Injectable furosemide was first approved for use by the US Food and Drug Administration in 1968.1 For more than 40 years, loop diuretics have been the mainstay of therapy for relief of congestion and fluid removal in patients admitted with acute decompensated heart failure (ADHF). Despite the widespread use of loop diuretics in clinical practice, robust data supporting their role is scarce. Furthermore, the optimal approach to the management of the patient with acute volume overload has not been well defined.

In this issue of the Journal of Hospital Medicine, Amer et al.2 present a meta‐analysis of randomized controlled trials comparing continuous infusion to bolus doses of furosemide in hospitalized patients with ADHF. The study demonstrates that continuous infusion is superior to bolus in terms of weight loss and urine output over 24 hours. Specifically, patients receiving a continuous infusion of furosemide had 240 mL/day (95% CI, 462.42 to 18.66) more urine and lost an additional 0.78 kg (95% CI, 1.54 to 0.03) in their hospital stay compared with patients receiving a bolus infusion. The heterogeneity in study designs for urine output and wide confidence intervals for urine output and weight loss create uncertainty about the superiority of continuous infusion. The small difference in daily urine output questions the clinical significance of the results. Many of the studies evaluated in the meta‐analysis lacked rigorous design and/or appropriately dosed furosemide.

Despite the shortcomings of the available studies, the authors have published a sound and reasonable meta‐analysis. This is the first meta‐analysis comparing the use of furosemide alone as a continuous infusion versus bolus dose in patients with ADHF. Additionally, Amer et al. are the first to include recent data from the DOSE trial,3 which showed no difference in volume loss between heart failure patients receiving bolus versus continuous infusions dosing of loop diuretics. Although the benefits of continuous infusion in the meta‐analysis by Amer et al. represent only a modest clinical advantage over bolus infusions, the authors should be commended for addressing an important controversy in the management of patients with volume overload.

Although the method of dose delivery is an important issue in the management of such patients, we believe that a number of critical factors must be taken into consideration to assure sufficient fluid removal and quick relief of congestion. Ensuring the delivery of an adequate loop diuretic dose is critical. Additionally, the dose response must be assessed at an appropriate interval so adjustments can be made in a timely manner. Using this method, diuretic dosing can be individualized based on response.

Current guidelines jointly published by the American Heart Association (AHA) and American College of Cardiology (ACC) do not provide clinicians with specific details about the optimal approach to volume‐overloaded patients.4 In a 2009 update, the ACC and AHA recommend diuretic use to optimize volume status and relieve signs and symptoms of congestion without inducing excessively rapid reduction in intravascular volume.4 They further recommend that patients already receiving a loop diuretic who present with volume overload should receive a dose of diuretic equal to or higher than the outpatient dose. Urine output and congestion should be reassessed serially, and diuretics should be titrated accordingly. Current guidelines do not adequately address several topics, including: (1) appropriate urine output in 24 hours, and how frequently urine output should be assessed; (2) optimal frequency of diuretic dosing; and (3) appropriate choice of diuretic.

An understanding of the pharmacokinetics of loop diuretics helps answer these questions. Intravenous furosemide and bumetanide have similar elimination half‐lives of 1 to 2 hours and peak intravenous action at 30 minutes.5, 6 Intravenous torsemide has not been widely available, but has a longer half‐life of 3 to 4 hours, with peak action in 1 to 2 hours.5, 6 The magnitude of a patient's diuretic response compared with the amount of drug administered is best represented by a sigmoid curve.5 Therefore, after a specific dose threshold, further natriuresis is not achieved. Based on the elimination half‐life, proper bolus dosing of furosemide or bumetanide should be every 4 to 8 hours in patients with volume overload and adequate blood pressure.6 The administration of a loading dose of loop diuretic is of paramount importance to rapidly achieve therapeutic levels immediately before initiating a continuous infusion. Without a proper loading dose, it can take up to 20 hours to achieve steady state serum levels of diuretic during continuous infusion.5 The ACC and AHA acknowledge this point in their guidelines for chronic heart failure by recommending a bolus dose before initiation of continuous infusion.7 The negative results of the DOSE trial may have been due to lack of a loading dose before infusion initiation.3 Additionally, the total volume loss during continuous infusion compared with bolus dosing might be greater if loading doses were consistently given before starting infusions in published studies. Overall, individual patient response to a diuretic dose is variable and dependent on several factors, including serum albumin level, renal and liver function, and diuretic resistance.5

Teamwork and collaboration are essential to overcome barriers to proper diuretic dosing and provide patients with safe and effective care. Closed loop communication between nurses, physicians, and pharmacists in structured daily interdisciplinary rounds appears to reduce adverse drug events in hospitalized patients.8 The increased mortality9, 10 associated with high doses of diuretic, as well as registry data suggesting that over 50% of patients are discharged with significant heart failure symptoms and minimal weight loss,11 call for a more structured approach toward fluid removal. A team‐based protocol that directs titration of medication, monitors response, and clearly outlines communication channels to adjust doses allows for more efficacious medication administration with lower rates of serious events. This method was used with a dosing algorithm for the administration of opioids for patients with acute pain syndromes.12 Serious or fatal opioid‐related adverse drug events were reduced to zero using this communication‐enhancing approach.12 A similar approach should be used for diuretic dosing in patients who are admitted with ADHF.

We believe frequent follow‐up of diuretic response is critical in the successful treatment of the volume‐overloaded patient. Many clinicians who treat hospitalized patients with ADHF prescribe a fixed daily diuretic dose and evaluate the natriuretic response based on 24‐hour urine output and weight loss. This can lead to unnecessary increases in length of hospital stay. We recommend using a protocol for diuretic administration that includes more frequent assessment and follow‐up of dose response. After a diuretic dose is given, nurses communicate with the physician about the amount of urine output after a prespecified time based on an understanding of the pharmacokinetics of the medication administered. If the urine output is not within the desired range, then the diuretic dose can be increased and immediately administered. If the urine output is above a desired range, doses can be decreased, delayed, or held. With optimal protocol dosing for loop diuretics, continuous infusion may be superfluous. In one study, Peacock et al.13 evaluated a diuretic protocol used to treat patients with ADHF who were admitted to an observation unit. This protocol set 2‐hour urine output goals after loop diuretic bolus doses were administered. If the urine output goals were not met, the diuretic dose was doubled and 2‐hour urine measurements were repeated.13 Limits were set on maximum dosing to ensure patient safety, and electrolytes and renal function were monitored. Using this protocol with other ADHF multidisciplinary interventions, 90‐day heart failure readmission rates decreased by 64% (P = 0.007) with a trend toward decreased 90‐day mortality.13 Although the multidisciplinary approach may have been the major contributor to these outcomes, the diuretic protocol allowed rapid achievement of euvolemia in an observation unit patient population with ADHF. Future investigation needs to specifically evaluate dosing protocols and patient safety because of the association between high doses of diuretics and increased mortality. However, studies showing that high diuretic doses are harmful may simply reflect the fact that patients who require high doses of diuretic have more advanced cardiac or renal disease. In such situations, the clinician needs to be aware of the possibility of decreased cardiac output, hypotension, and intrinsic renal disease as potential barriers to diuresis.

Currently, clinicians have no clear evidence‐based strategies for using diuretics to safely reduce congestion in patients with ADHF. As shown by Amer et al.,2 continuous furosemide infusion may provide more effective weight and volume loss than bolus injections. More rigorous studies comparing effectively dosed diuretics regimens are needed. These studies should optimize diuretic use by accounting for individual patient characteristics and drug pharmacokinetics, using a protocol that monitors response in an appropriate interval, and facilitates care team communication. Ultimately, the mode of diuretic administration is only 1 part of developing a process to remove fluid in patients with ADHF.

Acknowledgements

Disclosure: Nothing to report.

Injectable furosemide was first approved for use by the US Food and Drug Administration in 1968.1 For more than 40 years, loop diuretics have been the mainstay of therapy for relief of congestion and fluid removal in patients admitted with acute decompensated heart failure (ADHF). Despite the widespread use of loop diuretics in clinical practice, robust data supporting their role is scarce. Furthermore, the optimal approach to the management of the patient with acute volume overload has not been well defined.

In this issue of the Journal of Hospital Medicine, Amer et al.2 present a meta‐analysis of randomized controlled trials comparing continuous infusion to bolus doses of furosemide in hospitalized patients with ADHF. The study demonstrates that continuous infusion is superior to bolus in terms of weight loss and urine output over 24 hours. Specifically, patients receiving a continuous infusion of furosemide had 240 mL/day (95% CI, 462.42 to 18.66) more urine and lost an additional 0.78 kg (95% CI, 1.54 to 0.03) in their hospital stay compared with patients receiving a bolus infusion. The heterogeneity in study designs for urine output and wide confidence intervals for urine output and weight loss create uncertainty about the superiority of continuous infusion. The small difference in daily urine output questions the clinical significance of the results. Many of the studies evaluated in the meta‐analysis lacked rigorous design and/or appropriately dosed furosemide.

Despite the shortcomings of the available studies, the authors have published a sound and reasonable meta‐analysis. This is the first meta‐analysis comparing the use of furosemide alone as a continuous infusion versus bolus dose in patients with ADHF. Additionally, Amer et al. are the first to include recent data from the DOSE trial,3 which showed no difference in volume loss between heart failure patients receiving bolus versus continuous infusions dosing of loop diuretics. Although the benefits of continuous infusion in the meta‐analysis by Amer et al. represent only a modest clinical advantage over bolus infusions, the authors should be commended for addressing an important controversy in the management of patients with volume overload.

Although the method of dose delivery is an important issue in the management of such patients, we believe that a number of critical factors must be taken into consideration to assure sufficient fluid removal and quick relief of congestion. Ensuring the delivery of an adequate loop diuretic dose is critical. Additionally, the dose response must be assessed at an appropriate interval so adjustments can be made in a timely manner. Using this method, diuretic dosing can be individualized based on response.

Current guidelines jointly published by the American Heart Association (AHA) and American College of Cardiology (ACC) do not provide clinicians with specific details about the optimal approach to volume‐overloaded patients.4 In a 2009 update, the ACC and AHA recommend diuretic use to optimize volume status and relieve signs and symptoms of congestion without inducing excessively rapid reduction in intravascular volume.4 They further recommend that patients already receiving a loop diuretic who present with volume overload should receive a dose of diuretic equal to or higher than the outpatient dose. Urine output and congestion should be reassessed serially, and diuretics should be titrated accordingly. Current guidelines do not adequately address several topics, including: (1) appropriate urine output in 24 hours, and how frequently urine output should be assessed; (2) optimal frequency of diuretic dosing; and (3) appropriate choice of diuretic.

An understanding of the pharmacokinetics of loop diuretics helps answer these questions. Intravenous furosemide and bumetanide have similar elimination half‐lives of 1 to 2 hours and peak intravenous action at 30 minutes.5, 6 Intravenous torsemide has not been widely available, but has a longer half‐life of 3 to 4 hours, with peak action in 1 to 2 hours.5, 6 The magnitude of a patient's diuretic response compared with the amount of drug administered is best represented by a sigmoid curve.5 Therefore, after a specific dose threshold, further natriuresis is not achieved. Based on the elimination half‐life, proper bolus dosing of furosemide or bumetanide should be every 4 to 8 hours in patients with volume overload and adequate blood pressure.6 The administration of a loading dose of loop diuretic is of paramount importance to rapidly achieve therapeutic levels immediately before initiating a continuous infusion. Without a proper loading dose, it can take up to 20 hours to achieve steady state serum levels of diuretic during continuous infusion.5 The ACC and AHA acknowledge this point in their guidelines for chronic heart failure by recommending a bolus dose before initiation of continuous infusion.7 The negative results of the DOSE trial may have been due to lack of a loading dose before infusion initiation.3 Additionally, the total volume loss during continuous infusion compared with bolus dosing might be greater if loading doses were consistently given before starting infusions in published studies. Overall, individual patient response to a diuretic dose is variable and dependent on several factors, including serum albumin level, renal and liver function, and diuretic resistance.5

Teamwork and collaboration are essential to overcome barriers to proper diuretic dosing and provide patients with safe and effective care. Closed loop communication between nurses, physicians, and pharmacists in structured daily interdisciplinary rounds appears to reduce adverse drug events in hospitalized patients.8 The increased mortality9, 10 associated with high doses of diuretic, as well as registry data suggesting that over 50% of patients are discharged with significant heart failure symptoms and minimal weight loss,11 call for a more structured approach toward fluid removal. A team‐based protocol that directs titration of medication, monitors response, and clearly outlines communication channels to adjust doses allows for more efficacious medication administration with lower rates of serious events. This method was used with a dosing algorithm for the administration of opioids for patients with acute pain syndromes.12 Serious or fatal opioid‐related adverse drug events were reduced to zero using this communication‐enhancing approach.12 A similar approach should be used for diuretic dosing in patients who are admitted with ADHF.

