- Email: [email protected]
How Can We Improve Quality of Care for Patients With Cirrhosis?
Editorials, continued 20. Littman DR, Rudensky AY. Th17 and regulatory T cells in mediating and restraining inflammation. Cell 2010;140:845– 858. 21. Snanoudj R, Frangie C, Deroure B, et al. The blockade of T-cell co-stimulation as a therapeutic stratagem for immunosuppression: Focus on belatacept. Biologics 2007;1:203–213. 22. Tiede I, Fritz G, Strand S, et al. CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4⫹ T lymphocytes. J Clin Invest 2003;111:1133–1145. 23. Ebert EC, Panja A, Praveen R. Human intestinal intraepithelial lymphocytes and epithelial cells coinduce interleukin-8 production through the CD2-CD58 interaction. Am J Physiol Gastrointest Liver Physiol 2009;296:G671– 677. 24. Sandborn WJ, Colombel JF, Frankel M, et al. Anti-CD3 antibody visilizumab is not effective in patients with intravenous corticosteroid-refractory ulcerative colitis. Gut 2010;59:1485–1492. 25. Sands BE, Sandborn WJ, Creed TJ, et al. Basiliximab does not increase efficacy of corticosteroids in patients with steroid-refractory ulcerative colitis. Gastroenterology 2012 Apr 28 [Epub ahead of print]. 26. Feagan BG, Greenberg GR, Wild G, et al. Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin. N Engl J Med 2005;352:2499 –2507.
Reprint requests Address requests for reprints to: R.S. Blumberg, MD, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. e-mail: [email protected]. Acknowledgments The authors thank Dr Josh Korzenik for helpful discussions and Dr Lukas Niederreiter for help with the illustration. Funding RSB was supported by NIH DK051362, DK044319, DK053056, DK088199, Harvard Digestive Diseases Center (NIH DK034854); AK by the European Research Council Grant agreement n° 260961 and the National Institute for Health Research Cambridge Biomedical Research Centre. LM was supported by NIH AI044236, AI084952, DK072201 and DK086605. Conflicts of interest The authors disclose no conflicts. © 2012 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2012.05.015
How Can We Improve Quality of Care for Patients With Cirrhosis? See “The quality of care provided to patients with cirrhosis and ascites in the Department of Veterans Affairs,” by Kanwal F, Kramer JR, Buchanan P, et al, on page 70.
T
he US health care system ranks among the best in the world for treating rare and complex conditions, but performs less well on preventative and systems-based care.1 For this reason, along with various social and cultural factors, we receive far less value for our health care dollars than any other country (Figure 1). This problem can be addressed via 2 avenues, namely reducing costs and improving quality. However, to improve quality one must first be able to measure it. Doing so has challenged health services researchers for years, ever since Avedis Donabedian first categorized quality of care into structure, process, and outcomes.2 Cirrhosis is a complex condition where good medical care can significantly impact patient morbidity and mortality, but until recently there was no proven way to systematically assess that care. In this issue of GASTROENTEROLOGY, Kanwal et al3 describe an important advance in this field. Among a cohort of 774 patients with cirrhosis and ascites seen at 3 Veteran’s Affairs (VA) medical centers between 2002 and 2007, they report the proportion of eligible patients whose treatment met 8 quality indicators previously developed by their group.4 They found that only 33% of patients received all indicated care. For example, only 30% of patients with spontaneous bacterial peritonitis received antibiotics for secondary prophylaxis within 30 days of discharge, and 49% of
patients with gastrointestinal bleeding received antibiotics during that hospitalization. These results are consistent with prior single-center studies, and raise several important questions.5 Why is it that our health care system can only manage to deliver appropriate care one-third of the time? One reason is the exponentially expanding volume of medical knowledge, which makes it difficult for generalist physicians to keep up on current standards of care for all diseases. Improved education may help, but is not the only answer—tertiary care specialists do not necessarily perform much better.6 The majority of the deficit may lie in the structure of our health care system, which is better suited for treating acute issues than chronic conditions.5 Care is episodic, symptomdriven, and reactive rather than proactive, which explains why Kanwal et al3 found better performance on indicators of reactive care than on those measuring preventative care. A final and important reason why performance will never be 100% is that the practice of medicine is a complex scientific and social art. In everyday practice, there exist all kinds of justifiable reasons why providers rationally choose not to deliver certain care. For example, in the case of paracentesis, the volume of ascites may be insufficient or the patient may refuse the procedure. In the parlance of quality measurement, these reasons are called “denominator exclusions.” By reviewing individual charts, Kanwal et al3 found such denominator exclusions in 37.5% of cases where the quality indicator was not met, and there may have been more cases where the reasons were not documented. These undocumented reasons may explain the association between higher comorbidity index and lower performance on quality indicators. 17
Editorials, continued
Figure 1. Return on investment of health care dollars by countries (adapted with permission from http://ucatlas.ucsc.edu/ spend.php).
