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Medical Care of Adults With Down SyndromeA Clinical Guideline

Educational Objective
To review the clinical management of adults with Down syndrome.
1 Credit CME
Abstract

Importance  Down syndrome is the most common chromosomal condition, and average life expectancy has increased substantially, from 25 years in 1983 to 60 years in 2020. Despite the unique clinical comorbidities among adults with Down syndrome, there are no clinical guidelines for the care of these patients.

Objective  To develop an evidence-based clinical practice guideline for adults with Down syndrome.

Evidence Review  The Global Down Syndrome Foundation Medical Care Guidelines for Adults with Down Syndrome Workgroup (n = 13) developed 10 Population/Intervention/ Comparison/Outcome (PICO) questions for adults with Down syndrome addressing multiple clinical areas including mental health (2 questions), dementia, screening or treatment of diabetes, cardiovascular disease, obesity, osteoporosis, atlantoaxial instability, thyroid disease, and celiac disease. These questions guided the literature search in MEDLINE, EMBASE, PubMed, PsychINFO, Cochrane Library, and the TRIP Database, searched from January 1, 2000, to February 26, 2018, with an updated search through August 6, 2020. Using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology and the Evidence-to-Decision framework, in January 2019, the 13-member Workgroup and 16 additional clinical and scientific experts, nurses, patient representatives, and a methodologist developed clinical recommendations. A statement of good practice was made when there was a high level of certainty that the recommendation would do more good than harm, but there was little direct evidence.

Findings  From 11 295 literature citations associated with 10 PICO questions, 20 relevant studies were identified. An updated search identified 2 additional studies, for a total of 22 included studies (3 systematic reviews, 19 primary studies), which were reviewed and synthesized. Based on this analysis, 14 recommendations and 4 statements of good practice were developed. Overall, the evidence base was limited. Only 1 strong recommendation was formulated: screening for Alzheimer-type dementia starting at age 40 years. Four recommendations (managing risk factors for cardiovascular disease and stroke prevention, screening for obesity, and evaluation for secondary causes of osteoporosis) agreed with existing guidance for individuals without Down syndrome. Two recommendations for diabetes screening recommend earlier initiation of screening and at shorter intervals given the high prevalence and earlier onset in adults with Down syndrome.

Conclusions and Relevance  These evidence-based clinical guidelines provide recommendations to support primary care of adults with Down syndrome. The lack of high-quality evidence limits the strength of the recommendations and highlights the need for additional research.

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Article Information

Corresponding Author: Amy Y. Tsou, MD, MSc, Evidence-Based Practice Center, Center for Clinical Excellence and Guidelines, ECRI, 5200 Butler Pike, Plymouth Meeting, PA 19462 (atsou@ECRI.org).

Accepted for Publication: September 1, 2020.

Author Contributions: Drs Tsou and Capone had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Tsou, Bulova, Capone, Chicoine, Gelaro, Martin, McKelvey, Peterson, Tyler, Wells, Whitten.

Acquisition, analysis, or interpretation of data: Tsou, Capone, Chicoine, Gelaro, Harville, Martin, McGuire, McKelvey, Peterson, Tyler, Wells, Whitten.

Drafting of the manuscript: Tsou, Bulova, Capone, Harville, Martin, McGuire, McKelvey, Peterson, Tyler, Wells.

Critical revision of the manuscript for important intellectual content: Tsou, Bulova, Capone, Chicoine, Gelaro, Harville, Martin, McKelvey, Peterson, Tyler, Wells, Whitten.

Obtained funding: Gelaro, Whitten.

Administrative, technical, or material support: Tsou, Bulova, Capone, Gelaro, Harville, Peterson, Tyler, Wells, Whitten.

Supervision: Tsou, Capone, Chicoine, Gelaro, McKelvey, Whitten.

Conflict of Interest Disclosures: Dr Capone reported receiving grants from the LuMind Foundation and serving on the board of directors of the Down Syndrome Medical Interest Group–USA (DSMIG-USA), the steering committee of the Down Syndrome International Health Guideline Project, the clinical and scientific advisory board of the National Down Syndrome Society, and the executive committee of the LuMind Down Syndrome–Clinical Trials Network. Dr Chicoine reported receiving personal fees from Woodbine House Publishing, serving as the current treasurer of DSMIG-USA, the clinical advisory board for the National Down Syndrome Society, and the executive committee of the LuMind Down Syndrome–Clinical Trials Network. Drs Bulova, Capone, Chicoine, Martin, McGuire, McKelvey, and Peterson and Mss Gelaro and Whitten are current members of the DSMIG-USA. No other authors reported disclosures.

Funding/Support: This work was funded and supported by the Global Down Syndrome Foundation (GLOBAL; a 501 c3 nonprofit organization dedicated to improving the lives of people with Down syndrome through research, medical care, education, and advocacy) and by generous donations from the Down syndrome community (Supplement 1). No government funding supported the work.