We believe frequent follow‐up of diuretic response is critical in the successful treatment of the volume‐overloaded patient. Many clinicians who treat hospitalized patients with ADHF prescribe a fixed daily diuretic dose and evaluate the natriuretic response based on 24‐hour urine output and weight loss. This can lead to unnecessary increases in length of hospital stay. We recommend using a protocol for diuretic administration that includes more frequent assessment and follow‐up of dose response. After a diuretic dose is given, nurses communicate with the physician about the amount of urine output after a prespecified time based on an understanding of the pharmacokinetics of the medication administered. If the urine output is not within the desired range, then the diuretic dose can be increased and immediately administered. If the urine output is above a desired range, doses can be decreased, delayed, or held. With optimal protocol dosing for loop diuretics, continuous infusion may be superfluous. In one study, Peacock et al.13 evaluated a diuretic protocol used to treat patients with ADHF who were admitted to an observation unit. This protocol set 2‐hour urine output goals after loop diuretic bolus doses were administered. If the urine output goals were not met, the diuretic dose was doubled and 2‐hour urine measurements were repeated.13 Limits were set on maximum dosing to ensure patient safety, and electrolytes and renal function were monitored. Using this protocol with other ADHF multidisciplinary interventions, 90‐day heart failure readmission rates decreased by 64% (P = 0.007) with a trend toward decreased 90‐day mortality.13 Although the multidisciplinary approach may have been the major contributor to these outcomes, the diuretic protocol allowed rapid achievement of euvolemia in an observation unit patient population with ADHF. Future investigation needs to specifically evaluate dosing protocols and patient safety because of the association between high doses of diuretics and increased mortality. However, studies showing that high diuretic doses are harmful may simply reflect the fact that patients who require high doses of diuretic have more advanced cardiac or renal disease. In such situations, the clinician needs to be aware of the possibility of decreased cardiac output, hypotension, and intrinsic renal disease as potential barriers to diuresis.

Currently, clinicians have no clear evidence‐based strategies for using diuretics to safely reduce congestion in patients with ADHF. As shown by Amer et al.,2 continuous furosemide infusion may provide more effective weight and volume loss than bolus injections. More rigorous studies comparing effectively dosed diuretics regimens are needed. These studies should optimize diuretic use by accounting for individual patient characteristics and drug pharmacokinetics, using a protocol that monitors response in an appropriate interval, and facilitates care team communication. Ultimately, the mode of diuretic administration is only 1 part of developing a process to remove fluid in patients with ADHF.

Acknowledgements

Disclosure: Nothing to report.

Injectable furosemide was first approved for use by the US Food and Drug Administration in 1968.1 For more than 40 years, loop diuretics have been the mainstay of therapy for relief of congestion and fluid removal in patients admitted with acute decompensated heart failure (ADHF). Despite the widespread use of loop diuretics in clinical practice, robust data supporting their role is scarce. Furthermore, the optimal approach to the management of the patient with acute volume overload has not been well defined.

In this issue of the Journal of Hospital Medicine, Amer et al.2 present a meta‐analysis of randomized controlled trials comparing continuous infusion to bolus doses of furosemide in hospitalized patients with ADHF. The study demonstrates that continuous infusion is superior to bolus in terms of weight loss and urine output over 24 hours. Specifically, patients receiving a continuous infusion of furosemide had 240 mL/day (95% CI, 462.42 to 18.66) more urine and lost an additional 0.78 kg (95% CI, 1.54 to 0.03) in their hospital stay compared with patients receiving a bolus infusion. The heterogeneity in study designs for urine output and wide confidence intervals for urine output and weight loss create uncertainty about the superiority of continuous infusion. The small difference in daily urine output questions the clinical significance of the results. Many of the studies evaluated in the meta‐analysis lacked rigorous design and/or appropriately dosed furosemide.

Despite the shortcomings of the available studies, the authors have published a sound and reasonable meta‐analysis. This is the first meta‐analysis comparing the use of furosemide alone as a continuous infusion versus bolus dose in patients with ADHF. Additionally, Amer et al. are the first to include recent data from the DOSE trial,3 which showed no difference in volume loss between heart failure patients receiving bolus versus continuous infusions dosing of loop diuretics. Although the benefits of continuous infusion in the meta‐analysis by Amer et al. represent only a modest clinical advantage over bolus infusions, the authors should be commended for addressing an important controversy in the management of patients with volume overload.

Although the method of dose delivery is an important issue in the management of such patients, we believe that a number of critical factors must be taken into consideration to assure sufficient fluid removal and quick relief of congestion. Ensuring the delivery of an adequate loop diuretic dose is critical. Additionally, the dose response must be assessed at an appropriate interval so adjustments can be made in a timely manner. Using this method, diuretic dosing can be individualized based on response.

Current guidelines jointly published by the American Heart Association (AHA) and American College of Cardiology (ACC) do not provide clinicians with specific details about the optimal approach to volume‐overloaded patients.4 In a 2009 update, the ACC and AHA recommend diuretic use to optimize volume status and relieve signs and symptoms of congestion without inducing excessively rapid reduction in intravascular volume.4 They further recommend that patients already receiving a loop diuretic who present with volume overload should receive a dose of diuretic equal to or higher than the outpatient dose. Urine output and congestion should be reassessed serially, and diuretics should be titrated accordingly. Current guidelines do not adequately address several topics, including: (1) appropriate urine output in 24 hours, and how frequently urine output should be assessed; (2) optimal frequency of diuretic dosing; and (3) appropriate choice of diuretic.

An understanding of the pharmacokinetics of loop diuretics helps answer these questions. Intravenous furosemide and bumetanide have similar elimination half‐lives of 1 to 2 hours and peak intravenous action at 30 minutes.5, 6 Intravenous torsemide has not been widely available, but has a longer half‐life of 3 to 4 hours, with peak action in 1 to 2 hours.5, 6 The magnitude of a patient's diuretic response compared with the amount of drug administered is best represented by a sigmoid curve.5 Therefore, after a specific dose threshold, further natriuresis is not achieved. Based on the elimination half‐life, proper bolus dosing of furosemide or bumetanide should be every 4 to 8 hours in patients with volume overload and adequate blood pressure.6 The administration of a loading dose of loop diuretic is of paramount importance to rapidly achieve therapeutic levels immediately before initiating a continuous infusion. Without a proper loading dose, it can take up to 20 hours to achieve steady state serum levels of diuretic during continuous infusion.5 The ACC and AHA acknowledge this point in their guidelines for chronic heart failure by recommending a bolus dose before initiation of continuous infusion.7 The negative results of the DOSE trial may have been due to lack of a loading dose before infusion initiation.3 Additionally, the total volume loss during continuous infusion compared with bolus dosing might be greater if loading doses were consistently given before starting infusions in published studies. Overall, individual patient response to a diuretic dose is variable and dependent on several factors, including serum albumin level, renal and liver function, and diuretic resistance.5

Teamwork and collaboration are essential to overcome barriers to proper diuretic dosing and provide patients with safe and effective care. Closed loop communication between nurses, physicians, and pharmacists in structured daily interdisciplinary rounds appears to reduce adverse drug events in hospitalized patients.8 The increased mortality9, 10 associated with high doses of diuretic, as well as registry data suggesting that over 50% of patients are discharged with significant heart failure symptoms and minimal weight loss,11 call for a more structured approach toward fluid removal. A team‐based protocol that directs titration of medication, monitors response, and clearly outlines communication channels to adjust doses allows for more efficacious medication administration with lower rates of serious events. This method was used with a dosing algorithm for the administration of opioids for patients with acute pain syndromes.12 Serious or fatal opioid‐related adverse drug events were reduced to zero using this communication‐enhancing approach.12 A similar approach should be used for diuretic dosing in patients who are admitted with ADHF.

We believe frequent follow‐up of diuretic response is critical in the successful treatment of the volume‐overloaded patient. Many clinicians who treat hospitalized patients with ADHF prescribe a fixed daily diuretic dose and evaluate the natriuretic response based on 24‐hour urine output and weight loss. This can lead to unnecessary increases in length of hospital stay. We recommend using a protocol for diuretic administration that includes more frequent assessment and follow‐up of dose response. After a diuretic dose is given, nurses communicate with the physician about the amount of urine output after a prespecified time based on an understanding of the pharmacokinetics of the medication administered. If the urine output is not within the desired range, then the diuretic dose can be increased and immediately administered. If the urine output is above a desired range, doses can be decreased, delayed, or held. With optimal protocol dosing for loop diuretics, continuous infusion may be superfluous. In one study, Peacock et al.13 evaluated a diuretic protocol used to treat patients with ADHF who were admitted to an observation unit. This protocol set 2‐hour urine output goals after loop diuretic bolus doses were administered. If the urine output goals were not met, the diuretic dose was doubled and 2‐hour urine measurements were repeated.13 Limits were set on maximum dosing to ensure patient safety, and electrolytes and renal function were monitored. Using this protocol with other ADHF multidisciplinary interventions, 90‐day heart failure readmission rates decreased by 64% (P = 0.007) with a trend toward decreased 90‐day mortality.13 Although the multidisciplinary approach may have been the major contributor to these outcomes, the diuretic protocol allowed rapid achievement of euvolemia in an observation unit patient population with ADHF. Future investigation needs to specifically evaluate dosing protocols and patient safety because of the association between high doses of diuretics and increased mortality. However, studies showing that high diuretic doses are harmful may simply reflect the fact that patients who require high doses of diuretic have more advanced cardiac or renal disease. In such situations, the clinician needs to be aware of the possibility of decreased cardiac output, hypotension, and intrinsic renal disease as potential barriers to diuresis.

Currently, clinicians have no clear evidence‐based strategies for using diuretics to safely reduce congestion in patients with ADHF. As shown by Amer et al.,2 continuous furosemide infusion may provide more effective weight and volume loss than bolus injections. More rigorous studies comparing effectively dosed diuretics regimens are needed. These studies should optimize diuretic use by accounting for individual patient characteristics and drug pharmacokinetics, using a protocol that monitors response in an appropriate interval, and facilitates care team communication. Ultimately, the mode of diuretic administration is only 1 part of developing a process to remove fluid in patients with ADHF.

Acknowledgements

Disclosure: Nothing to report.

SAN DIEGO – Long after the event, hematopoietic stem cell recipients still bear a heavier burden of physical and emotional problems than do their siblings, and greater use of specialized health care, according to investigators at the annual meeting of the American Society of Hematology.

In all, 74% of transplant survivors reported having a chronic health condition at least 10 years on, compared with 39% of age-matched siblings in the Bone Marrow Transplant Survivor Study.

"The difference was especially prominent for severe or life-threatening conditions: 25% of the survivors versus 8% of the siblings reported having a severe, life threatening condition," said Dr. Can-Lan Sun, director of survey research at City of Hope Medical Center in Duarte, Calif., on behalf of coauthors at a press briefing.

"Survivors were five times more likely to report a severe life-threatening condition than siblings," she added.

The cumulative incidence of chronic health conditions over 15 years of follow-up was 71%, and the cumulative incidence of severe, life-threatening events was 40%, the authors found.

