News Release 

Long-term use of rituximab associated with lower rates of AAV relapse

Embargoed news from Annals of Internal Medicine

American College of Physicians

Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing to the terms of the embargo not only on their own behalf, but also on behalf of the organization they represent.

1. Long-term use of rituximab associated with lower rates of AAV relapse



Patient Summary:

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An extra 18 months of rituximab infusions were associated with lower rates of relapse compared with standard maintenance therapy in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). These findings suggest that long-term rituximab use should be the standard of care. Findings from a randomized trial are published in Annals of Internal Medicine.

Prognosis of AAV, a life-threatening illness in which there is inflammation of the blood vessels in the body, has improved with treatment that includes glucocorticoids and rituximab to get the disease into remission. Patients are then given 4 infusions of rituximab over 18 months to maintain remission, but relapses of AAV are still common.

Researchers from Cochin Hospital, Paris, France randomly assigned 97 patients in 39 centers in France to receive infusions of either rituximab (n=50) or placebo (n=47) every 6 months over an 18 month period after they had already achieved complete remission and after a first phase of 18-month rituximab maintenance therapy in a previous trial. Participants were examined for disease activity and asked to report side effects. At month 28, the percentage of participants who experienced a relapse was lower in the rituximab group (4 percent) than in the placebo group (26 percent). Twelve participants in the rituximab group reported a serious side effect (including 6 who had serious infections) and 14 participants in the placebo group reported a serious side effect (including 4 who had serious infections). According to the researchers, these findings suggest that long-term use of rituximab is effective and probably safe and should be considered the standard of care for patients with AAV.

The author of an accompanying editorial from Cleveland Clinic recognizes that the authors make a convincing argument for long-term use of rituximab therapy, but raises the question of how long therapy should continue. Rituximab therapy was associated with some serious side effects for some patients. The author suggests that individual patient characteristics and risk factors should be considered when determining who would benefit from long-term therapy.

Media contacts: For an embargoed PDF please contact Lauren Evans at To speak with the lead author, Pierre Charles, MD, please contact

2. Prolonged exposure to heat may lead to metabolic alkalosis in patients with cystic fibrosis

Patient working long hours in the hot sun may have been right that his job "was killing him"


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In rare cases, prolonged exposure to heat may lead to metabolic alkalosis in patients with cystic fibrosis. A case report is published in Annals of Internal Medicine.

Chloride-deficient metabolic alkalosis usually has an obvious cause, but the situation can be more complicated in patients with cystic fibrosis. Researchers from Dartmouth Hitchcock Medical Center report the case of a 32-year-old man with known cystic fibrosis who complained of weakness, fatigue, and failure to thrive for several days. He worked long hours in the sun as a painter and felt that his job "was killing him." Laboratory tests showed severe metabolic alkalosis.

Most patients who develop chloride-deficient metabolic alkalosis lose chloride in their gastrointestinal tract or urine. Cystic fibrosis is an inherited disorder characterized by excessive chloride content in sweat. According to the researchers, this patient illustrates how sweat can be an important loss of electrolytes that can occasionally lead to chloride-deficient metabolic alkalosis in patients with cystic fibrosis. This patient also shows that otherwise normal persons can develop similar problems in extremely hot environments.

Media contacts: For an embargoed PDF please contact Lauren Evans at To speak with the lead author, Sudip Ghimire, MD, can be reached at

3. Physician practices face challenges adopting behavioral health integration



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While one in five adults has a clinically significant mental or substance use disorder, behavioral health integration into U.S. physician practices is still uncommon. Findings from a qualitative study published in Annals of Internal Medicine shed light on what physicians say are the barriers to adoption.

Stigma and behavioral health workforce shortages result in a substantial mismatch between the prevalence of mental health disorders and the proportion of persons who receive effective treatment. One potential solution is integrating behavioral health into medical care. As such, determining barriers to adoption is critical.

