Jane Salodof MacNeil

LAS VEGAS — Physicians need to monitor diabetic patients in weight loss program more closely than nondiabetic ones, Holly R. Wyatt, M.D., said at the annual meeting of the North American Association for the Study of Obesity.

These patients are more difficult to manage than the general population, according to Dr. Wyatt, medical director of the Colorado Weight Center for Human Nutrition at the University of Colorado Health Sciences Center in Denver. Nonetheless, they can lose weight, she said, and they will be able to reduce or stop many of their medications if they do.

“You have to become an expert and believe you can help your patients lose weight,” she rallied clinicians at the meeting, cosponsored by the American Diabetes Association. “We're not talking a huge amount of weight loss; we are talking a realistic amount,” she said.

Diabetic patients need a multipronged approach, incorporating diet, activity, behavioral counseling, and medication, Dr. Wyatt said. Diet by itself is not enough. Moreover, adjustments will be necessary when the goal shifts from short-term weight loss to long-term weight maintenance.

Restricting calories is most important early on, according to Dr. Wyatt, but the clinician has to produce a plan the patient can follow. “Just telling patients to eat less is not an approach. You have to do more than that,” she said. For example, she cited meal replacements (such as Slim Fast) as being very effective in the short term because they help patients control portions.

Clinicians must monitor blood glucose and insulin levels as these will change when diabetic patients start to lose weight. The physician may need to stop or reduce insulin and some other medications by 25%-50%, Dr. Wyatt advised.

Exercise is critical to long-term success in weight maintenance, she said. But telling sedentary patients to move more does not work any better than telling then to eat less, she said. Instead, she recommended writing an exercise prescription for these patients.

“One of the most effective is a pedometer, and slowly getting them up to 10,000 steps a week,” she said. An interim goal would be having the patients increase their steps by 500 over baseline each week.

“At the end of the day when they look at the pedometer, they know they made a difference,” she said.

“Self-monitoring is absolutely critical,” Dr. Wyatt continued. “Patients who use food and activity diaries are more successful than those who don't.”

Physicians should use all available tools, including medication, according to Dr. Wyatt. Weight-loss drugs can help maintain 10% weight loss at 1 year, she said.

Finally, Dr. Wyatt said the physician should not become discouraged if a patient starts to gain back weight.

“When patients come in and they've regained some weight, you feel like they failed and you failed as caregiver,” she said. “No one failed. It's common in a chronic disease. Some people fail several times before they actually succeed.”

LAS VEGAS — Physicians need to monitor diabetic patients in weight loss program more closely than nondiabetic ones, Holly R. Wyatt, M.D., said at the annual meeting of the North American Association for the Study of Obesity.

These patients are more difficult to manage than the general population, according to Dr. Wyatt, medical director of the Colorado Weight Center for Human Nutrition at the University of Colorado Health Sciences Center in Denver. Nonetheless, they can lose weight, she said, and they will be able to reduce or stop many of their medications if they do.

“You have to become an expert and believe you can help your patients lose weight,” she rallied clinicians at the meeting, cosponsored by the American Diabetes Association. “We're not talking a huge amount of weight loss; we are talking a realistic amount,” she said.

Diabetic patients need a multipronged approach, incorporating diet, activity, behavioral counseling, and medication, Dr. Wyatt said. Diet by itself is not enough. Moreover, adjustments will be necessary when the goal shifts from short-term weight loss to long-term weight maintenance.

Restricting calories is most important early on, according to Dr. Wyatt, but the clinician has to produce a plan the patient can follow. “Just telling patients to eat less is not an approach. You have to do more than that,” she said. For example, she cited meal replacements (such as Slim Fast) as being very effective in the short term because they help patients control portions.

Clinicians must monitor blood glucose and insulin levels as these will change when diabetic patients start to lose weight. The physician may need to stop or reduce insulin and some other medications by 25%-50%, Dr. Wyatt advised.

Exercise is critical to long-term success in weight maintenance, she said. But telling sedentary patients to move more does not work any better than telling then to eat less, she said. Instead, she recommended writing an exercise prescription for these patients.

“One of the most effective is a pedometer, and slowly getting them up to 10,000 steps a week,” she said. An interim goal would be having the patients increase their steps by 500 over baseline each week.

“At the end of the day when they look at the pedometer, they know they made a difference,” she said.

“Self-monitoring is absolutely critical,” Dr. Wyatt continued. “Patients who use food and activity diaries are more successful than those who don't.”

Physicians should use all available tools, including medication, according to Dr. Wyatt. Weight-loss drugs can help maintain 10% weight loss at 1 year, she said.

Finally, Dr. Wyatt said the physician should not become discouraged if a patient starts to gain back weight.

“When patients come in and they've regained some weight, you feel like they failed and you failed as caregiver,” she said. “No one failed. It's common in a chronic disease. Some people fail several times before they actually succeed.”

LAS VEGAS — Physicians need to monitor diabetic patients in weight loss program more closely than nondiabetic ones, Holly R. Wyatt, M.D., said at the annual meeting of the North American Association for the Study of Obesity.

These patients are more difficult to manage than the general population, according to Dr. Wyatt, medical director of the Colorado Weight Center for Human Nutrition at the University of Colorado Health Sciences Center in Denver. Nonetheless, they can lose weight, she said, and they will be able to reduce or stop many of their medications if they do.

“You have to become an expert and believe you can help your patients lose weight,” she rallied clinicians at the meeting, cosponsored by the American Diabetes Association. “We're not talking a huge amount of weight loss; we are talking a realistic amount,” she said.

Diabetic patients need a multipronged approach, incorporating diet, activity, behavioral counseling, and medication, Dr. Wyatt said. Diet by itself is not enough. Moreover, adjustments will be necessary when the goal shifts from short-term weight loss to long-term weight maintenance.

Restricting calories is most important early on, according to Dr. Wyatt, but the clinician has to produce a plan the patient can follow. “Just telling patients to eat less is not an approach. You have to do more than that,” she said. For example, she cited meal replacements (such as Slim Fast) as being very effective in the short term because they help patients control portions.

Clinicians must monitor blood glucose and insulin levels as these will change when diabetic patients start to lose weight. The physician may need to stop or reduce insulin and some other medications by 25%-50%, Dr. Wyatt advised.

Exercise is critical to long-term success in weight maintenance, she said. But telling sedentary patients to move more does not work any better than telling then to eat less, she said. Instead, she recommended writing an exercise prescription for these patients.

“One of the most effective is a pedometer, and slowly getting them up to 10,000 steps a week,” she said. An interim goal would be having the patients increase their steps by 500 over baseline each week.

“At the end of the day when they look at the pedometer, they know they made a difference,” she said.

“Self-monitoring is absolutely critical,” Dr. Wyatt continued. “Patients who use food and activity diaries are more successful than those who don't.”

Physicians should use all available tools, including medication, according to Dr. Wyatt. Weight-loss drugs can help maintain 10% weight loss at 1 year, she said.

Finally, Dr. Wyatt said the physician should not become discouraged if a patient starts to gain back weight.

“When patients come in and they've regained some weight, you feel like they failed and you failed as caregiver,” she said. “No one failed. It's common in a chronic disease. Some people fail several times before they actually succeed.”

LAS VEGAS — Genetic variations in two major antioxidant enzymes may increase the risk of pancreatic cancer in people with diabetes mellitus, according to preliminary data presented at the annual meeting of the North American Association for the Study of Obesity.

In an ongoing, hospital-based, case-control study, pancreatic cancer risk was nearly four times higher (odds ratio, 3.8) in diabetic patients who had a catalase variant. The risk was nearly six times higher (odds ratio, 5.7) if they had a variant of superoxide dismutase. The patient population included both type 1 and type 2 diabetics; most had type 2 diabetes, said Manal M. Hassan, M.D., a molecular epidemiologist at the University of Texas M.D. Anderson Cancer Center, Houston.

Type 2 diabetes is a significant risk factor for pancreatic cancer. The researchers hypothesized that an impaired defense against oxidative stress makes some patients more susceptible to pancreatic cancer.

The study has so far compared 556 confirmed cases of adenocarcinoma of the pancreas with 344 spouses of M.D. Anderson patients who had other forms of cancer. The goal is to enroll 800 pancreatic cancer cases, Dr. Hassan said.

The researchers hope to develop a model to identify patients who are most susceptible. “A large-scale study, to assess the interaction between our findings and obesity indicators such as weight change, is warranted,” the researchers concluded at the meeting, which was cosponsored by the American Diabetes Association.

LAS VEGAS — Genetic variations in two major antioxidant enzymes may increase the risk of pancreatic cancer in people with diabetes mellitus, according to preliminary data presented at the annual meeting of the North American Association for the Study of Obesity.

In an ongoing, hospital-based, case-control study, pancreatic cancer risk was nearly four times higher (odds ratio, 3.8) in diabetic patients who had a catalase variant. The risk was nearly six times higher (odds ratio, 5.7) if they had a variant of superoxide dismutase. The patient population included both type 1 and type 2 diabetics; most had type 2 diabetes, said Manal M. Hassan, M.D., a molecular epidemiologist at the University of Texas M.D. Anderson Cancer Center, Houston.

Type 2 diabetes is a significant risk factor for pancreatic cancer. The researchers hypothesized that an impaired defense against oxidative stress makes some patients more susceptible to pancreatic cancer.

The study has so far compared 556 confirmed cases of adenocarcinoma of the pancreas with 344 spouses of M.D. Anderson patients who had other forms of cancer. The goal is to enroll 800 pancreatic cancer cases, Dr. Hassan said.

The researchers hope to develop a model to identify patients who are most susceptible. “A large-scale study, to assess the interaction between our findings and obesity indicators such as weight change, is warranted,” the researchers concluded at the meeting, which was cosponsored by the American Diabetes Association.

