Executive Summary of the 2013 International Society for Clinical Densitometry Position Development Conference on Body Composition

Transcription

1 Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health, vol. 16, no. 4, 489e495, 2013 Ó Copyright 2013 by The International Society for Clinical Densitometry /16:489e495/$ Position Development Conference on Bone Densitometry Executive Summary of the 2013 International Society for Clinical Densitometry Position Development Conference on Body Composition John A. Shepherd,*,1 Sanford Baim, 2 John P. Bilezikian, 3 and John T. Schousboe 4 1 Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, CA, USA; 2 Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, USA; 3 Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA; and 4 Park Nicollet Osteoporosis Center and Division of Health Policy and Management, University of Minnesota, Minneapolis, MN, USA Abstract There have been many scientific advances in measurement of fat and lean body mass as determined by dual-energy X-ray absorptiometry (DXA). The International Society for Clinical Densitometry (ISCD) convened a Position Development Conference (PDC) on the use of DXA for body composition measurement. Previously, no guidelines to the use of DXA for body composition existed. The recommendations pertain to clinically relevant issues regarding DXA indications of use, acquisition, analysis, quality control, interpretation, and reporting were addressed. The topics and questions for consideration were developed by the ISCD Board of Directors and the Scientific Advisory Committee and were designed to address the needs of clinical practitioners. Three Task Forces were created and assigned these questions and asked to conduct comprehensive literature reviews. The Task Forces included participants from 6 countries and a variety of interests including academic institutions, private clinics, and industry. Reports with proposed Position Statements were then presented to an international panel of experts with backgrounds in DXA and bone densitometry and a variety of fields that use body composition measures. The PDC was held in Tampa, FL, contemporaneously with the Annual Meeting of the ISCD, March 21 through March 23, This report describes the methodology of the 2013 ISCD Body Composition PDC and summarizes the results. Three separate articles in this issue will detail the rationale, discussion, and additional research topics for each question the Task Forces addressed. Key Words: Dual-energy X-ray absorptiometry; guidelines; official positions; recommendations; standards. Introduction The International Society for Clinical Densitometry (ISCD) is a nonprofit professional organization dedicated to the advancement of assessment of musculoskeletal health, particularly (but not limited to) bone densitometry. A major focus of the Society is the development of guidelines and establishment of standards for bone densitometry, assessment of fracture risk, and other aspect of musculoskeletal measurement. Received 08/14/13; Accepted 08/14/13. *Address correspondence to: John A. Shepherd, PhD, CCD, University of California at San Francisco, 1 Irving St, Suite A-C108B, San Francisco, CA john.shepherd@ucsf.edu In recognition of the many scientific advances in measurement of fat and lean body mass as determined by dual-energy X-ray absorptiometry (DXA), the ISCD convened a Position Development Conference (PDC) on the use of DXA for body composition measurement. Previous PDCs had not addressed body composition guidelines. The Society conducts PDCs every 2e3 yr to develop guidelines and standards (expressed as Position Statements) for new technologies used to assess musculoskeletal health and fracture risk and to update older guidelines and standards as new data become available. The ISCD Official Positions are widely used by clinicians and densitometry technologists as a reference regarding the indications for, acquisition of, 489

2 490 Shepherd et al. and interpretation and reporting of measures of musculoskeletal health and incorporation of those measures into fracture risk assessment. The curricula of the densitometry educational courses provided by ISCD are largely based on these Positions. The ISCD PDC process is designed to summarize and use the best scientific evidence available to develop and update Position Statements regarding musculoskeletal assessment. Because musculoskeletal assessment technologies are evolving, clinically important issues are sometimes addressed in the absence of robust evidence and, thus, largely based on expert opinion. However, the PDC process grades and highlights the limitations of the available evidence pertinent to each Statement and indicates where additional research is needed to improve the scientific evidence on which Positions are based and to resolve areas of ambiguity and controversy. Position statements from prior PDCs held in 