Betsy Bates

HONOLULU – Disappointing clinical trial results should not suggest that outcomes cannot be improved in traumatic brain injury, only that methodologies may need to be refined and study populations equalized as promising approaches come to the fore, Dr. D. James Cooper said during a plenary address at the annual congress of the Society of Critical Care Medicine.

To be sure, meaningful advances have been elusive, with various interventions producing hopeful improvements in animal models, then fizzling in human trials.

But the heterogeneity of the traumatic brain injury (TBI) population and “huge differences” in the specific trauma suffered may make study results look unfairly pessimistic, said Dr. Cooper, deputy director of the intensive care unit at Alfred Hospital, Melbourne.

Experimental treatments may be initiated too late, often because of logistical and informed-consent dilemmas, and older patients may be so unlikely to benefit that they negatively skew results.

Follow-up assessment periods may be too brief, because it increasingly appears that Glasgow Outcome Scale scores improve greatly over time, but at a very slow pace, he said.

A number of lessons have indeed been learned, even from negative clinical trials, and several promising approaches are currently under review.

Serious doubt has been cast on the efficacy of early high-dose steroids, for example, following the curtailment of the 10,000-patient randomized controlled MRC-CRASH (Corticosteroid Randomisation After Significant Head Injury) trial in the United Kingdom after excess deaths were reported in the steroid arm.

“It seems clear from the study that the use of an agent that has been very widely used, particularly in the developing world, clearly and unambiguously increases mortality, accounting for an absolute number of 3% excess deaths. I think it's abundantly clear … [that the] use of high-dose steroids should cease,” said Dr. Cooper, who also serves as associate director for Australia's National Trauma Research Institute.

Because they lower vasopressor requirements in TBI patients, lower-dose steroids are used quite commonly in the intensive care environment, he noted.

“There are no randomized controlled trials at all in this area, and it's clear to me, [based on the unequivocal MRC-CRASH results, that] there needs to be … a reevaluation” of this practice, said Dr. Cooper.

Another unexpected finding stemmed from the Australian SAFE-TBI (Saline Versus Albumin Fluid Evaluation-Traumatic Brain Injury) study, in which Dr. Cooper participated. That study of nearly 500 patients confirmed that albumin is independently associated with mortality in TBI patients when it is used for intravascular fluid resuscitation in the first 28 days. In contrast, saline was associated with lower mortality and better neurologic outcomes in patients with moderate to severe TBI.

The reasons remain unclear, although Dr. Cooper hypothesized that albumin may increase brain edema, prompting the use of other agents that could contribute to mortality; that it may increase bleeding or cause more coagulopathy; or that it may be the result of hemodilution.

A recent analysis of data from both the SAFE-TBI study and the earlier ATBIS (Australasian Traumatic Brain Injury Study) “[adds] to our strong feeling that saline alone might be worthwhile,” he said.

As a final note, Dr. Cooper outlined two ongoing international clinical trials of early decompressive craniectomy to reduce intracranial pressure, an approach he said may offer “considerable promise.”

The notion of temporarily removing the anterior portion of the skull is not a new idea, he stressed. But it has been controversial and not well studied, despite striking findings of benefit among young patients in small trials.

For example, the absolute risk of mortality was halved with early decompressive craniectomy versus medical therapy alone in a recent, 38-patient French study; but the trial was concluded early because of slow recruitment.

Dr. Cooper's government-sponsored DECRA (Early Decompression Craniectomy in Patients With Severe Traumatic Brain Injury) trial at 21 international sites (including 2 in the United States) is enrolling only patients younger than 60 years old with blunt diffuse brain injuries–strict criteria that may be more conducive to interpreting results, he said.

Thus far, 112 patients have been enrolled of 165 anticipated, which is “already many, many times higher than the largest study ever conducted of early decompressive craniectomy,” Dr. Cooper noted.

Among the first 42 patients randomized to receive surgery, the complication rate has been less than 10%, he said.

