Vol.15, No.1, 2012
Journal of Managed Care Medicine
Improving Outcomes and Reducing Costs with Minimally Invasive Procedures Outcomes and Cost Effectiveness of Collaborative Care Disease Management Approach in Depression Patients Treatment Strategies in the Management of Rheumatoid Arthritis Spirometry: Improving Patient Outcomes and Reducing Overall Costs for COPD Through Early Diagnosis and Annual Assessment Optimizing Treatment Strategies in the Management of Non-Small Cell Lung Cancer Chemotherapy-Induced Nausea and Vomiting(CINV): Perceptions, Mechanisms, and Treatment Guidelines Undertreated Pain Epidemic: Multi-Modality Approach to Pain Management Ignoring Real Interventions
L-METHYLFOLATE: A NOVEL FORM OF FOLATE MORE EFFICIENT THAN FOLIC ACID. Folic acid is syntheticly produced and NOT the active form of folate needed for the dietary management of the distinct nutritional requirements of several chronic disease states3; including depression1, early memory loss2, diabetic peripheral neuropathy3, and risk of neural tube defects4:
The conversion of folic acid to L-methylfolate involves a lengthy six step process: Prevalence of the MTHFR CT Polymorphism by Genotype.
L-methylfolate Synthetic Folic Acid DHF Reductase
Homozygous Polymorphism 9%
Dihydrofolate (Dietary Folate)
DHF Reductase
Tetrahydrofolate 10-formyl-THF
TT 9%
CC 44%
MTHFD1 Polymorphism
5, 10 Methyenyl THF
Normal
5, 10 Methylene THF
C7 47%
MTHFR Polymorphism
L-methylfolate
Heterozygous Polymorphism 47%
L-methylfolate
50% of the general population has an inborn error in the MTHFR enzyme which limits their capacity to convert folic acid to L-methylfolate5.
Additional Benefits of L-methlyfolate: •
L-methylfolate is 7 times more bioavailable than folic acid regardless if a patient has a MTHFR CT polymorphism or not.6
•
L-methylfolate is able to cross the “blood brain” barrier to acid in the synthesis of neurotransmitters and other neurological benefits, unlike folic acid.7
•
L-methylfolate is less likely to mask a vitamin B12 deficiency compared to folic acid.8
•
L-methylfolate reduces toxic levels of homocysteine significantly greater than folic acid.3
•
L-methylfolate increases RBC folate better than folic acid.9
L-methylfolate is available in several commercial formulations.
DPN TOTAL SYMPTOMS
Mother Nature’s Folate
Deplin® is a medical food, dispensed by prescription, for the clinical dietary management of the metabolic imbalances associated with depression and schizophrenia. Use under medical supervision. CerefolinNAC® is an orally administered medical food for use only under medical supervision for the dietary management of certain metabolic processes indentified with mild cognitive impairment. Metanx® is a medical food dispensed by prescription for the dietary management of endothelial dysfunction in patients with diabetic peripheral neuropathy. Neevo® and NeevoDHA® are medical foods for use under medical supervision for the dietary management of impaired metabolic processes in women under a doctor’s care who face high to intermediate risk pregnancies and are unable to fully metabolize or absorb folic acid. references: 1. Stahl, S. Novel Therapeutics for Depression: L-methylfolate as a Trimonoamine and Antidepressant-Augmenting Agent, CNS Spectrums, 2007, 12:10, 739-744 2. Durga J.et al. Effects of 3-year Folic Acid Supplementation on Cognitive Function in Older Adults in the FACIT trial: A randomized, double-blind, controlled trial. The Lancet. 2007:369:208-215 3. Walker ML Jr, Morris LM. Vascular Disease Management. 2007;2(1):1-8. 4. LamarsY, et.al. Natural folate form for prevention of nueral tube defects: Effect of supplementation with (6S)-5-methlytetrahydrofolate versus folic acid red cell folate concentration. Cuvillier Verlag, Gottingen 2006 pp 43-59: ISBN 3-86537-756-4 5. Papakostas G., Serum Folate, Vitamin B12, and Homocysteine in Major Depressive Disorder, Part 1: Predictors of Clinical Response in Fluoxetine-Resistant Depression, J. Clinical Psychiatry; 2004, 1090-1905 6. Willems FF, et al. Pharmacokentic study on the utlilization of 5-methyltetrahydrofolate and folic acid in patients with coronary artery disease. Br J Pharmacol. 2004; 141: 825-830 7. Smith l, Hyland K, Kendall B. Clinical role of pteridine therapy in tetrahydrobiopterin deficiency. J Inherit Metab Dis 1985;8(suppl 10:39-45 8. Scott, J.M. et al. The Methylfolate Trap. A Physiological Response in Man to Prevent Methyl Group Deficiency in Kwashiokor and an Explanation for Folic-Acid-Included Exacerbation of Subacute Combined Degeneration in Pernicious Anemia; Lancet. 1981 2:337-340 9. Lamers Y. Red blood cell folate concentrations increase more after supplementation with (6S)-5-methyltetrahydrofolat than with folic acid in women of childbearing age. Am J Clin Nutr 2006;83:842-850
© cerefolinnAc , Deplin , MetAnx , neevo ®
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JMCM Journal of Managed care medicine 4435 Waterfront Drive, Suite 101 Glen Allen, VA 23060 (804) 527-1905 fax (804) 747-5316
Editor-In-Chief
Journal of Managed Care Medicine The Official Journal of the National Association of Managed Care Physicians American Association of Integrated HealthCare Delivery Systems American College of Managed Care Medicine American Association of Managed Care Nurses A Peer-Reviewed Publication
Vol. 15, No. 1, 2012
J. Ronald Hunt, MD
publisher Katie Eads
director of communications Jeremy Williams
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ISSN: 1094-1525. The Journal of Managed Care is published by Association Services Inc. Corporate and Circulation offices: 4435 Waterfront Drive, Suite 101, Glen Allen, VA 23060; Tel (804) 527-1905; Fax (804) 747-5316. Editorial and Production offices: P.O. Box 71895, Richmond, VA 23255-1895; Tel (804) 658-4253; Fax (703) 997-5842. Advertising offices: Sloane Reed, 4435 Waterfront Drive Ste 101, Glen Allen, VA 23060 Tel (804) 527-1905, Fax (804) 7475316. Subscription Rates: one year $95 in the United States; one year $105 in Canada; one year $120 international. Back issues are available for $15 each. All rights reserved. Copyright 2012. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage or retrieval system, without written consent from the publisher. The publisher does not guarantee, either expressly or by implication, the factual accuracy of the articles and descriptions herein, nor does the publisher guarantee the accuracy of any views or opinions offered by the authors of said articles or descriptions. POSTMASTER: Send address changes to The Journal of Managed Care Medicine, 4435 Waterfront Drive, Suite 101, Glen Allen, VA 23060.
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TABLE OF CONTENTS Improving Outcomes and Reducing Costs with Minimally Invasive Procedures William E. Johnson, MD, MBA............................................................................ 5 Outcomes and Cost Effectiveness of Collaborative Care Disease Management Approach in Depression Patients Roueen Rafeyan, MD......................................................................................... 10 Treatment Strategies in the Management of Rheumatoid Arthritis Wesley Mizutani, MD, MBA................................................................................15 Spirometry: Improving Patient Outcomes and Reducing Overall Costs for COPD Through Early Diagnosis and Annual Assessment Rob Sussman, MD.............................................................................................. 18 Optimizing Treatment Strategies in the Management of Non-Small Cell Lung Cancer Greg Otterson, MD........................................................................................... 22 Chemotherapy-Induced Nausea and Vomiting(CINV): Perceptions, Mechanisms, and Treatment Guidelines Charles Loprinzi, MD......................................................................................... 25 Undertreated Pain Epidemic: Multi-Modality Approach to Pain Management Mark Rosenberg, MD, PhD............................................................................... 30 Ignoring Real Interventions Dexter Shurney, MD, MBA, MPH...................................................................... 38
Journal of Managed Care Medicine Instructions for Authors The Journal of Managed Care Medicine is a peer-reviewed national publication. Original articles dealing with the business or clinical side of managed care are welcome. Manuscript length generally should range between 10 to 15 typed pages, including a summary with key points, exhibits, and references. All submissions should include the following elements: • One printed copy of the manuscript, including illustrations/figures/tables • Contact numbers (phone and fax), complete mailing address, and e-mail address for designated corresponding author • Electronic version on CD or via e-mail in Microsoft Word • Bibliography/References, following the format of the AMA Manual of Style, 9th Ed. • Brief biography of author(s) < 50 words and including academic/corporate affiliations • Copyright transfer letter For a complete copy of authors’ guidelines, contact JMCM’s Managing Editor, Barry Barnum, (804) 658-4253. Forward submissions to Journal of Managed Care Medicine P.O. Box 71895 • Richmond, VA 23255-1895
www.namcp.org | Vol. 15, No. 1 | Journal of Managed Care Medicine 3
Editorial Review Board Alan Adler, MD, MS Medical Director Independence Blue Cross Madeleine Biondolillo, MD Director, Healthcare Safety and Quality Massachusetts Department of Public Health Paul Bluestein, MD Chief Medical Officer Connecticare Anthony Bonagura, MD Medical Director Aetna Inc. Philip M. Bonaparte, MD Chief Medical Officer Horizon NJ Health D. Kete Cockrell, MD Medical Director International Medical Group Pat Deverka, MD, MS, MBE Senior Research Director Center for Medical Technology Policy Stan N. Finkelstein, MD Co-Director, Program on the Pharmaceutical Industry Director, Harvard-MIT Division of Health Sciences & Technology Massachusetts Institute of Technology Howard Garber, MD, MPH Medical Director Johns Hopkins Health Care Mary Parish Gavinski, MD Chief Medical Officer Community Care Annetine Gelijns, PhD Co-Director International Center for Health Outcomes and Innovation Research (InCHOIR) Columbia University Uwe G. Goehlert, MD, MSC, MPH, MBA, FAAFP Staff Physician Northwestern Medical Center Department of Emergency Medicine Steven E. Goldberg, MD, MBA VP and Chief of Medical Affairs Express Scripts Atul Grover, MD, PhD Associate Director Association of American Medical Colleges Humberto Guerra-Garcia, MD, MPH, FACP Chief Medical Officer United Healthcare Community PlanDelaware
Leo M. Hartz, MD, MHM VP Clinical Advocacy/Chief Medical Officer Blue Cross of Northeast PA
Gary R. Proctor, MD Chief Medical Officer, Federal Division ValueOptions Inc.
Barry K. Herman, MD, MMM Executive Medical Director Clinical Research and Medical Affairs Sunovion Pharmaceuticals, Inc.
John W. Richards Jr., MD, MMM, CPE President/CEO Innovative Health Strategies
Kathy Hudson, PhD Director, Genetics and Public Policy Center Johns Hopkins University Thomas Kaye, RPh, MBA, FASHP Senior Pharmacy Director Passport Health Plan Stephen Keir, DrPH Co-Director Center for Quality of Life/Supportive Care Research Robert Preston Tisch Brain Tumor Center Duke University Medical Center Fernando C. Larach, MD, FACR, MBA President A-Bay Area Medical Clinics, PA Catherine Marino, MD Chief Medical Officer MagnaCare Jeff Martin, PharmD Clinical Account Director Innoviant Inc. Peter W. McCauley Sr., MD, CPE Medical Director Gottlieb/West Towns PHO Inc. Wesley Mizutani, MD Talbert Medical Group Thomas Morrow, MD Director Genentech Lawrence Mullany, MD, MBA Medical Director United Healthcare Ray Mummery, MD, CMCE Chief Medical Officer, Dimension Health Denis O’Connell, MD Regional Medical Director Blue Cross Blue Shield of NC A. Mark Parker, MD, MBA Medical Director Quality Assessment Systems Inc.
4 Journal of Managed Care Medicine | Vol. 15, No. 1 | www.namcp.org
Kevin Roache, MD, MMM, CPE, FACPE Vice President Medical Affairs Peoples Health, Inc. Aran Ron, MD, MBA, MPH President and Chief Operating Officer Group Health Inc. Mark R. Rosenberg, MD, PhD President/CEO BHM Healthcare Solutions Jay Schechtman, MD, MBA Senior VP, Chief Medical Officer Healthfirst Nancy Single, PhD Assistant Director for Strategic Planning and Program The Ohio State University Comprehensive Cancer Center Robert H. Small, MD Behavioral Health Medical Director TriWest Healthcare Alliance Jacque J. Sokolov, MD Chairman SSB Solutions Scott Spradlin, DO, FACPF, ACOI VP Medical Affairs/Chief Medical Officer Group Health Plan Bruce Steffens, MD Market Medical Director Iowa– Central Illinois United Healthcare William D. Strampel, DO, FACOI Dean, Michigan State University College of Osteopathic Medicine Jeff Taylor, RPh, MS Pharmacy Director Aetna Prentiss Taylor Jr., MD Regional Medical Center Director Advocate Health Care Pam Thomas, MD, MPH, FACOEM Consulting Medical Director Wellness, Health and Productivity Management Strategies
Improving Outcomes and Reducing Costs with Minimally Invasive Procedures William E. Johnson, MD, MBA
Summary Techniques for performing surgery which minimize the number and size of incisions are becoming more prevalent and accepted. Developing a program to encourage appropriate use of minimally invasive surgical procedures can provide significant clinical and financial benefits for patients, payors, and employers. Key Points • Minimally invasive procedures are performed through small incisions or a natural orifice. • The adoption rate for minimally invasive procedures varies by type of surgery and area of the country. • The goal should be to have 90 to 95 percent of appropriate procedures done in a minimally invasive manner. • These procedures provide significant clinical benefits including less pain, less scarring, decreased infection, and shorter length of stay. • Minimally invasive procedures improve outcomes and provide signifigant savings, which will help decrease the rising cost of healthcare.. • A program to encourage appropriate use of minimally invasive procedures can be developed and implemented based on the individual needs of an organization. • Even without a structured benefit design program, educational programs about minimally invasive surgery can drive change in the marketplace.
