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Preventing renal disease progression: Can complete renin-angiotensin-aldosterone blockade work?
Perhaps the most daunting challenge for any primary care physician, nephrologist, or other internal medicine specialist is how to prevent the progression of chronic kidney disease.
A MAJOR HEALTH CARE CRISIS
Ten to 20 million people in the United States have chronic kidney disease, with diabetic nephropathy and arterial hypertension accounting for two-thirds of cases. In 2007, the US Renal Data System1 reported that, at the end of 2005, 341,319 patients were receiving dialysis and another 143,693 had received renal transplants.
The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiatives2 has raised the level of awareness of chronic kidney disease among physicians and the general public. We have become more adept at diagnosing chronic kidney disease, in particular by calculating the estimated glomerular filtration rate, and we are starting to learn how to sort out the patients designated as having chronic kidney disease by this calculation but without “true” kidney disease. Nevertheless, the medical profession is still struggling to determine the best way to prevent progression in chronic kidney disease, and no single innovative approach currently exists. Should the emphasis be on the blood pressure target, the level of proteinuria reduction, the classes of medications to be used, or on other factors such as lipid control, vitamin D repletion,3 or glycemic control?
WHY INHIBIT THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM?
Over the last 20 years, investigators have devoted much effort to controlling the adverse effects of the renin-angiotensin-aldosterone system on the renal vasculature and parenchyma. We now understand that this system is a complex cascade and that angiotensin II plays a key role.
Angiotensin II enhances the vascular tone of both the afferent and the efferent glomerular arterioles, helps regulate intraglomerular pressure and glomerular filtration, and stimulates the adrenal cortex to release aldosterone. In addition, it has several nonhemodynamic effects. In particular, it may alter the selective permeability of the glomerular capillary barrier by influencing podocyte morphology and by directing a reorganization of its actin cytostructure.
Podocytes are highly differentiated pericyte-like cells that are essential for normal kidney function, but they have limited regenerative ability. Angiotensin II stimulation can lead to podocyte injury via mechanical stress due to increased intraglomerular pressure or an increase in cytosolic calcium,4 formation of bridging between the parietal basement membrane and the glomerular basement membrane,5 and extension of the extracapillary disease process to the glomerular-proximal tubular junction.6 These alterations can result in progressive atrophy, cell death, subsequent fibrosis, and irreversible loss in functioning renal parenchyma.
EVIDENCE FOR AND AGAINST COMBINATION THERAPY
In theory, by completely inhibiting the renin-angiotensin-aldosterone system in some patients with proteinuric chronic kidney disease (as Dr. Sheldon Hirsch suggests in this issue of the Cleveland Clinic Journal of Medicine7), we might be better able to prevent progressive renal injury than with an incomplete blockade of this system.
The rationale for complete blockade stems from evidence that long-term treatment with an angiotensin-converting enzyme (ACE) inhibitor results in the accumulation of angiotensin I, the escape of angiotensin II generation by ACE-independent enzymes (chymases), and the inhibition of angiotensin-(1–7) formation that partially antagonizes the effects of angiotensin II. In addition, aldosterone may injure the kidney by its rapid nongenomic effect on the renal vasculature, resulting in increased renal vascular resistance, with afferent and efferent vasoconstriction. Therefore, treatment with either an ACE inhibitor or an angiotensin receptor blocker (ARB) by itself may delay but not prevent end-stage renal disease for most patients with proteinuric chronic kidney disease.8
Combining an ACE inhibitor and an ARB
Regimens in which an ACE inhibitor is combined with an ARB may achieve their therapeutic benefit of lowering proteinuria by modulating the compensatory events in kidney injury that stress “normal” nephrons, inhibiting the podocyte injury responsible for contiguous damage in the tubulointerstitial area, and limiting fibrosis and inflammation. However, few trials actually showed that combining an ACE inhibitor with an ARB leads to greater renal protection in the long term than with either agent alone, despite a greater chance of lowering the protein excretion rate.9,10
The COOPERATE study. The Combination Treatment of Angiotensin II Receptor Blocker and Angiotensin-Converting-Enzyme Inhibitor in Non-diabetic Renal Disease (COOPERATE) study11 evaluated the renoprotective effects of the combination of trandolapril (Mavik, an ACE inhibitor) and losartan (Cozaar, an ARB). Significantly fewer patients reached one of the end points (doubling of the serum creatinine concentration or end-stage renal disease) with the combined therapy than with either agent alone.
Kunz et al12 recently performed a meta-analysis, which indicated that the combination of an ACE inhibitor and an ARB reduces proteinuria to a greater extent than either drug alone. However, the total number of patients in each trial was less than 30 on average, the duration of therapy rarely exceeded 1 year, and the effect on changes in the glomerular filtration rate or the need for dialysis was not reported.
ONTARGET. In the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET),13 combination therapy had no clear benefit in the group at the highest renal risk (ie, with overt diabetic nephropathy), and it was associated with a trend toward worse results in the low-risk group. Most participants in ONTARGET did not have microalbuminuria or macroalbuminuria, and of interest, these patients without protein excretion were at increased risk for renal events, such as acute renal failure requiring dialysis.
Phillips et al14 recently reported on the safety profile of patients with symptomatic left ventricular dysfunction treated with the combination of an ACE inhibitor and an ARB. Even in these nonrenal patients there was a significantly higher risk of worsening renal dysfunction (relative risk 4.87, 95% confidence interval 2.39–9.94) and hyperkalemia (relative risk 4.87, 95% confidence interval 2.39–9.94) with combination therapy.
Adding an aldosterone blocker to an ACE inhibitor, ARB, or both
There is little evidence that aldosterone plays a role in the progression of chronic kidney disease. However, several studies found that combining an aldosterone blocker with an ACE inhibitor, ARB, or both had an additional impact on reducing proteinuria and modulating the rate of change in the glomerular filtration rate.15–17
When aldosterone antagonists were added to an ACE inhibitor, an ARB, or both combined, proteinuria was reduced, but there was little effect on preserving the glomerular filtration rate.17 However, most of the studies were small, with short observation periods. Hyperkalemia is a risk when using aldosterone antagonists in combination with ACE inhibitors and ARBs, especially in patients with glomerular filtration rates less than 30 mL/minute.18
Adding a renin inhibitor to an ACE inhibitor or an ARB
Few studies have examined combination therapy with either an ACE inhibitor or ARB plus a renin inhibitor, the newest class of agents that block this system.
Parving et al19 recently reported the results of combining aliskiren (Tekturna, a renin inhibitor) with losartan in 599 patients with type 2 diabetes and nephropathy. At 6 months, the renin inhibitor showed a renoprotective effect that was independent of its blood-pressure-lowering effect in those who were receiving maximal recommended doses of the ARB.
OTHER FACTORS ALSO INFLUENCE PROGRESSION
Even though there is broad agreement that an approach that neutralizes the effects of the renin-angiotensin-aldosterone system on the kidney would lower blood pressure and protein excretion rates, whether it would change the natural history of chronic kidney disease and prevent progression is less clear. In reality, a number of factors other than the renin-angiotensin-aldosterone system are responsible for the progression of chronic kidney disease. These other factors may help explain why control of this system does not totally prevent deterioration of chronic kidney disease, although the rate may be slowed.
MORE QUESTIONS THAN ANSWERS
A number of provocative questions arise from Dr. Hirsch’s discussion of complete renin-angiotensin-aldosterone system blockade to prevent disease progression:
- Will decreasing proteinuria to a specific target (< 500 mg/day) prevent progression?
- How low should the blood pressure target be set to modulate progression, and should it be the same in all age groups?
- Should complete blockade be applied all at once or in a stepwise fashion depending on the glomerular filtration rate, the level of proteinuria, or both?
- Which patients would benefit most from complete blockade?
- Is direct renin inhibition a critical component of complete blockade?
- What model of chronic disease management is required to avoid unexpected complications if this treatment approach is embraced?
Currently, therefore, there are more questions than answers. This strategy is an intriguing, opinion-based option, but for now it should only be applied to patients with proteinuria and evidence of early progression despite standard therapy who can be closely monitored, and it is not for the faint of heart. In view of the risks of hyperkalemia, hypotension, and perhaps even worsening renal function, more data from carefully designed trials are needed before the general medical community widely applies a complete blockade of the renin-angiotensin-aldosterone pathway to prevent progressive chronic kidney disease.
- United States Renal Data System. Annual data report. www.usrds.org/adr.htm. Accessed 9/5/2008.
- National Kidney Foundation. NKF K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. www.kidney.org/Professionals/Kdoqi/guidelines_ckd/toc.htm. Accessed 9/5/2008.
- Remuzzi A. Vitamin D, insulin resistance, and renal disease. Kidney Int. 2007; 71:96–98.
- Pavenstadt H, Kriz W, Kretzler M. Cell biology of the glomerular podocyte. Physiol Rev. 2003; 83:253–307.
- Kriz W, Gretz N, Lemley KV. Progression of glomerular diseases: is the podocyte the culprit? Kidney Int 1998; 54:687–697.
- Endlich N, Endlich K. Stretch, tension and adhesion—adaptive mechanisms of the actin cytoskeleton in podocytes. Eur J Cell Biol. 2006; 85:229–234.
- Hirsch S. An update on proteinuric chronic kidney disease: the dual-goal approach. Cleve Clin J Med. 2008; 75:705–713.
- Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med. 1993; 329:1456–1462.
- Wolf G, Ritz E. Combination therapy with ACE inhibitors and angiotensin II receptor blockers to halt progression of chronic renal disease: pathophysiology and indications. Kidney Int. 2005; 67:799–812.
- Campbell R, Sangalli F, Perticucci E, et al. Effects of combined ACE inhibitor and angiotensin II antagonist treatment in human chronic nephropathies. Kidney Int. 2003; 63:1094–1103.
- Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T. Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. Lancet. 2003; 361:117–124.
- Kunz R, Friedrich C, Wolbers M, Mann JF. Meta-analysis: effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal disease. Ann Intern Med. 2008; 148:30–48.
- Mann JF, Schmieder RE, McQueen M, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet. 2008; 372:547–553.
- Phillips CO, Kashani A, Ko DK, Francis G, Krumholz HM. Adverse effects of combination angiotensin II receptor blockers plus angiotensin-converting enzyme inhibitors for left ventricular dysfunction: a quantitative review of data from randomized clinical trials. Arch Intern Med. 2007; 167:1930–1936.
- Epstein M. Adding spironolactone to conventional antihypertensives reduces albuminuria in patients with diabetic nephropathy. Nat Clin Pract Nephrol. 2006; 2:310–311.
- Rossing K, Schjoedt KJ, Smidt UM, Boomsma F, Parving HH. Beneficial effects of adding spironolactone to recommended antihypertensive treatment in diabetic nephropathy: a randomized, double-masked, cross-over study. Diabetes Care. 2005; 28:2106–2112.
- Bianchi S, Bigazzi R, Campese VM. Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease. Kidney Int. 2006; 70:2116–2123.
- Bomback AS, Kshirsagar AV, Amamoo MA, Klemmer PJ. Change in proteinuria after adding aldosterone blockers to ACE inhibitors or angiotensin receptor blockers in CKD: a systematic review. Am J Kidney Dis. 2008; 51:199–211.
- Parving HH, Persson F, Lewis JB, Lewis EJ, Hollenberg NK. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med. 2008; 358:2433–2446.
Perhaps the most daunting challenge for any primary care physician, nephrologist, or other internal medicine specialist is how to prevent the progression of chronic kidney disease.
A MAJOR HEALTH CARE CRISIS
Ten to 20 million people in the United States have chronic kidney disease, with diabetic nephropathy and arterial hypertension accounting for two-thirds of cases. In 2007, the US Renal Data System1 reported that, at the end of 2005, 341,319 patients were receiving dialysis and another 143,693 had received renal transplants.
The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiatives2 has raised the level of awareness of chronic kidney disease among physicians and the general public. We have become more adept at diagnosing chronic kidney disease, in particular by calculating the estimated glomerular filtration rate, and we are starting to learn how to sort out the patients designated as having chronic kidney disease by this calculation but without “true” kidney disease. Nevertheless, the medical profession is still struggling to determine the best way to prevent progression in chronic kidney disease, and no single innovative approach currently exists. Should the emphasis be on the blood pressure target, the level of proteinuria reduction, the classes of medications to be used, or on other factors such as lipid control, vitamin D repletion,3 or glycemic control?
WHY INHIBIT THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM?
Over the last 20 years, investigators have devoted much effort to controlling the adverse effects of the renin-angiotensin-aldosterone system on the renal vasculature and parenchyma. We now understand that this system is a complex cascade and that angiotensin II plays a key role.
Angiotensin II enhances the vascular tone of both the afferent and the efferent glomerular arterioles, helps regulate intraglomerular pressure and glomerular filtration, and stimulates the adrenal cortex to release aldosterone. In addition, it has several nonhemodynamic effects. In particular, it may alter the selective permeability of the glomerular capillary barrier by influencing podocyte morphology and by directing a reorganization of its actin cytostructure.
Podocytes are highly differentiated pericyte-like cells that are essential for normal kidney function, but they have limited regenerative ability. Angiotensin II stimulation can lead to podocyte injury via mechanical stress due to increased intraglomerular pressure or an increase in cytosolic calcium,4 formation of bridging between the parietal basement membrane and the glomerular basement membrane,5 and extension of the extracapillary disease process to the glomerular-proximal tubular junction.6 These alterations can result in progressive atrophy, cell death, subsequent fibrosis, and irreversible loss in functioning renal parenchyma.
EVIDENCE FOR AND AGAINST COMBINATION THERAPY
In theory, by completely inhibiting the renin-angiotensin-aldosterone system in some patients with proteinuric chronic kidney disease (as Dr. Sheldon Hirsch suggests in this issue of the Cleveland Clinic Journal of Medicine7), we might be better able to prevent progressive renal injury than with an incomplete blockade of this system.
The rationale for complete blockade stems from evidence that long-term treatment with an angiotensin-converting enzyme (ACE) inhibitor results in the accumulation of angiotensin I, the escape of angiotensin II generation by ACE-independent enzymes (chymases), and the inhibition of angiotensin-(1–7) formation that partially antagonizes the effects of angiotensin II. In addition, aldosterone may injure the kidney by its rapid nongenomic effect on the renal vasculature, resulting in increased renal vascular resistance, with afferent and efferent vasoconstriction. Therefore, treatment with either an ACE inhibitor or an angiotensin receptor blocker (ARB) by itself may delay but not prevent end-stage renal disease for most patients with proteinuric chronic kidney disease.8
Combining an ACE inhibitor and an ARB
Regimens in which an ACE inhibitor is combined with an ARB may achieve their therapeutic benefit of lowering proteinuria by modulating the compensatory events in kidney injury that stress “normal” nephrons, inhibiting the podocyte injury responsible for contiguous damage in the tubulointerstitial area, and limiting fibrosis and inflammation. However, few trials actually showed that combining an ACE inhibitor with an ARB leads to greater renal protection in the long term than with either agent alone, despite a greater chance of lowering the protein excretion rate.9,10
The COOPERATE study. The Combination Treatment of Angiotensin II Receptor Blocker and Angiotensin-Converting-Enzyme Inhibitor in Non-diabetic Renal Disease (COOPERATE) study11 evaluated the renoprotective effects of the combination of trandolapril (Mavik, an ACE inhibitor) and losartan (Cozaar, an ARB). Significantly fewer patients reached one of the end points (doubling of the serum creatinine concentration or end-stage renal disease) with the combined therapy than with either agent alone.
Kunz et al12 recently performed a meta-analysis, which indicated that the combination of an ACE inhibitor and an ARB reduces proteinuria to a greater extent than either drug alone. However, the total number of patients in each trial was less than 30 on average, the duration of therapy rarely exceeded 1 year, and the effect on changes in the glomerular filtration rate or the need for dialysis was not reported.
ONTARGET. In the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET),13 combination therapy had no clear benefit in the group at the highest renal risk (ie, with overt diabetic nephropathy), and it was associated with a trend toward worse results in the low-risk group. Most participants in ONTARGET did not have microalbuminuria or macroalbuminuria, and of interest, these patients without protein excretion were at increased risk for renal events, such as acute renal failure requiring dialysis.
Phillips et al14 recently reported on the safety profile of patients with symptomatic left ventricular dysfunction treated with the combination of an ACE inhibitor and an ARB. Even in these nonrenal patients there was a significantly higher risk of worsening renal dysfunction (relative risk 4.87, 95% confidence interval 2.39–9.94) and hyperkalemia (relative risk 4.87, 95% confidence interval 2.39–9.94) with combination therapy.
Adding an aldosterone blocker to an ACE inhibitor, ARB, or both
There is little evidence that aldosterone plays a role in the progression of chronic kidney disease. However, several studies found that combining an aldosterone blocker with an ACE inhibitor, ARB, or both had an additional impact on reducing proteinuria and modulating the rate of change in the glomerular filtration rate.15–17
When aldosterone antagonists were added to an ACE inhibitor, an ARB, or both combined, proteinuria was reduced, but there was little effect on preserving the glomerular filtration rate.17 However, most of the studies were small, with short observation periods. Hyperkalemia is a risk when using aldosterone antagonists in combination with ACE inhibitors and ARBs, especially in patients with glomerular filtration rates less than 30 mL/minute.18
Adding a renin inhibitor to an ACE inhibitor or an ARB
Few studies have examined combination therapy with either an ACE inhibitor or ARB plus a renin inhibitor, the newest class of agents that block this system.
Parving et al19 recently reported the results of combining aliskiren (Tekturna, a renin inhibitor) with losartan in 599 patients with type 2 diabetes and nephropathy. At 6 months, the renin inhibitor showed a renoprotective effect that was independent of its blood-pressure-lowering effect in those who were receiving maximal recommended doses of the ARB.
OTHER FACTORS ALSO INFLUENCE PROGRESSION
Even though there is broad agreement that an approach that neutralizes the effects of the renin-angiotensin-aldosterone system on the kidney would lower blood pressure and protein excretion rates, whether it would change the natural history of chronic kidney disease and prevent progression is less clear. In reality, a number of factors other than the renin-angiotensin-aldosterone system are responsible for the progression of chronic kidney disease. These other factors may help explain why control of this system does not totally prevent deterioration of chronic kidney disease, although the rate may be slowed.
MORE QUESTIONS THAN ANSWERS
A number of provocative questions arise from Dr. Hirsch’s discussion of complete renin-angiotensin-aldosterone system blockade to prevent disease progression:
- Will decreasing proteinuria to a specific target (< 500 mg/day) prevent progression?
- How low should the blood pressure target be set to modulate progression, and should it be the same in all age groups?
- Should complete blockade be applied all at once or in a stepwise fashion depending on the glomerular filtration rate, the level of proteinuria, or both?
- Which patients would benefit most from complete blockade?
- Is direct renin inhibition a critical component of complete blockade?
- What model of chronic disease management is required to avoid unexpected complications if this treatment approach is embraced?
Currently, therefore, there are more questions than answers. This strategy is an intriguing, opinion-based option, but for now it should only be applied to patients with proteinuria and evidence of early progression despite standard therapy who can be closely monitored, and it is not for the faint of heart. In view of the risks of hyperkalemia, hypotension, and perhaps even worsening renal function, more data from carefully designed trials are needed before the general medical community widely applies a complete blockade of the renin-angiotensin-aldosterone pathway to prevent progressive chronic kidney disease.
Perhaps the most daunting challenge for any primary care physician, nephrologist, or other internal medicine specialist is how to prevent the progression of chronic kidney disease.
A MAJOR HEALTH CARE CRISIS
Ten to 20 million people in the United States have chronic kidney disease, with diabetic nephropathy and arterial hypertension accounting for two-thirds of cases. In 2007, the US Renal Data System1 reported that, at the end of 2005, 341,319 patients were receiving dialysis and another 143,693 had received renal transplants.
The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiatives2 has raised the level of awareness of chronic kidney disease among physicians and the general public. We have become more adept at diagnosing chronic kidney disease, in particular by calculating the estimated glomerular filtration rate, and we are starting to learn how to sort out the patients designated as having chronic kidney disease by this calculation but without “true” kidney disease. Nevertheless, the medical profession is still struggling to determine the best way to prevent progression in chronic kidney disease, and no single innovative approach currently exists. Should the emphasis be on the blood pressure target, the level of proteinuria reduction, the classes of medications to be used, or on other factors such as lipid control, vitamin D repletion,3 or glycemic control?
WHY INHIBIT THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM?
Over the last 20 years, investigators have devoted much effort to controlling the adverse effects of the renin-angiotensin-aldosterone system on the renal vasculature and parenchyma. We now understand that this system is a complex cascade and that angiotensin II plays a key role.
Angiotensin II enhances the vascular tone of both the afferent and the efferent glomerular arterioles, helps regulate intraglomerular pressure and glomerular filtration, and stimulates the adrenal cortex to release aldosterone. In addition, it has several nonhemodynamic effects. In particular, it may alter the selective permeability of the glomerular capillary barrier by influencing podocyte morphology and by directing a reorganization of its actin cytostructure.
Podocytes are highly differentiated pericyte-like cells that are essential for normal kidney function, but they have limited regenerative ability. Angiotensin II stimulation can lead to podocyte injury via mechanical stress due to increased intraglomerular pressure or an increase in cytosolic calcium,4 formation of bridging between the parietal basement membrane and the glomerular basement membrane,5 and extension of the extracapillary disease process to the glomerular-proximal tubular junction.6 These alterations can result in progressive atrophy, cell death, subsequent fibrosis, and irreversible loss in functioning renal parenchyma.
EVIDENCE FOR AND AGAINST COMBINATION THERAPY
In theory, by completely inhibiting the renin-angiotensin-aldosterone system in some patients with proteinuric chronic kidney disease (as Dr. Sheldon Hirsch suggests in this issue of the Cleveland Clinic Journal of Medicine7), we might be better able to prevent progressive renal injury than with an incomplete blockade of this system.
The rationale for complete blockade stems from evidence that long-term treatment with an angiotensin-converting enzyme (ACE) inhibitor results in the accumulation of angiotensin I, the escape of angiotensin II generation by ACE-independent enzymes (chymases), and the inhibition of angiotensin-(1–7) formation that partially antagonizes the effects of angiotensin II. In addition, aldosterone may injure the kidney by its rapid nongenomic effect on the renal vasculature, resulting in increased renal vascular resistance, with afferent and efferent vasoconstriction. Therefore, treatment with either an ACE inhibitor or an angiotensin receptor blocker (ARB) by itself may delay but not prevent end-stage renal disease for most patients with proteinuric chronic kidney disease.8
Combining an ACE inhibitor and an ARB
Regimens in which an ACE inhibitor is combined with an ARB may achieve their therapeutic benefit of lowering proteinuria by modulating the compensatory events in kidney injury that stress “normal” nephrons, inhibiting the podocyte injury responsible for contiguous damage in the tubulointerstitial area, and limiting fibrosis and inflammation. However, few trials actually showed that combining an ACE inhibitor with an ARB leads to greater renal protection in the long term than with either agent alone, despite a greater chance of lowering the protein excretion rate.9,10
The COOPERATE study. The Combination Treatment of Angiotensin II Receptor Blocker and Angiotensin-Converting-Enzyme Inhibitor in Non-diabetic Renal Disease (COOPERATE) study11 evaluated the renoprotective effects of the combination of trandolapril (Mavik, an ACE inhibitor) and losartan (Cozaar, an ARB). Significantly fewer patients reached one of the end points (doubling of the serum creatinine concentration or end-stage renal disease) with the combined therapy than with either agent alone.
Kunz et al12 recently performed a meta-analysis, which indicated that the combination of an ACE inhibitor and an ARB reduces proteinuria to a greater extent than either drug alone. However, the total number of patients in each trial was less than 30 on average, the duration of therapy rarely exceeded 1 year, and the effect on changes in the glomerular filtration rate or the need for dialysis was not reported.
ONTARGET. In the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET),13 combination therapy had no clear benefit in the group at the highest renal risk (ie, with overt diabetic nephropathy), and it was associated with a trend toward worse results in the low-risk group. Most participants in ONTARGET did not have microalbuminuria or macroalbuminuria, and of interest, these patients without protein excretion were at increased risk for renal events, such as acute renal failure requiring dialysis.
Phillips et al14 recently reported on the safety profile of patients with symptomatic left ventricular dysfunction treated with the combination of an ACE inhibitor and an ARB. Even in these nonrenal patients there was a significantly higher risk of worsening renal dysfunction (relative risk 4.87, 95% confidence interval 2.39–9.94) and hyperkalemia (relative risk 4.87, 95% confidence interval 2.39–9.94) with combination therapy.
Adding an aldosterone blocker to an ACE inhibitor, ARB, or both
There is little evidence that aldosterone plays a role in the progression of chronic kidney disease. However, several studies found that combining an aldosterone blocker with an ACE inhibitor, ARB, or both had an additional impact on reducing proteinuria and modulating the rate of change in the glomerular filtration rate.15–17
When aldosterone antagonists were added to an ACE inhibitor, an ARB, or both combined, proteinuria was reduced, but there was little effect on preserving the glomerular filtration rate.17 However, most of the studies were small, with short observation periods. Hyperkalemia is a risk when using aldosterone antagonists in combination with ACE inhibitors and ARBs, especially in patients with glomerular filtration rates less than 30 mL/minute.18
Adding a renin inhibitor to an ACE inhibitor or an ARB
Few studies have examined combination therapy with either an ACE inhibitor or ARB plus a renin inhibitor, the newest class of agents that block this system.
Parving et al19 recently reported the results of combining aliskiren (Tekturna, a renin inhibitor) with losartan in 599 patients with type 2 diabetes and nephropathy. At 6 months, the renin inhibitor showed a renoprotective effect that was independent of its blood-pressure-lowering effect in those who were receiving maximal recommended doses of the ARB.
OTHER FACTORS ALSO INFLUENCE PROGRESSION
Even though there is broad agreement that an approach that neutralizes the effects of the renin-angiotensin-aldosterone system on the kidney would lower blood pressure and protein excretion rates, whether it would change the natural history of chronic kidney disease and prevent progression is less clear. In reality, a number of factors other than the renin-angiotensin-aldosterone system are responsible for the progression of chronic kidney disease. These other factors may help explain why control of this system does not totally prevent deterioration of chronic kidney disease, although the rate may be slowed.
MORE QUESTIONS THAN ANSWERS
A number of provocative questions arise from Dr. Hirsch’s discussion of complete renin-angiotensin-aldosterone system blockade to prevent disease progression:
- Will decreasing proteinuria to a specific target (< 500 mg/day) prevent progression?
- How low should the blood pressure target be set to modulate progression, and should it be the same in all age groups?
- Should complete blockade be applied all at once or in a stepwise fashion depending on the glomerular filtration rate, the level of proteinuria, or both?
- Which patients would benefit most from complete blockade?
- Is direct renin inhibition a critical component of complete blockade?
- What model of chronic disease management is required to avoid unexpected complications if this treatment approach is embraced?
Currently, therefore, there are more questions than answers. This strategy is an intriguing, opinion-based option, but for now it should only be applied to patients with proteinuria and evidence of early progression despite standard therapy who can be closely monitored, and it is not for the faint of heart. In view of the risks of hyperkalemia, hypotension, and perhaps even worsening renal function, more data from carefully designed trials are needed before the general medical community widely applies a complete blockade of the renin-angiotensin-aldosterone pathway to prevent progressive chronic kidney disease.
- United States Renal Data System. Annual data report. www.usrds.org/adr.htm. Accessed 9/5/2008.
- National Kidney Foundation. NKF K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. www.kidney.org/Professionals/Kdoqi/guidelines_ckd/toc.htm. Accessed 9/5/2008.
- Remuzzi A. Vitamin D, insulin resistance, and renal disease. Kidney Int. 2007; 71:96–98.
- Pavenstadt H, Kriz W, Kretzler M. Cell biology of the glomerular podocyte. Physiol Rev. 2003; 83:253–307.
- Kriz W, Gretz N, Lemley KV. Progression of glomerular diseases: is the podocyte the culprit? Kidney Int 1998; 54:687–697.
- Endlich N, Endlich K. Stretch, tension and adhesion—adaptive mechanisms of the actin cytoskeleton in podocytes. Eur J Cell Biol. 2006; 85:229–234.
- Hirsch S. An update on proteinuric chronic kidney disease: the dual-goal approach. Cleve Clin J Med. 2008; 75:705–713.
- Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med. 1993; 329:1456–1462.
- Wolf G, Ritz E. Combination therapy with ACE inhibitors and angiotensin II receptor blockers to halt progression of chronic renal disease: pathophysiology and indications. Kidney Int. 2005; 67:799–812.
- Campbell R, Sangalli F, Perticucci E, et al. Effects of combined ACE inhibitor and angiotensin II antagonist treatment in human chronic nephropathies. Kidney Int. 2003; 63:1094–1103.
- Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T. Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. Lancet. 2003; 361:117–124.
- Kunz R, Friedrich C, Wolbers M, Mann JF. Meta-analysis: effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal disease. Ann Intern Med. 2008; 148:30–48.
- Mann JF, Schmieder RE, McQueen M, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet. 2008; 372:547–553.
- Phillips CO, Kashani A, Ko DK, Francis G, Krumholz HM. Adverse effects of combination angiotensin II receptor blockers plus angiotensin-converting enzyme inhibitors for left ventricular dysfunction: a quantitative review of data from randomized clinical trials. Arch Intern Med. 2007; 167:1930–1936.
- Epstein M. Adding spironolactone to conventional antihypertensives reduces albuminuria in patients with diabetic nephropathy. Nat Clin Pract Nephrol. 2006; 2:310–311.
- Rossing K, Schjoedt KJ, Smidt UM, Boomsma F, Parving HH. Beneficial effects of adding spironolactone to recommended antihypertensive treatment in diabetic nephropathy: a randomized, double-masked, cross-over study. Diabetes Care. 2005; 28:2106–2112.
- Bianchi S, Bigazzi R, Campese VM. Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease. Kidney Int. 2006; 70:2116–2123.
- Bomback AS, Kshirsagar AV, Amamoo MA, Klemmer PJ. Change in proteinuria after adding aldosterone blockers to ACE inhibitors or angiotensin receptor blockers in CKD: a systematic review. Am J Kidney Dis. 2008; 51:199–211.
- Parving HH, Persson F, Lewis JB, Lewis EJ, Hollenberg NK. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med. 2008; 358:2433–2446.
- United States Renal Data System. Annual data report. www.usrds.org/adr.htm. Accessed 9/5/2008.
- National Kidney Foundation. NKF K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. www.kidney.org/Professionals/Kdoqi/guidelines_ckd/toc.htm. Accessed 9/5/2008.
- Remuzzi A. Vitamin D, insulin resistance, and renal disease. Kidney Int. 2007; 71:96–98.
- Pavenstadt H, Kriz W, Kretzler M. Cell biology of the glomerular podocyte. Physiol Rev. 2003; 83:253–307.
- Kriz W, Gretz N, Lemley KV. Progression of glomerular diseases: is the podocyte the culprit? Kidney Int 1998; 54:687–697.
- Endlich N, Endlich K. Stretch, tension and adhesion—adaptive mechanisms of the actin cytoskeleton in podocytes. Eur J Cell Biol. 2006; 85:229–234.
- Hirsch S. An update on proteinuric chronic kidney disease: the dual-goal approach. Cleve Clin J Med. 2008; 75:705–713.
- Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med. 1993; 329:1456–1462.
- Wolf G, Ritz E. Combination therapy with ACE inhibitors and angiotensin II receptor blockers to halt progression of chronic renal disease: pathophysiology and indications. Kidney Int. 2005; 67:799–812.
- Campbell R, Sangalli F, Perticucci E, et al. Effects of combined ACE inhibitor and angiotensin II antagonist treatment in human chronic nephropathies. Kidney Int. 2003; 63:1094–1103.
- Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T. Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. Lancet. 2003; 361:117–124.
- Kunz R, Friedrich C, Wolbers M, Mann JF. Meta-analysis: effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal disease. Ann Intern Med. 2008; 148:30–48.
- Mann JF, Schmieder RE, McQueen M, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet. 2008; 372:547–553.
- Phillips CO, Kashani A, Ko DK, Francis G, Krumholz HM. Adverse effects of combination angiotensin II receptor blockers plus angiotensin-converting enzyme inhibitors for left ventricular dysfunction: a quantitative review of data from randomized clinical trials. Arch Intern Med. 2007; 167:1930–1936.
- Epstein M. Adding spironolactone to conventional antihypertensives reduces albuminuria in patients with diabetic nephropathy. Nat Clin Pract Nephrol. 2006; 2:310–311.
- Rossing K, Schjoedt KJ, Smidt UM, Boomsma F, Parving HH. Beneficial effects of adding spironolactone to recommended antihypertensive treatment in diabetic nephropathy: a randomized, double-masked, cross-over study. Diabetes Care. 2005; 28:2106–2112.
- Bianchi S, Bigazzi R, Campese VM. Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease. Kidney Int. 2006; 70:2116–2123.
- Bomback AS, Kshirsagar AV, Amamoo MA, Klemmer PJ. Change in proteinuria after adding aldosterone blockers to ACE inhibitors or angiotensin receptor blockers in CKD: a systematic review. Am J Kidney Dis. 2008; 51:199–211.
- Parving HH, Persson F, Lewis JB, Lewis EJ, Hollenberg NK. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med. 2008; 358:2433–2446.
Editorial
In a minute or two the Caterpillar got down off the mushroom, and crawled away in the grass, merely remarking as it went, One side will make you grow taller, and the other side will make you grow shorter.
One side of WHAT? The other side of WHAT? thought Alice to herself.
Of the mushroom, said the Caterpillar.1
As a hospitalist of about 6 years, I enjoy hospital medicine and hope, over the course of my career, to see it develop into an increasingly respected, diverse, and influential specialty. There is abundant evidence that this is occurring, primarily through the praiseworthy efforts of the leadership and members of the Society of Hospital Medicine (SHM). Efforts to prove our value to inpatient care and align ourselves with quality improvement, as promoted early in the hospitalist movement,2 are coming to fruition. However, I would like to raise a flag of concern; and this is based on my experience working as a hospitalist in 10 community hospitals in 5 states, including positions as a locum tenens hospitalist, staff hospitalist, medical director of a hospitalist group, and full‐time teaching hospitalist for a community hospital residency program. I believe that hospitalists, particularly those working in community hospitals (approximately 80% of all hospitalists),3 are currently at a critical crossroad, with the option of either actively expanding their clinical, administrative, and quality improvement roles or allowing these roles to stagnate or atrophy. As in any career, we are, like Alice, perched on a mushroom, one side of which will make us grow taller and the other side of which will make us grow shorter. Which side are we choosing in our careers as hospitalists?
Hospitalists currently have numerous opportunities to expand their clinical, administrative, and quality improvement roles and responsibilities (Table 1), and these opportunities are in full alignment with the mission statement of SHM: to promote the highest quality of care for all hospitalized patients.4 My concern is that, for one reason or another, hospitalists in some settings are shrinking away from roles that they could or should fill, and this is a trend that I believe could affect our specialty adversely over time and that we, as an organization, should find ways to prevent. Although family medicine and traditional internal medicine physicians who work in the hospital face similar challenges, if we as hospitalists wish to qualify one day as board‐certified hospital medicine specialists, we are obligated to develop knowledge and skill sets that are truly unique to our profession.5 Holding to this goal, we cannot settle into a narrow comfort zone. I believe that the development of the hospital medicine core competencies by SHM6 was an important step in helping us define our intended reach, but even so, what are the specific growth factors or inhibitors that are influencing the expansion or shrinking of hospitalists and hospital medicine groups?