"We have many more survivors than we used to, and we’re very thankful for that, but I think it’s important to realize that once a transplant is over, it’s not really over – and that there are some long-term effects either because of the transplant procedure, or because of the chemotherapy that the patient had to get to the transplant," commented Dr. Stephanie J. Lee, professor of medicine at the University of Washington, and a transplant specialist at the Fred Hutchinson Cancer Research Center, both in Seattle.

Dr. Lee moderated the briefing but was not involved in the study.

The authors conducted a retrospective study that surveyed 366 hematopoietic cell transplantation (HCT) survivors of at least 10 years’ duration and compared outcomes of chronic health conditions and psychological health with those of 309 aged-matched siblings. The severe and/or life-threatening conditions they considered included:

• Impaired hearing (loss not corrected by hearing aids).

• Legal blindness.

• Dialysis support.

• Gastrointestinal problems (surgery for intestinal obstruction, rectal or anal strictures, or cirrhosis.

• Cardiovascular disease (coronary artery disease, congestive heart failure, stroke).

• Joint replacement.

• Diabetes.

• Subsequent cancers.

The majority of survivors (65%) had received allogeneic transplants from a relative, 27% had autologous transplants, and 8% received HCT from unrelated donors. In all, 72% of patients had a conditioning regimen with total body irradiation and cyclophosphamide or etoposide, or both.

Indications for transplant were acute myeloid leukemia (28%), chronic myeloid leukemia (17%), acute lymphocytic leukemia (17%), non-Hodgkin’s lymphoma (11%), Hodgkin’s lymphoma (7%), aplastic anemia, or others (10%).

In an analysis adjusted for age at questionnaire, sex, race/ethnicity, education level attained, income and insurance status, they found that the relative risk (RR) for survivors to have any grade 1-4 condition was 2.16. The RR for having a grade 1 or 2 condition was 2.24, and for having a grade 3 or 4 condition was 5.64 (P less than .001 for all comparisons).

In addition, an analysis of adverse psychological outcomes, adjusted for the same factors, showed that survivors had an RR for somatic distress (unexplained physical symptoms such as pain, fatigue, etc.) of 2.73 (P = .03).

"Among survivors, females, those with low income, and those with poor health status were more likely to report somatic distress," Dr. Sun said.

In contrast, there were no significant differences between survivors and siblings in risk for anxiety, depression, or global distress.

Survivors also reported high use of health care services, with 78% reporting receiving a general physical examination within the past 2 years, and nearly two-thirds reporting that they had returned to the cancer center for ongoing care.

"As HCT continues to be a curative option for a variety of hematological malignancies, the burden of long-term physical and emotional morbidity formed by HCT recipients who have survived at least 10 years is substantial," Dr. Sun concluded.

The study was supported by a National Institutes of Health grant and a Leukemia & Lymphoma Society Scholar award to Dr. Sun. Neither she nor Dr. Lee had reported conflicts of interest.

SAN DIEGO – Long after the event, hematopoietic stem cell recipients still bear a heavier burden of physical and emotional problems than do their siblings, and greater use of specialized health care, according to investigators at the annual meeting of the American Society of Hematology.

In all, 74% of transplant survivors reported having a chronic health condition at least 10 years on, compared with 39% of age-matched siblings in the Bone Marrow Transplant Survivor Study.

"The difference was especially prominent for severe or life-threatening conditions: 25% of the survivors versus 8% of the siblings reported having a severe, life threatening condition," said Dr. Can-Lan Sun, director of survey research at City of Hope Medical Center in Duarte, Calif., on behalf of coauthors at a press briefing.

"Survivors were five times more likely to report a severe life-threatening condition than siblings," she added.

The cumulative incidence of chronic health conditions over 15 years of follow-up was 71%, and the cumulative incidence of severe, life-threatening events was 40%, the authors found.

"We have many more survivors than we used to, and we’re very thankful for that, but I think it’s important to realize that once a transplant is over, it’s not really over – and that there are some long-term effects either because of the transplant procedure, or because of the chemotherapy that the patient had to get to the transplant," commented Dr. Stephanie J. Lee, professor of medicine at the University of Washington, and a transplant specialist at the Fred Hutchinson Cancer Research Center, both in Seattle.

Dr. Lee moderated the briefing but was not involved in the study.

The authors conducted a retrospective study that surveyed 366 hematopoietic cell transplantation (HCT) survivors of at least 10 years’ duration and compared outcomes of chronic health conditions and psychological health with those of 309 aged-matched siblings. The severe and/or life-threatening conditions they considered included:

• Impaired hearing (loss not corrected by hearing aids).

• Legal blindness.

• Dialysis support.

• Gastrointestinal problems (surgery for intestinal obstruction, rectal or anal strictures, or cirrhosis.

• Cardiovascular disease (coronary artery disease, congestive heart failure, stroke).

• Joint replacement.

• Diabetes.

• Subsequent cancers.

The majority of survivors (65%) had received allogeneic transplants from a relative, 27% had autologous transplants, and 8% received HCT from unrelated donors. In all, 72% of patients had a conditioning regimen with total body irradiation and cyclophosphamide or etoposide, or both.

Indications for transplant were acute myeloid leukemia (28%), chronic myeloid leukemia (17%), acute lymphocytic leukemia (17%), non-Hodgkin’s lymphoma (11%), Hodgkin’s lymphoma (7%), aplastic anemia, or others (10%).

In an analysis adjusted for age at questionnaire, sex, race/ethnicity, education level attained, income and insurance status, they found that the relative risk (RR) for survivors to have any grade 1-4 condition was 2.16. The RR for having a grade 1 or 2 condition was 2.24, and for having a grade 3 or 4 condition was 5.64 (P less than .001 for all comparisons).

In addition, an analysis of adverse psychological outcomes, adjusted for the same factors, showed that survivors had an RR for somatic distress (unexplained physical symptoms such as pain, fatigue, etc.) of 2.73 (P = .03).

"Among survivors, females, those with low income, and those with poor health status were more likely to report somatic distress," Dr. Sun said.

In contrast, there were no significant differences between survivors and siblings in risk for anxiety, depression, or global distress.

Survivors also reported high use of health care services, with 78% reporting receiving a general physical examination within the past 2 years, and nearly two-thirds reporting that they had returned to the cancer center for ongoing care.

"As HCT continues to be a curative option for a variety of hematological malignancies, the burden of long-term physical and emotional morbidity formed by HCT recipients who have survived at least 10 years is substantial," Dr. Sun concluded.

The study was supported by a National Institutes of Health grant and a Leukemia & Lymphoma Society Scholar award to Dr. Sun. Neither she nor Dr. Lee had reported conflicts of interest.

SAN DIEGO – Long after the event, hematopoietic stem cell recipients still bear a heavier burden of physical and emotional problems than do their siblings, and greater use of specialized health care, according to investigators at the annual meeting of the American Society of Hematology.

In all, 74% of transplant survivors reported having a chronic health condition at least 10 years on, compared with 39% of age-matched siblings in the Bone Marrow Transplant Survivor Study.

"The difference was especially prominent for severe or life-threatening conditions: 25% of the survivors versus 8% of the siblings reported having a severe, life threatening condition," said Dr. Can-Lan Sun, director of survey research at City of Hope Medical Center in Duarte, Calif., on behalf of coauthors at a press briefing.

"Survivors were five times more likely to report a severe life-threatening condition than siblings," she added.

The cumulative incidence of chronic health conditions over 15 years of follow-up was 71%, and the cumulative incidence of severe, life-threatening events was 40%, the authors found.

"We have many more survivors than we used to, and we’re very thankful for that, but I think it’s important to realize that once a transplant is over, it’s not really over – and that there are some long-term effects either because of the transplant procedure, or because of the chemotherapy that the patient had to get to the transplant," commented Dr. Stephanie J. Lee, professor of medicine at the University of Washington, and a transplant specialist at the Fred Hutchinson Cancer Research Center, both in Seattle.

Dr. Lee moderated the briefing but was not involved in the study.

The authors conducted a retrospective study that surveyed 366 hematopoietic cell transplantation (HCT) survivors of at least 10 years’ duration and compared outcomes of chronic health conditions and psychological health with those of 309 aged-matched siblings. The severe and/or life-threatening conditions they considered included:

• Impaired hearing (loss not corrected by hearing aids).

• Legal blindness.

• Dialysis support.

• Gastrointestinal problems (surgery for intestinal obstruction, rectal or anal strictures, or cirrhosis.

• Cardiovascular disease (coronary artery disease, congestive heart failure, stroke).

• Joint replacement.

• Diabetes.

• Subsequent cancers.

The majority of survivors (65%) had received allogeneic transplants from a relative, 27% had autologous transplants, and 8% received HCT from unrelated donors. In all, 72% of patients had a conditioning regimen with total body irradiation and cyclophosphamide or etoposide, or both.

Indications for transplant were acute myeloid leukemia (28%), chronic myeloid leukemia (17%), acute lymphocytic leukemia (17%), non-Hodgkin’s lymphoma (11%), Hodgkin’s lymphoma (7%), aplastic anemia, or others (10%).

In an analysis adjusted for age at questionnaire, sex, race/ethnicity, education level attained, income and insurance status, they found that the relative risk (RR) for survivors to have any grade 1-4 condition was 2.16. The RR for having a grade 1 or 2 condition was 2.24, and for having a grade 3 or 4 condition was 5.64 (P less than .001 for all comparisons).

In addition, an analysis of adverse psychological outcomes, adjusted for the same factors, showed that survivors had an RR for somatic distress (unexplained physical symptoms such as pain, fatigue, etc.) of 2.73 (P = .03).

"Among survivors, females, those with low income, and those with poor health status were more likely to report somatic distress," Dr. Sun said.

In contrast, there were no significant differences between survivors and siblings in risk for anxiety, depression, or global distress.

Survivors also reported high use of health care services, with 78% reporting receiving a general physical examination within the past 2 years, and nearly two-thirds reporting that they had returned to the cancer center for ongoing care.

"As HCT continues to be a curative option for a variety of hematological malignancies, the burden of long-term physical and emotional morbidity formed by HCT recipients who have survived at least 10 years is substantial," Dr. Sun concluded.

The study was supported by a National Institutes of Health grant and a Leukemia & Lymphoma Society Scholar award to Dr. Sun. Neither she nor Dr. Lee had reported conflicts of interest.

SAN DIEGO – Filgrastim-mobilized peripheral blood stem cells convey no survival advantage over bone marrow transplants when the donor is not an HLA-identical sibling of the recipient, investigators have reported.

Two-year overall survival among 273 patients randomized to receive filgrastim (Neupogen)-mobilized peripheral blood stem cells (PBSC) from an unrelated donor was 51% in an intention-to-treat analysis, compared with 46% of 278 patients randomized to bone-marrow transplants (BMT), also from an unrelated donor (P=.288).

Moreover, filgrastim/PBSC was associated with an increased incidence of chronic extensive graft-versus host disease (GVHD) of 48%, compared with 32% for BMT (P less than .001). The incidence of acute GVHD did not differ between treatment types, Dr. Claudio Anasetti reported at the annual meeting of the American Society of Hematology.

PBSC was significantly better at engraftment, however, with only 7 patients (2.7%) experiencing either primary or secondary graft failure, compared with 24 (9.1%) of those who received BMT (P=.002).

Currently, around 75% of unrelated adult donor transplants use PBSC.

There are still some patients who might benefit from PBSC, he said, including those who are at increased risk for graft rejection. The incidence of rejection-related deaths was 8% among patients on BMT vs. 0% of patients on PBSC (P=.002). Patients at risk for rejection who do not receive pre-transplant immunosuppression, such as those with the myelodysplastic syndrome, may benefit more from PBSC, said Dr. Anasetti of the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Fla.

Similarly, heavily pre-treated patients with systemic infections who require rapid reconstitution with blood cells also may benefit from PBSC over bone marrow, he said.