LAS VEGAS — Genetic variations in two major antioxidant enzymes may increase the risk of pancreatic cancer in people with diabetes mellitus, according to preliminary data presented at the annual meeting of the North American Association for the Study of Obesity.

In an ongoing, hospital-based, case-control study, pancreatic cancer risk was nearly four times higher (odds ratio, 3.8) in diabetic patients who had a catalase variant. The risk was nearly six times higher (odds ratio, 5.7) if they had a variant of superoxide dismutase. The patient population included both type 1 and type 2 diabetics; most had type 2 diabetes, said Manal M. Hassan, M.D., a molecular epidemiologist at the University of Texas M.D. Anderson Cancer Center, Houston.

Type 2 diabetes is a significant risk factor for pancreatic cancer. The researchers hypothesized that an impaired defense against oxidative stress makes some patients more susceptible to pancreatic cancer.

The study has so far compared 556 confirmed cases of adenocarcinoma of the pancreas with 344 spouses of M.D. Anderson patients who had other forms of cancer. The goal is to enroll 800 pancreatic cancer cases, Dr. Hassan said.

The researchers hope to develop a model to identify patients who are most susceptible. “A large-scale study, to assess the interaction between our findings and obesity indicators such as weight change, is warranted,” the researchers concluded at the meeting, which was cosponsored by the American Diabetes Association.

PHOENIX, ARIZ. — Small increases in serum creatinine that are not currently viewed as signaling renal dysfunction are highly predictive of mortality in patients with severe sepsis, William Macias, M.D., reported at a meeting sponsored by the Society of Critical Care Medicine.

In a review of data on 1,226 patients, 28-day mortality reached 42.9% in patients whose creatinine rose by 0.2-0.49 mg/dL from baseline during the first 24 hours, said Dr. Macias of Lilly Research Laboratories in Indianapolis.

When an increase in creatinine met or exceeded the current marker of 0.5 mg/dL on day 1, 57.7% of patients died within 28 days. Mortality was 25.7% for patients with early increases of less than 0.2 mg/dL.

“The current definition may be too insensitive to detect acute kidney injury in patients with severe sepsis,” Dr. Macias said. Relative serum creatinine increases that are greater than 25%—as well as acute increases of 0.5 mg/dL or greater—are associated with significant increases in mortality.

The researchers drew the patient population from placebo groups in the Integrated Database of Severe Sepsis and Xigris Therapy, a repository of data from trials for Lilly's drotrecogin alfa activated. The investigators were interested in patients with moderate increases of 0.2-0.49 mg/dL in serum creatinine because these are not currently associated with kidney injury.

“If you have increases from 0.2 to less than 0.5 [mg/dL], you have mortality of 40%” regardless of baseline level, Dr. Macias said. “If you have increases greater than 0.5 [mg/dL], you have mortality greater than 50%—no matter where they started.”

Deaths typically occurred within 5 days if creatinine levels rose on day 1. Patients with high baseline creatinine that did not rise tended to die after day 15. “It was the same pattern over and over again. If you have an increase in creatinine you pay a very, very early penalty,” he said.

PHOENIX, ARIZ. — Small increases in serum creatinine that are not currently viewed as signaling renal dysfunction are highly predictive of mortality in patients with severe sepsis, William Macias, M.D., reported at a meeting sponsored by the Society of Critical Care Medicine.

In a review of data on 1,226 patients, 28-day mortality reached 42.9% in patients whose creatinine rose by 0.2-0.49 mg/dL from baseline during the first 24 hours, said Dr. Macias of Lilly Research Laboratories in Indianapolis.

When an increase in creatinine met or exceeded the current marker of 0.5 mg/dL on day 1, 57.7% of patients died within 28 days. Mortality was 25.7% for patients with early increases of less than 0.2 mg/dL.

“The current definition may be too insensitive to detect acute kidney injury in patients with severe sepsis,” Dr. Macias said. Relative serum creatinine increases that are greater than 25%—as well as acute increases of 0.5 mg/dL or greater—are associated with significant increases in mortality.

The researchers drew the patient population from placebo groups in the Integrated Database of Severe Sepsis and Xigris Therapy, a repository of data from trials for Lilly's drotrecogin alfa activated. The investigators were interested in patients with moderate increases of 0.2-0.49 mg/dL in serum creatinine because these are not currently associated with kidney injury.

“If you have increases from 0.2 to less than 0.5 [mg/dL], you have mortality of 40%” regardless of baseline level, Dr. Macias said. “If you have increases greater than 0.5 [mg/dL], you have mortality greater than 50%—no matter where they started.”

Deaths typically occurred within 5 days if creatinine levels rose on day 1. Patients with high baseline creatinine that did not rise tended to die after day 15. “It was the same pattern over and over again. If you have an increase in creatinine you pay a very, very early penalty,” he said.

PHOENIX, ARIZ. — Small increases in serum creatinine that are not currently viewed as signaling renal dysfunction are highly predictive of mortality in patients with severe sepsis, William Macias, M.D., reported at a meeting sponsored by the Society of Critical Care Medicine.

In a review of data on 1,226 patients, 28-day mortality reached 42.9% in patients whose creatinine rose by 0.2-0.49 mg/dL from baseline during the first 24 hours, said Dr. Macias of Lilly Research Laboratories in Indianapolis.

When an increase in creatinine met or exceeded the current marker of 0.5 mg/dL on day 1, 57.7% of patients died within 28 days. Mortality was 25.7% for patients with early increases of less than 0.2 mg/dL.

“The current definition may be too insensitive to detect acute kidney injury in patients with severe sepsis,” Dr. Macias said. Relative serum creatinine increases that are greater than 25%—as well as acute increases of 0.5 mg/dL or greater—are associated with significant increases in mortality.

The researchers drew the patient population from placebo groups in the Integrated Database of Severe Sepsis and Xigris Therapy, a repository of data from trials for Lilly's drotrecogin alfa activated. The investigators were interested in patients with moderate increases of 0.2-0.49 mg/dL in serum creatinine because these are not currently associated with kidney injury.

“If you have increases from 0.2 to less than 0.5 [mg/dL], you have mortality of 40%” regardless of baseline level, Dr. Macias said. “If you have increases greater than 0.5 [mg/dL], you have mortality greater than 50%—no matter where they started.”

Deaths typically occurred within 5 days if creatinine levels rose on day 1. Patients with high baseline creatinine that did not rise tended to die after day 15. “It was the same pattern over and over again. If you have an increase in creatinine you pay a very, very early penalty,” he said.

PHOENIX, ARIZ. — The emergency department at a California hospital has reduced in-hospital sepsis mortality from 42% to 22% with a 6-hour protocol of rapid interventions, H. Bryant Nguyen, M.D., reported at a meeting sponsored by the Society of Critical Care Medicine.

Data on 208 sepsis patients treated from the start of the program in October 2003 through the end of 2004 show that the greatest benefit occurs when the protocol is completed on time, said Dr. Nguyen of Loma Linda (Calif.) University.

Mortality was 12.5% among the 24 patients who received all of the interventions within 6 hours, but was 34.2% among the 184 patients in whom the “STOP Sepsis Bundle” protocol was started but not completed within 6 hours. The difference in mortality was highly significant (P =.008).

STOP stands for Strategies to Timely Obviate the Progression of sepsis in the emergency department. Dr. Nguyen modeled the STOP Sepsis Bundle protocol after the 6-hour Severe Sepsis bundle promoted by the Institute for Healthcare Improvement (IHI) and the international Surviving Sepsis Campaign (SSC). Despite strong support for such an intervention, no one had previously established that it was viable in a working emergency department. “Most of this is not currently performed in most emergency departments around the country, so the feasibility of implementing the 6-hour bundle is unknown,” he said.

As presented by Dr. Nguyen, Loma Linda's STOP Sepsis Bundle is set in motion for patients who meet three criteria: systemic inflammatory response syndrome (SIRS), a source of infection, and any one of the following: a systolic blood pressure less than 90 mm Hg after a 20 mL/kg fluid bolus, a serum lactate level of 4 mmol/L or higher, or more than one acute organ dysfunction.

The protocol comprises five components, of which the first three must be completed within 6 hours:

▸ Begin hemodynamic monitoring (central venous pressure [CVP] and central venous oxygen saturation [ScvO2]) within 2 hours.

▸ Start broad-spectrum antibiotics within 4 hours.

▸ Use early goal-directed therapy (EGDT), with these goals to be achieved within 6 hours and maintained until admission: CVP of at least 8 mm Hg, mean arterial pressure (MAP) of at least 65 mm Hg, and ScvO2 of at least 70%.

▸ Obtain serial lactate levels to monitor for lactate clearance.

▸ Initiate corticosteroid treatment if the patient is on a vasopressor.

Dr. Nguyen said he focused on goals to be achieved rather than methods in customizing the SSC/IHI bundle. His modifications drew praise from Jean-Louis Vincent, M.D., a member of the SSC panel who worked on its sepsis bundle. Dr. Vincent, chair of the department of intensive care at Erasme University Hospital in Brussels, chaired the sepsis research session at the meeting.

“You have not really implemented the bundle of the Surviving Sepsis Campaign,” he told Dr. Nguyen. “You have implemented a better bundle. … You changed it to improve it.”

“There is only so much in 6 hours you can do, no matter how you word it,” Dr. Nguyen said in his response.

He described a gradual implementation process in which bundle components were added at 3-month intervals. The phase-in started with staff education, and included nursing in-service training sessions every 6 months, grand rounds, quality improvement reports every 2 months, and continuous review of data.

“EGDT is easy to initiate but appears to be the most challenging component to complete,” said Dr. Nguyen, a former student of EGDT champion Emanuel P. Rivers, M.D., at Henry Ford Hospital, Detroit.