2001, 2003, 2005, 2007, and 2010 have been published (1e6). The most recent PDC was held in Tampa, FL, March 21 through March 23, This article describes the methodology of this PDC, and the results from the topics regarding the indications for, acquisition of, and interpretation and reporting of body composition analysis studies using DXA. Methodology The selection of topics for the 2013 ISCD PDC, the formation and composition of the 2013 ISCD Steering Committee, and the selection of scientific questions within each topic area are as described in the Executive Summary of the 2013 ISCD PDC on Bone Densitometry. The questions regarding the indications of use, acquisition, and reporting for DXA body composition are as follows. Indications of use for DXA body composition What are the clinical indications of DXA for body composition? patients with HIV? patients either considering or having recently had bariatric surgery? patients with sarcopenia? obese patients? What are the contraindications of DXA for body composition? DXA vs alternative technologies What are the advantages and disadvantages of alternatives measures of DXA for body composition? - When should DXA be used instead of computed tomography? - When should DXA be used instead of magnetic resonance imaging? - When should DXA be used instead of bioimpedance analysis or bioimpedance spectroscopy? - When should DXA be used instead of air and water displacement technologies? - When should DXA be used instead of anthropomorphic body composition measures such as waist circumference, hip circumference, mid-arm circumference, and skin-fold thicknesses? DXA body composition reports What DXA body composition measures should appear on reports? - What measures should appear on all reports? - What additional measures and indices should appear on reports for patients with HIV? - What additional measures and indices should appear on reports for patients undergoing a DXA evaluation for obesity? - What additional measures and indices should appear on reports for patients with sarcopenia? - What measures should be reported for individuals expected to have a rapid weight gain or loss? Reference data for body composition Which is the most appropriate database to be used as reference? - What reference database should be used to represent the general healthy population according to age, health status, race, physical activity? How should reference data be used in reporting DXA BC? - Should T-scores be used in reporting body composition measures? - Should Z-scores be used in reporting body composition measures? - Should percentile values be used in reporting body composition values? Reporting and interpretation of DXA body composition measures How are DXA body composition values used for risk stratification and monitoring? - How is DXA used in the diagnosis of sarcopenia? - How is DXA used in the diagnosis of HIV-related complications, such as lypodystrophy and lypoatrophy? - How is DXA used in the diagnosis of obesity? Accuracy and precision assessment What phantoms and procedures should be used for quality control (QC) monitoring and cross-calibration for whole-body outcomes? - What phantoms should be used to assure a DXA system is working within specifications and with stable calibration over time? - How do you cross-calibrate measures between systems from different manufacturers? - How to cross-calibrate measures between systems of the same manufacturer?

3 2013 ISCD PDC BC Summary 491 How should the accuracy of percent fat mass, fat mass, and lean mass be ascertained in the clinical setting? - What phantoms are available to ascertain absolute accuracy? Acquisition of DXA body composition measures in patients What is the optimal way to prepare and position a patient for whole-body scans? - How should the hands, arms, legs, and feet be positioned? - How should very obese or patients that do not fit within the scan limits be positioned? Considerations regarding analysis and repeatability of measures How should whole-body scans be analyzed? - How should arms, legs, and head be sectioned from the trunk? - If observed in the scan at the time of analysis, how should removable artifacts be dealt with? - If observed in the scan at the time of analysis, how should nonremovable artifacts be dealt with? How should precision be assessed for body composition measures? What is the minimum precision acceptable for a DXA site? - What is the minimum precision for fat tissue assessment? - What is the minimum precision for lean tissue assessment? 