HONOLULU – Disappointing clinical trial results should not suggest that outcomes cannot be improved in traumatic brain injury, only that methodologies may need to be refined and study populations equalized as promising approaches come to the fore, Dr. D. James Cooper said during a plenary address at the annual congress of the Society of Critical Care Medicine.

To be sure, meaningful advances have been elusive, with various interventions producing hopeful improvements in animal models, then fizzling in human trials.

But the heterogeneity of the traumatic brain injury (TBI) population and “huge differences” in the specific trauma suffered may make study results look unfairly pessimistic, said Dr. Cooper, deputy director of the intensive care unit at Alfred Hospital, Melbourne.

Experimental treatments may be initiated too late, often because of logistical and informed-consent dilemmas, and older patients may be so unlikely to benefit that they negatively skew results.

Follow-up assessment periods may be too brief, because it increasingly appears that Glasgow Outcome Scale scores improve greatly over time, but at a very slow pace, he said.

A number of lessons have indeed been learned, even from negative clinical trials, and several promising approaches are currently under review.

Serious doubt has been cast on the efficacy of early high-dose steroids, for example, following the curtailment of the 10,000-patient randomized controlled MRC-CRASH (Corticosteroid Randomisation After Significant Head Injury) trial in the United Kingdom after excess deaths were reported in the steroid arm.

“It seems clear from the study that the use of an agent that has been very widely used, particularly in the developing world, clearly and unambiguously increases mortality, accounting for an absolute number of 3% excess deaths. I think it's abundantly clear … [that the] use of high-dose steroids should cease,” said Dr. Cooper, who also serves as associate director for Australia's National Trauma Research Institute.

Because they lower vasopressor requirements in TBI patients, lower-dose steroids are used quite commonly in the intensive care environment, he noted.

“There are no randomized controlled trials at all in this area, and it's clear to me, [based on the unequivocal MRC-CRASH results, that] there needs to be … a reevaluation” of this practice, said Dr. Cooper.

Another unexpected finding stemmed from the Australian SAFE-TBI (Saline Versus Albumin Fluid Evaluation-Traumatic Brain Injury) study, in which Dr. Cooper participated. That study of nearly 500 patients confirmed that albumin is independently associated with mortality in TBI patients when it is used for intravascular fluid resuscitation in the first 28 days. In contrast, saline was associated with lower mortality and better neurologic outcomes in patients with moderate to severe TBI.

The reasons remain unclear, although Dr. Cooper hypothesized that albumin may increase brain edema, prompting the use of other agents that could contribute to mortality; that it may increase bleeding or cause more coagulopathy; or that it may be the result of hemodilution.

A recent analysis of data from both the SAFE-TBI study and the earlier ATBIS (Australasian Traumatic Brain Injury Study) “[adds] to our strong feeling that saline alone might be worthwhile,” he said.

As a final note, Dr. Cooper outlined two ongoing international clinical trials of early decompressive craniectomy to reduce intracranial pressure, an approach he said may offer “considerable promise.”

The notion of temporarily removing the anterior portion of the skull is not a new idea, he stressed. But it has been controversial and not well studied, despite striking findings of benefit among young patients in small trials.

For example, the absolute risk of mortality was halved with early decompressive craniectomy versus medical therapy alone in a recent, 38-patient French study; but the trial was concluded early because of slow recruitment.

Dr. Cooper's government-sponsored DECRA (Early Decompression Craniectomy in Patients With Severe Traumatic Brain Injury) trial at 21 international sites (including 2 in the United States) is enrolling only patients younger than 60 years old with blunt diffuse brain injuries–strict criteria that may be more conducive to interpreting results, he said.

Thus far, 112 patients have been enrolled of 165 anticipated, which is “already many, many times higher than the largest study ever conducted of early decompressive craniectomy,” Dr. Cooper noted.

Among the first 42 patients randomized to receive surgery, the complication rate has been less than 10%, he said.

HONOLULU – Disappointing clinical trial results should not suggest that outcomes cannot be improved in traumatic brain injury, only that methodologies may need to be refined and study populations equalized as promising approaches come to the fore, Dr. D. James Cooper said during a plenary address at the annual congress of the Society of Critical Care Medicine.