1. Quality improvement |
a. Participating in quality assessments, making and implementing plans for improvement, and assessing effects of interventions |
b. Assessing patient and family satisfaction with inpatient care and making and implementing plans for improvement |
c. Assessing primary care physician, emergency room, subspecialist, and hospital staff satisfaction with inpatient care and making and implementing plans for improvement |
d. Participating in the development and revision of clinical guidelines, pathways, and order sets to improve efficiency and uniformity of care on the basis of current evidence |
e. Developing multidisciplinary hospitalist rounds to improve the coordination and quality of care |
2. Professional development |
a. Developing new areas of knowledge and skill, such as certification in geriatric or palliative care medicine |
b. Developing processes of peer review (including chart review or case review) to ensure quality and uniformity of care within the hospitalist group |
c. Developing a system of continuing medical education for the hospitalist group to keep abreast of the latest evidence‐based guidelines |
3. Expansion of services |
a. Developing an in‐house procedure team to perform bedside procedures for other physicians |
b. Providing cross‐coverage for intensivists or other subspecialists at night or on weekends |
c. Developing, participating in, and improving rapid response teams and cardiac arrest teams |
d. Providing care or coverage for additional clinical areas, such as long‐term acute care hospital units or transitional care units |
e. Meeting with subspecialist groups to identify any inpatient needs they have that could be filled by hospitalists |
4. Teaching |
a. Participating in the medical education of residents and medical students |
b. Participating in nursing education efforts |
c. Promoting hospital medicine topics by speaking at hospital grand rounds or other local continuing medical education venues |
d. Promoting community health by participating in community education talks or workshops |
5. Utilization management |
a. Participating in utilization management committees |
b. Evaluating the length of stay and cost per case for specific diagnosis‐related groups and making and implementing plans for improvement |
c. Demonstrating cost savings and overall value to the hospital |
d. Reviewing and improving clinical documentation to optimize hospital billing processes |
6. Information technology |
a. Participating in the development and improvement of the electronic medical record system and the computerized physician order entry system |
7. Administrative |
a. Strategically planning with hospital administration to determine areas of highest priority |
8. Research |
a. Performing and publishing clinical research unique to the hospital setting |
On the basis of my observations, I believe that this problem is due in large part to a misalignment of incentives. Specifically, I believe that the expansion of hospitalist roles and responsibilities is often counteraligned with the bottom‐line productivity goals of the group. That is, to maintain high productivity, a hospitalist has a tendency to minimize his or her role in ways that save time. For example, there may be a tendency to overuse subspecialty consultations, which can take away some of the burden of complex clinical decision making, or to quickly transfer patients that are sicker and require more time to a higher level of care (if available). There may also be a tendency to avoid performing inpatient procedures (a significant part of the core competencies) because of time constraints and the demands of a higher census. Excessively rapid rounding results, and this diminishes other claimed benefits of the hospitalist model of care: patient satisfaction, safety, quality, and communication. Length‐of‐stay measures also suffer as productivity exceeds the limits of efficient care. Moreover, in such a productivity‐based environment, there is certainly no incentive for hospitalists to become enthusiastically involved in hospital committees, education, or quality improvement efforts, all of which are critical to the development of hospital medicine as a unique subspecialty. In essence, the incentive to expand one's role as a hospitalist in such a setting is almost completely absent, and I believe that this puts the future influence and reach of our specialty at significant risk.
Particularly as hospitals face increasing scrutiny about their quality and safety, and especially as the costs of hospital care increase and reimbursements threaten to decline, the value of hospitalists to the hospital has become different from that of all other physicians. Their value lies not in sheer productivity but in their ability to improve the cost, quality, efficiency, and safety of inpatient care simultaneously. If hospitalists settle into or are forced into a lesser role, hospital medicine will not be worthy of consideration as a unique subspecialty. Some of the remaining roles of the shrunken hospitalist may, at some point and in some settings, shift to nonphysicians,7 with a decline in the ratio of physicians to mid‐level providers in hospital medicine programs, and the jobs of some hospitalists will be effectively eliminated. Market forces will lead to improved training of mid‐level providers, allowing hospitals to fill inpatient care needs in a more cost‐effective way.
Having worked with some very capable nurse practitioners in 4 different community hospitals, I believe that a well‐trained mid‐level provider, with appropriate physician backup, can effectively manage many of the typical general medical admissions and surgical consultations seen in a community hospital setting. I admit that this may not be the case in larger referral centers or academic medical centers.
In developing and defining this new specialty and also in training new physicians for the field, we do not want to lose this transient opportunity to define ourselves as broadly as possible, pushing beyond traditional internal medicine to new areas of inpatient care and management and managing more complex conditions than a traditional primary care physician would typically manage, conditions that have always fallen within the broad spectrum of inpatient internal medicine (Table 2). If we instead develop a tendency to admit, consult, and walk away and do not have the time or appropriate incentives to expand our roles in other important ways (noted in Table 1) because of a focus on productivity, what is our specialty destined to become?
Medical Condition | Potential Consult |
---|---|
Instructions: For each clinical condition, describe what testing and management of the condition that you, as a hospital medicine specialist, would independently perform before consulting the associated subspecialist. Identify what specific clinical findings would prompt a consultation. Also, ask yourself into which areas you could reasonably expand your clinical practice as a hospitalist with additional experience, training, or study. | |
Abdominal pain | Gastroenterology |
Surgery | |
Abnormal electrocardiogram | Cardiology |
Abnormal thyroid‐stimulating hormone | Endocrinology |
Acute renal failure | Nephrology |
Anemia | Hematology |
Gastroenterology | |
Ascites | Gastroenterology |
Atrial fibrillation, new or uncontrolled | Cardiology |
Bacteremia | Infectious disease |
Central venous access | Surgery |
Anesthesiology | |
Chest pain | Cardiology |
Chronic obstructive pulmonary disease | Pulmonary |
Delirium/mental status change | Neurology |
Psychiatry | |
Depression/anxiety | Psychiatry |
Diabetes, uncontrolled | Endocrinology |
Diabetic ketoacidosis | Endocrinology |
Diarrhea | Gastroenterology |
End‐of‐life care | Palliative care |
Fever | Infectious disease |
Gastrointestinal bleed | Gastroenterology |
Grief | Chaplain |
Heart murmur | Cardiology |
Hematuria | Urology |
Hypercalcemia | Endocrine |
Hypertension, uncontrolled | Cardiology |
Nephrology | |
Hyponatremia | Nephrology |
Hypoxia/respiratory failure | Pulmonary |
Infection | Infectious disease |
Joint effusion | Orthopedics |
Rheumatology | |
Kidney stone | Urology |
Meningitis | Infectious disease |
Neutropenic fever | Hematology/oncology |
Nonsustained ventricular tachycardia | Cardiology |
Nose bleed | Ear, nose, and throat |
Pain | Pain management |
Paroxysmal supraventricular tachycardia | Cardiology |
Pleural effusion | Pulmonary |
Preoperative clearance | Cardiology |
Pulmonary | |
Pulmonary embolism | Pulmonary |
Hematology | |
Rash | Dermatology |
Stroke | Neurology |
Syncope | Neurology |
Cardiology | |
Thrombocytopenia | Hematology |
Unstable angina | Cardiology |
Urinary retention | Urology |
Venous thromboembolism | Hematology |
That said, how can incentives be restructured to encourage hospitalists to expand their universe? Perhaps the simplest way of influencing the incentive structure of hospital medicine programs is more selectivity in the choice of jobs: seeking out jobs that offer us clear incentives (typically financial) to expand our universe by rewarding efforts to improve the quality, safety, and efficiency of inpatient care. According to the SHM 20052006 survey, about two‐thirds of responding hospital medicine programs reimbursed their physicians with a mix of salary and productivity/performance bonuses, with productivity being the dominant incentive (more than 80%). However, bonuses based on quality/efficiency measures were also being rewarded (about 60%), as well as bonuses for committee or project work (about 25%). Of all responding groups, that leaves about 60% of programs with no financial incentives for quality/efficiency measures. There is certainly room for progress in this area, and we can influence the process positively by requesting that such incentives be added to our contract before making a final commitment to a job or by negotiating changes to our current incentive structure at the time of contract renewal. This would be in the best interest of our individual careers as well as our specialty.
As we consider different job opportunities, we may also wish to consider the possible effect of the employment model on the incentive structure. Although it may seem logical that hospital‐employed groups would have broader goals than independent groups and thus might be more motivated to provide proper incentives, I do not believe that this is the case universally. Conversely, private groups who might be expected to focus more on productivity measures may actually offer excellent growth‐promoting incentives. In either case, careful consideration of the incentive structure is warranted when we choose to work in a given employment model.
Perhaps another way of encouraging hospitalists to expand their role would be through a program of national recognition, potentially established by SHM, that would allow individual hospitalists to formally claim specialization in a particular area of hospital medicine and benefit from such distinctions. For example, a hospitalist that was particularly proficient with inpatient procedures could submit documentation of procedures completed in a given time period and subsequently receive a formal designation as a certified procedural hospitalist or something similar. Alternatively, a hospitalist who preferred to focus on quality improvement efforts could submit information regarding his involvement with quality improvement initiatives and results and, on the basis of defined criteria, receive a formal designation as a quality improvement hospitalist. This approach could apply to any area of focus, and more than one designation could be achieved by each hospitalist. As the specialty of hospital medicine matures, these designations (similar to academic rank) could eventually correlate with salary ranges or incentive bonuses as hospitals learned to value the diverse skills of individual hospitalists.
Discouraging overconsultation of subspecialists while concurrently encouraging the broadening of our clinical skills is particularly difficult to address. The only solution to this issue that I can imagine would be to somehow align physician reimbursement more closely to the actual complexity of and time spent in managing patients with multiple comorbidities. Currently, the actual hospitalist physician reimbursement for subsequent visits of patients, with or without subspecialists involved, likely does not vary much. However, if hospitalists knew their extra effort in managing more complex conditions would be reimbursed differently (ie, billing for critical care time), they would certainly tend to broaden their practice to the benefit of their careers and the future of the specialty.
In summary, I believe that misaligned incentives are causing some hospitalists to underestimate their potential; this has the potential to adversely affect the future of the specialty of hospital medicine. I hope that this opinion will serve to generate discussion on the potential origins of and solutions to this problem and ultimately promote the future expansion of our hospital medicine universe, so that we do not find ourselves in Alice's predicament:
Well, I should like to be a LITTLE larger, sir, if you wouldn't mind said Alice: three inches is such a wretched height to be.1
- Alice's Adventures in Wonderland.London, England:McMillan 1865. .
- Reflections: the hospitalist movement a decade later.J Hosp Med.2006;1:248–252. .
- Society of Hospital Medicine. 2005‐2006 SHM Survey: State of the Hospital Medicine Movement. Available at: http://www.hospitalmedicine.org/AM/Template.cfm?Section=Surveys22:102–104.
- Core competencies of hospital medicine: development and methodology.J Hosp Med.2006;1:48–56. , , , , .
- Trends in care by nonphysician clinicians in the United States.N Engl J Med.2003;348(2):130–137. , , , , .
In a minute or two the Caterpillar got down off the mushroom, and crawled away in the grass, merely remarking as it went, One side will make you grow taller, and the other side will make you grow shorter.
One side of WHAT? The other side of WHAT? thought Alice to herself.
Of the mushroom, said the Caterpillar.1
As a hospitalist of about 6 years, I enjoy hospital medicine and hope, over the course of my career, to see it develop into an increasingly respected, diverse, and influential specialty. There is abundant evidence that this is occurring, primarily through the praiseworthy efforts of the leadership and members of the Society of Hospital Medicine (SHM). Efforts to prove our value to inpatient care and align ourselves with quality improvement, as promoted early in the hospitalist movement,2 are coming to fruition. However, I would like to raise a flag of concern; and this is based on my experience working as a hospitalist in 10 community hospitals in 5 states, including positions as a locum tenens hospitalist, staff hospitalist, medical director of a hospitalist group, and full‐time teaching hospitalist for a community hospital residency program. I believe that hospitalists, particularly those working in community hospitals (approximately 80% of all hospitalists),3 are currently at a critical crossroad, with the option of either actively expanding their clinical, administrative, and quality improvement roles or allowing these roles to stagnate or atrophy. As in any career, we are, like Alice, perched on a mushroom, one side of which will make us grow taller and the other side of which will make us grow shorter. Which side are we choosing in our careers as hospitalists?
Hospitalists currently have numerous opportunities to expand their clinical, administrative, and quality improvement roles and responsibilities (Table 1), and these opportunities are in full alignment with the mission statement of SHM: to promote the highest quality of care for all hospitalized patients.4 My concern is that, for one reason or another, hospitalists in some settings are shrinking away from roles that they could or should fill, and this is a trend that I believe could affect our specialty adversely over time and that we, as an organization, should find ways to prevent. Although family medicine and traditional internal medicine physicians who work in the hospital face similar challenges, if we as hospitalists wish to qualify one day as board‐certified hospital medicine specialists, we are obligated to develop knowledge and skill sets that are truly unique to our profession.5 Holding to this goal, we cannot settle into a narrow comfort zone. I believe that the development of the hospital medicine core competencies by SHM6 was an important step in helping us define our intended reach, but even so, what are the specific growth factors or inhibitors that are influencing the expansion or shrinking of hospitalists and hospital medicine groups?
1. Quality improvement |
a. Participating in quality assessments, making and implementing plans for improvement, and assessing effects of interventions |
b. Assessing patient and family satisfaction with inpatient care and making and implementing plans for improvement |
c. Assessing primary care physician, emergency room, subspecialist, and hospital staff satisfaction with inpatient care and making and implementing plans for improvement |
d. Participating in the development and revision of clinical guidelines, pathways, and order sets to improve efficiency and uniformity of care on the basis of current evidence |
e. Developing multidisciplinary hospitalist rounds to improve the coordination and quality of care |
2. Professional development |
a. Developing new areas of knowledge and skill, such as certification in geriatric or palliative care medicine |
b. Developing processes of peer review (including chart review or case review) to ensure quality and uniformity of care within the hospitalist group |
c. Developing a system of continuing medical education for the hospitalist group to keep abreast of the latest evidence‐based guidelines |
3. Expansion of services |
a. Developing an in‐house procedure team to perform bedside procedures for other physicians |
b. Providing cross‐coverage for intensivists or other subspecialists at night or on weekends |
c. Developing, participating in, and improving rapid response teams and cardiac arrest teams |
d. Providing care or coverage for additional clinical areas, such as long‐term acute care hospital units or transitional care units |
e. Meeting with subspecialist groups to identify any inpatient needs they have that could be filled by hospitalists |
4. Teaching |
a. Participating in the medical education of residents and medical students |
b. Participating in nursing education efforts |
c. Promoting hospital medicine topics by speaking at hospital grand rounds or other local continuing medical education venues |
d. Promoting community health by participating in community education talks or workshops |
5. Utilization management |
a. Participating in utilization management committees |
b. Evaluating the length of stay and cost per case for specific diagnosis‐related groups and making and implementing plans for improvement |
c. Demonstrating cost savings and overall value to the hospital |
d. Reviewing and improving clinical documentation to optimize hospital billing processes |
6. Information technology |
a. Participating in the development and improvement of the electronic medical record system and the computerized physician order entry system |
7. Administrative |
a. Strategically planning with hospital administration to determine areas of highest priority |
8. Research |
a. Performing and publishing clinical research unique to the hospital setting |
On the basis of my observations, I believe that this problem is due in large part to a misalignment of incentives. Specifically, I believe that the expansion of hospitalist roles and responsibilities is often counteraligned with the bottom‐line productivity goals of the group. That is, to maintain high productivity, a hospitalist has a tendency to minimize his or her role in ways that save time. For example, there may be a tendency to overuse subspecialty consultations, which can take away some of the burden of complex clinical decision making, or to quickly transfer patients that are sicker and require more time to a higher level of care (if available). There may also be a tendency to avoid performing inpatient procedures (a significant part of the core competencies) because of time constraints and the demands of a higher census. Excessively rapid rounding results, and this diminishes other claimed benefits of the hospitalist model of care: patient satisfaction, safety, quality, and communication. Length‐of‐stay measures also suffer as productivity exceeds the limits of efficient care. Moreover, in such a productivity‐based environment, there is certainly no incentive for hospitalists to become enthusiastically involved in hospital committees, education, or quality improvement efforts, all of which are critical to the development of hospital medicine as a unique subspecialty. In essence, the incentive to expand one's role as a hospitalist in such a setting is almost completely absent, and I believe that this puts the future influence and reach of our specialty at significant risk.
Particularly as hospitals face increasing scrutiny about their quality and safety, and especially as the costs of hospital care increase and reimbursements threaten to decline, the value of hospitalists to the hospital has become different from that of all other physicians. Their value lies not in sheer productivity but in their ability to improve the cost, quality, efficiency, and safety of inpatient care simultaneously. If hospitalists settle into or are forced into a lesser role, hospital medicine will not be worthy of consideration as a unique subspecialty. Some of the remaining roles of the shrunken hospitalist may, at some point and in some settings, shift to nonphysicians,7 with a decline in the ratio of physicians to mid‐level providers in hospital medicine programs, and the jobs of some hospitalists will be effectively eliminated. Market forces will lead to improved training of mid‐level providers, allowing hospitals to fill inpatient care needs in a more cost‐effective way.
Having worked with some very capable nurse practitioners in 4 different community hospitals, I believe that a well‐trained mid‐level provider, with appropriate physician backup, can effectively manage many of the typical general medical admissions and surgical consultations seen in a community hospital setting. I admit that this may not be the case in larger referral centers or academic medical centers.
In developing and defining this new specialty and also in training new physicians for the field, we do not want to lose this transient opportunity to define ourselves as broadly as possible, pushing beyond traditional internal medicine to new areas of inpatient care and management and managing more complex conditions than a traditional primary care physician would typically manage, conditions that have always fallen within the broad spectrum of inpatient internal medicine (Table 2). If we instead develop a tendency to admit, consult, and walk away and do not have the time or appropriate incentives to expand our roles in other important ways (noted in Table 1) because of a focus on productivity, what is our specialty destined to become?
Medical Condition | Potential Consult |
---|---|
Instructions: For each clinical condition, describe what testing and management of the condition that you, as a hospital medicine specialist, would independently perform before consulting the associated subspecialist. Identify what specific clinical findings would prompt a consultation. Also, ask yourself into which areas you could reasonably expand your clinical practice as a hospitalist with additional experience, training, or study. | |
Abdominal pain | Gastroenterology |
Surgery | |
Abnormal electrocardiogram | Cardiology |
Abnormal thyroid‐stimulating hormone | Endocrinology |
Acute renal failure | Nephrology |
Anemia | Hematology |
Gastroenterology | |
Ascites | Gastroenterology |
Atrial fibrillation, new or uncontrolled | Cardiology |
Bacteremia | Infectious disease |
Central venous access | Surgery |
Anesthesiology | |
Chest pain | Cardiology |
Chronic obstructive pulmonary disease | Pulmonary |
Delirium/mental status change | Neurology |
Psychiatry | |
Depression/anxiety | Psychiatry |
Diabetes, uncontrolled | Endocrinology |
Diabetic ketoacidosis | Endocrinology |
Diarrhea | Gastroenterology |
End‐of‐life care | Palliative care |
Fever | Infectious disease |
Gastrointestinal bleed | Gastroenterology |
Grief | Chaplain |
Heart murmur | Cardiology |
Hematuria | Urology |
Hypercalcemia | Endocrine |
Hypertension, uncontrolled | Cardiology |
Nephrology | |
Hyponatremia | Nephrology |
Hypoxia/respiratory failure | Pulmonary |
Infection | Infectious disease |
Joint effusion | Orthopedics |
Rheumatology | |
Kidney stone | Urology |
Meningitis | Infectious disease |
Neutropenic fever | Hematology/oncology |
Nonsustained ventricular tachycardia | Cardiology |
Nose bleed | Ear, nose, and throat |
Pain | Pain management |
Paroxysmal supraventricular tachycardia | Cardiology |
Pleural effusion | Pulmonary |
Preoperative clearance | Cardiology |
Pulmonary | |
Pulmonary embolism | Pulmonary |
Hematology | |
Rash | Dermatology |
Stroke | Neurology |
Syncope | Neurology |
Cardiology | |
Thrombocytopenia | Hematology |
Unstable angina | Cardiology |
Urinary retention | Urology |
Venous thromboembolism | Hematology |
That said, how can incentives be restructured to encourage hospitalists to expand their universe? Perhaps the simplest way of influencing the incentive structure of hospital medicine programs is more selectivity in the choice of jobs: seeking out jobs that offer us clear incentives (typically financial) to expand our universe by rewarding efforts to improve the quality, safety, and efficiency of inpatient care. According to the SHM 20052006 survey, about two‐thirds of responding hospital medicine programs reimbursed their physicians with a mix of salary and productivity/performance bonuses, with productivity being the dominant incentive (more than 80%). However, bonuses based on quality/efficiency measures were also being rewarded (about 60%), as well as bonuses for committee or project work (about 25%). Of all responding groups, that leaves about 60% of programs with no financial incentives for quality/efficiency measures. There is certainly room for progress in this area, and we can influence the process positively by requesting that such incentives be added to our contract before making a final commitment to a job or by negotiating changes to our current incentive structure at the time of contract renewal. This would be in the best interest of our individual careers as well as our specialty.
As we consider different job opportunities, we may also wish to consider the possible effect of the employment model on the incentive structure. Although it may seem logical that hospital‐employed groups would have broader goals than independent groups and thus might be more motivated to provide proper incentives, I do not believe that this is the case universally. Conversely, private groups who might be expected to focus more on productivity measures may actually offer excellent growth‐promoting incentives. In either case, careful consideration of the incentive structure is warranted when we choose to work in a given employment model.
Perhaps another way of encouraging hospitalists to expand their role would be through a program of national recognition, potentially established by SHM, that would allow individual hospitalists to formally claim specialization in a particular area of hospital medicine and benefit from such distinctions. For example, a hospitalist that was particularly proficient with inpatient procedures could submit documentation of procedures completed in a given time period and subsequently receive a formal designation as a certified procedural hospitalist or something similar. Alternatively, a hospitalist who preferred to focus on quality improvement efforts could submit information regarding his involvement with quality improvement initiatives and results and, on the basis of defined criteria, receive a formal designation as a quality improvement hospitalist. This approach could apply to any area of focus, and more than one designation could be achieved by each hospitalist. As the specialty of hospital medicine matures, these designations (similar to academic rank) could eventually correlate with salary ranges or incentive bonuses as hospitals learned to value the diverse skills of individual hospitalists.
Discouraging overconsultation of subspecialists while concurrently encouraging the broadening of our clinical skills is particularly difficult to address. The only solution to this issue that I can imagine would be to somehow align physician reimbursement more closely to the actual complexity of and time spent in managing patients with multiple comorbidities. Currently, the actual hospitalist physician reimbursement for subsequent visits of patients, with or without subspecialists involved, likely does not vary much. However, if hospitalists knew their extra effort in managing more complex conditions would be reimbursed differently (ie, billing for critical care time), they would certainly tend to broaden their practice to the benefit of their careers and the future of the specialty.
In summary, I believe that misaligned incentives are causing some hospitalists to underestimate their potential; this has the potential to adversely affect the future of the specialty of hospital medicine. I hope that this opinion will serve to generate discussion on the potential origins of and solutions to this problem and ultimately promote the future expansion of our hospital medicine universe, so that we do not find ourselves in Alice's predicament:
Well, I should like to be a LITTLE larger, sir, if you wouldn't mind said Alice: three inches is such a wretched height to be.1
In a minute or two the Caterpillar got down off the mushroom, and crawled away in the grass, merely remarking as it went, One side will make you grow taller, and the other side will make you grow shorter.
One side of WHAT? The other side of WHAT? thought Alice to herself.
Of the mushroom, said the Caterpillar.1
As a hospitalist of about 6 years, I enjoy hospital medicine and hope, over the course of my career, to see it develop into an increasingly respected, diverse, and influential specialty. There is abundant evidence that this is occurring, primarily through the praiseworthy efforts of the leadership and members of the Society of Hospital Medicine (SHM). Efforts to prove our value to inpatient care and align ourselves with quality improvement, as promoted early in the hospitalist movement,2 are coming to fruition. However, I would like to raise a flag of concern; and this is based on my experience working as a hospitalist in 10 community hospitals in 5 states, including positions as a locum tenens hospitalist, staff hospitalist, medical director of a hospitalist group, and full‐time teaching hospitalist for a community hospital residency program. I believe that hospitalists, particularly those working in community hospitals (approximately 80% of all hospitalists),3 are currently at a critical crossroad, with the option of either actively expanding their clinical, administrative, and quality improvement roles or allowing these roles to stagnate or atrophy. As in any career, we are, like Alice, perched on a mushroom, one side of which will make us grow taller and the other side of which will make us grow shorter. Which side are we choosing in our careers as hospitalists?
Hospitalists currently have numerous opportunities to expand their clinical, administrative, and quality improvement roles and responsibilities (Table 1), and these opportunities are in full alignment with the mission statement of SHM: to promote the highest quality of care for all hospitalized patients.4 My concern is that, for one reason or another, hospitalists in some settings are shrinking away from roles that they could or should fill, and this is a trend that I believe could affect our specialty adversely over time and that we, as an organization, should find ways to prevent. Although family medicine and traditional internal medicine physicians who work in the hospital face similar challenges, if we as hospitalists wish to qualify one day as board‐certified hospital medicine specialists, we are obligated to develop knowledge and skill sets that are truly unique to our profession.5 Holding to this goal, we cannot settle into a narrow comfort zone. I believe that the development of the hospital medicine core competencies by SHM6 was an important step in helping us define our intended reach, but even so, what are the specific growth factors or inhibitors that are influencing the expansion or shrinking of hospitalists and hospital medicine groups?
1. Quality improvement |
a. Participating in quality assessments, making and implementing plans for improvement, and assessing effects of interventions |
b. Assessing patient and family satisfaction with inpatient care and making and implementing plans for improvement |
c. Assessing primary care physician, emergency room, subspecialist, and hospital staff satisfaction with inpatient care and making and implementing plans for improvement |
d. Participating in the development and revision of clinical guidelines, pathways, and order sets to improve efficiency and uniformity of care on the basis of current evidence |
e. Developing multidisciplinary hospitalist rounds to improve the coordination and quality of care |
2. Professional development |
a. Developing new areas of knowledge and skill, such as certification in geriatric or palliative care medicine |
b. Developing processes of peer review (including chart review or case review) to ensure quality and uniformity of care within the hospitalist group |
c. Developing a system of continuing medical education for the hospitalist group to keep abreast of the latest evidence‐based guidelines |
3. Expansion of services |
a. Developing an in‐house procedure team to perform bedside procedures for other physicians |
b. Providing cross‐coverage for intensivists or other subspecialists at night or on weekends |
c. Developing, participating in, and improving rapid response teams and cardiac arrest teams |
d. Providing care or coverage for additional clinical areas, such as long‐term acute care hospital units or transitional care units |
e. Meeting with subspecialist groups to identify any inpatient needs they have that could be filled by hospitalists |
4. Teaching |
a. Participating in the medical education of residents and medical students |
b. Participating in nursing education efforts |
c. Promoting hospital medicine topics by speaking at hospital grand rounds or other local continuing medical education venues |
d. Promoting community health by participating in community education talks or workshops |
5. Utilization management |
a. Participating in utilization management committees |
b. Evaluating the length of stay and cost per case for specific diagnosis‐related groups and making and implementing plans for improvement |
c. Demonstrating cost savings and overall value to the hospital |
d. Reviewing and improving clinical documentation to optimize hospital billing processes |
6. Information technology |
a. Participating in the development and improvement of the electronic medical record system and the computerized physician order entry system |
7. Administrative |
a. Strategically planning with hospital administration to determine areas of highest priority |
8. Research |
a. Performing and publishing clinical research unique to the hospital setting |
On the basis of my observations, I believe that this problem is due in large part to a misalignment of incentives. Specifically, I believe that the expansion of hospitalist roles and responsibilities is often counteraligned with the bottom‐line productivity goals of the group. That is, to maintain high productivity, a hospitalist has a tendency to minimize his or her role in ways that save time. For example, there may be a tendency to overuse subspecialty consultations, which can take away some of the burden of complex clinical decision making, or to quickly transfer patients that are sicker and require more time to a higher level of care (if available). There may also be a tendency to avoid performing inpatient procedures (a significant part of the core competencies) because of time constraints and the demands of a higher census. Excessively rapid rounding results, and this diminishes other claimed benefits of the hospitalist model of care: patient satisfaction, safety, quality, and communication. Length‐of‐stay measures also suffer as productivity exceeds the limits of efficient care. Moreover, in such a productivity‐based environment, there is certainly no incentive for hospitalists to become enthusiastically involved in hospital committees, education, or quality improvement efforts, all of which are critical to the development of hospital medicine as a unique subspecialty. In essence, the incentive to expand one's role as a hospitalist in such a setting is almost completely absent, and I believe that this puts the future influence and reach of our specialty at significant risk.
Particularly as hospitals face increasing scrutiny about their quality and safety, and especially as the costs of hospital care increase and reimbursements threaten to decline, the value of hospitalists to the hospital has become different from that of all other physicians. Their value lies not in sheer productivity but in their ability to improve the cost, quality, efficiency, and safety of inpatient care simultaneously. If hospitalists settle into or are forced into a lesser role, hospital medicine will not be worthy of consideration as a unique subspecialty. Some of the remaining roles of the shrunken hospitalist may, at some point and in some settings, shift to nonphysicians,7 with a decline in the ratio of physicians to mid‐level providers in hospital medicine programs, and the jobs of some hospitalists will be effectively eliminated. Market forces will lead to improved training of mid‐level providers, allowing hospitals to fill inpatient care needs in a more cost‐effective way.
Having worked with some very capable nurse practitioners in 4 different community hospitals, I believe that a well‐trained mid‐level provider, with appropriate physician backup, can effectively manage many of the typical general medical admissions and surgical consultations seen in a community hospital setting. I admit that this may not be the case in larger referral centers or academic medical centers.
In developing and defining this new specialty and also in training new physicians for the field, we do not want to lose this transient opportunity to define ourselves as broadly as possible, pushing beyond traditional internal medicine to new areas of inpatient care and management and managing more complex conditions than a traditional primary care physician would typically manage, conditions that have always fallen within the broad spectrum of inpatient internal medicine (Table 2). If we instead develop a tendency to admit, consult, and walk away and do not have the time or appropriate incentives to expand our roles in other important ways (noted in Table 1) because of a focus on productivity, what is our specialty destined to become?
Medical Condition | Potential Consult |
---|---|
Instructions: For each clinical condition, describe what testing and management of the condition that you, as a hospital medicine specialist, would independently perform before consulting the associated subspecialist. Identify what specific clinical findings would prompt a consultation. Also, ask yourself into which areas you could reasonably expand your clinical practice as a hospitalist with additional experience, training, or study. | |
Abdominal pain | Gastroenterology |
Surgery | |
Abnormal electrocardiogram | Cardiology |
Abnormal thyroid‐stimulating hormone | Endocrinology |
Acute renal failure | Nephrology |
Anemia | Hematology |
Gastroenterology | |
Ascites | Gastroenterology |
Atrial fibrillation, new or uncontrolled | Cardiology |
Bacteremia | Infectious disease |
Central venous access | Surgery |
Anesthesiology | |
Chest pain | Cardiology |
Chronic obstructive pulmonary disease | Pulmonary |
Delirium/mental status change | Neurology |
Psychiatry | |
Depression/anxiety | Psychiatry |
Diabetes, uncontrolled | Endocrinology |
Diabetic ketoacidosis | Endocrinology |
Diarrhea | Gastroenterology |
End‐of‐life care | Palliative care |
Fever | Infectious disease |
Gastrointestinal bleed | Gastroenterology |
Grief | Chaplain |
Heart murmur | Cardiology |
Hematuria | Urology |
Hypercalcemia | Endocrine |
Hypertension, uncontrolled | Cardiology |
Nephrology | |
Hyponatremia | Nephrology |
Hypoxia/respiratory failure | Pulmonary |
Infection | Infectious disease |
Joint effusion | Orthopedics |
Rheumatology | |
Kidney stone | Urology |
Meningitis | Infectious disease |
Neutropenic fever | Hematology/oncology |
Nonsustained ventricular tachycardia | Cardiology |
Nose bleed | Ear, nose, and throat |
Pain | Pain management |
Paroxysmal supraventricular tachycardia | Cardiology |
Pleural effusion | Pulmonary |
Preoperative clearance | Cardiology |
Pulmonary | |
Pulmonary embolism | Pulmonary |
Hematology | |
Rash | Dermatology |
Stroke | Neurology |
Syncope | Neurology |
Cardiology | |
Thrombocytopenia | Hematology |
Unstable angina | Cardiology |
Urinary retention | Urology |
Venous thromboembolism | Hematology |
That said, how can incentives be restructured to encourage hospitalists to expand their universe? Perhaps the simplest way of influencing the incentive structure of hospital medicine programs is more selectivity in the choice of jobs: seeking out jobs that offer us clear incentives (typically financial) to expand our universe by rewarding efforts to improve the quality, safety, and efficiency of inpatient care. According to the SHM 20052006 survey, about two‐thirds of responding hospital medicine programs reimbursed their physicians with a mix of salary and productivity/performance bonuses, with productivity being the dominant incentive (more than 80%). However, bonuses based on quality/efficiency measures were also being rewarded (about 60%), as well as bonuses for committee or project work (about 25%). Of all responding groups, that leaves about 60% of programs with no financial incentives for quality/efficiency measures. There is certainly room for progress in this area, and we can influence the process positively by requesting that such incentives be added to our contract before making a final commitment to a job or by negotiating changes to our current incentive structure at the time of contract renewal. This would be in the best interest of our individual careers as well as our specialty.
As we consider different job opportunities, we may also wish to consider the possible effect of the employment model on the incentive structure. Although it may seem logical that hospital‐employed groups would have broader goals than independent groups and thus might be more motivated to provide proper incentives, I do not believe that this is the case universally. Conversely, private groups who might be expected to focus more on productivity measures may actually offer excellent growth‐promoting incentives. In either case, careful consideration of the incentive structure is warranted when we choose to work in a given employment model.
Perhaps another way of encouraging hospitalists to expand their role would be through a program of national recognition, potentially established by SHM, that would allow individual hospitalists to formally claim specialization in a particular area of hospital medicine and benefit from such distinctions. For example, a hospitalist that was particularly proficient with inpatient procedures could submit documentation of procedures completed in a given time period and subsequently receive a formal designation as a certified procedural hospitalist or something similar. Alternatively, a hospitalist who preferred to focus on quality improvement efforts could submit information regarding his involvement with quality improvement initiatives and results and, on the basis of defined criteria, receive a formal designation as a quality improvement hospitalist. This approach could apply to any area of focus, and more than one designation could be achieved by each hospitalist. As the specialty of hospital medicine matures, these designations (similar to academic rank) could eventually correlate with salary ranges or incentive bonuses as hospitals learned to value the diverse skills of individual hospitalists.
Discouraging overconsultation of subspecialists while concurrently encouraging the broadening of our clinical skills is particularly difficult to address. The only solution to this issue that I can imagine would be to somehow align physician reimbursement more closely to the actual complexity of and time spent in managing patients with multiple comorbidities. Currently, the actual hospitalist physician reimbursement for subsequent visits of patients, with or without subspecialists involved, likely does not vary much. However, if hospitalists knew their extra effort in managing more complex conditions would be reimbursed differently (ie, billing for critical care time), they would certainly tend to broaden their practice to the benefit of their careers and the future of the specialty.
In summary, I believe that misaligned incentives are causing some hospitalists to underestimate their potential; this has the potential to adversely affect the future of the specialty of hospital medicine. I hope that this opinion will serve to generate discussion on the potential origins of and solutions to this problem and ultimately promote the future expansion of our hospital medicine universe, so that we do not find ourselves in Alice's predicament:
Well, I should like to be a LITTLE larger, sir, if you wouldn't mind said Alice: three inches is such a wretched height to be.1
- Alice's Adventures in Wonderland.London, England:McMillan 1865. .
- Reflections: the hospitalist movement a decade later.J Hosp Med.2006;1:248–252. .
- Society of Hospital Medicine. 2005‐2006 SHM Survey: State of the Hospital Medicine Movement. Available at: http://www.hospitalmedicine.org/AM/Template.cfm?Section=Surveys22:102–104.
- Core competencies of hospital medicine: development and methodology.J Hosp Med.2006;1:48–56. , , , , .
- Trends in care by nonphysician clinicians in the United States.N Engl J Med.2003;348(2):130–137. , , , , .
- Alice's Adventures in Wonderland.London, England:McMillan 1865. .
- Reflections: the hospitalist movement a decade later.J Hosp Med.2006;1:248–252. .
- Society of Hospital Medicine. 2005‐2006 SHM Survey: State of the Hospital Medicine Movement. Available at: http://www.hospitalmedicine.org/AM/Template.cfm?Section=Surveys22:102–104.
- Core competencies of hospital medicine: development and methodology.J Hosp Med.2006;1:48–56. , , , , .
- Trends in care by nonphysician clinicians in the United States.N Engl J Med.2003;348(2):130–137. , , , , .
Editorial
Accelerating the development of clinical research in academic hospitalist programs is a worthwhile goal if pursued with clarity, objectivity, and a thorough understanding of the process and its implications. In their articles, Flanders et al.1 and Wright et al.2 identify major barriers to growing academic hospitalist programs. These barriers include the need for protected time, the shortage of trained research faculty, the lack of infrastructure, and the limited availability of senior mentors. Both Flanders et al. and Wright et al. offer smart and innovative ways of addressing these issues. However, building an academic program from the ground up is more complex and challenging than it may seem at first glance. It takes time, patience, creativity, diplomacy, and the ability to recruit collaborators and advocates who are willing to share infrastructure and resources.
Although both articles add significantly to the discussion of strategies for creating an academic hospitalist program, they are unclear about the definition of academic in this context. The term academic is often misunderstood to be synonymous with research. However, research is just one component of an academic program, which also includes education, quality improvement (QI), administration, and program development. It may be helpful, therefore, to replace academic with scholarship, which can be defined as a process that involves peer review and dissemination of ideas at local, regional, and national levels. Scholarship also goes beyond research, encompassing education and other areas such as QI. Although academic programs are not necessarily involved with funded research, there is usually an expectation of peer review, through either presentations at regional and national meetings or publication. For the purposes of this discussion, the term academic hospitalist program will be defined broadly to include any program affiliated with a university that is involved in the teaching of residents and medical students and whose faculty is required to participate in a promotions process.
