Editors and Publishers

A Product of NEJM Group — Owned & Published by the
MASSACHUSETTS MEDICAL SOCIETY

NEJM Group Editor
Jeffrey M. Drazen, MD

Vice President for Publishing, NEJM Group
Christopher R. Lynch

Education Editor, NEJM Group
Ole-Petter Riksfjord Hamnvik, MB BCh BAO, MMSc

Founding Editor
Graham T. McMahon, MD, MMSc

Internal Medicine Board Review Editors

Deputy Reviewers
Allan S. Brett, MD
Patricia A. Kritek, MD, EdM
C. Christopher Smith, MD

Associate Reviewers
Daniel P. Hunt, MD
Stephen Joseph Huot, MD, PhD
Sylvia Cheney McKean, MD
Stuart B. Mushlin, MD
Daniel Randall, MD, MPH

Pediatrics Board Review Editors

Senior Reviewers
Deborah Lehman, MD
Shannon E. Scott-Vernaglia, MD

Family Medicine Board Review Editors

Senior Reviewer
Mark T. Nadeau, MD, MBA, FAAFP

Deputy Reviewer
Paul Gordon, MD

Associate Reviewers
Frank J. Domino, MD
Alan Ehrlich, MD
Caroline R. Richardson, MD

Pain Management and Opioids Editors

Senior Reviewer
Daniel P. Alford, MD, MPH

Section Editors

Additional Content Reviewers

Martha E. Billings, MD (Sleep Medicine)
Richa Chibbar, MD (Gastroenterology)
Jean M. Connors, MD (Hematology)
Kimberly W. Keefe, MD (Reproductive Endocrinology)
Tia Kostas, MD (Geriatrics)
Sarah Little, MD (Obstetrics)
Lachelle D. Weeks, MD, PhD (Hematology/Oncology)

Past Editors

Alexander M. Djuricich, MD (Education Editor, 2016)
Thomas M. Best, MD, PhD (Sports Medicine, 2014–2016)
John Betjemann, MD (Neurology, 2015–2016)
Vincent W. Chiang, MD (Pediatric Emergency Medicine, 2014–2020)
Joanne E. Cox, MD (Pediatrics, 2014)
Michael Furman Greene, MD (OB/GYN, 2013–2014)
Manu Hegde, MD, PhD (Neurology, 2016–2019)
James V. Hennessey, MD (Endocrinology, 2013–2016)
L. David Hillis, MD (Cardiology, 2013–2014)
Donald M. Hilty, MD (Psychiatry, 2013)
S. Andrew Josephson, MD (Neurology, 2013–2015)
Amel Karaa, MD (Pediatric Metabolic Diseases/Genetics, 2017–2019)
Richard A. Lange, MD, MBA (Cardiology, 2013–2014)
Paul A. Monach, MD (Rheumatology, 2013–2015)
Alan C. Moss, MD (Gastroenterology, 2015–2019)
Anju Nohria, MD (Cardiology, 2015)
Timothy T. Nostrant, MD (Gastroenterology, 2013–2015)
Judith S. Palfrey, MD (Pediatrics, 2014)
Arturo P. Saavedra, MD, PhD, MBA (Dermatology, 2013–2015)
Srinath Sanda, MD (Pediatric Endocrinology, 2017–2018)
Paul E. Sax, MD (Infectious Disease, 2013)
Bradford J. Shingleton, MD (Ophthalmology, 2013–2017)
Kaveh G. Shojania, MD (Patient Safety, 2014–2019)
Derrick J. Todd, MD, PhD (Rheumatology, 2015–2020)
Andrew A. Wagner, MD (Urology, 2016–2019)