Minimally invasive surgeries are procedures performed through small incisions or a natural orifice using video cameras and specialized instrumentation. This approach is often referred to as laparoscopic surgery. The revolution in surgical procedures began in the early 1980s when one large incision was replaced with multiple small incisions. The first procedures done in this manner were appendix and gallbladder removals. As this revolution occurred, advantages of small incisions were seen. The revolution came about because of technological advances in surgical tools and the development of cameras for visualizing through small spaces. The next evolution was to do these operations through even smaller and fewer incisions, ultimately down to only one tiny incision. The next progression was to perform natural orifice surgery, which is currently in its infancy. There are limitations to natural orifice surgery because of limited orifices and internal areas that can be reached from these openings.
Approximately 4.4 million open procedures are performed annually, many could be done with a minimally invasive approach. The adoption rate for minimally invasive procedures (MIP) varies by type of surgery and area of the country (Exhibit 1). This exhibit shows where the opportunities are to increase the rate of MIP. Managed care’s goal should be to have 90 to 95 percent of appropriate procedures done in a minimally invasive manner. There are major clinical benefits of MIP compared to open surgical procedures. There is less pain, scarring, and recovery time. Additionally, there are shorter length of hospital stays.1 With certain procedures, there are lower nosocomial infection and readmission rates.2 The benefits of MIPs varies by procedure (Exhibit 2).3-7 Lower rates of nosocomial infections have been seen with cholecystectomy and hysterectomy.2 MIP reduces the odds of readmission with nosocomial infection by 65.4 percent. Reducing nosocomial infections has a significant impact
www.namcp.org | Vol. 15, No. 1 | Journal of Managed Care Medicine 5
Exhibit 1: MIP Adoption Rates
Procedure Rate of MIP Cholecystectomy – Removal of the Gallbladder
95%
Reflux Surgery – Surgery of Gastroesophageal Reflux Disease
90%
Bariatric Surgery – Weight Loss Surgery
90%
Appendectomy – Removal of Appendix
82%
Hysterectomy – Removal of Uterus
44%
Ventral Hernia Surgery – Abdominal Repair
35%
VATS – Pulmonary Wedge Resection
35%
Colectomy – Partial or Complete Removal of Colon
28%
VATS – Lobectomy
27%
Inguinal Hernia Surgery – Groin Repair
19%
Hemorrhoidectomy – Removal of Hemorrhoids
9%
VATS, video assisted thoracic surgery
on reducing costs. Return on investment (ROI) is immediate and sustainable with an MIP program.3 In addition to savings from reduced length of stay, reduced need for pain medications, and reduced infections, additional savings are generated by having many of the procedures done on an outpatient basis. The overall cost impact of MIP versus open procedures is shown in Exhibit 3.1,3 For employer groups, there is a clear ROI. Employees are quicker to return to work and other normal activities. This leads to reduced absenteeism and improved presenteeism leading to increased productivity.7 The length of short-term disability is also shortened with MIPs.8 Based on best practices of plans throughout the country, a 10-step process for implementing a MIP program is outlined in Exhibit 4. Steps one through three are necessary for a plan to develop ideas and identify areas of opportunity. Continuing through all 10 steps will lead to a fully integrated MIP program. Based on an organization’s needs, interests, and objectives, a few or all steps may be chosen. For a managed care organization to increase the rates of MIPs, they need to know their data (Step 1). Each region in the country has different adoption rates for these procedures. Based on their own data, plans can calculate the potential costs savings
for implementing a MIP program. Additionally, before implementation, plans have to do geographic mapping of their MIP trained surgeons. This will identify gaps in availability (Step 5). The goals of an MIP program are to enhance outcomes and improve quality which will ultimately reduce costs. Even if a plan does not implement an entire benefit design program, educating the plan’s market on the benefits of MIP can help drive the shift in procedures from open to minimally invasive and from inpatient to outpatient. This education may be communicated through the plan’s website, newsletters, or educational mailings. Exhibit 5 provides several examples of MIP programs from across the country. Discussions of two examples follow: The Colorado Springs School District is a selffunded organization with 6400 covered lives. This group was looking for cost savings on health care in order to have more money for direct education of their children. This group involved all players in deciding how to save money. They provided a financial copay incentive for having a MIP. Initially, colectomy, hysterectomy, and cholecystectomy were the included procedures. A year later, bariatric surgery was added. To make the program a success, the provider directory identified MIP trained surgeons and MIP education was pro-
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Exhibit 2: MIP Has Been Shown to Reduce Risk of Complications and Length of Stay3-7
Reduction in Reduction in incidence Reduction in overall Reduction in infection rates of sepsis complications length of stay (Blood infection) Colectomy
37%
64%
31%
4.2 days
Appendectomy
20%
55%
34%
.64 days
LH versus TAH
17%
50%
41%
1.1 days
VH versus TAH
22%
50%
17%
.96 days
VATS Lobectomy
Not Significant
Not Reported
14.8%
1.68 days
VATS Pulmonary Wedge Resection
72%
Not Reported
Not Reported
1.90 days
LH = Laparoscopic Hysterectomy VH = Vaginal Hysterectomy TAH = Total Abdominal Hysterectomy VATS = Video assisted thoracic surgery
P <.05, VATS P = 0.000 † When comparing open versus laparoscopic approaches and controlling for the following factors: age, gender, type of insurance, case mix index and complexity of disease
Exhibit 3: MIP Impact on Overall Costs1-3
MIP Versus Open Difference in Cost of Episode of Care Colectomy
$15,181*
Cholecystectomy
$3,299*
Appendectomy
$700–$1,032*
Hysterectomy
$1,218*
VATS – Pulmonary Wedge Resections
$2,582
VATS – Lobectomy
$12,817
*Risk Adjusted
vided at open enrollment and throughout the year. Primary care providers were also informed about the program. This group achieved a two-year savings of $1 million and 100 percent adoption rate of MIP for colectomy, cholecystectomy, and bariatric surgery (Exhibit 6). ODS Health implemented a MIP program for their own employees and provided both an educational program and a valued based imbedded program for their clients. To begin the process, ODS
Health analyzed their surgery data and compared it with available national data and data from national leaders in MIP implementation. This group focused on moving procedures from open to minimally invasive and from inpatient to outpatient setting. They calculated their procedure volume, total costs for each episode of care, percentage of inpatient and outpatient, and percentage of MIP and open procedures. This allowed them to find areas of opportunity. For example, 92 percent of gallbladder surger-
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Exhibit 4: 10 Steps to Implementing MIP 1. Analyze opportunity Evaluate opportunities for MIP versus conventional surgery using actual surgical data. 2. Identify target Based on data from step 1, determine plan’s level of commitment to MIP and which surgical procedures to include. 3. Develop business plan Create the plan’s strategic business objectives, business plan, and value proposition for internal teams and employer customers. 4. Design benefit plan 5. Build provider directory Building a network of MIP providers will help members and PCPs navigate the available options. 6. Educate patients It is important to give patients the information they need - about outcomes, benefits, and even payment reductions - to make good decisions about surgery. 7. Provide health coaching Today’s health care providers help patients manage a variety of conditions so it’s critical to give them what they need to best serve their patients. 8. Integrate with CM/DM Tools can help facilitate communication with Case Manager or Disease Manager who may be involved in a patient’s decision to choose MIP. 9. Inform providers Regular communication with providers is critical, from education programs to bulletins that enhance their skills and help them stay abreast of benefit changes. 10. Celebrate. Assess. Once MIP is up and running in the organization, the next step is planning the evaluation.
Exhibit 5: Selected Examples
Organization Location Outcome Date Initiated Colorado Springs School CO Co-pay differential for MIP District 11 Pre-authorization initiated Employee Education MIP Trained Surgeons designated in directory
July 2007
Colorado Springs Utilities CO Co-pay differential for MIP Pre-authorization initiated Employee Education
January 2010
Hannaford Bros. ME Co-pay differential for MIP Pre-authorization initiated Employee Education MIP surgeons certified/FLS
January 2009
Clovis Community CA Co-pay differential for MIP Medical Center Pre-authorization initiated Employee Education
January 2010
Whirlpool MI Co-pay differential for MIP Pre-authorization initiated Employee Education
January 2010
8 Journal of Managed Care Medicine | Vol. 15, No. 1 | www.namcp.org
Exhibit 6: Colorado Springs School District 11 Two-Year Outcomes
Procedure
2007 MIP Adoption Rates
2009 MIP Adoption Rates
Hysterectomy
28%
81%
Cholecystectomy
93%
100%
Colectomy
33%
100%
Bariatric Surgery
93%
100%
Two-year savings of $1 Million
ies were already being done as MIPs but 37 percent were still done on an inpatient basis which was an area of opportunity. ODS Health implemented a copay differential for MIP versus open procedures. If a patient could have a given procedure done minimally invasive, the copay was much lower. Options for plans include waiving the copay, a reduced amount of copay, or a reduced coinsurance. If a patient could not have a MIP or chose to not have it done, they were not penalized with higher costs. Some plans may choose to have increased out-of-pocket costs for open procedures. In 2010, ODS Health implemented their program with outpatient cholecystectomy, hysterectomy, colectomy, fundoplication, and non-emergent appendectomy. The next phase to be implemented will include bariatric surgery, ventral hernia repair, VATS wedge or lobectomy, and inguinal hernia.
3. Fullum TM, Ladapo JA, Borah BJ, et al. Comparison of the clinical and economic outcomes between open and minimally invasive appendectomy and colectomy: evidence from a large commercial payor database. Surg Endosc. 2010;24:845-53. 4. Warren L, Ladapo JA, Borah BJ, Gunnarsson CL. Open abdominal versus laparoscopic and vaginal hysterectomy: analysis of a large United States payer measuring quality and cost of care. J Minim Invasive Gynecol. 2009;16:581-8. 5. Whitson BA, Groth SS, Duval SJ, et al. Surgery for early-stage non-small cell lung cancer: a systematic review of the video-assisted thoracoscopic surgery versus thoracotomy approaches to lobectomy. Ann Thorac Surg. 2008;86:200816; discussion 2016-8. 6. Howington JA, Gunnarsson C, Maddaus MA, et al. In-hospital Clinical and Economic Consequences of Pulmonary Wedge Resections for Cancer Using Video-Assisted Thoracoscopic Techniques vs. Traditional Open Resections: A Retrospective Database Analysis. Chest. 2011 Jul 21. [Epub ahead of print] 7. Roumm A, Pizzi L, Belsky A, et al. Minimally invasive: minimally reimbursed? An examination of six laparoscopic surgical procedures. Surg Innov. 2005;12:261-87. 8. The Reed Group - Medical Disability Advisor. Duration Guidelines. Available at www.mdguidelines.com. Accessed on 2/23/2011.
Conclusion
Minimally invasive procedures provide significant patient and payor benefits. A minimally invasive procedure program can be developed and implemented based on the individual needs of an organization. Such a program provides significant improvements in outcomes and quality for the patient, and it provides cost savings. JMCM William E. Johnson, MD, MBA is the Senior Vice President and Chief Medical Officer of ODS Health in Portland, OR.
References 1. Gunnarsson C, Rizzo JA, Hochheiser L. The effects of laparoscopic surgery and nosocomial infections on the cost of care: evidence from three common surgical procedures. Value Health. 2009;12:47-54. 2. Brill A, Ghosh K, Gunnarsson C, et al. The effects of laparoscopic cholecystectomy, hysterectomy, and appendectomy on nosocomial infection risks. Surg Endosc. 2008; 22:1112-8.
www.namcp.org | Vol. 15, No. 1 | Journal of Managed Care Medicine 9
Outcomes and Cost Effectiveness of Collaborative Care Disease Management Approach in Depression Patients Roueen Rafeyan, MD For a CME/CEU version of this article, please go to www.namcp.org/cmeonline.htm, and then click the activity title.
Summary There are many reasons why it is important for managed care systems to ensure adequate treatment of depression in their patients. The best chance for achieving and maintaining remission of symptoms occurs when the patient is treated early in the disease process with combination therapy and has complicating comorbid conditions adequately treated. Because the majority of depression is treated in the primary care setting, managed care should consider implementing some type of integration of behavioral health into primary care to improve the outcomes and cost effectiveness of depression treatment. Key Points • The impact of major depression on patients, families, and society can be devastating. • Depression is frequently associated with and may negatively impact medical disorders. • Depression may result in structural and functional changes in the brain. • Comorbid anxiety, substance abuse, and chronic pain can complicate treatment of depression and must be addressed. • Integration of behavioral health into primary care management can improve outcomes and reduce overall costs.