Patients who received the complete bundle not only had a survival advantage, they also had shorter lengths of stay in the hospital (although the difference was not statistically significant): 8.1 days vs. 11.9 days for the larger cohort of sepsis patients (P = .06). “Completion of the bundle is associated with improved outcome and possibly a decrease in resource consumption in terms of length of stay,” he concluded.

The staff has reached the point where it is comfortable with the arduous protocol, he added. “We treat them [sepsis patients] as a trauma patient. We treat them as a cardiac arrest patient. We invest the time for 2-3 hours,” he said. “If we don't, in 6 hours they arrest.”

PHOENIX, ARIZ. — The emergency department at a California hospital has reduced in-hospital sepsis mortality from 42% to 22% with a 6-hour protocol of rapid interventions, H. Bryant Nguyen, M.D., reported at a meeting sponsored by the Society of Critical Care Medicine.

Data on 208 sepsis patients treated from the start of the program in October 2003 through the end of 2004 show that the greatest benefit occurs when the protocol is completed on time, said Dr. Nguyen of Loma Linda (Calif.) University.

Mortality was 12.5% among the 24 patients who received all of the interventions within 6 hours, but was 34.2% among the 184 patients in whom the “STOP Sepsis Bundle” protocol was started but not completed within 6 hours. The difference in mortality was highly significant (P =.008).

STOP stands for Strategies to Timely Obviate the Progression of sepsis in the emergency department. Dr. Nguyen modeled the STOP Sepsis Bundle protocol after the 6-hour Severe Sepsis bundle promoted by the Institute for Healthcare Improvement (IHI) and the international Surviving Sepsis Campaign (SSC). Despite strong support for such an intervention, no one had previously established that it was viable in a working emergency department. “Most of this is not currently performed in most emergency departments around the country, so the feasibility of implementing the 6-hour bundle is unknown,” he said.

As presented by Dr. Nguyen, Loma Linda's STOP Sepsis Bundle is set in motion for patients who meet three criteria: systemic inflammatory response syndrome (SIRS), a source of infection, and any one of the following: a systolic blood pressure less than 90 mm Hg after a 20 mL/kg fluid bolus, a serum lactate level of 4 mmol/L or higher, or more than one acute organ dysfunction.

The protocol comprises five components, of which the first three must be completed within 6 hours:

▸ Begin hemodynamic monitoring (central venous pressure [CVP] and central venous oxygen saturation [ScvO2]) within 2 hours.

▸ Start broad-spectrum antibiotics within 4 hours.

▸ Use early goal-directed therapy (EGDT), with these goals to be achieved within 6 hours and maintained until admission: CVP of at least 8 mm Hg, mean arterial pressure (MAP) of at least 65 mm Hg, and ScvO2 of at least 70%.

▸ Obtain serial lactate levels to monitor for lactate clearance.

▸ Initiate corticosteroid treatment if the patient is on a vasopressor.

Dr. Nguyen said he focused on goals to be achieved rather than methods in customizing the SSC/IHI bundle. His modifications drew praise from Jean-Louis Vincent, M.D., a member of the SSC panel who worked on its sepsis bundle. Dr. Vincent, chair of the department of intensive care at Erasme University Hospital in Brussels, chaired the sepsis research session at the meeting.

“You have not really implemented the bundle of the Surviving Sepsis Campaign,” he told Dr. Nguyen. “You have implemented a better bundle. … You changed it to improve it.”

“There is only so much in 6 hours you can do, no matter how you word it,” Dr. Nguyen said in his response.

He described a gradual implementation process in which bundle components were added at 3-month intervals. The phase-in started with staff education, and included nursing in-service training sessions every 6 months, grand rounds, quality improvement reports every 2 months, and continuous review of data.

“EGDT is easy to initiate but appears to be the most challenging component to complete,” said Dr. Nguyen, a former student of EGDT champion Emanuel P. Rivers, M.D., at Henry Ford Hospital, Detroit.

Patients who received the complete bundle not only had a survival advantage, they also had shorter lengths of stay in the hospital (although the difference was not statistically significant): 8.1 days vs. 11.9 days for the larger cohort of sepsis patients (P = .06). “Completion of the bundle is associated with improved outcome and possibly a decrease in resource consumption in terms of length of stay,” he concluded.

The staff has reached the point where it is comfortable with the arduous protocol, he added. “We treat them [sepsis patients] as a trauma patient. We treat them as a cardiac arrest patient. We invest the time for 2-3 hours,” he said. “If we don't, in 6 hours they arrest.”

PHOENIX, ARIZ. — The emergency department at a California hospital has reduced in-hospital sepsis mortality from 42% to 22% with a 6-hour protocol of rapid interventions, H. Bryant Nguyen, M.D., reported at a meeting sponsored by the Society of Critical Care Medicine.

Data on 208 sepsis patients treated from the start of the program in October 2003 through the end of 2004 show that the greatest benefit occurs when the protocol is completed on time, said Dr. Nguyen of Loma Linda (Calif.) University.

Mortality was 12.5% among the 24 patients who received all of the interventions within 6 hours, but was 34.2% among the 184 patients in whom the “STOP Sepsis Bundle” protocol was started but not completed within 6 hours. The difference in mortality was highly significant (P =.008).

STOP stands for Strategies to Timely Obviate the Progression of sepsis in the emergency department. Dr. Nguyen modeled the STOP Sepsis Bundle protocol after the 6-hour Severe Sepsis bundle promoted by the Institute for Healthcare Improvement (IHI) and the international Surviving Sepsis Campaign (SSC). Despite strong support for such an intervention, no one had previously established that it was viable in a working emergency department. “Most of this is not currently performed in most emergency departments around the country, so the feasibility of implementing the 6-hour bundle is unknown,” he said.

As presented by Dr. Nguyen, Loma Linda's STOP Sepsis Bundle is set in motion for patients who meet three criteria: systemic inflammatory response syndrome (SIRS), a source of infection, and any one of the following: a systolic blood pressure less than 90 mm Hg after a 20 mL/kg fluid bolus, a serum lactate level of 4 mmol/L or higher, or more than one acute organ dysfunction.

The protocol comprises five components, of which the first three must be completed within 6 hours:

▸ Begin hemodynamic monitoring (central venous pressure [CVP] and central venous oxygen saturation [ScvO2]) within 2 hours.

▸ Start broad-spectrum antibiotics within 4 hours.

▸ Use early goal-directed therapy (EGDT), with these goals to be achieved within 6 hours and maintained until admission: CVP of at least 8 mm Hg, mean arterial pressure (MAP) of at least 65 mm Hg, and ScvO2 of at least 70%.

▸ Obtain serial lactate levels to monitor for lactate clearance.

▸ Initiate corticosteroid treatment if the patient is on a vasopressor.

Dr. Nguyen said he focused on goals to be achieved rather than methods in customizing the SSC/IHI bundle. His modifications drew praise from Jean-Louis Vincent, M.D., a member of the SSC panel who worked on its sepsis bundle. Dr. Vincent, chair of the department of intensive care at Erasme University Hospital in Brussels, chaired the sepsis research session at the meeting.

“You have not really implemented the bundle of the Surviving Sepsis Campaign,” he told Dr. Nguyen. “You have implemented a better bundle. … You changed it to improve it.”

“There is only so much in 6 hours you can do, no matter how you word it,” Dr. Nguyen said in his response.

He described a gradual implementation process in which bundle components were added at 3-month intervals. The phase-in started with staff education, and included nursing in-service training sessions every 6 months, grand rounds, quality improvement reports every 2 months, and continuous review of data.

“EGDT is easy to initiate but appears to be the most challenging component to complete,” said Dr. Nguyen, a former student of EGDT champion Emanuel P. Rivers, M.D., at Henry Ford Hospital, Detroit.

Patients who received the complete bundle not only had a survival advantage, they also had shorter lengths of stay in the hospital (although the difference was not statistically significant): 8.1 days vs. 11.9 days for the larger cohort of sepsis patients (P = .06). “Completion of the bundle is associated with improved outcome and possibly a decrease in resource consumption in terms of length of stay,” he concluded.

The staff has reached the point where it is comfortable with the arduous protocol, he added. “We treat them [sepsis patients] as a trauma patient. We treat them as a cardiac arrest patient. We invest the time for 2-3 hours,” he said. “If we don't, in 6 hours they arrest.”

SCOTTSDALE, ARIZ. — The validity of large, randomized multicenter clinical trials to evaluate treatments for traumatic brain injury was called into question by numerous speakers during the annual meeting of the Neurocritical Care Society.

Speaking on therapeutic hypothermia, Donald Marion, M.D., refused to condemn the treatment when its promise in small single-hospital studies was not borne out in a large, randomized, multicenter trial, the findings of which showed the regimen was no better than current therapies.

Dr. Marion, a neurosurgeon and senior research fellow at the Brain Trauma Foundation, New York, took aim at the process. “Are valid multicenter clinical trials for severe traumatic brain injury possible?” he asked in a leadoff presentation, which became the talk of a 3-day meeting “I really think there is something about phase III trials that impact the outcomes independent of the treatment you are trying to use.”

Large, randomized, multicenter trials might be unsuited to the realities of neurocritical care for head trauma, according to Dr. Marion. The cases are too complicated “with multiple physiological variables that can affect outcome and, unfortunately, multiple critical care physicians making treatment decisions,” he said, adding that patients with traumatic brain injury often have other severe injuries that further complicate their randomization.

Dr. Marion estimated that 15-20 drugs, including tirilazad mesylate, have failed multicenter trials in traumatic brain injury.