This study was not without limitations. The findings may not be representative of medical care outside of those 3 VA centers, and some experts may argue whether some of the metrics (such as diagnostic paracentesis in every outpatient with cirrhosis and new-onset ascites) are truly necessary. However, the value of this research lies primarily in advancing our understanding of quality measurement in cirrhosis. In order to function effectively, quality indicators must not only be medically justified, but also (1) be collectable using automated systems to reduce measurement burden, (2) have a clear numerator, denominator, and denominator exclusions for the sake of consistency, (3) be linked to the actions of one provider or one institution, and (4) occur with sufficient frequency to produce reliable estimates.7 The authors performed extensive chart validation to demonstrate that the numerators and denominators could be reliably measured using administrative data. Some of the indicators had relatively few denominator exclusions, and can thus be measured in an automated fashion. It remains unclear whether these indicators can be linked to 1 provider or institution in an open health care system outside of the VA, or whether they occur with sufficient frequency to produce reliable estimates. Thus, although this paper represents a significant advance, these metrics are not quite ready for profiling individual physicians or institutions. In summary, this study demonstrates that the quality of care delivered to patients with cirrhosis and ascites is far from adequate. How can this quality be improved? One idea is to publicly report quality indicators, and perhaps tie these indicators to reimbursement. After all, medicine is one of the only commercial markets without a clear quality– demand relationship.8 However, caution must be used to avoid unanticipated consequences. In diabetes, it has previously been 18
shown that physicians can more easily improve their quality scores by discharging their patient with the lowest hemoglobin A1C, rather than struggling to improve the numbers of the entire patient cohort.9 For this reason, thoughtful analysis of proposed quality indicators, as begun by Kanwal et al,3 is vitally important. Another way to improve quality of care in cirrhosis is to apply principles of chronic disease management. One component involves setting up protocols for continuous management of patients between visits.5 In our institution, we enroll patients in a cirrhosis registry, with periodic performance assessment and reminders for scheduled testing. By doing so, we have improved our rates of screening for hepatocellular carcinoma from 74% to 93%.10 Other institutions are developing more innovative models of care, such as educating community physicians, and optimizing communication and coordination between providers.11 An additional finding that deserves comment is that, in multivariable hierarchical regression, being seen by a gastroenterologist and being at an academic-affiliated facility were both significantly associated with better overall quality of care (odds ratios of 1.33 and 1.73, respectively). Similar findings have been reported previously.12 In the current health care environment, with the advent of accountable care organizations (ACO) and other initiatives, the pendulum may be swinging back to focus on primary care. Efforts by Kanwal et al3 and others will help to ensure that gastroenterologists have a seat at the health care table of the future.