In any given year, 19 million American adults, 9.5 percent of the population in the United States, suffer from depressive disorders. The incidence rate of depression among the general population is 17 to 24 percent. In females, the incidence rate is closer to 24 percent. The average age of onset 50 years ago was 29 but today is 14.5 years. There is an urgency to treat this disease for several reasons. When untreated, this may be a fatal disease. Those suffering from major depression may experience suicide rates of 10 to 15 percent. Depression is the leading cause of disability in the U.S. By 2020, it is projected that depression will be the leading cause of disability worldwide. Depression leads to lowered work productivity. Presenteeism, low performance while at work transformed to lost workday equivalents, is a major issue for employers.1 Thirty to 67 percent of the workplace costs of depression are related to presenteeism.1,2 Physicians should ask their patients about work functioning to determine treatment efficacy. Absenteeism related to depression is also a major
employer issue. Patients with painful physical symptoms of depression miss an average of 9.4 days per month, while patients with depression but not pain miss 4.5 days of work.3 Depression also affects families. As shown in the STAR*D trial, remission of a mother’s depression has a positive impact on both mothers and their children (Exhibit 1).4 Unsuccessful treatment of a mother’s depression can lead to depression, anxiety, and behavior issues in her children. Depression has a significant effect on health scores, especially when the patient has another chronic disease. The most impact on health scores is seen with the combination of diabetes and depression.5 It is very difficult to control diabetes and other chronic diseases in the depressed patient. There is also a relationship between depression and stroke. Depression increases the risk of stroke significantly.6 It also increases the risk of stroke mortality. Patients with five or more depressive symptoms at baseline had increased risk of stroke mortality.7 Stroke patients have an increased risk of developing depression.8 Post-stroke depression independently
10 Journal of Managed Care Medicine | Vol. 15, No. 1 | www.namcp.org
% of Children with Diagnosis of Any Depressive, Anxiety, or Disruptive Behavior Disorders
Exhibit 1: STAR*D: A Mother’s Depression and Remission Impact the Next Generation4
Diagnosis of Children (Aged 7-17 Years) with Depressed Mothers Baseline 3 Months
100 60 50
Children with no disorder symptoms at baseline (n = 68)
43%
40
35%
30
• All those with remitting mothers remained symp tom-free
24%
20 10 0 HAM-D17 Total = 14
Children of Mothers Who Children of Mothers Did Not Remit (n = 76) Who Remitted (n = 38)
increases risk of death by 13 percent.9 There are similar findings in a relationship between depression and cardiovascular disease. The prevalence of depression is increased between 15 and 25 percent in coronary artery disease, acute myocardial infarction (MI), angina, and heart failure.10 Depressed patients have an increased risk for MI, cardiac death, and mortality from all causes.11 Depression post-MI is associated with a fourfold increase in risk of mortality in the six months after the MI.12 Another urgent reason to treat depression is that repeated episodes of depression are associated with functional and structural changes in the brain.13
• 17% of children with non-remitting mothers acquired a disorder within 3 months
Aggressive, early, and sustained treatment might prevent the disease from becoming chronic with eventual neuronal damage and chronic progressive neurodegenerative disease.14 The first few episodes of depression in an individual may be caused by psychosocial stressors – loss of job, spouse, etc (Exhibit 2).15 After three episodes, the patient has greater than a 90 percent chance of another relapse. After about the fifth or sixth episode, depressive episodes continue without psychosocial stress. It appears that this is due to changes in the brain with atrophy in certain areas. Treatment for depression includes biological inter-
Exhibit 2: Progression of Depression: Adverse Effects of Each Successive Episode15
10 Likelihood of recent life stress precipitating depression
Risk (Odds Ratio)
8
Risk (OR) of depression onset per month
6 4 2 0
Female subjects only N = 2395 0
1
2
3
4
5
6
7-8
9-11
Number of Previous Depressive Episodes
www.namcp.org | Vol. 15, No. 1 | Journal of Managed Care Medicine 11
Exhibit 3: STAR*D Trial Results19 Step
Regimens
Remission Rates
Step 1
Citalopram 40 mg/day
25.4%
Step 2
Switch to either Bupropion SR, Sertraline, Venalfaxine XR, Cognitive behavioral therapy (CT), CT + Citalopram, Citalopram + Bupropion SR, or Citalopram + Busprione
25.1%
Step 3
Switch to either Mitrazepine, Nortriptyline, Lithium + Bupropion SR, Sertraline, Venalfaxine XR, or Citalopram
17.8%
Step 4
Switch to Tranylcypromine or Mitrazepine + Venalfaxine XR
10.1%
Exhibit 4: Interventions to Reduce Noncompliance • Educate patients regarding the disease and treatment options. • Discuss common side effects of the antidepressant medication openly with patients. • Reassure patients that other medication options will be explored in case of side effects. • Emphasize that these medications need to be taken on a daily basis to be effective. • Reassure patients that antidepressant medications are not addicting and they do not cause end-organ damage. • Share with patients that continued treatment with medication has a neuro-protective effect.
ventions (antidepressants), psychological interventions (psychotherapy), and social interventions. Social interventions help the patient get out of problem social situations such as an abusive marriage. The biopsychosocial approach, which combines all of these interventions, is the most effective. The goal of depression treatment is to achieve remission (no symptoms) and keep the patient in remission. Patients who reach remission have functional ability equivalent to those without depression. Those who only respond to treatment (~50 percent reduction in symptoms) are as functionally impaired as those who do not respond to treatment. Unfortunately, many patients receive inadequate treatment. Some studies have shown that about 50 percent of patients with major depression receive some type of treatment but only 22 percent receive adequate treatment.16 The best rate of recovery for depression patients is during the first six months of symptoms.17 After that, it becomes more difficult for patients to recover. Clinicians may think their patients are responding well to medications but without the use of validated tools like the Hamilton Depression scale, it may be
impossible to tell if the patient has achieved remission. Different depression symptoms respond differently to medications. Emotional symptoms tend to improve more than physical symptoms, especially pain. Improving painful symptoms greater than 50 percent increases the likelihood of remission. Additionally, the fewer symptoms a patient has remaining after treatment, the longer the time till relapse (231 weeks versus 68 weeks).18 The STAR*D trial examined the effectiveness of various antidepressants in achieving remission. Forty-three percent of the study sites in this trial were in primary care. This trial used a stepped approach. The remission rates and the regimens at each step are shown in Exhibit 3.19 This trial illustrates that the remission rate declines with each additional step in therapy. Unfortunately, only about one-fourth of patients will achieve remission with the first treatment chosen. Noncompliance is an important reason for suboptimal treatment outcomes. Seventy-five percent of antidepressants are discontinued by month four. Patients frequently report that the medication was not
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Exhibit 5: The Continuum of Integration Model Desirability
Attributes
Separate Space and - - Mission
Traditional BH Specialty Model
1.1 Referral Relationship +
Preferred provider/ limited information exchange
Co-location ++ On-Site BH Unit/ Separate Team Collaborative Care +++
On site/shared cases w/BH Specialist
Integrated Care +++++
BHC as PC Team Member
BH, behavioral health; pc, primary care
effective after a week, made them feel worse, or they stopped because they felt better. Some interventions to reduce noncompliance are shown in Exhibit 4. Management of patients who are not responding to treatment includes reconsidering the diagnosis and referring the patient to a psychiatrist. It may require case management, involving pharmacists to monitor medication compliance, and more aggressive pharmacotherapy. One option for more aggressive therapy is to add a second-generation antipsychotic agent to target dopamine, which is not targeted by most antidepressants. The second-generation antipsychotics which are FDA approved for add-on therapy in depression are aripiprazole, olanzapine in combination with fluoxetine, and quetiapine. Adding these agents can lead to a quick improvement in depression scores. Depression has a high comorbidity with many conditions such as anxiety disorders which can complicate treatment. High anxiety levels are associated with higher suicide risk and reduced remission rates. Patients with high levels of anxiety frequently utilize medical services. Anxiety needs to be addressed with aggressive treatment. Short-term use of benzodiazepines, along with antidepressant medication, is recommended for these patients. Patients can be referred for individual therapy; cognitive behavioral therapy (CBT) is most effective in the setting of comorbid anxiety. Although frequently missed in clinical interviews, substance abuse and dependence significantly impacts the effectiveness of depression treatment. Some type of substance abuse screening should occur in all patients with depression and those who are positive should be referred for treatment of their substance
issues. These patients need to be educated that treating depression and anxiety in the presence of active drug or alcohol abuse is minimally effective and at times dangerous. Clinicians need to avoid getting frustrated with patients who have repeated substance abuse relapses. Addiction is a chronic disease and requires lifelong treatment. Pain is yet another complicating factor. Chronic pain frequently results in depression and exacerbates existing depression. Depressive symptoms lower pain threshold and result in exaggerated pain response. Improvement of pain symptoms increases the odds for remission. Aggressive treatment of depressive symptoms will allow for better pain management and reduce utilization of medical services. Tricyclic and serotonin norepinephrine reuptake inhibitor (SNRIs) antidepressants are most effective for these patients. Because of their safety and tolerability profile, the SNRIs are preferred Optimizing outcomes in depression requires examining how mental health care is currently delivered. Seventy percent of all primary care visits have psychosocial drivers. Fifty percent of all mental health care services are delivered by a primary care provider (PCP). Sixty- seven percent of all psychoactive agents and eighty percent of antidepressants are prescribed by PCPs. Mental health outcomes in primary care treated patients are currently only slightly better than spontaneous recovery. One way to improve the delivery of mental health care is to integrate primary care and behavioral health practices. There are numerous benefits of integration. Some of the benefits include improved recognition of mental health disorders, improved PCP skills in medication prescription practices, and
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increased use of behavioral interventions by PCPs. Integration has been shown to improve depression remission rates, self management skills for patients with chronic conditions, clinical outcomes compared with treatment in either sector alone, and patient adherence and retention in treatment. Initially, integrating behavioral health increases costs but overall results in reduced costs. Integration adds $264.00 per case of depression treated in primary care. The treatment success rate and overall patient adherence to treatment doubles with this expenditure. The result of integration is a positive cost-effectiveness index of $491.00 per case of depression treated.20 Integration can occur on a continuum (Exhibit 5). The most desirable is to have a behavioral health clinician as part of the primary care team. The hallmarks of a successful primary care behavioral health service include timely access for PCPs, behavioral health care use by all PCPs, the use of behavioral health interventions more frequently by PCPs, and the service is provided as part of the health care process. The behavioral health service should be viewed as a form of primary care delivered to all appropriate patients.
decrements in health: results from the World Health Surveys. Lancet. 2007;370:851-8. 6. Jonas BS, Mussolino ME. Symptoms of depression as a prospective risk factor for stroke. Psychosom Med. 2000;62:463-71. 7. Everson SA, Roberts RE, Goldberg DE, Kaplan GA. Depressive symptoms and increased risk of stroke mortality over a 29-year period. Arch Intern Med. 1998;158:1133-8. 8. Aben I, Denollet J, Lousberg R, et al. Personality and vulnerability to depression in stroke patients: a 1-year prospective follow-up study. Stroke. 2002;33:2391-5. 9. Williams LS, Ghose SS, Swindle RW. Depression and other mental health diagnoses increase mortality risk after ischemic stroke. Am J Psychiatry. 2004;161:1090-5. 10. Musselman DL, Evans DL, Nemeroff CB. The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment. Arch Gen Psychiatry. 1998;55:580-92. 11. Barefoot JC, Schroll M. Symptoms of depression, acute myocardial infarction, and total mortality in a community sample. Circulation. 1996;93:1976-80. 12. Frasure-Smith N, Lespérance F, Talajic M. Depression following myocardial infarction. Impact on 6-month survival. JAMA. 1993;270:1819-25. 13. Nestler EJ, Barrot M, DiLeone RJ, et al. Neurobiology of depression. Neuron. 2002;34:13-25. 14. Manji HK, Quiroz JA, Sporn J, et al. Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression. Biol Psychiatry. 2003;53:707-42. 15. Kendler KS, Thornton LM, Gardner CO. Stressful life events and previous
Conclusion
Depression has a major impact on patients, families, employers, managed care, and society. Effective management to achieve remission and prevent longterm brain changes requires a biopsychosocial approach and addressing complicating comorbidities. When seeking to improve depression outcomes in their patient population, managed care should consider integration of behavioral health services into primary care delivery. JMCM
episodes in the etiology of major depression in women: an evaluation of the “kindling” hypothesis. Am J Psychiatry. 2000;157:1243-51. 16. Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003;289:3095-105. 17. Keller MB, Lavori PW, Mueller TI, et al. Time to recovery, chronicity, and levels of psychopathology in major depression. A 5-year prospective follow-up of 431 subjects. Arch Gen Psychiatry. 1992;49:809-16. 18. Judd LL, Akiskal HS, Maser JD, et al. Major depressive disorder: a prospective study of residual subthreshold depressive symptoms as predictor of rapid relapse. J Affect Disord. 1998;50:97-108.
Roueen Rafeyan, MD is Medical Director at the Behavior Health Psy-
19. Pigott H, Leventhal A, Alter G, Boren J. Efficacy and Effectiveness of Antide-
chiatric and Substance Abuse Program and is an Assistant Professor in
pressants: Current Status of Research. Psychother Psychosom. 2010;79:267–79.
the Department of Psychiatry at Rush University.
20. Von Korff M, Katon W, Bush T, et al. Treatment costs, cost offset, and costeffectiveness of collaborative management of depression. Psychosom Med.
References
1998;60:143-9.
1. Kessler RC, Akiskal HS, Ames M, et al. Prevalence and effects of mood disorders on work performance in a nationally representative sample of U.S. workers. Am J Psychiatry. 2006;163:1561-8. 2. Greenberg PE, Kessler RC, Birnbaum HG, et al. The economic burden of depression in the United States: how did it change between 1990 and 2000? J Clin Psychiatry. 2003;64:1465-75. 3. Demyttenaere K, Bonnewyn A, Bruffaerts R, et al. Comorbid painful physical symptoms and depression: prevalence, work loss, and help seeking. J Affect Disord. 2006 ;92:185-93. 4. Weissman MM, Pilowsky DJ, Wickramaratne PJ, et al. Remissions in maternal depression and child psychopathology: a STAR*D-child report. JAMA. 2006;295:1389-98. 5. Moussavi S, Chatterji S, Verdes E, et al. Depression, chronic diseases, and
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Treatment Strategies in the Management of Rheumatoid Arthritis Wesley Mizutani, MD, MBA For a CME/CEU version of this article, please go to www.namcp.org/cmeonline.htm, and then click the activity title.