2013 Body Composition PDC Structure Formation and Function of Task Forces Three Task Forces were formed to address the questions in 3 primary areas: indications of use, reporting, and acquisition and analysis of body composition studies using DXA. Task Force chairs were selected because of their high level of expertise in these areas. Along with the Steering Committee, they selected additional experts in the field to serve as Task Force members. Each Task Force was asked to perform a literature search using the methodology of previous PDCs, focused on PubMed, Medline, and Embase databases. With insights from the more recently published literature, the Task Forces had the option to refine the questions, initially proposed, in consultation with the Steering Committee. Each Task Force then drafted proposed Position Statements to address the questions that had been assigned. The Task Force chairs, in consultation with Task Force members, then wrote Position Papers describing the proposed Position Statements, supported by documented references to the literature. Formation and Function of the Expert Panel Starting with the Adult and Pediatric PDCs of 2007, the ISCD PDCs have followed the RAND-UCLA method of rating the appropriateness of candidate Position Statements (RAND-UCLA Appropriateness Method [RAM]) that is described in more detail in the next section. This method requires that an Expert Panel, wholly separate from the Task Forces, be formed to review the proposed Position Statements and supportive documents and rate them. Expert Panel members were chosen on the basis of 4 criteria: (a) acknowledged expertise in at least one of the topic areas; (b) representative of different geographic regions; (c) representative of other professional societies with a commitment to the field of musculoskeletal measurement; and (d) a keen ability to weigh scientific evidence. Accordingly, 13 international experts were invited and agreed to serve on the Expert Panel, were able to attend all presentations and deliberations regarding Body Composition Analysis, and rated the body composition analysis statements PDC Procedures The 2013 PDC procedures, including the literature reviews performed by the Task Forces, formulation of Statements to address the questions posed to the Task Forces, and the rating process of those Statements, all followed a modified RAM (2,4,7). The RAM not only includes ratings as to whether a Statement is appropriate but also explicitly grades the quality of the evidence on which the Statement is based. This process recognizes that although based on the currently available evidence, a statement may be considered to be appropriate, even though the evidence may be weak. Grading of the quality of evidence places the statement in the appropriate context. The Task Forces presented the proposed statements and the supporting scientific evidence for each Statement in 2 steps. The Task Forces finished their literature reviews and draft documents by February These were sent to all Expert Panelists, who conducted their initial round of rating from February 24 through March 11, 2013, without consulting each other. Grading of the Official Positions All Statements were rated by each Expert Panelist in 4 areas. 1. Appropriateness: The appropriateness of each statement was voted on a scale of 1e9 with 1 representing highly inappropriate and 9 representing highly appropriate. Statements that had a median score of 1e3 were rated as inappropriate, those with a median score of 4e6 as uncertain, and those with a median score of 7e9 as appropriate. Statements were considered to be appropriate without disagreement if, in addition to a median score of 7 to 9, no more than 3 Expert Panelist ratings fell outside this range. 2. Quality of evidence: The quality of the evidence supporting each statement was rated as being Good, Fair, or Poor. Good evidence was from 2 or more welldesigned prospective studies (randomized controlled trials

4 492 Shepherd et al. or high-quality observational studies). Fair evidence was judged to be sufficient to determine effects on outcomes but limited by the number, quality, or consistency of the available studies. Poor evidence was judged to be insufficient to determine effects or consequences of implementing the Statement on outcomes because of the number of available studies, flaws in their design or conduct, major gaps in the chain of evidence, or conflicting evidence. 3. Strength of recommendation: The strength of the recommendation to implement the Statement was rated as: (A) strong recommendation supported by the available evidence; (B) recommendation supported by the available evidence; or (C) recommendation supported primarily by expert opinion. It should be noted that a Statement could be rated as being supported by a good quality of evidence and yet have a level C strength of recommendation, if the beneficial consequences of implementation of the Statement were judged to be slight or offset by negative consequences. 