To be sure, meaningful advances have been elusive, with various interventions producing hopeful improvements in animal models, then fizzling in human trials.

But the heterogeneity of the traumatic brain injury (TBI) population and “huge differences” in the specific trauma suffered may make study results look unfairly pessimistic, said Dr. Cooper, deputy director of the intensive care unit at Alfred Hospital, Melbourne.

Experimental treatments may be initiated too late, often because of logistical and informed-consent dilemmas, and older patients may be so unlikely to benefit that they negatively skew results.

Follow-up assessment periods may be too brief, because it increasingly appears that Glasgow Outcome Scale scores improve greatly over time, but at a very slow pace, he said.

A number of lessons have indeed been learned, even from negative clinical trials, and several promising approaches are currently under review.

Serious doubt has been cast on the efficacy of early high-dose steroids, for example, following the curtailment of the 10,000-patient randomized controlled MRC-CRASH (Corticosteroid Randomisation After Significant Head Injury) trial in the United Kingdom after excess deaths were reported in the steroid arm.

“It seems clear from the study that the use of an agent that has been very widely used, particularly in the developing world, clearly and unambiguously increases mortality, accounting for an absolute number of 3% excess deaths. I think it's abundantly clear … [that the] use of high-dose steroids should cease,” said Dr. Cooper, who also serves as associate director for Australia's National Trauma Research Institute.

Because they lower vasopressor requirements in TBI patients, lower-dose steroids are used quite commonly in the intensive care environment, he noted.

“There are no randomized controlled trials at all in this area, and it's clear to me, [based on the unequivocal MRC-CRASH results, that] there needs to be … a reevaluation” of this practice, said Dr. Cooper.

Another unexpected finding stemmed from the Australian SAFE-TBI (Saline Versus Albumin Fluid Evaluation-Traumatic Brain Injury) study, in which Dr. Cooper participated. That study of nearly 500 patients confirmed that albumin is independently associated with mortality in TBI patients when it is used for intravascular fluid resuscitation in the first 28 days. In contrast, saline was associated with lower mortality and better neurologic outcomes in patients with moderate to severe TBI.

The reasons remain unclear, although Dr. Cooper hypothesized that albumin may increase brain edema, prompting the use of other agents that could contribute to mortality; that it may increase bleeding or cause more coagulopathy; or that it may be the result of hemodilution.

A recent analysis of data from both the SAFE-TBI study and the earlier ATBIS (Australasian Traumatic Brain Injury Study) “[adds] to our strong feeling that saline alone might be worthwhile,” he said.

As a final note, Dr. Cooper outlined two ongoing international clinical trials of early decompressive craniectomy to reduce intracranial pressure, an approach he said may offer “considerable promise.”

The notion of temporarily removing the anterior portion of the skull is not a new idea, he stressed. But it has been controversial and not well studied, despite striking findings of benefit among young patients in small trials.

For example, the absolute risk of mortality was halved with early decompressive craniectomy versus medical therapy alone in a recent, 38-patient French study; but the trial was concluded early because of slow recruitment.

Dr. Cooper's government-sponsored DECRA (Early Decompression Craniectomy in Patients With Severe Traumatic Brain Injury) trial at 21 international sites (including 2 in the United States) is enrolling only patients younger than 60 years old with blunt diffuse brain injuries–strict criteria that may be more conducive to interpreting results, he said.

Thus far, 112 patients have been enrolled of 165 anticipated, which is “already many, many times higher than the largest study ever conducted of early decompressive craniectomy,” Dr. Cooper noted.

Among the first 42 patients randomized to receive surgery, the complication rate has been less than 10%, he said.

Sweeping new clinical guidelines issued by the American College of Chest Physicians provide updated recommendations on how to prevent and manage thrombosis in surgical patients and special risk groups, including pregnant women, children, obese patients, and patients with prosthetic heart valves or a history of cardiovascular disease or stroke.