Summary Without effective treatment, rheumatoid arthritis (RA) is a leading cause of disability. Early diagnosis and effective treatment reduces joint damage, disability, and comorbidities. Biologic DMARDs play a significant role in effective treatment but can result in significant adverse effects such as infections. Managed care can reduce the risk of infections with these agents by implementing proactive prevention guidelines. Key Points • Early diagnosis and treatment leads to better outcomes. • Early successful treatment can also prevent comorbidities. • Measuring RA activity with valid tools is critical to successful treatment outcomes. • Measuring therapy response every three months and adjusting therapy accordingly improves outcomes. • Managed care should consider proactive guidelines for preventing infections in patients treated with biologic DMARDs.
Rheumatoid arthritis (RA) has a significant impact on patients. Approximately 2.2 million adults in the United States have RA. Seventy-five percent of these patients are women. One in three percent of women will develop RA in a lifetime. RA is the leading cause of chronic disability per capita. Twenty to 30 percent of RA patients become permanently disabled during the first three years of disease. It also results in reduced life expectancy. Studies have shown a variety of comorbidities associated with RA, including chronic obstructive pulmonary disease, heart failure, coronary artery disease, dementia, and lymphoma. The patient does not die from their joint disease but succumbs because of the accelerated comorbid conditions. Early treatment has been shown to improve the outcomes achieved with this disease. A study was done comparing RA patients who were treated within two weeks of diagnosis to those that had a delay in treatment of three months after diagnosis. The RA patients who had delayed treatment had five times as many erosions as did the early treat-
ment group at 24 months.1 Anderson and colleagues showed that the longer a patient with RA has the disease the less likely they are to respond to treatment.2 A methodological approach to treatment can also result in better outcomes. The BeSt trial looked at patients with early RA (less than two years) and compared methotrexate (MTX) gradual escalation, MTX in combination with disease modify antirheumatic drugs (DMARDs), and MTX in combination with tumor necrosis factor (TNF) inhibitors (biologic DMARD).3 Validated outcome measures of efficacy were used to choose treatment dosing. After one year, 74 percent of patients in the MTX/ TNF inhibitor group achieved low-level disease activity. At four years, 49 percent of patients in all groups maintained a remission, based on the Disease Activity Score. There was evidence that the MTX/ TNF inhibitor group had significantly less radiographic progression then did the other treatment groups. In fact, 51 percent of the biologic group was able to discontinue therapy by four years and remain disease free for 35 months. If the biologic therapy
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Exhibit 1: 2010 ACR Guidelines for RA5 • Have at least one joint with definite clinical synovitis • Need score of 6/10 or greater based on following Joints involved • 1 large joint = 0 • 2-10 large joints = 1 • 1-3 small joints = 2 • 4-10 small joints = 3 • > 10 joints = 5 Serology • Negative RF and CCP = 0 • Low positive RF or low positive CCP = 2 • High positive RF or high positive CCP = 3 Acute phase reactants • Normal CRP or ESR = 0 • Abnormal CRP or ESR= 1 Duration of Symptoms • < 6 weeks = 0 • > 6 weeks = 1 RF, rheumatoid factor; CCP, anti-cyclic citrullinated peptide antibody; CRP, C reactive protein; ESR, Erythrocyte Sedimentation Rate
Exhibit 2: Biologic DMARDs
TNF Inhibitors • Etanercept • Infliximab • Adalimumab • Certolizumab pegol • Golimumab
Anti IL1 •Anakinra Anti T cell •Abatacept Anti IL6 •Tocilizumab Anti B cell •Rituximab
IL, interleukin
initiation was delayed, less then one-third were able to discontinue biologic therapy without flare. Because patients die from comorbid diseases, studies have tried to establish whether early treatment improves outcomes of comorbid disease. Westlake and colleagues performed a meta-analysis which showed cardiovascular (CVD) death in patients ever treated with MTX was reduced by 70 percent compared with those that never took MTX.4 This analysis also showed MTX use leading to a clinical response led to a decrease in CVD morbidity by 15 to 35 percent. One large study in the analysis showed a 35 percent decreased risk of CVD events in patients treated with MTX in the year prior to
CVD diagnosis. In 2010, the American College of Rheumatology revised the diagnostic criteria to allow for earlier diagnosis (Exhibit 1).5 The criteria are heavily weighted on small joints versus large joints and now allows for seronegative early RA. To achieve optimal outcomes, clinicians need to use a standardized methodology to evaluate RA patients and then adjust treatment. The BeSt trial implemented a “tight control” goal which explains why their results far surpassed prior trials using MTX monotherapy or combination therapy.3 In that trial, the need for therapy adjustments was determined by the Disease Activity Score (DAS) every three months. Thus, measuring therapy response every three months and adjusting therapy accordingly improves outcomes. There are three benchmark validated measures to assess therapy efficacy. These include the DAS 28, Clinical Disease Activity Index (CDAI), and Rapid 3. The DAS 28 scores 28 different joints on tenderness and swelling. The CDAI is a patient administered visual analogue scale and physician assessment. Community rheumatologists may complain they do not have time to do these standardized measures. Rapid 3 is a patient survey that has some validation if used to treat to a target. The nonbiologic DMARDS include hydroxychloroquine, sulfasalazine, MTX, and leflunomide. MTX is still considered the gold standard, first-line agent. Leflunomide is used in those patients who cannot tolerate MTX or have failed it but are not yet ready to move on to a biologic. Hydroxychloroquine and sulfasalazine are considered third-line agents. Combination therapy with nonbiologic DMARDs has fallen out of favor since the introduction of biologic agents. Exhibit 2 lists all the biologic DMARDs for treating RA. When considering the biologic agents, there really is no proven difference in efficacy among them. Until there are more head-to-head studies, one cannot argue that one agent is better than another. In general, 60 percent of patients will have a 20 percent improvement (ACR20) when started on a biologic agent, 40 percent will have a 50 percent improvement (ACR50), and 20 percent will have a 70 percent improvement (ACR70). The side effect profiles are similar with a primary focus on malignancies and infections. Higher disease severity in RA has been associated with a greater risk of lymphoma. Whether biologics increase risk for lymphoma beyond this inherent risk is unclear. The biologic agents do increase risk for infections, particularly opportunistic infections, and tubercu-
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losis (TB). There are several risk reduction strategies for infections. Biologics should be temporarily stopped in patients with significant infections that require antibiotic treatment. All patients who are being considered for biologic treatment should be screened for latent TB. It is important to recognize that many RA patients may be anergic so that a negative TB test may not be accurate. Patients with a positive TB test and negative chest x-ray should receive treatment for latent TB if: • They reside in an institutional setting. • They have a history of Substance Abuse. • They work in a setting where there are TB patients. • They have CXR evidence of prior TB. • They frequent endemic areas where TB incidence is high. Patients with a history of BCG vaccination will always have a positive PPD test. If they also have a negative chest x-ray, the clinician should consider using a test for the release of interferon gamma using TB specific antibodies (QuantiFeron TB Gold or TSPOT.TB). Patients with a positive test and negative chest x-ray but who have never received treatment for latent TB should be treated prior to initiation of biologic unless contraindicated. Managed care should consider implementing proactive guidelines to prevent infections in patients on biologic DMARDs. Proactive guidelines should include TB screening, TB treatment, and holding biologic therapy during active infections.
improved outcomes. Early successful treatment can also prevent comorbidities. Tools to measure RA activity are critical to successful treatment outcomes. Proactive guidelines relating to infections with biologics is a potential area of intervention by managed care. JMCM Wesley Mizutani, MD, MBA is an Associate Clinical Professor of Medicine at UCSD School of Medicine and the Medical Director of Clinical Research with the Talbert Medical Group.
References 1. Lard LR, Visser H, Speyer I, et al. Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies. Am J Med. 2001;111:446-51. 2. Anderson JJ, Wells G, Verhoeven AC, Felson DT. Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration. Arthritis Rheum. 2000;43:22-9. 3. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum. 2005;52:3381-90. 4. Westlake SL, Colebatch AN, Baird J, Kiely P, et al. The effect of methotrexate on cardiovascular disease in patients with rheumatoid arthritis: a systematic literature review. Rheumatology (Oxford). 2010;49:295-307. 5. American College of Rheumatology. 2010 Rheumatoid Arthritis Classification Criteria. Available at http://www.rheumatology.org/practice/clinical/ classification/ra/ra_2010.asp
Conclusion
Early diagnosis and early treatment of RA leads to
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Spirometry: Improving Patient Outcomes and Reducing Overall Costs for COPD Through Early Diagnosis and Annual Assessment Rob Sussman, MD For a CME/CEU version of this article, please go to www.namcp.org/cmeonline.htm, and then click the activity title.
Summary COPD is a costly disease that is responsible for hospitalizations, emergency room visits and general physician outpatient treatments. Spirometry is the gold standard for diagnosing COPD; however, only one in three patients receives a spirometrybased screening. Once COPD is diagnosed, it is important that patients receive annual spirometry to assess the stage of their disease. Key Points • Spirometry must be used to confirm diagnosis of COPD. • The indications for spirometry in COPD include screening high-risk populations, confirming diagnosis, assessing severity, monitoring progression, and assessing suitability for lung volume reduction surgery and transplant. • Smokers with at least one symptom of COPD should be screened with spirometry. • Therapy should be based on disease severity and symptoms. • Smoking cessation is the only treatment that alters progression of COPD.
Chronic obstructive pulmonary disease (COPD) is a preventable, treatable, and progressive disease characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases. In the United States, about 90 percent of COPD is smoking related. COPD results in 1.5 million emergency room visits and more than 700,000 hospital admissions each year. The estimated costs of COPD in 2007 were $49.9 billion per year. Fifty to 75 percent of costs are exacerbation related. As of 2008, COPD is the third leading cause of death in the U.S. The incidence of COPD has risen dramatically in recent years because of very high rates of smokers 20 to 30 years ago. Approximately 21 percent of men and women currently smoke which is much lower than in the past and will eventually lead to lower rates of COPD. Women are more susceptible to the effects of smoke -- they get COPD and lung cancer more often and more of them are dying from the disease. COPD is a disease of airflow limitation and there
is only one way to diagnosis it – spirometry. Spirometry assesses lung function by measuring the total volume of air the patient can expel from the lungs after a maximal inhalation. Underuse leads to inaccurate COPD diagnosis and treatment. In primary care, more than 50 percent of COPD patients are not being diagnosed with spirometry. Portable, hand-held spirometers are available and are accurate for use in screening patients (Exhibit 1). Spirometry measures forced vital capacity (FVC) and forced expiratory volume (FEV1). FVC is the total volume of air that can be forcibly exhaled. FEV1 is the volume of air in the first second of a forced exhalation. Values obtained have to be compared to predicted normal values based on patient age, size, gender, and ethnic origin. For example, a 90-year-old, 4-foot tall woman will not have the same lung capacity as a 20-year-old, 6-foot tall man. A normal FEV1 is 80 percent or greater of predicted. Most important for the diagnosis of COPD is the ratio of FEV1 to FVC which should be 70 to 80 percent. If the ratio is less than 70 percent and the FEV1 is less than 80 percent, the patient has obstruction
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which could be asthma or COPD. The distinguishing factor between these two diseases is whether the obstruction is completely reversible with the use of a bronchodilator. Patients with asthma typically will have complete reversal of their obstruction after a dose of a bronchodilatory, whereas patients with COPD will have improvement in their values but not complete reversal of obstruction. Spirometry results will also include a flow volume loop, which is a visual representation of the obstruction. There are several indications for spirometry in COPD (Exhibit 2). There are some other limited indications including to establish disability, preoperative assessment, and for workplace screening. About 10 percent of cases of COPD in the U.S. are related to chronic workplace exposures. COPD is both overdiagnosed and underdiagnosed. The assumption that everyone who smokes has COPD is incorrect. If someone smokes their entire life, the risk of developing COPD is somewhere between 25 and 50 percent. Most smokers with shortness of breath do not have COPD. Spirometry is essential to avoid misdiagnosis. Accurate testing and interpretation is also necessary. The person conducting and interpreting the test needs to be trained in both methodology and how to recognize submaximal effort of patients during testing. Many patients who are misdiagnosed with this disease get referred to pulmonary specialists because they are not responding to medications. They may have been on multiple different medications. Many patients with pulmonary fibrosis or heart failure are misdiagnosed as having COPD. An incorrect diagnosis subjects patients to side effects from unnecessary medications. It deprives patients of appropriate treatment for the actual condition and costs the health care system. COPD meds can cost $2,000 to $4,000 yearly. Correct diagnosis is important so the proper treatment can be initiated and smoking cessation can be instituted. Eighty-one percent of COPD cases are diagnosed in the moderate to severe stages. If managed care wishes to impact this disease, patients need to be diagnosed earlier. If spirometry is normal, another cause for the patient’s symptoms should be sought. Exhibit 3 shows the stages of this disease from mild to very severe and the treatment at each stage.1 The stepped care treatment approach as defined by the GOLD guidelines uses symptoms and FEV1 to determine treatment. Spirometry helps to determine appropriate treatment based on disease severity (along with symptoms) and determines appropriate usage of inhaled steroids. Inhaled corticosteroids have a role in treating COPD in certain patients. They reduce the frequen-
Exhibit 1: Hand-held Spirometers
Exhibit 2: Spirometry Indications • Confirm diagnosis
YES
• Assess severity
YES
• Response to therapy
NO
• Determine progression
YES (once per year)
• During exacerbation
NO
• Screening smokers
YES (if symptomatic)
cy of exacerbations in COPD patients with an FEV1 less than 50 percent and at least one exacerbation in the prior year (Exhibit 4).2,3 Exacerbations account for 50 to 75 percent of the costs of COPD. Inhaled corticosteroids do not reduce mortality nor do they slow progression of the disease. Additionally, they increase the risk of pneumonia and osteoporosis. Thus, inappropriate use of ICS increases potential for side effects but appropriate use has value. Another area for possible use of spirometry is to measure medication efficacy. In most patients, clinicians usually assess response clinically. Occasionally, spirometric confirmation is helpful but is not routinely recommended. Spirometry should be done if there is a significant increase or decrease in symptoms. A significant decrease in symptoms may mean the patient actually has asthma. Some patients may also have bronchospasm from the inhaled medications. There are no medications that are definitively proven to alter progression in COPD. The only intervention to slow progression is smoking cessation. Because COPD is a progressive disease, spirometry can be used to assess progression to adjust therapy. Lung function will likely worsen over time, even with the best care. Symptoms and spirometry need to be monitored at least yearly. Spirometry is not helpful during a COPD exacerbation. Spirometry is used to evaluate patients for lung transplantation and lung volume reduction surgery.