4. Applicability: Statements were rated as applicable throughout the world (Worldwide) or applicable according to local requirements (Local). Second Round Expert Panel Voting at the PDC in Tampa, FL The Task Forces revised their initial documents and presented these revised documents in detail to the Expert Panel in sessions open to the public on March 21 and March 22, Statements that were rated as inappropriate in the first round of rating were not considered further or presented. Statements that were rated as appropriate without disagreement in the first round of Expert Panel voting were presented briefly and, with a few exceptions, accepted and rated again as appropriate in their original wording and content. A few of these Statements, however, were altered at the behest of the Expert Panel before being rated as appropriate during the second round. The majority of time in the open sessions was spent debating statements that were rated as uncertain. Some of these statements were rated as inappropriate on the second round votes, some were again voted as uncertain, and some that were voted as uncertain on the first round were voted appropriate without disagreement on the second round. Final Selection and Approval of the 2013 ISCD Official Positions The Expert Panel, Task Force chairs, and the 2013 PDC Steering Committee met again in closed session on March 23 to refine the final wording of the statements that would be submitted to the ISCD Board of Directors for review and approval. The final statements rated as Appropriate without Disagreement, along with their ratings regarding quality of evidence, strength of recommendation, and applicability, and the supporting literature reviews were posted to the ISCD Web site in early June for review by the ISCD Board of Directors. The ISCD Board of Directors voted to approve all these statements on June 27, The rationale for the positions on indications of use, acquisition, and reporting and further discussion and suggestions for additional research are presented in 3 separate articles also in the issue (8e10). Participants The list of individuals who comprised the 2013 PDC Steering Committee, served on each of the Task Forces, or served on the Expert Panel is shown in the Appendix. Financial Support The following industry partners gave financial support that made the Position Development Conference possible: Amgen, Inc.; Merck, Inc.; Eli Lilly, Inc.; and Hologic, Inc. Cumulative ISCD Official Positions A summary of all the bone and body composition positions from the two 2013 PDCs and all positions still current from prior PDCs are shown in the Appendix 2 of the Executive Summary of the 2013 PDC on Bone Densitometry (11). New ISCD Official Positions on Body Composition Indications 1. DXA total body composition with regional analysis can be used in the following conditions: a. In patients living with HIV to assess fat distribution in those using antiretroviral agents associated with a risk of lipoatrophy (currently stavudine [d4t] and zidovudine [ZDV, AZT]). Grade: Good-B-W b. In obese patients undergoing bariatric surgery (or medical, diet, or weight loss regimens with anticipated large weight loss) to assess fat and lean mass changes when weight loss exceeds approximately 10%. The impact on clinical outcomes is uncertain. Grade: Poor-C-W c. In patients with muscle weakness or poor physical functioning to assess fat and lean mass. The impact on clinical outcomes is uncertain. 2. Pregnancy is a contraindication to DXA body composition. Limitations in the use of clinical DXA for total body composition or bone mineral density are weight over the table limit, recent administration of contrast material, and/or artifact. Radiopharmaceutical agents may interfere with accuracy of results using systems from some DXA manufacturers.

5 2013 ISCD PDC BC Summary 493 Acquisition 1. No phantom has been identified to remove systematic differences in body composition when comparing in vivo results across manufacturers. Grade: Good-B-W 2. An in vivo cross-calibration study is necessary when comparing in vivo results across manufacturers. 3. Cross-calibrating systems of the same make and model can be performed with an appropriate whole-body phantom. 4. Changes in body composition measures can be evaluated between 2 different systems of the same make and model if the systems have been cross-calibrated with an appropriate total body phantom. 5. When changing hardware, but not the entire system, or when replacing a system with the same technology (make and model), cross-calibration should be performed by having 1 technologist do 10 whole-body phantom scans, with repositioning, before and after hardware change. If O2% difference in mean percent fat mass, fat mass, or lean mass is observed, contact the manufacturer for service/correction. 