These physicians have strong individual biases that make complying with uniform protocols difficult, especially if the investigators are working at many different centers, he continued. Consistency within a center may make single-center studies a better measure of new treatments for head trauma, he suggested.

“My bias is very strongly that there is a lot of noise in multicenter trials that may have drowned out the potential benefit of a lot of therapies in the past,” he said.

As chair of the hypothermia session, Michael N. Diringer, M.D., of Washington University, St. Louis, expressed surprise: “This is the first time I've heard someone argue we might want to think twice about how we interpret the results from multicenter trials,” he said. “The ability to perform trials on very sick, very complicated patients across centers—to get everybody to do the same thing—is an enormous and maybe potentially impossible task.”

Stefan Schwab, M.D., also complained of inconsistent protocols as a major problem in his talk on therapeutic hypothermia for stroke. However, he disagreed with Dr. Marion's position. Studies have used different temperatures, times to cooling, duration of cooling, etc., according to Dr. Schwab of the University of Heidelberg in Germany. What is needed, he said, is one large, randomized, multicenter trial with agreed-upon protocols.

“In my view, just randomized trials can show whether there is significance,” he said, arguing that small studies can be too selective. “Pick one right patient in one center and one right patient in another center and you come up with 20 right patients overall,” he said. “We want to treat patients with stroke with hypothermia all over the world.”

Raj K. Narayan, M.D., of the University of Cincinnati, argued that therapeutic hypothermia should not be a standard therapy, so long as it passes muster only in small studies. “Large randomized trials have some limitations, and certainly small trials have limitations. Just so long as we are all aware what those limitations are, large randomized trials are, in general, one of the strongest ways of figuring things out,” he said.

For Maxwell S. Damian, M.D., of the University of Leicester, England, the issues raised by Dr. Marion are a concern as his group advances beyond its single-center study of hypothermia in combination with coenzyme Q10 for head trauma. “That actually has been influencing our multicenter trial,” he said. “We are restricting it to people we know personally who have a similar regimen of hypothermia. It's a big problem—method.”

Another researcher, Michael F. Stiefel, M.D., of the University of Pennsylvania, Philadelphia, ruled out randomized trials in his group's work on brain tissue oxygen monitoring. He said it is now standard at his hospital based on data from a single-center study presented at the meeting.

“A lot of what we do in neurosurgery has never been randomized. We use something, and we see if it works. That's what we do. We wouldn't feel comfortable randomizing now.” he said.

SCOTTSDALE, ARIZ. — The validity of large, randomized multicenter clinical trials to evaluate treatments for traumatic brain injury was called into question by numerous speakers during the annual meeting of the Neurocritical Care Society.

Speaking on therapeutic hypothermia, Donald Marion, M.D., refused to condemn the treatment when its promise in small single-hospital studies was not borne out in a large, randomized, multicenter trial, the findings of which showed the regimen was no better than current therapies.

Dr. Marion, a neurosurgeon and senior research fellow at the Brain Trauma Foundation, New York, took aim at the process. “Are valid multicenter clinical trials for severe traumatic brain injury possible?” he asked in a leadoff presentation, which became the talk of a 3-day meeting “I really think there is something about phase III trials that impact the outcomes independent of the treatment you are trying to use.”

Large, randomized, multicenter trials might be unsuited to the realities of neurocritical care for head trauma, according to Dr. Marion. The cases are too complicated “with multiple physiological variables that can affect outcome and, unfortunately, multiple critical care physicians making treatment decisions,” he said, adding that patients with traumatic brain injury often have other severe injuries that further complicate their randomization.

Dr. Marion estimated that 15-20 drugs, including tirilazad mesylate, have failed multicenter trials in traumatic brain injury.

These physicians have strong individual biases that make complying with uniform protocols difficult, especially if the investigators are working at many different centers, he continued. Consistency within a center may make single-center studies a better measure of new treatments for head trauma, he suggested.

“My bias is very strongly that there is a lot of noise in multicenter trials that may have drowned out the potential benefit of a lot of therapies in the past,” he said.

As chair of the hypothermia session, Michael N. Diringer, M.D., of Washington University, St. Louis, expressed surprise: “This is the first time I've heard someone argue we might want to think twice about how we interpret the results from multicenter trials,” he said. “The ability to perform trials on very sick, very complicated patients across centers—to get everybody to do the same thing—is an enormous and maybe potentially impossible task.”

Stefan Schwab, M.D., also complained of inconsistent protocols as a major problem in his talk on therapeutic hypothermia for stroke. However, he disagreed with Dr. Marion's position. Studies have used different temperatures, times to cooling, duration of cooling, etc., according to Dr. Schwab of the University of Heidelberg in Germany. What is needed, he said, is one large, randomized, multicenter trial with agreed-upon protocols.

“In my view, just randomized trials can show whether there is significance,” he said, arguing that small studies can be too selective. “Pick one right patient in one center and one right patient in another center and you come up with 20 right patients overall,” he said. “We want to treat patients with stroke with hypothermia all over the world.”

Raj K. Narayan, M.D., of the University of Cincinnati, argued that therapeutic hypothermia should not be a standard therapy, so long as it passes muster only in small studies. “Large randomized trials have some limitations, and certainly small trials have limitations. Just so long as we are all aware what those limitations are, large randomized trials are, in general, one of the strongest ways of figuring things out,” he said.

For Maxwell S. Damian, M.D., of the University of Leicester, England, the issues raised by Dr. Marion are a concern as his group advances beyond its single-center study of hypothermia in combination with coenzyme Q10 for head trauma. “That actually has been influencing our multicenter trial,” he said. “We are restricting it to people we know personally who have a similar regimen of hypothermia. It's a big problem—method.”

Another researcher, Michael F. Stiefel, M.D., of the University of Pennsylvania, Philadelphia, ruled out randomized trials in his group's work on brain tissue oxygen monitoring. He said it is now standard at his hospital based on data from a single-center study presented at the meeting.

“A lot of what we do in neurosurgery has never been randomized. We use something, and we see if it works. That's what we do. We wouldn't feel comfortable randomizing now.” he said.

SCOTTSDALE, ARIZ. — The validity of large, randomized multicenter clinical trials to evaluate treatments for traumatic brain injury was called into question by numerous speakers during the annual meeting of the Neurocritical Care Society.

Speaking on therapeutic hypothermia, Donald Marion, M.D., refused to condemn the treatment when its promise in small single-hospital studies was not borne out in a large, randomized, multicenter trial, the findings of which showed the regimen was no better than current therapies.

Dr. Marion, a neurosurgeon and senior research fellow at the Brain Trauma Foundation, New York, took aim at the process. “Are valid multicenter clinical trials for severe traumatic brain injury possible?” he asked in a leadoff presentation, which became the talk of a 3-day meeting “I really think there is something about phase III trials that impact the outcomes independent of the treatment you are trying to use.”

Large, randomized, multicenter trials might be unsuited to the realities of neurocritical care for head trauma, according to Dr. Marion. The cases are too complicated “with multiple physiological variables that can affect outcome and, unfortunately, multiple critical care physicians making treatment decisions,” he said, adding that patients with traumatic brain injury often have other severe injuries that further complicate their randomization.

Dr. Marion estimated that 15-20 drugs, including tirilazad mesylate, have failed multicenter trials in traumatic brain injury.

These physicians have strong individual biases that make complying with uniform protocols difficult, especially if the investigators are working at many different centers, he continued. Consistency within a center may make single-center studies a better measure of new treatments for head trauma, he suggested.

“My bias is very strongly that there is a lot of noise in multicenter trials that may have drowned out the potential benefit of a lot of therapies in the past,” he said.

As chair of the hypothermia session, Michael N. Diringer, M.D., of Washington University, St. Louis, expressed surprise: “This is the first time I've heard someone argue we might want to think twice about how we interpret the results from multicenter trials,” he said. “The ability to perform trials on very sick, very complicated patients across centers—to get everybody to do the same thing—is an enormous and maybe potentially impossible task.”

Stefan Schwab, M.D., also complained of inconsistent protocols as a major problem in his talk on therapeutic hypothermia for stroke. However, he disagreed with Dr. Marion's position. Studies have used different temperatures, times to cooling, duration of cooling, etc., according to Dr. Schwab of the University of Heidelberg in Germany. What is needed, he said, is one large, randomized, multicenter trial with agreed-upon protocols.

“In my view, just randomized trials can show whether there is significance,” he said, arguing that small studies can be too selective. “Pick one right patient in one center and one right patient in another center and you come up with 20 right patients overall,” he said. “We want to treat patients with stroke with hypothermia all over the world.”

Raj K. Narayan, M.D., of the University of Cincinnati, argued that therapeutic hypothermia should not be a standard therapy, so long as it passes muster only in small studies. “Large randomized trials have some limitations, and certainly small trials have limitations. Just so long as we are all aware what those limitations are, large randomized trials are, in general, one of the strongest ways of figuring things out,” he said.

For Maxwell S. Damian, M.D., of the University of Leicester, England, the issues raised by Dr. Marion are a concern as his group advances beyond its single-center study of hypothermia in combination with coenzyme Q10 for head trauma. “That actually has been influencing our multicenter trial,” he said. “We are restricting it to people we know personally who have a similar regimen of hypothermia. It's a big problem—method.”

Another researcher, Michael F. Stiefel, M.D., of the University of Pennsylvania, Philadelphia, ruled out randomized trials in his group's work on brain tissue oxygen monitoring. He said it is now standard at his hospital based on data from a single-center study presented at the meeting.

“A lot of what we do in neurosurgery has never been randomized. We use something, and we see if it works. That's what we do. We wouldn't feel comfortable randomizing now.” he said.

PHOENIX, ARIZ. — Magnetic resonance imaging provides more detail about traumatic brain and spinal cord injuries but computerized tomography is much faster, according to a colonel in the U.S. Army Medical Corps who served in Afghanistan.