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Exhibit 3: Treatment by COPD Stage1
Stage 0. At Risk
Stage I. Mild
Stage II. Moderate
Stage III. Severe
Stage IV. Very Severe
Chronic symptoms Exposures to risk factors Normal spirometry
FEV1/FVC<70% FEV1>80% With or without symptoms
FEV1/FVC<70% 50%>FEV1<80% With or without symptoms
FEV1/FVC<70% 30%>FEV1<50% With or without symptoms
FEV1/FVC<70% FEV1<30% or presence of chronic respiratory failure or night heart failure
Avoidance of risk factor(s); influenza vaccination
Add short-acting bronchodilator when needed
Add regular treatment with one or more long-acting bronchodilators Add rehabilitation
Add inhaled glucocorticosteroids if repeated exacerbations
Adapted from Table 8. Initiative Obstructive Lung Disease (GOLD) Executive Summary. Updated 2003. Available at: http://www.goldcopd.com.
Add long-term oxygen if chronic respiratory failure Consider surgical treatments
Exhibit 4: ICS and Exacerbation Reduction2
30.5% Reduction
Annual Rate of Moderate/ Severe Exacerbations
1.8 1.6 1.4
1.53
NNT = 2.1
1.2 1
1.06
0.8 0.6 0.4 0.2 0
LABA
ICS/LABA
LABA, long acting beta agonist; ICS, inhaled corticosteroid
There are three significant criteria for a good screening test: 1) if not detected early, the disease will progress and cause significant morbidity and mortality, 2) treatment is available that is more effective at an early stage of disease, and 3) a safe, costeffective and accurate screening test is available. Screening for COPD with spirometry meets criteria
one and three. For criteria two, in the early stages most patients do not need medications but would benefit from smoking cessation. With smoking cessation, the patientâ&#x20AC;&#x2122;s lung function never goes back to normal but will improve slightly and progression is definitely slowed. Early identification of disease combined with intensive
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smoking cessation efforts should reduce progression to end-stage disease. Screening all smokers is controversial and is probably not cost effective given that not all long-term smokers will develop COPD. A majority of people with early COPD identified in screening programs had at least one symptom. Thus, patients should be screened if at least one symptom such as cough, sputum production, or dyspnea is present. Although many patients and clinicians think smoker’s cough is normal, it usually indicates underlying reduction in lung function. Unfortunately, identifying early COPD does not result in higher smoking cessation rates. Smokers tend to be in denial. Making it personal with a personalized smoking risk assessment may improve rates. This type of approach is under study. This approach combines spirometry results and smoking history to provide an individual assessment of the risk of developing COPD, lung cancer, heart attack and stroke. For example, this type of assessment will give the patient individualized risk numbers for each consequence of smoking. By “personalizing” smoking cessation counseling, the motivation to quit will hopefully improve. Medicare has proposed quality performance stan-
dards for accountable care organizations. For COPD at-risk populations, the proposed measures are spirometry evaluation, smoking cessation counseling, and bronchodilator therapy based on FEV1. Conclusion
The diagnosis of COPD must be confirmed with spirometry. Spirometry is also useful for determining appropriate treatment and monitoring progression. Therapy should be based on disease severity and symptoms. Because smoking cessation is the only treatment that alters progression, COPD needs to be diagnosed early so cessation can be instituted. Personalized smoking risk assessment is under evaluation for improving cessation rates. JMCM Rob Sussman, MD is Co-Director of Clinical Research at Pulmonary & Allergy Associates of NJ.
References 1. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2010. Available from: http://www.goldcopd.org/. 2. Ferguson GT, Anzueto A, Fei R, et al. Effect of fluticasone propionate/salmeterol (250/50 microg) or salmeterol (50 microg) on COPD exacerbations. Respir Med. 2008;102:1099-108.
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Optimizing Treatment Strategies in the Management of Non-Small Cell Lung Cancer Greg Otterson, MD For a CME/CEU version of this article, please go to www.namcp.org/cmeonline.htm, and then click the activity title.
Summary The management of non-small cell lung cancer (NSCLC) continues to evolve as more genetic mutations and other predictive biologic markers are discovered and targeted therapies are developed. Targeted therapies such as bevacizumab, erlotinib, and crizotinib are only appropriate for select groups of patients. The use of targeted therapies is leading to more individualized therapy. Key Points • Survival in NSCLC is dependent on the stage of disease at diagnosis. • Patients with nonsquamous cell NSCLC benefit from bevacizumab and pemetrexed. • Patients with EGFR mutations benefit from erlotinib. • Nonsmokers or light smokers with adenocarcinoma should be tested for EGFR mutation. status in order to make first-line treatment decisions. • Patients with EML-ALK mutations benefit from crizotinib. • Patients without genetic mutations typically benefit from platinum-based chemotherapy.
Lung cancer is the greatest cause of cancer deaths worldwide and in the U.S. There were an estimated 222,520 new cases in 2011 with 157,300 deaths. Lung cancer accounts for 15 percent of cancer cases and 28 percent of cancer deaths. Lung cancer results in more deaths each year than colon/rectum, breast, or prostate cancer. Approximately, 13 percent of cases are in never- smokers (~25-30,000 cases/year). The recent good news with lung cancer was a slight dip in deaths from lung cancer in U.S. women. The overall five-year survival for lung cancer has improved slightly since the 1970s (Exhibit 1).1 Survival in patients with advanced non-small cell lung cancer (NSCLC) has been improved but is still very low (Exhibit 2). Survival in NSCLC is dependent on the stage of disease at diagnosis. Patients in the earliest stages can have a 60 to 70 percent five-year survival compared with a 1 percent five-year survival in advanced disease. Many different groups publish guidelines for managing NSCLC, including the National Comprehensive Cancer Network (NCCN). NCCN
is an organization of 21 cancer centers across the country dedicated to improving the quality and effectiveness of care provided to patients with cancer. NCCN has 135 different guidelines, which are updated yearly. The NCCN guidelines are different from other guidelines because the expert panels explicitly address areas with lower levels of evidence. The expert panel recommendations of other groups are largely driven by high-level evidence (i.e., if a phase III study hasn’t examined the question they state there is insufficient data to address). The levels of evidence used by NCCN are shown in Exhibit 3.2 Before 1995, many oncologists did not give chemotherapy to patients with advanced NSCLC. Cisplatin-based chemotherapy was then shown to improve short-term (up to one year) survival outcomes with metastatic NSCLC and chemotherapy use became more common. After data showed cisplatinbased therapy was beneficial, the next controversy to resolve was the best combination chemotherapy regimen. As long as cisplatin was included in the regimen, a large trial showed that it did not matter in terms of survival which agents were given.3
22 Journal of Managed Care Medicine | Vol. 15, No. 1 | www.namcp.org
Exhibit 1: Five-Year Survival for Lung Cancer1
20
Percent
15
14%
* 15%
12%
10 5 0 1974-1976
1983-1985
1995-2001
*P<0.05 vs 1974-1976
Exhibit 2: NSCLC Advanced Disease Survival
Survival
Best supportive care
1990
2000
2010
Median survival
4 mo
6 mo
8 mo
10 mo
1 yr
10%
20%
30%
40%
2 yr
0%
<5%
10%
15%
The next advancement in therapy for advanced NSCLC was the development of bevacizumab (Avastin速), a recombinant humanized monoclonal antibody to vascular endothelial growth factor (VEGF). Only patients with nonsquamous cell disease (adenocarcinoma or large cell lung cancer) benefit from this agent. The discovery that patients who have certain lung cancer histologies benefit from a particular therapy was a significant advance in the treatment of this disease. Patients with nonsquamous cell NSCLC achieve an improved progression-free survival and a median survival benefit of approximately two months with the addition of this agent to standard chemotherapy.4 The addition of this agent to cisplatin and paclitaxel does increase risk of neutropenia, proteinuria, and bleeding events. With this agent, it was found that patients with squamous cell disease or a history of hemoptysis had an unacceptable risk of death. Another example of where histology NSCLC is important is pemetrexed. Pemetrexed (Alimta速), a chemotherapy agent used primarily in Europe, has shown benefit in patients with nonsquamous cell
disease. The benefit is approximately 1.4 months improvement in median survival.5 Erlotinib (Tarceva速) is a tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor (EGFR). Mutations of the EGFR gene occur in approximately 10 to 13 percent of unselected NSCLC patients. EGFR mutations are more common in women, Asians, adenocarcinomas, and never-smokers.6 Most patients who harbor these mutations have a significant response to erlotinib. In second- or third-line therapy, erlotinib improves median survival by about two months and one-year survival in patients with EGFR mutations.7 Even if the patients with mutations have very poor performance status, erlotinib should be considered. Patients without mutations do not benefit from this agent but do benefit from chemotherapy. Nonsmokers or light smokers with adenocarcinoma should be tested for EGFR mutation status in order to make first-line treatment decisions. If mutation status is positive, the patient should receive erlotinib first line. If mutation status is negative or unavailable, the patient should receive chemotherapy.
www.namcp.org | Vol. 15, No. 1 | Journal of Managed Care Medicine 23
Exhibit 3: Levels of Evidence2 Recommendations in the NCCN Guidelines are classified according to the following: NCCN Categories of Evidence and Consensus Category 1:
The recommendation is based on high–level evidence (e.g., randomized controlled trials) and there is uniform consensus.
Category 2A: The recommendation is based on lower–level evidence and there is uniform consensus. Category 2B:
The recommendation is based on lower–level evidence and there is nonuniform consensus (but no major disagreement).
Category 3:
The recommendation is based on any level of evidence but reflects major disagreement.
One new therapy, crizotinib (Xalkori®), targets the EML-ALK fusion gene. Anaplastic lymphoma kinase (ALK) fuses to echinoderm microtuble-associated protein-like 4 (EML) and is an oncogene.8 This genetic mutation is found in about 4 percent of lung cancers, especially among younger, nonsmokers with adenocarcinoma. Approximately 10,000 lung cancer patients in the U.S. would be expected to have this mutation. In one trial in 82 ALK-positive patients who were given crizotinib, the oneyear overall survival was 74 percent and the twoyear overall survival was 54 percent.9 Other biologic markers are being investigated to help select therapy. Excision repair cross-complementation group 1 (ERCC1) is one example, which may be a prognostic factor for prognosis and cisplatin response. High levels of expression of ERCC1 is associated with good prognosis.10 Cisplatin causes DNA damage, which is repaired by ERCC1. Lack of ERCC1 (and other components of DNA repair system) limits repair of cisplatin-induced damage leading to cancer cell death. Negative ERCC1 expression is predictive for cisplatin response.11 Limited data suggest that ERCC1 expression can be used to choose therapy.12
References 1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin. 2006;56(2):106-30. 2. National Comprehensive Cancer Network. NCCN Categories of Evidence and Consensus. Available at www.nccn.org/professionals/physician_gls/categories_of_consensus.asp 3. Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002;346(2):92-8. 4. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355(24):2542-50. 5. Scagliotti G. Optimizing chemotherapy for patients with advanced non-small cell lung cancer. J Thorac Oncol. 2007;2 (Suppl 2):S86-91. 6. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350(21):2129-39. 7. Fuster LM, Sandler AB. Select clinical trials of erlotinib (OSI-774) in nonsmall-cell lung cancer with emphasis on phase III outcomes. Clin Lung Cancer. 2004;6 Suppl 1:S24-9. 8. Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010;363(18):1693-703. 9. Shaw AT, Yeap BY, Solomon BJ, et al. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol. 2011;12(11):1004-12. 10. Zheng Z, Chen T, Li X, et al. DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer. N Engl J Med. 2007;356(8):800-8.
Conclusion
There are still many issues to be resolved with lung cancer. Smoking cessation still needs to be a major public health target. As more is understood about the molecular basis of non-small cell lung cancer, more targeted therapies are being developed. Although only appropriate for select groups of patients, targeted therapy is leading to more individualized therapy. JMCM
11. Olaussen KA, Dunant A, Fouret P, et al. DNA repair by ERCC1 in nonsmall-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 2006;355(10):983-91. 12. Soria JC. ERCC1-tailored chemotherapy in lung cancer: the first prospective randomized trial. J Clin Oncol. 2007;25(19):2648-9.
Greg Otterson, MD is with The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.
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Chemotherapy-Induced Nausea and Vomiting (CINV): Perceptions, Mechanisms, and Treatment Guidelines Charles Loprinzi, MD For a CME/CEU version of this article, please go to www.namcp.org/cmeonline.htm, and then click the activity title.