6. No total body phantoms are available at this time that can be used as absolute reference standards for soft-tissue composition or bone mineral mass. Grade: Good-A-W 7. The QC program at a DXA body composition facility should include adherence to manufacturer guidelines for system maintenance. In addition, if not recommended in the manufacturer protocol, the following QC procedures are advised: a. Perform periodic (at least once per week) body composition phantom scans for any DXA system as an independent assessment of system calibration. b. Plot and review data from calibration and body composition phantom scans. c. Verify the body composition phantom mean percent fat mass and tissue mass after any service performed on the densitometer. d. Establish and enforce corrective action thresholds that trigger a call for service. e. Maintain service logs. f. Comply with radiation surveys and regulatory government inspections, radiation surveys, and regulatory requirements. All graded: Fair-B-W 8. Consistent positioning and preparation (e.g., fasting state, clothing, time of day, physical activity, empty bladder) of the patient are important for precise measures. 9. Positioning of the arms, hands, legs, and feet whenever possible should be according to the National Health and Nutrition Examination Survey (NHANES) method (palms down isolated from the body, feet neutral, ankles strapped, arms straight or slightly angled, face up with neutral chin). 10. Offset scanning should be used in patients who are too wide to fit within the scan boundaries, using a validated procedure for a specific scanner model. 11. Every technologist should perform an in vivo precision assessment for all body composition measures of interest using patients who are representative of the clinic s patient population. 12. The minimum acceptable precision for an individual technologist is 3%, 2%, and 2% for total fat mass, total lean mass, and percent fat mass, respectively. 13. Consistently use manufacturer s recommendations for region of interest (ROI) placement. 14. Consistently use manufacturer s recommendations for artifact removal. Analysis and Reporting 1. For adults, total body (with head) values of body mass index (BMI), bone mineral density (BMD), bone mineral content (BMC), total mass, total lean mass, total fat mass, and percent fat mass should appear on all reports. 2. Total body BMC as represented in the NHANES 1999e2004 reference data should be used when using DXA in 4-compartment models. 3. DXA measures of adiposity and lean mass include visceral adipose tissue (VAT), appendicular lean mass index (ALMI: appendicular lean mass/ht 2 ), android/gynoid percent fat mass ratio, trunk to leg fat mass ratio, lean mass index (LMI: total lean mass/ht 2 ), fat mass index (fat mass/ ht 2 ) are optional. The clinical utility of these measures is currently uncertain. 4. When comparing with the US population, the NHANES 1999e2004 body composition data are most appropriate for different races, both sexes, and for ages from 8 to 85 yr. [Note: reference to a population does not imply health status.] Grade: Fair-C-L 5. Both Z-scores and percentiles are appropriate to report if derived using methods to adjust for non-normality. 6. The use of DXA adiposity measures (percent fat mass or fat mass index) may be useful in risk-stratifying patients for cardiometabolic outcomes. Specific thresholds to define obesity have not been established.

6 494 Shepherd et al. 7. Low lean mass could be defined using appendicular lean mass divided by height squared with Z-scores derived from a young adult, race, and sex-matched population. Thresholds for low lean mass from consensus guidelines for sarcopenia await confirmation. Acknowledgments As was true of prior PDCs, the 2013 ISCD PDC was possible only through the extensive voluntary efforts of large numbers of individuals, notably the clinical and scientific experts who donated countless hours over the past 18 mo as Task Force chairs, Task Force members, or Expert Panel members. The ISCD wishes to acknowledge and thank these individuals for their extraordinary service. Additionally, the staff of ISCD plays a crucial role organizing the logistics and infrastructure of these conferences so that they can run smoothly. Those of us on the Steering Committee of the 2013 ISCD PDC thank them for their efforts and support. References 1. Baim S, Binkley N, Bilezikian JP, et al Official Positions of the International Society for Clinical Densitometry and executive summary of the 2007 ISCD Position Development Conference. J Clin Densitom 11(1):75e Baim S, Leonard MB, Bianchi ML, et al Official Positions of the International Society for Clinical Densitometry and executive summary of the 2007 ISCD Pediatric Position Development Conference. J Clin Densitom 11(1):6e Binkley N, Bilezikian JP, Kendler DL, et al Official positions of the International Society for Clinical Densitometry and Executive Summary of the 2005 Position Development Conference. J Clin Densitom 9(1):4e Hans DB, Kanis JA, Baim S, et al Joint Official Positions of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX((R)). Executive Summary 2010 Position Development Conference Interpretation use FRAX(R) in clinical practice. J Clin Densitom 14(3): 171e Lenchik L, Leib ES, Hamdy RC, et al Executive summary International Society for Clinical Densitometry Position Development Conference Denver, Colorado July 20-22, J Clin Densitom 5(Suppl):S1eS3. 