Separate sections address patients with inherited thrombophilias and treatment of deep vein thrombosis and pulmonary embolism.

Unveiled in the June issue of Chest, the guidelines represent the first major revision in the recommendations since 2004. Compiled by more than 90 experts, the 700 recommendations run more than 1,000 pages, although a concise, 38-page executive summary is available (Chest 2008;133:71S-109 [doi:10.1378/chest.08–0693]). In accordance with many new clinical guidelines, grades are assigned to each recommendation or suggestion, based on the quality of the available evidence and the strength of the recommendation.

Among the most noteworthy recommendations is a renewed call for venous thromboembolism (VTE) prophylaxis of most hospitalized patients.

“For every general hospital, we recommend that a formal, active strategy that addresses the prevention of VTE be developed … in the form of a written, institution-wide thrombo-prophylaxis policy,” the guidelines state.

Computer decision support systems, preprinted orders, and periodic audits and feedback mechanisms are advocated by the committee, while “passive methods” such as educational meetings and handouts are deemed inadequate as standalone strategies to increase adherence to thromboprophylaxis.

“Despite very good evidence, prophylaxis is still underutilized in people who would benefit,” Dr. Jack Hirsh said in an interview.

Hospitals need to have firm policies and enforce them, he added. “Instead of surgeons or physicians kicking a box, saying they should be used, the box should only have to be kicked when they are not used,” said Dr. Hirsh, professor emeritus of medicine at McMaster University and founding director of the Henderson Research Center, both in Hamilton, Ont.

In the new guidelines, the recommendation for VTE prophylaxis has been expanded beyond major general, gynecologic, and orthopedic surgeries to include bariatric and coronary artery bypass surgery.

No prophylaxis is recommended for low-risk patients undergoing laparoscopic surgery or knee arthroscopy, or those taking long airplane flights.

As expected, the new guidelines reaffirm the position of the American College of Chest Physicians that aspirin alone is not sufficient therapy to prevent venous thromboembolism in any patient population, because more effective alternatives are available, including heparin, low-molecular-weight heparin, and a synthetic, selective factor Xa inhibitor, fondaparinux, which was approved by the FDA in 2001.

Many of the guidelines now mentioning fondaparinux as an alternative anticoagulant rate the evidence for its use as 1A, meaning that the supportive data are strong.

Dr. Geno J. Merli, chief medical officer of Thomas Jefferson University Hospital, Philadelphia, welcomed the renewed emphasis on prophylaxis therapy that does not depend solely on aspirin.

“Aspirin is still being widely used for prophylaxis,” he said, noting that some consensus-based guidelines for orthopedic surgery still advocate the use of aspirin as a solo preventive agent.

The length of recommended postsurgical prophylaxis has been extended in the guidelines to 28 days (and in some surgeries, 35 days) for most general, gynecologic, and orthopedic procedures, he noted. Previously, prophylaxis was generally advised for 2 weeks following surgery.

A new chapter greatly expands evidence-based guidance concerning the perioperative management of patients on antithrombotic therapy who require emergency or elective surgery. Detailed sections provide advice for specific conditions and surgical circumstances, ranging from minor dermatologic surgery to hip fracture.

“This [publication] is not meant to be read from cover to cover,” Dr. Hirsh said. “It is an encyclopedic reference to be used by physicians if the patient has had a stroke, is at risk of stroke, has had a heart attack, is at risk of heart attack, has atrial fibrillation, has an inherited thrombophilia, or is pregnant and on antithrombotic therapy.”

Among the most pivotal changes in the recommendations are guidelines on patients with atrial fibrillation, management of pregnant women and children, and treatment of DVT.

▸ Atrial fibrillation. Antithrombotic therapy in patients with atrial fibrillation is awarded the strongest evidence grade (1A), reflecting widespread agreement of findings from randomized, controlled trials.

Target international normalized ratio ranges, drug choices, and dosages are detailed in the new guidelines in the hopes that primary care physicians will use the document to guide therapy, Dr. Hirsh said.