In head traumas, MRI is superior for all pathologies except skull fracture and acute subarachnoid hemorrhage, Geoffrey S.F. Ling, M.D., said at a meeting sponsored by the Society of Critical Care Medicine. It can give far more information about edema, diffuse axonal injury, contusions, hematomas, and posterior fossa lesions, but these can all be diagnosed more quickly with CT scans, he said; rarely does information gathered with an MRI change clinical management of the patient.

Consequently, Dr. Ling, director of the division of critical care medicine at the Uniformed Services University of the Health Sciences in Bethesda, Md., said he reserves use of MRI to establish a diagnosis in a patient who is not improving after several days in an intensive care unit and to establish a prognosis.

Dr. Ling recommended CT scans for all patients at high risk for intracranial pathology. These would include patients with focal neural signs, penetrating wounds, depressed skull fractures that are palpable, and impaired motor skills in the absence of alcohol or drugs.

CT scans should also be considered in moderate-risk cases: patients with a history of changed mental status, amnesia, progressive headache, serious facial injury, vomiting, evidence of a skull fracture, multiple traumas, possible child abuse, and age younger than 2 years.

“If the patient was knocked out for more than 5 minutes, I would go ahead and do a CT scan,” he said. Plain x-rays should be used only in cervical spine injuries such as whiplash, for which they can diagnose tiny fractures, according to Dr. Ling. “The only time I will use plain films is for the neck,” he said.

PHOENIX, ARIZ. — Magnetic resonance imaging provides more detail about traumatic brain and spinal cord injuries but computerized tomography is much faster, according to a colonel in the U.S. Army Medical Corps who served in Afghanistan.

In head traumas, MRI is superior for all pathologies except skull fracture and acute subarachnoid hemorrhage, Geoffrey S.F. Ling, M.D., said at a meeting sponsored by the Society of Critical Care Medicine. It can give far more information about edema, diffuse axonal injury, contusions, hematomas, and posterior fossa lesions, but these can all be diagnosed more quickly with CT scans, he said; rarely does information gathered with an MRI change clinical management of the patient.

Consequently, Dr. Ling, director of the division of critical care medicine at the Uniformed Services University of the Health Sciences in Bethesda, Md., said he reserves use of MRI to establish a diagnosis in a patient who is not improving after several days in an intensive care unit and to establish a prognosis.

Dr. Ling recommended CT scans for all patients at high risk for intracranial pathology. These would include patients with focal neural signs, penetrating wounds, depressed skull fractures that are palpable, and impaired motor skills in the absence of alcohol or drugs.

CT scans should also be considered in moderate-risk cases: patients with a history of changed mental status, amnesia, progressive headache, serious facial injury, vomiting, evidence of a skull fracture, multiple traumas, possible child abuse, and age younger than 2 years.

“If the patient was knocked out for more than 5 minutes, I would go ahead and do a CT scan,” he said. Plain x-rays should be used only in cervical spine injuries such as whiplash, for which they can diagnose tiny fractures, according to Dr. Ling. “The only time I will use plain films is for the neck,” he said.

PHOENIX, ARIZ. — Magnetic resonance imaging provides more detail about traumatic brain and spinal cord injuries but computerized tomography is much faster, according to a colonel in the U.S. Army Medical Corps who served in Afghanistan.

In head traumas, MRI is superior for all pathologies except skull fracture and acute subarachnoid hemorrhage, Geoffrey S.F. Ling, M.D., said at a meeting sponsored by the Society of Critical Care Medicine. It can give far more information about edema, diffuse axonal injury, contusions, hematomas, and posterior fossa lesions, but these can all be diagnosed more quickly with CT scans, he said; rarely does information gathered with an MRI change clinical management of the patient.

Consequently, Dr. Ling, director of the division of critical care medicine at the Uniformed Services University of the Health Sciences in Bethesda, Md., said he reserves use of MRI to establish a diagnosis in a patient who is not improving after several days in an intensive care unit and to establish a prognosis.

Dr. Ling recommended CT scans for all patients at high risk for intracranial pathology. These would include patients with focal neural signs, penetrating wounds, depressed skull fractures that are palpable, and impaired motor skills in the absence of alcohol or drugs.

CT scans should also be considered in moderate-risk cases: patients with a history of changed mental status, amnesia, progressive headache, serious facial injury, vomiting, evidence of a skull fracture, multiple traumas, possible child abuse, and age younger than 2 years.

“If the patient was knocked out for more than 5 minutes, I would go ahead and do a CT scan,” he said. Plain x-rays should be used only in cervical spine injuries such as whiplash, for which they can diagnose tiny fractures, according to Dr. Ling. “The only time I will use plain films is for the neck,” he said.

PHOENIX, ARIZ. — Small increases in serum creatinine that are not currently viewed as signaling renal dysfunction are highly predictive of mortality in patients with severe sepsis, William Macias, M.D., reported at a meeting sponsored by the Society of Critical Care Medicine.

In a review of data on 1,226 patients, 28-day mortality reached 42.9% in patients whose creatinine rose by 0.2-0.49 mg/dL from baseline during the first 24 hours, said Dr. Macias of Lilly Research Laboratories in Indianapolis.

When an increase in creatinine met or exceeded the current marker of 0.5 mg/dL on day 1, 57.7% of patients died within 28 days. Mortality was 25.7% for patients with early increases of less than 0.2 mg/dL.

“The current definition may be too insensitive to detect acute kidney injury in patients with severe sepsis,” Dr. Macias said. Relative serum creatinine increases that are greater than 25%—as well as acute increases of 0.5 mg/dL or greater—are associated with significant increases in mortality.

The researchers drew the patient population from placebo groups in the Integrated Database of Severe Sepsis and Xigris Therapy, a repository of data from trials for Lilly's drotrecogin alfa activated (Xigris). The investigators were interested in patients with moderate increases of 0.2-0.49 mg/dL in serum creatinine because these are not currently associated with kidney injury.

“If you have increases from 0.2 to less than 0.5 [mg/dL], you have mortality of 40%” regardless of baseline level, Dr. Macias said. “If you have increases greater than 0.5 [mg/dL], you have mortality greater than 50%—no matter where they started.”

Deaths typically occurred within 5 days if creatinine levels rose on day 1. Patients with high baseline creatinine that did not rise tended to die after day 15, he said.

PHOENIX, ARIZ. — Small increases in serum creatinine that are not currently viewed as signaling renal dysfunction are highly predictive of mortality in patients with severe sepsis, William Macias, M.D., reported at a meeting sponsored by the Society of Critical Care Medicine.

In a review of data on 1,226 patients, 28-day mortality reached 42.9% in patients whose creatinine rose by 0.2-0.49 mg/dL from baseline during the first 24 hours, said Dr. Macias of Lilly Research Laboratories in Indianapolis.

When an increase in creatinine met or exceeded the current marker of 0.5 mg/dL on day 1, 57.7% of patients died within 28 days. Mortality was 25.7% for patients with early increases of less than 0.2 mg/dL.

“The current definition may be too insensitive to detect acute kidney injury in patients with severe sepsis,” Dr. Macias said. Relative serum creatinine increases that are greater than 25%—as well as acute increases of 0.5 mg/dL or greater—are associated with significant increases in mortality.

The researchers drew the patient population from placebo groups in the Integrated Database of Severe Sepsis and Xigris Therapy, a repository of data from trials for Lilly's drotrecogin alfa activated (Xigris). The investigators were interested in patients with moderate increases of 0.2-0.49 mg/dL in serum creatinine because these are not currently associated with kidney injury.

“If you have increases from 0.2 to less than 0.5 [mg/dL], you have mortality of 40%” regardless of baseline level, Dr. Macias said. “If you have increases greater than 0.5 [mg/dL], you have mortality greater than 50%—no matter where they started.”

Deaths typically occurred within 5 days if creatinine levels rose on day 1. Patients with high baseline creatinine that did not rise tended to die after day 15, he said.

PHOENIX, ARIZ. — Small increases in serum creatinine that are not currently viewed as signaling renal dysfunction are highly predictive of mortality in patients with severe sepsis, William Macias, M.D., reported at a meeting sponsored by the Society of Critical Care Medicine.

In a review of data on 1,226 patients, 28-day mortality reached 42.9% in patients whose creatinine rose by 0.2-0.49 mg/dL from baseline during the first 24 hours, said Dr. Macias of Lilly Research Laboratories in Indianapolis.

When an increase in creatinine met or exceeded the current marker of 0.5 mg/dL on day 1, 57.7% of patients died within 28 days. Mortality was 25.7% for patients with early increases of less than 0.2 mg/dL.

“The current definition may be too insensitive to detect acute kidney injury in patients with severe sepsis,” Dr. Macias said. Relative serum creatinine increases that are greater than 25%—as well as acute increases of 0.5 mg/dL or greater—are associated with significant increases in mortality.

The researchers drew the patient population from placebo groups in the Integrated Database of Severe Sepsis and Xigris Therapy, a repository of data from trials for Lilly's drotrecogin alfa activated (Xigris). The investigators were interested in patients with moderate increases of 0.2-0.49 mg/dL in serum creatinine because these are not currently associated with kidney injury.

“If you have increases from 0.2 to less than 0.5 [mg/dL], you have mortality of 40%” regardless of baseline level, Dr. Macias said. “If you have increases greater than 0.5 [mg/dL], you have mortality greater than 50%—no matter where they started.”

Deaths typically occurred within 5 days if creatinine levels rose on day 1. Patients with high baseline creatinine that did not rise tended to die after day 15, he said.