Content Programs

NEJM Knowledge+ Publishers

Managing Director, NEJM Group Education and Applied Knowledge
Kathleen Charlton

General Manager, NEJM Group Education Programs
Michelle Haché

General Manager, Education Content & Product Development
Matthew O’Rourke

Managing Editor
Catherine Tomeo Ryan

Editorial Systems Manager
Josette Akresh-Gonzales

Production Coordinator
Kyle Simmons

NEJM Knowledge+ Product Manager
Melissa Elmore

Education Operations Manager
Leokadia Marchwinski

Production Operations Specialist
Karen O’Brien

Director, Sales and Business Development
David Robbins

Account Manager
Christopher Bracken

Marketing Manager, Undergraduate and Graduate Medical Education
Ellen McCullough

Customer Relationship Marketing Manager
Kristin Burati

Director, Accreditation and Recognition
Danna Muir, MBA

Massachusetts Medical Society Leadership

David A. Rosman, MD, MBA, President

Lois Dehls Cornell, Executive Vice President

Committee on Publications
Lynda M. Young, MD, Chair
James A. Feldman, MD, Vice Chair

Burt A. Adelman, MD
Edward W. Boyer, MD
Henry L. Dorkin, MD
Subramanyan Jaysankar, MD
Paul M. Ridker, MD
John B. Wong, MD
Beverly Woo, MD

Program Director Advisory Board

Advisory Board Members

Margaret Baumgarten, MD
Associate Professor, Ghent Family Medicine Residency Program
Director, Associated Chair for Graduate Medical Education, Family and Community Medicine Department

Michael Coppolino, MD
Associate Internal Medicine Program Director
Critical Care Medicine
Kaiser Permanente San Francisco

Joao Ferreira, MD
University of Arizona Health Sciences
Assistant Professor, Medicine (Clinical Scholar Track)
Associate Director, Internal Medicine Residency Program – Tucson Campus

Charles W. Graeber, MD
Adjunct Assistant Professor of Medicine
Mayo Clinic College of Medicine and Science
Professor of Internal Medicine
University of Central Florida, College of Medicine
Program Director
NCH Healthcare System Internal Medicine Residency
Affiliate of the Mayo Clinic School of Medicine and Science

Meredith Plant, MD
Assistant Professor of Pediatrics
Associate Program Director, USF Morsani College of Medicine

Sydney Primis, MD
Pediatric Residency Program Director
Vice Chair of Education, Department of Pediatrics
Levine Children’s Hospital, Atrium Health

Salvatore P. Sparich, Jr., DO
Program Director
Geisinger Kistler Family Medicine Residency

Amber L. Stephens, DO
Family Medicine Program Director
SOVAH Health

David Walsh, MD
Vanderbilt University Medical Center

Complete List of Contributors by Specialty

Conflict of Interest Disclosures

NEJM Knowledge+ Internal Medicine Board Review
NEJM Knowledge+ Pediatrics Board Review
NEJM Knowledge+ Family Medicine Board Review
NEJM Knowledge+ Pain Management and Opioids

Cardiology

Cleveland Clinic

Site Director
Benico Barzilai, MD

Contributors
Kia Afshar, MD
Justin M. Dunn, MD, MPH
Andrew L. Goodman, MD
James E. Lai, MD
Junyang Lou, MD, PhD
Michael D. McCulloch, MD
Parag R. Patel, MD
Marwa A. Sabe, MD
Todd Senn, MD
Brian Stegman, MD
Amanda Vest, MD

University of Texas Southwestern Medical Center

Site Director
Amit Khera, MD, MSc

Contributors
Anish B. Bhatt, MD
Sonia Garg, MD
Hurst M. Hall, MD
Elizabeth A. Hardin, MD
Houman Khalili, MD
David Lofthus, MD
Phuong-Khanh J. Nguyen-Trong, MD
Andre Paixao, MD
Vishal Patel, MD
Vijay Raja, MD
Christopher Regan, MD
Monika Sanghavi, MD
Jainy Savla, MD

Yale University School of Medicine

Site Director
Parul U. Gandhi, MD

Contributors
Eric J. Brandt, MD
Virginia K., Workman, MD
Cesia Gallegos, MD

Pulmonology

University of Colorado School of Medicine

Site Director
Mark W. Geraci, MD

Contributors
Walter D. Conwell, MD
Silpa Dhoma, MD
Gregory A. Hickey, MD
Christine M. Lin, MD
Derek Linderman, MD
Madison Macht, MD
Susan K. Mathai, MD
Michael Mohning, MD
Steven Pugliese, MD
Jeffrey C. Robinson, MD
Marvin I. Schwarz, MD
Alexandra Smart, MD
George M. Solomon, MD
Peter Sottile, MD
Amanda Stream, MD
Andrew Waas, MD