Summary The best treatment for chemotherapy-induced nausea and vomiting (CINV) is prevention. The regimen used for prevention needs to cover both acute and delayed CINV and will vary depending on the emetogenic potential of the chemotherapy regimen being used. Improved understanding of the pathophysiology of this adverse effect has lead to the development of new agents which better target the underlying pathology. Key Points • CINV can be acute, delayed, or anticipatory. • The best treatment is prevention with a regimen that covers both acute and delayed CINV. • The regimen will depend on the emetogenic potential of the chemotherapy given. • Even with treatment with antiemetics, a significant number of patients will experience acute and delayed nausea. • Newer agents such as aprepitant and palonosetron are beneficial in preventing delayed CINV. • Unusual agents such as olanzapine, gabapentin, and megesterol are being investigated as alternatives to approved antiemetics.
Chemotherapy-induced nausea and vomiting (CINV) may be classified as acute), delayed, or anticipatory. Acute CINV occurs within the first 24 hours after chemotherapy administration. Delayed CINV begins more than 24 hours after chemotherapy. Delayed CINV can last for up to six days. Without any type of preventive treatment, the incidence of delayed CINV is 20 to 90 percent, primarily depending on the type of chemotherapy used. Anticipatory CINV begins before acute chemotherapy-related symptoms would be expected to occur. Although mild nausea and vomiting may be discomforting, more severe cases may result in dehydration, malnutrition, and electrolyte imbalance. CINV can affect quality of life, the desire to continue with antitumor therapy, and survival.1 Studies have demonstrated that nausea and vomiting secondary to chemotherapy impair a patient’s ability to complete household tasks, enjoy meals, and maintain activities of daily living and recreation.1,2 Patients consistently rank nausea and/or vomiting
among the most severe side effects of chemotherapy.3-5 As better antiemetics have been developed, nausea has become the primary problem. Patient- and treatment-related risk factors exist for developing CINV (Exhibit 1). Younger women are especially at risk. Treatment-related risk factors include high emetogenicity (compared with moderate or low emetogenicity) of the chemotherapy agent and high drug dose. Chemotherapy agents can be classified based on acute emetogenicity (Exhibit 2) from minimal to high risk.6 In an international prospective observational study of 298 patients from 14 oncology practices performed in 2001-2002, patient and health care provider ratings of efficacy of antiemetics was compared.7 Ninety-seven percent of patients received a serotonin (5-HT3) receptor antagonist prior to receipt of moderately or highly emetogenic chemotherapy. Physicians and nurses overestimated the efficacy of antiemetic treatment for the majority of patients. The greatest discrepancy between predicted and actual nausea and emesis occurred for
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Exhibit 1: Chemotherapy-Induced Emesis Risk Factors • Patient-related risk factors – Younger age (<50 years) – Female gender – No/minimal prior history of alcohol use – Prior CINV – Anxiety – Hx of morning sickness or motion sickness – Other medical conditions(e.g., intest. obstr., brain mets) • Treatment-related risk factors – High emetogenicity of chemotherapy agents/regimens – High Drug dose, rapid infusion rate
Exhibit 2: ASCO 2006 Antiemetic Consensus Guidelines 6 Emetic Risk Group
Risk (% of Patients)
Acute Prevention
Delayed Prevention
High (+AC)
>90%
5-HT3 + DEX + aprepitant
DEX + aprepitant
Moderate (excluding AC combinations)
30-90%
5-HT3 + DEX
Oral DEX (preferred) 5-HT3 (alternate)
Low
10-30%
DEX (20mg)
No preventative measures
Minimal
< 10%
No preventative measures
No preventative measures
DEX, dexamethasone; AC, anthracycline-cyclophosphamide.
the delayed period, with physicians and nurses underestimating the incidence of nausea/vomiting by nearly 30 percent. Of interest, even with treatment with antiemetics, 35 percent of patients experienced acute nausea and more than 50 percent experienced delayed nausea. The evolution of antiemetic agents during the past 20 years parallels advances in understanding the pathophysiology of CINV. In the early 1960s, phenothiazines became the first class of agents demonstrated to reduce emesis by targeting the dopamine receptor. During the late 1970s, the introduction of cisplatin, a highly emetogenic agent, provided stimulus for further antiemetic research because the inevitable side effect of nausea and vomiting threatened the use of this effective agent. Beginning in the 1980s, high-dose metoclopramide provided a new antiemetic option. Also during the 1980s, the value of combination regimens for improving antiemetic efficacy was recognized. In addition, predictive variables were identified, including such treatmentrelated factors as the inherent emetogenicity of the chemotherapeutic agent and patient-related factors. The first 5-HT3 receptor antagonist launched in 1991 and continued research led to its combined use with dexamethasone for improved results. This
regimen became the standard of care. The extensive research regarding 5-HT3 receptor antagonists also clarified the existence and persistence of delayed nausea and vomiting following chemotherapy and helped fuel development of agents active on other neurotransmitters and receptor systems, such as substance P and NK1 receptors. 2003 marked the launch of an NK1 receptor, representing the first in a new class of antiemetic agents. The proposed pathophysiology of CINV involves two different mechanisms—one located in the central nervous system (central) and the other mediated in the gastrointestinal (GI) tract (peripheral). The central mechanism is hypothesized to occur by activation of the chemoreceptor trigger zone (CTZ) by a chemotherapeutic agent. The CTZ is found within the area postrema of the brain, which lacks a blood-brain barrier and can be accessed through either the blood or cerebrospinal fluid. Once activated, the CTZ releases multiple neurotransmitters, which in turn activate the brain stem vomiting center. The peripheral mechanism is postulated to occur by a chemotherapeutic agent causing local GI irritation and damage to the GI mucosa, which results in the release of neurotransmitters. This activates receptors in the GI tract, which are mediated
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Exhibit 3: Neurotransmitters/Treatments Associated with Emesis
Dopamine/ Dopamine RAs
Histamine
Serotonin/ 5-HT3 RAs
Endorphins Emetic reflex
Substance P/ NK-1 RAs
Acetylcholine
GABA
Cannabinoids
RAs = receptor antagonists; 5HT 3 = serotonin; GABA = gamma-aminobutyric acid; NK = neurokinin.
by afferent fibers of the vagus nerve. The activated vagal afferent fibers send signals to the brain stem vomiting centers. In both instances, neurotransmitters may act independently or in combination to induce vomiting. Numerous neurotransmitters are known to be involved in the development of emesis (Exhibit 3). Antiemetics all appear to work in the chemoreceptor trigger zone. Some may also have peripheral effects. The best approach to treating CINV is to prevent it from ever occurring. For highly emetic agents, prophylaxis is necessary, whereas for minimal or low emetogenic agents, prophylaxis may not be needed. Four 5-HT3 receptor antagonists are approved for use in the United States for CINV - palonosetron (Aloxi速), ondansetron (Zofran速), dolasetron (Anzemet 速), and granisetron (Kytril速). 5-HT3 antagonists are considered first-line treatments for emesis associated with chemotherapy. Clinical studies have shown that a regimen containing a 5-HT3 receptor antagonist is highly effective in preventing acute vomiting, but demonstrates variable efficacy for delayed events. Based on extensive research and as reflected in guidelines, the most effective use of 5-HT3 receptor antagonists is in combination with dexamethasone. When examining differences among the 5-HT3 receptor antagonists, the newest agent, palonosetron, which is only available in intravenous form, appears to have a much longer duration of effect. This appears to be due to an extended plasma elimination half-life (approximately 40 hours) and higher binding affinity. Palonosetron has a 30-fold+ higher binding affinity for the 5-HT3 receptor compared with other agents in the class.8 In a trial comparing palonosetron with ondansetron but which did
not include dexamethasone treatment, palonosetron resulted in about a 10 percent improvement in acute CINV prevention and about a 20 percent improvement in delayed CINV.9 Dexamethasone is effective for preventing both acute and delayed CINV. Addition of dexamethasone to 5-HT3 antagonists results in a 10 to 20 percent improvement in emesis prevention. Substance P is a neurotransmitter that relays noxious sensory information to the brain. Substance P, which belongs to the group of peptides known as neurokinins, exerts its effect by binding to the neurokinin (NK1) receptor. High concentrations of NK1 receptors are located in brain regions implicated in the emetic reflex. Thus, the primary mechanism of NK1 receptor blockade action appears to be central. One neurokinin (NK-1) antagonist, aprepitant (Emend), is FDA approved. As a single agent, aprepitant is less effective than 5-HT3 antagonists in preventing acute emesis. However, when combined with 5-HT3 antagonists and dexamethasone, it is effective in preventing delayed emesis.10 Aprepitant added to standard therapy for preventing CINV with highly emetogenic chemotherapy improves the rate of CINV prevention by about 10 percent for acute and 20 percent for delayed.11 The dose of dexamethasone given is less when aprepitant is used because aprepitant decreases the clearance of dexamethasone due to inhibition of CYP450 3A4 activity. Fosaprepitant (also Emend brand name) is the intravenous form of aprepitant. Given in conjunction with dexamethasone and a 5-HT3 antagonist, a single dose of fosaprepitant is comparable to three days of oral aprepitant.12 Casopitant is an investigational agent in this class that has shown similar results. The ASCO antiemetic consensus guidelines are
www.namcp.org | Vol. 15, No. 1 | Journal of Managed Care Medicine 27
Exhibit 4: Mayo Clinic Antiemetic Regimens Emesis Potential
Regimen
Grade 1 (Minimal)
Dexamethasone 20 mg PO (optional) Prochlorperazine 10 mg PO pre-treatment (optional) Prochlorperazine 10 mg PO every six hours prn (#10)
Grade 2 (Low)
Prochlorperazine 10 mg PO pre-treatment Dexamethasone 20 mg PO (optional) Prochlorperazine 10 mg PO every six hours prn (#10)
Grade 3 (Moderate)
Dexamethasone 20 mg PO or IV pre-treatment Granisetron 1 mg PO or IV pre-treatment Dexamethasone 4 mg PO for days 2 and 3 (optional) Prochlorperazine 10 mg PO every six hours prn (#10) Lorazepam 1 mg PO every 2 hours prn
Grade 4 (High)
Dexamethasone 12 mg PO or IV pre-treatment Granisetron 2 mg PO or IV pre-treatment Dexamethasone 8 mg PO daily for days 2-4 Aprepitant 150 mg IV on day 1 of chemotherapy Prochlorperazine 10 mg PO every six hours prn (#10) Lorazepam 1 mg PO every 2 hours prn
Grade 5 (High dose cisplatin & failure of Grade 4)
Dexamethasone 12 mg PO or IV pre-treatment (20 mg PO or IV if aprepitant is not used) Palonosetron 0.25 mg IV pre-treatment Dexamethasone 8 mg PO daily for days 2-4 Aprepitant 150 mg IV day 1 of chemotherapy Prochlorperazine 10 mg PO every 6 hours prn (#10) Lorazepam 1 mg PO every 2 hours prn
summarized in Exhibit 2.6 The guideline developers added that women receiving combination of anthracycline + cyclophosphamide represents a situation with a particularly great risk of CINV, and risk appears to increase during multiple cycles although this combination has not been considered highly emetogenic in the past. In the Mayo Clinic guidelines, an additional classification of emetic potential is added to the four classes already shown in Exhibit 2. This fifth grade is very high-dose cisplatin regimens and failure of grade 4 anti-emetic therapy. Because chemotherapy ordering is computerized at the Mayo Clinic, the appropriate antiemetic regimen is automatically ordered along with the chemotherapy. The physician can override the automatic orders. The regimens at each level are shown in Exhibit 4. Because of the expense, palonosetron is reserved for grade 5. Because of the expense of these agents (Exhibit 5), other agents which work in a similar manner have been investigated. One of these is olanzapine, an atypical antipsychotic agent. In a moderate size
trial (n=241), olanzapine successfully prevented acute and delayed CINV as well as aprepitant when added to a standard regimen of dexamethasone and palonosetron.13 Olanzapine may be efficacious because of effects on many different neurotransmitters, including dopamine and serotonin and it has antianxiety effects. Gabapentin (Neurontin), an anticonvulsant which is also used to treat chronic pain syndromes, is another agent which has been studied for CINV. In small studies, it has shown effectiveness for reducing delayed nausea.14 Megesterol acetate (Megace) which is sometimes used to stimulate appetite has also been studied for preventing CINV. Conclusion
As our understanding of the pathologic mechanisms of CINV continue to evolve, new regimens that target more than one neurotransmitter and more than one type of CINV are being developed. Delayed CINV is an especially underestimated problem that can be improved with the newer agents such as apre-
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Exhibit 5: The Cost of Progress
Non-Medicare
Medicare
Medicare Pt responsibility
Granisetron 1 mg Tab
$18
$4
$0.8
Dexa 4 mg tab
$1
$1
$0.2
$189 + $24 admin fee
$43
Fosaprepitant $230 + $93 admin fee $192 + $24 admin fee 115 mg IV
$44
Aprepitant Tri-Pack
$89
Palonosetron $350 + $93 admin fee 0.25 mg IV
$388
$358
pitant and palonosetron. JMCM
ble-blind study. Support Care Cancer. 2010;18(4):423-31.
Charles Loprinzi, MD is the Regis Professor of Breast Cancer Research
vention of chemotherapy-induced nausea and vomiting associated with cisplatin
12. Grunberg S, Chua D, Maru A, et al. Single-dose fosaprepitant for the preat the Mayo Clinic College of Medicine in Rochester, MN.
therapy: randomized, double-blind study protocol--EASE. J Clin Oncol. 2011;29(11):1495-501.