All members of an academic division should be expected to participate in scholarship, whether it is education, QI projects, or research. If there is a strong expectation that traditional National Institute of Health (NIH) funded research will take place, this expectation must come with sufficient resources. Without infrastructure for research and investment in research faculty, procuring NIH funds for research is not a reasonable expectation. Organizers of hospitalist programs currently within academic divisions of general internal medicine should consider ways to better integrate programs into the existing research infrastructure in their divisions. For either freestanding hospitalist programs or programs within academic divisions of general internal medicine, investments in infrastructure and faculty are needed to nurture this area of research and build an academic focus in hospital medicine. However, if obtaining NIH research funds is not the expectation and resources are not available for hospitalists or for any other division or department at that institution, then academic expectations should focus on other pursuits. Examples include participation in the education and QI initiatives.
For programs with expectations of both funded research and other scholarship, a successful program will most likely include a small core of skilled clinical researchers working closely with well‐trained clinical educators, all of whom are involved in scholarship. Both clinical educators and researchers need to be continuously developing, and to reach their full potential, all should have access to infrastructure that supports these activities, including resources such as MPH‐level project managers, research assistants, database managers, and, most importantly, appropriate mentors.
Clinician educators must be both proficient clinicians and dedicated teachers. Ideally, they should have strong familiarity with educational theory in addition to skills in hands‐on teaching. Their responsibilities include mastering the skills that students need, staying up to the minute in their areas of expertise, and serving as role models in their attitudes toward patients, colleagues, and their work.3 Many hospitalists may not have these skills when they begin, often fresh out of residency, and will need help developing them.
PROTECTED TIME
Protected time is crucial to the success of any academic program. Finding this time presents a challenge for any clinical group, but the challenge is exacerbated for hospitalists, who face tremendous pressure to serve full‐time clinical jobs with little emphasis on academic elements such as education, QI, and participation in funded research. As both Wright et al.2 and Flanders et al.1 point out, to build a group of well‐developed academic clinician educators, academic hospitalists not on track for funding need to be given adequate protected time to participate in committees, sharpen their teaching skills, develop QI projects that can be converted to scholarships, participate in research, and present at national and regional meetings.
The requirements of protected time for researchers are more challenging than those for educators. Building a newly funded research unit within a hospitalist group, as with any group, will entail hiring fellowship trained faculty with significant protected time (approximately 80%) to give them time to obtain funding such as a K award and eventually become independent investigators with RO1 grant funding. Building research units requires support from collaborators with infrastructure and mentors already in place that can be tapped during the incubation stage of the academic program. For most hospitalist programs, infrastructure and mentors will be found in their divisions of general internal medicine.
Protected time should be considered an integral element of academic hospitalist positionsnot a perkas long as the time is used responsibly and productively. As both Wright et al.2 and Flanders et al.1 correctly point out, herein lies the major challenge of creating any kind of academic program: How will the program support protected time for both educators and researchers? In most instances, significant seed money will be needed to support junior faculty over the first few years of their careers. It is noteworthy that building a federally funded hospital medicine research program will be particularly difficult in today's economy because funding levels at the NIH, Agency for Healthcare Research and Quality, Health Resources and Services Administration, and other traditional funders of clinical research either are flat or have been reduced dramatically.
To many Academic Medical Centers (AMC), it may not be immediately obvious why a strong Academic Hospitalist program is in their economic best interest. Hospitalist programs may confront consistently high levels of turnover and a shrinking supply of general internists. The associated high costs of hiring new, junior faculty include the time and effort needed to interview, credential, train, and most importantly build familiarity with the complex systems encountered in maneuvering through a hospital, especially one with widespread dissemination of electronic medical records for documentation and order entry. However, hospitalists provided with opportunities for academic development are more likely to stay on the job longer and perform at a higher level, providing convincing motivation for hospitals to invest in their academic hospitalist programs. Retaining high‐quality hospitalists may be one of the most cost‐efficient methods for an AMC to support a hospital medicine program.
STRATEGIES IN ACTION
Flanders et al.1 point to a shortage of well‐trained clinician investigators with a focus on inpatient research as a barrier to the development of academic hospitalist programming. They describe a strategy of collaboration with specialty groups. This highlights the importance of collaboration with more well‐established research units as a key ingredient to building a new academic unit. Wright et al.2 describe their mentorship program and how they created protected time for scholarship for hospitalists, including supporting mentors' time. These examples highlight another key benchmark of a viable academic program, mentoring, and the importance of ensuring that mentors have time for this essential effort.
However, it is critically important to remember that all politics is local, to quote the late Tip O'Neill, long‐time speaker of the US House of Representatives. What works in one setting may not work as well in a different contexthence the need for creativity and political acumen.
For example, although the specialty‐group collaboration described by Flanders et al.1 may be helpful in one setting, other strategic alliances may work on a larger scale and over a longer time period. Most hospital medicine groups are currently within academic divisions of general internal medicine, where infrastructure and mentoring may already exist for both research and educational scholarship. In those cases, fostering interaction between the division's hospitalists and its researchers would be a critical first step. The programming and growth developed in this way can be leveraged to support ongoing academic activities by hospitalists rather than being limited to a single project.
In the Division of General Internal Medicine at Mount Sinai, which houses the academic hospitalists, building research entailed collaboration with the well‐established Departments of Geriatrics and Health Policy, which had preexisting research infrastructure and mentors. At the same time, we developed a research fellowship program by applying jointly with the Division of General Pediatrics for federal grant support. Such diversity of collaboration enhanced our application.
LOOKING AHEAD
Putting the academic into academic hospitalist programs is the key to the future of hospital medicine. To be successful, one must consider all the issues described in light of available resources and the local and federal political landscape. As Flanders et al.1 and Wright et al.2 emphasize, collaboration will be the main component for success in the current academic landscape.
- The University of Michigan Specialist‐Hospitalist Allied Research Program (SHARP): jumpstarting hospital medicine research.J Hosp Med.2008;3(4):308–313. , , , .
- An innovative approach to supporting hospitalist physicians towards academic success.J Hosp Med.2008;3(4):314–318. , , , .
- The clinician‐educator—present and future roles.J Gen Intern Med.1997;12 (suppl 2):S1–S4. , , .
Accelerating the development of clinical research in academic hospitalist programs is a worthwhile goal if pursued with clarity, objectivity, and a thorough understanding of the process and its implications. In their articles, Flanders et al.1 and Wright et al.2 identify major barriers to growing academic hospitalist programs. These barriers include the need for protected time, the shortage of trained research faculty, the lack of infrastructure, and the limited availability of senior mentors. Both Flanders et al. and Wright et al. offer smart and innovative ways of addressing these issues. However, building an academic program from the ground up is more complex and challenging than it may seem at first glance. It takes time, patience, creativity, diplomacy, and the ability to recruit collaborators and advocates who are willing to share infrastructure and resources.
Although both articles add significantly to the discussion of strategies for creating an academic hospitalist program, they are unclear about the definition of academic in this context. The term academic is often misunderstood to be synonymous with research. However, research is just one component of an academic program, which also includes education, quality improvement (QI), administration, and program development. It may be helpful, therefore, to replace academic with scholarship, which can be defined as a process that involves peer review and dissemination of ideas at local, regional, and national levels. Scholarship also goes beyond research, encompassing education and other areas such as QI. Although academic programs are not necessarily involved with funded research, there is usually an expectation of peer review, through either presentations at regional and national meetings or publication. For the purposes of this discussion, the term academic hospitalist program will be defined broadly to include any program affiliated with a university that is involved in the teaching of residents and medical students and whose faculty is required to participate in a promotions process.
All members of an academic division should be expected to participate in scholarship, whether it is education, QI projects, or research. If there is a strong expectation that traditional National Institute of Health (NIH) funded research will take place, this expectation must come with sufficient resources. Without infrastructure for research and investment in research faculty, procuring NIH funds for research is not a reasonable expectation. Organizers of hospitalist programs currently within academic divisions of general internal medicine should consider ways to better integrate programs into the existing research infrastructure in their divisions. For either freestanding hospitalist programs or programs within academic divisions of general internal medicine, investments in infrastructure and faculty are needed to nurture this area of research and build an academic focus in hospital medicine. However, if obtaining NIH research funds is not the expectation and resources are not available for hospitalists or for any other division or department at that institution, then academic expectations should focus on other pursuits. Examples include participation in the education and QI initiatives.
For programs with expectations of both funded research and other scholarship, a successful program will most likely include a small core of skilled clinical researchers working closely with well‐trained clinical educators, all of whom are involved in scholarship. Both clinical educators and researchers need to be continuously developing, and to reach their full potential, all should have access to infrastructure that supports these activities, including resources such as MPH‐level project managers, research assistants, database managers, and, most importantly, appropriate mentors.
Clinician educators must be both proficient clinicians and dedicated teachers. Ideally, they should have strong familiarity with educational theory in addition to skills in hands‐on teaching. Their responsibilities include mastering the skills that students need, staying up to the minute in their areas of expertise, and serving as role models in their attitudes toward patients, colleagues, and their work.3 Many hospitalists may not have these skills when they begin, often fresh out of residency, and will need help developing them.
PROTECTED TIME
Protected time is crucial to the success of any academic program. Finding this time presents a challenge for any clinical group, but the challenge is exacerbated for hospitalists, who face tremendous pressure to serve full‐time clinical jobs with little emphasis on academic elements such as education, QI, and participation in funded research. As both Wright et al.2 and Flanders et al.1 point out, to build a group of well‐developed academic clinician educators, academic hospitalists not on track for funding need to be given adequate protected time to participate in committees, sharpen their teaching skills, develop QI projects that can be converted to scholarships, participate in research, and present at national and regional meetings.
The requirements of protected time for researchers are more challenging than those for educators. Building a newly funded research unit within a hospitalist group, as with any group, will entail hiring fellowship trained faculty with significant protected time (approximately 80%) to give them time to obtain funding such as a K award and eventually become independent investigators with RO1 grant funding. Building research units requires support from collaborators with infrastructure and mentors already in place that can be tapped during the incubation stage of the academic program. For most hospitalist programs, infrastructure and mentors will be found in their divisions of general internal medicine.
Protected time should be considered an integral element of academic hospitalist positionsnot a perkas long as the time is used responsibly and productively. As both Wright et al.2 and Flanders et al.1 correctly point out, herein lies the major challenge of creating any kind of academic program: How will the program support protected time for both educators and researchers? In most instances, significant seed money will be needed to support junior faculty over the first few years of their careers. It is noteworthy that building a federally funded hospital medicine research program will be particularly difficult in today's economy because funding levels at the NIH, Agency for Healthcare Research and Quality, Health Resources and Services Administration, and other traditional funders of clinical research either are flat or have been reduced dramatically.
To many Academic Medical Centers (AMC), it may not be immediately obvious why a strong Academic Hospitalist program is in their economic best interest. Hospitalist programs may confront consistently high levels of turnover and a shrinking supply of general internists. The associated high costs of hiring new, junior faculty include the time and effort needed to interview, credential, train, and most importantly build familiarity with the complex systems encountered in maneuvering through a hospital, especially one with widespread dissemination of electronic medical records for documentation and order entry. However, hospitalists provided with opportunities for academic development are more likely to stay on the job longer and perform at a higher level, providing convincing motivation for hospitals to invest in their academic hospitalist programs. Retaining high‐quality hospitalists may be one of the most cost‐efficient methods for an AMC to support a hospital medicine program.
STRATEGIES IN ACTION
Flanders et al.1 point to a shortage of well‐trained clinician investigators with a focus on inpatient research as a barrier to the development of academic hospitalist programming. They describe a strategy of collaboration with specialty groups. This highlights the importance of collaboration with more well‐established research units as a key ingredient to building a new academic unit. Wright et al.2 describe their mentorship program and how they created protected time for scholarship for hospitalists, including supporting mentors' time. These examples highlight another key benchmark of a viable academic program, mentoring, and the importance of ensuring that mentors have time for this essential effort.
However, it is critically important to remember that all politics is local, to quote the late Tip O'Neill, long‐time speaker of the US House of Representatives. What works in one setting may not work as well in a different contexthence the need for creativity and political acumen.
For example, although the specialty‐group collaboration described by Flanders et al.1 may be helpful in one setting, other strategic alliances may work on a larger scale and over a longer time period. Most hospital medicine groups are currently within academic divisions of general internal medicine, where infrastructure and mentoring may already exist for both research and educational scholarship. In those cases, fostering interaction between the division's hospitalists and its researchers would be a critical first step. The programming and growth developed in this way can be leveraged to support ongoing academic activities by hospitalists rather than being limited to a single project.
In the Division of General Internal Medicine at Mount Sinai, which houses the academic hospitalists, building research entailed collaboration with the well‐established Departments of Geriatrics and Health Policy, which had preexisting research infrastructure and mentors. At the same time, we developed a research fellowship program by applying jointly with the Division of General Pediatrics for federal grant support. Such diversity of collaboration enhanced our application.
LOOKING AHEAD
Putting the academic into academic hospitalist programs is the key to the future of hospital medicine. To be successful, one must consider all the issues described in light of available resources and the local and federal political landscape. As Flanders et al.1 and Wright et al.2 emphasize, collaboration will be the main component for success in the current academic landscape.
Accelerating the development of clinical research in academic hospitalist programs is a worthwhile goal if pursued with clarity, objectivity, and a thorough understanding of the process and its implications. In their articles, Flanders et al.1 and Wright et al.2 identify major barriers to growing academic hospitalist programs. These barriers include the need for protected time, the shortage of trained research faculty, the lack of infrastructure, and the limited availability of senior mentors. Both Flanders et al. and Wright et al. offer smart and innovative ways of addressing these issues. However, building an academic program from the ground up is more complex and challenging than it may seem at first glance. It takes time, patience, creativity, diplomacy, and the ability to recruit collaborators and advocates who are willing to share infrastructure and resources.
Although both articles add significantly to the discussion of strategies for creating an academic hospitalist program, they are unclear about the definition of academic in this context. The term academic is often misunderstood to be synonymous with research. However, research is just one component of an academic program, which also includes education, quality improvement (QI), administration, and program development. It may be helpful, therefore, to replace academic with scholarship, which can be defined as a process that involves peer review and dissemination of ideas at local, regional, and national levels. Scholarship also goes beyond research, encompassing education and other areas such as QI. Although academic programs are not necessarily involved with funded research, there is usually an expectation of peer review, through either presentations at regional and national meetings or publication. For the purposes of this discussion, the term academic hospitalist program will be defined broadly to include any program affiliated with a university that is involved in the teaching of residents and medical students and whose faculty is required to participate in a promotions process.
All members of an academic division should be expected to participate in scholarship, whether it is education, QI projects, or research. If there is a strong expectation that traditional National Institute of Health (NIH) funded research will take place, this expectation must come with sufficient resources. Without infrastructure for research and investment in research faculty, procuring NIH funds for research is not a reasonable expectation. Organizers of hospitalist programs currently within academic divisions of general internal medicine should consider ways to better integrate programs into the existing research infrastructure in their divisions. For either freestanding hospitalist programs or programs within academic divisions of general internal medicine, investments in infrastructure and faculty are needed to nurture this area of research and build an academic focus in hospital medicine. However, if obtaining NIH research funds is not the expectation and resources are not available for hospitalists or for any other division or department at that institution, then academic expectations should focus on other pursuits. Examples include participation in the education and QI initiatives.
For programs with expectations of both funded research and other scholarship, a successful program will most likely include a small core of skilled clinical researchers working closely with well‐trained clinical educators, all of whom are involved in scholarship. Both clinical educators and researchers need to be continuously developing, and to reach their full potential, all should have access to infrastructure that supports these activities, including resources such as MPH‐level project managers, research assistants, database managers, and, most importantly, appropriate mentors.
Clinician educators must be both proficient clinicians and dedicated teachers. Ideally, they should have strong familiarity with educational theory in addition to skills in hands‐on teaching. Their responsibilities include mastering the skills that students need, staying up to the minute in their areas of expertise, and serving as role models in their attitudes toward patients, colleagues, and their work.3 Many hospitalists may not have these skills when they begin, often fresh out of residency, and will need help developing them.
PROTECTED TIME
Protected time is crucial to the success of any academic program. Finding this time presents a challenge for any clinical group, but the challenge is exacerbated for hospitalists, who face tremendous pressure to serve full‐time clinical jobs with little emphasis on academic elements such as education, QI, and participation in funded research. As both Wright et al.2 and Flanders et al.1 point out, to build a group of well‐developed academic clinician educators, academic hospitalists not on track for funding need to be given adequate protected time to participate in committees, sharpen their teaching skills, develop QI projects that can be converted to scholarships, participate in research, and present at national and regional meetings.
The requirements of protected time for researchers are more challenging than those for educators. Building a newly funded research unit within a hospitalist group, as with any group, will entail hiring fellowship trained faculty with significant protected time (approximately 80%) to give them time to obtain funding such as a K award and eventually become independent investigators with RO1 grant funding. Building research units requires support from collaborators with infrastructure and mentors already in place that can be tapped during the incubation stage of the academic program. For most hospitalist programs, infrastructure and mentors will be found in their divisions of general internal medicine.
Protected time should be considered an integral element of academic hospitalist positionsnot a perkas long as the time is used responsibly and productively. As both Wright et al.2 and Flanders et al.1 correctly point out, herein lies the major challenge of creating any kind of academic program: How will the program support protected time for both educators and researchers? In most instances, significant seed money will be needed to support junior faculty over the first few years of their careers. It is noteworthy that building a federally funded hospital medicine research program will be particularly difficult in today's economy because funding levels at the NIH, Agency for Healthcare Research and Quality, Health Resources and Services Administration, and other traditional funders of clinical research either are flat or have been reduced dramatically.
To many Academic Medical Centers (AMC), it may not be immediately obvious why a strong Academic Hospitalist program is in their economic best interest. Hospitalist programs may confront consistently high levels of turnover and a shrinking supply of general internists. The associated high costs of hiring new, junior faculty include the time and effort needed to interview, credential, train, and most importantly build familiarity with the complex systems encountered in maneuvering through a hospital, especially one with widespread dissemination of electronic medical records for documentation and order entry. However, hospitalists provided with opportunities for academic development are more likely to stay on the job longer and perform at a higher level, providing convincing motivation for hospitals to invest in their academic hospitalist programs. Retaining high‐quality hospitalists may be one of the most cost‐efficient methods for an AMC to support a hospital medicine program.
STRATEGIES IN ACTION
Flanders et al.1 point to a shortage of well‐trained clinician investigators with a focus on inpatient research as a barrier to the development of academic hospitalist programming. They describe a strategy of collaboration with specialty groups. This highlights the importance of collaboration with more well‐established research units as a key ingredient to building a new academic unit. Wright et al.2 describe their mentorship program and how they created protected time for scholarship for hospitalists, including supporting mentors' time. These examples highlight another key benchmark of a viable academic program, mentoring, and the importance of ensuring that mentors have time for this essential effort.
However, it is critically important to remember that all politics is local, to quote the late Tip O'Neill, long‐time speaker of the US House of Representatives. What works in one setting may not work as well in a different contexthence the need for creativity and political acumen.
For example, although the specialty‐group collaboration described by Flanders et al.1 may be helpful in one setting, other strategic alliances may work on a larger scale and over a longer time period. Most hospital medicine groups are currently within academic divisions of general internal medicine, where infrastructure and mentoring may already exist for both research and educational scholarship. In those cases, fostering interaction between the division's hospitalists and its researchers would be a critical first step. The programming and growth developed in this way can be leveraged to support ongoing academic activities by hospitalists rather than being limited to a single project.
In the Division of General Internal Medicine at Mount Sinai, which houses the academic hospitalists, building research entailed collaboration with the well‐established Departments of Geriatrics and Health Policy, which had preexisting research infrastructure and mentors. At the same time, we developed a research fellowship program by applying jointly with the Division of General Pediatrics for federal grant support. Such diversity of collaboration enhanced our application.
LOOKING AHEAD
Putting the academic into academic hospitalist programs is the key to the future of hospital medicine. To be successful, one must consider all the issues described in light of available resources and the local and federal political landscape. As Flanders et al.1 and Wright et al.2 emphasize, collaboration will be the main component for success in the current academic landscape.
- The University of Michigan Specialist‐Hospitalist Allied Research Program (SHARP): jumpstarting hospital medicine research.J Hosp Med.2008;3(4):308–313. , , , .
- An innovative approach to supporting hospitalist physicians towards academic success.J Hosp Med.2008;3(4):314–318. , , , .
- The clinician‐educator—present and future roles.J Gen Intern Med.1997;12 (suppl 2):S1–S4. , , .
- The University of Michigan Specialist‐Hospitalist Allied Research Program (SHARP): jumpstarting hospital medicine research.J Hosp Med.2008;3(4):308–313. , , , .
- An innovative approach to supporting hospitalist physicians towards academic success.J Hosp Med.2008;3(4):314–318. , , , .
- The clinician‐educator—present and future roles.J Gen Intern Med.1997;12 (suppl 2):S1–S4. , , .
Handoffs
To the seasoned intensivist, discussions with family members of critically ill patients in the intensive care unit (ICU) can be very predictable. However, this does not imply that these dialogues are straightforward or simple. Each day, we spend a significant amount of time meeting with family members at different stages of their loved one's ICU stay. Some family members are satisfied with these exchanges while others leave them distraught or in emotional shambles. At times, intensivists do not always effectively communicate with family members.13 Both the team and the families come to the ICU table with different sets of perspectives, expectations, conversational skill sets, life experiences, and tolerances for stress. These differences are magnified when the ICU course turns rocky.
We thought it useful to illustrate ICU dialogues with family members as we perceive them. We focus on the potential checkpoints where miscommunication and misunderstanding may occur throughout the roller coaster ICU experience. To this end, over the past few years, our Critical Care Medicine group has been collecting thought‐provoking comments from various family conferences. Herein, we present the dynamic phases of an ICU encounter contextually inserting relevant quotes.
The specter of a loved one lying helplessly in an ICU bed, attached to imposing machines, with tubes coming out on all sides can be quite numbing and frightening. No amount of schooling or training can really prepare a person for this emotionally taxing situation. Disbelief reigns! We frequently hear, How can a person go from being fine one day to being so sick the next? or He was shoveling snow just last week! or, She was just fine after surgery, talking, walking, and eating.
Not only is the ICU a strange and scary place, but oftentimes, in the midst of our first meeting with family members of newly admitted ICU patients, we quickly realize that they are not really sure who we are or what we do. It seems to us that Critical Care Medicine as a medical specialty suffers from a lack of brand recognition. Often the family members say, You're a what? An intensivist? We've never heard of an intensivist. Do you also work in the Emergency Room? I heard someone mention critical care, is that the same as intensive care? Or sometimes we get whacked, What about getting a real doctor, like a cardiologist or a pulmonologist!
Family members immediately find different ways to let us know how much the patient means to them. They try to impress upon us the vitality and unique nature of their loved ones in the hope that this will make us all work harder. He's a real fighter and never gives up. Or He's a young and healthy 90. Or You have to take extra care of her, she's very special, she's the mother of eight children. Sometimes political or social connections are used to further incentivize or push the ICU team. He's best friends with Mr. Z who is on the Board of Trustees, or She's friends with this or that politician.
But, Google has really altered the nature of our family discussions; everyone, it seems, can now be a doctor. We used to hear I'm not a doctor, but Now, the inevitable internet search leads to I've been doing some reading on the web about this new drug and I've heard that it's a wonder drug. Why isn't my mother getting it? Or What is the APACHE III score of my sister and how are you using this value?
Just as intensivists regularly look at reams of lab data and calculate all types of organ failure and prognostication scores, family members similarly reframe the ICU discussion to a numbers game. This approach to seemingly getting our arms around the complicated big picture is used in many aspects of our lives, whether tracking our retirement portfolios or determining the odds of next week's football game. Doctor, what are her chances for improvement ‐ 50/50, 30/70 or 80/20? Even one in a million? Over time, family members even become experts at looking at the bedside monitors and devices. I've been watching the numbers, I see that the heart rate is down and you were able to decrease the oxygen on the respirator to 80%, and the blood oxygen is still over 90%, so my father must be better, right?
As the days go by, some families become more desperate. They seek good news or even any news from every person they meet. And the ICU environment certainly offers family members a myriad of people with whom to converse. Unfortunately, this frantic search for information leads them to receive conflicting and unreliable data. Frustration results, Why do we keep getting mixed messages? Or, Doctor, we like the hospital, but why can't all of you get the story straight? As family members gather together with other patients' families in the waiting room day and night, they often share their ICU stories with each other. We'll overhear someone say, What about the new antibiotic the patient in Bed 8 is getting? Shouldn't my husband be getting that too? I see everyone is gowning up, I keep hearing about that bad Staph bug going around, my father better not catch it.
Occasionally we become concerned, even perplexed, when we cannot successfully convey our message to the family despite our best intentions and efforts. Some families are just in denial; the reality of no progress and/or likely poor outcome cannot be heard, much less accepted. Doctor, I have been badgered with the truth enough. I just don't want to believe it. Or, Doctor, don't you ever have any good news to report to us? The insatiable need for prolonged and repetitive family conferences may deflect time away from the care of other patients and meeting with other families.
Unfortunately, some patients get stuck in the ICU, either not improving, or just steadily deteriorating despite aggressive care. We broach treatment limitation or end of life care with the family as we realize that further ICU care is not going to be beneficial. Sometimes this news is greeted with stunned silence. The family often pleads for their loved one to be able to stay a little bit longer in the ICU, Let's just see how he does for a few more days or over the weekend. Or, We just need to buy some more time until everything turns around. Or other approaches are used to postpone the inevitable ICU transfer. Doctor, our 50th wedding anniversary is in two weeks, so let's continue to keep him in the ICU. Or, You can't discharge my mother, she averages 14.5 alarms per hour, how can the ward ever take care of her?
And then comes the quest for the miracle, Don't you believe in miracles? Haven't you ever seen someone in this condition get better? Are you giving up? We'll never give up! Or, ignoring the express wishes of the patient, Oh, Doctor, my father did have an advanced directive, but I'm not sure whether I want to give it to you. Or, the message now gets personal What would you do if this was your mother or father?
Such questions highlight the existential dichotomy of critical care. As intensivists, we sometimes have to reconcile the family members' unrealistic view of prognosis, overly hopeful expectations, and desire for endless futile ICU care with our own understandings of prognosis, goals of care, and appropriate use of ICU beds. Where, and when should we draw the line? How do we all let go?4
This collection of comments and thoughts reflects a synthesis of many different discussions conducted under diverse conditions. Thankfully, not all of the individual elements of the scenario described above occur with each patient. Family members and intensivists commonly have amicable discourse resulting in an acceptable degree of understanding and consensus regarding the prognosis and care plan. However, on occasion, things just don't go as well as hoped for, neither in clinical outcomes nor in our discussions. While effective ICU communication strategies have been designed and studied,512 even the best of these may not prevent conflict and disagreement. Nevertheless, our challenge as critical care practitioners is to ensure that our dialogues with family members are honest and direct and that we communicate in a timely, consistent and empathetic manner.
Well, onto the next family meeting!
Acknowledgements
The authors thank the current and past critical care fellows for their contributions to this manuscript. We are particularly indebted to the ICU nurses, patient representatives and social workers of the Memorial Sloan‐Kettering Cancer Center, New York, New York who provide daily clinical and emotional support to our ICU patients and their families and to the CCM attending team.
- Half the families of intensive care unit patients experience inadequate communication with physicians.Crit Care Med2000;28(8):3044–3049. , , , et al.
- Missed opportunities during family conferences about end‐of‐life care in the intensive care unit.Am J Respir Crit Care Med2005;171:844–849. , , , et al.
- Impact on family satisfaction: The Critical Care Family Assistance Program.Chest2005;128:76S–80S. , .
- The art of letting go.NEJM2007;357:3–5. .
- The family conference as a focus to improve communication about end‐of‐life care in the intensive care unit: opportunities for improvement.Crit Care Med2001;29:suppl 2:N26–N33. , , , et al.
- A communication strategy and brochure for relatives of patients dying in the ICU.N Engl J Med2007:356:469–478. , , , et al.
- The healing power of listening in the ICU.N Engl J Med2007;356:513–515. , .
- The pressure to withhold or withdraw life‐sustaining therapy from critically ill patients in the United States.Am J Respir Crit Care Med2007;175(11):1104–1108. , .
- An intensive communication intervention for the critically ill.Am J Med2000;109:469–475. , , , et al.
- Improving family communications at the end of life: implications for length of stay in the intensive care unit and resource use.Am J Crit Care2003;12(4)317–323. , , .
- Conflict associated with decisions to limit life‐sustaining treatment in intensive care units.J Gen Intern Med2001;16(5)339–341. , , , et al.
- Families looking back: one year after discussion of withdrawal or withholding of life‐sustaining support.Crit Care Med2001;29(1)197–201. , , , et al.
To the seasoned intensivist, discussions with family members of critically ill patients in the intensive care unit (ICU) can be very predictable. However, this does not imply that these dialogues are straightforward or simple. Each day, we spend a significant amount of time meeting with family members at different stages of their loved one's ICU stay. Some family members are satisfied with these exchanges while others leave them distraught or in emotional shambles. At times, intensivists do not always effectively communicate with family members.13 Both the team and the families come to the ICU table with different sets of perspectives, expectations, conversational skill sets, life experiences, and tolerances for stress. These differences are magnified when the ICU course turns rocky.
We thought it useful to illustrate ICU dialogues with family members as we perceive them. We focus on the potential checkpoints where miscommunication and misunderstanding may occur throughout the roller coaster ICU experience. To this end, over the past few years, our Critical Care Medicine group has been collecting thought‐provoking comments from various family conferences. Herein, we present the dynamic phases of an ICU encounter contextually inserting relevant quotes.
The specter of a loved one lying helplessly in an ICU bed, attached to imposing machines, with tubes coming out on all sides can be quite numbing and frightening. No amount of schooling or training can really prepare a person for this emotionally taxing situation. Disbelief reigns! We frequently hear, How can a person go from being fine one day to being so sick the next? or He was shoveling snow just last week! or, She was just fine after surgery, talking, walking, and eating.
Not only is the ICU a strange and scary place, but oftentimes, in the midst of our first meeting with family members of newly admitted ICU patients, we quickly realize that they are not really sure who we are or what we do. It seems to us that Critical Care Medicine as a medical specialty suffers from a lack of brand recognition. Often the family members say, You're a what? An intensivist? We've never heard of an intensivist. Do you also work in the Emergency Room? I heard someone mention critical care, is that the same as intensive care? Or sometimes we get whacked, What about getting a real doctor, like a cardiologist or a pulmonologist!
Family members immediately find different ways to let us know how much the patient means to them. They try to impress upon us the vitality and unique nature of their loved ones in the hope that this will make us all work harder. He's a real fighter and never gives up. Or He's a young and healthy 90. Or You have to take extra care of her, she's very special, she's the mother of eight children. Sometimes political or social connections are used to further incentivize or push the ICU team. He's best friends with Mr. Z who is on the Board of Trustees, or She's friends with this or that politician.
But, Google has really altered the nature of our family discussions; everyone, it seems, can now be a doctor. We used to hear I'm not a doctor, but Now, the inevitable internet search leads to I've been doing some reading on the web about this new drug and I've heard that it's a wonder drug. Why isn't my mother getting it? Or What is the APACHE III score of my sister and how are you using this value?
Just as intensivists regularly look at reams of lab data and calculate all types of organ failure and prognostication scores, family members similarly reframe the ICU discussion to a numbers game. This approach to seemingly getting our arms around the complicated big picture is used in many aspects of our lives, whether tracking our retirement portfolios or determining the odds of next week's football game. Doctor, what are her chances for improvement ‐ 50/50, 30/70 or 80/20? Even one in a million? Over time, family members even become experts at looking at the bedside monitors and devices. I've been watching the numbers, I see that the heart rate is down and you were able to decrease the oxygen on the respirator to 80%, and the blood oxygen is still over 90%, so my father must be better, right?
As the days go by, some families become more desperate. They seek good news or even any news from every person they meet. And the ICU environment certainly offers family members a myriad of people with whom to converse. Unfortunately, this frantic search for information leads them to receive conflicting and unreliable data. Frustration results, Why do we keep getting mixed messages? Or, Doctor, we like the hospital, but why can't all of you get the story straight? As family members gather together with other patients' families in the waiting room day and night, they often share their ICU stories with each other. We'll overhear someone say, What about the new antibiotic the patient in Bed 8 is getting? Shouldn't my husband be getting that too? I see everyone is gowning up, I keep hearing about that bad Staph bug going around, my father better not catch it.
Occasionally we become concerned, even perplexed, when we cannot successfully convey our message to the family despite our best intentions and efforts. Some families are just in denial; the reality of no progress and/or likely poor outcome cannot be heard, much less accepted. Doctor, I have been badgered with the truth enough. I just don't want to believe it. Or, Doctor, don't you ever have any good news to report to us? The insatiable need for prolonged and repetitive family conferences may deflect time away from the care of other patients and meeting with other families.
Unfortunately, some patients get stuck in the ICU, either not improving, or just steadily deteriorating despite aggressive care. We broach treatment limitation or end of life care with the family as we realize that further ICU care is not going to be beneficial. Sometimes this news is greeted with stunned silence. The family often pleads for their loved one to be able to stay a little bit longer in the ICU, Let's just see how he does for a few more days or over the weekend. Or, We just need to buy some more time until everything turns around. Or other approaches are used to postpone the inevitable ICU transfer. Doctor, our 50th wedding anniversary is in two weeks, so let's continue to keep him in the ICU. Or, You can't discharge my mother, she averages 14.5 alarms per hour, how can the ward ever take care of her?
And then comes the quest for the miracle, Don't you believe in miracles? Haven't you ever seen someone in this condition get better? Are you giving up? We'll never give up! Or, ignoring the express wishes of the patient, Oh, Doctor, my father did have an advanced directive, but I'm not sure whether I want to give it to you. Or, the message now gets personal What would you do if this was your mother or father?
Such questions highlight the existential dichotomy of critical care. As intensivists, we sometimes have to reconcile the family members' unrealistic view of prognosis, overly hopeful expectations, and desire for endless futile ICU care with our own understandings of prognosis, goals of care, and appropriate use of ICU beds. Where, and when should we draw the line? How do we all let go?4
This collection of comments and thoughts reflects a synthesis of many different discussions conducted under diverse conditions. Thankfully, not all of the individual elements of the scenario described above occur with each patient. Family members and intensivists commonly have amicable discourse resulting in an acceptable degree of understanding and consensus regarding the prognosis and care plan. However, on occasion, things just don't go as well as hoped for, neither in clinical outcomes nor in our discussions. While effective ICU communication strategies have been designed and studied,512 even the best of these may not prevent conflict and disagreement. Nevertheless, our challenge as critical care practitioners is to ensure that our dialogues with family members are honest and direct and that we communicate in a timely, consistent and empathetic manner.
Well, onto the next family meeting!
Acknowledgements
The authors thank the current and past critical care fellows for their contributions to this manuscript. We are particularly indebted to the ICU nurses, patient representatives and social workers of the Memorial Sloan‐Kettering Cancer Center, New York, New York who provide daily clinical and emotional support to our ICU patients and their families and to the CCM attending team.
To the seasoned intensivist, discussions with family members of critically ill patients in the intensive care unit (ICU) can be very predictable. However, this does not imply that these dialogues are straightforward or simple. Each day, we spend a significant amount of time meeting with family members at different stages of their loved one's ICU stay. Some family members are satisfied with these exchanges while others leave them distraught or in emotional shambles. At times, intensivists do not always effectively communicate with family members.13 Both the team and the families come to the ICU table with different sets of perspectives, expectations, conversational skill sets, life experiences, and tolerances for stress. These differences are magnified when the ICU course turns rocky.
We thought it useful to illustrate ICU dialogues with family members as we perceive them. We focus on the potential checkpoints where miscommunication and misunderstanding may occur throughout the roller coaster ICU experience. To this end, over the past few years, our Critical Care Medicine group has been collecting thought‐provoking comments from various family conferences. Herein, we present the dynamic phases of an ICU encounter contextually inserting relevant quotes.
The specter of a loved one lying helplessly in an ICU bed, attached to imposing machines, with tubes coming out on all sides can be quite numbing and frightening. No amount of schooling or training can really prepare a person for this emotionally taxing situation. Disbelief reigns! We frequently hear, How can a person go from being fine one day to being so sick the next? or He was shoveling snow just last week! or, She was just fine after surgery, talking, walking, and eating.
Not only is the ICU a strange and scary place, but oftentimes, in the midst of our first meeting with family members of newly admitted ICU patients, we quickly realize that they are not really sure who we are or what we do. It seems to us that Critical Care Medicine as a medical specialty suffers from a lack of brand recognition. Often the family members say, You're a what? An intensivist? We've never heard of an intensivist. Do you also work in the Emergency Room? I heard someone mention critical care, is that the same as intensive care? Or sometimes we get whacked, What about getting a real doctor, like a cardiologist or a pulmonologist!