The Ohio State University Wexner Medical Center

Site Director
Jennifer W. McCallister, MD

Contributors
Avraham Z. Cooper, MD
Megan Conroy, MD
Ryan Story, MD
Stephen Doyle, DO

Infectious Disease

Emory University

Site Director
Wendy S. Armstrong, MD

Contributors
Sol Aldrete, MD
Valeria Cantos, MD
Emily J. Cartwright, MD
Jonathan Colsanti, MD, MSPH
Cecile Delille, MD, MSc
Jessica Fairley, MD
Mary Foote, MD, MPH
Rachel Friedman-Moraco, MD
Emily P. Hyle, MD
Jesse T. Jacob, MD
Sheetal Kandiah, MD, MPH
Colleen F. Kelley, MD, MPH
Colleen S. Kraft, MD, MSc
Aneesh K. Mehta, MD
Andre Melendez, MD
Caitlyn Moran, MD, MSc
Varun K. Phadke, MD
Paulina Rebolledo, MD, MSc
Marcos Schechter, MD
Jennifer O. Spicer, MD, MPH
Jay B. Varkey, MD
Brian R. Wood, MD

Gastroenterology

Massachusetts General Hospital

Site Directors
Andrew T. Chan, MD
Daniel S. Pratt, MD

Contributors
Nitin K. Gupta, MD
Lindsay Y. King, MD
Gauree Gupta Konijeti, MD, MPH
Jay Luther, MD
Joanna M. Peloquin, MD
Ying Wu, MD

Brigham and Women’s Hospital

Site Director
Molly Perencevich, MD

Contributors
Ahmad Najdat Bazarbashi, MD
Jennifer A. Inra, MD
Navin Kumar, MD
Andrew Storm, MD
Allison L. Yang, MD

Endocrinology

Brigham and Women’s Hospital

Site Director
Robert G. Dluhy, MD

Contributors
Tobin M. Abraham, MD
Adi Barlev-Ehrenberg, MD, MS
Anna L. Goldman, MD
Norra Kwong, MD
Eva S. Liu, MD
Chevon M. Rariy, MD
Amir Tirosh, MD, PhD

University of Chicago

Site Director
Meltem Zeytinoglu, MD

Contributors
Isabel Casimiro, MD, PhD
Laura T. Dickens, MD
Mizuho S. Mimoto, MD, PhD

University of Colorado School of Medicine

Site Director
Marc-Andre Cornier, MD

Contributor
David R. Saxon, MD

Rheumatology

Brigham and Women’s Hospital

Site Director
Simon M. Helfgott, MD

Contributors
Fadi Badlissi, MD
Medha Barbhaiya, MD
Mollie Nicole Carruthers, MD
Candace H. Feldman, MD, MPH
Julia Ford, MD
Lydia Gedmintas, MD, MPH
Sicong Huang, MD
Eli Miloslavsky, MD
Jennifer Meara Nashel, MD
Erin H. Penn, MD, MS
Monica P. Ramirez, MD, MPH
Deepak A. Rao, MD, PhD
Naina Rastalsky, MD
Jeffrey A. Sparks, MD

Hematology

Stanford University Medical Center

Site Director
Jason Robert Gotlib, MD

Contributors
Oyebimpe Adesina, MD
Anosheh Afghahi, MD
Caroline Berube, MD
Rondeep S. Brar, MD
Steven Chan, MD
Shira Dinner, MD
Magali Fontaine, MD, PhD
Wan-Jen Hong, MD
David J. Iberri, MD
Brian A. Jonas, MD, PhD
Michael Khodadoust, MD, PhD
David Kurtz, MD
Lawrence Leung, MD
Lauren Maeda, MD
Beth A. Martin, MD
Everett Meyer, MD
Siddhartha Mitra, MD, PhD
Rupa Narayan, MD
David Nguyen, MD
Mary-Elizabeth Muchmore Percival, MD
Elie Richa, MD
Gabriel Rivera, MD
Stanley Schrier, MD
Alexander Ungewickell, MD, PhD
James L. Zehnder, MD

