Should This Patient Be Screened for Pancreatic Cancer?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 173, No 11

Because pancreatic cancer is typically advanced at the time of diagnosis, it has a very low 5-year survival rate and may become the second leading cause of cancer death in the United States. A screening program to find early-stage pancreatic cancer is needed but has been challenging to develop because of the lack of an effective screening test. In 2019, the U.S. Preventive Services Task Force performed an evidence review and updated its guidance, confirming its 2004 “D” recommendation against routine screening for average-risk patients. Here, 2 experts review the updated guideline and recent evidence and discuss whether a patient with a family history of pancreatic cancer should undergo screening.

Comparative Effectiveness and Harms of Antibiotics for Outpatient Diverticulitis: Two Nationwide Cohort Studies: Annals of Internal Medicine: Vol 174, No 6

Background: Outpatient diverticulitis is commonly treated with either a combination of metronidazole and a fluoroquinolone (metronidazole-with-fluoroquinolone) or amoxicillin–clavulanate alone. The U.S. Food and Drug Administration advised that fluoroquinolones be reserved for conditions with no alternative treatment options. The comparative effectiveness of metronidazole-with-fluoroquinolone versus amoxicillin–clavulanate for diverticulitis is uncertain. Objective: To determine the effectiveness and harms of metronidazole-with-fluoroquinolone versus amoxicillin–clavulanate for outpatient diverticulitis. Design: Active-comparator, new-user, retrospective cohort studies. Setting: Nationwide population-based claims data on U.S. residents aged 18 to 64 years with private employer-sponsored insurance (2000 to 2018) or those aged 65 years or older with Medicare (2006 to 2015). Participants: Immunocompetent adults with diverticulitis in the outpatient setting. Intervention: Metronidazole-with-fluoroquinolone or amoxicillin–clavulanate. Measurements: 1-year risks for inpatient admission, urgent surgery, and Clostridioides difficile infection (CDI) and 3-year risk for elective surgery. Results: In MarketScan (IBM Watson Health), new users of metronidazole-with-fluoroquinolone (n = 106 361) and amoxicillin–clavulanate (n = 13 160) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [95% CI, −0.3 to 0.6]), 1-year urgent surgery risk (risk difference, 0.0 percentage points [CI, −0.1 to 0.1]), 3-year elective surgery risk (risk difference, 0.2 percentage points [CI, −0.3 to 0.7]), or 1-year CDI risk (risk difference, 0.0 percentage points [CI, −0.1 to 0.1]) between groups. In Medicare, new users of metronidazole-with-fluoroquinolone (n = 17 639) and amoxicillin–clavulanate (n = 2709) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [CI, −0.7 to 0.9]), 1-year urgent surgery risk (risk difference, −0.2 percentage points [CI, −0.6 to 0.1]), or 3-year elective surgery risk (risk difference, −0.3 percentage points [CI, −1.1 to 0.4]) between groups. The 1-year CDI risk was higher for metronidazole-with-fluoroquinolone than for amoxicillin–clavulanate (risk difference, 0.6 percentage points [CI, 0.2 to 1.0]). Limitation: Residual confounding is possible, and not all harms associated with these antibiotics, most notably drug-induced liver injury, could be assessed. Conclusion: Treating diverticulitis in the outpatient setting with amoxicillin–clavulanate may reduce the risk for fluoroquinolone-related harms without adversely affecting diverticulitis-specific outcomes. Primary Funding Source: National Institutes of Health.

Primary Care Physicians and Spending on Low-Value Care

Effectiveness and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients With Valvular Atrial Fibrillation: A Population-Based Cohort Study: Annals of Internal Medicine: Vol 174, No 7