Family members immediately find different ways to let us know how much the patient means to them. They try to impress upon us the vitality and unique nature of their loved ones in the hope that this will make us all work harder. He's a real fighter and never gives up. Or He's a young and healthy 90. Or You have to take extra care of her, she's very special, she's the mother of eight children. Sometimes political or social connections are used to further incentivize or push the ICU team. He's best friends with Mr. Z who is on the Board of Trustees, or She's friends with this or that politician.
But, Google has really altered the nature of our family discussions; everyone, it seems, can now be a doctor. We used to hear I'm not a doctor, but Now, the inevitable internet search leads to I've been doing some reading on the web about this new drug and I've heard that it's a wonder drug. Why isn't my mother getting it? Or What is the APACHE III score of my sister and how are you using this value?
Just as intensivists regularly look at reams of lab data and calculate all types of organ failure and prognostication scores, family members similarly reframe the ICU discussion to a numbers game. This approach to seemingly getting our arms around the complicated big picture is used in many aspects of our lives, whether tracking our retirement portfolios or determining the odds of next week's football game. Doctor, what are her chances for improvement ‐ 50/50, 30/70 or 80/20? Even one in a million? Over time, family members even become experts at looking at the bedside monitors and devices. I've been watching the numbers, I see that the heart rate is down and you were able to decrease the oxygen on the respirator to 80%, and the blood oxygen is still over 90%, so my father must be better, right?
As the days go by, some families become more desperate. They seek good news or even any news from every person they meet. And the ICU environment certainly offers family members a myriad of people with whom to converse. Unfortunately, this frantic search for information leads them to receive conflicting and unreliable data. Frustration results, Why do we keep getting mixed messages? Or, Doctor, we like the hospital, but why can't all of you get the story straight? As family members gather together with other patients' families in the waiting room day and night, they often share their ICU stories with each other. We'll overhear someone say, What about the new antibiotic the patient in Bed 8 is getting? Shouldn't my husband be getting that too? I see everyone is gowning up, I keep hearing about that bad Staph bug going around, my father better not catch it.
Occasionally we become concerned, even perplexed, when we cannot successfully convey our message to the family despite our best intentions and efforts. Some families are just in denial; the reality of no progress and/or likely poor outcome cannot be heard, much less accepted. Doctor, I have been badgered with the truth enough. I just don't want to believe it. Or, Doctor, don't you ever have any good news to report to us? The insatiable need for prolonged and repetitive family conferences may deflect time away from the care of other patients and meeting with other families.
Unfortunately, some patients get stuck in the ICU, either not improving, or just steadily deteriorating despite aggressive care. We broach treatment limitation or end of life care with the family as we realize that further ICU care is not going to be beneficial. Sometimes this news is greeted with stunned silence. The family often pleads for their loved one to be able to stay a little bit longer in the ICU, Let's just see how he does for a few more days or over the weekend. Or, We just need to buy some more time until everything turns around. Or other approaches are used to postpone the inevitable ICU transfer. Doctor, our 50th wedding anniversary is in two weeks, so let's continue to keep him in the ICU. Or, You can't discharge my mother, she averages 14.5 alarms per hour, how can the ward ever take care of her?
And then comes the quest for the miracle, Don't you believe in miracles? Haven't you ever seen someone in this condition get better? Are you giving up? We'll never give up! Or, ignoring the express wishes of the patient, Oh, Doctor, my father did have an advanced directive, but I'm not sure whether I want to give it to you. Or, the message now gets personal What would you do if this was your mother or father?
Such questions highlight the existential dichotomy of critical care. As intensivists, we sometimes have to reconcile the family members' unrealistic view of prognosis, overly hopeful expectations, and desire for endless futile ICU care with our own understandings of prognosis, goals of care, and appropriate use of ICU beds. Where, and when should we draw the line? How do we all let go?4
This collection of comments and thoughts reflects a synthesis of many different discussions conducted under diverse conditions. Thankfully, not all of the individual elements of the scenario described above occur with each patient. Family members and intensivists commonly have amicable discourse resulting in an acceptable degree of understanding and consensus regarding the prognosis and care plan. However, on occasion, things just don't go as well as hoped for, neither in clinical outcomes nor in our discussions. While effective ICU communication strategies have been designed and studied,512 even the best of these may not prevent conflict and disagreement. Nevertheless, our challenge as critical care practitioners is to ensure that our dialogues with family members are honest and direct and that we communicate in a timely, consistent and empathetic manner.
Well, onto the next family meeting!
Acknowledgements
The authors thank the current and past critical care fellows for their contributions to this manuscript. We are particularly indebted to the ICU nurses, patient representatives and social workers of the Memorial Sloan‐Kettering Cancer Center, New York, New York who provide daily clinical and emotional support to our ICU patients and their families and to the CCM attending team.
- Half the families of intensive care unit patients experience inadequate communication with physicians.Crit Care Med2000;28(8):3044–3049. , , , et al.
- Missed opportunities during family conferences about end‐of‐life care in the intensive care unit.Am J Respir Crit Care Med2005;171:844–849. , , , et al.
- Impact on family satisfaction: The Critical Care Family Assistance Program.Chest2005;128:76S–80S. , .
- The art of letting go.NEJM2007;357:3–5. .
- The family conference as a focus to improve communication about end‐of‐life care in the intensive care unit: opportunities for improvement.Crit Care Med2001;29:suppl 2:N26–N33. , , , et al.
- A communication strategy and brochure for relatives of patients dying in the ICU.N Engl J Med2007:356:469–478. , , , et al.
- The healing power of listening in the ICU.N Engl J Med2007;356:513–515. , .
- The pressure to withhold or withdraw life‐sustaining therapy from critically ill patients in the United States.Am J Respir Crit Care Med2007;175(11):1104–1108. , .
- An intensive communication intervention for the critically ill.Am J Med2000;109:469–475. , , , et al.
- Improving family communications at the end of life: implications for length of stay in the intensive care unit and resource use.Am J Crit Care2003;12(4)317–323. , , .
- Conflict associated with decisions to limit life‐sustaining treatment in intensive care units.J Gen Intern Med2001;16(5)339–341. , , , et al.
- Families looking back: one year after discussion of withdrawal or withholding of life‐sustaining support.Crit Care Med2001;29(1)197–201. , , , et al.
- Half the families of intensive care unit patients experience inadequate communication with physicians.Crit Care Med2000;28(8):3044–3049. , , , et al.
- Missed opportunities during family conferences about end‐of‐life care in the intensive care unit.Am J Respir Crit Care Med2005;171:844–849. , , , et al.
- Impact on family satisfaction: The Critical Care Family Assistance Program.Chest2005;128:76S–80S. , .
- The art of letting go.NEJM2007;357:3–5. .
- The family conference as a focus to improve communication about end‐of‐life care in the intensive care unit: opportunities for improvement.Crit Care Med2001;29:suppl 2:N26–N33. , , , et al.
- A communication strategy and brochure for relatives of patients dying in the ICU.N Engl J Med2007:356:469–478. , , , et al.
- The healing power of listening in the ICU.N Engl J Med2007;356:513–515. , .
- The pressure to withhold or withdraw life‐sustaining therapy from critically ill patients in the United States.Am J Respir Crit Care Med2007;175(11):1104–1108. , .
- An intensive communication intervention for the critically ill.Am J Med2000;109:469–475. , , , et al.
- Improving family communications at the end of life: implications for length of stay in the intensive care unit and resource use.Am J Crit Care2003;12(4)317–323. , , .
- Conflict associated with decisions to limit life‐sustaining treatment in intensive care units.J Gen Intern Med2001;16(5)339–341. , , , et al.
- Families looking back: one year after discussion of withdrawal or withholding of life‐sustaining support.Crit Care Med2001;29(1)197–201. , , , et al.
Given the ENHANCE trial results, ezetimibe is still unproven
Ezetimibe (Zetia) was licensed by the US Food and Drug Administration in 2002 on the basis of its ability to reduce low-density lipoprotein cholesterol (LDL-C) levels. The reductions are mild, approximately 15%,1 which is comparable to the effects of a stringent diet and exercise or of a statin in titrated doses.
However, there was no evidence that ezetimbe, which has a unique mechanism of action, delivers a benefit in terms of clinical outcomes. Despite this, the use of ezetimibe (alone or in fixed-dose combination with simvastatin, a preparation sold as Vytorin) grew rapidly, generating annual sales of $5.2 billion. Clinicians and the manufacturer (Merck/Schering-Plough) broadly assumed that LDL-C reduction would carry ezetimibe’s day as clinical trials emerged.
The assumption seemed reasonable, since evidence from the past 3 decades has established a clear link between lowering LDL-C levels via diverse mechanisms and positive clinical outcomes, particularly lower rates of cardiovascular disease and death. Indeed, LDL-C measurement is now a focus of cardiovascular risk assessment and management, as reflected in national treatment guidelines.
THE ENHANCE TRIAL: EZETIMIBE FAILS A KEY TEST
Unexpectedly, ezetimibe failed its first step in clinical trial validation, the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial.2 Apart from the scientifically irrelevant political regulatory intrigue generated by the sponsor’s conduct in this trial, ENHANCE’s findings challenge us to confront issues of what we assume vs what we really know, and how to interpret the complex results of clinical trials.
To be fair to the trial’s investigators, ENHANCE achieved its objective of enrolling a population with a very high LDL-C level, which is ezetimibe’s target and has been widely used in the study of atherosclerosis progression as a marker of potential drug benefit. Nevertheless, and even though the LDL-C level 2 years later was 52 mg/dL lower in the group receiving ezetimibe/simvastatin than in the group receiving simvastatin alone (Zocor), at LDL-C levels that are typically associated with atherosclerosis progression (140–190 mg/dL), ezetimibe failed to reduce the progression of atherosclerosis.
In fact, after 2 years of therapy, the intima-media thickness had increased more in the ezetimibe/simvastatin group than in the simvastatin-only group, most notably in the most-diseased carotid and femoral segments, although the differences between groups were not statistically significant. A lack of effect or a trend toward a worse effect with ezetimibe was seen in 22 of 25 subgroups, including key subgroups based on prior statin treatment (patients with no prior statin therapy did not benefit), baseline carotid intima-media thickness (patients with thicker arteries did not benefit), and baseline LDL-C levels (those with higher baseline levels did not benefit) (Figure 1).
These trends are particularly worrisome, given that the ezetimibe/simvastatin group achieved a greater reduction in C-reactive protein levels, which typically has resulted in superior outcomes in atherosclerosis3 and clinical effects4 in combination with LDL-C reduction.
In view of these findings, should clinicians stand firm and continue to use ezetimibe? Or should we reevaluate our position and await more data about this unique, first-in-class compound?
WISHFUL POST HOC HYPOTHESES
In this issue of the Cleveland Clinic Journal of Medicine, Dr. Michael Davidson,5 a respected lipid expert but one invested in ezetimibe’s development, assures us that all is in order and that the results of ENHANCE can be explained away by several arguments, most notably that most of the trial’s participants had previously received lipid-lowering treatment, which obscured the effects of ezetimibe. Moreover, he argues that ezetimibe’s mechanism of action is well understood and that the drug is safe and well tolerated and thus should remain a first-line treatment for hyperlipidemia.
These arguments may eventually prove to be correct, but as of now they are merely wishful post hoc hypotheses awaiting more data apart from ENHANCE. Negative clinical trials do occur as a matter of chance, but we should be cautious in any attempts to explain away a trial that was designed, executed, and reported as conceived simply because the results do not match our expectations.
Confronted with ENHANCE, the astute clinician should ask three questions: Do we really understand ezetimibe’s mechanism of action? Do other lines of evidence indicate the drug is beneficial? And how reliable is the arterial thickness as a surrogate end point?
DO WE UNDERSTAND EZETIMIBE’S MECHANISM OF ACTION?
Do we understand ezetimibe’s full mechanism of action? Not really.
True, ezetimibe inhibits cholesterol transport, a process that is integral both to cholesterol’s enteric absorption and to its systemic clearance. But although Dr. Davidson asserts that ezetimibe has cellular effects similar to those of statins, in fact it has the opposite effect on HMG-coA reductase, and no effects on LDL receptors.6
Furthermore, although initial studies suggested that ezetimibe inhibits enteric cholesterol absorption by inhibiting the Niemann-Pick C1L1 (NPC1L1) receptor, more recent investigations call this into serious question and point more definitively at a receptor known as scavenger receptor-B1 (SR-B1). As stated in a recent editorial, “SR-B1 in the apical site of enterocytes is the primary high-affinity site of cholesterol uptake and ezetimibe can inhibit this process. Moreover, the [possibility is ruled out] of NPC1L1 being a major player in this cholesterol uptake. This is at variance with the view of the colleagues from Schering-Plough who claim the same for NPC1L1.”7
SR-B1 is also a high-affinity receptor for high-density lipoprotein8 and thus is active in the antiatherosclerotic process of reverse cholesterol transport, inhibition of which significantly accelerates the development of atherosclerosis.9
Additionally, in vitro and thus unrelated to the effects of changing cholesterol concentration, ezetimibe down-regulates SR-B1 and another key cholesterol transporter protein called ABCA1.10 Further, ezetimibe induces down-regulation of raft protein domains, including CD36,11 another effect opposite to that of statins.
These little-recognized effects of ezetimibe are among many that are completely unrelated to enteric cholesterol absorption. Yet, they are likely to be active within the liver and systemically where these proteins reside, and they are putatively proatherosclerotic. Contrary to often-cited opinion, ezetimibe is systemically absorbed, with 11% of the compound excreted in the urine.12 Thus, the compound is systemically available to exert these same actions in the liver and elsewhere. Moreover, the absorbed drug is glucuronidated and is extensively recirculated in the liver in a form (its glucuronide) that is more potent than the parent compound.
In sum, present opinion is that ezetimibe inhibits lipid transport and interacts with a variety of receptors, not only in the gut but also systemically at the cell membrane and also inside the cell, focally disrupting several tightly regulated biologic processes.7 Thus, although ezetimibe reduces serum LDL-C levels via its effect in the gut, this effect may well be offset or even overridden systemically by other, unmeasurable effects, leading to counterintuitive results in terms of atherosclerosis or clinical events.
This would not be the first time a lipid-lowering drug has disappointed us: torcetrapib, another transport inhibitor, dramatically raises serum high-density lipoprotein cholesterol levels and reduces LDL-C but was found not only to have no effect on atherosclerosis, but also to potentiate adverse clinical outcomes.
The net impact of these other actions of ezetimibe is not known. We will discover its true clinical effects only through studies of endothelial function, atherosclerosis, and clinical cardiovascular outcomes. ENHANCE, which looked at atherosclerosis, is thus our strongest signal to date on the net effect of ezetimibe.
DO OTHER LINES OF EVIDENCE INDICATE EZETIMIBE IS BENEFICIAL?
Can we be reassured that ENHANCE’s results are spurious on the basis of other lines of evidence? Again, not really.
Experiments in animals, particularly in mice,13 have shown that ezetimibe may be antiatherosclerotic, although mice are considered the “worst model”7 for the study of ezetimibe, and notably, LDL-C levels were lowered far more in these experiments than they are clinically. Enthusiasm for these animal models should be tempered by interspecies variability in ezetimibe’s “off-target” effects and in the recent failure of other lipid transport drugs in human trials (torcetrapib and ACAT inhibitors) that had shown initial success in animals. No animal model is established for evaluating drugs of ezetimibe’s class, given its complex mechanism of action.
In human studies, the only other surrogate of the net effect of ezetimibe is endothelial function. Among several randomized clinical trials of ezetimibe,14–18 only one was designed to compare the effects of ezetimibe alone, ezetimibe plus a statin, and a statin by itself in titrated or in maximum doses.15 After 4 weeks of therapy, all groups had lower LDL-C levels. However, ezetimibe monotherapy and ezetimibe/simvastatin combination therapy had no detectable effect on the arterial response to acetylcholine, but atorvastatin (Lipitor) monotherapy did. To be fair, the other (very small) trials showed mixed results, thus keeping the hypothesis of ezetimibe’s benefit alive, but with nothing close to a clear signal of benefit.
IS ARTERIAL THICKNESS RELIABLE AS A SURROGATE END POINT?
Was the principal problem in ENHANCE the use of carotid intima-media thickness as the primary end point? No.
This issue has received a lot of attention, much of which I believe is misinformed. No trial end point is infallible, including carotid intima-media thickness, and one must remain open to the possibility of chance findings. However, it has been a relatively reasonable end point in trials of diverse cardiovascular preventive strategies, including lipid-lowering, blood-pressure-lowering, and lifestyle interventions and as a directional biomarker of clinical atherosclerotic events.
We should be cautious about comparing data on carotid intima-media thickness from different trials, as Dr. Davidson attempts to do, in view of methodologic and population differences: each trial must be considered independently. Of greatest concern in ENHANCE is the consistency among intima-media thickness end points, including strong trends toward adverse effects in the most diseased carotid and femoral segments.
Moreover, ENHANCE’s detractors contend that the carotid intima-media thickness of the studied population was normal, citing this as evidence of delipidation from prior treatment. Although not impossible (as shown by the work of Zhao and colleagues in the setting of prolonged, intense lipid-lowering therapy19), at the moment this hypothesis is a matter of conjecture in the ENHANCE participants, particularly because their LDL-C levels were still quite elevated during the trial and conceivably even before randomization.
But these patients were not normal: they were typical patients with familial hypercholesterolemia with extremely elevated LDL-C levels and abnormally thick arteries for their age. Population screening estimates show that, for age and sex, the carotid intima-media thickness values in ENHANCE would lie in the upper quartile of those in the general population.20 Moreover, their mean value is consistent with that in similar-aged groups of patients with familial hypercholesterolemia, even with lower rates of prior statin pretreatment.21
The most convincing evidence for the validity of the ENHANCE findings comes from the published subgroup data (Figure 1). In participants whose baseline carotid intima-media thickness was above the median at baseline, the thickness increased more with ezetimibe/simvastatin than with simvastatin alone. The same was true in the subgroup with above-average LDL-C levels at baseline. The subgroups with no prior statin treatment, low-dose prior statin treatment, and high-dose prior statin showed no heterogeneity of response: their carotid intima-media thickness increased more with ezetimibe/simvastatin than with simvastatin alone. None of these differences was statistically significant; however, these prespecified subgroup data seemingly invalidate arguments against the ENHANCE results based on carotid intima-media thickness findings.
In this context, ENHANCE can only be interpreted as a strong initial negative signal, a “red flag” about ezetimibe’s net health benefits.
WHAT NEXT?
The proper present focus of this debate is not on LDL-C but rather on ezetimibe, its unique mechanism of action, and on the need for more evidence about this complex compound.
At present, ezetimibe’s mechanism of action is not fully understood, and its benefit—for now, only mild LDL-C reduction—is too uncertain for us to be spending $5.2 billion a year for it. Its manufacturer is fortunate that the drug is even licensed, given the current and seemingly appropriate regulatory changes under which drugs introducing new therapeutic classes are scrutinized more closely for benefits and risks. “Safe and well tolerated,” as contended by Dr. Davidson, is not nearly enough: drugs must show clinically important benefits. We still know too little about this drug, the manufacturer of which has invested far more in marketing than in science, a point on which Dr. Davidson and I agree.
In 2008, ezetimibe is an appropriate candidate for testing in clinical trials, and in years to come it may be worthy of clinical attention—if rigorous and objectively conducted clinical trials prove its worth. At present, clinical equipoise dictates that ezetimibe is not an appropriate alternative to a statin in titrated doses, to the addition of other lipid-lowering drugs to a statin, to greater attention to drug adherence, or to lifestyle modification.
For the moment, given the ENHANCE results, the clinical usefulness of ezetimibe still remains to be proven. Much more evidence is needed before we can confidently reembrace the clinical use of ezetimibe.
- Ballantyne CM, Houri J, Notarbartolo A, et al. Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation 2003; 107:2409–2415.
- Kastelein JJ, Akdim F, Stroes ES, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med 2008; 358:1431–1443.
- Kent SM, Taylor AJ. Usefulness of lowering low-density lipoprotein cholesterol to < 70 mg/dL and usefulness of C-reactive protein in patient selection. Am J Cardiol 2003; 92:1224–1227.
- Nissen SE, Tuzcu EM, Schoenhagen P, et al. Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med 2005; 352:29–38.
- Davidson MH. Interpreting the ENHANCE trial. Is ezetimibe/simvastatin no better than simvastatin alone? Leessons learned and clinical implications. Cleve Clin J Med 2008; 75:479–491.
- Gouni-Berthold I, Berthold HK, Gylling H, et al. Effects of ezetimibe and/or simvastatin on LDL receptor protein expression and on LDL receptor and HMG-CoA reductase gene expression: a randomized trial in healthy men. Atherosclerosis 2008; 198:198–207.
- Spener F. Ezetimibe in search of receptor(s)—still a never-ending challenge in cholesterol absorption and transport. Biochim Biophys Acta 2007; 1771:1113–1116.
- Acton S, Rigotti A, Landschulz KT, Xu S, Hobbs HH, Krieger M. Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science 1996; 271:518–520.
- Kitayama K, Nishizawa T, Abe K, et al. Blockade of scavenger receptor class B type I raises high density lipoprotein cholesterol levels but exacerbates atherosclerotic lesion formation in apolipoprotein E deficient mice. J Pharm Pharmacol 2006; 58:1629–1638.
- During A, Dawson HD, Harrison EH. Carotenoid transport is decreased and expression of the lipid transporters SR-BI, NPC1L1, and ABCA1 is downregulated in Caco-2 cells treated with ezetimibe. J Nutr 2005; 135:2305–2312.
- Orso E, Werner T, Wolf Z, Bandulik S, Kramer W, Schmitz G. Ezetimib influences the expression of raft-associated antigens in human monocytes. Cytometry A 2006; 69:206–208.
- Patrick JE, Kosoglou T, Stauber KL, et al. Disposition of the selective cholesterol absorption inhibitor ezetimibe in healthy male subjects. Drug Metab Dispos 2002; 30:430–437.
- Kuhlencordt PJ, Padmapriya P, Rutzel S, et al. Ezetimibe potently reduces vascular inflammation and arteriosclerosis in eNOS-deficient ApoE ko mice. Atherosclerosis 2008; April 6.
- Bulut D, Hanefeld C, Bulut-Streich N, Graf C, Mugge A, Spiecker M. Endothelial function in the forearm circulation of patients with the metabolic syndrome—effect of different lipid-lowering regimens. Cardiology 2005; 104:176–180.
- Fichtlscherer S, Schmidt-Lucke C, Bojunga S, et al. Differential effects of short-term lipid lowering with ezetimibe and statins on endothelial function in patients with CAD: clinical evidence for ‘pleiotropic’ functions of statin therapy. Eur Heart J 2006; 27:1182–1190.
- Landmesser U, Bahlmann F, Mueller M, et al. Simvastatin versus ezetimibe: pleiotropic and lipid-lowering effects on endothelial function in humans. Circulation 2005; 111:2356–2363.
- Maki-Petaja KM, Booth AD, Hall FC, et al. Ezetimibe and simvastatin reduce inflammation, disease activity, and aortic stiffness and improve endothelial function in rheumatoid arthritis. J Am Coll Cardiol 2007; 50:852–858.
- Settergren M, Bohm F, Ryden L, Pernow J. Cholesterol lowering is more important than pleiotropic effects of statins for endothelial function in patients with dysglycaemia and coronary artery disease. Eur Heart J 2008 April 25.
- Zhao XQ, Yuan C, Hatsukami TS, et al. Effects of prolonged intensive lipid-lowering therapy on the characteristics of carotid atherosclerotic plaques in vivo by MRI: a case-control study. Arterioscler Thromb Vasc Biol 2001; 21:1623–1629.
- Stein JH, Korcarz CE, Hurst RT, et al. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascular Medicine. J Am Soc Echocardiogr 2008; 21:93–111.
- Junyent M, Cofan M, Nunez I, Gilabert R, Zambon D, Ros E. Influence of HDL cholesterol on preclinical carotid atherosclerosis in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 2006; 26:1107–1113.
Ezetimibe (Zetia) was licensed by the US Food and Drug Administration in 2002 on the basis of its ability to reduce low-density lipoprotein cholesterol (LDL-C) levels. The reductions are mild, approximately 15%,1 which is comparable to the effects of a stringent diet and exercise or of a statin in titrated doses.
However, there was no evidence that ezetimbe, which has a unique mechanism of action, delivers a benefit in terms of clinical outcomes. Despite this, the use of ezetimibe (alone or in fixed-dose combination with simvastatin, a preparation sold as Vytorin) grew rapidly, generating annual sales of $5.2 billion. Clinicians and the manufacturer (Merck/Schering-Plough) broadly assumed that LDL-C reduction would carry ezetimibe’s day as clinical trials emerged.
The assumption seemed reasonable, since evidence from the past 3 decades has established a clear link between lowering LDL-C levels via diverse mechanisms and positive clinical outcomes, particularly lower rates of cardiovascular disease and death. Indeed, LDL-C measurement is now a focus of cardiovascular risk assessment and management, as reflected in national treatment guidelines.
THE ENHANCE TRIAL: EZETIMIBE FAILS A KEY TEST
Unexpectedly, ezetimibe failed its first step in clinical trial validation, the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial.2 Apart from the scientifically irrelevant political regulatory intrigue generated by the sponsor’s conduct in this trial, ENHANCE’s findings challenge us to confront issues of what we assume vs what we really know, and how to interpret the complex results of clinical trials.
To be fair to the trial’s investigators, ENHANCE achieved its objective of enrolling a population with a very high LDL-C level, which is ezetimibe’s target and has been widely used in the study of atherosclerosis progression as a marker of potential drug benefit. Nevertheless, and even though the LDL-C level 2 years later was 52 mg/dL lower in the group receiving ezetimibe/simvastatin than in the group receiving simvastatin alone (Zocor), at LDL-C levels that are typically associated with atherosclerosis progression (140–190 mg/dL), ezetimibe failed to reduce the progression of atherosclerosis.
In fact, after 2 years of therapy, the intima-media thickness had increased more in the ezetimibe/simvastatin group than in the simvastatin-only group, most notably in the most-diseased carotid and femoral segments, although the differences between groups were not statistically significant. A lack of effect or a trend toward a worse effect with ezetimibe was seen in 22 of 25 subgroups, including key subgroups based on prior statin treatment (patients with no prior statin therapy did not benefit), baseline carotid intima-media thickness (patients with thicker arteries did not benefit), and baseline LDL-C levels (those with higher baseline levels did not benefit) (Figure 1).
These trends are particularly worrisome, given that the ezetimibe/simvastatin group achieved a greater reduction in C-reactive protein levels, which typically has resulted in superior outcomes in atherosclerosis3 and clinical effects4 in combination with LDL-C reduction.
In view of these findings, should clinicians stand firm and continue to use ezetimibe? Or should we reevaluate our position and await more data about this unique, first-in-class compound?
WISHFUL POST HOC HYPOTHESES
In this issue of the Cleveland Clinic Journal of Medicine, Dr. Michael Davidson,5 a respected lipid expert but one invested in ezetimibe’s development, assures us that all is in order and that the results of ENHANCE can be explained away by several arguments, most notably that most of the trial’s participants had previously received lipid-lowering treatment, which obscured the effects of ezetimibe. Moreover, he argues that ezetimibe’s mechanism of action is well understood and that the drug is safe and well tolerated and thus should remain a first-line treatment for hyperlipidemia.
These arguments may eventually prove to be correct, but as of now they are merely wishful post hoc hypotheses awaiting more data apart from ENHANCE. Negative clinical trials do occur as a matter of chance, but we should be cautious in any attempts to explain away a trial that was designed, executed, and reported as conceived simply because the results do not match our expectations.
Confronted with ENHANCE, the astute clinician should ask three questions: Do we really understand ezetimibe’s mechanism of action? Do other lines of evidence indicate the drug is beneficial? And how reliable is the arterial thickness as a surrogate end point?
DO WE UNDERSTAND EZETIMIBE’S MECHANISM OF ACTION?
Do we understand ezetimibe’s full mechanism of action? Not really.
True, ezetimibe inhibits cholesterol transport, a process that is integral both to cholesterol’s enteric absorption and to its systemic clearance. But although Dr. Davidson asserts that ezetimibe has cellular effects similar to those of statins, in fact it has the opposite effect on HMG-coA reductase, and no effects on LDL receptors.6
Furthermore, although initial studies suggested that ezetimibe inhibits enteric cholesterol absorption by inhibiting the Niemann-Pick C1L1 (NPC1L1) receptor, more recent investigations call this into serious question and point more definitively at a receptor known as scavenger receptor-B1 (SR-B1). As stated in a recent editorial, “SR-B1 in the apical site of enterocytes is the primary high-affinity site of cholesterol uptake and ezetimibe can inhibit this process. Moreover, the [possibility is ruled out] of NPC1L1 being a major player in this cholesterol uptake. This is at variance with the view of the colleagues from Schering-Plough who claim the same for NPC1L1.”7
SR-B1 is also a high-affinity receptor for high-density lipoprotein8 and thus is active in the antiatherosclerotic process of reverse cholesterol transport, inhibition of which significantly accelerates the development of atherosclerosis.9
Additionally, in vitro and thus unrelated to the effects of changing cholesterol concentration, ezetimibe down-regulates SR-B1 and another key cholesterol transporter protein called ABCA1.10 Further, ezetimibe induces down-regulation of raft protein domains, including CD36,11 another effect opposite to that of statins.
These little-recognized effects of ezetimibe are among many that are completely unrelated to enteric cholesterol absorption. Yet, they are likely to be active within the liver and systemically where these proteins reside, and they are putatively proatherosclerotic. Contrary to often-cited opinion, ezetimibe is systemically absorbed, with 11% of the compound excreted in the urine.12 Thus, the compound is systemically available to exert these same actions in the liver and elsewhere. Moreover, the absorbed drug is glucuronidated and is extensively recirculated in the liver in a form (its glucuronide) that is more potent than the parent compound.
In sum, present opinion is that ezetimibe inhibits lipid transport and interacts with a variety of receptors, not only in the gut but also systemically at the cell membrane and also inside the cell, focally disrupting several tightly regulated biologic processes.7 Thus, although ezetimibe reduces serum LDL-C levels via its effect in the gut, this effect may well be offset or even overridden systemically by other, unmeasurable effects, leading to counterintuitive results in terms of atherosclerosis or clinical events.
This would not be the first time a lipid-lowering drug has disappointed us: torcetrapib, another transport inhibitor, dramatically raises serum high-density lipoprotein cholesterol levels and reduces LDL-C but was found not only to have no effect on atherosclerosis, but also to potentiate adverse clinical outcomes.
The net impact of these other actions of ezetimibe is not known. We will discover its true clinical effects only through studies of endothelial function, atherosclerosis, and clinical cardiovascular outcomes. ENHANCE, which looked at atherosclerosis, is thus our strongest signal to date on the net effect of ezetimibe.
DO OTHER LINES OF EVIDENCE INDICATE EZETIMIBE IS BENEFICIAL?
Can we be reassured that ENHANCE’s results are spurious on the basis of other lines of evidence? Again, not really.
Experiments in animals, particularly in mice,13 have shown that ezetimibe may be antiatherosclerotic, although mice are considered the “worst model”7 for the study of ezetimibe, and notably, LDL-C levels were lowered far more in these experiments than they are clinically. Enthusiasm for these animal models should be tempered by interspecies variability in ezetimibe’s “off-target” effects and in the recent failure of other lipid transport drugs in human trials (torcetrapib and ACAT inhibitors) that had shown initial success in animals. No animal model is established for evaluating drugs of ezetimibe’s class, given its complex mechanism of action.
In human studies, the only other surrogate of the net effect of ezetimibe is endothelial function. Among several randomized clinical trials of ezetimibe,14–18 only one was designed to compare the effects of ezetimibe alone, ezetimibe plus a statin, and a statin by itself in titrated or in maximum doses.15 After 4 weeks of therapy, all groups had lower LDL-C levels. However, ezetimibe monotherapy and ezetimibe/simvastatin combination therapy had no detectable effect on the arterial response to acetylcholine, but atorvastatin (Lipitor) monotherapy did. To be fair, the other (very small) trials showed mixed results, thus keeping the hypothesis of ezetimibe’s benefit alive, but with nothing close to a clear signal of benefit.
IS ARTERIAL THICKNESS RELIABLE AS A SURROGATE END POINT?
Was the principal problem in ENHANCE the use of carotid intima-media thickness as the primary end point? No.
This issue has received a lot of attention, much of which I believe is misinformed. No trial end point is infallible, including carotid intima-media thickness, and one must remain open to the possibility of chance findings. However, it has been a relatively reasonable end point in trials of diverse cardiovascular preventive strategies, including lipid-lowering, blood-pressure-lowering, and lifestyle interventions and as a directional biomarker of clinical atherosclerotic events.
We should be cautious about comparing data on carotid intima-media thickness from different trials, as Dr. Davidson attempts to do, in view of methodologic and population differences: each trial must be considered independently. Of greatest concern in ENHANCE is the consistency among intima-media thickness end points, including strong trends toward adverse effects in the most diseased carotid and femoral segments.
Moreover, ENHANCE’s detractors contend that the carotid intima-media thickness of the studied population was normal, citing this as evidence of delipidation from prior treatment. Although not impossible (as shown by the work of Zhao and colleagues in the setting of prolonged, intense lipid-lowering therapy19), at the moment this hypothesis is a matter of conjecture in the ENHANCE participants, particularly because their LDL-C levels were still quite elevated during the trial and conceivably even before randomization.
But these patients were not normal: they were typical patients with familial hypercholesterolemia with extremely elevated LDL-C levels and abnormally thick arteries for their age. Population screening estimates show that, for age and sex, the carotid intima-media thickness values in ENHANCE would lie in the upper quartile of those in the general population.20 Moreover, their mean value is consistent with that in similar-aged groups of patients with familial hypercholesterolemia, even with lower rates of prior statin pretreatment.21
The most convincing evidence for the validity of the ENHANCE findings comes from the published subgroup data (Figure 1). In participants whose baseline carotid intima-media thickness was above the median at baseline, the thickness increased more with ezetimibe/simvastatin than with simvastatin alone. The same was true in the subgroup with above-average LDL-C levels at baseline. The subgroups with no prior statin treatment, low-dose prior statin treatment, and high-dose prior statin showed no heterogeneity of response: their carotid intima-media thickness increased more with ezetimibe/simvastatin than with simvastatin alone. None of these differences was statistically significant; however, these prespecified subgroup data seemingly invalidate arguments against the ENHANCE results based on carotid intima-media thickness findings.
In this context, ENHANCE can only be interpreted as a strong initial negative signal, a “red flag” about ezetimibe’s net health benefits.
WHAT NEXT?
The proper present focus of this debate is not on LDL-C but rather on ezetimibe, its unique mechanism of action, and on the need for more evidence about this complex compound.
At present, ezetimibe’s mechanism of action is not fully understood, and its benefit—for now, only mild LDL-C reduction—is too uncertain for us to be spending $5.2 billion a year for it. Its manufacturer is fortunate that the drug is even licensed, given the current and seemingly appropriate regulatory changes under which drugs introducing new therapeutic classes are scrutinized more closely for benefits and risks. “Safe and well tolerated,” as contended by Dr. Davidson, is not nearly enough: drugs must show clinically important benefits. We still know too little about this drug, the manufacturer of which has invested far more in marketing than in science, a point on which Dr. Davidson and I agree.
In 2008, ezetimibe is an appropriate candidate for testing in clinical trials, and in years to come it may be worthy of clinical attention—if rigorous and objectively conducted clinical trials prove its worth. At present, clinical equipoise dictates that ezetimibe is not an appropriate alternative to a statin in titrated doses, to the addition of other lipid-lowering drugs to a statin, to greater attention to drug adherence, or to lifestyle modification.
For the moment, given the ENHANCE results, the clinical usefulness of ezetimibe still remains to be proven. Much more evidence is needed before we can confidently reembrace the clinical use of ezetimibe.
Ezetimibe (Zetia) was licensed by the US Food and Drug Administration in 2002 on the basis of its ability to reduce low-density lipoprotein cholesterol (LDL-C) levels. The reductions are mild, approximately 15%,1 which is comparable to the effects of a stringent diet and exercise or of a statin in titrated doses.
However, there was no evidence that ezetimbe, which has a unique mechanism of action, delivers a benefit in terms of clinical outcomes. Despite this, the use of ezetimibe (alone or in fixed-dose combination with simvastatin, a preparation sold as Vytorin) grew rapidly, generating annual sales of $5.2 billion. Clinicians and the manufacturer (Merck/Schering-Plough) broadly assumed that LDL-C reduction would carry ezetimibe’s day as clinical trials emerged.