MICHAEL L. VOLK Division of Gastroenterology and Hepatology University of Michigan Health System Ann Arbor, Michigan
Editorials, continued References 1. US Institute of Medicine, Committee on Quality of Health Care in America. Crossing the quality chasm: a new health system for the 21st century. Washington, DC: National Academy Press; 2001. 2. Donabedian A. The quality of medical care. Science 1978;200: 856 – 864. 3. Kanwal F, Kramer JR, Buchanan P, et al. The quality of care provided to patients with cirrhosis and ascites in the Department of Veterans Affairs. Gastroenterology 2012;143:70 –77. 4. Kanwal F, Kramer J, Asch SM, et al. An explicit quality indicator set for measurement of quality of care in patients with cirrhosis. Clin Gastroenterol Hepatol 2010;8:709 –717. 5. Volk ML, Piette JD, Singal AS, et al. Chronic disease management for patients with cirrhosis. Gastroenterology 2010;139:14 –16 e1. 6. Bassett JT, Volk ML. Can quality of care for patients with cirrhosis be measured? Dig Dis Sci 2011;56:3488 –3491. 7. National Quality Forum. ABC’s of measurement. Washington, DC: National Quality Forum; 2010. 8. Phelps CE. Health economics. Boston: Addison Wesley; 2003. 9. Hofer TP, Hayward RA, Greenfield S, et al. The unreliability of individual physician ”report cards” for assessing the costs and quality of care of a chronic disease. JAMA 1999;281:2098 –2105. 10. Singal AG, Volk ML, Rakoski MO, et al. Patient involvement in healthcare is associated with higher rates of surveillance for hepatocellular carcinoma. J Clin Gastroenterol 2011;45:727–732.
11. Arora S, Thornton K, Murata G, et al. Outcomes of treatment for hepatitis C virus infection by primary care providers. N Engl J Med 2011;364:2199 –2207. 12. Bini EJ, Weinshel EH, Generoso R, et al. Impact of gastroenterology consultation on the outcomes of patients admitted to the hospital with decompensated cirrhosis. Hepatology 2001;34:1089–1095.
Reprint requests Address requests for reprints to: Michael L. Volk, MD, MSc, Division of Gastroenterology and Hepatology, University of Michigan Health System, 300 N Ingalls, 7C27, Ann Arbor, Michigan 48103. e-mail: [email protected] Funding Dr Volk is funded by K23DK085304 from the National Institutes of Health. Conflicts of interest The author discloses no conflicts. © 2012 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2012.05.014
Mesenchymal Stem Cells and Prostaglandins May Be Critical for Intestinal Wound Repair See “Igf2bp1 is required for full induction of Ptgs2 mRNA in colonic mesenchymal stem cells in mice,” by Manieri NA, Drylewicz MR, Miyoshi H, et al, on page 110.
T
he article by Manieri et al1 adds new information and tantalizing novel ideas to presently held concepts pertaining to the current paradigm for intestinal wound healing. Based on studies of the healing of full-thickness biopsies of the colon in prostaglandin endoperoxide synthase Ptgs 2 (Cox2)⫺/⫺ and wild-type mice, the current article proposes that (1) prostaglandins are the key initiators and critical molecule for wound healing in the intestine and (2) colonic mesenchymal stem cells (cMSC), which express the highest levels of Ptgs2 protein in the lamina propria after intestinal wounding, are the critical cells involved. Further, it identifies insulin-like growth factor 2 binding protein 1 (Igf2bp1) as a novel Ptgs2 mRNAbinding protein that binds to the AU-rich elements in the 3= untranslated end of the message imparting message stability and translational efficiency, serving as a scaffold for other RNA binding proteins and directing its intracellular location. Igf2bp1 is an oncofetal protein expressed in embryos, where it is important in development, but also is overexpressed in a high percentage of colorectal carcinomas. Thus, the article has translational value because this binding factor is a potential target for cancer chemopre-
ventative development, because agents inhibiting this mRNA-binding factor might have fewer side effects than nonsteroidal anti-inflammatory drugs or other Ptgs2-inhibitors. The classic model of wound healing, based mainly on studies of the integument but on intestine as well, proposes a cascade of 4 separate phases.2–5 The hemostasis phase begins when the wound is inflicted and platelet degranulation and fibrin formation provide hemostasis and a provisional matrix on and in which the subsequent events of healing take place. Early response cytokine and chemokine genes in the epithelium and lamina propria stromal cells and leukocytes are activated by the innate immune system. Release of prostaglandins, inflammatory and regulatory cytokines (the initial Th1 response was rapidly followed by a Th2 response), chemotactic cytokines (eg, platelet-derived growth factor), and chemokines initiate the inflammatory phase, with all the traditional host manifestations of inflammation. The relative importance of various leukocytes (neutrophils, macrophages, dendritic cells, and lymphocytes) and fibroblasts (especially activated fibroblasts or myofibroblasts) in this process is not clear. It is clear in cutaneous wound healing that myofibroblasts form adhesion complexes to matrix and to each other and then contract to reduce the area of the wound. During the proliferative phase, myofibroblasts secrete collagen and other matrix molecules (glycoproteins and pro19