6. The Writing Group for the ISCD Position Development Conference Executive Summary. J Clin Densitom 7(1):7e Fitch K, Bernstein S, Aguilar M, et al The RAND/UCLA Appropriateness Methods User s Manual. Santa Monica: The RAND Corp. 8. Kendler DL, Borges JL, Fielding RA, et al The Official Positions of the International Society for Clinical Densitometry: indications of use and reporting of DXA for body composition. J Clin Densitom 16(4):496e Hangartner T, Warner S, Braillon P, et al The Official Positions of the International Society for Clinical Densitometry: acquisition of DXA body composition and considerations regarding analysis and repeatability of measures. J Clin Densitom 16(4):520e Petak SM, Barbu C, Yu E, et al The Official Positions of the International Society for Clinical Densitometry: body composition analysis reporting. J Clin Densitom 16(4):508e Schousboe JT, Shepherd JA, Bilezikian JP, Baim S Executive Summary of the 2013 ISCD Position Development Conference on Bone Densitometry. J Clin Densitom 16(4): 489e495. Appendix 2013 ISCD PDC Steering Committee John T. Schousboe, MD, PhD; Park Nicollet Health Service & University of Minnesota, MN, USA. John A. Shepherd, PhD CCD; University of California at San Francisco, San Francisco, CA, USA. Sanford Baim, MD; University of Miami, Miami, FL, USA. John P. Bilezikian, MD; College of Physicians and Surgeons, New York, NY, USA ISCD PDC Expert Panelists Neil Binkley, MD; University of Wisconsin, Madison, WI, USA. Marjery Gass, MD; Center for Specialized Women s Health, Cleveland Clinic, Cleveland, OH, USA. Meryl S. LeBoff MD; Skeletal Health and Osteoporosis Center, Brigham s and Women s Hospital, Boston, MA, USA. David B. Allison, PhD; University of Alabama School of Public Health, Birmingham, AL, USA.* Eric S. Orwoll, MD; Oregon Health & Science University, Portland, OR, USA. Steven Heymsfeld, MD; Pennington Biomedical Research Center, Baton Rouge, LA, USA. Didier B. Hans, PhD; University of Lausanne, Switzerland. Eugene McCloskey MB, BCh, MD; University of Sheffield, Sheffield, UK. Peggy M. Cawton, PhD, MPH; California Pacific Medical Center, San Francisco, CA, USA. Mary K. Oates, MD; Marian Regional Medical Center, Santa Maria, CA, USA. Catalina Poiana, MD, PhD; Carol Davila University of Medicine and Pharmacy & C.I. Parhon Institute, Romania. Angela Cheung, MD, PhD; University Health Network, Toronto, ON, Canada. E. Michael Lewiecki, MD; New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM, USA. *Dr Allison served as an Expert Panelist only for the Body Composition Analysis topics ISCD Body Composition PDC Task Forces John Shepherd, PhD CCD (Overall Task Force Chair); University of California at San Francisco, San Francisco, CA, USA. DXA Body Composition Indications David Kendler, MD, CCD (Chair); University of British Columbia, Vancouver Canada. Joao Lindolfo C. Borges, MD; Universidade Catolica de Brasilia, Brazil.

7 2013 ISCD PDC BC Summary 495 Bruno Muzzi Camargos, MD, CCD, CDT; Hospital Mater Dei, Belo Horizonte, Brazil. Roger Fielding, PhD; Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition at Research Center on Aging at Tufts University, Boston, MA, USA. Akira Itabashi, MD, PhD, CCD; Saitama Ctr For Bone Research Kubojima Clinic, Kubojima, Japan. Diane Krueger, BS, CBDT; University of Wisconsin, Madison, WI, USA. Kathleen Mulligan, PhD; University of California at San Francisco, San Francisco, CA, USA. Chih-Hsing Wu, MD, CCD; Department of Family Medicine, National Cheng Kung University Hospital, Tainan, Taiwan. Elaine W. Yu, MD, CCD; Harvard Medical School, Massachusetts General Hospital, Boston MA, USA. Acquisition and Analysis Thomas Hangartner, PhD (Chair); BioMedical Imaging Laboratory, Wright State University, Dayton, OH, USA. Pierre Brallion, MD; Hospital Debrousse, Lyon, France. Larry Jankowski, CBDT; Illinois Bone & Joint Institute, Chicago, IL, USA. Sally Warner, PhD CCD; Perceptive Medical Imaging, Billerica, MA, USA. Reporting Steven Petak, MD, CCD (Chair); Houston Methodist HospitaleDepartment of Medicine, Houston TX, USA. Carmen Barbu, MD, PhD, CCD; Carol Davila University, Elias Hospital, Bucharest, Romania. Roger Fielding, PhD; Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition at Research Center on Aging at Tufts University, Boston, MA, USA. Kathleen Mulligan, PhD; University of California at San Francisco, San Francisco, CA, USA. Brian Sabowitz, MD, FACP, CCD; University of Texas Health Sciences Center, Department of Endocrinology, Diabetes, and Metabolism, San Antonio, TX, USA. Chih-Hsing Wu, MD, CCD; Department of Family Medicine, National Cheng Kung University Hospital, Tainan, Taiwan. Elaine W. Yu, MD, CCD; Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.