The assumption seemed reasonable, since evidence from the past 3 decades has established a clear link between lowering LDL-C levels via diverse mechanisms and positive clinical outcomes, particularly lower rates of cardiovascular disease and death. Indeed, LDL-C measurement is now a focus of cardiovascular risk assessment and management, as reflected in national treatment guidelines.
THE ENHANCE TRIAL: EZETIMIBE FAILS A KEY TEST
Unexpectedly, ezetimibe failed its first step in clinical trial validation, the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial.2 Apart from the scientifically irrelevant political regulatory intrigue generated by the sponsor’s conduct in this trial, ENHANCE’s findings challenge us to confront issues of what we assume vs what we really know, and how to interpret the complex results of clinical trials.
To be fair to the trial’s investigators, ENHANCE achieved its objective of enrolling a population with a very high LDL-C level, which is ezetimibe’s target and has been widely used in the study of atherosclerosis progression as a marker of potential drug benefit. Nevertheless, and even though the LDL-C level 2 years later was 52 mg/dL lower in the group receiving ezetimibe/simvastatin than in the group receiving simvastatin alone (Zocor), at LDL-C levels that are typically associated with atherosclerosis progression (140–190 mg/dL), ezetimibe failed to reduce the progression of atherosclerosis.
In fact, after 2 years of therapy, the intima-media thickness had increased more in the ezetimibe/simvastatin group than in the simvastatin-only group, most notably in the most-diseased carotid and femoral segments, although the differences between groups were not statistically significant. A lack of effect or a trend toward a worse effect with ezetimibe was seen in 22 of 25 subgroups, including key subgroups based on prior statin treatment (patients with no prior statin therapy did not benefit), baseline carotid intima-media thickness (patients with thicker arteries did not benefit), and baseline LDL-C levels (those with higher baseline levels did not benefit) (Figure 1).
These trends are particularly worrisome, given that the ezetimibe/simvastatin group achieved a greater reduction in C-reactive protein levels, which typically has resulted in superior outcomes in atherosclerosis3 and clinical effects4 in combination with LDL-C reduction.
In view of these findings, should clinicians stand firm and continue to use ezetimibe? Or should we reevaluate our position and await more data about this unique, first-in-class compound?
WISHFUL POST HOC HYPOTHESES
In this issue of the Cleveland Clinic Journal of Medicine, Dr. Michael Davidson,5 a respected lipid expert but one invested in ezetimibe’s development, assures us that all is in order and that the results of ENHANCE can be explained away by several arguments, most notably that most of the trial’s participants had previously received lipid-lowering treatment, which obscured the effects of ezetimibe. Moreover, he argues that ezetimibe’s mechanism of action is well understood and that the drug is safe and well tolerated and thus should remain a first-line treatment for hyperlipidemia.
These arguments may eventually prove to be correct, but as of now they are merely wishful post hoc hypotheses awaiting more data apart from ENHANCE. Negative clinical trials do occur as a matter of chance, but we should be cautious in any attempts to explain away a trial that was designed, executed, and reported as conceived simply because the results do not match our expectations.
Confronted with ENHANCE, the astute clinician should ask three questions: Do we really understand ezetimibe’s mechanism of action? Do other lines of evidence indicate the drug is beneficial? And how reliable is the arterial thickness as a surrogate end point?
DO WE UNDERSTAND EZETIMIBE’S MECHANISM OF ACTION?
Do we understand ezetimibe’s full mechanism of action? Not really.
True, ezetimibe inhibits cholesterol transport, a process that is integral both to cholesterol’s enteric absorption and to its systemic clearance. But although Dr. Davidson asserts that ezetimibe has cellular effects similar to those of statins, in fact it has the opposite effect on HMG-coA reductase, and no effects on LDL receptors.6
Furthermore, although initial studies suggested that ezetimibe inhibits enteric cholesterol absorption by inhibiting the Niemann-Pick C1L1 (NPC1L1) receptor, more recent investigations call this into serious question and point more definitively at a receptor known as scavenger receptor-B1 (SR-B1). As stated in a recent editorial, “SR-B1 in the apical site of enterocytes is the primary high-affinity site of cholesterol uptake and ezetimibe can inhibit this process. Moreover, the [possibility is ruled out] of NPC1L1 being a major player in this cholesterol uptake. This is at variance with the view of the colleagues from Schering-Plough who claim the same for NPC1L1.”7
SR-B1 is also a high-affinity receptor for high-density lipoprotein8 and thus is active in the antiatherosclerotic process of reverse cholesterol transport, inhibition of which significantly accelerates the development of atherosclerosis.9
Additionally, in vitro and thus unrelated to the effects of changing cholesterol concentration, ezetimibe down-regulates SR-B1 and another key cholesterol transporter protein called ABCA1.10 Further, ezetimibe induces down-regulation of raft protein domains, including CD36,11 another effect opposite to that of statins.
These little-recognized effects of ezetimibe are among many that are completely unrelated to enteric cholesterol absorption. Yet, they are likely to be active within the liver and systemically where these proteins reside, and they are putatively proatherosclerotic. Contrary to often-cited opinion, ezetimibe is systemically absorbed, with 11% of the compound excreted in the urine.12 Thus, the compound is systemically available to exert these same actions in the liver and elsewhere. Moreover, the absorbed drug is glucuronidated and is extensively recirculated in the liver in a form (its glucuronide) that is more potent than the parent compound.
In sum, present opinion is that ezetimibe inhibits lipid transport and interacts with a variety of receptors, not only in the gut but also systemically at the cell membrane and also inside the cell, focally disrupting several tightly regulated biologic processes.7 Thus, although ezetimibe reduces serum LDL-C levels via its effect in the gut, this effect may well be offset or even overridden systemically by other, unmeasurable effects, leading to counterintuitive results in terms of atherosclerosis or clinical events.
This would not be the first time a lipid-lowering drug has disappointed us: torcetrapib, another transport inhibitor, dramatically raises serum high-density lipoprotein cholesterol levels and reduces LDL-C but was found not only to have no effect on atherosclerosis, but also to potentiate adverse clinical outcomes.
The net impact of these other actions of ezetimibe is not known. We will discover its true clinical effects only through studies of endothelial function, atherosclerosis, and clinical cardiovascular outcomes. ENHANCE, which looked at atherosclerosis, is thus our strongest signal to date on the net effect of ezetimibe.
DO OTHER LINES OF EVIDENCE INDICATE EZETIMIBE IS BENEFICIAL?
Can we be reassured that ENHANCE’s results are spurious on the basis of other lines of evidence? Again, not really.
Experiments in animals, particularly in mice,13 have shown that ezetimibe may be antiatherosclerotic, although mice are considered the “worst model”7 for the study of ezetimibe, and notably, LDL-C levels were lowered far more in these experiments than they are clinically. Enthusiasm for these animal models should be tempered by interspecies variability in ezetimibe’s “off-target” effects and in the recent failure of other lipid transport drugs in human trials (torcetrapib and ACAT inhibitors) that had shown initial success in animals. No animal model is established for evaluating drugs of ezetimibe’s class, given its complex mechanism of action.
In human studies, the only other surrogate of the net effect of ezetimibe is endothelial function. Among several randomized clinical trials of ezetimibe,14–18 only one was designed to compare the effects of ezetimibe alone, ezetimibe plus a statin, and a statin by itself in titrated or in maximum doses.15 After 4 weeks of therapy, all groups had lower LDL-C levels. However, ezetimibe monotherapy and ezetimibe/simvastatin combination therapy had no detectable effect on the arterial response to acetylcholine, but atorvastatin (Lipitor) monotherapy did. To be fair, the other (very small) trials showed mixed results, thus keeping the hypothesis of ezetimibe’s benefit alive, but with nothing close to a clear signal of benefit.
IS ARTERIAL THICKNESS RELIABLE AS A SURROGATE END POINT?
Was the principal problem in ENHANCE the use of carotid intima-media thickness as the primary end point? No.
This issue has received a lot of attention, much of which I believe is misinformed. No trial end point is infallible, including carotid intima-media thickness, and one must remain open to the possibility of chance findings. However, it has been a relatively reasonable end point in trials of diverse cardiovascular preventive strategies, including lipid-lowering, blood-pressure-lowering, and lifestyle interventions and as a directional biomarker of clinical atherosclerotic events.
We should be cautious about comparing data on carotid intima-media thickness from different trials, as Dr. Davidson attempts to do, in view of methodologic and population differences: each trial must be considered independently. Of greatest concern in ENHANCE is the consistency among intima-media thickness end points, including strong trends toward adverse effects in the most diseased carotid and femoral segments.
Moreover, ENHANCE’s detractors contend that the carotid intima-media thickness of the studied population was normal, citing this as evidence of delipidation from prior treatment. Although not impossible (as shown by the work of Zhao and colleagues in the setting of prolonged, intense lipid-lowering therapy19), at the moment this hypothesis is a matter of conjecture in the ENHANCE participants, particularly because their LDL-C levels were still quite elevated during the trial and conceivably even before randomization.
But these patients were not normal: they were typical patients with familial hypercholesterolemia with extremely elevated LDL-C levels and abnormally thick arteries for their age. Population screening estimates show that, for age and sex, the carotid intima-media thickness values in ENHANCE would lie in the upper quartile of those in the general population.20 Moreover, their mean value is consistent with that in similar-aged groups of patients with familial hypercholesterolemia, even with lower rates of prior statin pretreatment.21
The most convincing evidence for the validity of the ENHANCE findings comes from the published subgroup data (Figure 1). In participants whose baseline carotid intima-media thickness was above the median at baseline, the thickness increased more with ezetimibe/simvastatin than with simvastatin alone. The same was true in the subgroup with above-average LDL-C levels at baseline. The subgroups with no prior statin treatment, low-dose prior statin treatment, and high-dose prior statin showed no heterogeneity of response: their carotid intima-media thickness increased more with ezetimibe/simvastatin than with simvastatin alone. None of these differences was statistically significant; however, these prespecified subgroup data seemingly invalidate arguments against the ENHANCE results based on carotid intima-media thickness findings.
In this context, ENHANCE can only be interpreted as a strong initial negative signal, a “red flag” about ezetimibe’s net health benefits.
WHAT NEXT?
The proper present focus of this debate is not on LDL-C but rather on ezetimibe, its unique mechanism of action, and on the need for more evidence about this complex compound.
At present, ezetimibe’s mechanism of action is not fully understood, and its benefit—for now, only mild LDL-C reduction—is too uncertain for us to be spending $5.2 billion a year for it. Its manufacturer is fortunate that the drug is even licensed, given the current and seemingly appropriate regulatory changes under which drugs introducing new therapeutic classes are scrutinized more closely for benefits and risks. “Safe and well tolerated,” as contended by Dr. Davidson, is not nearly enough: drugs must show clinically important benefits. We still know too little about this drug, the manufacturer of which has invested far more in marketing than in science, a point on which Dr. Davidson and I agree.
In 2008, ezetimibe is an appropriate candidate for testing in clinical trials, and in years to come it may be worthy of clinical attention—if rigorous and objectively conducted clinical trials prove its worth. At present, clinical equipoise dictates that ezetimibe is not an appropriate alternative to a statin in titrated doses, to the addition of other lipid-lowering drugs to a statin, to greater attention to drug adherence, or to lifestyle modification.
For the moment, given the ENHANCE results, the clinical usefulness of ezetimibe still remains to be proven. Much more evidence is needed before we can confidently reembrace the clinical use of ezetimibe.
- Ballantyne CM, Houri J, Notarbartolo A, et al. Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation 2003; 107:2409–2415.
- Kastelein JJ, Akdim F, Stroes ES, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med 2008; 358:1431–1443.
- Kent SM, Taylor AJ. Usefulness of lowering low-density lipoprotein cholesterol to < 70 mg/dL and usefulness of C-reactive protein in patient selection. Am J Cardiol 2003; 92:1224–1227.
- Nissen SE, Tuzcu EM, Schoenhagen P, et al. Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med 2005; 352:29–38.
- Davidson MH. Interpreting the ENHANCE trial. Is ezetimibe/simvastatin no better than simvastatin alone? Leessons learned and clinical implications. Cleve Clin J Med 2008; 75:479–491.
- Gouni-Berthold I, Berthold HK, Gylling H, et al. Effects of ezetimibe and/or simvastatin on LDL receptor protein expression and on LDL receptor and HMG-CoA reductase gene expression: a randomized trial in healthy men. Atherosclerosis 2008; 198:198–207.
- Spener F. Ezetimibe in search of receptor(s)—still a never-ending challenge in cholesterol absorption and transport. Biochim Biophys Acta 2007; 1771:1113–1116.
- Acton S, Rigotti A, Landschulz KT, Xu S, Hobbs HH, Krieger M. Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science 1996; 271:518–520.
- Kitayama K, Nishizawa T, Abe K, et al. Blockade of scavenger receptor class B type I raises high density lipoprotein cholesterol levels but exacerbates atherosclerotic lesion formation in apolipoprotein E deficient mice. J Pharm Pharmacol 2006; 58:1629–1638.
- During A, Dawson HD, Harrison EH. Carotenoid transport is decreased and expression of the lipid transporters SR-BI, NPC1L1, and ABCA1 is downregulated in Caco-2 cells treated with ezetimibe. J Nutr 2005; 135:2305–2312.
- Orso E, Werner T, Wolf Z, Bandulik S, Kramer W, Schmitz G. Ezetimib influences the expression of raft-associated antigens in human monocytes. Cytometry A 2006; 69:206–208.
- Patrick JE, Kosoglou T, Stauber KL, et al. Disposition of the selective cholesterol absorption inhibitor ezetimibe in healthy male subjects. Drug Metab Dispos 2002; 30:430–437.
- Kuhlencordt PJ, Padmapriya P, Rutzel S, et al. Ezetimibe potently reduces vascular inflammation and arteriosclerosis in eNOS-deficient ApoE ko mice. Atherosclerosis 2008; April 6.
- Bulut D, Hanefeld C, Bulut-Streich N, Graf C, Mugge A, Spiecker M. Endothelial function in the forearm circulation of patients with the metabolic syndrome—effect of different lipid-lowering regimens. Cardiology 2005; 104:176–180.
- Fichtlscherer S, Schmidt-Lucke C, Bojunga S, et al. Differential effects of short-term lipid lowering with ezetimibe and statins on endothelial function in patients with CAD: clinical evidence for ‘pleiotropic’ functions of statin therapy. Eur Heart J 2006; 27:1182–1190.
- Landmesser U, Bahlmann F, Mueller M, et al. Simvastatin versus ezetimibe: pleiotropic and lipid-lowering effects on endothelial function in humans. Circulation 2005; 111:2356–2363.
- Maki-Petaja KM, Booth AD, Hall FC, et al. Ezetimibe and simvastatin reduce inflammation, disease activity, and aortic stiffness and improve endothelial function in rheumatoid arthritis. J Am Coll Cardiol 2007; 50:852–858.
- Settergren M, Bohm F, Ryden L, Pernow J. Cholesterol lowering is more important than pleiotropic effects of statins for endothelial function in patients with dysglycaemia and coronary artery disease. Eur Heart J 2008 April 25.
- Zhao XQ, Yuan C, Hatsukami TS, et al. Effects of prolonged intensive lipid-lowering therapy on the characteristics of carotid atherosclerotic plaques in vivo by MRI: a case-control study. Arterioscler Thromb Vasc Biol 2001; 21:1623–1629.
- Stein JH, Korcarz CE, Hurst RT, et al. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascular Medicine. J Am Soc Echocardiogr 2008; 21:93–111.
- Junyent M, Cofan M, Nunez I, Gilabert R, Zambon D, Ros E. Influence of HDL cholesterol on preclinical carotid atherosclerosis in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 2006; 26:1107–1113.
- Ballantyne CM, Houri J, Notarbartolo A, et al. Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation 2003; 107:2409–2415.
- Kastelein JJ, Akdim F, Stroes ES, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med 2008; 358:1431–1443.
- Kent SM, Taylor AJ. Usefulness of lowering low-density lipoprotein cholesterol to < 70 mg/dL and usefulness of C-reactive protein in patient selection. Am J Cardiol 2003; 92:1224–1227.
- Nissen SE, Tuzcu EM, Schoenhagen P, et al. Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med 2005; 352:29–38.
- Davidson MH. Interpreting the ENHANCE trial. Is ezetimibe/simvastatin no better than simvastatin alone? Leessons learned and clinical implications. Cleve Clin J Med 2008; 75:479–491.
- Gouni-Berthold I, Berthold HK, Gylling H, et al. Effects of ezetimibe and/or simvastatin on LDL receptor protein expression and on LDL receptor and HMG-CoA reductase gene expression: a randomized trial in healthy men. Atherosclerosis 2008; 198:198–207.
- Spener F. Ezetimibe in search of receptor(s)—still a never-ending challenge in cholesterol absorption and transport. Biochim Biophys Acta 2007; 1771:1113–1116.
- Acton S, Rigotti A, Landschulz KT, Xu S, Hobbs HH, Krieger M. Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science 1996; 271:518–520.
- Kitayama K, Nishizawa T, Abe K, et al. Blockade of scavenger receptor class B type I raises high density lipoprotein cholesterol levels but exacerbates atherosclerotic lesion formation in apolipoprotein E deficient mice. J Pharm Pharmacol 2006; 58:1629–1638.
- During A, Dawson HD, Harrison EH. Carotenoid transport is decreased and expression of the lipid transporters SR-BI, NPC1L1, and ABCA1 is downregulated in Caco-2 cells treated with ezetimibe. J Nutr 2005; 135:2305–2312.
- Orso E, Werner T, Wolf Z, Bandulik S, Kramer W, Schmitz G. Ezetimib influences the expression of raft-associated antigens in human monocytes. Cytometry A 2006; 69:206–208.
- Patrick JE, Kosoglou T, Stauber KL, et al. Disposition of the selective cholesterol absorption inhibitor ezetimibe in healthy male subjects. Drug Metab Dispos 2002; 30:430–437.
- Kuhlencordt PJ, Padmapriya P, Rutzel S, et al. Ezetimibe potently reduces vascular inflammation and arteriosclerosis in eNOS-deficient ApoE ko mice. Atherosclerosis 2008; April 6.
- Bulut D, Hanefeld C, Bulut-Streich N, Graf C, Mugge A, Spiecker M. Endothelial function in the forearm circulation of patients with the metabolic syndrome—effect of different lipid-lowering regimens. Cardiology 2005; 104:176–180.
- Fichtlscherer S, Schmidt-Lucke C, Bojunga S, et al. Differential effects of short-term lipid lowering with ezetimibe and statins on endothelial function in patients with CAD: clinical evidence for ‘pleiotropic’ functions of statin therapy. Eur Heart J 2006; 27:1182–1190.
- Landmesser U, Bahlmann F, Mueller M, et al. Simvastatin versus ezetimibe: pleiotropic and lipid-lowering effects on endothelial function in humans. Circulation 2005; 111:2356–2363.
- Maki-Petaja KM, Booth AD, Hall FC, et al. Ezetimibe and simvastatin reduce inflammation, disease activity, and aortic stiffness and improve endothelial function in rheumatoid arthritis. J Am Coll Cardiol 2007; 50:852–858.
- Settergren M, Bohm F, Ryden L, Pernow J. Cholesterol lowering is more important than pleiotropic effects of statins for endothelial function in patients with dysglycaemia and coronary artery disease. Eur Heart J 2008 April 25.
- Zhao XQ, Yuan C, Hatsukami TS, et al. Effects of prolonged intensive lipid-lowering therapy on the characteristics of carotid atherosclerotic plaques in vivo by MRI: a case-control study. Arterioscler Thromb Vasc Biol 2001; 21:1623–1629.
- Stein JH, Korcarz CE, Hurst RT, et al. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascular Medicine. J Am Soc Echocardiogr 2008; 21:93–111.
- Junyent M, Cofan M, Nunez I, Gilabert R, Zambon D, Ros E. Influence of HDL cholesterol on preclinical carotid atherosclerosis in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 2006; 26:1107–1113.
Who do you want taking care of your parent?
Specialist or generalist? The question of which physicians are best suited to treat patients with a single condition or in a particular care setting has been the subject of study and debate for decades.13 Investigators have asked whether cardiologists provide better care for patients with acute myocardial infarction1 or whether intensivists achieve superior outcomes in critical care settings.2 One implication of these studies is that a hospital or health plan armed with this knowledge would be capable of improving outcomes by directing a greater proportion of patients to the superior physician group. In fact, much of the literature reporting on the effect of hospitalists is simply a new variation on this old theme.48 Of course, to realize any potential gains, there must be an adequate number of specialists or the ability to increase the supply quickly. Neither option tends to be especially realistic. Further, these studies have a tendency to create false dilemmas because consultation and comanagement are more common than single‐handed care.
Because studies comparing the outcomes of physician groups are generally not randomized trials, minimizing the threat of selection bias (ie, patient prognosis influencing treatment assignment) is of paramount importance. For example, one can imagine how patients with a particularly poor prognosis in the setting of acute myocardial infarction (perhaps related to age or the presence of multiple comorbidities) might be preferentially directed toward a general medicine service, especially when remunerative cardiac intervention is unlikely. In such instances, comparing simple mortality rates would erroneously lead to the conclusion that patients cared for by cardiologists had better outcomes.
Multivariable modeling techniques like logistic and liner regression and more recently, propensity‐based methods, are the standard approaches used to adjust for differences in patient characteristics stemming from nonrandom assignment. When propensity methods are used, a multivariable model is created to predict the likelihood, or propensity, of a patient receiving treatment. Because it is not necessary to be parsimonious in the development of propensity models, they can include many factors and interaction terms that might be left out of a standard multivariable logistic regression. Then, the outcomes of patients with a similar treatment propensity who did receive the intervention can be compared to the outcomes of those who did not. Some have gone so far as to use the term pseudorandomized trial to describe this approach because it is often capable balancing covariates between the treated and nontreated patients. However, as sophisticated as this form of modeling may be, these techniques at best are only capable of reducing bias related to measured confounders. Residual bias from confounders that go unmeasured remains a threatand is particularly common when relying on administrative data sources.
In this issue of the Journal of Hospital Medicine, Gillum and Johnston9 apply a version of instrumental variable analysis, a technique borrowed from econometrics, to address the issue of unmeasured confounding head‐on. The approach, called group‐treatment analysis, is based on the relatively simple notion that if neurologist care is superior to that provided by generalists, all other things being equal, hospitals that admit a large proportion of their patients to neurologists should have better outcomes than those admitting a smaller proportion. This approach has theoretical advantages over propensity adjustment because it does not attempt to control for differences between treated and untreated patients at the individual hospital level, where, presumably, the problem of selection bias is more potent. Although their standard multivariable models suggested that patients admitted to a neurologist were 40% less likely to die while hospitalized than patients admitted to generalists, Gillum and Johnston found that after adjusting for the institutional rate of neurologist admission, any apparent benefit had disappeared. Similar results were observed in their analyses of length of stay and cost.
In some ways, the findings of this study are more startling for the questions they raise about the presence of residual bias in observational studies using conventional multivariable methods than for the fact that generalist care was found to be as safe as neurologist care and add to a growing body of evidence suggesting that stronger methods are required to deal with residual bias in observational studies.10
Although the results largely speak for themselves and should be reassuring given that most patients with ischemic stroke in the United States are and will continue to be cared for by generalists, a number of important questions remain unanswered. First, the focus of this study was on short‐term outcomes. Because functional status and quality of life probably matter as much or more to stroke patients than in‐hospital mortality and certainly length of stay or cost, we can only hope that it is safe to extrapolate from the authors' mortality findings. Second, this study relied on data from the late 1990s, before the widespread availability of hospitalists. How generalizable the findings would be in today's environment is uncertain. On a more practical level, the authors were unable to assess the impact of formal or informal consultation by a neurologist. If this played a significant role (a reasonable assumption, I think), this would have blurred any distinction between the 2 physician groups. For this reason one cannot draw any conclusions about a more pragmatic questionthe necessity or benefit of neurologist consultation in patients with ischemic stroke.
Looking ahead, researchers hoping to improve the outcomes of patients with acute ischemic stroke should focus on developing novel models of collaboration between hospitalists and neurologists, instead of simply trying to prove that a neurologist should take care of a patient suffering a stroke alone versus a hospitalist without help from a neurologist. We also should recognize that the use of protocols and checklists or leveraging information technology investments may provide clinical decision support that improves care more than just consulting a specialist or having them care for the patient.
- Treatment and outcomes of acute myocardial infarction among patients of cardiologists and generalist physicians.Arch Intern Med.1997;157:2570–2576. , , , .
- Physician staffing patterns and clinical outcomes in critically ill patients: a systematic review.JAMA.2002;288:2151–2162. , , , , , .
- A comparison of outcomes resulting from generalist vs specialist care for a single discrete medical condition: a systematic review and methodologic critique.Arch Intern Med.2007;167:10–20. , , , et al.
- Implementation of a voluntary hospitalist service at a community teaching hospital: improved clinical efficiency and patient outcomes.Ann Intern Med.2002;137:859–865. , , , et al.
- A comparison of two hospitalist models with traditional care in a community teaching hospital.Am J Med.2005;118:536–543. , , , et al.
- Associations with reduced length of stay and costs on an academic hospitalist service.Am J Manag Care.2004;10:561–568. , , , , , .
- Outcomes of care by hospitalists, general internists, and family physicians. [see comment].N Engl J Med.2007;357:2589–2600. , , , , , .
- Reorganizing an academic medical service: impact on cost, quality, patient satisfaction, and education.JAMA.1998;279:1560–1565. , , , et al.
- Influence of physician specialty on outcomes after acute ischemic stroke.J Hosp Med2008;3:184–192. , .
- Analysis of observational studies in the presence of treatment selection bias: effects of invasive cardiac management on AMI survival using propensity score and instrumental variable methods.JAMA.2007;297:278–285. , , , , , .
Specialist or generalist? The question of which physicians are best suited to treat patients with a single condition or in a particular care setting has been the subject of study and debate for decades.13 Investigators have asked whether cardiologists provide better care for patients with acute myocardial infarction1 or whether intensivists achieve superior outcomes in critical care settings.2 One implication of these studies is that a hospital or health plan armed with this knowledge would be capable of improving outcomes by directing a greater proportion of patients to the superior physician group. In fact, much of the literature reporting on the effect of hospitalists is simply a new variation on this old theme.48 Of course, to realize any potential gains, there must be an adequate number of specialists or the ability to increase the supply quickly. Neither option tends to be especially realistic. Further, these studies have a tendency to create false dilemmas because consultation and comanagement are more common than single‐handed care.
Because studies comparing the outcomes of physician groups are generally not randomized trials, minimizing the threat of selection bias (ie, patient prognosis influencing treatment assignment) is of paramount importance. For example, one can imagine how patients with a particularly poor prognosis in the setting of acute myocardial infarction (perhaps related to age or the presence of multiple comorbidities) might be preferentially directed toward a general medicine service, especially when remunerative cardiac intervention is unlikely. In such instances, comparing simple mortality rates would erroneously lead to the conclusion that patients cared for by cardiologists had better outcomes.
Multivariable modeling techniques like logistic and liner regression and more recently, propensity‐based methods, are the standard approaches used to adjust for differences in patient characteristics stemming from nonrandom assignment. When propensity methods are used, a multivariable model is created to predict the likelihood, or propensity, of a patient receiving treatment. Because it is not necessary to be parsimonious in the development of propensity models, they can include many factors and interaction terms that might be left out of a standard multivariable logistic regression. Then, the outcomes of patients with a similar treatment propensity who did receive the intervention can be compared to the outcomes of those who did not. Some have gone so far as to use the term pseudorandomized trial to describe this approach because it is often capable balancing covariates between the treated and nontreated patients. However, as sophisticated as this form of modeling may be, these techniques at best are only capable of reducing bias related to measured confounders. Residual bias from confounders that go unmeasured remains a threatand is particularly common when relying on administrative data sources.
In this issue of the Journal of Hospital Medicine, Gillum and Johnston9 apply a version of instrumental variable analysis, a technique borrowed from econometrics, to address the issue of unmeasured confounding head‐on. The approach, called group‐treatment analysis, is based on the relatively simple notion that if neurologist care is superior to that provided by generalists, all other things being equal, hospitals that admit a large proportion of their patients to neurologists should have better outcomes than those admitting a smaller proportion. This approach has theoretical advantages over propensity adjustment because it does not attempt to control for differences between treated and untreated patients at the individual hospital level, where, presumably, the problem of selection bias is more potent. Although their standard multivariable models suggested that patients admitted to a neurologist were 40% less likely to die while hospitalized than patients admitted to generalists, Gillum and Johnston found that after adjusting for the institutional rate of neurologist admission, any apparent benefit had disappeared. Similar results were observed in their analyses of length of stay and cost.
In some ways, the findings of this study are more startling for the questions they raise about the presence of residual bias in observational studies using conventional multivariable methods than for the fact that generalist care was found to be as safe as neurologist care and add to a growing body of evidence suggesting that stronger methods are required to deal with residual bias in observational studies.10
Although the results largely speak for themselves and should be reassuring given that most patients with ischemic stroke in the United States are and will continue to be cared for by generalists, a number of important questions remain unanswered. First, the focus of this study was on short‐term outcomes. Because functional status and quality of life probably matter as much or more to stroke patients than in‐hospital mortality and certainly length of stay or cost, we can only hope that it is safe to extrapolate from the authors' mortality findings. Second, this study relied on data from the late 1990s, before the widespread availability of hospitalists. How generalizable the findings would be in today's environment is uncertain. On a more practical level, the authors were unable to assess the impact of formal or informal consultation by a neurologist. If this played a significant role (a reasonable assumption, I think), this would have blurred any distinction between the 2 physician groups. For this reason one cannot draw any conclusions about a more pragmatic questionthe necessity or benefit of neurologist consultation in patients with ischemic stroke.
Looking ahead, researchers hoping to improve the outcomes of patients with acute ischemic stroke should focus on developing novel models of collaboration between hospitalists and neurologists, instead of simply trying to prove that a neurologist should take care of a patient suffering a stroke alone versus a hospitalist without help from a neurologist. We also should recognize that the use of protocols and checklists or leveraging information technology investments may provide clinical decision support that improves care more than just consulting a specialist or having them care for the patient.
Specialist or generalist? The question of which physicians are best suited to treat patients with a single condition or in a particular care setting has been the subject of study and debate for decades.13 Investigators have asked whether cardiologists provide better care for patients with acute myocardial infarction1 or whether intensivists achieve superior outcomes in critical care settings.2 One implication of these studies is that a hospital or health plan armed with this knowledge would be capable of improving outcomes by directing a greater proportion of patients to the superior physician group. In fact, much of the literature reporting on the effect of hospitalists is simply a new variation on this old theme.48 Of course, to realize any potential gains, there must be an adequate number of specialists or the ability to increase the supply quickly. Neither option tends to be especially realistic. Further, these studies have a tendency to create false dilemmas because consultation and comanagement are more common than single‐handed care.
Because studies comparing the outcomes of physician groups are generally not randomized trials, minimizing the threat of selection bias (ie, patient prognosis influencing treatment assignment) is of paramount importance. For example, one can imagine how patients with a particularly poor prognosis in the setting of acute myocardial infarction (perhaps related to age or the presence of multiple comorbidities) might be preferentially directed toward a general medicine service, especially when remunerative cardiac intervention is unlikely. In such instances, comparing simple mortality rates would erroneously lead to the conclusion that patients cared for by cardiologists had better outcomes.
Multivariable modeling techniques like logistic and liner regression and more recently, propensity‐based methods, are the standard approaches used to adjust for differences in patient characteristics stemming from nonrandom assignment. When propensity methods are used, a multivariable model is created to predict the likelihood, or propensity, of a patient receiving treatment. Because it is not necessary to be parsimonious in the development of propensity models, they can include many factors and interaction terms that might be left out of a standard multivariable logistic regression. Then, the outcomes of patients with a similar treatment propensity who did receive the intervention can be compared to the outcomes of those who did not. Some have gone so far as to use the term pseudorandomized trial to describe this approach because it is often capable balancing covariates between the treated and nontreated patients. However, as sophisticated as this form of modeling may be, these techniques at best are only capable of reducing bias related to measured confounders. Residual bias from confounders that go unmeasured remains a threatand is particularly common when relying on administrative data sources.
In this issue of the Journal of Hospital Medicine, Gillum and Johnston9 apply a version of instrumental variable analysis, a technique borrowed from econometrics, to address the issue of unmeasured confounding head‐on. The approach, called group‐treatment analysis, is based on the relatively simple notion that if neurologist care is superior to that provided by generalists, all other things being equal, hospitals that admit a large proportion of their patients to neurologists should have better outcomes than those admitting a smaller proportion. This approach has theoretical advantages over propensity adjustment because it does not attempt to control for differences between treated and untreated patients at the individual hospital level, where, presumably, the problem of selection bias is more potent. Although their standard multivariable models suggested that patients admitted to a neurologist were 40% less likely to die while hospitalized than patients admitted to generalists, Gillum and Johnston found that after adjusting for the institutional rate of neurologist admission, any apparent benefit had disappeared. Similar results were observed in their analyses of length of stay and cost.
In some ways, the findings of this study are more startling for the questions they raise about the presence of residual bias in observational studies using conventional multivariable methods than for the fact that generalist care was found to be as safe as neurologist care and add to a growing body of evidence suggesting that stronger methods are required to deal with residual bias in observational studies.10
Although the results largely speak for themselves and should be reassuring given that most patients with ischemic stroke in the United States are and will continue to be cared for by generalists, a number of important questions remain unanswered. First, the focus of this study was on short‐term outcomes. Because functional status and quality of life probably matter as much or more to stroke patients than in‐hospital mortality and certainly length of stay or cost, we can only hope that it is safe to extrapolate from the authors' mortality findings. Second, this study relied on data from the late 1990s, before the widespread availability of hospitalists. How generalizable the findings would be in today's environment is uncertain. On a more practical level, the authors were unable to assess the impact of formal or informal consultation by a neurologist. If this played a significant role (a reasonable assumption, I think), this would have blurred any distinction between the 2 physician groups. For this reason one cannot draw any conclusions about a more pragmatic questionthe necessity or benefit of neurologist consultation in patients with ischemic stroke.
Looking ahead, researchers hoping to improve the outcomes of patients with acute ischemic stroke should focus on developing novel models of collaboration between hospitalists and neurologists, instead of simply trying to prove that a neurologist should take care of a patient suffering a stroke alone versus a hospitalist without help from a neurologist. We also should recognize that the use of protocols and checklists or leveraging information technology investments may provide clinical decision support that improves care more than just consulting a specialist or having them care for the patient.
- Treatment and outcomes of acute myocardial infarction among patients of cardiologists and generalist physicians.Arch Intern Med.1997;157:2570–2576. , , , .
- Physician staffing patterns and clinical outcomes in critically ill patients: a systematic review.JAMA.2002;288:2151–2162. , , , , , .
- A comparison of outcomes resulting from generalist vs specialist care for a single discrete medical condition: a systematic review and methodologic critique.Arch Intern Med.2007;167:10–20. , , , et al.
- Implementation of a voluntary hospitalist service at a community teaching hospital: improved clinical efficiency and patient outcomes.Ann Intern Med.2002;137:859–865. , , , et al.
- A comparison of two hospitalist models with traditional care in a community teaching hospital.Am J Med.2005;118:536–543. , , , et al.
- Associations with reduced length of stay and costs on an academic hospitalist service.Am J Manag Care.2004;10:561–568. , , , , , .
- Outcomes of care by hospitalists, general internists, and family physicians. [see comment].N Engl J Med.2007;357:2589–2600. , , , , , .
- Reorganizing an academic medical service: impact on cost, quality, patient satisfaction, and education.JAMA.1998;279:1560–1565. , , , et al.
- Influence of physician specialty on outcomes after acute ischemic stroke.J Hosp Med2008;3:184–192. , .
- Analysis of observational studies in the presence of treatment selection bias: effects of invasive cardiac management on AMI survival using propensity score and instrumental variable methods.JAMA.2007;297:278–285. , , , , , .
- Treatment and outcomes of acute myocardial infarction among patients of cardiologists and generalist physicians.Arch Intern Med.1997;157:2570–2576. , , , .
- Physician staffing patterns and clinical outcomes in critically ill patients: a systematic review.JAMA.2002;288:2151–2162. , , , , , .
- A comparison of outcomes resulting from generalist vs specialist care for a single discrete medical condition: a systematic review and methodologic critique.Arch Intern Med.2007;167:10–20. , , , et al.
- Implementation of a voluntary hospitalist service at a community teaching hospital: improved clinical efficiency and patient outcomes.Ann Intern Med.2002;137:859–865. , , , et al.
- A comparison of two hospitalist models with traditional care in a community teaching hospital.Am J Med.2005;118:536–543. , , , et al.
- Associations with reduced length of stay and costs on an academic hospitalist service.Am J Manag Care.2004;10:561–568. , , , , , .
- Outcomes of care by hospitalists, general internists, and family physicians. [see comment].N Engl J Med.2007;357:2589–2600. , , , , , .
- Reorganizing an academic medical service: impact on cost, quality, patient satisfaction, and education.JAMA.1998;279:1560–1565. , , , et al.