“There is marked underutilization of warfarin [in atrial fibrillation patients], not by cardiologists, but by family physicians. The logistics of monitoring are difficult,” he said.

As a result, the guidelines include one entire section that addresses the nuts and bolts of monitoring. Evidence is cited that affirms the rationale for using computer assistance to adjust dosages based on monitoring data.

▸ Pregnant women. Dr. Hirsh identified new guidelines for pregnancy as among “the most controversial and, I think, the most important” in the document.

Randomized trials are difficult to conduct in this population, so most of the recommendations receive a 2C grade that reflects weak evidence, noted Dr. Shannon M. Bates, who oversaw the chapter on pregnancy issues.

Nonetheless, “a great deal of work has gone into making sure that our recommendations are unbiased and clearly reflect the available data,” said Dr. Bates, director of the adult hematology residency training program at McMaster University Medical Centre in Hamilton, Ont.

“By distilling this information into clear recommendations that include a reflection of the quality of available data, we hope to make it easier for physicians to provide the best evidence-based care to their patients,” she added.

Key elements of the pregnancy guidelines include a recommendation against routine prophylaxis other than early mobilization in patients undergoing cesarean section; a recommendation against testing for inherited hypercoagulable states in women with a history of pregnancy complications; and deletion of a previous recommendation advocating antithrombotic therapy in women with pregnancy complications and a known inherited hypercoagulable state.

Guidelines were eased for patients who have inherited hypercoagulable states because the association of these conditions and pregnancy complications is backed by scant evidence, while screening and interventions are costly, might carry some degree of risk, and might provoke needless anxiety for women, Dr. Bates said.

The new guidelines also provide detailed recommendations for management of women with prosthetic heart valves who are considering pregnancy.

▸ Children. Greatly expanded guidelines “pretty well cover every conceivable thrombotic issue” in neonates and children, Dr. Hirsh noted.

Stroke is one of the 10 leading causes of death in childhood, but it is difficult to diagnose and predict based on risk factors. Therefore, the new guidelines recommend that any child with arterial ischemic stroke receive initial antithrombotic therapy until the underlying causes are understood, followed by maintenance therapy to prevent recurrence.

Detailed sections offer guidelines on the prevention of thrombotic events in children with congenital heart disease, including sections on ventricular assist devices and prosthetic heart valves.

▸ Treatment of DVT. The guidelines offer two options—one monitored and one unmonitored—for subcutaneous heparin administration for acute DVT, Dr. Merli said in an interview.

The first regimen calls for an initial dose of 17,500 U or a weight-adjusted dose of about 250 U/kg every 12 hours, with the dose adjusted to achieve and maintain an activated partial thromboplastin time (aPTT) prolongation that corresponds to plasma heparin levels of 0.3–0.7 IU/mL anti-Xa activity when measured 6 hours after injection (rather than beginning therapy with the smaller initial dose).

The second option is a fixed-dose, unmonitored regimen that calls for an initial dose of 333 U/kg followed by a twice-daily dose of 250 U/kg.

“It's good to have choices,” Dr. Merli said.

The guidelines also suggest for the first time the use of catheter-directed thrombolysis with thrombus fragmentation and/or aspiration in “selected patients with extensive acute proximal DVT who have a low risk of bleeding,” but advocate this pharmacomechanical approach only if “appropriate expertise and resources are available.”

The guidelines also acknowledge the feasibility of reducing international normalized ratio monitoring during anticoagulation therapy in very low risk patients with an unprovoked DVT who have been intensively monitored for 3 months following standard protocols, Dr. Merli noted.

'It's good to have choices' for treatment of acute DVT. DR. MERLI

Sweeping new clinical guidelines issued by the American College of Chest Physicians provide updated recommendations on how to prevent and manage thrombosis in surgical patients and special risk groups, including pregnant women, children, obese patients, and patients with prosthetic heart valves or a history of cardiovascular disease or stroke.

Separate sections address patients with inherited thrombophilias and treatment of deep vein thrombosis and pulmonary embolism.

