Adapted D-dimer thresholds safe and efficient for ruling out acute pulmonary embolism, even in high-risk patients

1. Diagnostic strategies with adapted D-dimer thresholds safe and efficient for ruling out acute pulmonary embolism, even in high-risk patients
Abstract: https://www.acpjournals.org/doi/10.7326/M21-2625
Editorial: https://www.acpjournals.org/doi/10.7326/M21-4295
URL goes live when the embargo lifts
An international systematic review and individual-patient data meta-analysis (IPDMA) from over 20,000 patients with suspected pulmonary embolism (PE) shows that diagnostic strategies for ruling out PE applying adapted D-dimer thresholds (to age of clinical pre-test probability) are safe and efficient for widespread practice, even in specific patient subgroups with a high PE risk, thereby reducing the need for imaging tests. Since the benefit of these diagnostic strategies is foremost dependent on their correct application, the authors propose standardizing one strategy in each individual hospital, rather than choosing a particular strategy based on the characteristics of individual patients. From an efficiency perspective, the authors support the application of strategies with adapted D-dimer thresholds. These findings are published in Annals of Internal Medicine.

Currently recommended diagnostic strategies for suspected acute PE consist of a standardized assessment of the clinical pre-test probability using a validated clinical decision rule, such as the Wells rule, revised Geneva score or the YEARS algorithm, combined with D-dimer testing. The combination of a non-high clinical probability and a normal D-dimer test safely rules out acute PE, without imaging. With the recent introduction and validation of D-dimer thresholds dependent on age or clinical pre-test probability, the proportion of patients requiring an imaging test has decreased significantly. While the overall safety and efficiency of these strategies have been demonstrated in large management studies, there are concerns that these strategies may be less safe and efficient in specific patient subgroups, such as patients with cancer, patients with a history of venous thromboembolism (VTE) and elderly patients or inpatients.

Researchers from this large international collaboration project studied individual patient data of 20,553 patients with suspected PE from 16 studies, to evaluate the safety and efficiency of the Wells and revised Geneva scores combined with fixed and adapted D-dimer thresholds, as well as the YEARS algorithm, for ruling out acute PE across subgroups of high-risk patients. They found that both efficiency and predicted failure rates were generally highest for strategies with adapted D-dimer thresholds. Specifically, the considerable increase in efficiency with the use of adapted D-dimer thresholds was highest in the patient subgroups, where efficiency could be increased with up to 3-fold, yet this was accompanied by predicted failure rates between 2-4%. According to the authors, a higher failure rate is to be expected in groups with a higher PE risk, according to the theorem of Bayes and the presence of differential verification bias (in particular for classifying fatal events and subsegmental PE cases) likely overestimated the predicted failure rates of strategies with adapted D-dimer thresholds in their IPDMA. They conclude that all studied strategies for ruling out PE in this IPDMA might be considered safe across the predefined patient subgroups, with highest efficiency but also highest predicted failure rate for strategies with adapted D-dimer thresholds. From an efficiency perspective, the authors support the application and standardization of strategies with adapted D-dimer thresholds.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with the corresponding author, Frederikus A. Klok, MD, PhD, please email f.a.klok@lumc.nl.
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2. Physicians debate treatment for hospitalized patients with community-acquired pneumonia in latest Beyond the Guidelines discussion
‘Beyond the Guidelines’ features are based on the Department of Medicine Grand Rounds at Beth Israel Deaconess Medical Center
Abstract: https://www.acpjournals.org/doi/10.7326/M21-3650
URL goes live when the embargo lifts
In a new Annals ‘Beyond the Guidelines’ feature, a general internist and critical care physician discuss treating a patient hospitalized with community-acquired pneumonia (CAP), specifically disease severity stratification methods, whether to use adjunctive corticosteroids, and when to prescribe empirical treatment for multidrug-resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. All ‘Beyond the Guidelines’ features are based on the Department of Medicine Grand Rounds at Beth Israel Deaconess Medical Center (BIDMC) in Boston and include print, video, and educational components published in Annals of Internal Medicine.

1.5 million Americans are hospitalized every year for CAP. Of those patients, 200,000 die within 30 days of hospitalization. Several guidelines exist to guide clinicians in the diagnosis and management of these patients, most notably the 2019 guidelines from the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA).

BIDMC Grand Rounds discussants, Joshua P. Metlay, MD, PhD, a general internist and co-chair of the committee that wrote the 2019 ATS/IDSA guideline, and Ari Moskowitz, MD, a pulmonary and critical care physician, debate the management and treatment of a 75-year-old man with restrictive lung disease who is hospitalized with CAP.

In their discussion, Drs. Metlay and Moskowitz disagree about the usefulness of the IDSA/ATS severity criteria in the patient’s case. Dr. Metlay argues that the criteria are helpful markers of illness and uses them to classify the patient’s condition as non-severe. Dr. Moskowitz argues that the criteria’s binary nature and similar weighting of heterogeneous components are significant flaws; as such, he does not rely on them in classifying the patient’s condition as severe. The discussants disagree about the use of corticosteroids as an appropriate treatment for the patient’s condition. Drs. Metlay and Moskowitz also disagree on the decision of whether to treat the patient for MRSA and Pseudomonas aeruginosa. Dr. Metlay recommends cultures to identify the presence of these organisms without immediately beginning such treatment, while Dr. Moskowitz would immediately administer antibiotics for these organisms in light of the patient’s previous hospitalization and comorbid conditions.

A complete list of ‘Beyond the Guidelines’ topics is available at www.annals.org/grandrounds.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with corresponding author, Zahir Kanjee, MD, MPH, please contact zkanjee@bidmc.harvard.edu.
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Also new in this issue:
Smoking Cessation
Manish S. Patel, MD; Sheetal B. Patel, MD; Michael B. Steinberg, MD, MPH
In the Clinic
A new ‘In the Clinic’ practice guide published in Annals of Internal Medicine discusses the health consequences of smoking, prevention and treatment of smoking related diseases, and areas for practice improvement around smoking cessation.
Abstract: https://www.acpjournals.org/doi/10.7326/M21-2931