PHOENIX, ARIZ. — In-hospital sepsis mortality was reduced from 42% to 22% with a 6-hour protocol of rapid interventions, H. Bryant Nguyen, M.D., reported at a meeting sponsored by the Society of Critical Care Medicine.

Data on 208 sepsis patients treated from the start of the program in October 2003 through the end of 2004 show that the greatest benefit occurs when the protocol is completed on time, said Dr. Nguyen of Loma Linda (Calif.) University.

Mortality was 12.5% among the 24 patients who received all of the interventions within 6 hours, but was 34.2% among the 184 patients in whom the “STOP Sepsis Bundle” protocol was started but not completed within 6 hours. The difference in mortality was highly significant (P =.008).

STOP stands for Strategies to Timely Obviate the Progression of Sepsis in the Emergency Department. Dr. Nguyen modeled the STOP Sepsis Bundle protocol after the 6-hour Severe Sepsis bundle promoted by the Institute for Healthcare Improvement (IHI) and the international Surviving Sepsis Campaign (SSC).

As presented by Dr. Nguyen, Loma Linda's STOP Sepsis Bundle is set in motion for patients who meet three criteria: systemic inflammatory response syndrome (SIRS), a source of infection, and any one of the following: a systolic blood pressure less than 90 mm Hg after a 20 mL/kg fluid bolus, a serum lactate level of 4 mmol/L or higher, or more than one acute organ dysfunction.

The protocol comprises five components, of which the first three must be completed within 6 hours:

▸ Begin hemodynamic monitoring (central venous pressure [CVP] and central venous oxygen saturation [ScvO₂]) within 2 hours.

▸ Start broad-spectrum antibiotics within 4 hours.

▸ Use early goal-directed therapy (EGDT), with these goals to be achieved within 6 hours and maintained until admission: CVP of at least 8 mm Hg, mean arterial pressure (MAP) of at least 65 mm Hg, and ScvO₂ of at least 70%.

▸ Obtain serial lactate levels to monitor for lactate clearance.

▸ Initiate corticosteroid treatment if the patient is on a vasopressor.

Dr. Nguyen said he focused on goals to be achieved rather than methods in customizing the SSC/IHI bundle. His modifications drew praise from Jean-Louis Vincent, M.D., a member of the SSC panel who worked on its sepsis bundle. Dr. Vincent, chair of the department of intensive care at Erasme University Hospital in Brussels, chaired the sepsis research session at the meeting.

“You have not really implemented the bundle of the Surviving Sepsis Campaign,” he told Dr. Nguyen. “You have implemented a better bundle. … You changed it to improve it.”

Dr. Nguyen described a gradual implementation process in which bundle components were added at 3-month intervals. The phase-in started with staff education, and included nursing in-service training sessions every 6 months, grand rounds, quality improvement reports every 2 months, and continuous review of data.

“EGDT is easy to initiate but appears to be the most challenging component to complete,” said Dr. Nguyen.

Patients who received the complete bundle not only had a survival advantage, they had shorter lengths of stay in the hospital (although the difference was not statistically significant): 8.1 days vs. 11.9 days for the larger cohort of sepsis patients (P = .06). “Completion of the bundle is associated with improved outcome and possibly a decrease in resource consumption in terms of length of stay,” he concluded.

The staff has reached the point where it is comfortable with the arduous protocol, he added. “We treat them [sepsis patients] as a trauma patient. We treat them as a cardiac arrest patient. We invest the time for 2-3 hours,” he said. “If we don't, in 6 hours they arrest.”

PHOENIX, ARIZ. — In-hospital sepsis mortality was reduced from 42% to 22% with a 6-hour protocol of rapid interventions, H. Bryant Nguyen, M.D., reported at a meeting sponsored by the Society of Critical Care Medicine.

Data on 208 sepsis patients treated from the start of the program in October 2003 through the end of 2004 show that the greatest benefit occurs when the protocol is completed on time, said Dr. Nguyen of Loma Linda (Calif.) University.

Mortality was 12.5% among the 24 patients who received all of the interventions within 6 hours, but was 34.2% among the 184 patients in whom the “STOP Sepsis Bundle” protocol was started but not completed within 6 hours. The difference in mortality was highly significant (P =.008).

STOP stands for Strategies to Timely Obviate the Progression of Sepsis in the Emergency Department. Dr. Nguyen modeled the STOP Sepsis Bundle protocol after the 6-hour Severe Sepsis bundle promoted by the Institute for Healthcare Improvement (IHI) and the international Surviving Sepsis Campaign (SSC).

As presented by Dr. Nguyen, Loma Linda's STOP Sepsis Bundle is set in motion for patients who meet three criteria: systemic inflammatory response syndrome (SIRS), a source of infection, and any one of the following: a systolic blood pressure less than 90 mm Hg after a 20 mL/kg fluid bolus, a serum lactate level of 4 mmol/L or higher, or more than one acute organ dysfunction.

The protocol comprises five components, of which the first three must be completed within 6 hours:

▸ Begin hemodynamic monitoring (central venous pressure [CVP] and central venous oxygen saturation [ScvO₂]) within 2 hours.

▸ Start broad-spectrum antibiotics within 4 hours.

▸ Use early goal-directed therapy (EGDT), with these goals to be achieved within 6 hours and maintained until admission: CVP of at least 8 mm Hg, mean arterial pressure (MAP) of at least 65 mm Hg, and ScvO₂ of at least 70%.

▸ Obtain serial lactate levels to monitor for lactate clearance.

▸ Initiate corticosteroid treatment if the patient is on a vasopressor.

Dr. Nguyen said he focused on goals to be achieved rather than methods in customizing the SSC/IHI bundle. His modifications drew praise from Jean-Louis Vincent, M.D., a member of the SSC panel who worked on its sepsis bundle. Dr. Vincent, chair of the department of intensive care at Erasme University Hospital in Brussels, chaired the sepsis research session at the meeting.

“You have not really implemented the bundle of the Surviving Sepsis Campaign,” he told Dr. Nguyen. “You have implemented a better bundle. … You changed it to improve it.”

Dr. Nguyen described a gradual implementation process in which bundle components were added at 3-month intervals. The phase-in started with staff education, and included nursing in-service training sessions every 6 months, grand rounds, quality improvement reports every 2 months, and continuous review of data.

“EGDT is easy to initiate but appears to be the most challenging component to complete,” said Dr. Nguyen.

Patients who received the complete bundle not only had a survival advantage, they had shorter lengths of stay in the hospital (although the difference was not statistically significant): 8.1 days vs. 11.9 days for the larger cohort of sepsis patients (P = .06). “Completion of the bundle is associated with improved outcome and possibly a decrease in resource consumption in terms of length of stay,” he concluded.

The staff has reached the point where it is comfortable with the arduous protocol, he added. “We treat them [sepsis patients] as a trauma patient. We treat them as a cardiac arrest patient. We invest the time for 2-3 hours,” he said. “If we don't, in 6 hours they arrest.”

PHOENIX, ARIZ. — In-hospital sepsis mortality was reduced from 42% to 22% with a 6-hour protocol of rapid interventions, H. Bryant Nguyen, M.D., reported at a meeting sponsored by the Society of Critical Care Medicine.

Data on 208 sepsis patients treated from the start of the program in October 2003 through the end of 2004 show that the greatest benefit occurs when the protocol is completed on time, said Dr. Nguyen of Loma Linda (Calif.) University.

Mortality was 12.5% among the 24 patients who received all of the interventions within 6 hours, but was 34.2% among the 184 patients in whom the “STOP Sepsis Bundle” protocol was started but not completed within 6 hours. The difference in mortality was highly significant (P =.008).

STOP stands for Strategies to Timely Obviate the Progression of Sepsis in the Emergency Department. Dr. Nguyen modeled the STOP Sepsis Bundle protocol after the 6-hour Severe Sepsis bundle promoted by the Institute for Healthcare Improvement (IHI) and the international Surviving Sepsis Campaign (SSC).

As presented by Dr. Nguyen, Loma Linda's STOP Sepsis Bundle is set in motion for patients who meet three criteria: systemic inflammatory response syndrome (SIRS), a source of infection, and any one of the following: a systolic blood pressure less than 90 mm Hg after a 20 mL/kg fluid bolus, a serum lactate level of 4 mmol/L or higher, or more than one acute organ dysfunction.

The protocol comprises five components, of which the first three must be completed within 6 hours:

▸ Begin hemodynamic monitoring (central venous pressure [CVP] and central venous oxygen saturation [ScvO₂]) within 2 hours.

▸ Start broad-spectrum antibiotics within 4 hours.

▸ Use early goal-directed therapy (EGDT), with these goals to be achieved within 6 hours and maintained until admission: CVP of at least 8 mm Hg, mean arterial pressure (MAP) of at least 65 mm Hg, and ScvO₂ of at least 70%.

▸ Obtain serial lactate levels to monitor for lactate clearance.

▸ Initiate corticosteroid treatment if the patient is on a vasopressor.

Dr. Nguyen said he focused on goals to be achieved rather than methods in customizing the SSC/IHI bundle. His modifications drew praise from Jean-Louis Vincent, M.D., a member of the SSC panel who worked on its sepsis bundle. Dr. Vincent, chair of the department of intensive care at Erasme University Hospital in Brussels, chaired the sepsis research session at the meeting.

“You have not really implemented the bundle of the Surviving Sepsis Campaign,” he told Dr. Nguyen. “You have implemented a better bundle. … You changed it to improve it.”

Dr. Nguyen described a gradual implementation process in which bundle components were added at 3-month intervals. The phase-in started with staff education, and included nursing in-service training sessions every 6 months, grand rounds, quality improvement reports every 2 months, and continuous review of data.

“EGDT is easy to initiate but appears to be the most challenging component to complete,” said Dr. Nguyen.