Researchers from Rand Corporation conducted semi-structured interviews with a diverse group of 47 physician practice leaders and clinicians, 20 experts, and five vendors at 30 physician practices to describe factors influencing physician practices' implementation of behavioral health integration. The yielded important insights about the motivations and barriers to integration. Practices were motivated to integrate behavioral health care to better meet the needs of their patients, as well as to enhance the reputation of their practice. Their approach to integration was tailored to their local resources, financial incentives, and patient populations. Barriers to integration included cultural differences and incomplete information flow between behavioral and nonbehavioral health clinicians and billing difficulties. Payment for service was an issue related to integration, as few saw a positive financial return on investment.

In an accompanying editorial, Sue Bornstein, MD of Texas Medical Home Initiative says that the value that primary care and cognitive services bring to the U.S. health care system is underappreciated. She suggests that fundamental changes must occur in payment and delivery systems in order for primary care to reach its full potential for achieving better health for persons and populations. The current pandemic has exposed the fragile state of primary care and underscores the need to strengthen the foundations of our system.

Media contacts: For an embargoed PDF please contact Lauren Evans at To speak with the lead author, Peggy G. Chen, MD, MS, can be reached through Warren Robak at 4. Supplement to Annals provides guidance on conducting research on issues related to the use of electronic health records

Intro Abstract:

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Over the past decade, Electronic Health Records (EHRs) have become ubiquitous in the United States, but their implementation with regard to care delivery, reporting, and research has not reached its full potential. A supplement published in Annals of Internal Medicine aims to guide those carrying out improvement and innovation efforts in the EHR era toward more robust approaches that will in turn provide more robust results. In addition, it aims to provide guidance as to how to describe findings in ways that are rigorous and understandable. And finally, the articles contained in the supplement should frame a more useful and actionable body of literature about how to implement change in the digital era.

Andrew Auerbach, MD, MPH from the University of California, San Francisco, and David W. Bates, MD, MSc from Brigham and Women's Hospital, solicited a group of papers that cover key issues in translating research into the digital era, focusing on cross-cutting issues in the new era. The papers answer questions such as, What are the factors that define high-quality research of this type? What should researchers be attentive to when designing, conducting, and reporting their work? What should clinicians, administrators, patients, and policymakers be looking for as they consider the application of the results of such research into their own endeavors? Content includes:

  • Getting Value From Electronic Health Records: Research Needed to Improve Practice

  • Designing, Conducting, and Reporting Clinical Decision Support Studies: Recommendations and Call to Action

  • Using Electronic Health Record Portals to Improve Patient Engagement: Research Priorities and Best Practices

  • Reporting and Implementation of Interventions Involving Machine Learning and Artificial Intelligence

  • Randomized Controlled Trials of Electronic Health Record Interventions: Design, Conduct, and Reporting Considerations

  • Context and Approach in Reporting Evaluations of Electronic Health Record-Based Implementation Projects

  • Recommendations for the Conduct and Reporting of Research Involving Flexible Electronic Health Record-Based Interventions

  • Research and Reporting Considerations for Observational Studies Using Electronic Health Record Data

  • Studying Workflow and Workarounds in Electronic Health Record-Supported Work to Improve Health System Performance

Media contacts: For an embargoed PDF please contact Lauren Evans at To speak with the lead author, Anand Vaidya, MD, MMSc, please contact Elaine St. Peter at


Also in this issue:

Transparent Reporting of Multivariable Prediction Models in Journal and Conference Abstracts: TRIPOD for Abstracts

Pauline Heus, MSc; Johannes B. Reitsma, MD, PhD; Gary S. Collins, PhD; Johanna A.A.G. Damen, PhD;

Rob J.P.M. Scholten, MD, PhD; Douglas G. Altman, DSc†; Karel G.M. Moons, PhD; and Lotty Hooft, PhD

Research and Reporting Methods


Should You Recommend Inhaled Corticosteroids for This Patient With Chronic Obstructive Pulmonary Disease? | Grand Rounds Discussion From Beth Israel Deaconess Medical Center

B. Burns, MD, MPH; Asha Anandaiah, MD; Mary Rice, MD, MPH; and Gerald Smetana, MD

Beyond the Guidelines


In The Clinic: Systemic Lupus Erythematosus Update

Marianthi Kiriakidou, MD; Cathy Lee Ching, MD

In the Clinic


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