Previous randomized trials in HLA-identical siblings demonstrated that filgrastim-mobilized PBSC compared to BMT improved engraftment kinetics, increased risks of acute and chronic GVHD, but also decreased relapse and improved survival in patients with high risk leukemia. Dr. Anasetti and his associates performed the current study to compare outcomes of PBSC and marrow transplants from unrelated donors.

A physician who performs stem-cell transplants but was not involved in the study said that the findings run contrary to what she and many of her colleagues had expected.

The investigators enrolled patients with acute myeloid leukemia (AML), chronic myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndrome, chronic myelomonocytic leukemia, and mycosis fungoides from 50 centers in the United States and Canada. The patients were randomized on a 1:1 ratio to either PBSC or BMT and stratified by transplant center and disease risk.

A total of 5% of the 278 patients randomized to BMT did not receive a transplant, and 4.3% crossed over to PBSC. Of 273 assigned to PBSC, 4.3% were not transplanted, and 0.4% crossed over to BMT.

The majority of patients (90%) were adults age 21 or older, 47% had AML, 28% had high-risk disease, 48% underwent pre-transplant conditioning with cyclophosphamide plus total body irradiation, and 71% received tacrolimus (Prograf) plus methotrexate for GVHD prophylaxis.

Over 36-months median follow-up, there were no significant differences in either overall non-relapse deaths or in relapse rates, each of which occurred in about 30% of patients. Significantly more patients who received PBSC died from chronic GVHD: 21% compared with 10% of those who had received BMT (P=.002).

Patients on PBSC had better neutrophil engraftment at 5 days (P less than .001) and platelet engraftment at 7 days (P less than .001) than those who received BMT, however.

At 2-year follow-up, 57 of those who had received bone marrow were off of immunosuppressive therapy, compared with 37% of those who had received PBSC (P=.026).

Preplanned subset analyses showed no interactions between treatment arms in either disease risk, donor HLA matching, or patient age.

Future clinical research needs to focus on transplant approaches that can offset specific risks, such as prevention of graft failure with BMT, and prevention of acute and chronic GVHD with either source, Dr. Anasetti said.

The trial was funded by the National Heart, Lung and Blood Institute and National Cancer Institute. Dr. Anasetti disclosed off-label use of cyclophosphamide, busulfan, melphalan, fludarabine, anti-thymocyte globulin, and irradiation to eradicate malignancy, and tacrolimus, cyclosporine, methotrexate for GVHD prophylaxis. Co-author Daniel J. Weisdorf disclosed consulting for and receiving research funding from Genzyme. Co-author Peter Westervelt disclosed serving on a speakers bureau for Novartis.

SAN DIEGO – Filgrastim-mobilized peripheral blood stem cells convey no survival advantage over bone marrow transplants when the donor is not an HLA-identical sibling of the recipient, investigators have reported.

Two-year overall survival among 273 patients randomized to receive filgrastim (Neupogen)-mobilized peripheral blood stem cells (PBSC) from an unrelated donor was 51% in an intention-to-treat analysis, compared with 46% of 278 patients randomized to bone-marrow transplants (BMT), also from an unrelated donor (P=.288).

Moreover, filgrastim/PBSC was associated with an increased incidence of chronic extensive graft-versus host disease (GVHD) of 48%, compared with 32% for BMT (P less than .001). The incidence of acute GVHD did not differ between treatment types, Dr. Claudio Anasetti reported at the annual meeting of the American Society of Hematology.

PBSC was significantly better at engraftment, however, with only 7 patients (2.7%) experiencing either primary or secondary graft failure, compared with 24 (9.1%) of those who received BMT (P=.002).

Currently, around 75% of unrelated adult donor transplants use PBSC.

There are still some patients who might benefit from PBSC, he said, including those who are at increased risk for graft rejection. The incidence of rejection-related deaths was 8% among patients on BMT vs. 0% of patients on PBSC (P=.002). Patients at risk for rejection who do not receive pre-transplant immunosuppression, such as those with the myelodysplastic syndrome, may benefit more from PBSC, said Dr. Anasetti of the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Fla.

Similarly, heavily pre-treated patients with systemic infections who require rapid reconstitution with blood cells also may benefit from PBSC over bone marrow, he said.

Previous randomized trials in HLA-identical siblings demonstrated that filgrastim-mobilized PBSC compared to BMT improved engraftment kinetics, increased risks of acute and chronic GVHD, but also decreased relapse and improved survival in patients with high risk leukemia. Dr. Anasetti and his associates performed the current study to compare outcomes of PBSC and marrow transplants from unrelated donors.

A physician who performs stem-cell transplants but was not involved in the study said that the findings run contrary to what she and many of her colleagues had expected.

The investigators enrolled patients with acute myeloid leukemia (AML), chronic myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndrome, chronic myelomonocytic leukemia, and mycosis fungoides from 50 centers in the United States and Canada. The patients were randomized on a 1:1 ratio to either PBSC or BMT and stratified by transplant center and disease risk.

A total of 5% of the 278 patients randomized to BMT did not receive a transplant, and 4.3% crossed over to PBSC. Of 273 assigned to PBSC, 4.3% were not transplanted, and 0.4% crossed over to BMT.

The majority of patients (90%) were adults age 21 or older, 47% had AML, 28% had high-risk disease, 48% underwent pre-transplant conditioning with cyclophosphamide plus total body irradiation, and 71% received tacrolimus (Prograf) plus methotrexate for GVHD prophylaxis.

Over 36-months median follow-up, there were no significant differences in either overall non-relapse deaths or in relapse rates, each of which occurred in about 30% of patients. Significantly more patients who received PBSC died from chronic GVHD: 21% compared with 10% of those who had received BMT (P=.002).

Patients on PBSC had better neutrophil engraftment at 5 days (P less than .001) and platelet engraftment at 7 days (P less than .001) than those who received BMT, however.

At 2-year follow-up, 57 of those who had received bone marrow were off of immunosuppressive therapy, compared with 37% of those who had received PBSC (P=.026).

Preplanned subset analyses showed no interactions between treatment arms in either disease risk, donor HLA matching, or patient age.

Future clinical research needs to focus on transplant approaches that can offset specific risks, such as prevention of graft failure with BMT, and prevention of acute and chronic GVHD with either source, Dr. Anasetti said.

The trial was funded by the National Heart, Lung and Blood Institute and National Cancer Institute. Dr. Anasetti disclosed off-label use of cyclophosphamide, busulfan, melphalan, fludarabine, anti-thymocyte globulin, and irradiation to eradicate malignancy, and tacrolimus, cyclosporine, methotrexate for GVHD prophylaxis. Co-author Daniel J. Weisdorf disclosed consulting for and receiving research funding from Genzyme. Co-author Peter Westervelt disclosed serving on a speakers bureau for Novartis.

SAN DIEGO – Filgrastim-mobilized peripheral blood stem cells convey no survival advantage over bone marrow transplants when the donor is not an HLA-identical sibling of the recipient, investigators have reported.

Two-year overall survival among 273 patients randomized to receive filgrastim (Neupogen)-mobilized peripheral blood stem cells (PBSC) from an unrelated donor was 51% in an intention-to-treat analysis, compared with 46% of 278 patients randomized to bone-marrow transplants (BMT), also from an unrelated donor (P=.288).

Moreover, filgrastim/PBSC was associated with an increased incidence of chronic extensive graft-versus host disease (GVHD) of 48%, compared with 32% for BMT (P less than .001). The incidence of acute GVHD did not differ between treatment types, Dr. Claudio Anasetti reported at the annual meeting of the American Society of Hematology.

PBSC was significantly better at engraftment, however, with only 7 patients (2.7%) experiencing either primary or secondary graft failure, compared with 24 (9.1%) of those who received BMT (P=.002).

Currently, around 75% of unrelated adult donor transplants use PBSC.

There are still some patients who might benefit from PBSC, he said, including those who are at increased risk for graft rejection. The incidence of rejection-related deaths was 8% among patients on BMT vs. 0% of patients on PBSC (P=.002). Patients at risk for rejection who do not receive pre-transplant immunosuppression, such as those with the myelodysplastic syndrome, may benefit more from PBSC, said Dr. Anasetti of the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Fla.

Similarly, heavily pre-treated patients with systemic infections who require rapid reconstitution with blood cells also may benefit from PBSC over bone marrow, he said.

Previous randomized trials in HLA-identical siblings demonstrated that filgrastim-mobilized PBSC compared to BMT improved engraftment kinetics, increased risks of acute and chronic GVHD, but also decreased relapse and improved survival in patients with high risk leukemia. Dr. Anasetti and his associates performed the current study to compare outcomes of PBSC and marrow transplants from unrelated donors.

A physician who performs stem-cell transplants but was not involved in the study said that the findings run contrary to what she and many of her colleagues had expected.

The investigators enrolled patients with acute myeloid leukemia (AML), chronic myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndrome, chronic myelomonocytic leukemia, and mycosis fungoides from 50 centers in the United States and Canada. The patients were randomized on a 1:1 ratio to either PBSC or BMT and stratified by transplant center and disease risk.

A total of 5% of the 278 patients randomized to BMT did not receive a transplant, and 4.3% crossed over to PBSC. Of 273 assigned to PBSC, 4.3% were not transplanted, and 0.4% crossed over to BMT.

The majority of patients (90%) were adults age 21 or older, 47% had AML, 28% had high-risk disease, 48% underwent pre-transplant conditioning with cyclophosphamide plus total body irradiation, and 71% received tacrolimus (Prograf) plus methotrexate for GVHD prophylaxis.

Over 36-months median follow-up, there were no significant differences in either overall non-relapse deaths or in relapse rates, each of which occurred in about 30% of patients. Significantly more patients who received PBSC died from chronic GVHD: 21% compared with 10% of those who had received BMT (P=.002).

Patients on PBSC had better neutrophil engraftment at 5 days (P less than .001) and platelet engraftment at 7 days (P less than .001) than those who received BMT, however.

At 2-year follow-up, 57 of those who had received bone marrow were off of immunosuppressive therapy, compared with 37% of those who had received PBSC (P=.026).

Preplanned subset analyses showed no interactions between treatment arms in either disease risk, donor HLA matching, or patient age.

Future clinical research needs to focus on transplant approaches that can offset specific risks, such as prevention of graft failure with BMT, and prevention of acute and chronic GVHD with either source, Dr. Anasetti said.

The trial was funded by the National Heart, Lung and Blood Institute and National Cancer Institute. Dr. Anasetti disclosed off-label use of cyclophosphamide, busulfan, melphalan, fludarabine, anti-thymocyte globulin, and irradiation to eradicate malignancy, and tacrolimus, cyclosporine, methotrexate for GVHD prophylaxis. Co-author Daniel J. Weisdorf disclosed consulting for and receiving research funding from Genzyme. Co-author Peter Westervelt disclosed serving on a speakers bureau for Novartis.

ORLANDO – Although higher systolic blood pressure and LDL cholesterol are traditional risk factors for cardiovascular disease, each may have a different effect on the cerebrovascular and coronary systems.

Pooled analysis of three landmark studies done on the cholesterol-lowering agent atorvastatin in high-risk patients showed that higher baseline systolic blood pressure is predictive of a significantly higher risk of stroke. Meanwhile, higher baseline LDL cholesterol is predictive of a significantly higher risk of coronary events, the analysis showed.

The findings have implications on both research design and clinical practice, Dr. Prakash C. Deedwania, the study’s lead author, said at the annual scientific sessions of the American Heart Association.

Patients who might be at risk of both stroke and coronary events should be treated aggressively to reduce systolic blood pressure and LDL cholesterol, he said.

Dr. Deedwania and his colleagues pooled data on 21,727 patients from three trials: Treating to New Targets (TNT), which compared 10 mg with 80 mg atorvastatin in patients with stable coronary heart disease and LDL levels below 130 mg/dL (N. Engl. J. Med. 2005;352:1425-35), Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL), which compared high-dose (80 mg) atorvastatin with normal-dose (20-40 mg) simvastatin in post-MI patients (JAMA 2005;294:2437-45), and the Collaborative Atorvastatin Diabetes Study (CARDS), which compared 20 mg atorvastatin with placebo in patients with type 2 diabetes and without established coronary heart disease (Lancet 2004;364:685-96).