Patients who received the complete bundle not only had a survival advantage, they had shorter lengths of stay in the hospital (although the difference was not statistically significant): 8.1 days vs. 11.9 days for the larger cohort of sepsis patients (P = .06). “Completion of the bundle is associated with improved outcome and possibly a decrease in resource consumption in terms of length of stay,” he concluded.

The staff has reached the point where it is comfortable with the arduous protocol, he added. “We treat them [sepsis patients] as a trauma patient. We treat them as a cardiac arrest patient. We invest the time for 2-3 hours,” he said. “If we don't, in 6 hours they arrest.”

PHOENIX, ARIZ. — Risk of death from sepsis increases by 6%-10% with every hour that passes from the onset of septic shock until the start of effective antimicrobial therapy, according to a review of more than 2,600 consecutive cases at 15 intensive care units in five U.S. and Canadian cities.

“You already have a substantially increased risk of death if you get antibiotics by the second hour after onset of hypotension compared with the first hour—and that odds ratio continues to climb out to 36 hours,” principal investigator Anand Kumar, M.D., said at a meeting sponsored by the Society of Critical Care Medicine.

But relatively few patients received appropriate antibiotics within 2 hours.

Dr. Kumar, head of the emergency department at the University of Manitoba in Winnipeg, reported that at every hospital studied, “Only half of septic shock patients received an antibiotic within 6 hours of onset of recurrent or persistent hypotension.”

Early administration of appropriate antibiotics is crucial because it eliminates the source of sepsis, according to Dr. Kumar. “You can keep the patients alive for days, but if you don't eliminate the source in the first couple of hours, they are not going to make it.”

All told, 44% of 2,731 septic shock patients reviewed by Dr. Kumar and his colleagues survived to hospital discharge. Removing patients who were moribund at presentation (those who required intubation or cardiopulmonary resuscitation in the field) reduced the population to 2,675 patients, but barely nudged the survival rate up to 48%.

The population had slightly more men than women and an average age of 62.5 years.

Nosocomial infections accounted for 42% of cases. Malignancy was the most common comorbidity (20%), followed by chemotherapy and elective surgery, each about 15%. The average Acute Physiology and Chronic Health Evaluation II score was 25.9.

Dr. Kumar said emergency departments were about an hour faster than other areas of the hospital in delivering antibiotics, but still too slow. The median emergency department time to treat was 4.5-5 hours, he said.

The investigation started with animal studies. In those experiments, mortality was held to 10% if the animals were given an antibiotic within a 12-hour window before the onset of hypotension, according to Dr. Kumar. The mortality became 80% if the antibiotic was started 15 hours afterward, and 100% at 24 hours.

In the human retrospective study reported at the meeting, 89% of patients who received an appropriate antibiotic within the first half hour survived, he said. By the second hour, the survival rate dropped to 84%, and it continued to drop at a rate of 7.5% every hour thereafter.

Subset analyses by numerous factors mostly produced P values of .0001 without changing the risk, according to Dr. Kumar. Patients who were obviously sicker at presentation received antibiotics faster, improving their odds of surviving, he said.

Only about 50 patients, all in the United States, had methicillin-resistant Staphylococcus aureus, which was not seen in Winnipeg, according to Dr. Kumar.

He noted that the investigators focused on time to effective antibiotics. If the first choice is not effective, the effects of any initial delay can be all the more overwhelming, he said.

Dr. Kumar called for hospitals to use medical response teams with algorithm protocols for patients in septic shock. He reported that his hospital has instituted the following changes in response to the study:

▸ Staff can start intravenous antibiotics in hypotensive sepsis patients without waiting for approval.

▸ Nurses have been told that the first dose of any new antibiotic is an automatic stat order.

▸ No sepsis patient is transferred to an intensive care unit without receiving an antibiotic before leaving the emergency department.

Many physicians do not realize that an antibiotic order may wait for hours if it is not marked “stat,” according to Dr. Kumar. If the patient is transferred to an ICU, more hours might pass before the antibiotic is delivered with scheduled medications, he warned.

“These simple administrative changes can reduce time to antibiotics by 2 hours,” he said. “And, if these data hold, that's a translation to a 15% absolute improvement in mortality.”

PHOENIX, ARIZ. — Risk of death from sepsis increases by 6%-10% with every hour that passes from the onset of septic shock until the start of effective antimicrobial therapy, according to a review of more than 2,600 consecutive cases at 15 intensive care units in five U.S. and Canadian cities.

“You already have a substantially increased risk of death if you get antibiotics by the second hour after onset of hypotension compared with the first hour—and that odds ratio continues to climb out to 36 hours,” principal investigator Anand Kumar, M.D., said at a meeting sponsored by the Society of Critical Care Medicine.

But relatively few patients received appropriate antibiotics within 2 hours.

Dr. Kumar, head of the emergency department at the University of Manitoba in Winnipeg, reported that at every hospital studied, “Only half of septic shock patients received an antibiotic within 6 hours of onset of recurrent or persistent hypotension.”

Early administration of appropriate antibiotics is crucial because it eliminates the source of sepsis, according to Dr. Kumar. “You can keep the patients alive for days, but if you don't eliminate the source in the first couple of hours, they are not going to make it.”

All told, 44% of 2,731 septic shock patients reviewed by Dr. Kumar and his colleagues survived to hospital discharge. Removing patients who were moribund at presentation (those who required intubation or cardiopulmonary resuscitation in the field) reduced the population to 2,675 patients, but barely nudged the survival rate up to 48%.

The population had slightly more men than women and an average age of 62.5 years.

Nosocomial infections accounted for 42% of cases. Malignancy was the most common comorbidity (20%), followed by chemotherapy and elective surgery, each about 15%. The average Acute Physiology and Chronic Health Evaluation II score was 25.9.

Dr. Kumar said emergency departments were about an hour faster than other areas of the hospital in delivering antibiotics, but still too slow. The median emergency department time to treat was 4.5-5 hours, he said.

The investigation started with animal studies. In those experiments, mortality was held to 10% if the animals were given an antibiotic within a 12-hour window before the onset of hypotension, according to Dr. Kumar. The mortality became 80% if the antibiotic was started 15 hours afterward, and 100% at 24 hours.

In the human retrospective study reported at the meeting, 89% of patients who received an appropriate antibiotic within the first half hour survived, he said. By the second hour, the survival rate dropped to 84%, and it continued to drop at a rate of 7.5% every hour thereafter.

Subset analyses by numerous factors mostly produced P values of .0001 without changing the risk, according to Dr. Kumar. Patients who were obviously sicker at presentation received antibiotics faster, improving their odds of surviving, he said.

Only about 50 patients, all in the United States, had methicillin-resistant Staphylococcus aureus, which was not seen in Winnipeg, according to Dr. Kumar.

He noted that the investigators focused on time to effective antibiotics. If the first choice is not effective, the effects of any initial delay can be all the more overwhelming, he said.

Dr. Kumar called for hospitals to use medical response teams with algorithm protocols for patients in septic shock. He reported that his hospital has instituted the following changes in response to the study:

▸ Staff can start intravenous antibiotics in hypotensive sepsis patients without waiting for approval.

▸ Nurses have been told that the first dose of any new antibiotic is an automatic stat order.

▸ No sepsis patient is transferred to an intensive care unit without receiving an antibiotic before leaving the emergency department.

Many physicians do not realize that an antibiotic order may wait for hours if it is not marked “stat,” according to Dr. Kumar. If the patient is transferred to an ICU, more hours might pass before the antibiotic is delivered with scheduled medications, he warned.

“These simple administrative changes can reduce time to antibiotics by 2 hours,” he said. “And, if these data hold, that's a translation to a 15% absolute improvement in mortality.”

PHOENIX, ARIZ. — Risk of death from sepsis increases by 6%-10% with every hour that passes from the onset of septic shock until the start of effective antimicrobial therapy, according to a review of more than 2,600 consecutive cases at 15 intensive care units in five U.S. and Canadian cities.

“You already have a substantially increased risk of death if you get antibiotics by the second hour after onset of hypotension compared with the first hour—and that odds ratio continues to climb out to 36 hours,” principal investigator Anand Kumar, M.D., said at a meeting sponsored by the Society of Critical Care Medicine.

But relatively few patients received appropriate antibiotics within 2 hours.

Dr. Kumar, head of the emergency department at the University of Manitoba in Winnipeg, reported that at every hospital studied, “Only half of septic shock patients received an antibiotic within 6 hours of onset of recurrent or persistent hypotension.”

Early administration of appropriate antibiotics is crucial because it eliminates the source of sepsis, according to Dr. Kumar. “You can keep the patients alive for days, but if you don't eliminate the source in the first couple of hours, they are not going to make it.”

All told, 44% of 2,731 septic shock patients reviewed by Dr. Kumar and his colleagues survived to hospital discharge. Removing patients who were moribund at presentation (those who required intubation or cardiopulmonary resuscitation in the field) reduced the population to 2,675 patients, but barely nudged the survival rate up to 48%.

The population had slightly more men than women and an average age of 62.5 years.

Nosocomial infections accounted for 42% of cases. Malignancy was the most common comorbidity (20%), followed by chemotherapy and elective surgery, each about 15%. The average Acute Physiology and Chronic Health Evaluation II score was 25.9.

Dr. Kumar said emergency departments were about an hour faster than other areas of the hospital in delivering antibiotics, but still too slow. The median emergency department time to treat was 4.5-5 hours, he said.

The investigation started with animal studies. In those experiments, mortality was held to 10% if the animals were given an antibiotic within a 12-hour window before the onset of hypotension, according to Dr. Kumar. The mortality became 80% if the antibiotic was started 15 hours afterward, and 100% at 24 hours.