Oncology

The University of Texas MD Anderson Cancer Center

Site Director
Ahmed Eid, MD, MEd

Contributors
Carlos H. Barcenas, MD, MSc
Isabella C. Glitza, MD, PhD
Marc S. Hoffmann, MD
Sylvia Jaramillo, MD
Meghan S. Karuturi, MD
Syed Mohamman Ali Kazmi, MD
John Linford, MD
Marc Matrana, MD
Van Morris, MD
Sarah Mougalian, MD
Krina Patel, MD
Kanwal P. Raghav, MD
Ishwaria Subbiah, MD
Nizar M. Tannir, MD
Jennifer Wang, MD
Jeff Yorio, MD
Alex Zarzour, MD

Nephrology/Urology

Mayo Clinic

Site Director
Suzanne M. Norby, MD

Contributors
Hatem Amer, MD
Bhavna Chopra, MD
Mireille El Ters, MD
Ziad M. El-Zoghby, MD
Sandra M. Herrmann, MD
Musab S. Hommos, MD
Kianoush B. Kashani, MD
Mira T. Keddis, MD
Angela K. Muriithi, MD
Carlos R. Franco Palacios, MD
Qi Qian, MD
Michael Selby, MD
Leslie Thomas, MD
Ladan Zand, MD

Neurology

Johns Hopkins University School of Medicine

Site Directors
Peter W. Kaplan, MD
Emily L. Johnson, MD

Contributors
Brin Freund, MD
Charlene E. Gamaldo, MD
Lindsey Hayes, MD, PhD
Dalila W. Lewis, MD
Rafael H. Llinás, MD
Thomas E. Lloyd, MD, PhD
Zoltan Mari, MD
Elisabeth B. Marsh, MD
Abhay R. Moghekar, MD
Payam Mohassel, MD
Suraj Rajan, MBBS, MSc
Aruna Rao, MD
Jack Ratchford, MD, MSc
Jason Rosenberg, MD

Psychiatry

McLean Hospital

Site Director
Felicia Anne Smith, MD

Contributors
Gaston Baslet, MD
Eugene Victor Beresin, MD
Christina Brezing, MD
Stephanie Cincotta, MD
Jennifer Gatchel, MD, PhD
Alex S. Keuroghlian, MD, MSc
Rachel Ross, MD, PhD
Kathy Sanders, MD
Theodore Allan Stern, MD
John Taylor, MD, MBA
Oriana Vesga Lopez, MD
Joji Suzuki, MD
Heather Vestal, MD, MHS
Ying Wang, MD
Lazaro Zayas Jr., MD

Dermatology

Hospital of the University of Pennsylvania

Site Director
Misha A. Rosenbach, MD

Contributors
Robert G. Micheletti, MD
Lisa K. Pappas-Taffer, MD
Evan W. Piette, MD
James R. Treat, MD
Kanade Shinkai, MD, PhD
Karolyn A. Wanat, MD

Allergy/Immunology

University of Wisconsin Hospital and Clinics

Site Director
James E. Gern, MD

Contributors
William Busse, MD
Daniel J. Jackson, MD
Sujani Kakumanu, MD
Robert F. Lemanske Jr., MD
Sameer K. Mathur, MD, PhD
Mark H. Moss, MD
Christine M. Seroogy, MD

Otolaryngology

Massachusetts Eye and Ear Infirmary

Site Director
Stacey Tutt Gray, MD

Contributors
Megan M. Abbott, MD, MPH
Dunia Abdul-Aziz, MD
Margaret S. Carter, MD
Gillian Diercks, MD
Rebecca J. Hammon, MD
Elliott Kozin, MD
Aaron Remenschneider, MD, MPH
Daniel Roberts, MD, PhD

OB/GYN

University of Maryland Medical Center

Site Director
May Hsieh Blanchard, MD

Contributors
Kiranpreet K. Chawla, MD
Katrina S. Mark, MD
Vadim M. Morozov, MD

University of Washington, Department of Family Medicine

Site Director
Amanda Kost, MD

Contributors
Jeanne Cawse-Lucas, MD
David V. Evans, MD
Emily M. Godfrey, MD, MPH
Misbah Keen, MD
Pamela Pentin, MD
Jaqueline Raetz, MD
Richard Waters, MD
Ying Zhang, MD