Results showed that with each 10-mm Hg increase in baseline systolic blood pressure, the risk of a fatal or nonfatal stroke increased by 16%. Meanwhile, each 10-mg/dL increase in baseline LDL cholesterol increased the risk of coronary events by 5%. Both differences were significantly different.

Dr. Deedwania said that the reduction in LDL cholesterol has been associated with a decrease in the risk of stroke, "but perhaps by a different mechanism."

The authors also looked at a subgroup of patients with type 2 diabetes (5,408 patients from the three trials), and found results consistent with the larger cohort.

Although systolic blood pressure is known to be a powerful predictor of stroke, many clinicians may not be aware that LDL cholesterol is not associated with an increased risk of stroke, said Dr. Deedwania. "What predicts baseline risk is different than what happens in treatment, so there are yet many lessons to be learned from these trials."

Dr. Deedwania has received research grants from Pfizer. He has been a consultant to and on the advisory boards of Pfizer and Novartis.

ORLANDO – Although higher systolic blood pressure and LDL cholesterol are traditional risk factors for cardiovascular disease, each may have a different effect on the cerebrovascular and coronary systems.

Pooled analysis of three landmark studies done on the cholesterol-lowering agent atorvastatin in high-risk patients showed that higher baseline systolic blood pressure is predictive of a significantly higher risk of stroke. Meanwhile, higher baseline LDL cholesterol is predictive of a significantly higher risk of coronary events, the analysis showed.

The findings have implications on both research design and clinical practice, Dr. Prakash C. Deedwania, the study’s lead author, said at the annual scientific sessions of the American Heart Association.

Patients who might be at risk of both stroke and coronary events should be treated aggressively to reduce systolic blood pressure and LDL cholesterol, he said.

Dr. Deedwania and his colleagues pooled data on 21,727 patients from three trials: Treating to New Targets (TNT), which compared 10 mg with 80 mg atorvastatin in patients with stable coronary heart disease and LDL levels below 130 mg/dL (N. Engl. J. Med. 2005;352:1425-35), Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL), which compared high-dose (80 mg) atorvastatin with normal-dose (20-40 mg) simvastatin in post-MI patients (JAMA 2005;294:2437-45), and the Collaborative Atorvastatin Diabetes Study (CARDS), which compared 20 mg atorvastatin with placebo in patients with type 2 diabetes and without established coronary heart disease (Lancet 2004;364:685-96).

Results showed that with each 10-mm Hg increase in baseline systolic blood pressure, the risk of a fatal or nonfatal stroke increased by 16%. Meanwhile, each 10-mg/dL increase in baseline LDL cholesterol increased the risk of coronary events by 5%. Both differences were significantly different.

Dr. Deedwania said that the reduction in LDL cholesterol has been associated with a decrease in the risk of stroke, "but perhaps by a different mechanism."

The authors also looked at a subgroup of patients with type 2 diabetes (5,408 patients from the three trials), and found results consistent with the larger cohort.

Although systolic blood pressure is known to be a powerful predictor of stroke, many clinicians may not be aware that LDL cholesterol is not associated with an increased risk of stroke, said Dr. Deedwania. "What predicts baseline risk is different than what happens in treatment, so there are yet many lessons to be learned from these trials."

Dr. Deedwania has received research grants from Pfizer. He has been a consultant to and on the advisory boards of Pfizer and Novartis.

ORLANDO – Although higher systolic blood pressure and LDL cholesterol are traditional risk factors for cardiovascular disease, each may have a different effect on the cerebrovascular and coronary systems.

Pooled analysis of three landmark studies done on the cholesterol-lowering agent atorvastatin in high-risk patients showed that higher baseline systolic blood pressure is predictive of a significantly higher risk of stroke. Meanwhile, higher baseline LDL cholesterol is predictive of a significantly higher risk of coronary events, the analysis showed.

The findings have implications on both research design and clinical practice, Dr. Prakash C. Deedwania, the study’s lead author, said at the annual scientific sessions of the American Heart Association.

Patients who might be at risk of both stroke and coronary events should be treated aggressively to reduce systolic blood pressure and LDL cholesterol, he said.

Dr. Deedwania and his colleagues pooled data on 21,727 patients from three trials: Treating to New Targets (TNT), which compared 10 mg with 80 mg atorvastatin in patients with stable coronary heart disease and LDL levels below 130 mg/dL (N. Engl. J. Med. 2005;352:1425-35), Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL), which compared high-dose (80 mg) atorvastatin with normal-dose (20-40 mg) simvastatin in post-MI patients (JAMA 2005;294:2437-45), and the Collaborative Atorvastatin Diabetes Study (CARDS), which compared 20 mg atorvastatin with placebo in patients with type 2 diabetes and without established coronary heart disease (Lancet 2004;364:685-96).

Results showed that with each 10-mm Hg increase in baseline systolic blood pressure, the risk of a fatal or nonfatal stroke increased by 16%. Meanwhile, each 10-mg/dL increase in baseline LDL cholesterol increased the risk of coronary events by 5%. Both differences were significantly different.

Dr. Deedwania said that the reduction in LDL cholesterol has been associated with a decrease in the risk of stroke, "but perhaps by a different mechanism."

The authors also looked at a subgroup of patients with type 2 diabetes (5,408 patients from the three trials), and found results consistent with the larger cohort.

Although systolic blood pressure is known to be a powerful predictor of stroke, many clinicians may not be aware that LDL cholesterol is not associated with an increased risk of stroke, said Dr. Deedwania. "What predicts baseline risk is different than what happens in treatment, so there are yet many lessons to be learned from these trials."

Dr. Deedwania has received research grants from Pfizer. He has been a consultant to and on the advisory boards of Pfizer and Novartis.

Begin by thinking about this diagnosis. If you don’t consider immunodeficiency during your routine evaluations, you are likely to miss one of these relatively rare conditions. Screening is of the utmost importance with more than 175 pediatric primary immunodeficiencies identified.

Considering immunodeficiencies appropriately is important – they represent sharp needles in the pediatrician’s haystack. You might be thinking: How am I going to recognize these important needles in my busy practice? My advice is to look for the hallmarks – infections that are recurrent, severe, or unusual.

Courtesy Children's Hospital of Philadelphia

I use a Statue of Liberty analogy. Give me your five sickest kids – the ones who hound your triage nurse, the ones who always page you after hours – and then think about immunodeficiency as a possible diagnosis. A child with recurrent infections who requires and responds to antibiotics frequently is a likely candidate.

Upper and lower respiratory tract infections are common in this patient population. About half of children with an immunodeficiency will have antibodies and will most typically present with involvement of the sinuses and/or the ears, including in some cases, bronchitis or pneumonia.

Severe combined immunodeficiency syndrome (SCIDS) is particularly alarming. If you practice in one of the states that require newborn screening for this condition – California, Louisiana, Massachusetts, New York, or Wisconsin – you are likely to receive a call at some point from your state laboratory. The number of calls you get alerting you to a positive result will vary by the size of your practice: SCIDS affects about 1 in 50,000 live births. There was a case in Wisconsin where a baby with SCIDS was identified quickly and cured (J. Allergy Clin. Immunol. 2011;127:535-38).

A newborn with SCIDS lacks the capacity to make functional T cells, and there is a movement to expand this screening to all 50 states.

As with any confirmed immunodeficiency, working in concert with an immunologist becomes essential. Expertise is important because there are therapeutic options for almost every patient with a primary immunodeficiency diagnosis. A subspecialist can help you devise an effective management plan. It is a matter of pediatricians feeling empowered, not feeling that children with primary immunodeficiencies are too complex to manage.

I am fine with a pediatrician calling for a direct referral. It is appropriate not to manage the diagnostic evaluation of these children if you feel uncomfortable. With that said, there are opportunities for pediatricians to manage these patients as well. I know some pediatricians are as adept at this as I am.

For example, you can screen a child with a suspected immunodeficiency for the presence of antibodies. Keep quantity and quality in mind. Quantity is a check of how full the tank is; for example, assess their levels of IgG, IgM, and IgA.

Quality assessment can be more challenging, but there are appropriate, point-of-contact screenings you can perform without too much effort. Most importantly these would include checking the antibody titers against vaccines you have provided, such as a tetanus titer or pneumococcal titers.

A complete blood count with differential, for example, provides important information, including the percentage and number of lymphocytes and neutrophils. If the absolute levels are low, then it becomes relevant to think: Why? Viral suppression is a true cause, but it’s overrated, so be sure to reevaluate a low count and remember to consider immunodeficiency if a low value persists.

If you suspect immunodeficiency in a baby, for example, check the infant’s lymphocyte count against the age-specific normal value. This varies, but the lower limit for normal for a healthy child under 1 year of age is about 3,500/mcL.

This might surprise you, but a child with low or no lymphocytes can quickly require emergency medical attention.

Other tests are more in the domain of the specialist or more appropriate in specific situations. In addition, the assay order forms and specialty laboratories can be tricky. Right next to IgG, for example, the IgG subclasses are often listed. These subclass evaluations are expensive and of little value in routine clinical assessment.

The bottom line is: Think about primary immunodeficiency. If you are uncomfortable in carrying forward a diagnostic evaluation – call an immunologist. We are happy to help. Statistically speaking, the needle is in your haystack. A pediatric practice looking after 10,000 children should be following 5 with primary immunodeficiency. Do you know who yours are?

This column, "Subspecialist Consult," appears regularly in Pediatric News, an Elsevier publication. Dr. Orange is a pediatric immunologist in the division of allergy and immunology at Children’s Hospital of Philadelphia. He disclosed that he is a medical adviser to the Immunodeficiency Foundation and a consultant to three manufacturers of immunoglobulin therapies: Baxter Healthcare, Talecris Biotherapeutics, and CSL Behring. He also receives research grants from Octapharma USA.

Begin by thinking about this diagnosis. If you don’t consider immunodeficiency during your routine evaluations, you are likely to miss one of these relatively rare conditions. Screening is of the utmost importance with more than 175 pediatric primary immunodeficiencies identified.

Considering immunodeficiencies appropriately is important – they represent sharp needles in the pediatrician’s haystack. You might be thinking: How am I going to recognize these important needles in my busy practice? My advice is to look for the hallmarks – infections that are recurrent, severe, or unusual.

Courtesy Children's Hospital of Philadelphia

I use a Statue of Liberty analogy. Give me your five sickest kids – the ones who hound your triage nurse, the ones who always page you after hours – and then think about immunodeficiency as a possible diagnosis. A child with recurrent infections who requires and responds to antibiotics frequently is a likely candidate.

Upper and lower respiratory tract infections are common in this patient population. About half of children with an immunodeficiency will have antibodies and will most typically present with involvement of the sinuses and/or the ears, including in some cases, bronchitis or pneumonia.

Severe combined immunodeficiency syndrome (SCIDS) is particularly alarming. If you practice in one of the states that require newborn screening for this condition – California, Louisiana, Massachusetts, New York, or Wisconsin – you are likely to receive a call at some point from your state laboratory. The number of calls you get alerting you to a positive result will vary by the size of your practice: SCIDS affects about 1 in 50,000 live births. There was a case in Wisconsin where a baby with SCIDS was identified quickly and cured (J. Allergy Clin. Immunol. 2011;127:535-38).

A newborn with SCIDS lacks the capacity to make functional T cells, and there is a movement to expand this screening to all 50 states.

As with any confirmed immunodeficiency, working in concert with an immunologist becomes essential. Expertise is important because there are therapeutic options for almost every patient with a primary immunodeficiency diagnosis. A subspecialist can help you devise an effective management plan. It is a matter of pediatricians feeling empowered, not feeling that children with primary immunodeficiencies are too complex to manage.

I am fine with a pediatrician calling for a direct referral. It is appropriate not to manage the diagnostic evaluation of these children if you feel uncomfortable. With that said, there are opportunities for pediatricians to manage these patients as well. I know some pediatricians are as adept at this as I am.