In the human retrospective study reported at the meeting, 89% of patients who received an appropriate antibiotic within the first half hour survived, he said. By the second hour, the survival rate dropped to 84%, and it continued to drop at a rate of 7.5% every hour thereafter.

Subset analyses by numerous factors mostly produced P values of .0001 without changing the risk, according to Dr. Kumar. Patients who were obviously sicker at presentation received antibiotics faster, improving their odds of surviving, he said.

Only about 50 patients, all in the United States, had methicillin-resistant Staphylococcus aureus, which was not seen in Winnipeg, according to Dr. Kumar.

He noted that the investigators focused on time to effective antibiotics. If the first choice is not effective, the effects of any initial delay can be all the more overwhelming, he said.

Dr. Kumar called for hospitals to use medical response teams with algorithm protocols for patients in septic shock. He reported that his hospital has instituted the following changes in response to the study:

▸ Staff can start intravenous antibiotics in hypotensive sepsis patients without waiting for approval.

▸ Nurses have been told that the first dose of any new antibiotic is an automatic stat order.

▸ No sepsis patient is transferred to an intensive care unit without receiving an antibiotic before leaving the emergency department.

Many physicians do not realize that an antibiotic order may wait for hours if it is not marked “stat,” according to Dr. Kumar. If the patient is transferred to an ICU, more hours might pass before the antibiotic is delivered with scheduled medications, he warned.

“These simple administrative changes can reduce time to antibiotics by 2 hours,” he said. “And, if these data hold, that's a translation to a 15% absolute improvement in mortality.”

HOUSTON — Whether to treat genital warts may seem like a no-brainer, but Peter J. Lynch, M.D., has a list of reasons for not trying to eradicate some vulvar lesions.

Many genital warts resolve spontaneously. The underlying cause, human papillomavirus (HPV), is “nearly universal,” and destroying the lesion will not eradicate latent virus in the host, he said at a conference on vulvovaginal diseases sponsored by Baylor College of Medicine.

“There's a high rate of recurrence with all forms of treatment and a high cost for treatment, both economically and psychologically, with very little benefit,” said Dr. Lynch, a dermatologist in Sacramento. Still, he included himself among the majority of clinicians who treat genital warts. Patient wishes, concerns about cancer risks, and legal vulnerability make genital warts difficult to ignore.

Vulvar warts must be characterized and the source of infection confirmed before they are treated. Vulvar lesions from HPV infection are highly variable, he said, listing the most common forms:

▸ Filiform warts (condyloma acuminata) are taller than they are wide. They are about a quarter-inch to a half an inch long and skin colored or slightly pink. The tip is a little thicker than the stalk and often consists of brush-like bristles.

▸ Papules or nodules are as wide as they are tall—usually about the size of a pencil eraser (but sometimes as large as a plum), and skin colored or light brown. They are usually smooth but can feel rough if located in dry anogenital tissue.

▸ Flat warts are small, bare-topped, barely elevated papules that are wider than they are tall. They are about a quarter-inch in diameter and skin colored, pink, tan, or dark brown. The most common type of wart in the vulva, flat warts can coalesce into flat-topped plaques.

Dr. Lynch recommended biopsy to make certain the cause is HPV infection and to rule out malignancy. Once vulvar HPV infection is established, other anogenital areas should be examined to rule out possible HPV infection there. The next step is to choose among these three therapeutic options:

▸ Home-based medical therapy, in which the patient applies a 5% cream of imiquimod (Aldara) or podofilox (Condylox). The weekly frequency might be every other day for imiquimod or 3 days in a row for podofilox. About a third of patients have complete clearance after 2 months of treatment, Dr. Lynch said.

▸ Office-based medical therapy lets the clinician monitor compliance. He characterized this choice as inconvenient for patient and clinician, and the response rate is similar to home-based treatment.

▸ Office-based destructive treatment can be quite effective. Treatments requiring anesthesia (electrosurgery, excision, laser therapy) can have a 100% response rate. Treatments that can be done without anesthesia (cryotherapy, podophyllin, tri- or bichloracetic acid, and 5-fluorouracil) lead to complete clearance in two-thirds of patients.

His advice: “Either use home therapy, where the patient treats herself … or go to destructive therapy. Expect at least a 35% recurrence rate with either approach. Medical therapy in the office has all the disadvantages of home therapy without any improvement in results.”

HOUSTON — Whether to treat genital warts may seem like a no-brainer, but Peter J. Lynch, M.D., has a list of reasons for not trying to eradicate some vulvar lesions.

Many genital warts resolve spontaneously. The underlying cause, human papillomavirus (HPV), is “nearly universal,” and destroying the lesion will not eradicate latent virus in the host, he said at a conference on vulvovaginal diseases sponsored by Baylor College of Medicine.

“There's a high rate of recurrence with all forms of treatment and a high cost for treatment, both economically and psychologically, with very little benefit,” said Dr. Lynch, a dermatologist in Sacramento. Still, he included himself among the majority of clinicians who treat genital warts. Patient wishes, concerns about cancer risks, and legal vulnerability make genital warts difficult to ignore.

Vulvar warts must be characterized and the source of infection confirmed before they are treated. Vulvar lesions from HPV infection are highly variable, he said, listing the most common forms:

▸ Filiform warts (condyloma acuminata) are taller than they are wide. They are about a quarter-inch to a half an inch long and skin colored or slightly pink. The tip is a little thicker than the stalk and often consists of brush-like bristles.

▸ Papules or nodules are as wide as they are tall—usually about the size of a pencil eraser (but sometimes as large as a plum), and skin colored or light brown. They are usually smooth but can feel rough if located in dry anogenital tissue.

▸ Flat warts are small, bare-topped, barely elevated papules that are wider than they are tall. They are about a quarter-inch in diameter and skin colored, pink, tan, or dark brown. The most common type of wart in the vulva, flat warts can coalesce into flat-topped plaques.

Dr. Lynch recommended biopsy to make certain the cause is HPV infection and to rule out malignancy. Once vulvar HPV infection is established, other anogenital areas should be examined to rule out possible HPV infection there. The next step is to choose among these three therapeutic options:

▸ Home-based medical therapy, in which the patient applies a 5% cream of imiquimod (Aldara) or podofilox (Condylox). The weekly frequency might be every other day for imiquimod or 3 days in a row for podofilox. About a third of patients have complete clearance after 2 months of treatment, Dr. Lynch said.

▸ Office-based medical therapy lets the clinician monitor compliance. He characterized this choice as inconvenient for patient and clinician, and the response rate is similar to home-based treatment.

▸ Office-based destructive treatment can be quite effective. Treatments requiring anesthesia (electrosurgery, excision, laser therapy) can have a 100% response rate. Treatments that can be done without anesthesia (cryotherapy, podophyllin, tri- or bichloracetic acid, and 5-fluorouracil) lead to complete clearance in two-thirds of patients.

His advice: “Either use home therapy, where the patient treats herself … or go to destructive therapy. Expect at least a 35% recurrence rate with either approach. Medical therapy in the office has all the disadvantages of home therapy without any improvement in results.”

HOUSTON — Whether to treat genital warts may seem like a no-brainer, but Peter J. Lynch, M.D., has a list of reasons for not trying to eradicate some vulvar lesions.

Many genital warts resolve spontaneously. The underlying cause, human papillomavirus (HPV), is “nearly universal,” and destroying the lesion will not eradicate latent virus in the host, he said at a conference on vulvovaginal diseases sponsored by Baylor College of Medicine.

“There's a high rate of recurrence with all forms of treatment and a high cost for treatment, both economically and psychologically, with very little benefit,” said Dr. Lynch, a dermatologist in Sacramento. Still, he included himself among the majority of clinicians who treat genital warts. Patient wishes, concerns about cancer risks, and legal vulnerability make genital warts difficult to ignore.

Vulvar warts must be characterized and the source of infection confirmed before they are treated. Vulvar lesions from HPV infection are highly variable, he said, listing the most common forms:

▸ Filiform warts (condyloma acuminata) are taller than they are wide. They are about a quarter-inch to a half an inch long and skin colored or slightly pink. The tip is a little thicker than the stalk and often consists of brush-like bristles.

▸ Papules or nodules are as wide as they are tall—usually about the size of a pencil eraser (but sometimes as large as a plum), and skin colored or light brown. They are usually smooth but can feel rough if located in dry anogenital tissue.

▸ Flat warts are small, bare-topped, barely elevated papules that are wider than they are tall. They are about a quarter-inch in diameter and skin colored, pink, tan, or dark brown. The most common type of wart in the vulva, flat warts can coalesce into flat-topped plaques.

Dr. Lynch recommended biopsy to make certain the cause is HPV infection and to rule out malignancy. Once vulvar HPV infection is established, other anogenital areas should be examined to rule out possible HPV infection there. The next step is to choose among these three therapeutic options:

▸ Home-based medical therapy, in which the patient applies a 5% cream of imiquimod (Aldara) or podofilox (Condylox). The weekly frequency might be every other day for imiquimod or 3 days in a row for podofilox. About a third of patients have complete clearance after 2 months of treatment, Dr. Lynch said.

▸ Office-based medical therapy lets the clinician monitor compliance. He characterized this choice as inconvenient for patient and clinician, and the response rate is similar to home-based treatment.

▸ Office-based destructive treatment can be quite effective. Treatments requiring anesthesia (electrosurgery, excision, laser therapy) can have a 100% response rate. Treatments that can be done without anesthesia (cryotherapy, podophyllin, tri- or bichloracetic acid, and 5-fluorouracil) lead to complete clearance in two-thirds of patients.

His advice: “Either use home therapy, where the patient treats herself … or go to destructive therapy. Expect at least a 35% recurrence rate with either approach. Medical therapy in the office has all the disadvantages of home therapy without any improvement in results.”