Ophthalmology

Wills Eye Institute

Site Directors
Brad H. Feldman, MD
Sagun Pendse, MD

Contributors
David R. Lally, MD
Jared D. Peterson, MD
David A. Salz, MD
Adiel G. Smith, MD

Pain Management and Opioids

Soraya Azari, MD
Erica J. Bial, MD, MS
Patrick K. Cronin, MD
Amy L. Fitzpatrick, MD
Peter D. Friedmann, MD, MPH
Douglas L. Gourlay, MD, MSc
Ellie Grossman, MD, MPH
Scott E. Hadland, MD, MPH, MS
David B. Hathaway, MD
Jeoffrey Hill, MD
Janet J. Ho, MD, MPH
Mohammed A. Issa, MD
Amy J. Kennedy, MD
Stacy E. Melanson, MD, PhD
Karen A. O’Brien, MD
Christine Pace, MD
Daniel K. Partain, MD
Michael D. Perloff, MD, PhD
Cara Poland, MD, MEd
Shari S. Rogal, MD, MPH
Serena L. Roth, MD
Payel J. Roy, MD
Seddon R. Savage, MD, MS
Christine S. Soran, MD, MPH
Scott Steiger, MD
Jacob J. Strand, MD
Joji Suzuki, MD
David Tian, MD, MPP
Donald N.S. Unger, MFA, PhD
Lauren VanDam, MD
Sarah E. Wakeman, MD
Melissa B. Weimer, DO, MCR
Zoe M. Weinstein, MD, MS

Sports Medicine

University of Arizona, Department of Family and Community Medicine

Site Director
Holly Good McNulty, MD

Contributors
Sagir G. Bera, DO, MPH, MS
Allison Lane, MD
Daphne A. Scott, MD
Krista A. Sunderman, MD
Matthew A. Tennison, MD
Brett Toresdahl, MD
Anna Waterbrook, MD

Research/Statistics

Contributors
Krista M. Nottage, MBBS
Ken Wu, MBBS
Ahmad Zaheen, MD, MSc

Patient Safety

Site Director
James Song-Jeng Yeh, MD (Brigham and Women’s Hospital)

Contributors
Kate E. Humphrey, MD (Boston Children’s Hospital)
Jeffrey Bruckel, MD (Massachusetts General Hospital)
Julie Fu, MD, MA (Boston Medical Center)
Kiran Gupta, MD (Brigham and Women’s Hospital)
Michelle P. Lin, MD, MPH (Brigham and Women’s Hospital)
Sonali Saluja, MD (Cambridge Health Alliance)

General Medicine

Indiana University School of Medicine

Site Director
Curtis A. Wright, MD

Contributors
James M. Hotz, MD
Archana M. Mahankali, MD
Joshua D. Pinner, MD
Allyson Thomas, MD

Pediatrics

Children’s Hospital Colorado

Site Director
Scott R. Auerbach, MD

Contributors
Daniel E. Ehrmann, MD, MS
Dana Irrer, MD
Amanda McIntosh, MD
Melissa Wehrmann, MD

Children’s Hospital at Montefiore

Site Director
Mary Spiciarich, MD

Contributors
Cristina Fernandez-Carbonell, MD
Daniel Noam Lax, MD
Bridget A. Leone, MD
Isaac A. Molinero, MD
Mohamad Saifeddine, MD

Children’s Hospital of Philadelphia

Site Directors
Jeanine C. Ronan, MD
Rebecca Tenney-Soeiro, MD

Contributors
Adelaide E. Barnes, MD
Maya Lynn Dewan, MD, MPH
Caitlin W. Elgarten, MD
Nina A. Fainberg, MD
Rebecca D. Ganetzky, MD
Dylan Graetz, MD, MPH
Nicole Hames, MD
Joelle B. Karlik, MD
Chén C. Kenyon, MD, MSHP
Marissa J. Kilberg, MD
Emilie R. Korn, MD
Pamela Mazzeo, MD
Christina McClam, MD
Susan E. McClory, MD, PhD
Erika J. Mejia, MD
Elana B. Mitchel, MD
Evan William Orenstein, MD
Erin Pete Devon, MD
Stacey R. Rose, MD
Jennifer Salant, MD
Eloise Salmon, MD
Margarita Sergonis, MD
Levon H. Utidjian, MD
Nicole R. Washington, MD
Anna K. Weiss, MD, MSc

