evidence suggests that “medical reversals” may be quite common. In an evaluation of 35 trials that were published in a major clinical journal in 2009 and that tested an established clinical practice, 16 (46%) reported results consistent with current beneficial practice, 16 (46%) reported evidence that contradicted current practice and constituted a reversal, and another 3 (9%) were inconclusive. Perhaps high-profile general medical journals are more prone to publish unusual results and less inclined to defend a clinical practice or specialized turf than specialty journals. However, it is unlikely that the selection filter in favor of reversal publications is stronger than the selection filter favoring the validation of standard of care. The mere testing of a standard of care generates interest because many standards of care are never tested. In another evaluation of trials published in 3 major general medical journals or high–impact factor specialty journals, of the 39 mostcited randomized trials published in 1990-2003 that found a significant benefit of a clinical intervention, 9 (23%) found effects stronger than those found in subsequent studies and 19 (49%) found results replicated in subsequent studies, but 11 (28%) remained largely unchallenged, with no large trial conducted on the same question. Many medical reversals involve conditions for which the standard of care has been promoted over the years based primarily on pathophysiological considerations. Often one or more trials exist, but they have not tested clinically relevant outcomes or have been biased. For example, vertebroplasty—the injection of polymethylmethacrylate cement into fractured bone—gained popularity in the early 2000s for the treatment of osteoporotic fractures. Initial studies addressed the pathophysiology of this therapy, delineated the technical skills required to optimally perform the procedure, and furthered the discussion about the benefits of vertebroplasty. Claims of benefit were strongly contradicted in 2 randomized trials that included a sham pro-

Reversals of Established Medical Practices: Evidence to Abandon Ship

W e use the term reversal to signify the phenomenon of a new trial—superior to predecessors because of better design, increased power, or more appropriate controls—contradicting current clinical practice. In recent years, a number of such reversals have occurred. Use of hormone therapy, the class 1C antiarrhythmic agents, and the pulmonary artery catheter have decreased when trials demonstrated that they are either less effective than previously thought or harmful.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/1105961/ilt1010_1675_1676.pdf

Adam S. Cifu

Papers

A Decade of Reversal: An Analysis of 146 Contradicted Medical Practices

Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults

Reversals of Established Medical Practices: Evidence to Abandon Ship

The frequency of medical reversal.

Treatment of Osteoporosis