Unveiled in the June issue of Chest, the guidelines represent the first major revision in the recommendations since 2004. Compiled by more than 90 experts, the 700 recommendations run more than 1,000 pages, although a concise, 38-page executive summary is available (Chest 2008;133:71S-109 [doi:10.1378/chest.08–0693]). In accordance with many new clinical guidelines, grades are assigned to each recommendation or suggestion, based on the quality of the available evidence and the strength of the recommendation.

Among the most noteworthy recommendations is a renewed call for venous thromboembolism (VTE) prophylaxis of most hospitalized patients.

“For every general hospital, we recommend that a formal, active strategy that addresses the prevention of VTE be developed … in the form of a written, institution-wide thrombo-prophylaxis policy,” the guidelines state.

Computer decision support systems, preprinted orders, and periodic audits and feedback mechanisms are advocated by the committee, while “passive methods” such as educational meetings and handouts are deemed inadequate as standalone strategies to increase adherence to thromboprophylaxis.

“Despite very good evidence, prophylaxis is still underutilized in people who would benefit,” Dr. Jack Hirsh said in an interview.

Hospitals need to have firm policies and enforce them, he added. “Instead of surgeons or physicians kicking a box, saying they should be used, the box should only have to be kicked when they are not used,” said Dr. Hirsh, professor emeritus of medicine at McMaster University and founding director of the Henderson Research Center, both in Hamilton, Ont.

In the new guidelines, the recommendation for VTE prophylaxis has been expanded beyond major general, gynecologic, and orthopedic surgeries to include bariatric and coronary artery bypass surgery.

No prophylaxis is recommended for low-risk patients undergoing laparoscopic surgery or knee arthroscopy, or those taking long airplane flights.

As expected, the new guidelines reaffirm the position of the American College of Chest Physicians that aspirin alone is not sufficient therapy to prevent venous thromboembolism in any patient population, because more effective alternatives are available, including heparin, low-molecular-weight heparin, and a synthetic, selective factor Xa inhibitor, fondaparinux, which was approved by the FDA in 2001.

Many of the guidelines now mentioning fondaparinux as an alternative anticoagulant rate the evidence for its use as 1A, meaning that the supportive data are strong.

Dr. Geno J. Merli, chief medical officer of Thomas Jefferson University Hospital, Philadelphia, welcomed the renewed emphasis on prophylaxis therapy that does not depend solely on aspirin.

“Aspirin is still being widely used for prophylaxis,” he said, noting that some consensus-based guidelines for orthopedic surgery still advocate the use of aspirin as a solo preventive agent.

The length of recommended postsurgical prophylaxis has been extended in the guidelines to 28 days (and in some surgeries, 35 days) for most general, gynecologic, and orthopedic procedures, he noted. Previously, prophylaxis was generally advised for 2 weeks following surgery.

A new chapter greatly expands evidence-based guidance concerning the perioperative management of patients on antithrombotic therapy who require emergency or elective surgery. Detailed sections provide advice for specific conditions and surgical circumstances, ranging from minor dermatologic surgery to hip fracture.

“This [publication] is not meant to be read from cover to cover,” Dr. Hirsh said. “It is an encyclopedic reference to be used by physicians if the patient has had a stroke, is at risk of stroke, has had a heart attack, is at risk of heart attack, has atrial fibrillation, has an inherited thrombophilia, or is pregnant and on antithrombotic therapy.”

Among the most pivotal changes in the recommendations are guidelines on patients with atrial fibrillation, management of pregnant women and children, and treatment of DVT.

▸ Atrial fibrillation. Antithrombotic therapy in patients with atrial fibrillation is awarded the strongest evidence grade (1A), reflecting widespread agreement of findings from randomized, controlled trials.

Target international normalized ratio ranges, drug choices, and dosages are detailed in the new guidelines in the hopes that primary care physicians will use the document to guide therapy, Dr. Hirsh said.