Cincinnati Children’s Hospital Medical Center

Site Director
Jennifer Lynn Huggins, MD

Contributors
Khalid Abulaban, MD
Armand Antommaria, MD, PhD
Stefanie Woolridge Benoit, MD
Kate E. Berz, DO
Michal Feldon, MD
Barbara E. Hallinan, MD, PhD
Sophia Hufnagel, MD
Melissa Jimenez, MD
Jordan Jones, DO
Oriaku A. Kas-Osoka, MD
Kelsey Logan, MD, MPH
Ernest Pedapati, MD
Kirsten Simonton, MD
Rachel M. Thienprayoon, MD
Denise Warrick, MD

Hasbro Children’s Hospital

Site Directors
Lauren Allister, MD
Michael Herzlinger, MD
Lisa Swartz Topor, MD, MMSc

Contributors
Dyadin Esharif, MD
Meghan E. Fredette, MD
Natasha Gill, MD
Juanita K. Hodax, MD
Julie Leviter, MD
Laura Mercurio, MD
Muhammad Safwan Riaz, MD
Sakina H. Sojar, MD
Hoi See Tsao, MD

Massachusetts General Hospital

Site Directors
Michael R. Flaherty, DO
Kevin S. Gipson, MD
Christopher J. Moran, MD
Benjamin A. Nelson, MD

Contributors
Awab Ali Ibrahim, MD
Ryan Carroll, MD, MPH
Michelle L. Chiu, MD
Brian M. Cummings, MD
Carlos I. Duran, MD
Chadi M. El Saleeby, MD, MS
Kelly J. Gardner, MD MEd
Nina L. Gluchowski, MD
Monica Hajirawala, MD
Sarah Hendrickson, MD
Ann Y. Kao, MD, MPH
Thomas B. Kinane, MD
Katherine L. Olshan, MD
Meryl K. Perlman, MD
Stephanie Ruest, MD
Takara Stanley, MD
Jeffrey Sumner, MD
Avram Z. Traum, MD

St. Jude Children’s Research Hospital

Site Director
Justin Baker, MD

Contributors
Kari L. Bjornard, MD, MPH
Lindsay Blazin, MD
Stephanie B. Dixon, MD
Jessica A. Gartrell, MD
Dylan Graetz, MD, MPH
Akshay Sharma, MBBS
Michael Terao, MD

University of Michigan Hospital and Health Systems

Site Directors
Heather L. Burrows, MD, PhD
Namita Sachdev, MD

Contributors
Mark N. Hakim, MD
Amy E. Hepper, MD
Sharon Kileny, MD
Debra M. Langlois, MD
John Schmidt, MD
Maria S. Skoczylas, MD

Vanderbilt University

Site Director
Sandra A. Moutsios, MD

Contributors
Cassandra C. Brady, MD
Whitney L. Browning, MD
Alaina M. Davis, MD
Maie El-Sourady, MD, MS
Cristina M. Estrada, MD
Geoffrey M. Fleming, MD
Maria Gillam-Krakauer, MD
Jennifer K. Green, MD, MPH
Tiffany Hines, MD
Ashley Rowatt Karpinos, MD, MPH
Jaime Kaye Otillio, MD
Devang J. Pastakia, MD
Mary E. Romano, MD, MPH
Cosby A. Stone, Jr., MD, MPH

Washington University

Site Director
Andrew J. White, MD

Contributors
Tara C. Copper, MD, MS
Michele M. Estabrook, MD
Sarah K. Garwood, MD
Elizabeth Harrison, MD
Carrie A. Nalisnick, MD
Erin Marie O’Brien, MD
Cassandra Pruitt, MD
Patrick J. Reich, MD