Reprint requests Address requests for reprints to: R.S. Blumberg, MD, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. e-mail: [email protected]. Acknowledgments The authors thank Dr Josh Korzenik for helpful discussions and Dr Lukas Niederreiter for help with the illustration. Funding RSB was supported by NIH DK051362, DK044319, DK053056, DK088199, Harvard Digestive Diseases Center (NIH DK034854); AK by the European Research Council Grant agreement n° 260961 and the National Institute for Health Research Cambridge Biomedical Research Centre. LM was supported by NIH AI044236, AI084952, DK072201 and DK086605. Conflicts of interest The authors disclose no conflicts. © 2012 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2012.05.015
How Can We Improve Quality of Care for Patients With Cirrhosis? See “The quality of care provided to patients with cirrhosis and ascites in the Department of Veterans Affairs,” by Kanwal F, Kramer JR, Buchanan P, et al, on page 70.
T
he US health care system ranks among the best in the world for treating rare and complex conditions, but performs less well on preventative and systems-based care.1 For this reason, along with various social and cultural factors, we receive far less value for our health care dollars than any other country (Figure 1). This problem can be addressed via 2 avenues, namely reducing costs and improving quality. However, to improve quality one must first be able to measure it. Doing so has challenged health services researchers for years, ever since Avedis Donabedian first categorized quality of care into structure, process, and outcomes.2 Cirrhosis is a complex condition where good medical care can significantly impact patient morbidity and mortality, but until recently there was no proven way to systematically assess that care. In this issue of GASTROENTEROLOGY, Kanwal et al3 describe an important advance in this field. Among a cohort of 774 patients with cirrhosis and ascites seen at 3 Veteran’s Affairs (VA) medical centers between 2002 and 2007, they report the proportion of eligible patients whose treatment met 8 quality indicators previously developed by their group.4 They found that only 33% of patients received all indicated care. For example, only 30% of patients with spontaneous bacterial peritonitis received antibiotics for secondary prophylaxis within 30 days of discharge, and 49% of
patients with gastrointestinal bleeding received antibiotics during that hospitalization. These results are consistent with prior single-center studies, and raise several important questions.5 Why is it that our health care system can only manage to deliver appropriate care one-third of the time? One reason is the exponentially expanding volume of medical knowledge, which makes it difficult for generalist physicians to keep up on current standards of care for all diseases. Improved education may help, but is not the only answer—tertiary care specialists do not necessarily perform much better.6 The majority of the deficit may lie in the structure of our health care system, which is better suited for treating acute issues than chronic conditions.5 Care is episodic, symptomdriven, and reactive rather than proactive, which explains why Kanwal et al3 found better performance on indicators of reactive care than on those measuring preventative care. A final and important reason why performance will never be 100% is that the practice of medicine is a complex scientific and social art. In everyday practice, there exist all kinds of justifiable reasons why providers rationally choose not to deliver certain care. For example, in the case of paracentesis, the volume of ascites may be insufficient or the patient may refuse the procedure. In the parlance of quality measurement, these reasons are called “denominator exclusions.” By reviewing individual charts, Kanwal et al3 found such denominator exclusions in 37.5% of cases where the quality indicator was not met, and there may have been more cases where the reasons were not documented. These undocumented reasons may explain the association between higher comorbidity index and lower performance on quality indicators. 17
Editorials, continued
Figure 1. Return on investment of health care dollars by countries (adapted with permission from http://ucatlas.ucsc.edu/ spend.php).