“There is marked underutilization of warfarin [in atrial fibrillation patients], not by cardiologists, but by family physicians. The logistics of monitoring are difficult,” he said.

As a result, the guidelines include one entire section that addresses the nuts and bolts of monitoring. Evidence is cited that affirms the rationale for using computer assistance to adjust dosages based on monitoring data.

▸ Pregnant women. Dr. Hirsh identified new guidelines for pregnancy as among “the most controversial and, I think, the most important” in the document.

Randomized trials are difficult to conduct in this population, so most of the recommendations receive a 2C grade that reflects weak evidence, noted Dr. Shannon M. Bates, who oversaw the chapter on pregnancy issues.

Nonetheless, “a great deal of work has gone into making sure that our recommendations are unbiased and clearly reflect the available data,” said Dr. Bates, director of the adult hematology residency training program at McMaster University Medical Centre in Hamilton, Ont.

“By distilling this information into clear recommendations that include a reflection of the quality of available data, we hope to make it easier for physicians to provide the best evidence-based care to their patients,” she added.

Key elements of the pregnancy guidelines include a recommendation against routine prophylaxis other than early mobilization in patients undergoing cesarean section; a recommendation against testing for inherited hypercoagulable states in women with a history of pregnancy complications; and deletion of a previous recommendation advocating antithrombotic therapy in women with pregnancy complications and a known inherited hypercoagulable state.

Guidelines were eased for patients who have inherited hypercoagulable states because the association of these conditions and pregnancy complications is backed by scant evidence, while screening and interventions are costly, might carry some degree of risk, and might provoke needless anxiety for women, Dr. Bates said.

The new guidelines also provide detailed recommendations for management of women with prosthetic heart valves who are considering pregnancy.

▸ Children. Greatly expanded guidelines “pretty well cover every conceivable thrombotic issue” in neonates and children, Dr. Hirsh noted.

Stroke is one of the 10 leading causes of death in childhood, but it is difficult to diagnose and predict based on risk factors. Therefore, the new guidelines recommend that any child with arterial ischemic stroke receive initial antithrombotic therapy until the underlying causes are understood, followed by maintenance therapy to prevent recurrence.

Detailed sections offer guidelines on the prevention of thrombotic events in children with congenital heart disease, including sections on ventricular assist devices and prosthetic heart valves.

▸ Treatment of DVT. The guidelines offer two options—one monitored and one unmonitored—for subcutaneous heparin administration for acute DVT, Dr. Merli said in an interview.

The first regimen calls for an initial dose of 17,500 U or a weight-adjusted dose of about 250 U/kg every 12 hours, with the dose adjusted to achieve and maintain an activated partial thromboplastin time (aPTT) prolongation that corresponds to plasma heparin levels of 0.3–0.7 IU/mL anti-Xa activity when measured 6 hours after injection (rather than beginning therapy with the smaller initial dose).

The second option is a fixed-dose, unmonitored regimen that calls for an initial dose of 333 U/kg followed by a twice-daily dose of 250 U/kg.

“It's good to have choices,” Dr. Merli said.

The guidelines also suggest for the first time the use of catheter-directed thrombolysis with thrombus fragmentation and/or aspiration in “selected patients with extensive acute proximal DVT who have a low risk of bleeding,” but advocate this pharmacomechanical approach only if “appropriate expertise and resources are available.”

The guidelines also acknowledge the feasibility of reducing international normalized ratio monitoring during anticoagulation therapy in very low risk patients with an unprovoked DVT who have been intensively monitored for 3 months following standard protocols, Dr. Merli noted.

'It's good to have choices' for treatment of acute DVT. DR. MERLI

Sweeping new clinical guidelines issued by the American College of Chest Physicians provide updated recommendations on how to prevent and manage thrombosis in surgical patients and special risk groups, including pregnant women, children, obese patients, and patients with prosthetic heart valves or a history of cardiovascular disease or stroke.

Separate sections address patients with inherited thrombophilias and treatment of deep vein thrombosis and pulmonary embolism.