References
13. Navari RM, Gray SE, Kerr AC. Olanzapine Versus Aprepitant for the Pre-
1. Lindley CM, Hirsch JD, O’Neill CV et al. Quality of life consequences of
vention of Chemotherapy-Induced Nausea and Vomiting: A Randomized
chemotherapy-induced emesis. Qual Life Res. 1992;1:331-340.4.
Phase III Trial. J Support Oncol. 2011;9(5):188-95.
2. O’Brien BJ, Rusthoven J, Rocchi A et al. Impact of chemotherapy-associated
14. Cruz FM, de Iracema Gomes Cubero D, Taranto P, et al. Gabapentin for the
nausea and vomiting on patients’ functional status and on costs: survey of five
prevention of chemotherapy- induced nausea and vomiting: a pilot study. Sup-
Canadian centres. Can Med Assoc J. 1993;149:296-302.
port Care Cancer. 2011 Apr 5.
3. Griffin AM, Butow PN, Coates AS, et al. On the receiving end. V: Patient perceptions of the side effects of cancer chemotherapy in 1993. Ann Oncol. 1996;7:189-195. 4. De Boer-Dennert M, de Wit R, Schmitz PIM, et al. Patient perceptions of the side-effects of chemotherapy: the influence of 5-HT3 antagonists. Br J Cancer. 1997;76:1055-61. 5. Lindley C. Perception of chemotherapy side effects: cancer vs noncancer patients. Cancer Pract. 1999;7:59-65. 6. Kris MG, Hesketh PJ, Somerfield MR, et al. American Society of Clinical Oncology Guideline for Antiemetics in Oncology: Update 2006. J Clin Oncol. 2006;24:2932-47. 7. Grunberg SM, Hansen M, Deuson RR, et al. Incidence of chemotherapyinduced nausea and emesis after modern antiemetics. Cancer. 2004;100:2261-8. 8. Aloxi® [package insert]. Bloomington, MN, USA: MGI Pharma, Inc.; 2004. 9. Gralla R et al. Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol. 2003;14:1570-7. 10. Hesketh PJ. Potential role of NK1 receptor antagonists in chemotherapyinduced nausea and vomiting. Support Care Cancer. 2001;9:350-4. 11. Rapoport BL, Jordan K, Boice JA, et al. Aprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with a broad range of moderately emetogenic chemotherapies and tumor types: a randomized, dou-
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Undertreated Pain Epidemic: Multi-Modality Approach to Pain Management Mark Rosenberg, MD, PhD For a CME/CEU version of this article, please go to www.namcp.org/cmeonline.htm, and then click the activity title.
Summary Management of pain, particularly chronic pain, is an important topic for anyone who works in managed care. Because the management of pain is complex, a comprehensive approach to assessment and management using validated tools and guidelines is necessary for optimal care. Additionally, individual clinicians involved in the care of pain patients require significant knowledge and abilities to provide effective care. Key Points • Pain is costly on many levels, impacting the patient, society, managed care, and employers. • Chronic pain is complex and multifactorial. • Adequate pain management requires a comprehensive assessment and, for many patients, a multi-modality treatment strategy. • Pain diaries and scales are useful in quantifying pain to improve assessment and management. • The 4A’s (Analgesia, Adverse effects, Activities of daily living, and Aberrant drug taking) of pain treatment outcomes can be used to assess outcomes at each health care visit. • Pain management clinicians need knowledge of self, pain, and standard of care, and the ability to serve as an advocate.
Pain is one of the most common reasons why patients present to medical providers, and one of the most prevalent medical complaints in the U.S. According to the National Center for Health Statistics Report, one out of 10 Americans have experienced pain that lasted longer than one year.1 Similarly, three out of five Americans 65 and older have experienced pain lasting more than one year.2 Between 1988 to 1994 and 1999 to 2002, the percentage of adults who took a narcotic to alleviate pain in the past month rose from 3.2 percent to 4.2 percent. Pain is associated with high health care utilization and the societal costs related to treatment are compounded by the loss in productivity associated with persistent pain. Loss of productivity in the workplace due to chronic pain is estimated to cost $61.2 billion per year. The total annual cost of poorly controlled persistent pain most likely exceeds $100 billion per year.3 According to the International Association for the Study of Pain (IASP), pain is defined as an unpleasant sensory and emotional experience which we
primarily associate with tissue damage, or describe in terms of such damage, or both. Exhibit 1 shows another definition of pain using the three hierarchical levels of pain. There is an important implication of both the IASP definition and the hierarchical model of pain. As a perception, pain may or may not correlate with an identifiable source of injury. Pain is often multifactorial and complex. The pain someone experiences does not always correlate with an organic cause. When pain becomes chronic, positive and negative adaptations and psychological issues add to the physiological and structural causes of the pain syndrome. Because there is no objective indicator for pain, it is almost always best to believe that the patient is experiencing what is reported. There are different types of pain. Nociceptive pain is pain due to ongoing activation of the nociceptive system by tissue injury. Tissue injury activates primary afferent neurons called nociceptors, which are small diameter neurons found in the muscle, joints, and some visceral tissues. This is typical acute pain.
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Exhibit 1: Three Hierarchical Levels of Pain
SensoryDiscriminative Component
• location • intensity • quality
Motivation-Affective Component
• depression • anxiety
Cognitive-Evaluation Component
• Thoughts concerning the cause and significance of the pain
Exhibit 2: Initial Pain Assessment Guidelines Overview Steps of the Initial Assessment
Crucial Components
Step 1: Obtain a detailed history:
• Assessment of pain characteristics • Related concerns/comorbidities (physical and psychiatric) • Prior diagnosis and therapies
Step 2: Conduct a physical examination:
• Emphasize the neurological and musculoskeletal examination
Step 3: Obtain and review past medical records and diagnostic studies:
• Thorough review of past medical records • Thorough review of previous medications
Step 4: Develop a formulation including:
1) Working diagnoses for the pain etiology, pain syndrome and inferred pathophysiology, and 2) Plan of care including need for additional diagnostic studies and initial treatments for the pain and related concerns
Neuropathic pain is pain resulting from direct injury or dysfunction of the peripheral or central nervous system. Neuropathic pain syndromes are chronic pain disorders caused by lesion or disease of the parts of the nervous system that normally signal pain. Pain can also be classified as idiopathic or psychogenic. Idiopathic pain is when reasonable inferences about the sustaining pathosphysiology of a pain syndrome cannot be made, and there is no positive evidence that the etiology is psychiatric. Pain that is sustained by psychological factors and is subject to a specific psychiatric diagnosis is classified as psychogenic. There is most commonly not a single source of chronic pain, but more often, a highly complex relationship consisting of multiple concurrent fac-
tors which are responsible for the origination and presentation of pain. Because of the complicated factors involved in pain, the management of pain depends on a comprehensive assessment. The process of assessment can be straightforward and brief in the setting of acute pain. It increases in complexity and time required as the pain becomes persistent. Psychosocial and psychiatric evaluations should be a fundamental part of any pain assessment, and are especially important in the management of chronic pain. Exhibit 2 provides an overview of initial pain assessment. A full patient history is a crucial component in the assessment of pain characteristics and should include details from past medical history,
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Exhibit 3: Unidimensional Pain Scales
10
Numeric Rating Scale (NRS) Hurts Worst
No Pain 0
Moderate Unbearable Pain Pain 1
2 3
4
5 6 7
8 9 10
9 8
Hurts Whole Lot
7 6
No Pain
Visual Analog Scale (VAS)
Hurts Even More
Worst Possible Pain
5 4
Hurts Little More
3 2
which may reveal problems relating to the patient’s pain (e.g., history of diabetes, toxic exposures, or alcoholism pointing toward a diagnosis of neuropathy), or disorders that would influence treatment decision making. A medication history, including efficacy of treatment, any nonprescription drug use, medications recently stopped, dietary supplements, assessment of compliance, determination of all prescribers/pharmacies used, and any barriers to treatment (problems paying for, obtaining, or taking medications) is also necessary. Controlled prescription drugs, such as opioids, are an important part of pain management. In order to mitigate the risk for misuse and abuse, a thorough understanding of the patients substance use history should be part of any initial assessment including current use of tobacco and alcohol products, specific questions about other drug use, and family history of alcohol or drug abuse. Any positive response should elicit a series of follow-up questions about frequency and general use pattern as well as questions related to any efforts to obtain help in stopping. This information is useful to stratify the risk of problems should the decision be made to offer a controlled prescription drug during the course of treatment. It is important to know the patient’s day-to-day activities, including sleep patterns, impact of the pain on work and personal relationships, present level of physical activity, and effects on function, mood, and any other domains of quality of life. A pain diary (written daily record by the patient) can
INTENSE, DREADFUL HORRIBLE Unable to do most activities because of pain. MISERABLE DISTRESSING Unable to do some activities because of pain. NAGGING PAIN UNCOMFORTABLE TROUBLESOME Can do most activities with rest periods.
1
MILD PAIN ANNOYING Pain is present but does not limit activity.
0
NO PAIN
Hurts Little Bit
No Hurt
WORST PAIN POSSIBLE UNBEARABLE Unable to do any activities because of pain.
be utilized over the course of treatment to give the provider a more comprehensive look at the course of the pain over treatment and can also be beneficial in targeting an approach to pain management. A physical examination should be conducted at the time of the initial pain assessment and repeated over time as required by the clinical situation. The examination should include mental status, physical inspection (posture, guarding, splinting, signs of sympathetic dysfunction), vital signs, and neurological assessment. A diagnostic evaluation should be performed when a diagnosis is lacking, and when the test will yield meaningful and actionable information (such as a change in treatment). Quantifying pain is an essential part of any ongoing pain assessment. There are a variety of pain assessment tools available. The clinician should select a pain assessment tool and incorporate that tool into routine clinical use. The tools should be used in a standardized way and systematically utilized across an organization. Whether simple or complex, the pain management tool utilized should include the time frame of the pain, clinical context of the pain, and average intensity over a fixed period of time. Additionally, pain management tools can be used to provide information on the course of pain over time by asking the following questions: • What is your pain on average? • What is your pain at its worst? • What is your pain at its least?
32 Journal of Managed Care Medicine | Vol. 15, No. 1 | www.namcp.org
The choice of a pain scale may vary depending on a patient’s age, abilities, and other factors. A numeric rating scale is an example of a unidimensional pain scale. It is a simple to use rating scale that can work both in the clinical setting and at home by the patient to quantify and keep track of pain. This scale can effectively be utilized to clarify
the relationship between pain and activity and the effectiveness of current pain treatment. Visual analog scales are another way to approach pain measurement and are similar to the numeric rating system. Because the measurement is linear, it allows further expression of pain, not limiting the pain to 10 discreet levels of intensity. Pictorial pain scales can be
Exhibit 4: Multidimensional Pain Scales McGill Pain Questionnaire Patient’s Name__________________________________________________ Date___________________ Time__________am/pm PRI S ______________ A________________ E_________________ M_______________ PRI(T)_ ________________ PPI________ (1-10) (11-15) (16) (17-20) (1-20)
1 FLICKERING QUIVERING PULSING THROBBING BEATING POUNDING
_____ _____ _____ _____ _____ _____
2 JUMPING FLASHING SHOOTING
_____ 14 PUNISHING _____ GRUELLING _____ CRUEL VICIOUS _____ KILLING _____ _____ 15 WRETCHED _____ BLINDING _____ 16 ANNOYING _____ TROUBLESOME _____ MISERABLE _____ INTENSE UNBEARABLE _____ _____ 17 SPREADING _____ RADIATING _____ PENETRATING _____ PIERCING
_____ _____ _____ _____ _____
_____ _____ _____ _____ _____
10 TENDER TAUT RASPING SPLITTING
_____ 18 TIGHT _____ NUMB _____ DRAWING SQUEEZING _____ TEARING _____ _____ 19 COOL _____ COLD FREEZING _____ _____ 20 NAGGING _____ NAUSEATING _____ AGONIZING DREADFUL _____ TORTURING _____ _____ PPI _____ z0 NO PAIN _____ z1 MILD z2 DISCOMFORTING _____ z3 DISTRESSING _____ z4 HORRIBLE _____ z5 EXCRUCIATING _____
11 TIRING EXHAUSTING
_____ _____
3 PRICKING BORING DRILLING STABBING LANCINATING 4 SHARP CUTTING LACERATING 5 PINCHING PRESSING GNAWING CRAMPING CRUSHING 6 TUGGING PULLING WRENCHING 7 HOT BURNING SCALDING SEARING 8 TINGLING ITCHY SMARTING STINGING 9 DULL SORE HURTING ACHING HEAVY
12 SICKENING SUFFOCATING
_____ _____
13 FEARFUL FRIGHTFUL TERRIFYING
_____ _____ _____
BRIEF MOMENTARY TRANSIENT
___ ___ ___
RHYTHMIC ___ PERIODIC ___ INTERMITTENT ___
CONTINUOUS STEADY CONSTANT
___ ___ ___
_____ _____ _____ _____ _____ _____ _____ _____ _____ _____ _____
_____ _____ _____
E = EXTERNAL I = INTERNAL
COMMENTS:
_____ _____ _____ _____ _____
____ ____ ____ ____ ____ ____
www.namcp.org | Vol. 15, No. 1 | Journal of Managed Care Medicine 33
especially useful for pediatric patients, for patients with cognitive barriers, and for patients who may have language barriers. Exhibit 3 shows examples of unidimensional pain scales. These are good for use in primary care practices. Multidimensional pain scales are more complicated but provide more information (Exhibit 4). An
example is the McGill Pain Questionnaire. This is a multidimensional clinical tool that assesses pain in three dimensions â&#x20AC;&#x201C; sensory, affective, and evaluative. Another example is the Brief Pain Inventory (BPI), a measurement tool taking five to 15 minutes to administer. The BPI includes seven intensity scales and seven scales assessing impact of pain. Because these
Exhibit 4: Multidimensional Pain Scales FORM 3.2 Brief Pain Inventory Date:__________ /__________ /____________
Time:__________
Name:_ ______________________ ___________________ ________________ Last First Middle Initial 1) Throughout our lives, most of us have had pain from time to time (such as minor headaches, sprains, and toothaches). Have you had pain other than everyday kinds of pain today?