For example, you can screen a child with a suspected immunodeficiency for the presence of antibodies. Keep quantity and quality in mind. Quantity is a check of how full the tank is; for example, assess their levels of IgG, IgM, and IgA.

Quality assessment can be more challenging, but there are appropriate, point-of-contact screenings you can perform without too much effort. Most importantly these would include checking the antibody titers against vaccines you have provided, such as a tetanus titer or pneumococcal titers.

A complete blood count with differential, for example, provides important information, including the percentage and number of lymphocytes and neutrophils. If the absolute levels are low, then it becomes relevant to think: Why? Viral suppression is a true cause, but it’s overrated, so be sure to reevaluate a low count and remember to consider immunodeficiency if a low value persists.

If you suspect immunodeficiency in a baby, for example, check the infant’s lymphocyte count against the age-specific normal value. This varies, but the lower limit for normal for a healthy child under 1 year of age is about 3,500/mcL.

This might surprise you, but a child with low or no lymphocytes can quickly require emergency medical attention.

Other tests are more in the domain of the specialist or more appropriate in specific situations. In addition, the assay order forms and specialty laboratories can be tricky. Right next to IgG, for example, the IgG subclasses are often listed. These subclass evaluations are expensive and of little value in routine clinical assessment.

The bottom line is: Think about primary immunodeficiency. If you are uncomfortable in carrying forward a diagnostic evaluation – call an immunologist. We are happy to help. Statistically speaking, the needle is in your haystack. A pediatric practice looking after 10,000 children should be following 5 with primary immunodeficiency. Do you know who yours are?

This column, "Subspecialist Consult," appears regularly in Pediatric News, an Elsevier publication. Dr. Orange is a pediatric immunologist in the division of allergy and immunology at Children’s Hospital of Philadelphia. He disclosed that he is a medical adviser to the Immunodeficiency Foundation and a consultant to three manufacturers of immunoglobulin therapies: Baxter Healthcare, Talecris Biotherapeutics, and CSL Behring. He also receives research grants from Octapharma USA.

Begin by thinking about this diagnosis. If you don’t consider immunodeficiency during your routine evaluations, you are likely to miss one of these relatively rare conditions. Screening is of the utmost importance with more than 175 pediatric primary immunodeficiencies identified.

Considering immunodeficiencies appropriately is important – they represent sharp needles in the pediatrician’s haystack. You might be thinking: How am I going to recognize these important needles in my busy practice? My advice is to look for the hallmarks – infections that are recurrent, severe, or unusual.

Courtesy Children's Hospital of Philadelphia

I use a Statue of Liberty analogy. Give me your five sickest kids – the ones who hound your triage nurse, the ones who always page you after hours – and then think about immunodeficiency as a possible diagnosis. A child with recurrent infections who requires and responds to antibiotics frequently is a likely candidate.

Upper and lower respiratory tract infections are common in this patient population. About half of children with an immunodeficiency will have antibodies and will most typically present with involvement of the sinuses and/or the ears, including in some cases, bronchitis or pneumonia.

Severe combined immunodeficiency syndrome (SCIDS) is particularly alarming. If you practice in one of the states that require newborn screening for this condition – California, Louisiana, Massachusetts, New York, or Wisconsin – you are likely to receive a call at some point from your state laboratory. The number of calls you get alerting you to a positive result will vary by the size of your practice: SCIDS affects about 1 in 50,000 live births. There was a case in Wisconsin where a baby with SCIDS was identified quickly and cured (J. Allergy Clin. Immunol. 2011;127:535-38).

A newborn with SCIDS lacks the capacity to make functional T cells, and there is a movement to expand this screening to all 50 states.

As with any confirmed immunodeficiency, working in concert with an immunologist becomes essential. Expertise is important because there are therapeutic options for almost every patient with a primary immunodeficiency diagnosis. A subspecialist can help you devise an effective management plan. It is a matter of pediatricians feeling empowered, not feeling that children with primary immunodeficiencies are too complex to manage.

I am fine with a pediatrician calling for a direct referral. It is appropriate not to manage the diagnostic evaluation of these children if you feel uncomfortable. With that said, there are opportunities for pediatricians to manage these patients as well. I know some pediatricians are as adept at this as I am.

For example, you can screen a child with a suspected immunodeficiency for the presence of antibodies. Keep quantity and quality in mind. Quantity is a check of how full the tank is; for example, assess their levels of IgG, IgM, and IgA.

Quality assessment can be more challenging, but there are appropriate, point-of-contact screenings you can perform without too much effort. Most importantly these would include checking the antibody titers against vaccines you have provided, such as a tetanus titer or pneumococcal titers.

A complete blood count with differential, for example, provides important information, including the percentage and number of lymphocytes and neutrophils. If the absolute levels are low, then it becomes relevant to think: Why? Viral suppression is a true cause, but it’s overrated, so be sure to reevaluate a low count and remember to consider immunodeficiency if a low value persists.

If you suspect immunodeficiency in a baby, for example, check the infant’s lymphocyte count against the age-specific normal value. This varies, but the lower limit for normal for a healthy child under 1 year of age is about 3,500/mcL.

This might surprise you, but a child with low or no lymphocytes can quickly require emergency medical attention.

Other tests are more in the domain of the specialist or more appropriate in specific situations. In addition, the assay order forms and specialty laboratories can be tricky. Right next to IgG, for example, the IgG subclasses are often listed. These subclass evaluations are expensive and of little value in routine clinical assessment.

The bottom line is: Think about primary immunodeficiency. If you are uncomfortable in carrying forward a diagnostic evaluation – call an immunologist. We are happy to help. Statistically speaking, the needle is in your haystack. A pediatric practice looking after 10,000 children should be following 5 with primary immunodeficiency. Do you know who yours are?

This column, "Subspecialist Consult," appears regularly in Pediatric News, an Elsevier publication. Dr. Orange is a pediatric immunologist in the division of allergy and immunology at Children’s Hospital of Philadelphia. He disclosed that he is a medical adviser to the Immunodeficiency Foundation and a consultant to three manufacturers of immunoglobulin therapies: Baxter Healthcare, Talecris Biotherapeutics, and CSL Behring. He also receives research grants from Octapharma USA.

Clostridium difficile has been on the radar of infectious disease (ID) experts for the better part of a decade now. But how mindful are hospitalists of the problem, and how seriously are they taking it?

“I think we’re getting there,” says Danielle Scheurer, MD, MSCR, SFHM, a hospitalist and medical director of quality at the Medical University of South Carolina in Charleston. But she adds, “Because the bugs are invisible, you feel a little bit disconnected from your direct role in all this.”

Stuart Cohen, MD, an ID expert at the University of California Davis and a fellow with the Infectious Diseases Society of America, says not everyone is as concerned about C. diff as they should be.

“I think most people still see C. diff as just basically being a nuisance, and so they don’t really take it quite so seriously. Until somebody sees a patient have to get a colectomy or die from C. diff, I don’t think that there’s necessarily an appreciation to the severity of the illness,” he says. “You don’t really get this sense that it’s anything other than, ‘Well, we’ll just give them some vancomycin or we’ll just give them some metronidazole and we’ll take care of it.’”

Ketino Kobaidze, MD, a hospitalist at Emory University Hospital Midtown in Atlanta, says she thinks hospitalists should be more involved in antibiotic stewardship efforts and in research efforts to combat C. diff.

“I’m sure everybody knows and everybody takes it into consideration,” she says. But she also says not all hospitalists view C. diff as an acute problem that warrants urgent treatment “or we might be in trouble,” she says. “I’m not sure about that.”

Dr. Scheurer says the solution to treating C. diff properly is keeping a mindset on the safety of your patients. “Then it can motivate you and your group,” she says. “Every single number affects a person. It’s not just a rate. Zero is the goal.”

Tom Collins is a freelance medical writer based in Florida.

 

Clostridium difficile has been on the radar of infectious disease (ID) experts for the better part of a decade now. But how mindful are hospitalists of the problem, and how seriously are they taking it?

“I think we’re getting there,” says Danielle Scheurer, MD, MSCR, SFHM, a hospitalist and medical director of quality at the Medical University of South Carolina in Charleston. But she adds, “Because the bugs are invisible, you feel a little bit disconnected from your direct role in all this.”

Stuart Cohen, MD, an ID expert at the University of California Davis and a fellow with the Infectious Diseases Society of America, says not everyone is as concerned about C. diff as they should be.

“I think most people still see C. diff as just basically being a nuisance, and so they don’t really take it quite so seriously. Until somebody sees a patient have to get a colectomy or die from C. diff, I don’t think that there’s necessarily an appreciation to the severity of the illness,” he says. “You don’t really get this sense that it’s anything other than, ‘Well, we’ll just give them some vancomycin or we’ll just give them some metronidazole and we’ll take care of it.’”

Ketino Kobaidze, MD, a hospitalist at Emory University Hospital Midtown in Atlanta, says she thinks hospitalists should be more involved in antibiotic stewardship efforts and in research efforts to combat C. diff.

“I’m sure everybody knows and everybody takes it into consideration,” she says. But she also says not all hospitalists view C. diff as an acute problem that warrants urgent treatment “or we might be in trouble,” she says. “I’m not sure about that.”

Dr. Scheurer says the solution to treating C. diff properly is keeping a mindset on the safety of your patients. “Then it can motivate you and your group,” she says. “Every single number affects a person. It’s not just a rate. Zero is the goal.”

Tom Collins is a freelance medical writer based in Florida.

 

Clostridium difficile has been on the radar of infectious disease (ID) experts for the better part of a decade now. But how mindful are hospitalists of the problem, and how seriously are they taking it?

“I think we’re getting there,” says Danielle Scheurer, MD, MSCR, SFHM, a hospitalist and medical director of quality at the Medical University of South Carolina in Charleston. But she adds, “Because the bugs are invisible, you feel a little bit disconnected from your direct role in all this.”

Stuart Cohen, MD, an ID expert at the University of California Davis and a fellow with the Infectious Diseases Society of America, says not everyone is as concerned about C. diff as they should be.

“I think most people still see C. diff as just basically being a nuisance, and so they don’t really take it quite so seriously. Until somebody sees a patient have to get a colectomy or die from C. diff, I don’t think that there’s necessarily an appreciation to the severity of the illness,” he says. “You don’t really get this sense that it’s anything other than, ‘Well, we’ll just give them some vancomycin or we’ll just give them some metronidazole and we’ll take care of it.’”

Ketino Kobaidze, MD, a hospitalist at Emory University Hospital Midtown in Atlanta, says she thinks hospitalists should be more involved in antibiotic stewardship efforts and in research efforts to combat C. diff.

“I’m sure everybody knows and everybody takes it into consideration,” she says. But she also says not all hospitalists view C. diff as an acute problem that warrants urgent treatment “or we might be in trouble,” she says. “I’m not sure about that.”

Dr. Scheurer says the solution to treating C. diff properly is keeping a mindset on the safety of your patients. “Then it can motivate you and your group,” she says. “Every single number affects a person. It’s not just a rate. Zero is the goal.”

Tom Collins is a freelance medical writer based in Florida.

 

The Schumacher Group, which bills itself as the third-largest emergency and HM management firm in the U.S., is incorporating the use of smartphone applications, or apps, through its EDs nationwide. A similar technology could soon be in the offing for its HM operation.

The Lafayette, La.-based firm announced late last month that it was partnering with iTriage, a company that produces a free healthcare app for consumers, at its ED operation at North Okaloosa Medical Center in Crestview, Fla. The app will let patients and others learn details about the hospital and its services. And while David Grace, MD, FHM, the firm’s senior medical officer for hospital medicine, says there are no immediate plans to expand the usage to HM, the topic is being discussed.

"We're investigating it," he says, adding he sees a multitude of potential uses for healthcare apps, especially if they empower HM patients to become more involved in their care.

"I think any information that we can supply patients, whether we supply it or it's supplied through some other media, I think is a good thing," he says. "It increases their engagement. And any time the patient is more engaged in their healthcare, I think you develop better plans, better outcomes."