This study was not without limitations. The findings may not be representative of medical care outside of those 3 VA centers, and some experts may argue whether some of the metrics (such as diagnostic paracentesis in every outpatient with cirrhosis and new-onset ascites) are truly necessary. However, the value of this research lies primarily in advancing our understanding of quality measurement in cirrhosis. In order to function effectively, quality indicators must not only be medically justified, but also (1) be collectable using automated systems to reduce measurement burden, (2) have a clear numerator, denominator, and denominator exclusions for the sake of consistency, (3) be linked to the actions of one provider or one institution, and (4) occur with sufficient frequency to produce reliable estimates.7 The authors performed extensive chart validation to demonstrate that the numerators and denominators could be reliably measured using administrative data. Some of the indicators had relatively few denominator exclusions, and can thus be measured in an automated fashion. It remains unclear whether these indicators can be linked to 1 provider or institution in an open health care system outside of the VA, or whether they occur with sufficient frequency to produce reliable estimates. Thus, although this paper represents a significant advance, these metrics are not quite ready for profiling individual physicians or institutions. In summary, this study demonstrates that the quality of care delivered to patients with cirrhosis and ascites is far from adequate. How can this quality be improved? One idea is to publicly report quality indicators, and perhaps tie these indicators to reimbursement. After all, medicine is one of the only commercial markets without a clear quality– demand relationship.8 However, caution must be used to avoid unanticipated consequences. In diabetes, it has previously been 18
shown that physicians can more easily improve their quality scores by discharging their patient with the lowest hemoglobin A1C, rather than struggling to improve the numbers of the entire patient cohort.9 For this reason, thoughtful analysis of proposed quality indicators, as begun by Kanwal et al,3 is vitally important. Another way to improve quality of care in cirrhosis is to apply principles of chronic disease management. One component involves setting up protocols for continuous management of patients between visits.5 In our institution, we enroll patients in a cirrhosis registry, with periodic performance assessment and reminders for scheduled testing. By doing so, we have improved our rates of screening for hepatocellular carcinoma from 74% to 93%.10 Other institutions are developing more innovative models of care, such as educating community physicians, and optimizing communication and coordination between providers.11 An additional finding that deserves comment is that, in multivariable hierarchical regression, being seen by a gastroenterologist and being at an academic-affiliated facility were both significantly associated with better overall quality of care (odds ratios of 1.33 and 1.73, respectively). Similar findings have been reported previously.12 In the current health care environment, with the advent of accountable care organizations (ACO) and other initiatives, the pendulum may be swinging back to focus on primary care. Efforts by Kanwal et al3 and others will help to ensure that gastroenterologists have a seat at the health care table of the future.
MICHAEL L. VOLK Division of Gastroenterology and Hepatology University of Michigan Health System Ann Arbor, Michigan
Editorials, continued References 1. US Institute of Medicine, Committee on Quality of Health Care in America. Crossing the quality chasm: a new health system for the 21st century. Washington, DC: National Academy Press; 2001. 2. Donabedian A. The quality of medical care. Science 1978;200: 856 – 864. 3. Kanwal F, Kramer JR, Buchanan P, et al. The quality of care provided to patients with cirrhosis and ascites in the Department of Veterans Affairs. Gastroenterology 2012;143:70 –77. 4. Kanwal F, Kramer J, Asch SM, et al. An explicit quality indicator set for measurement of quality of care in patients with cirrhosis. Clin Gastroenterol Hepatol 2010;8:709 –717. 5. Volk ML, Piette JD, Singal AS, et al. Chronic disease management for patients with cirrhosis. Gastroenterology 2010;139:14 –16 e1. 6. Bassett JT, Volk ML. Can quality of care for patients with cirrhosis be measured? Dig Dis Sci 2011;56:3488 –3491. 7. National Quality Forum. ABC’s of measurement. Washington, DC: National Quality Forum; 2010. 8. Phelps CE. Health economics. Boston: Addison Wesley; 2003. 9. Hofer TP, Hayward RA, Greenfield S, et al. The unreliability of individual physician ”report cards” for assessing the costs and quality of care of a chronic disease. JAMA 1999;281:2098 –2105. 10. Singal AG, Volk ML, Rakoski MO, et al. Patient involvement in healthcare is associated with higher rates of surveillance for hepatocellular carcinoma. J Clin Gastroenterol 2011;45:727–732.