Background: Direct oral anticoagulants (DOACs) are increasingly used in place of warfarin, but evidence about their effectiveness and safety in patients with valvular atrial fibrillation (AF) remains limited. Objective: To assess the effectiveness and safety of DOACs compared with warfarin in patients with valvular AF. Design: New-user retrospective propensity score–matched cohort study. Setting: U.S.-based commercial health care database from 1 January 2010 to 30 June 2019. Participants: Adults with valvular AF who were newly prescribed DOACs or warfarin. Measurements: The primary effectiveness outcome was a composite of ischemic stroke or systemic embolism. The primary safety outcome was a composite of intracranial or gastrointestinal bleeding. Results: Among a total of 56 336 patients with valvular AF matched on propensity score, use of DOACs (vs. warfarin) was associated with lower risk for ischemic stroke or systemic embolism (hazard ratio [HR], 0.64 [95% CI, 0.59 to 0.70]) and major bleeding events (HR, 0.67 [CI, 0.63 to 0.72]). The results for the effectiveness and safety outcomes remained consistent for apixaban (HRs, 0.54 [CI, 0.47 to 0.61] and 0.52 [CI, 0.47 to 0.57], respectively) and rivaroxaban (HRs, 0.74 [CI, 0.64 to 0.86] and 0.87 [CI, 0.79 to 0.96], respectively); with dabigatran, results were consistent for the major bleeding outcome (HR, 0.81 [CI, 0.68 to 0.97]) but not for effectiveness (HR, 1.03 [CI, 0.81 to 1.31]). Limitation: Relatively short follow-up; inability to ascertain disease severity. Conclusion: In this comparative effectiveness study using practice-based claims data, patients with valvular AF who were new users of DOACs had lower risks for ischemic stroke or systemic embolism and major bleeding than new users of warfarin. These data may be used to guide risk–benefit discussions regarding anticoagulant choices for patients with valvular AF. Primary Funding Source: None.

SARS-CoV-2: The Growing Case for Potential Transmission in a Building via Wastewater Plumbing Systems

Fighting Prejudice and Absorbing Refugees From Nazism: The National Committee for the Resettlement of Foreign Physicians, 1939–1945

In the 1930s and 1940s, the medical profession reacted with hostility and erected formidable barriers to refugee physicians from Nazi-dominated Europe who sought to practice medicine in the United States. Yet, refugee physicians ultimately succeeded, with 77% of them working as doctors by 1945 and 98.6% by 1947. Although physician skills are readily transferable, and the United States had a genuine need for doctors after World War II drew 55 000 physicians into the military, refugee physicians' success can be attributed to the courageous physician leaders who lobbied on their behalf and the creation of the National Committee for the Resettlement of Foreign Physicians—an organization that helped immigrant physicians pass licensing examinations, identify locations for employment, and overcome barriers to integration into American society.

Cases in Precision Medicine: Genetic Testing to Predict Future Risk for Disease in a Healthy Patient

Genetic testing is performed more routinely in clinical practice, and direct-to-consumer tests are widely available. It has obvious appeal as a preventive health measure. Clinicians and their healthy patients increasingly inquire about genetic testing as a tool for predicting diseases, such as cancer, heart disease, or dementia. Despite demonstrated utility for diagnosis in the setting of many diseases, genetic testing still has many limitations as a predictive tool for healthy persons. This article uses a hypothetical case to review key considerations for predictive genetic testing.

Burst Case Scenario: Why Shorter May Not Be Any Better When It Comes to Corticosteroids

Life After May 25

How to Quantify and Interpret Treatment Effects in Comparative Clinical Studies of COVID-19

Clinical trials of treatments for coronavirus disease 2019 (COVID-19) draw intense public attention. More than ever, valid, transparent, and intuitive summaries of the treatment effects, including efficacy and harm, are needed. In recently published and ongoing randomized comparative trials evaluating treatments for COVID-19, time to a positive outcome, such as recovery or improvement, has repeatedly been used as either the primary or key secondary end point. Because patients may die before recovery or improvement, data analysis of this end point faces a competing risk problem. Commonly used survival analysis techniques, such as the Kaplan–Meier method, often are not appropriate for such situations. Moreover, almost all trials have quantified treatment effects by using the hazard ratio, which is difficult to interpret for a positive event, especially in the presence of competing risks. Using 2 recent trials evaluating treatments (remdesivir and convalescent plasma) for COVID-19 as examples, a valid, well-established yet underused procedure is presented for estimating the cumulative recovery or improvement rate curve across the study period. Furthermore, an intuitive and clinically interpretable summary of treatment efficacy based on this curve is also proposed. Clinical investigators are encouraged to consider applying these methods for quantifying treatment effects in future studies of COVID-19.