Role of Funder/Sponsor: GLOBAL determined the need for updated, evidence-based guidelines, contracted ECRI, recruited the Workgroup, and provided organizational, administrative, and financial support including fundraising. ECRI and the author Workgroup designed, managed, analyzed the data. The author Workgroup interpreted the data, prepared and approved of the manuscript, and decided to submit the manuscript for publication.

Global Down Syndrome Foundation Medical Care Guidelines for Adults With Down Syndrome Workgroup: Behavior Committee: Lead authors: George Capone (Johns Hopkins School of Medicine, Baltimore, Maryland); Dennis E. McGuire; Coauthors: Bryn Gelaro (Global Down Syndrome Foundation); Volunteers: Anna J. Esbensen (University of Cincinnati College of Medicine and Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio); Jarrett Barnhill (University of North Carolina, Chapel Hill). Dementia Committee: Lead authors: George Capone (Johns Hopkins School of Medicine, Baltimore, Maryland); Brian Chicoine (Advocate Medical Group Adult Down Syndrome Center, Park Ridge, Illinois); Dennis E. McGuire; Coauthors: Bryn Gelaro (Global Down Syndrome Foundation); Volunteers: Seth M. Keller (Virtua Health, New Jersey); Ira T. Lott (University of California, Irvine). Diabetes Committee: Lead authors: Moya Peterson (University of Kansas Medical Center, Kansas City); Brian Chicoine (Advocate Medical Group Adult Down Syndrome Center, Park Ridge, Illinois); Volunteers: Stephanie L. Santoro (Massachusetts General Hospital, Boston); Mary M. Stephens (Christiana Care Health System, Wilmington, Delaware). Cardiovascular Committee: Lead authors: Peter Bulova (University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania); Brian Chicoine (Advocate Medical Group Adult Down Syndrome Center, Park Ridge, Illinois); Barry A. Martin (University of Colorado School of Medicine, Aurora); Volunteers: Robert H. Eckel (University of Colorado, Anschutz Medical Campus, Aurora); Elizabeth Yeung (University of Colorado, Anschutz Medical Center and Children’s Hospital Colorado, Aurora). Obesity Committee: Lead authors: Peter Bulova (University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania); George Capone (Johns Hopkins School of Medicine, Baltimore, Maryland); Moya Peterson (University of Kansas School of Medicine, Kansas City); Volunteers: Judy L. Kim (Baylor College of Medicine, Houston, Texas); Joan Medlen; Kamala G. Cotts (University of Chicago, Chicago, Illinois). Atlantoaxial Instability Committee: Lead authors: Barry A. Martin (University of Colorado School of Medicine, Aurora); Moya Peterson (University of Kansas Medical Center, Kansas City); Volunteers: James E. Hunt (University of Arkansas for Medical Sciences and Arkansas Children’s Hospital, Little Rock); Paul J. Camarata (University of Kansas School of Medicine, Kansas City); Mary M. Stephens (Christiana Care Health System, Wilmington, Delaware). Osteoporosis Committee: Lead authors: Kent D. McKelvey (University of Arkansas for Medical Sciences, Little Rock); Carl Tyler (Cleveland Clinic Lerner College of Medicine and Case Western Reserve University School of Medicine, Cleveland, Ohio); Coauthors: Michael D. Wells (Developmental Disabilities–Practice-Based Research Network); Volunteers: Micol Rothman (Division of Endocrinology, Metabolism & Diabetes and Department of Psychiatry, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora). Thyroid Committee: Lead authors: Kent D. McKelvey (University of Arkansas for Medical Sciences, Little Rock); Barry A. Martin (University of Colorado School of Medicine, Aurora); Volunteers: Donald Bodenner (University of Arkansas for Medical Sciences, Little Rock); Michael T. McDermott (University of Colorado Hospital, Aurora). Celiac Disease Committee: Lead authors: Kent D. McKelvey (University of Arkansas for Medical Sciences, Little Rock); Terry O. Harville (University of Arkansas for Medical Sciences, Little Rock); Carl Tyler (Cleveland Clinic Lerner College of Medicine and Case Western Reserve University School of Medicine, Cleveland, Ohio); Coauthors: Michael D. Wells (Developmental Disabilities–Practice-Based Research Network).

Additional Contributions: We thank ECRI for conducting the literature review, synthesizing the evidence report, providing methodological support for drafting recommendations, providing administrative support and providing medical editing services. We also thank the contributors who served on the GLOBAL Workgroup volunteer committees. Last, the following individuals contributed to the review of the future research section: Joaquín M. Espinosa, PhD (Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora), Lina R. Patel, PsyD (Anna and John J. Sie Center for Down Syndrome, Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora), Michael S. Rafii, MD, PhD (Department of Neurology, Keck School of Medicine of USC, Los Angeles, California).

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