1. Yes
2. No
2) On the diagram shade in the areas where you feel pain. Put an X on the area that hurts the most
Left Right
8) In the past 24 hours, how much relief have pain treatments or medications provided? Please circle the one percentage that most shows how much relief you have received. 0% 10 No relief
20
30
40
50
60
70
80
9) Circle the one number that describes how, during the past 24 hours, pain has interfered with your: A. General activity 0 1 Does not interfere
2
B. Mood
0
1
3
4
5
6
7
8
3
4
5
6
7
8
Left
3) Please rate your pain by circling the one number that best describes your pain at its worst in the past 24 hours. 2
3
4
5
6
2
7
8 9 10 pain as bad as you can imagine
C. Walking ability
0
1
2
3
4
5
1
2
3
4
5
Does not interfere
0 1 No pain
E. Relations with other people
3
4
5
6
7
8 9 10 pain as bad as you can imagine
0
1
2
Does not interfere
0 1 No pain
F. Sleep
3
4
5
6
7
8 9 10 pain as bad as you can imagine
0
1
3
4
2
3
4
Does not interfere
0 1 No pain
G. Enjoyment of life
3
4
5
6
7
8 9 10 pain as bad as you can imagine
7) What treatments or medications are you receiving for your pain? ___________________________________________________________________ ___________________________________________________________________
7
8
0
1
Does not interfere
6
7
9
10
Completely interferes
8
9
10
5
6
7
8
9
10
Completely interferes
6) Please rate your pain by circling the one number that tells how much pain you have right now. 2
10
Completely interferes
5) Please rate your pain by circling the one number that best describes your pain on the average. 2
6
Does not interfere D. Normal work (includes both work outside the home and housework). 0
9
Completely interferes
4) Please rate your pain by circling the one number that best describes your pain at its least in the past 24 hours. 2
9 10 Completely interferes
Right
Does not interfere
0 1 No pain
90 100% Complete relief
5
6
7
8
9
10
Completely interferes
2
3
4
5
6
7
8
9
10
Completely interferes
Medscape Source: Pain Manag Nurs Š 2008 W.B. Saunders
34 Journal of Managed Care Medicine | Vol. 15, No. 1 | www.namcp.org
Exhibit 5: The Four “A’s” of Pain Treatment Outcomes 4
Analgesia (Pain Relief)
Activities of daily living (psychosocial functioning)
Adverse effects (side effects)
Aberrant drug taking (addiction-related outcomes)
are more complicated to administer, the best use for these is within a pain clinic or pain-based practice. Treatment Outcomes of Pain Survey (TOPS) is another instrument useful for the assessment of persistent pain. Additionally, TOPS allows for the tracking of large numbers of patients in key functional domains, but lacks the sensitivity to determine individual patient changes. TOPS is currently useful for research purposes and could potentially be adopted for individual clinical practices. Goals of treating pain vary from patient to patient. In acute pain, the goal is to reduce pain as quickly as possible. For persistent cancer-related pain, comfort of the patient is most important. Other comorbidities and symptoms also need to be treated. Reducing pain intensity and restoring function are the overriding goals with chronic pain (not due to cancer). Comorbidities that can complicate pain management such as anxiety and depression also need to be managed. Clinicians should be assessing outcomes in pain patients at each visit. The use of the 4A’s of pain treatment outcomes is an easy way to remember the areas to assess (Exhibit 5).4 There are many different types of interventions to manage pain. These include pharmacologic, rehabilitative, psychological, interventional, surgical, and complimentary and alternative strategies (Exhibit 6). For pharmacologic therapy, the World Health Organization suggests using an analgesic ladder that begins with nonopioid medications and works its way up to opioids. Adjunctive therapies such as antidepressants, anticonvulsants, bisphosphonates, and corticosteroids can also be used to manage pain depending on the type or source of pain. Specific rehabilitative treatment such as physical therapy or work hardening programs may be pre-
scribed as part of a cognitive behavioral therapy (CBT) program or separately. Some patients with acute pain should be given specific instructions for exercise or referral to a physical therapist, as a firstline approach to pain therapy aiming for functional restoration. Programs may be available through hospitals, free-standing facilities, government services or corporate entities, including vocational assessment and training, job retraining programs, work hardening programs, and rehabilitation-orientated pain management programs. Psychological interventions usually are encompassed under the broad framework of cognitivebehavioral therapy. Included in this approach are strategies that can be taught to the patient and may lessen pain intensity, improve coping, increase function, and reduce overall disability. These strategies include education about pain and its impact and cognitive strategies to reduce catastrophization and helplessness. It includes training in cognitive therapies such as biofeedback, relaxation and imagery and specific behavioral interventions such as graduated exercises, pacing, and sleep hygiene. Overall, therapy interventions should be integrated into a comprehensive evaluation and management plan. Disability and physical, psychosocial and psychiatric comorbidities have to be assessed and managed as part of the approach to pain management. The source of pain should be identified and treated, if possible. Analgesic therapies should be individualized and placebos should not be used. Clinicians need to recognize the value of a multimodality approach that uses pharmacologic and nonpharmacologic therapies. In many cases, particularly those characterized by persistent pain, recurrent pain, a high level of associated disability, or
www.namcp.org | Vol. 15, No. 1 | Journal of Managed Care Medicine 35
Exhibit 6: Categories of Analgesic Strategies
Type of Analgesic Strategy
Examples
Pharmacologic
Nonopioid drugs Opioid drugs Adjuvant analgesics
Rehabilitative
Physical and occupational therapy Modalities (heat, cold, ultrasound, electrical stimulation)
Psychological
Cognitive-behavioral therapy Specific treatments (e.g., biofeedback) Other types of psychotherapy
Interventional
Injection therapy Neural blockade Implant therapies
Surgical
Neurectomy, nerve decompression, cordotomy
Complimentary and Alternative
Acupuncture, massage, chiropractic, nutraceutricals, energy therapies, non-Western medicine
a prior poor response to analgesics, the patient can benefit from a multi-modality strategy. Analgesic medications should be used rationally, based on a case-by case analysis of benefit and risk. Lastly, the input of consultants should be obtained if there is uncertainty about the value of specific therapies. The medical director and nurse case manager have significant roles in managing pain. Both are responsible and accountable to ensure that a patient receives an appropriate evidence- based assessment and intervention. These interventions must effectively treat the patient’s pain and meet the recognized standard of care. In order to accomplish this, it is essential for providers to have knowledge of self, knowledge of pain, knowledge of standard of care, and the ability to serve as an advocate. Knowledge of self is acknowledging one’s biases and limitations. A knowledge of self including attitudes, values, beliefs, and cultural background is essential, as these factors may affect clinicians when assessing pain The greatest barrier to a patient achieving effective pain management may be the clinical staff ’s individual experiences with pain, personal use of medications or nonpharmacological methods to manage pain, and family or significant others’ history or experience with substances for pain control or mood-altering effect. When a clinician is influenced by these personal factors, they may not be able to effectively or objectively evaluate or manage the patient. Clinicians must have a fundamental knowledge
of pain in relation to many areas. They must know how to effectively use standardized pain assessment tools. They must be knowledgeable regarding the difference in categories of pain and the most likely potential sources of pain. Each must have the ability to assess the patient’s individual pain patterns, experiences, and expressions of pain. Knowledge of pharmacologic and nonpharmacologic interventions including current standards and guidelines is also necessary. Another factor is knowledge of standard of care in pain management. The standard of care includes acknowledging the patient’s pain, identifying the source of the pain, assessing the pain at regular intervals, reporting the patient’s level of pain, and developing an interdisciplinary plan for effective pain management. Implementing pain management strategies, aggressively treating side effects, providing education to the patient, and evaluating the effectiveness of strategies are also components of the pain standard of care. Lastly, documenting and reporting intervention and outcomes and advocating for the patient are also necessary. One of the most important pieces of the management process is advocacy. When advocating for the patient, it is crucial to utilize and reference current evidence-based pain management standards and guidelines. The clinician should consult and collaborate with pain management experts to assure an effective interdisciplinary treatment plan to address patient pain. When a patient’s pain needs are not
36 Journal of Managed Care Medicine | Vol. 15, No. 1 | www.namcp.org
being met, the clinician should continue to advocate through other means. The clinician should also ensure that pain management needs are properly addressed for populations known to be at risk for undermanagement.
References 1. Watkins EA, Wollan PC, Melton LJ 3rd, Yawn BP. A population in pain: report from the Olmsted County health study. Pain Med. 2008;9:166-74. 2. Blay SL, Anreoli SB, Gastal FL. Chronic painful physical conditions, disturbed sleep and psychiatric morbidity: results from an elderly survey. Ann Clin Psychiatry. 2007;19:169-74.
Conclusion
3. Von Korff M, Lin EH, Fenton JJ, Suanders K. Frequency and priority of pain
Pain is costly on many levels, impacting the patient, society, managed care, and employers. Managing chronic pain is complex and many times requires a multi-modal strategy. Clinicians should be using validated tools to quantify pain to determine if pain goals are being met. Pain management clinicians need knowledge of self, pain, and standard of care, and the ability to serve as an advocate in order to be effective. JMCM
patientsâ&#x20AC;&#x2122; health care use. Clin J Pain. 2007;23:400-8. 4. Passik SD, Weinreb HJ. Managing chronic nonmalignant pain: overcoming obstacles to the use of opioids. Adv Ther. 2000;17:70-83.
Mark Rosenberg MD, PhD is President and CEO of BHM Healthcare Solutions in St Louis, MO.
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Ignoring Real Interventions By Dexter Shurney, MD, MBA, MPH
Sometimes we get so hung up on chasing the esoteric that we ignore simple solutions. Take for instance the heated debate, in the wake of U.S. health care reform, on the merits of comparative effectiveness research (CER). Although there is a pressing need for comparative effectiveness research to improve health outcomes and potentially reduce costs, a greater concern may be how will the findings be used and put into daily practice by providers and accepted by payers. Because of a general lack of information on the relative effectiveness and reluctance on the part of payers to reimburse, too often better approaches to care can suffer from slow adoption. For a number of years, the attributes of diet and lifestyle have been very relevant to the prevention and the treatment of diabetes. In 2002, a NIDDK study showed that lifestyle intervention reduced the incidence of diabetes by 58 percent and the use of metformin by 31 percent, as compared with a placebo. In comparison, the lifestyle intervention was significantly more effective than metformin. Yet nearly a decade later, and despite the recognized evidence, little has changed in the way pre-diabetics are counseled on diet and lifestyle. In 2009, a landmark study was published by Neal Barnard, MD which was a head-to-head comparison of the recommended American Diabetics Association (ADA) diet to a Vegetarian/Vegan diet in Type-2 diabetics. The findings were remarkable. Essentially, roughly half of the diabetics put on a vegetarian diet were able to come off their insulin within 16 days. For those who still required insulin, the mean dose was reduced by half. On the vegetarian diet, the diabetes actually got significantly better. Alternatively, those on the ADA diet showed only a slowing of the progression of the disease. Not to disparage the ADA diet, but these findings raise the question of whether the standard ADA diet is truly the optimal diet for diabetics. From this trial and others like it, it would appear that a vegetarian or vegan diet is probably a far better choice. Just this year, researchers from Harvard School of Public Health analyzed dietary intake data from more than 200,000 people gathered for over a de-
cade. When adjusted for family history, age, weight, and physical activity, they found that diets containing red meat were strongly correlated to increased rates of type-2 diabetes. As little as two-ounces per day of processed meat like hot dogs, bacon, and common deli favorites increased the risk of diabetes by 50 percent. Unprocessed meat, while not as bad, was nevertheless, culpable and was associated with a 20 percent greater risk. They also concluded that substituting whole grains, nuts, and even lowfat dairy, like yogurt, for a serving a day might lower the risk of developing type-2 diabetes by 16 percent. While these and other observational and clinical trials indicate a benefit of vegetarian and vegan diets for diabetes management, providers have been slow to embrace the concepts and put them into practice with their diabetic patients. Why is any of this significant? Itâ&#x20AC;&#x2122;s significant for many reasons, not the least of which is to change the all too pervasive mindset that lifestyle and diets are not real interventions. Too often lifestyle recommendations appearing in guidelines hold a position of distain among providers as merely a compulsory box to check on the way to prescribing the next medication. Nevertheless, meaningful lifestyle modification is a better and simpler alternative for many patients willing to give it a try. For patients to be able to make informed decisions regarding such matters, however, they must be presented the opportunity and the practical knowledge on how to make the switch. Unfortunately, at present, absent the necessary guidance, few patients are given the chance. Imagine what would happen if patients were routinely counseled to adopt a vegetarian diet when faced with a pending or confirmed diagnosis of diabetes. How many lives might be saved and families spared the painful burden of living with someone with the disease, if this were common practice? Dexter Shurney, MD, MBA, MPH is the Chief Medical Director, Employee Health Plan HR-Benefits and an Assistant Professor, Division of Public Health and Internal Medicine, at Vanderbilt University and Medical Center.
38 Journal of Managed Care Medicine | Vol. 15, No. 1 | www.namcp.org
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