- Influence of physician specialty on outcomes after acute ischemic stroke.J Hosp Med2008;3:184–192. , .
- Analysis of observational studies in the presence of treatment selection bias: effects of invasive cardiac management on AMI survival using propensity score and instrumental variable methods.JAMA.2007;297:278–285. , , , , , .
Improving nurse working conditions: Towards safer models of hospital care
Over the past decade, an emerging body of literature established a link between nurses' working conditions and their ability to provide safe care. Nurses who are not at their best are both prone to making errors themselves, and less able to serve as effective safety nets for their patients, intercepting errors made by physicians and others.1 Excessive nurse workloads predict an increased rate of adverse events,2, 3 and, by their own reports, nurses working shifts of >12 hours are at greatly increased risk of making medical errors.4, 5 On the basis of these and related findings, the Institute of Medicine has recommended: a) that efforts be made to assure appropriate nurse workloads and b) that nurses work no more than 12 hours per day and 60 hours per week;6 but these recommendations have not been broadly enforced.7
Two articles in the current issue of the Journal of Hospital Medicine add to our understanding of the relationship between nurse working conditions and safety, and substantiate the need to improve nurses' working conditions. In the first, Surani et al. conducted a pilot study of 20 night nurses working 12‐hour shifts in which well‐validated, objective tools revealed that ICU nurses were suffering from pathologic levels of drowsiness on the job.8 The topic is of importance as recent survey work demonstrated that nurses working >12 hours and resident‐physicians working shifts of 24 of more hours make significantly more medical errors and suffer many more occupational injuries than those working less exhausting schedules.4, 5, 912 Objective data on resident‐physicians has corroborated these findings,13, 14 but objective data measuring sleepiness in nurses has been lacking. Surani et al.'s study helps to fill this need. Further, this study suggests that hospitals should not be complacent about the safety of 12‐hour shifts, which may still be associated with dangerous levels of drowsiness‐induced impairment. Careful management of the number of consecutive night shifts,15 or further reductions in nursing work hours even beyond the 12‐hour limit endorsed by the IOM may be in orderparticularly in high‐risk critical care environmentsthough further research substantiating Surani et al.'s findings and comparing alternative scheduling options would be valuable.
The second study by Conway et al. analyzed data for acute care hospitals in California from 1993 to 2004, and found that following the passage of nurse staffing legislation in 1999 and its implementation in 2004, nurse‐patient staffing ratios increased significantly.16 Safety‐net hospitals, however, with high proportions of vulnerable patient populations, were least likely to achieve mandated ratios. As the authors point out, diverting funds to achieve mandated ratios in under‐funded safety net hospitals could potentially lead to reductions in other essential services, though whether such an eventuality might come to pass has not been adequately assessed to date.
In light of these data, where should we go from here? Public and professional concerns over the impact of fewer nurses on the delivery of care have led to the passage of legislation or adoption of regulations by many states in an attempt to ensure safe care. Examples include elimination of mandatory overtime in the following states: CT, IL, ME, MD, MN, NJ, NH, OR, RI, WA, WV, CA, MO, and TX; implementation of nurse staffing plans with input from staff nurses (WA, IL, OR, RI, TX), and mandates of specific nurse to patient ratios (CA [as discussed by Conway et al.] and FL).17 Proposed legislation regarding nurse staffing and nurse‐to‐patient ratios is currently under consideration in many additional states. Legislation broadly restricting nurse work hours has not been passed by the federal government or individual states, but some hospital systems including the Veteran's Administration now have policies prohibiting shifts of greater than 12 hours and work weeks of greater than 60 hours.18
Unfortunately, several major barriers have made the implementation of safer work hours and workloads challenging, and uncertainty about the effectiveness of implementation efforts remains. A major challenge has been the presence of a serious shortage of nurses, which is expected to peak by 2020.19 A lack of nurses will make both staffing and scheduling initiatives difficult. Over the next 10 to 15 years, policies that fund nursing education or otherwise address this shortfall will consequently be essential.
A second challenge in efforts to implement safer work schedules appears to be an absence of knowledge about the hazards of sleep deprivation, compounded by financial pressures that may lead to unsafe schedules. Some nurses oppose restriction of work hours citing that they know when they are tired, their schedule works for their personal life, and they should be allowed to work as much as they want to earn the salary they want/need. Unfortunately, it has been well‐demonstrated that chronically sleep‐deprived individuals routinely under‐estimate their level of impairment, calling into question the ability of nurses and others working extreme hours to accurately judge their abilities to perform safely.20
Clearly, education on the effects of fatigue on performance is needed, as are widespread efforts to implement safe schedules. Further study of work injuries, medical errors, and their relation to fatigue and specific work schedules is warranted, as well as studies of the impact of fatigue on sick calls and absenteeism. In many tightly staffed hospitals, overtime is used to provide coverage for sick calls, which in turn potentiates further risk of fatigue. As a profession, nurses need to take the fear factor out of saying I'm tired and advocate for adequate breaks, naps, and diet. Nurse leaders often find that offering 12‐hour shifts is required to recruit nurses, and that rotating shiftssometimes in a manner that can lead to significant circadian misalignmenthelps balance the schedule and preference for day shifts. They are also aware that a scheduled 3‐day work week is attractive to many nurses, as it allows those desiring greater income to work additional shifts through an agency at premium pay, though this may lead to further sleep deprivation. It is easy to conceive how these factors can lead to a serious conundrum.
How best to address concerns over nurse staffing remains a subject of ongoing debate. Higher nurse‐to‐patient ratios have been associated in multiple studies and a meta‐analysis with lower rates of complications and mortality.3, 21 Understanding the causal relationship between ratios and outcomes, however, has been complicated by consideration of confounding hospital variables and varying acuity of patient care between centers. The number of patients a nurse can safely care for at any one time is likely a product of the acuity of the patients, the education and experience of the nurse, and the makeup of the team available to care for the patients' needs. How well implementation of mandates regarding nurse‐patient ratios can address this complex need is unclear, and should be a focus of future research.
Leadership is essential in implementing work hour standards and staffing plans to promote a high‐quality nursing environment. Hospitals with poor operating margins, poor leadership, or poor environments of care will be unable to retain nurses to meet care requirements. Magnet hospitals, with nurse leaders who promote RN empowerment, can develop less stressful work environments with lower turnover rates and greater job satisfaction, which positively impacts quality of care. The Magnet Recognition Program, developed by the American Nurses Credentialing Center (ANCC), has recognized less than 300 hospitals in the US as providing nursing excellence (
State and federal regulation may address initial safety needs, but it cannot in isolation address all of the elements that contribute to high‐quality care. While data are limited, it is possible that in financially constrained hospitals, suboptimal implementation of mandates may potentially lead to misuse of limited resources. Future research should directly assess the net effects of implementing nurse scheduling and staffing policies on mortality, hospital complication rates, and the safety of patient care processes across diverse medical centers and patient care settings. Building upon the research of Surani, Conway, and their colleagues, such research could help promote the further development of optimal care policies and the quality of patient care.
- Recovery from medical errors: the critical care nursing safety net.Jt Comm J Qual Patient Saf2006;32(2):63–72. , , , , , , et al.
- Hospital workload and adverse events.Med Care2007;45(5):448–455. , , , , , , et al.
- Nurse staffing and quality of patient care.Evid Rep Technol Assess (Full Rep)2007(151):1–115. , , , , .
- The working hours of hospital staff nurses and patient safety.Health Aff (Millwood)2004;23(4):202–212. , , , , .
- Effects of critical care nurses' work hours on vigilance and patients' safety.Am J Crit Care2006;15(1):30–37. , , , .
- Institute of Medicine.Keeping Patients Safe: Transforming the Work Environment of Nurses.2006. Washington, DC, The National Academies Press.
- How Long and How Much Are Nurses Now Working?Am J Nursing2006;106(4):60–71. , , , , .
- Sleepiness in Critical Care Nurses: Results of a Pilot Study.J Hosp Med20083(3):200–205. , , , , .
- Work schedule characteristics and substance use in nurses.Am J Ind Med1998;34(3):266–271. , .
- Extended work shifts and the risk of motor vehicle crashes among interns.N Engl J Med2005;352(2):125–134. , , , , , , et al.
- Impact of extended‐duration shifts on medical errors, adverse events, and attentional failures.PLoS Med2006;3(12):e487. , , , , , , et al.
- Extended work duration and the risk of self‐reported percutaneous injuries in interns.JAMA2006;296(9):1055–1062. , , , , , , et al.
- Effect of reducing interns' weekly work hours on sleep and attentional failures.N Engl J Med2004;351(18):1829–1837. , , , , , , et al.
- Effect of reducing interns' work hours on serious medical errors in intensive care units.N Engl J Med2004;351(18):1838–1848. , , , , , , et al.
- Shift work, safety and productivity.Occup Med (Lond)2003;53(2):95–101. , .
- Nurse Staffing Ratios: Trends and Policy Implications for Hospitalists and the Safety Net.J Hosp Med20083(3):193–199. , , , .
- American Nurses Association. Nationwide State Legislative Agenda, 2007–2008 Reports. Accessed May 12,2008 at http://www.nursingworld.org/MainMenuCategories/ANAPoliticalPower/State/StateLegislativeAgenda.aspx
- United States Department of Veteran Affairs. Law Gives VA Flexible Pay for Physicians, Schedules for Nurses.2004. Accessed May 12, 2008 at http://www1.va.gov/opa/pressrel/pressrelease.cfm?id=916.
- 2004. Rockville, MD, National Center for Health Workforce Analysis, Health Resources and Services Administration Accessed May 12, 2008 at https://www.ncsbn.org/Projected_Supply_Demand_Shortage_RNs.pdf. , , . What is Behind HRSA's Projected Supply, Demand, and Shortage of Registered Nurses?
- The cumulative cost of additional wakefulness: Dose‐response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation.Sleep2003;26(2):117–126. , , , .
- Hospital nurse staffing and patient mortality, nurse burnout, and job dissatisfaction.JAMA2002;288(16):1987–1993. , , , , .
Over the past decade, an emerging body of literature established a link between nurses' working conditions and their ability to provide safe care. Nurses who are not at their best are both prone to making errors themselves, and less able to serve as effective safety nets for their patients, intercepting errors made by physicians and others.1 Excessive nurse workloads predict an increased rate of adverse events,2, 3 and, by their own reports, nurses working shifts of >12 hours are at greatly increased risk of making medical errors.4, 5 On the basis of these and related findings, the Institute of Medicine has recommended: a) that efforts be made to assure appropriate nurse workloads and b) that nurses work no more than 12 hours per day and 60 hours per week;6 but these recommendations have not been broadly enforced.7
Two articles in the current issue of the Journal of Hospital Medicine add to our understanding of the relationship between nurse working conditions and safety, and substantiate the need to improve nurses' working conditions. In the first, Surani et al. conducted a pilot study of 20 night nurses working 12‐hour shifts in which well‐validated, objective tools revealed that ICU nurses were suffering from pathologic levels of drowsiness on the job.8 The topic is of importance as recent survey work demonstrated that nurses working >12 hours and resident‐physicians working shifts of 24 of more hours make significantly more medical errors and suffer many more occupational injuries than those working less exhausting schedules.4, 5, 912 Objective data on resident‐physicians has corroborated these findings,13, 14 but objective data measuring sleepiness in nurses has been lacking. Surani et al.'s study helps to fill this need. Further, this study suggests that hospitals should not be complacent about the safety of 12‐hour shifts, which may still be associated with dangerous levels of drowsiness‐induced impairment. Careful management of the number of consecutive night shifts,15 or further reductions in nursing work hours even beyond the 12‐hour limit endorsed by the IOM may be in orderparticularly in high‐risk critical care environmentsthough further research substantiating Surani et al.'s findings and comparing alternative scheduling options would be valuable.
The second study by Conway et al. analyzed data for acute care hospitals in California from 1993 to 2004, and found that following the passage of nurse staffing legislation in 1999 and its implementation in 2004, nurse‐patient staffing ratios increased significantly.16 Safety‐net hospitals, however, with high proportions of vulnerable patient populations, were least likely to achieve mandated ratios. As the authors point out, diverting funds to achieve mandated ratios in under‐funded safety net hospitals could potentially lead to reductions in other essential services, though whether such an eventuality might come to pass has not been adequately assessed to date.
In light of these data, where should we go from here? Public and professional concerns over the impact of fewer nurses on the delivery of care have led to the passage of legislation or adoption of regulations by many states in an attempt to ensure safe care. Examples include elimination of mandatory overtime in the following states: CT, IL, ME, MD, MN, NJ, NH, OR, RI, WA, WV, CA, MO, and TX; implementation of nurse staffing plans with input from staff nurses (WA, IL, OR, RI, TX), and mandates of specific nurse to patient ratios (CA [as discussed by Conway et al.] and FL).17 Proposed legislation regarding nurse staffing and nurse‐to‐patient ratios is currently under consideration in many additional states. Legislation broadly restricting nurse work hours has not been passed by the federal government or individual states, but some hospital systems including the Veteran's Administration now have policies prohibiting shifts of greater than 12 hours and work weeks of greater than 60 hours.18
Unfortunately, several major barriers have made the implementation of safer work hours and workloads challenging, and uncertainty about the effectiveness of implementation efforts remains. A major challenge has been the presence of a serious shortage of nurses, which is expected to peak by 2020.19 A lack of nurses will make both staffing and scheduling initiatives difficult. Over the next 10 to 15 years, policies that fund nursing education or otherwise address this shortfall will consequently be essential.
A second challenge in efforts to implement safer work schedules appears to be an absence of knowledge about the hazards of sleep deprivation, compounded by financial pressures that may lead to unsafe schedules. Some nurses oppose restriction of work hours citing that they know when they are tired, their schedule works for their personal life, and they should be allowed to work as much as they want to earn the salary they want/need. Unfortunately, it has been well‐demonstrated that chronically sleep‐deprived individuals routinely under‐estimate their level of impairment, calling into question the ability of nurses and others working extreme hours to accurately judge their abilities to perform safely.20
Clearly, education on the effects of fatigue on performance is needed, as are widespread efforts to implement safe schedules. Further study of work injuries, medical errors, and their relation to fatigue and specific work schedules is warranted, as well as studies of the impact of fatigue on sick calls and absenteeism. In many tightly staffed hospitals, overtime is used to provide coverage for sick calls, which in turn potentiates further risk of fatigue. As a profession, nurses need to take the fear factor out of saying I'm tired and advocate for adequate breaks, naps, and diet. Nurse leaders often find that offering 12‐hour shifts is required to recruit nurses, and that rotating shiftssometimes in a manner that can lead to significant circadian misalignmenthelps balance the schedule and preference for day shifts. They are also aware that a scheduled 3‐day work week is attractive to many nurses, as it allows those desiring greater income to work additional shifts through an agency at premium pay, though this may lead to further sleep deprivation. It is easy to conceive how these factors can lead to a serious conundrum.
How best to address concerns over nurse staffing remains a subject of ongoing debate. Higher nurse‐to‐patient ratios have been associated in multiple studies and a meta‐analysis with lower rates of complications and mortality.3, 21 Understanding the causal relationship between ratios and outcomes, however, has been complicated by consideration of confounding hospital variables and varying acuity of patient care between centers. The number of patients a nurse can safely care for at any one time is likely a product of the acuity of the patients, the education and experience of the nurse, and the makeup of the team available to care for the patients' needs. How well implementation of mandates regarding nurse‐patient ratios can address this complex need is unclear, and should be a focus of future research.
Leadership is essential in implementing work hour standards and staffing plans to promote a high‐quality nursing environment. Hospitals with poor operating margins, poor leadership, or poor environments of care will be unable to retain nurses to meet care requirements. Magnet hospitals, with nurse leaders who promote RN empowerment, can develop less stressful work environments with lower turnover rates and greater job satisfaction, which positively impacts quality of care. The Magnet Recognition Program, developed by the American Nurses Credentialing Center (ANCC), has recognized less than 300 hospitals in the US as providing nursing excellence (
State and federal regulation may address initial safety needs, but it cannot in isolation address all of the elements that contribute to high‐quality care. While data are limited, it is possible that in financially constrained hospitals, suboptimal implementation of mandates may potentially lead to misuse of limited resources. Future research should directly assess the net effects of implementing nurse scheduling and staffing policies on mortality, hospital complication rates, and the safety of patient care processes across diverse medical centers and patient care settings. Building upon the research of Surani, Conway, and their colleagues, such research could help promote the further development of optimal care policies and the quality of patient care.
Over the past decade, an emerging body of literature established a link between nurses' working conditions and their ability to provide safe care. Nurses who are not at their best are both prone to making errors themselves, and less able to serve as effective safety nets for their patients, intercepting errors made by physicians and others.1 Excessive nurse workloads predict an increased rate of adverse events,2, 3 and, by their own reports, nurses working shifts of >12 hours are at greatly increased risk of making medical errors.4, 5 On the basis of these and related findings, the Institute of Medicine has recommended: a) that efforts be made to assure appropriate nurse workloads and b) that nurses work no more than 12 hours per day and 60 hours per week;6 but these recommendations have not been broadly enforced.7
Two articles in the current issue of the Journal of Hospital Medicine add to our understanding of the relationship between nurse working conditions and safety, and substantiate the need to improve nurses' working conditions. In the first, Surani et al. conducted a pilot study of 20 night nurses working 12‐hour shifts in which well‐validated, objective tools revealed that ICU nurses were suffering from pathologic levels of drowsiness on the job.8 The topic is of importance as recent survey work demonstrated that nurses working >12 hours and resident‐physicians working shifts of 24 of more hours make significantly more medical errors and suffer many more occupational injuries than those working less exhausting schedules.4, 5, 912 Objective data on resident‐physicians has corroborated these findings,13, 14 but objective data measuring sleepiness in nurses has been lacking. Surani et al.'s study helps to fill this need. Further, this study suggests that hospitals should not be complacent about the safety of 12‐hour shifts, which may still be associated with dangerous levels of drowsiness‐induced impairment. Careful management of the number of consecutive night shifts,15 or further reductions in nursing work hours even beyond the 12‐hour limit endorsed by the IOM may be in orderparticularly in high‐risk critical care environmentsthough further research substantiating Surani et al.'s findings and comparing alternative scheduling options would be valuable.
The second study by Conway et al. analyzed data for acute care hospitals in California from 1993 to 2004, and found that following the passage of nurse staffing legislation in 1999 and its implementation in 2004, nurse‐patient staffing ratios increased significantly.16 Safety‐net hospitals, however, with high proportions of vulnerable patient populations, were least likely to achieve mandated ratios. As the authors point out, diverting funds to achieve mandated ratios in under‐funded safety net hospitals could potentially lead to reductions in other essential services, though whether such an eventuality might come to pass has not been adequately assessed to date.
In light of these data, where should we go from here? Public and professional concerns over the impact of fewer nurses on the delivery of care have led to the passage of legislation or adoption of regulations by many states in an attempt to ensure safe care. Examples include elimination of mandatory overtime in the following states: CT, IL, ME, MD, MN, NJ, NH, OR, RI, WA, WV, CA, MO, and TX; implementation of nurse staffing plans with input from staff nurses (WA, IL, OR, RI, TX), and mandates of specific nurse to patient ratios (CA [as discussed by Conway et al.] and FL).17 Proposed legislation regarding nurse staffing and nurse‐to‐patient ratios is currently under consideration in many additional states. Legislation broadly restricting nurse work hours has not been passed by the federal government or individual states, but some hospital systems including the Veteran's Administration now have policies prohibiting shifts of greater than 12 hours and work weeks of greater than 60 hours.18
Unfortunately, several major barriers have made the implementation of safer work hours and workloads challenging, and uncertainty about the effectiveness of implementation efforts remains. A major challenge has been the presence of a serious shortage of nurses, which is expected to peak by 2020.19 A lack of nurses will make both staffing and scheduling initiatives difficult. Over the next 10 to 15 years, policies that fund nursing education or otherwise address this shortfall will consequently be essential.
A second challenge in efforts to implement safer work schedules appears to be an absence of knowledge about the hazards of sleep deprivation, compounded by financial pressures that may lead to unsafe schedules. Some nurses oppose restriction of work hours citing that they know when they are tired, their schedule works for their personal life, and they should be allowed to work as much as they want to earn the salary they want/need. Unfortunately, it has been well‐demonstrated that chronically sleep‐deprived individuals routinely under‐estimate their level of impairment, calling into question the ability of nurses and others working extreme hours to accurately judge their abilities to perform safely.20
Clearly, education on the effects of fatigue on performance is needed, as are widespread efforts to implement safe schedules. Further study of work injuries, medical errors, and their relation to fatigue and specific work schedules is warranted, as well as studies of the impact of fatigue on sick calls and absenteeism. In many tightly staffed hospitals, overtime is used to provide coverage for sick calls, which in turn potentiates further risk of fatigue. As a profession, nurses need to take the fear factor out of saying I'm tired and advocate for adequate breaks, naps, and diet. Nurse leaders often find that offering 12‐hour shifts is required to recruit nurses, and that rotating shiftssometimes in a manner that can lead to significant circadian misalignmenthelps balance the schedule and preference for day shifts. They are also aware that a scheduled 3‐day work week is attractive to many nurses, as it allows those desiring greater income to work additional shifts through an agency at premium pay, though this may lead to further sleep deprivation. It is easy to conceive how these factors can lead to a serious conundrum.
How best to address concerns over nurse staffing remains a subject of ongoing debate. Higher nurse‐to‐patient ratios have been associated in multiple studies and a meta‐analysis with lower rates of complications and mortality.3, 21 Understanding the causal relationship between ratios and outcomes, however, has been complicated by consideration of confounding hospital variables and varying acuity of patient care between centers. The number of patients a nurse can safely care for at any one time is likely a product of the acuity of the patients, the education and experience of the nurse, and the makeup of the team available to care for the patients' needs. How well implementation of mandates regarding nurse‐patient ratios can address this complex need is unclear, and should be a focus of future research.
Leadership is essential in implementing work hour standards and staffing plans to promote a high‐quality nursing environment. Hospitals with poor operating margins, poor leadership, or poor environments of care will be unable to retain nurses to meet care requirements. Magnet hospitals, with nurse leaders who promote RN empowerment, can develop less stressful work environments with lower turnover rates and greater job satisfaction, which positively impacts quality of care. The Magnet Recognition Program, developed by the American Nurses Credentialing Center (ANCC), has recognized less than 300 hospitals in the US as providing nursing excellence (
State and federal regulation may address initial safety needs, but it cannot in isolation address all of the elements that contribute to high‐quality care. While data are limited, it is possible that in financially constrained hospitals, suboptimal implementation of mandates may potentially lead to misuse of limited resources. Future research should directly assess the net effects of implementing nurse scheduling and staffing policies on mortality, hospital complication rates, and the safety of patient care processes across diverse medical centers and patient care settings. Building upon the research of Surani, Conway, and their colleagues, such research could help promote the further development of optimal care policies and the quality of patient care.
- Recovery from medical errors: the critical care nursing safety net.Jt Comm J Qual Patient Saf2006;32(2):63–72. , , , , , , et al.
- Hospital workload and adverse events.Med Care2007;45(5):448–455. , , , , , , et al.
- Nurse staffing and quality of patient care.Evid Rep Technol Assess (Full Rep)2007(151):1–115. , , , , .
- The working hours of hospital staff nurses and patient safety.Health Aff (Millwood)2004;23(4):202–212. , , , , .
- Effects of critical care nurses' work hours on vigilance and patients' safety.Am J Crit Care2006;15(1):30–37. , , , .
- Institute of Medicine.Keeping Patients Safe: Transforming the Work Environment of Nurses.2006. Washington, DC, The National Academies Press.
- How Long and How Much Are Nurses Now Working?Am J Nursing2006;106(4):60–71. , , , , .
- Sleepiness in Critical Care Nurses: Results of a Pilot Study.J Hosp Med20083(3):200–205. , , , , .
- Work schedule characteristics and substance use in nurses.Am J Ind Med1998;34(3):266–271. , .
- Extended work shifts and the risk of motor vehicle crashes among interns.N Engl J Med2005;352(2):125–134. , , , , , , et al.
- Impact of extended‐duration shifts on medical errors, adverse events, and attentional failures.PLoS Med2006;3(12):e487. , , , , , , et al.
- Extended work duration and the risk of self‐reported percutaneous injuries in interns.JAMA2006;296(9):1055–1062. , , , , , , et al.
- Effect of reducing interns' weekly work hours on sleep and attentional failures.N Engl J Med2004;351(18):1829–1837. , , , , , , et al.
- Effect of reducing interns' work hours on serious medical errors in intensive care units.N Engl J Med2004;351(18):1838–1848. , , , , , , et al.
- Shift work, safety and productivity.Occup Med (Lond)2003;53(2):95–101. , .
- Nurse Staffing Ratios: Trends and Policy Implications for Hospitalists and the Safety Net.J Hosp Med20083(3):193–199. , , , .
- American Nurses Association. Nationwide State Legislative Agenda, 2007–2008 Reports. Accessed May 12,2008 at http://www.nursingworld.org/MainMenuCategories/ANAPoliticalPower/State/StateLegislativeAgenda.aspx
- United States Department of Veteran Affairs. Law Gives VA Flexible Pay for Physicians, Schedules for Nurses.2004. Accessed May 12, 2008 at http://www1.va.gov/opa/pressrel/pressrelease.cfm?id=916.
- 2004. Rockville, MD, National Center for Health Workforce Analysis, Health Resources and Services Administration Accessed May 12, 2008 at https://www.ncsbn.org/Projected_Supply_Demand_Shortage_RNs.pdf. , , . What is Behind HRSA's Projected Supply, Demand, and Shortage of Registered Nurses?
- The cumulative cost of additional wakefulness: Dose‐response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation.Sleep2003;26(2):117–126. , , , .
- Hospital nurse staffing and patient mortality, nurse burnout, and job dissatisfaction.JAMA2002;288(16):1987–1993. , , , , .
- Recovery from medical errors: the critical care nursing safety net.Jt Comm J Qual Patient Saf2006;32(2):63–72. , , , , , , et al.
- Hospital workload and adverse events.Med Care2007;45(5):448–455. , , , , , , et al.
- Nurse staffing and quality of patient care.Evid Rep Technol Assess (Full Rep)2007(151):1–115. , , , , .
- The working hours of hospital staff nurses and patient safety.Health Aff (Millwood)2004;23(4):202–212. , , , , .
- Effects of critical care nurses' work hours on vigilance and patients' safety.Am J Crit Care2006;15(1):30–37. , , , .
- Institute of Medicine.Keeping Patients Safe: Transforming the Work Environment of Nurses.2006. Washington, DC, The National Academies Press.
- How Long and How Much Are Nurses Now Working?Am J Nursing2006;106(4):60–71. , , , , .
- Sleepiness in Critical Care Nurses: Results of a Pilot Study.J Hosp Med20083(3):200–205. , , , , .
- Work schedule characteristics and substance use in nurses.Am J Ind Med1998;34(3):266–271. , .
- Extended work shifts and the risk of motor vehicle crashes among interns.N Engl J Med2005;352(2):125–134. , , , , , , et al.
- Impact of extended‐duration shifts on medical errors, adverse events, and attentional failures.PLoS Med2006;3(12):e487. , , , , , , et al.
- Extended work duration and the risk of self‐reported percutaneous injuries in interns.JAMA2006;296(9):1055–1062. , , , , , , et al.
- Effect of reducing interns' weekly work hours on sleep and attentional failures.N Engl J Med2004;351(18):1829–1837. , , , , , , et al.
- Effect of reducing interns' work hours on serious medical errors in intensive care units.N Engl J Med2004;351(18):1838–1848. , , , , , , et al.
- Shift work, safety and productivity.Occup Med (Lond)2003;53(2):95–101. , .
- Nurse Staffing Ratios: Trends and Policy Implications for Hospitalists and the Safety Net.J Hosp Med20083(3):193–199. , , , .
- American Nurses Association. Nationwide State Legislative Agenda, 2007–2008 Reports. Accessed May 12,2008 at http://www.nursingworld.org/MainMenuCategories/ANAPoliticalPower/State/StateLegislativeAgenda.aspx
- United States Department of Veteran Affairs. Law Gives VA Flexible Pay for Physicians, Schedules for Nurses.2004. Accessed May 12, 2008 at http://www1.va.gov/opa/pressrel/pressrelease.cfm?id=916.
- 2004. Rockville, MD, National Center for Health Workforce Analysis, Health Resources and Services Administration Accessed May 12, 2008 at https://www.ncsbn.org/Projected_Supply_Demand_Shortage_RNs.pdf. , , . What is Behind HRSA's Projected Supply, Demand, and Shortage of Registered Nurses?
- The cumulative cost of additional wakefulness: Dose‐response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation.Sleep2003;26(2):117–126. , , , .
- Hospital nurse staffing and patient mortality, nurse burnout, and job dissatisfaction.JAMA2002;288(16):1987–1993. , , , , .
How safe are erythropoiesis-stimulating agents?
The year 2007 was a rough one for erythropoiesis-stimulating agents (ESAs). Increasing concerns about their safety were raised in important meta-analyses of previously published data, specifically, the possibility that these agents increase the risk of venous thromboembolic phenomenona and shorten survival. These trends were seen primarily in studies of cancer patients.1 Meanwhile, front-page headlines in The New York Times were unkind: “Doctors reaping millions for use of anemia drugs.”2 However, the signals came earlier than 2007.
THE RISE AND POSSIBLE FALL OF ESAs
1989—These costly drugs are introduced and start their ascent to becoming one of the most widely used drug classes, helped along by direct-to-consumer advertising. (In one ad, Grandpa can run after the grandchildren despite being on chemotherapy because he uses erythropoietin!)
2001—A study declares that the higher the hemoglobin level rises in response to ESAs, the better the quality of life. It also hints that these agents improve survival.3
2002—The American Society of Hematology/American Society of Clinical Oncology Practice Guideline Writing Committee reviews the medical literature, performs a systematic review, and recommends that patients with low-risk myelodysplasia and those on chemotherapy who become anemic (with a hemoglobin level approaching 10 g/dL) have the option of receiving ESAs to raise their hemoglobin and decrease the need for transfusion.4
2003—Henke et al5 report that anemic patients with head and neck cancer who underwent radiotherapy and received erythropoietin in a randomized study had poorer survival and progression-free survival.
2005—Leyland-Jones et al,6 in another randomized study, report that patients with metastatic breast cancer receiving first-line chemotherapy (most of whom were not anemic) had a higher mortality rate if they received epoetin alfa.
2006—The guideline authors meet again to start the process of writing an update. A meta-analysis shows the thromboembolic risk and survival problems in a more systematic way, covering multiple studies.7
2007—The Centers for Medicare and Medicaid Services cuts back the reimbursement for the use of erythropoietin. The US Food and Drug Administration (FDA) publishes a black box warning suggesting that any hemoglobin level greater than 12 g/dL would be detrimental to a patient. The Guideline Writing Committee works on its document with this backdrop of turmoil.
2008—The updated guidelines are published. They recommend continuing to use ESAs for patients with low-risk myelodysplasia, and as an option to raise hemoglobin levels and prevent the need for transfusion in cancer patients undergoing chemotherapy whose hemoglobin level falls to 10 g/dL or less.8 The document includes stronger language against the use of ESAs in patients with anemia from cancer who are not undergoing chemotherapy. Meanwhile, some editorialists have suggested that it may be time to abandon ESAs because these drugs may promote more rapid tumor growth or pose a prohibitive risk of thromboembolic disease.9,10
In mid-March 2008, after reviewing the most recent data, an FDA panel calls for new limits on the use of ESAs: cancer patients who are undergoing treatment that could cure their cancer should not receive them, and neither should patients with advanced breast cancer or head and neck cancer. Furthermore, the FDA panel stipulates that when doctors do prescribe these drugs, they should warn patients of the possible dangers and seek their informed consent.
WHAT HAPPENS NOW?
Will the FDA take ESAs off the market? That is unlikely. Nephrologists need these drugs to avoid the need for transfusion in dialysis patients (see the accompanying article by Drs. Demirjian and Nurko on the use of ESAs in patients with chronic kidney disease on page 353 of this issue of the Journal). Some of the very first signals of harm with raising the hemoglobin too high came from the nephrology field.
Hematologists should still have the option of using ESAs in some settings, particularly in patients with low-risk myelodysplasia who are becoming more and more anemic and in those who have comorbid conditions in which lower hemoglobin levels are unsafe, particularly if they have coronary artery disease. They also should still be able to use ESAs for selected patients who develop severe chemotherapy-induced anemia and who become so weakened from their anemic state that their life and quality of life are threatened. If ESAs are taken away from the formulary of hematologists and oncologists, these specialists will rely on transfusions to treat their anemic patients, whether the anemia be due to myelodysplasia or to chemotherapy. Some say that the blood supply is so safe that we should not have the same worries about using blood transfusions as we did in the late 1980s. However, we all have seen patients who adamantly do not want transfusions.
Certainly, more events will transpire in the next year with the ESAs. There will probably be more data on erythropoietin receptors on the surface of tumor cells and what happens when pharmacologic doses of erythropoietin interact with these receptors. Patient-specific meta-analyses will probably shed more light on individual patients’ risk of thromboembolic disease and early death from the use of these agents.
The ESA story is far from over.
- Bohlius J, Wilson J, Seidenfeld J, et al. Erythropoietin or darbopoietin for patients with cancer. Cochrane Database Syst Rev 2007; 2:CD 003407.
- Berenson A, Pollack A. Doctors reaping millions for use of anemia drugs. New York Times, May 9, 2007, page1A.
- Littlewood TJ, Bajette E, Nortier JW, et al. Effects of epoetin alfa on hematologic parameters & quality of life in cancer patients receiving nonplatinum chemotherapy: results of a randomized, double-blind, placebo-controlled trial. J Clin Oncol 2001; 19:2865–2874.
- Rizzo JD, Lichtin AE, Woolf SH, et al. Use of epoetin in patients with cancer: evidence based clinical practice guidelines of the American Society of Clinical Oncology and the American Society of Hematology. J Clin Oncol 2002; 20:4083–4107.
- Henke M, Laszig R, Rube C, et al. Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double–blind, placebo-controlled trial. Lancet 2003; 362:1255–1260.
- Leyland-Jones B, Semiglazov V, Pawlicki M, et al. Maintaining normal hemoglobin levels with epoetin alfa in mainly nonanemic patients with metastatic breast cancer receiving first-line chemotherapy: a survival study. J Clin Oncol 2005; 23:5960–5972.
- Bohlius J, Wilson J, Seidenfeld J, et al. Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. J Natl Cancer Inst 2006; 98:708–714.
- Rizzo JD, Somerfield MR, Hagerty K, et al. Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update. Blood 2008; 111:25–41.
- Tefferi A. Pharmaceutical erythropoietin use in patients with cancer: is it time to abandon ship or just drop anchor? [editorial] Mayo Clin Proc 2007; 82:1316–1318.
- Anonymous. Erythropoietin analogues: an unnecessary class of drugs [editorial]. Lancet Oncol 2008; 9:81.
The year 2007 was a rough one for erythropoiesis-stimulating agents (ESAs). Increasing concerns about their safety were raised in important meta-analyses of previously published data, specifically, the possibility that these agents increase the risk of venous thromboembolic phenomenona and shorten survival. These trends were seen primarily in studies of cancer patients.1 Meanwhile, front-page headlines in The New York Times were unkind: “Doctors reaping millions for use of anemia drugs.”2 However, the signals came earlier than 2007.
THE RISE AND POSSIBLE FALL OF ESAs
1989—These costly drugs are introduced and start their ascent to becoming one of the most widely used drug classes, helped along by direct-to-consumer advertising. (In one ad, Grandpa can run after the grandchildren despite being on chemotherapy because he uses erythropoietin!)
2001—A study declares that the higher the hemoglobin level rises in response to ESAs, the better the quality of life. It also hints that these agents improve survival.3
2002—The American Society of Hematology/American Society of Clinical Oncology Practice Guideline Writing Committee reviews the medical literature, performs a systematic review, and recommends that patients with low-risk myelodysplasia and those on chemotherapy who become anemic (with a hemoglobin level approaching 10 g/dL) have the option of receiving ESAs to raise their hemoglobin and decrease the need for transfusion.4
2003—Henke et al5 report that anemic patients with head and neck cancer who underwent radiotherapy and received erythropoietin in a randomized study had poorer survival and progression-free survival.
2005—Leyland-Jones et al,6 in another randomized study, report that patients with metastatic breast cancer receiving first-line chemotherapy (most of whom were not anemic) had a higher mortality rate if they received epoetin alfa.
2006—The guideline authors meet again to start the process of writing an update. A meta-analysis shows the thromboembolic risk and survival problems in a more systematic way, covering multiple studies.7
2007—The Centers for Medicare and Medicaid Services cuts back the reimbursement for the use of erythropoietin. The US Food and Drug Administration (FDA) publishes a black box warning suggesting that any hemoglobin level greater than 12 g/dL would be detrimental to a patient. The Guideline Writing Committee works on its document with this backdrop of turmoil.