11. Arora S, Thornton K, Murata G, et al. Outcomes of treatment for hepatitis C virus infection by primary care providers. N Engl J Med 2011;364:2199 –2207. 12. Bini EJ, Weinshel EH, Generoso R, et al. Impact of gastroenterology consultation on the outcomes of patients admitted to the hospital with decompensated cirrhosis. Hepatology 2001;34:1089–1095.
Reprint requests Address requests for reprints to: Michael L. Volk, MD, MSc, Division of Gastroenterology and Hepatology, University of Michigan Health System, 300 N Ingalls, 7C27, Ann Arbor, Michigan 48103. e-mail: [email protected] Funding Dr Volk is funded by K23DK085304 from the National Institutes of Health. Conflicts of interest The author discloses no conflicts. © 2012 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2012.05.014
Mesenchymal Stem Cells and Prostaglandins May Be Critical for Intestinal Wound Repair See “Igf2bp1 is required for full induction of Ptgs2 mRNA in colonic mesenchymal stem cells in mice,” by Manieri NA, Drylewicz MR, Miyoshi H, et al, on page 110.
T
he article by Manieri et al1 adds new information and tantalizing novel ideas to presently held concepts pertaining to the current paradigm for intestinal wound healing. Based on studies of the healing of full-thickness biopsies of the colon in prostaglandin endoperoxide synthase Ptgs 2 (Cox2)⫺/⫺ and wild-type mice, the current article proposes that (1) prostaglandins are the key initiators and critical molecule for wound healing in the intestine and (2) colonic mesenchymal stem cells (cMSC), which express the highest levels of Ptgs2 protein in the lamina propria after intestinal wounding, are the critical cells involved. Further, it identifies insulin-like growth factor 2 binding protein 1 (Igf2bp1) as a novel Ptgs2 mRNAbinding protein that binds to the AU-rich elements in the 3= untranslated end of the message imparting message stability and translational efficiency, serving as a scaffold for other RNA binding proteins and directing its intracellular location. Igf2bp1 is an oncofetal protein expressed in embryos, where it is important in development, but also is overexpressed in a high percentage of colorectal carcinomas. Thus, the article has translational value because this binding factor is a potential target for cancer chemopre-
ventative development, because agents inhibiting this mRNA-binding factor might have fewer side effects than nonsteroidal anti-inflammatory drugs or other Ptgs2-inhibitors. The classic model of wound healing, based mainly on studies of the integument but on intestine as well, proposes a cascade of 4 separate phases.2–5 The hemostasis phase begins when the wound is inflicted and platelet degranulation and fibrin formation provide hemostasis and a provisional matrix on and in which the subsequent events of healing take place. Early response cytokine and chemokine genes in the epithelium and lamina propria stromal cells and leukocytes are activated by the innate immune system. Release of prostaglandins, inflammatory and regulatory cytokines (the initial Th1 response was rapidly followed by a Th2 response), chemotactic cytokines (eg, platelet-derived growth factor), and chemokines initiate the inflammatory phase, with all the traditional host manifestations of inflammation. The relative importance of various leukocytes (neutrophils, macrophages, dendritic cells, and lymphocytes) and fibroblasts (especially activated fibroblasts or myofibroblasts) in this process is not clear. It is clear in cutaneous wound healing that myofibroblasts form adhesion complexes to matrix and to each other and then contract to reduce the area of the wound. During the proliferative phase, myofibroblasts secrete collagen and other matrix molecules (glycoproteins and pro19