He cautions that there are potential pitfalls for physicians and patients. Patients need to be realistic about their breadth of knowledge, and doctors need to understand that a patient is not second-guessing them, just being interactive in the process.

It can "almost be one more line of safety checks in the whole healthcare continuum," Dr. Grace says. "The last time I looked, I've not seen too many practices of individuals out there hit 100% of everything 100% of the time. And while the errors numbers may be small, if you're the one discharged after a stroke not on an anti-platelet agent and have a massive stroke, that 1% was a pretty substantial number in your case."

The Schumacher Group, which bills itself as the third-largest emergency and HM management firm in the U.S., is incorporating the use of smartphone applications, or apps, through its EDs nationwide. A similar technology could soon be in the offing for its HM operation.

The Lafayette, La.-based firm announced late last month that it was partnering with iTriage, a company that produces a free healthcare app for consumers, at its ED operation at North Okaloosa Medical Center in Crestview, Fla. The app will let patients and others learn details about the hospital and its services. And while David Grace, MD, FHM, the firm’s senior medical officer for hospital medicine, says there are no immediate plans to expand the usage to HM, the topic is being discussed.

"We're investigating it," he says, adding he sees a multitude of potential uses for healthcare apps, especially if they empower HM patients to become more involved in their care.

"I think any information that we can supply patients, whether we supply it or it's supplied through some other media, I think is a good thing," he says. "It increases their engagement. And any time the patient is more engaged in their healthcare, I think you develop better plans, better outcomes."

He cautions that there are potential pitfalls for physicians and patients. Patients need to be realistic about their breadth of knowledge, and doctors need to understand that a patient is not second-guessing them, just being interactive in the process.

It can "almost be one more line of safety checks in the whole healthcare continuum," Dr. Grace says. "The last time I looked, I've not seen too many practices of individuals out there hit 100% of everything 100% of the time. And while the errors numbers may be small, if you're the one discharged after a stroke not on an anti-platelet agent and have a massive stroke, that 1% was a pretty substantial number in your case."

The Schumacher Group, which bills itself as the third-largest emergency and HM management firm in the U.S., is incorporating the use of smartphone applications, or apps, through its EDs nationwide. A similar technology could soon be in the offing for its HM operation.

The Lafayette, La.-based firm announced late last month that it was partnering with iTriage, a company that produces a free healthcare app for consumers, at its ED operation at North Okaloosa Medical Center in Crestview, Fla. The app will let patients and others learn details about the hospital and its services. And while David Grace, MD, FHM, the firm’s senior medical officer for hospital medicine, says there are no immediate plans to expand the usage to HM, the topic is being discussed.

"We're investigating it," he says, adding he sees a multitude of potential uses for healthcare apps, especially if they empower HM patients to become more involved in their care.

"I think any information that we can supply patients, whether we supply it or it's supplied through some other media, I think is a good thing," he says. "It increases their engagement. And any time the patient is more engaged in their healthcare, I think you develop better plans, better outcomes."

He cautions that there are potential pitfalls for physicians and patients. Patients need to be realistic about their breadth of knowledge, and doctors need to understand that a patient is not second-guessing them, just being interactive in the process.

It can "almost be one more line of safety checks in the whole healthcare continuum," Dr. Grace says. "The last time I looked, I've not seen too many practices of individuals out there hit 100% of everything 100% of the time. And while the errors numbers may be small, if you're the one discharged after a stroke not on an anti-platelet agent and have a massive stroke, that 1% was a pretty substantial number in your case."

Clinical question: In patients with candidemia, what are the incidence, risk factors, and antifungal treatment outcomes for ocular candidiasis?

Background: The incidence and treatment outcomes of ocular candidiasis have not been studied extensively.

Study design: Randomized noninferiority trial.

Setting: Multicenter study of 370 patients.

Synopsis: This study randomized 370 non-neutropenic patients with candidemia in a 2:1 ratio to receive voriconazole monotherapy or amphotericin B followed by fluconazole. Patients were treated for at least two weeks after the last positive blood culture, for a maximum duration of eight weeks. Baseline and follow-up fundoscopic examinations were performed.

Sixty (16%) patients were diagnosed with ocular candidiasis, of which six (1.6%) were diagnosed with endophthalmitis and 34 (9%) with chorioretinitis. Patients with ocular candidiasis had a longer duration of candidemia, and were more likely to be infected with Candida albicans.

Outcomes were not available in 19 patients with ocular candidiasis due to death or loss of follow-up. There was no significant difference between the cure rate of voriconazole (93.5% [29/31]), compared with the amphotericin B group (100% [10/10]).

Bottom line: Ocular candidiasis occurs in approximately 16% of non-neutropenic patients with candidemia. A longer duration of candidemia and infection with C. albicans were associated with ocular candidiasis. Both voriconazole and amphotericin B/fluconazole are effective in patients with ocular candidiasis.

Citation: Oude Lashof AM, Rothova A, Sobel JD, et al. Ocular manifestations of candidemia. Clin Infect Dis. 2011;53:262-268.

For more physician reviews of HM-related literature, check out our website.

Clinical question: In patients with candidemia, what are the incidence, risk factors, and antifungal treatment outcomes for ocular candidiasis?

Background: The incidence and treatment outcomes of ocular candidiasis have not been studied extensively.

Study design: Randomized noninferiority trial.

Setting: Multicenter study of 370 patients.

Synopsis: This study randomized 370 non-neutropenic patients with candidemia in a 2:1 ratio to receive voriconazole monotherapy or amphotericin B followed by fluconazole. Patients were treated for at least two weeks after the last positive blood culture, for a maximum duration of eight weeks. Baseline and follow-up fundoscopic examinations were performed.

Sixty (16%) patients were diagnosed with ocular candidiasis, of which six (1.6%) were diagnosed with endophthalmitis and 34 (9%) with chorioretinitis. Patients with ocular candidiasis had a longer duration of candidemia, and were more likely to be infected with Candida albicans.

Outcomes were not available in 19 patients with ocular candidiasis due to death or loss of follow-up. There was no significant difference between the cure rate of voriconazole (93.5% [29/31]), compared with the amphotericin B group (100% [10/10]).

Bottom line: Ocular candidiasis occurs in approximately 16% of non-neutropenic patients with candidemia. A longer duration of candidemia and infection with C. albicans were associated with ocular candidiasis. Both voriconazole and amphotericin B/fluconazole are effective in patients with ocular candidiasis.

Citation: Oude Lashof AM, Rothova A, Sobel JD, et al. Ocular manifestations of candidemia. Clin Infect Dis. 2011;53:262-268.

For more physician reviews of HM-related literature, check out our website.

Clinical question: In patients with candidemia, what are the incidence, risk factors, and antifungal treatment outcomes for ocular candidiasis?

Background: The incidence and treatment outcomes of ocular candidiasis have not been studied extensively.

Study design: Randomized noninferiority trial.

Setting: Multicenter study of 370 patients.

Synopsis: This study randomized 370 non-neutropenic patients with candidemia in a 2:1 ratio to receive voriconazole monotherapy or amphotericin B followed by fluconazole. Patients were treated for at least two weeks after the last positive blood culture, for a maximum duration of eight weeks. Baseline and follow-up fundoscopic examinations were performed.

Sixty (16%) patients were diagnosed with ocular candidiasis, of which six (1.6%) were diagnosed with endophthalmitis and 34 (9%) with chorioretinitis. Patients with ocular candidiasis had a longer duration of candidemia, and were more likely to be infected with Candida albicans.

Outcomes were not available in 19 patients with ocular candidiasis due to death or loss of follow-up. There was no significant difference between the cure rate of voriconazole (93.5% [29/31]), compared with the amphotericin B group (100% [10/10]).

Bottom line: Ocular candidiasis occurs in approximately 16% of non-neutropenic patients with candidemia. A longer duration of candidemia and infection with C. albicans were associated with ocular candidiasis. Both voriconazole and amphotericin B/fluconazole are effective in patients with ocular candidiasis.

Citation: Oude Lashof AM, Rothova A, Sobel JD, et al. Ocular manifestations of candidemia. Clin Infect Dis. 2011;53:262-268.

For more physician reviews of HM-related literature, check out our website.

In the changing healthcare landscape, hospitalists are being asked to be leaders and managers in their day-to-day activities. Often, the HM director will need to help provide hospitalists in their groups with the skills they need to succeed, says Bryce Gartland, MD, FHM, associate director of the hospital medicine division and medical director of care coordination at Emory Healthcare in Atlanta.

“Critical to that is making sure you’ve got a standardized structure in place for ensuring their professional growth and development,” he says.

HM group directors can invite experts to conduct feedback sessions on particular areas of concern or send their hospitalists to outside training, he says. For example, SHM hosts a Leadership Academy that offers a “Foundation for Effective Leadership” course, along with two more advanced leadership seminars.

The American College of Physicians offers the “Leadership Enhancement and Development” (LEAD) program, and the Center for the Health Professions at the University of California at San Francisco offers several leadership initiatives.

It also is incumbent on HM directors to get their physicians training in quality improvement (QI), asserts John Bulger, DO, FACP, FHM, chief quality officer and director of the HM service line for Geisinger Health System in Danville, Pa. “In my view, quality improvement is really where hospitalists make their hay in being a value added to the hospital,” he says.

SHM’s Center for Hospital Innovation and Improvement offers a wide variety of tools and resources to educate hospitalists on QI. SHM also has a Quality Improvement Skills pre-course at its annual meeting in April in San Diego.

The Institute for Healthcare Improvement, a nonprofit organization based in Cambridge, Mass., that focuses on healthcare best practices, and the Institute for Health Care Delivery Research at InterMountain Healthcare in Salt Lake City, Utah, have respected QI training programs.

QI training also comes from mentorship and putting hospitalists on QI-related committees. “That really has a twofold benefit for the hospital medicine group, because you are also able to stretch your reach,” Dr. Bulger says. “Now you’ve got a hospitalist on that committee who can report back to you and tell you what’s going on, and help you be involved in the changes going on in the hospital.”

Lisa Ryan is a freelance writer based in New Jersey.

In the changing healthcare landscape, hospitalists are being asked to be leaders and managers in their day-to-day activities. Often, the HM director will need to help provide hospitalists in their groups with the skills they need to succeed, says Bryce Gartland, MD, FHM, associate director of the hospital medicine division and medical director of care coordination at Emory Healthcare in Atlanta.

“Critical to that is making sure you’ve got a standardized structure in place for ensuring their professional growth and development,” he says.

HM group directors can invite experts to conduct feedback sessions on particular areas of concern or send their hospitalists to outside training, he says. For example, SHM hosts a Leadership Academy that offers a “Foundation for Effective Leadership” course, along with two more advanced leadership seminars.

The American College of Physicians offers the “Leadership Enhancement and Development” (LEAD) program, and the Center for the Health Professions at the University of California at San Francisco offers several leadership initiatives.

It also is incumbent on HM directors to get their physicians training in quality improvement (QI), asserts John Bulger, DO, FACP, FHM, chief quality officer and director of the HM service line for Geisinger Health System in Danville, Pa. “In my view, quality improvement is really where hospitalists make their hay in being a value added to the hospital,” he says.

SHM’s Center for Hospital Innovation and Improvement offers a wide variety of tools and resources to educate hospitalists on QI. SHM also has a Quality Improvement Skills pre-course at its annual meeting in April in San Diego.

The Institute for Healthcare Improvement, a nonprofit organization based in Cambridge, Mass., that focuses on healthcare best practices, and the Institute for Health Care Delivery Research at InterMountain Healthcare in Salt Lake City, Utah, have respected QI training programs.

QI training also comes from mentorship and putting hospitalists on QI-related committees. “That really has a twofold benefit for the hospital medicine group, because you are also able to stretch your reach,” Dr. Bulger says. “Now you’ve got a hospitalist on that committee who can report back to you and tell you what’s going on, and help you be involved in the changes going on in the hospital.”

Lisa Ryan is a freelance writer based in New Jersey.