2008—The updated guidelines are published. They recommend continuing to use ESAs for patients with low-risk myelodysplasia, and as an option to raise hemoglobin levels and prevent the need for transfusion in cancer patients undergoing chemotherapy whose hemoglobin level falls to 10 g/dL or less.8 The document includes stronger language against the use of ESAs in patients with anemia from cancer who are not undergoing chemotherapy. Meanwhile, some editorialists have suggested that it may be time to abandon ESAs because these drugs may promote more rapid tumor growth or pose a prohibitive risk of thromboembolic disease.9,10
In mid-March 2008, after reviewing the most recent data, an FDA panel calls for new limits on the use of ESAs: cancer patients who are undergoing treatment that could cure their cancer should not receive them, and neither should patients with advanced breast cancer or head and neck cancer. Furthermore, the FDA panel stipulates that when doctors do prescribe these drugs, they should warn patients of the possible dangers and seek their informed consent.
WHAT HAPPENS NOW?
Will the FDA take ESAs off the market? That is unlikely. Nephrologists need these drugs to avoid the need for transfusion in dialysis patients (see the accompanying article by Drs. Demirjian and Nurko on the use of ESAs in patients with chronic kidney disease on page 353 of this issue of the Journal). Some of the very first signals of harm with raising the hemoglobin too high came from the nephrology field.
Hematologists should still have the option of using ESAs in some settings, particularly in patients with low-risk myelodysplasia who are becoming more and more anemic and in those who have comorbid conditions in which lower hemoglobin levels are unsafe, particularly if they have coronary artery disease. They also should still be able to use ESAs for selected patients who develop severe chemotherapy-induced anemia and who become so weakened from their anemic state that their life and quality of life are threatened. If ESAs are taken away from the formulary of hematologists and oncologists, these specialists will rely on transfusions to treat their anemic patients, whether the anemia be due to myelodysplasia or to chemotherapy. Some say that the blood supply is so safe that we should not have the same worries about using blood transfusions as we did in the late 1980s. However, we all have seen patients who adamantly do not want transfusions.
Certainly, more events will transpire in the next year with the ESAs. There will probably be more data on erythropoietin receptors on the surface of tumor cells and what happens when pharmacologic doses of erythropoietin interact with these receptors. Patient-specific meta-analyses will probably shed more light on individual patients’ risk of thromboembolic disease and early death from the use of these agents.
The ESA story is far from over.
The year 2007 was a rough one for erythropoiesis-stimulating agents (ESAs). Increasing concerns about their safety were raised in important meta-analyses of previously published data, specifically, the possibility that these agents increase the risk of venous thromboembolic phenomenona and shorten survival. These trends were seen primarily in studies of cancer patients.1 Meanwhile, front-page headlines in The New York Times were unkind: “Doctors reaping millions for use of anemia drugs.”2 However, the signals came earlier than 2007.
THE RISE AND POSSIBLE FALL OF ESAs
1989—These costly drugs are introduced and start their ascent to becoming one of the most widely used drug classes, helped along by direct-to-consumer advertising. (In one ad, Grandpa can run after the grandchildren despite being on chemotherapy because he uses erythropoietin!)
2001—A study declares that the higher the hemoglobin level rises in response to ESAs, the better the quality of life. It also hints that these agents improve survival.3
2002—The American Society of Hematology/American Society of Clinical Oncology Practice Guideline Writing Committee reviews the medical literature, performs a systematic review, and recommends that patients with low-risk myelodysplasia and those on chemotherapy who become anemic (with a hemoglobin level approaching 10 g/dL) have the option of receiving ESAs to raise their hemoglobin and decrease the need for transfusion.4
2003—Henke et al5 report that anemic patients with head and neck cancer who underwent radiotherapy and received erythropoietin in a randomized study had poorer survival and progression-free survival.
2005—Leyland-Jones et al,6 in another randomized study, report that patients with metastatic breast cancer receiving first-line chemotherapy (most of whom were not anemic) had a higher mortality rate if they received epoetin alfa.
2006—The guideline authors meet again to start the process of writing an update. A meta-analysis shows the thromboembolic risk and survival problems in a more systematic way, covering multiple studies.7
2007—The Centers for Medicare and Medicaid Services cuts back the reimbursement for the use of erythropoietin. The US Food and Drug Administration (FDA) publishes a black box warning suggesting that any hemoglobin level greater than 12 g/dL would be detrimental to a patient. The Guideline Writing Committee works on its document with this backdrop of turmoil.
2008—The updated guidelines are published. They recommend continuing to use ESAs for patients with low-risk myelodysplasia, and as an option to raise hemoglobin levels and prevent the need for transfusion in cancer patients undergoing chemotherapy whose hemoglobin level falls to 10 g/dL or less.8 The document includes stronger language against the use of ESAs in patients with anemia from cancer who are not undergoing chemotherapy. Meanwhile, some editorialists have suggested that it may be time to abandon ESAs because these drugs may promote more rapid tumor growth or pose a prohibitive risk of thromboembolic disease.9,10
In mid-March 2008, after reviewing the most recent data, an FDA panel calls for new limits on the use of ESAs: cancer patients who are undergoing treatment that could cure their cancer should not receive them, and neither should patients with advanced breast cancer or head and neck cancer. Furthermore, the FDA panel stipulates that when doctors do prescribe these drugs, they should warn patients of the possible dangers and seek their informed consent.
WHAT HAPPENS NOW?
Will the FDA take ESAs off the market? That is unlikely. Nephrologists need these drugs to avoid the need for transfusion in dialysis patients (see the accompanying article by Drs. Demirjian and Nurko on the use of ESAs in patients with chronic kidney disease on page 353 of this issue of the Journal). Some of the very first signals of harm with raising the hemoglobin too high came from the nephrology field.
Hematologists should still have the option of using ESAs in some settings, particularly in patients with low-risk myelodysplasia who are becoming more and more anemic and in those who have comorbid conditions in which lower hemoglobin levels are unsafe, particularly if they have coronary artery disease. They also should still be able to use ESAs for selected patients who develop severe chemotherapy-induced anemia and who become so weakened from their anemic state that their life and quality of life are threatened. If ESAs are taken away from the formulary of hematologists and oncologists, these specialists will rely on transfusions to treat their anemic patients, whether the anemia be due to myelodysplasia or to chemotherapy. Some say that the blood supply is so safe that we should not have the same worries about using blood transfusions as we did in the late 1980s. However, we all have seen patients who adamantly do not want transfusions.
Certainly, more events will transpire in the next year with the ESAs. There will probably be more data on erythropoietin receptors on the surface of tumor cells and what happens when pharmacologic doses of erythropoietin interact with these receptors. Patient-specific meta-analyses will probably shed more light on individual patients’ risk of thromboembolic disease and early death from the use of these agents.
The ESA story is far from over.
- Bohlius J, Wilson J, Seidenfeld J, et al. Erythropoietin or darbopoietin for patients with cancer. Cochrane Database Syst Rev 2007; 2:CD 003407.
- Berenson A, Pollack A. Doctors reaping millions for use of anemia drugs. New York Times, May 9, 2007, page1A.
- Littlewood TJ, Bajette E, Nortier JW, et al. Effects of epoetin alfa on hematologic parameters & quality of life in cancer patients receiving nonplatinum chemotherapy: results of a randomized, double-blind, placebo-controlled trial. J Clin Oncol 2001; 19:2865–2874.
- Rizzo JD, Lichtin AE, Woolf SH, et al. Use of epoetin in patients with cancer: evidence based clinical practice guidelines of the American Society of Clinical Oncology and the American Society of Hematology. J Clin Oncol 2002; 20:4083–4107.
- Henke M, Laszig R, Rube C, et al. Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double–blind, placebo-controlled trial. Lancet 2003; 362:1255–1260.
- Leyland-Jones B, Semiglazov V, Pawlicki M, et al. Maintaining normal hemoglobin levels with epoetin alfa in mainly nonanemic patients with metastatic breast cancer receiving first-line chemotherapy: a survival study. J Clin Oncol 2005; 23:5960–5972.
- Bohlius J, Wilson J, Seidenfeld J, et al. Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. J Natl Cancer Inst 2006; 98:708–714.
- Rizzo JD, Somerfield MR, Hagerty K, et al. Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update. Blood 2008; 111:25–41.
- Tefferi A. Pharmaceutical erythropoietin use in patients with cancer: is it time to abandon ship or just drop anchor? [editorial] Mayo Clin Proc 2007; 82:1316–1318.
- Anonymous. Erythropoietin analogues: an unnecessary class of drugs [editorial]. Lancet Oncol 2008; 9:81.
- Bohlius J, Wilson J, Seidenfeld J, et al. Erythropoietin or darbopoietin for patients with cancer. Cochrane Database Syst Rev 2007; 2:CD 003407.
- Berenson A, Pollack A. Doctors reaping millions for use of anemia drugs. New York Times, May 9, 2007, page1A.
- Littlewood TJ, Bajette E, Nortier JW, et al. Effects of epoetin alfa on hematologic parameters & quality of life in cancer patients receiving nonplatinum chemotherapy: results of a randomized, double-blind, placebo-controlled trial. J Clin Oncol 2001; 19:2865–2874.
- Rizzo JD, Lichtin AE, Woolf SH, et al. Use of epoetin in patients with cancer: evidence based clinical practice guidelines of the American Society of Clinical Oncology and the American Society of Hematology. J Clin Oncol 2002; 20:4083–4107.
- Henke M, Laszig R, Rube C, et al. Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double–blind, placebo-controlled trial. Lancet 2003; 362:1255–1260.
- Leyland-Jones B, Semiglazov V, Pawlicki M, et al. Maintaining normal hemoglobin levels with epoetin alfa in mainly nonanemic patients with metastatic breast cancer receiving first-line chemotherapy: a survival study. J Clin Oncol 2005; 23:5960–5972.
- Bohlius J, Wilson J, Seidenfeld J, et al. Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. J Natl Cancer Inst 2006; 98:708–714.
- Rizzo JD, Somerfield MR, Hagerty K, et al. Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update. Blood 2008; 111:25–41.
- Tefferi A. Pharmaceutical erythropoietin use in patients with cancer: is it time to abandon ship or just drop anchor? [editorial] Mayo Clin Proc 2007; 82:1316–1318.
- Anonymous. Erythropoietin analogues: an unnecessary class of drugs [editorial]. Lancet Oncol 2008; 9:81.
ASHP–SHM Statement on Hospitalist–Pharmacist Collaboration
POSITION
The American Society of Health‐System Pharmacists (ASHP) and the Society of Hospital Medicine (SHM) believe that the rapidly emerging hospitalist model of inpatient care offers new and significant opportunities to optimize patient care through collaboration among hospitalists, hospital pharmacists (hereinafter, pharmacists), and other health care providers. The emerging model of care allows for deeper professional relationships among health care providers and promotes a shared interest in and responsibility for direct patient care, indirect patient care, and service activities. ASHP and SHM encourage hospitalists, pharmacists, and health care executives to seek out ways to foster collaboration between hospitalists and pharmacists.
The purpose of this consensus statement is to promote an understanding of the ways hospitalists and pharmacists can jointly optimize the care provided to patients in hospitals, examine opportunities for improving hospitalistpharmacist alliances that enhance patient care, suggest future directions for collaboration, and identify aspects of such collaboration that warrant further research.
BACKGROUND
Increases in health care spending and the expanding influence of managed care in the late 1980s and early 1990s resulted in calls for more efficient health care. The movement toward greater efficiency resulted in more emphasis on ambulatory care, fewer hospital admissions, shortened hospital stays, and an overall increase in the acuity of illness of hospitalized patients. The emphasis on ambulatory care increased the number and complexity of physician office visits, and the changing characteristics of office‐ and hospital‐based care placed significant demands on primary care physicians and contributed to the rise of hospital medicine.
In 1996, the term hospitalist was introduced into the health care lexicon.1 A hospitalist was defined as an inpatient physician who manages the care of hospitalized patients and facilitates the transfer of their care back to the primary care physician. The Society of Hospital Medicine has since defined a hospitalist as a physician whose primary professional focus is the general medical care of hospitalized patients and whose activities may include patient care, teaching, research, and leadership related to hospital medicine.2
The past decade has seen rapid growth of the number of hospitalists and the use of hospitalists by US hospitals.3 In 2005, 70% of hospitals with more than 200 beds used hospitalist services, and there were more than 16,000 hospitalists in practice.4 An estimated 20,000 hospitalists were practicing at more than 2600 US hospitals in 2007.5
Initially, many physicians expressed concern about the potential for hospitalists to interfere in the relationship between the patient and the primary care physician, as well as about the potential negative impact on continuity of care.6 However, subsequent studies demonstrated increasing acceptance of hospitalists by primary care physicians, with as many as 89% considering the hospitalist model to be superior to the historical model of hospital care provided by primary care physicians or by specialists working on rotations.7, 8 Numerous studies demonstrate the value of hospitalists in improving quality of care, decreasing hospital costs and length of stay, and reducing hospital readmissions.921
As early as 1921, hospital pharmacists in the American Pharmaceutical Association (now the American Pharmacists Association) had formed a committee to address their distinct concerns. During the 1930s, hospital pharmacists began to organize state organizations and to adhere to a set of minimum standards of practice. In 1942, the American Society of Hospital Pharmacists (now the American Society of Health‐System Pharmacists) was formed to establish minimum standards of pharmaceutical services in hospitals, provide interchange among pharmacists, promote new pharmaceutical techniques, and aid the medical profession in extending the economic and rational use of medications.22 As of 2005, there were approximately 50,000 pharmacists practicing in US hospitals.23
The modern mission of hospital pharmacy departments is to ensure optimal outcomes from the use of medicines.24 Although the focus of hospital pharmacy has traditionally been on the safe dispensing of medications, direct patient care by pharmacists (clinical pharmacy) has always been a component of hospital pharmacy practice. Following the rise of pharmaceutical care in the 1980s,25 these pharmacist services have expanded greatly. It has been estimated that 35%‐40% of hospital pharmacists are devoted to providing clinical services.23 A systematic review in 2006 documented improved outcomes when clinical pharmacists interacted with the health care team on patient rounds, interviewed patients, reconciled medications, and provided discharge counseling and follow‐up.26 These findings support those of other studies in which specific clinical pharmacy services were associated with improved therapeutic and economic outcomes.2731
OPPORTUNITIES FOR COLLABORATION BETWEEN PHARMACISTS AND HOSPITALISTS
Pharmacists and hospitalists have shared interests that provide strong incentives for collaboration. All health care professionals share, first, a commitment to and responsibility for providing safe and effective patient care. Physicians, pharmacists, and other health care providers have long collaborated in providing direct patient care. The emerging hospitalist model of care offers more opportunities for collaboration because pharmacists and hospitalists also share interest in and responsibility for indirect patient care and service activitiesdeveloping the institutional policies, processes, and infrastructure that support patient care.
Direct patient care activities typically performed by hospitalists include obtaining patient histories, conducting physical examinations, making diagnoses, developing treatment plans, monitoring patients' responses to therapy, performing follow‐up hospital visits, participating in family meetings, and providing discharge instructions.32 Specific clinical pharmacy services that have been associated with improved health care outcomes include providing drug information, managing medication protocols and adverse drug reactions, participating in medical rounds, gathering admission medication histories, interviewing patients, reconciling patient medications, and providing discharge counseling and follow‐up.2631
Pharmacists should be involved in the care of hospitalized patients and can collaborate with hospitalists in numerous ways, including:
-
Providing consultative services that foster appropriate, evidence‐based medication selection (eg, during rounds),
-
Providing drug information to physicians, nurses, and other clinicians,
-
Managing medication protocols under collaborative practice agreements,
-
Assisting in the development of treatment protocols,
-
Monitoring therapeutic responses (including laboratory test results),
-
Continuously assessing for and managing adverse drug reactions,
-
Gathering medication histories,
-
Reconciling medications as patients move across the continuum of hospital care, and
-
Providing patient and caretaker education, including discharge counseling and follow‐up.
Both hospitalists and pharmacists have a responsibility to ensure continuity as patients move across settings of care.
In addition to their direct patient care activities, hospitalists add value through their efforts in hospital service activities, student and resident education, and research. Typical service activities include participating in quality‐improvement and safety initiatives, developing institutional guidelines and protocols for the treatment of specific diseases, serving on hospital committees (eg, the pharmacy and therapeutics [P&T] committee), and working with others to introduce new technologies to the hospital setting.33, 34
Pharmacists also participate in hospital service activities, education, and research. For example, pharmacists serve on the P&T committee and are directly involved in managing the formulary system that guides an institution's medication use. As medication experts, pharmacists contribute to the development and implementation of patient care guidelines and other medication‐use policies. Pharmacist expertise is also integral to many quality‐improvement efforts (eg, surgical infection prophylaxis) and to technology initiatives (eg, bedside medication scanning and computerized prescriber‐order‐entry systems). Pharmacist provision of in‐service education on medications and medication use is invaluable for all health care providers.
These overlapping responsibilities provide hospitalists and pharmacists with opportunities to collaborate on activities that can have a profound effect on care in the hospital. Hospitalists and pharmacists can work together to ensure that care is evidence based, cost‐effective, and adherent to national guidelines; establish an institutional culture of safety; develop and implement quality‐improvement initiatives; meet accreditation standards; and, in many cases, foster the institution's education and research initiatives. Health professional education and research offers the opportunity to improve patient care provided not just by a single hospital but by other facilities as well.
OPPORTUNITIES TO IMPROVE COLLABORATION
ASHP and SHM believe that there are opportunities for improving collaboration between hospitalists and pharmacists. Barriers to collaboration include real and perceived professional boundaries, poor integration of technology systems, inadequate pharmacist and hospitalist staffing, time constraints, inadequate funding and resources, lack of third‐party compensation for clinical pharmacy services, and the competing obligations weighing on both professions.
Real and perceived professional boundaries can be addressed by clear communication and by enhanced interdisciplinary educational opportunities for all members of the health care team.3538 ASHP and SHM believe that while hospitalists should serve as the primary leaders of hospital care teams, all health care professionals should be willing to assume a leadership role in treating patients and, when appropriate, accept leadership by other team members. Like all members of the care team, pharmacists require timely access to hospitalists for consultation, as well as access to patient information. The vital flow of information and communication among health care providers should be conducive to collaborating and improving patient outcomes. ASHP and SHM believe that properly applied, well‐integrated technologies (eg, electronic medical records and personal digital assistants with clinical decision support systems, including drug information) can enhance communication among all members of the health care team.
Hospitalists and pharmacists can work together to overcome limitations created by inadequate funding and staffing by providing evidence to health care executives of the value of clinical pharmacist positions and pharmacisthospitalist collaboration. This evidence should examine the impact of these positions and such collaboration on therapeutic, safety, humanistic, and economic outcomes. Collaboration among all members of the health care team would also be encouraged by reforming the current fee‐for‐service reimbursement practices to base payment for care delivery on overall treatment goals (eg, a payment rate based on diagnosis).
CONCLUSIONS
An interdisciplinary approach to health care that includes physicians, pharmacists, nurses, and other health care professionals will improve the quality of patient care. Hospitalists and pharmacists need to collaborate with each other and with other health care professionals to optimize outcomes in hospitalized patients. ASHP and SHM believe that hospitalistpharmacist alliances should be encouraged and that the systems and technologies that enable collaboration and the incentives for such collaboration should be enhanced.
Acknowledgements
The following individuals and organizations are acknowledged for reviewing draft versions of this statement: Nicole M. Allcock, PharmD, BCPS; American Academy of Physician Assistants (AAPA); American Nurses Association (ANA); American Society of Consultant Pharmacists (ASCP); Philip Anderson, PharmD, FASHP; Linda C. Annecchini, MS, FASHP; John A. Armitstead, MS, FASHP; Carol Bickford, PhD. (ANA); Michael L. Brandt, BS, PharmD; John Bridges, PharmD; Tim R. Brown, PharmD; Gail M. Burniske, PharmD, BCPS; Margaret Chrymko, PharmD, FASHP; Steve Crane (AAPA); Karren Crowson, MBA; Lourdes M. Cuellar, MS, FASHP; Michele Danish, PharmD; Neil Davis; Jean Douglas, PharmD; Jillian James Foster, PharmD; Georgia W. Fox, PharmD; Nicole Gara (AAPA); Kathleen M. Gura, PharmD, BCNSP, FASHP; Stuart T. Haines, PharmD, FCCP, FASHP; Tom Hall, PharmD; John Hertig; Philip E. Johnson, MS, FASHP; Thomas J. Johnson, PharmD, BCPS; Michael Kelly, PharmD; Patricia Kienle, MPA, FASHP; Kathrin C. Kucharski, PharmD, BCPS; Sharon Kulesz (AAPA); Timothy R. Lanese, MBA, FASHP, FACHE; Bob McNellis, MPH, PA (AAPA); Joe Miller, MD (SHM); Rima Mohammad, PharmD, BCPS; Lynette R. Moser, PharmD; Joe E. Ness, MHA; Scott Oxenhandler, MD; Charles D. Ponte, PharmD, BC‐ADM, BCPS, CDE, FAPhA, FASHP, FCCP; James A. Ponto, MS, BCNP, FASHP; Michael D. Sanborn, MS; Phil Saucedo, MBA; Kenneth H. Schell, PharmD, FASHP, FCSHP; Edward C. Seidl, PharmD; Michele F. Shepherd, PharmD, MS, BCPS, FASHP; Jonalan Smith, PharmD (ASCP); Kelly M. Smith, PharmD; Miriam A. Mobley Smith, PharmD; Edward Stemley, MS, PharmD; Joe Strain, PharmD; James A. Trovato, PharmD, MBA, BCOP; Jennifer Tryon, PharmD, MS; Laura Wachter, BS, PharmD; William E. Wade, PharmD, FASHP, FCCP; Paul C. Walker, PharmD; Larry Wellikson, MD (SHM); Karl G. Williams, JD, MS; and John L. Woon, PharmD, FASHP.
- The emerging role of “hospitalists” in the American health care system.N Engl J Med.1996;335:514–517. , .
- Society of Hospital Medicine. Definition of a hospitalist. Available at: www.hospitalmedicine.org/Content/NavigationMenu/AboutSHM/DefinitionofaHospitalist/Definition_of_a_Hosp.htm. Accessed May 29,2007.
- The status of hospital medicine groups in the United States.J Hosp Med.2006;1:75–80. , , , et al.
- AHA Hospital Statistics.Chicago:American Hospital Association;2005.
- Hospital medicine specialty shows 20 percent growth. SHM analysis of 2005 American Hospital Association survey data. Available at: www.hospitalmedicine.org/AM/Template.cfm?Section=Press_Releases130:368–372.
- Physician attitudes toward and prevalence of the hospitalist model of care: results of a national survey.Am J Med.2000;109:648–653. , , , et al.
- Friend or foe? How primary care physicians perceive hospitalists.Arch Intern Med.2000;160:2902–2908. , , , et al.
- Reorganizing an academic medical service: impact on cost, quality, patient satisfaction, and education.JAMA.1998;279:1560–1565. , , , et al.
- The effect of full‐time faculty hospitalists on the efficiency of care at a community teaching hospital.Ann Intern Med.1998;129:197–203. , , .
- Economic effects of community versus hospital‐based faculty pneumonia care.J Gen Intern Med.1998;13:774–777. , , , et al.
- Implementation of a hospitalist system in a large health maintenance organization: the Kaiser Permanente experience.Ann Intern Med.1999;130:355–359. , , , et al.
- The Park Nicollet experience in establishing a hospitalist system.Ann Intern Med.1999;130:350–354. .
- Comparison of hospitalists and primary care internists in the care of patients with pneumonia.J Gen Intern Med.1999;14(suppl):S118. , , , et al.
- Comparing hospitalists' and community‐based primary care physicians' care of patients with pneumonia.J Gen Intern Med.2001;16(suppl):S215. , , , et al.
- Effects of hospitalists on cost, outcomes, and patient satisfaction in a rural health system.Am J Med.2000;108:621–626. , , , et al.
- The impact of an inpatient physician program on quality, utilization, and satisfaction.Am J Manag Care.2000;6:549–555. , , , et al.
- Evaluation of a pediatric hospitalist service: impact on length of stay and hospital charges.Pediatrics.2000;105:478–484. , .
- Outcomes of hospitalization in pediatric patients insured by HMOs: comparison of care by hospitalists and traditional academic providers.Pediatr Res.2000;47:204A. Abstract. , , , et al.
- Impact of a managed care hospitalist system in academic pediatrics.Pediatr Res.2000;47:228A. Abstract. , , , et al.
- Cost savings for patients with acute conditions cared for by pediatric hospitalists in a tertiary care center.Pediatr Res.2001;49:125A. Abstract. , , , et al.
- Overview of the history of pharmacy in the United States. In:Brown TR, ed.Handbook of Institutional Pharmacy Practice.Bethesda, MD:American Society of Health‐System Pharmacists;2006:19–32. .
- ASHP national survey of pharmacy practice in hospital settings: dispensing and administration—2005.Am J Health‐Syst Pharm.2006;63:327–345. , , .
- Perspectives on Hilton Head.Am J Hosp Pharm.1986;43:1439–1443. .
- American Society of Hospital Pharmacists.ASHP statement on pharmaceutical care.Am J Hosp Pharm.1993;50:1720–1723.
- Clinical pharmacists and inpatient medical care: a systematic review.Arch Intern Med.2006;166:955–964. , , , et al.
- Interrelationships among mortality rates, drug costs, total cost of care, and length of stay in United States hospitals: summary and recommendations for clinical pharmacy services and staffing.Pharmacotherapy.2001;21:129–141. , , .
- Clinical pharmacy services, hospital pharmacy staffing, and medication errors in United States hospitals.Pharmacotherapy.2002;22:134–147. , , .
- Clinical pharmacy services, pharmacy staffing, and adverse drug reactions in United States hospitals.Pharmacotherapy.2006;26:735–747. , .
- Evidence of the economic benefit of clinical pharmacy services: 1996‐2000.Pharmacotherapy.2003;23:113–132. , , , et al.
- Pharmacists on rounding teams reduce preventable adverse drug events in hospital general medicine units.Arch Intern Med.2003;163:2014–2018. , , , et al.
- How hospitalists spend their time: insights on efficiency and safety.J Hosp Med.2006;1:88–93. , , .
- Implications of the hospitalist model for medical students' education.Acad Med.2001;76:324–330. , .
- Hospitalists' perceptions of their residency training needs: results of a national survey.Am J Med.2001;111:247–254. , , , et al.
- Committee on the Health Professions Education Summit.Health professions education: a bridge to quality.Washington, DC:National Academy Press;2003.
- Developing an evidence base for interdisciplinary learning: a systematic review.J Adv Nurs.2001:31:228–237. , , , et al.
- Multiprofessional learning: the attitudes of medical, nursing, and pharmacy students to shared learning.Med Educ.2001;35:876–883. , , .
- Team working: palliative care as a model of interdisciplinary practice.Med J Aust.2003;179:S32–S34. , .
POSITION
The American Society of Health‐System Pharmacists (ASHP) and the Society of Hospital Medicine (SHM) believe that the rapidly emerging hospitalist model of inpatient care offers new and significant opportunities to optimize patient care through collaboration among hospitalists, hospital pharmacists (hereinafter, pharmacists), and other health care providers. The emerging model of care allows for deeper professional relationships among health care providers and promotes a shared interest in and responsibility for direct patient care, indirect patient care, and service activities. ASHP and SHM encourage hospitalists, pharmacists, and health care executives to seek out ways to foster collaboration between hospitalists and pharmacists.
The purpose of this consensus statement is to promote an understanding of the ways hospitalists and pharmacists can jointly optimize the care provided to patients in hospitals, examine opportunities for improving hospitalistpharmacist alliances that enhance patient care, suggest future directions for collaboration, and identify aspects of such collaboration that warrant further research.
BACKGROUND
Increases in health care spending and the expanding influence of managed care in the late 1980s and early 1990s resulted in calls for more efficient health care. The movement toward greater efficiency resulted in more emphasis on ambulatory care, fewer hospital admissions, shortened hospital stays, and an overall increase in the acuity of illness of hospitalized patients. The emphasis on ambulatory care increased the number and complexity of physician office visits, and the changing characteristics of office‐ and hospital‐based care placed significant demands on primary care physicians and contributed to the rise of hospital medicine.
In 1996, the term hospitalist was introduced into the health care lexicon.1 A hospitalist was defined as an inpatient physician who manages the care of hospitalized patients and facilitates the transfer of their care back to the primary care physician. The Society of Hospital Medicine has since defined a hospitalist as a physician whose primary professional focus is the general medical care of hospitalized patients and whose activities may include patient care, teaching, research, and leadership related to hospital medicine.2
The past decade has seen rapid growth of the number of hospitalists and the use of hospitalists by US hospitals.3 In 2005, 70% of hospitals with more than 200 beds used hospitalist services, and there were more than 16,000 hospitalists in practice.4 An estimated 20,000 hospitalists were practicing at more than 2600 US hospitals in 2007.5
Initially, many physicians expressed concern about the potential for hospitalists to interfere in the relationship between the patient and the primary care physician, as well as about the potential negative impact on continuity of care.6 However, subsequent studies demonstrated increasing acceptance of hospitalists by primary care physicians, with as many as 89% considering the hospitalist model to be superior to the historical model of hospital care provided by primary care physicians or by specialists working on rotations.7, 8 Numerous studies demonstrate the value of hospitalists in improving quality of care, decreasing hospital costs and length of stay, and reducing hospital readmissions.921
As early as 1921, hospital pharmacists in the American Pharmaceutical Association (now the American Pharmacists Association) had formed a committee to address their distinct concerns. During the 1930s, hospital pharmacists began to organize state organizations and to adhere to a set of minimum standards of practice. In 1942, the American Society of Hospital Pharmacists (now the American Society of Health‐System Pharmacists) was formed to establish minimum standards of pharmaceutical services in hospitals, provide interchange among pharmacists, promote new pharmaceutical techniques, and aid the medical profession in extending the economic and rational use of medications.22 As of 2005, there were approximately 50,000 pharmacists practicing in US hospitals.23
The modern mission of hospital pharmacy departments is to ensure optimal outcomes from the use of medicines.24 Although the focus of hospital pharmacy has traditionally been on the safe dispensing of medications, direct patient care by pharmacists (clinical pharmacy) has always been a component of hospital pharmacy practice. Following the rise of pharmaceutical care in the 1980s,25 these pharmacist services have expanded greatly. It has been estimated that 35%‐40% of hospital pharmacists are devoted to providing clinical services.23 A systematic review in 2006 documented improved outcomes when clinical pharmacists interacted with the health care team on patient rounds, interviewed patients, reconciled medications, and provided discharge counseling and follow‐up.26 These findings support those of other studies in which specific clinical pharmacy services were associated with improved therapeutic and economic outcomes.2731
OPPORTUNITIES FOR COLLABORATION BETWEEN PHARMACISTS AND HOSPITALISTS
Pharmacists and hospitalists have shared interests that provide strong incentives for collaboration. All health care professionals share, first, a commitment to and responsibility for providing safe and effective patient care. Physicians, pharmacists, and other health care providers have long collaborated in providing direct patient care. The emerging hospitalist model of care offers more opportunities for collaboration because pharmacists and hospitalists also share interest in and responsibility for indirect patient care and service activitiesdeveloping the institutional policies, processes, and infrastructure that support patient care.
Direct patient care activities typically performed by hospitalists include obtaining patient histories, conducting physical examinations, making diagnoses, developing treatment plans, monitoring patients' responses to therapy, performing follow‐up hospital visits, participating in family meetings, and providing discharge instructions.32 Specific clinical pharmacy services that have been associated with improved health care outcomes include providing drug information, managing medication protocols and adverse drug reactions, participating in medical rounds, gathering admission medication histories, interviewing patients, reconciling patient medications, and providing discharge counseling and follow‐up.2631
Pharmacists should be involved in the care of hospitalized patients and can collaborate with hospitalists in numerous ways, including:
-
Providing consultative services that foster appropriate, evidence‐based medication selection (eg, during rounds),
-
Providing drug information to physicians, nurses, and other clinicians,
-
Managing medication protocols under collaborative practice agreements,
-
Assisting in the development of treatment protocols,
-
Monitoring therapeutic responses (including laboratory test results),
-
Continuously assessing for and managing adverse drug reactions,
-
Gathering medication histories,
-
Reconciling medications as patients move across the continuum of hospital care, and
-
Providing patient and caretaker education, including discharge counseling and follow‐up.
Both hospitalists and pharmacists have a responsibility to ensure continuity as patients move across settings of care.
In addition to their direct patient care activities, hospitalists add value through their efforts in hospital service activities, student and resident education, and research. Typical service activities include participating in quality‐improvement and safety initiatives, developing institutional guidelines and protocols for the treatment of specific diseases, serving on hospital committees (eg, the pharmacy and therapeutics [P&T] committee), and working with others to introduce new technologies to the hospital setting.33, 34
Pharmacists also participate in hospital service activities, education, and research. For example, pharmacists serve on the P&T committee and are directly involved in managing the formulary system that guides an institution's medication use. As medication experts, pharmacists contribute to the development and implementation of patient care guidelines and other medication‐use policies. Pharmacist expertise is also integral to many quality‐improvement efforts (eg, surgical infection prophylaxis) and to technology initiatives (eg, bedside medication scanning and computerized prescriber‐order‐entry systems). Pharmacist provision of in‐service education on medications and medication use is invaluable for all health care providers.
These overlapping responsibilities provide hospitalists and pharmacists with opportunities to collaborate on activities that can have a profound effect on care in the hospital. Hospitalists and pharmacists can work together to ensure that care is evidence based, cost‐effective, and adherent to national guidelines; establish an institutional culture of safety; develop and implement quality‐improvement initiatives; meet accreditation standards; and, in many cases, foster the institution's education and research initiatives. Health professional education and research offers the opportunity to improve patient care provided not just by a single hospital but by other facilities as well.
OPPORTUNITIES TO IMPROVE COLLABORATION
ASHP and SHM believe that there are opportunities for improving collaboration between hospitalists and pharmacists. Barriers to collaboration include real and perceived professional boundaries, poor integration of technology systems, inadequate pharmacist and hospitalist staffing, time constraints, inadequate funding and resources, lack of third‐party compensation for clinical pharmacy services, and the competing obligations weighing on both professions.
Real and perceived professional boundaries can be addressed by clear communication and by enhanced interdisciplinary educational opportunities for all members of the health care team.3538 ASHP and SHM believe that while hospitalists should serve as the primary leaders of hospital care teams, all health care professionals should be willing to assume a leadership role in treating patients and, when appropriate, accept leadership by other team members. Like all members of the care team, pharmacists require timely access to hospitalists for consultation, as well as access to patient information. The vital flow of information and communication among health care providers should be conducive to collaborating and improving patient outcomes. ASHP and SHM believe that properly applied, well‐integrated technologies (eg, electronic medical records and personal digital assistants with clinical decision support systems, including drug information) can enhance communication among all members of the health care team.
Hospitalists and pharmacists can work together to overcome limitations created by inadequate funding and staffing by providing evidence to health care executives of the value of clinical pharmacist positions and pharmacisthospitalist collaboration. This evidence should examine the impact of these positions and such collaboration on therapeutic, safety, humanistic, and economic outcomes. Collaboration among all members of the health care team would also be encouraged by reforming the current fee‐for‐service reimbursement practices to base payment for care delivery on overall treatment goals (eg, a payment rate based on diagnosis).
CONCLUSIONS
An interdisciplinary approach to health care that includes physicians, pharmacists, nurses, and other health care professionals will improve the quality of patient care. Hospitalists and pharmacists need to collaborate with each other and with other health care professionals to optimize outcomes in hospitalized patients. ASHP and SHM believe that hospitalistpharmacist alliances should be encouraged and that the systems and technologies that enable collaboration and the incentives for such collaboration should be enhanced.
Acknowledgements
The following individuals and organizations are acknowledged for reviewing draft versions of this statement: Nicole M. Allcock, PharmD, BCPS; American Academy of Physician Assistants (AAPA); American Nurses Association (ANA); American Society of Consultant Pharmacists (ASCP); Philip Anderson, PharmD, FASHP; Linda C. Annecchini, MS, FASHP; John A. Armitstead, MS, FASHP; Carol Bickford, PhD. (ANA); Michael L. Brandt, BS, PharmD; John Bridges, PharmD; Tim R. Brown, PharmD; Gail M. Burniske, PharmD, BCPS; Margaret Chrymko, PharmD, FASHP; Steve Crane (AAPA); Karren Crowson, MBA; Lourdes M. Cuellar, MS, FASHP; Michele Danish, PharmD; Neil Davis; Jean Douglas, PharmD; Jillian James Foster, PharmD; Georgia W. Fox, PharmD; Nicole Gara (AAPA); Kathleen M. Gura, PharmD, BCNSP, FASHP; Stuart T. Haines, PharmD, FCCP, FASHP; Tom Hall, PharmD; John Hertig; Philip E. Johnson, MS, FASHP; Thomas J. Johnson, PharmD, BCPS; Michael Kelly, PharmD; Patricia Kienle, MPA, FASHP; Kathrin C. Kucharski, PharmD, BCPS; Sharon Kulesz (AAPA); Timothy R. Lanese, MBA, FASHP, FACHE; Bob McNellis, MPH, PA (AAPA); Joe Miller, MD (SHM); Rima Mohammad, PharmD, BCPS; Lynette R. Moser, PharmD; Joe E. Ness, MHA; Scott Oxenhandler, MD; Charles D. Ponte, PharmD, BC‐ADM, BCPS, CDE, FAPhA, FASHP, FCCP; James A. Ponto, MS, BCNP, FASHP; Michael D. Sanborn, MS; Phil Saucedo, MBA; Kenneth H. Schell, PharmD, FASHP, FCSHP; Edward C. Seidl, PharmD; Michele F. Shepherd, PharmD, MS, BCPS, FASHP; Jonalan Smith, PharmD (ASCP); Kelly M. Smith, PharmD; Miriam A. Mobley Smith, PharmD; Edward Stemley, MS, PharmD; Joe Strain, PharmD; James A. Trovato, PharmD, MBA, BCOP; Jennifer Tryon, PharmD, MS; Laura Wachter, BS, PharmD; William E. Wade, PharmD, FASHP, FCCP; Paul C. Walker, PharmD; Larry Wellikson, MD (SHM); Karl G. Williams, JD, MS; and John L. Woon, PharmD, FASHP.
POSITION
The American Society of Health‐System Pharmacists (ASHP) and the Society of Hospital Medicine (SHM) believe that the rapidly emerging hospitalist model of inpatient care offers new and significant opportunities to optimize patient care through collaboration among hospitalists, hospital pharmacists (hereinafter, pharmacists), and other health care providers. The emerging model of care allows for deeper professional relationships among health care providers and promotes a shared interest in and responsibility for direct patient care, indirect patient care, and service activities. ASHP and SHM encourage hospitalists, pharmacists, and health care executives to seek out ways to foster collaboration between hospitalists and pharmacists.
The purpose of this consensus statement is to promote an understanding of the ways hospitalists and pharmacists can jointly optimize the care provided to patients in hospitals, examine opportunities for improving hospitalistpharmacist alliances that enhance patient care, suggest future directions for collaboration, and identify aspects of such collaboration that warrant further research.
BACKGROUND
Increases in health care spending and the expanding influence of managed care in the late 1980s and early 1990s resulted in calls for more efficient health care. The movement toward greater efficiency resulted in more emphasis on ambulatory care, fewer hospital admissions, shortened hospital stays, and an overall increase in the acuity of illness of hospitalized patients. The emphasis on ambulatory care increased the number and complexity of physician office visits, and the changing characteristics of office‐ and hospital‐based care placed significant demands on primary care physicians and contributed to the rise of hospital medicine.
In 1996, the term hospitalist was introduced into the health care lexicon.1 A hospitalist was defined as an inpatient physician who manages the care of hospitalized patients and facilitates the transfer of their care back to the primary care physician. The Society of Hospital Medicine has since defined a hospitalist as a physician whose primary professional focus is the general medical care of hospitalized patients and whose activities may include patient care, teaching, research, and leadership related to hospital medicine.2
The past decade has seen rapid growth of the number of hospitalists and the use of hospitalists by US hospitals.3 In 2005, 70% of hospitals with more than 200 beds used hospitalist services, and there were more than 16,000 hospitalists in practice.4 An estimated 20,000 hospitalists were practicing at more than 2600 US hospitals in 2007.5
Initially, many physicians expressed concern about the potential for hospitalists to interfere in the relationship between the patient and the primary care physician, as well as about the potential negative impact on continuity of care.6 However, subsequent studies demonstrated increasing acceptance of hospitalists by primary care physicians, with as many as 89% considering the hospitalist model to be superior to the historical model of hospital care provided by primary care physicians or by specialists working on rotations.7, 8 Numerous studies demonstrate the value of hospitalists in improving quality of care, decreasing hospital costs and length of stay, and reducing hospital readmissions.921
As early as 1921, hospital pharmacists in the American Pharmaceutical Association (now the American Pharmacists Association) had formed a committee to address their distinct concerns. During the 1930s, hospital pharmacists began to organize state organizations and to adhere to a set of minimum standards of practice. In 1942, the American Society of Hospital Pharmacists (now the American Society of Health‐System Pharmacists) was formed to establish minimum standards of pharmaceutical services in hospitals, provide interchange among pharmacists, promote new pharmaceutical techniques, and aid the medical profession in extending the economic and rational use of medications.22 As of 2005, there were approximately 50,000 pharmacists practicing in US hospitals.23
The modern mission of hospital pharmacy departments is to ensure optimal outcomes from the use of medicines.24 Although the focus of hospital pharmacy has traditionally been on the safe dispensing of medications, direct patient care by pharmacists (clinical pharmacy) has always been a component of hospital pharmacy practice. Following the rise of pharmaceutical care in the 1980s,25 these pharmacist services have expanded greatly. It has been estimated that 35%‐40% of hospital pharmacists are devoted to providing clinical services.23 A systematic review in 2006 documented improved outcomes when clinical pharmacists interacted with the health care team on patient rounds, interviewed patients, reconciled medications, and provided discharge counseling and follow‐up.26 These findings support those of other studies in which specific clinical pharmacy services were associated with improved therapeutic and economic outcomes.2731
OPPORTUNITIES FOR COLLABORATION BETWEEN PHARMACISTS AND HOSPITALISTS
Pharmacists and hospitalists have shared interests that provide strong incentives for collaboration. All health care professionals share, first, a commitment to and responsibility for providing safe and effective patient care. Physicians, pharmacists, and other health care providers have long collaborated in providing direct patient care. The emerging hospitalist model of care offers more opportunities for collaboration because pharmacists and hospitalists also share interest in and responsibility for indirect patient care and service activitiesdeveloping the institutional policies, processes, and infrastructure that support patient care.
Direct patient care activities typically performed by hospitalists include obtaining patient histories, conducting physical examinations, making diagnoses, developing treatment plans, monitoring patients' responses to therapy, performing follow‐up hospital visits, participating in family meetings, and providing discharge instructions.32 Specific clinical pharmacy services that have been associated with improved health care outcomes include providing drug information, managing medication protocols and adverse drug reactions, participating in medical rounds, gathering admission medication histories, interviewing patients, reconciling patient medications, and providing discharge counseling and follow‐up.2631
Pharmacists should be involved in the care of hospitalized patients and can collaborate with hospitalists in numerous ways, including:
-
Providing consultative services that foster appropriate, evidence‐based medication selection (eg, during rounds),
-
Providing drug information to physicians, nurses, and other clinicians,
-
Managing medication protocols under collaborative practice agreements,
-
Assisting in the development of treatment protocols,
-
Monitoring therapeutic responses (including laboratory test results),
-
Continuously assessing for and managing adverse drug reactions,
-
Gathering medication histories,
-
Reconciling medications as patients move across the continuum of hospital care, and
-
Providing patient and caretaker education, including discharge counseling and follow‐up.
Both hospitalists and pharmacists have a responsibility to ensure continuity as patients move across settings of care.
In addition to their direct patient care activities, hospitalists add value through their efforts in hospital service activities, student and resident education, and research. Typical service activities include participating in quality‐improvement and safety initiatives, developing institutional guidelines and protocols for the treatment of specific diseases, serving on hospital committees (eg, the pharmacy and therapeutics [P&T] committee), and working with others to introduce new technologies to the hospital setting.33, 34
Pharmacists also participate in hospital service activities, education, and research. For example, pharmacists serve on the P&T committee and are directly involved in managing the formulary system that guides an institution's medication use. As medication experts, pharmacists contribute to the development and implementation of patient care guidelines and other medication‐use policies. Pharmacist expertise is also integral to many quality‐improvement efforts (eg, surgical infection prophylaxis) and to technology initiatives (eg, bedside medication scanning and computerized prescriber‐order‐entry systems). Pharmacist provision of in‐service education on medications and medication use is invaluable for all health care providers.
These overlapping responsibilities provide hospitalists and pharmacists with opportunities to collaborate on activities that can have a profound effect on care in the hospital. Hospitalists and pharmacists can work together to ensure that care is evidence based, cost‐effective, and adherent to national guidelines; establish an institutional culture of safety; develop and implement quality‐improvement initiatives; meet accreditation standards; and, in many cases, foster the institution's education and research initiatives. Health professional education and research offers the opportunity to improve patient care provided not just by a single hospital but by other facilities as well.
OPPORTUNITIES TO IMPROVE COLLABORATION
ASHP and SHM believe that there are opportunities for improving collaboration between hospitalists and pharmacists. Barriers to collaboration include real and perceived professional boundaries, poor integration of technology systems, inadequate pharmacist and hospitalist staffing, time constraints, inadequate funding and resources, lack of third‐party compensation for clinical pharmacy services, and the competing obligations weighing on both professions.
Real and perceived professional boundaries can be addressed by clear communication and by enhanced interdisciplinary educational opportunities for all members of the health care team.3538 ASHP and SHM believe that while hospitalists should serve as the primary leaders of hospital care teams, all health care professionals should be willing to assume a leadership role in treating patients and, when appropriate, accept leadership by other team members. Like all members of the care team, pharmacists require timely access to hospitalists for consultation, as well as access to patient information. The vital flow of information and communication among health care providers should be conducive to collaborating and improving patient outcomes. ASHP and SHM believe that properly applied, well‐integrated technologies (eg, electronic medical records and personal digital assistants with clinical decision support systems, including drug information) can enhance communication among all members of the health care team.
Hospitalists and pharmacists can work together to overcome limitations created by inadequate funding and staffing by providing evidence to health care executives of the value of clinical pharmacist positions and pharmacisthospitalist collaboration. This evidence should examine the impact of these positions and such collaboration on therapeutic, safety, humanistic, and economic outcomes. Collaboration among all members of the health care team would also be encouraged by reforming the current fee‐for‐service reimbursement practices to base payment for care delivery on overall treatment goals (eg, a payment rate based on diagnosis).
CONCLUSIONS
An interdisciplinary approach to health care that includes physicians, pharmacists, nurses, and other health care professionals will improve the quality of patient care. Hospitalists and pharmacists need to collaborate with each other and with other health care professionals to optimize outcomes in hospitalized patients. ASHP and SHM believe that hospitalistpharmacist alliances should be encouraged and that the systems and technologies that enable collaboration and the incentives for such collaboration should be enhanced.
Acknowledgements
The following individuals and organizations are acknowledged for reviewing draft versions of this statement: Nicole M. Allcock, PharmD, BCPS; American Academy of Physician Assistants (AAPA); American Nurses Association (ANA); American Society of Consultant Pharmacists (ASCP); Philip Anderson, PharmD, FASHP; Linda C. Annecchini, MS, FASHP; John A. Armitstead, MS, FASHP; Carol Bickford, PhD. (ANA); Michael L. Brandt, BS, PharmD; John Bridges, PharmD; Tim R. Brown, PharmD; Gail M. Burniske, PharmD, BCPS; Margaret Chrymko, PharmD, FASHP; Steve Crane (AAPA); Karren Crowson, MBA; Lourdes M. Cuellar, MS, FASHP; Michele Danish, PharmD; Neil Davis; Jean Douglas, PharmD; Jillian James Foster, PharmD; Georgia W. Fox, PharmD; Nicole Gara (AAPA); Kathleen M. Gura, PharmD, BCNSP, FASHP; Stuart T. Haines, PharmD, FCCP, FASHP; Tom Hall, PharmD; John Hertig; Philip E. Johnson, MS, FASHP; Thomas J. Johnson, PharmD, BCPS; Michael Kelly, PharmD; Patricia Kienle, MPA, FASHP; Kathrin C. Kucharski, PharmD, BCPS; Sharon Kulesz (AAPA); Timothy R. Lanese, MBA, FASHP, FACHE; Bob McNellis, MPH, PA (AAPA); Joe Miller, MD (SHM); Rima Mohammad, PharmD, BCPS; Lynette R. Moser, PharmD; Joe E. Ness, MHA; Scott Oxenhandler, MD; Charles D. Ponte, PharmD, BC‐ADM, BCPS, CDE, FAPhA, FASHP, FCCP; James A. Ponto, MS, BCNP, FASHP; Michael D. Sanborn, MS; Phil Saucedo, MBA; Kenneth H. Schell, PharmD, FASHP, FCSHP; Edward C. Seidl, PharmD; Michele F. Shepherd, PharmD, MS, BCPS, FASHP; Jonalan Smith, PharmD (ASCP); Kelly M. Smith, PharmD; Miriam A. Mobley Smith, PharmD; Edward Stemley, MS, PharmD; Joe Strain, PharmD; James A. Trovato, PharmD, MBA, BCOP; Jennifer Tryon, PharmD, MS; Laura Wachter, BS, PharmD; William E. Wade, PharmD, FASHP, FCCP; Paul C. Walker, PharmD; Larry Wellikson, MD (SHM); Karl G. Williams, JD, MS; and John L. Woon, PharmD, FASHP.
- The emerging role of “hospitalists” in the American health care system.N Engl J Med.1996;335:514–517. , .
- Society of Hospital Medicine. Definition of a hospitalist. Available at: www.hospitalmedicine.org/Content/NavigationMenu/AboutSHM/DefinitionofaHospitalist/Definition_of_a_Hosp.htm. Accessed May 29,2007.
- The status of hospital medicine groups in the United States.J Hosp Med.2006;1:75–80. , , , et al.
- AHA Hospital Statistics.Chicago:American Hospital Association;2005.
- Hospital medicine specialty shows 20 percent growth. SHM analysis of 2005 American Hospital Association survey data. Available at: www.hospitalmedicine.org/AM/Template.cfm?Section=Press_Releases130:368–372.
- Physician attitudes toward and prevalence of the hospitalist model of care: results of a national survey.Am J Med.2000;109:648–653. , , , et al.
- Friend or foe? How primary care physicians perceive hospitalists.Arch Intern Med.2000;160:2902–2908. , , , et al.
- Reorganizing an academic medical service: impact on cost, quality, patient satisfaction, and education.JAMA.1998;279:1560–1565. , , , et al.
- The effect of full‐time faculty hospitalists on the efficiency of care at a community teaching hospital.Ann Intern Med.1998;129:197–203. , , .
- Economic effects of community versus hospital‐based faculty pneumonia care.J Gen Intern Med.1998;13:774–777. , , , et al.
- Implementation of a hospitalist system in a large health maintenance organization: the Kaiser Permanente experience.Ann Intern Med.1999;130:355–359. , , , et al.
- The Park Nicollet experience in establishing a hospitalist system.Ann Intern Med.1999;130:350–354. .
- Comparison of hospitalists and primary care internists in the care of patients with pneumonia.J Gen Intern Med.1999;14(suppl):S118. , , , et al.
- Comparing hospitalists' and community‐based primary care physicians' care of patients with pneumonia.J Gen Intern Med.2001;16(suppl):S215. , , , et al.
- Effects of hospitalists on cost, outcomes, and patient satisfaction in a rural health system.Am J Med.2000;108:621–626. , , , et al.
- The impact of an inpatient physician program on quality, utilization, and satisfaction.Am J Manag Care.2000;6:549–555. , , , et al.
- Evaluation of a pediatric hospitalist service: impact on length of stay and hospital charges.Pediatrics.2000;105:478–484. , .
- Outcomes of hospitalization in pediatric patients insured by HMOs: comparison of care by hospitalists and traditional academic providers.Pediatr Res.2000;47:204A. Abstract. , , , et al.
- Impact of a managed care hospitalist system in academic pediatrics.Pediatr Res.2000;47:228A. Abstract. , , , et al.
- Cost savings for patients with acute conditions cared for by pediatric hospitalists in a tertiary care center.Pediatr Res.2001;49:125A. Abstract. , , , et al.
- Overview of the history of pharmacy in the United States. In:Brown TR, ed.Handbook of Institutional Pharmacy Practice.Bethesda, MD:American Society of Health‐System Pharmacists;2006:19–32. .
- ASHP national survey of pharmacy practice in hospital settings: dispensing and administration—2005.Am J Health‐Syst Pharm.2006;63:327–345. , , .
- Perspectives on Hilton Head.Am J Hosp Pharm.1986;43:1439–1443. .
- American Society of Hospital Pharmacists.ASHP statement on pharmaceutical care.Am J Hosp Pharm.1993;50:1720–1723.
- Clinical pharmacists and inpatient medical care: a systematic review.Arch Intern Med.2006;166:955–964. , , , et al.
- Interrelationships among mortality rates, drug costs, total cost of care, and length of stay in United States hospitals: summary and recommendations for clinical pharmacy services and staffing.Pharmacotherapy.2001;21:129–141. , , .
- Clinical pharmacy services, hospital pharmacy staffing, and medication errors in United States hospitals.Pharmacotherapy.2002;22:134–147. , , .
- Clinical pharmacy services, pharmacy staffing, and adverse drug reactions in United States hospitals.Pharmacotherapy.2006;26:735–747. , .
- Evidence of the economic benefit of clinical pharmacy services: 1996‐2000.Pharmacotherapy.2003;23:113–132. , , , et al.
- Pharmacists on rounding teams reduce preventable adverse drug events in hospital general medicine units.Arch Intern Med.2003;163:2014–2018. , , , et al.
- How hospitalists spend their time: insights on efficiency and safety.J Hosp Med.2006;1:88–93. , , .
- Implications of the hospitalist model for medical students' education.Acad Med.2001;76:324–330. , .
- Hospitalists' perceptions of their residency training needs: results of a national survey.Am J Med.2001;111:247–254. , , , et al.
- Committee on the Health Professions Education Summit.Health professions education: a bridge to quality.Washington, DC:National Academy Press;2003.
- Developing an evidence base for interdisciplinary learning: a systematic review.J Adv Nurs.2001:31:228–237. , , , et al.
- Multiprofessional learning: the attitudes of medical, nursing, and pharmacy students to shared learning.Med Educ.2001;35:876–883. , , .
- Team working: palliative care as a model of interdisciplinary practice.Med J Aust.2003;179:S32–S34. , .
- The emerging role of “hospitalists” in the American health care system.N Engl J Med.1996;335:514–517. , .
- Society of Hospital Medicine. Definition of a hospitalist. Available at: www.hospitalmedicine.org/Content/NavigationMenu/AboutSHM/DefinitionofaHospitalist/Definition_of_a_Hosp.htm. Accessed May 29,2007.
- The status of hospital medicine groups in the United States.J Hosp Med.2006;1:75–80. , , , et al.
- AHA Hospital Statistics.Chicago:American Hospital Association;2005.
- Hospital medicine specialty shows 20 percent growth. SHM analysis of 2005 American Hospital Association survey data. Available at: www.hospitalmedicine.org/AM/Template.cfm?Section=Press_Releases130:368–372.
- Physician attitudes toward and prevalence of the hospitalist model of care: results of a national survey.Am J Med.2000;109:648–653. , , , et al.
- Friend or foe? How primary care physicians perceive hospitalists.Arch Intern Med.2000;160:2902–2908. , , , et al.
- Reorganizing an academic medical service: impact on cost, quality, patient satisfaction, and education.JAMA.1998;279:1560–1565. , , , et al.
- The effect of full‐time faculty hospitalists on the efficiency of care at a community teaching hospital.Ann Intern Med.1998;129:197–203. , , .
- Economic effects of community versus hospital‐based faculty pneumonia care.J Gen Intern Med.1998;13:774–777. , , , et al.
- Implementation of a hospitalist system in a large health maintenance organization: the Kaiser Permanente experience.Ann Intern Med.1999;130:355–359. , , , et al.
- The Park Nicollet experience in establishing a hospitalist system.Ann Intern Med.1999;130:350–354. .
- Comparison of hospitalists and primary care internists in the care of patients with pneumonia.J Gen Intern Med.1999;14(suppl):S118. , , , et al.
- Comparing hospitalists' and community‐based primary care physicians' care of patients with pneumonia.J Gen Intern Med.2001;16(suppl):S215. , , , et al.
- Effects of hospitalists on cost, outcomes, and patient satisfaction in a rural health system.Am J Med.2000;108:621–626. , , , et al.
- The impact of an inpatient physician program on quality, utilization, and satisfaction.Am J Manag Care.2000;6:549–555. , , , et al.
- Evaluation of a pediatric hospitalist service: impact on length of stay and hospital charges.Pediatrics.2000;105:478–484. , .
- Outcomes of hospitalization in pediatric patients insured by HMOs: comparison of care by hospitalists and traditional academic providers.Pediatr Res.2000;47:204A. Abstract. , , , et al.
- Impact of a managed care hospitalist system in academic pediatrics.Pediatr Res.2000;47:228A. Abstract. , , , et al.
- Cost savings for patients with acute conditions cared for by pediatric hospitalists in a tertiary care center.Pediatr Res.2001;49:125A. Abstract. , , , et al.
- Overview of the history of pharmacy in the United States. In:Brown TR, ed.Handbook of Institutional Pharmacy Practice.Bethesda, MD:American Society of Health‐System Pharmacists;2006:19–32. .
- ASHP national survey of pharmacy practice in hospital settings: dispensing and administration—2005.Am J Health‐Syst Pharm.2006;63:327–345. , , .
- Perspectives on Hilton Head.Am J Hosp Pharm.1986;43:1439–1443. .
- American Society of Hospital Pharmacists.ASHP statement on pharmaceutical care.Am J Hosp Pharm.1993;50:1720–1723.
- Clinical pharmacists and inpatient medical care: a systematic review.Arch Intern Med.2006;166:955–964. , , , et al.
- Interrelationships among mortality rates, drug costs, total cost of care, and length of stay in United States hospitals: summary and recommendations for clinical pharmacy services and staffing.Pharmacotherapy.2001;21:129–141. , , .
- Clinical pharmacy services, hospital pharmacy staffing, and medication errors in United States hospitals.Pharmacotherapy.2002;22:134–147. , , .
- Clinical pharmacy services, pharmacy staffing, and adverse drug reactions in United States hospitals.Pharmacotherapy.2006;26:735–747. , .
- Evidence of the economic benefit of clinical pharmacy services: 1996‐2000.Pharmacotherapy.2003;23:113–132. , , , et al.
- Pharmacists on rounding teams reduce preventable adverse drug events in hospital general medicine units.Arch Intern Med.2003;163:2014–2018. , , , et al.
- How hospitalists spend their time: insights on efficiency and safety.J Hosp Med.2006;1:88–93. , , .
- Implications of the hospitalist model for medical students' education.Acad Med.2001;76:324–330. , .
- Hospitalists' perceptions of their residency training needs: results of a national survey.Am J Med.2001;111:247–254. , , , et al.
- Committee on the Health Professions Education Summit.Health professions education: a bridge to quality.Washington, DC:National Academy Press;2003.
- Developing an evidence base for interdisciplinary learning: a systematic review.J Adv Nurs.2001:31:228–237. , , , et al.
- Multiprofessional learning: the attitudes of medical, nursing, and pharmacy students to shared learning.Med Educ.2001;35:876–883. , , .
- Team working: palliative care as a model of interdisciplinary practice.Med J Aust.2003;179:S32–S34. , .
Handoffs
It had been a turbulent year. Death and disease in the family had taken a toll on my personal life. Though I was a newlywed, life was anything but bliss. That month I was the resident in the cardiac intensive care unit (CICU); a challenging rotation, where sleep was a luxury and the long nights on call added to the strain on my relationship with my wife. It was on one of those nights that I met Mr. and Mrs. Dubinski.
Mr. Dubinski was a pleasant man who looked younger than his 75 years. He had been brought to the hospital because his implantable cardioverter defibrillator (ICD) had fired twice that night. He was in good spirits and chatting amiably with his son. I asked him how he was doing. His pleasant expression changed to a worried one. I have been rather upset for the last few days, worried about my wife, he said.
It turned out that over the last few days Mrs. Dubinski had not been feeling well. This had troubled Mr. Dubinski, and he was often preoccupied with concerns about her. The couple had been married 55 years and had never spent a day apart. They had waited to seek medical advice. Her pain was intermittent, and they thought it would pass; they had some appointments coming up, and they thought they could wait it out. That night, Mrs. Dubinski had a particularly severe episode of pain that bothered her greatly and worried Mr. Dubinski even more. He said that he felt as though he was beginning to pass out, and as he began to faint, he felt a funny feeling in his chest. He had never had a shock from the ICD before, and he didn't know what happened. He sat down to compose himself and felt the same funny feeling in his chest again and also felt lightheaded. He described it, saying, I felt like I was going to explode from the inside. Concerned about his unusual symptoms and her worsening pain, Mr. and Mrs. Dubinski decided to come to the hospital.
Mr. Dubinski's electrocardiogram revealed many premature ventricular complexes (PVCs), and I suspected that one of these had triggered a malignant arrhythmia, which resulted in the device firing. He would need monitoring, and his ICD would be interrogated in the morning to ensure that it was functioning properly. I reassured Mr. Dubinski that the device seemed to have done what it was meant to do. It had almost certainly saved his life. He was relieved to hear this but wanted me to reassure his wife that even though he was going to the CICU, he was all right and it was nothing serious.
As I was wheeling Mr. Dubinski up, I walked past the nurse taking care of his wife. She pulled me aside for a moment and said, Looks like you'll be taking her, too; her troponin just came back at 5.96.
Mrs. Dubinski was a thin, older woman who looked uncomfortable. For about a week, she had been experiencing intermittent pain in her chest and abdomen and just felt that something was not right. Tonight her chest pain did not get better spontaneously, and she had a particularly long episode of pain that radiated to her left arm. She said she felt like she was going to explode from the inside. It was uncanny how she used the same words and expressions that her husband did. I suppose after 55 years of marriage, it should not have been surprising to me, but it was. When they had gotten to the emergency room Mrs. Dubinski had told the doctor about her own complaints. He ordered an electrocardiogram, which showed subtle changes consistent with myocardial ischemia. Her lab data confirmed that she was having a heart attack.
Mrs. Dubinski asked me what was going on. I gently explained to her that she was having a small heart attack. The stuttering episodes of chest pain in the past week probably meant that it had been coming on for a few days now. We could see some evidence of heart damage in her blood tests and the subtle changes in her electrocardiogram. I expected her to ask me more questions about the heart attack or what we were going to next. Instead, she said, Please don't tell my husband. It will only worry him more. I reassured her that I understood her concerns and told her that she was also going to be admitted to the CICU. She was fine with this, more worried about her husband than herself. Once in the CICU I kept my word to Mrs. Dubinski and told Mr. Dubinski a partial truththat his wife was being admitted for observation because we were worried about her.
I was genuinely touched by the deep bond between Mr. and Mrs. Dubinski. It amazed me to see that a man's heart could be stimulated by his wife's suffering in such a way that would have taken his life if not for his ICD. One could say that Mr. Dubinski was anxious about his wife's health, which led to an increased sympathetic drive and higher catecholamine levels. But as a young man at the beginning of a relationship with my wife, I thought there was much more here. Tonight, perhaps, because he cared so deeply, a PVC occurred right during the vulnerable period of the cardiac cycle in a person with a vulnerable heart, and a potentially lethal ventricular arrhythmia had ensued. And tonight my heart was also vulnerable, and I was moved. I thought of all the storms they must have weathered in their 55 years together and the love they had forged. It gave me hope for my own fledgling marriage and made me hope that one day my wife and I would be able to look back on many years of life together like Mr. and Mrs. Dubinski could, with 2 hearts beating as 1.
I had the privilege to know this couple for only 1 call night. By the time I was back on the CICU, Mrs. Dubinski had been transferred to another facility for angioplasty, and Mr. Dubinski had been discharged. Yet that was enough time for me to take part in the care of 2 amazing people and to witness the majesty of their love.
Note: Dubinski is a fictitious name.
It had been a turbulent year. Death and disease in the family had taken a toll on my personal life. Though I was a newlywed, life was anything but bliss. That month I was the resident in the cardiac intensive care unit (CICU); a challenging rotation, where sleep was a luxury and the long nights on call added to the strain on my relationship with my wife. It was on one of those nights that I met Mr. and Mrs. Dubinski.
Mr. Dubinski was a pleasant man who looked younger than his 75 years. He had been brought to the hospital because his implantable cardioverter defibrillator (ICD) had fired twice that night. He was in good spirits and chatting amiably with his son. I asked him how he was doing. His pleasant expression changed to a worried one. I have been rather upset for the last few days, worried about my wife, he said.
It turned out that over the last few days Mrs. Dubinski had not been feeling well. This had troubled Mr. Dubinski, and he was often preoccupied with concerns about her. The couple had been married 55 years and had never spent a day apart. They had waited to seek medical advice. Her pain was intermittent, and they thought it would pass; they had some appointments coming up, and they thought they could wait it out. That night, Mrs. Dubinski had a particularly severe episode of pain that bothered her greatly and worried Mr. Dubinski even more. He said that he felt as though he was beginning to pass out, and as he began to faint, he felt a funny feeling in his chest. He had never had a shock from the ICD before, and he didn't know what happened. He sat down to compose himself and felt the same funny feeling in his chest again and also felt lightheaded. He described it, saying, I felt like I was going to explode from the inside. Concerned about his unusual symptoms and her worsening pain, Mr. and Mrs. Dubinski decided to come to the hospital.
Mr. Dubinski's electrocardiogram revealed many premature ventricular complexes (PVCs), and I suspected that one of these had triggered a malignant arrhythmia, which resulted in the device firing. He would need monitoring, and his ICD would be interrogated in the morning to ensure that it was functioning properly. I reassured Mr. Dubinski that the device seemed to have done what it was meant to do. It had almost certainly saved his life. He was relieved to hear this but wanted me to reassure his wife that even though he was going to the CICU, he was all right and it was nothing serious.
As I was wheeling Mr. Dubinski up, I walked past the nurse taking care of his wife. She pulled me aside for a moment and said, Looks like you'll be taking her, too; her troponin just came back at 5.96.
Mrs. Dubinski was a thin, older woman who looked uncomfortable. For about a week, she had been experiencing intermittent pain in her chest and abdomen and just felt that something was not right. Tonight her chest pain did not get better spontaneously, and she had a particularly long episode of pain that radiated to her left arm. She said she felt like she was going to explode from the inside. It was uncanny how she used the same words and expressions that her husband did. I suppose after 55 years of marriage, it should not have been surprising to me, but it was. When they had gotten to the emergency room Mrs. Dubinski had told the doctor about her own complaints. He ordered an electrocardiogram, which showed subtle changes consistent with myocardial ischemia. Her lab data confirmed that she was having a heart attack.
Mrs. Dubinski asked me what was going on. I gently explained to her that she was having a small heart attack. The stuttering episodes of chest pain in the past week probably meant that it had been coming on for a few days now. We could see some evidence of heart damage in her blood tests and the subtle changes in her electrocardiogram. I expected her to ask me more questions about the heart attack or what we were going to next. Instead, she said, Please don't tell my husband. It will only worry him more. I reassured her that I understood her concerns and told her that she was also going to be admitted to the CICU. She was fine with this, more worried about her husband than herself. Once in the CICU I kept my word to Mrs. Dubinski and told Mr. Dubinski a partial truththat his wife was being admitted for observation because we were worried about her.
I was genuinely touched by the deep bond between Mr. and Mrs. Dubinski. It amazed me to see that a man's heart could be stimulated by his wife's suffering in such a way that would have taken his life if not for his ICD. One could say that Mr. Dubinski was anxious about his wife's health, which led to an increased sympathetic drive and higher catecholamine levels. But as a young man at the beginning of a relationship with my wife, I thought there was much more here. Tonight, perhaps, because he cared so deeply, a PVC occurred right during the vulnerable period of the cardiac cycle in a person with a vulnerable heart, and a potentially lethal ventricular arrhythmia had ensued. And tonight my heart was also vulnerable, and I was moved. I thought of all the storms they must have weathered in their 55 years together and the love they had forged. It gave me hope for my own fledgling marriage and made me hope that one day my wife and I would be able to look back on many years of life together like Mr. and Mrs. Dubinski could, with 2 hearts beating as 1.
I had the privilege to know this couple for only 1 call night. By the time I was back on the CICU, Mrs. Dubinski had been transferred to another facility for angioplasty, and Mr. Dubinski had been discharged. Yet that was enough time for me to take part in the care of 2 amazing people and to witness the majesty of their love.
Note: Dubinski is a fictitious name.
It had been a turbulent year. Death and disease in the family had taken a toll on my personal life. Though I was a newlywed, life was anything but bliss. That month I was the resident in the cardiac intensive care unit (CICU); a challenging rotation, where sleep was a luxury and the long nights on call added to the strain on my relationship with my wife. It was on one of those nights that I met Mr. and Mrs. Dubinski.
Mr. Dubinski was a pleasant man who looked younger than his 75 years. He had been brought to the hospital because his implantable cardioverter defibrillator (ICD) had fired twice that night. He was in good spirits and chatting amiably with his son. I asked him how he was doing. His pleasant expression changed to a worried one. I have been rather upset for the last few days, worried about my wife, he said.
It turned out that over the last few days Mrs. Dubinski had not been feeling well. This had troubled Mr. Dubinski, and he was often preoccupied with concerns about her. The couple had been married 55 years and had never spent a day apart. They had waited to seek medical advice. Her pain was intermittent, and they thought it would pass; they had some appointments coming up, and they thought they could wait it out. That night, Mrs. Dubinski had a particularly severe episode of pain that bothered her greatly and worried Mr. Dubinski even more. He said that he felt as though he was beginning to pass out, and as he began to faint, he felt a funny feeling in his chest. He had never had a shock from the ICD before, and he didn't know what happened. He sat down to compose himself and felt the same funny feeling in his chest again and also felt lightheaded. He described it, saying, I felt like I was going to explode from the inside. Concerned about his unusual symptoms and her worsening pain, Mr. and Mrs. Dubinski decided to come to the hospital.
Mr. Dubinski's electrocardiogram revealed many premature ventricular complexes (PVCs), and I suspected that one of these had triggered a malignant arrhythmia, which resulted in the device firing. He would need monitoring, and his ICD would be interrogated in the morning to ensure that it was functioning properly. I reassured Mr. Dubinski that the device seemed to have done what it was meant to do. It had almost certainly saved his life. He was relieved to hear this but wanted me to reassure his wife that even though he was going to the CICU, he was all right and it was nothing serious.
As I was wheeling Mr. Dubinski up, I walked past the nurse taking care of his wife. She pulled me aside for a moment and said, Looks like you'll be taking her, too; her troponin just came back at 5.96.
Mrs. Dubinski was a thin, older woman who looked uncomfortable. For about a week, she had been experiencing intermittent pain in her chest and abdomen and just felt that something was not right. Tonight her chest pain did not get better spontaneously, and she had a particularly long episode of pain that radiated to her left arm. She said she felt like she was going to explode from the inside. It was uncanny how she used the same words and expressions that her husband did. I suppose after 55 years of marriage, it should not have been surprising to me, but it was. When they had gotten to the emergency room Mrs. Dubinski had told the doctor about her own complaints. He ordered an electrocardiogram, which showed subtle changes consistent with myocardial ischemia. Her lab data confirmed that she was having a heart attack.
Mrs. Dubinski asked me what was going on. I gently explained to her that she was having a small heart attack. The stuttering episodes of chest pain in the past week probably meant that it had been coming on for a few days now. We could see some evidence of heart damage in her blood tests and the subtle changes in her electrocardiogram. I expected her to ask me more questions about the heart attack or what we were going to next. Instead, she said, Please don't tell my husband. It will only worry him more. I reassured her that I understood her concerns and told her that she was also going to be admitted to the CICU. She was fine with this, more worried about her husband than herself. Once in the CICU I kept my word to Mrs. Dubinski and told Mr. Dubinski a partial truththat his wife was being admitted for observation because we were worried about her.
I was genuinely touched by the deep bond between Mr. and Mrs. Dubinski. It amazed me to see that a man's heart could be stimulated by his wife's suffering in such a way that would have taken his life if not for his ICD. One could say that Mr. Dubinski was anxious about his wife's health, which led to an increased sympathetic drive and higher catecholamine levels. But as a young man at the beginning of a relationship with my wife, I thought there was much more here. Tonight, perhaps, because he cared so deeply, a PVC occurred right during the vulnerable period of the cardiac cycle in a person with a vulnerable heart, and a potentially lethal ventricular arrhythmia had ensued. And tonight my heart was also vulnerable, and I was moved. I thought of all the storms they must have weathered in their 55 years together and the love they had forged. It gave me hope for my own fledgling marriage and made me hope that one day my wife and I would be able to look back on many years of life together like Mr. and Mrs. Dubinski could, with 2 hearts beating as 1.
I had the privilege to know this couple for only 1 call night. By the time I was back on the CICU, Mrs. Dubinski had been transferred to another facility for angioplasty, and Mr. Dubinski had been discharged. Yet that was enough time for me to take part in the care of 2 amazing people and to witness the majesty of their love.
Note: Dubinski is a fictitious name.