In the changing healthcare landscape, hospitalists are being asked to be leaders and managers in their day-to-day activities. Often, the HM director will need to help provide hospitalists in their groups with the skills they need to succeed, says Bryce Gartland, MD, FHM, associate director of the hospital medicine division and medical director of care coordination at Emory Healthcare in Atlanta.

“Critical to that is making sure you’ve got a standardized structure in place for ensuring their professional growth and development,” he says.

HM group directors can invite experts to conduct feedback sessions on particular areas of concern or send their hospitalists to outside training, he says. For example, SHM hosts a Leadership Academy that offers a “Foundation for Effective Leadership” course, along with two more advanced leadership seminars.

The American College of Physicians offers the “Leadership Enhancement and Development” (LEAD) program, and the Center for the Health Professions at the University of California at San Francisco offers several leadership initiatives.

It also is incumbent on HM directors to get their physicians training in quality improvement (QI), asserts John Bulger, DO, FACP, FHM, chief quality officer and director of the HM service line for Geisinger Health System in Danville, Pa. “In my view, quality improvement is really where hospitalists make their hay in being a value added to the hospital,” he says.

SHM’s Center for Hospital Innovation and Improvement offers a wide variety of tools and resources to educate hospitalists on QI. SHM also has a Quality Improvement Skills pre-course at its annual meeting in April in San Diego.

The Institute for Healthcare Improvement, a nonprofit organization based in Cambridge, Mass., that focuses on healthcare best practices, and the Institute for Health Care Delivery Research at InterMountain Healthcare in Salt Lake City, Utah, have respected QI training programs.

QI training also comes from mentorship and putting hospitalists on QI-related committees. “That really has a twofold benefit for the hospital medicine group, because you are also able to stretch your reach,” Dr. Bulger says. “Now you’ve got a hospitalist on that committee who can report back to you and tell you what’s going on, and help you be involved in the changes going on in the hospital.”

Lisa Ryan is a freelance writer based in New Jersey.

Not all post-discharge clinics are established by hospitalist groups or their parent hospitals. As Tallahassee (Fla.) Memorial Hospital’s experience with a collaborative approach shows (see “Is a Post-Discharge Clinic in Your Hospital’s Future?”), health plans might take an interest in successful discharge protocols to prevent unnecessary readmissions. In other cases, medical specialty practices have established clinics for patients with specific diseases—CHF, COPD, even post-ICU delirium.

In Southern California, two large, established physician groups that assume financial risk or insurance functions see the potential benefit, given that their financial incentives are more obviously aligned to such clinics than are hospitals’. Cerritos, Calif.-based CareMore is a Medicare health plan that started out as a medical group and remains a care delivery system for Medicare Advantage patients, making significant use of hospitalists.

“We call ourselves ‘extensivists,’” says CareMore medical director and hospitalist Hyong Kim, MD. The company’s hospitalists generally

work mornings at an assigned hospital, then spend their afternoons either making rounds on CareMore patients at a skilled nursing facility or staffing one of the group’s post-discharge clinics, located in its disease-management-oriented comprehensive clinics. Hospitalists might even make take over from primary-care physicians (PCPs) the ongoing management of the most difficult or most frail patients, Dr. Kim says. That demands a change in mindset by the hospitalist to accept responsibility for the patient’s care across settings.

“This approach wouldn’t work in fee-for-service, but it works well in pre-paid environments. We pay our PCPs a capitated rate, and they continue to receive capitation after the hospitalist takes over the care,” he explains. “Our extensivists are salaried, with incentives based on readmissions.”

The company uses chronic-disease managers, who check in daily with the hospitalists. “We also have a house-call physician program, sending physicians and social workers to patients’ homes after discharge,” Dr. Kim says.

Torrance, Calif.-based HealthCare Partners, a large, physician-owned multispecialty medical group, operates in many ways like a health plan, says Tyler Jung, MD, medical director for hospitalists, high-risk groups, and post-discharge clinics. “We’re fully delegated. We accept financial risk from virtually all of the major health plans in the area,” he explains.

Dr. Jung’s team views the first 30 days after patients leave the hospital as “the riskiest time period for our members. We’ve had hospitalists for 15 to 20 years, and just recently we began looking at the post-discharge clinic option,” he says. “I’m still undecided: Is it a Band-Aid or something we need to intervene in the post-discharge period?”

HealthCare Partners operates six community care and disease management centers across Southern California, each of which houses a post-discharge clinic staffed by a doctor, social worker, and case manager. The post-discharge physicians are internists, not necessarily hospitalists, “although many moonlight in our hospitalist program and the most successful ones have hospitalist experience,” Dr. Jung says. “Our clinics are designed for 45-minute appointments: The patient meets with the doctor and maybe the social worker and case manager—a real multidisciplinary approach.”

Three-fourths of referrals are patients coming home from the hospital and a quarter are high-risk patients identified in primary-care clinics. “The first visit deals with medically complicated issues, but the next couple may have more to do with reinforcing the care plan that was established,” as well as looking at social issues, he says.

 

Finding the right physician is no easy task. “They’ve got to get it,” he says. “You need to be judicious about how long to keep the patient—versus referring them back to primary care—and setting limits is hard. We don’t have magic criteria for this. It’s mostly subjective right now.”

Another challenge is measuring success. “These clinics can be expensive to run, and we need to show the return on investment,” he says.

Larry Beresford is a freelance writer based in Oakland, Calif.

 

Not all post-discharge clinics are established by hospitalist groups or their parent hospitals. As Tallahassee (Fla.) Memorial Hospital’s experience with a collaborative approach shows (see “Is a Post-Discharge Clinic in Your Hospital’s Future?”), health plans might take an interest in successful discharge protocols to prevent unnecessary readmissions. In other cases, medical specialty practices have established clinics for patients with specific diseases—CHF, COPD, even post-ICU delirium.

In Southern California, two large, established physician groups that assume financial risk or insurance functions see the potential benefit, given that their financial incentives are more obviously aligned to such clinics than are hospitals’. Cerritos, Calif.-based CareMore is a Medicare health plan that started out as a medical group and remains a care delivery system for Medicare Advantage patients, making significant use of hospitalists.

“We call ourselves ‘extensivists,’” says CareMore medical director and hospitalist Hyong Kim, MD. The company’s hospitalists generally

work mornings at an assigned hospital, then spend their afternoons either making rounds on CareMore patients at a skilled nursing facility or staffing one of the group’s post-discharge clinics, located in its disease-management-oriented comprehensive clinics. Hospitalists might even make take over from primary-care physicians (PCPs) the ongoing management of the most difficult or most frail patients, Dr. Kim says. That demands a change in mindset by the hospitalist to accept responsibility for the patient’s care across settings.

“This approach wouldn’t work in fee-for-service, but it works well in pre-paid environments. We pay our PCPs a capitated rate, and they continue to receive capitation after the hospitalist takes over the care,” he explains. “Our extensivists are salaried, with incentives based on readmissions.”

The company uses chronic-disease managers, who check in daily with the hospitalists. “We also have a house-call physician program, sending physicians and social workers to patients’ homes after discharge,” Dr. Kim says.

Torrance, Calif.-based HealthCare Partners, a large, physician-owned multispecialty medical group, operates in many ways like a health plan, says Tyler Jung, MD, medical director for hospitalists, high-risk groups, and post-discharge clinics. “We’re fully delegated. We accept financial risk from virtually all of the major health plans in the area,” he explains.

Dr. Jung’s team views the first 30 days after patients leave the hospital as “the riskiest time period for our members. We’ve had hospitalists for 15 to 20 years, and just recently we began looking at the post-discharge clinic option,” he says. “I’m still undecided: Is it a Band-Aid or something we need to intervene in the post-discharge period?”

HealthCare Partners operates six community care and disease management centers across Southern California, each of which houses a post-discharge clinic staffed by a doctor, social worker, and case manager. The post-discharge physicians are internists, not necessarily hospitalists, “although many moonlight in our hospitalist program and the most successful ones have hospitalist experience,” Dr. Jung says. “Our clinics are designed for 45-minute appointments: The patient meets with the doctor and maybe the social worker and case manager—a real multidisciplinary approach.”

Three-fourths of referrals are patients coming home from the hospital and a quarter are high-risk patients identified in primary-care clinics. “The first visit deals with medically complicated issues, but the next couple may have more to do with reinforcing the care plan that was established,” as well as looking at social issues, he says.

 

Finding the right physician is no easy task. “They’ve got to get it,” he says. “You need to be judicious about how long to keep the patient—versus referring them back to primary care—and setting limits is hard. We don’t have magic criteria for this. It’s mostly subjective right now.”

Another challenge is measuring success. “These clinics can be expensive to run, and we need to show the return on investment,” he says.

Larry Beresford is a freelance writer based in Oakland, Calif.

 

Not all post-discharge clinics are established by hospitalist groups or their parent hospitals. As Tallahassee (Fla.) Memorial Hospital’s experience with a collaborative approach shows (see “Is a Post-Discharge Clinic in Your Hospital’s Future?”), health plans might take an interest in successful discharge protocols to prevent unnecessary readmissions. In other cases, medical specialty practices have established clinics for patients with specific diseases—CHF, COPD, even post-ICU delirium.

In Southern California, two large, established physician groups that assume financial risk or insurance functions see the potential benefit, given that their financial incentives are more obviously aligned to such clinics than are hospitals’. Cerritos, Calif.-based CareMore is a Medicare health plan that started out as a medical group and remains a care delivery system for Medicare Advantage patients, making significant use of hospitalists.

“We call ourselves ‘extensivists,’” says CareMore medical director and hospitalist Hyong Kim, MD. The company’s hospitalists generally

work mornings at an assigned hospital, then spend their afternoons either making rounds on CareMore patients at a skilled nursing facility or staffing one of the group’s post-discharge clinics, located in its disease-management-oriented comprehensive clinics. Hospitalists might even make take over from primary-care physicians (PCPs) the ongoing management of the most difficult or most frail patients, Dr. Kim says. That demands a change in mindset by the hospitalist to accept responsibility for the patient’s care across settings.

“This approach wouldn’t work in fee-for-service, but it works well in pre-paid environments. We pay our PCPs a capitated rate, and they continue to receive capitation after the hospitalist takes over the care,” he explains. “Our extensivists are salaried, with incentives based on readmissions.”

The company uses chronic-disease managers, who check in daily with the hospitalists. “We also have a house-call physician program, sending physicians and social workers to patients’ homes after discharge,” Dr. Kim says.

Torrance, Calif.-based HealthCare Partners, a large, physician-owned multispecialty medical group, operates in many ways like a health plan, says Tyler Jung, MD, medical director for hospitalists, high-risk groups, and post-discharge clinics. “We’re fully delegated. We accept financial risk from virtually all of the major health plans in the area,” he explains.

Dr. Jung’s team views the first 30 days after patients leave the hospital as “the riskiest time period for our members. We’ve had hospitalists for 15 to 20 years, and just recently we began looking at the post-discharge clinic option,” he says. “I’m still undecided: Is it a Band-Aid or something we need to intervene in the post-discharge period?”

HealthCare Partners operates six community care and disease management centers across Southern California, each of which houses a post-discharge clinic staffed by a doctor, social worker, and case manager. The post-discharge physicians are internists, not necessarily hospitalists, “although many moonlight in our hospitalist program and the most successful ones have hospitalist experience,” Dr. Jung says. “Our clinics are designed for 45-minute appointments: The patient meets with the doctor and maybe the social worker and case manager—a real multidisciplinary approach.”

Three-fourths of referrals are patients coming home from the hospital and a quarter are high-risk patients identified in primary-care clinics. “The first visit deals with medically complicated issues, but the next couple may have more to do with reinforcing the care plan that was established,” as well as looking at social issues, he says.

 

Finding the right physician is no easy task. “They’ve got to get it,” he says. “You need to be judicious about how long to keep the patient—versus referring them back to primary care—and setting limits is hard. We don’t have magic criteria for this. It’s mostly subjective right now.”

Another challenge is measuring success. “These clinics can be expensive to run, and we need to show the return on investment,” he says.

Larry Beresford is a freelance writer based in Oakland, Calif.