Unveiled in the June issue of Chest, the guidelines represent the first major revision in the recommendations since 2004. Compiled by more than 90 experts, the 700 recommendations run more than 1,000 pages, although a concise, 38-page executive summary is available (Chest 2008;133:71S-109 [doi:10.1378/chest.08–0693]). In accordance with many new clinical guidelines, grades are assigned to each recommendation or suggestion, based on the quality of the available evidence and the strength of the recommendation.

Among the most noteworthy recommendations is a renewed call for venous thromboembolism (VTE) prophylaxis of most hospitalized patients.

“For every general hospital, we recommend that a formal, active strategy that addresses the prevention of VTE be developed … in the form of a written, institution-wide thrombo-prophylaxis policy,” the guidelines state.

Computer decision support systems, preprinted orders, and periodic audits and feedback mechanisms are advocated by the committee, while “passive methods” such as educational meetings and handouts are deemed inadequate as standalone strategies to increase adherence to thromboprophylaxis.

“Despite very good evidence, prophylaxis is still underutilized in people who would benefit,” Dr. Jack Hirsh said in an interview.

Hospitals need to have firm policies and enforce them, he added. “Instead of surgeons or physicians kicking a box, saying they should be used, the box should only have to be kicked when they are not used,” said Dr. Hirsh, professor emeritus of medicine at McMaster University and founding director of the Henderson Research Center, both in Hamilton, Ont.

In the new guidelines, the recommendation for VTE prophylaxis has been expanded beyond major general, gynecologic, and orthopedic surgeries to include bariatric and coronary artery bypass surgery.

No prophylaxis is recommended for low-risk patients undergoing laparoscopic surgery or knee arthroscopy, or those taking long airplane flights.

As expected, the new guidelines reaffirm the position of the American College of Chest Physicians that aspirin alone is not sufficient therapy to prevent venous thromboembolism in any patient population, because more effective alternatives are available, including heparin, low-molecular-weight heparin, and a synthetic, selective factor Xa inhibitor, fondaparinux, which was approved by the FDA in 2001.

Many of the guidelines now mentioning fondaparinux as an alternative anticoagulant rate the evidence for its use as 1A, meaning that the supportive data are strong.

Dr. Geno J. Merli, chief medical officer of Thomas Jefferson University Hospital, Philadelphia, welcomed the renewed emphasis on prophylaxis therapy that does not depend solely on aspirin.

“Aspirin is still being widely used for prophylaxis,” he said, noting that some consensus-based guidelines for orthopedic surgery still advocate the use of aspirin as a solo preventive agent.

The length of recommended postsurgical prophylaxis has been extended in the guidelines to 28 days (and in some surgeries, 35 days) for most general, gynecologic, and orthopedic procedures, he noted. Previously, prophylaxis was generally advised for 2 weeks following surgery.

A new chapter greatly expands evidence-based guidance concerning the perioperative management of patients on antithrombotic therapy who require emergency or elective surgery. Detailed sections provide advice for specific conditions and surgical circumstances, ranging from minor dermatologic surgery to hip fracture.

“This [publication] is not meant to be read from cover to cover,” Dr. Hirsh said. “It is an encyclopedic reference to be used by physicians if the patient has had a stroke, is at risk of stroke, has had a heart attack, is at risk of heart attack, has atrial fibrillation, has an inherited thrombophilia, or is pregnant and on antithrombotic therapy.”

Among the most pivotal changes in the recommendations are guidelines on patients with atrial fibrillation, management of pregnant women and children, and treatment of DVT.

▸ Atrial fibrillation. Antithrombotic therapy in patients with atrial fibrillation is awarded the strongest evidence grade (1A), reflecting widespread agreement of findings from randomized, controlled trials.

Target international normalized ratio ranges, drug choices, and dosages are detailed in the new guidelines in the hopes that primary care physicians will use the document to guide therapy, Dr. Hirsh said.

“There is marked underutilization of warfarin [in atrial fibrillation patients], not by cardiologists, but by family physicians. The logistics of monitoring are difficult,” he said.

As a result, the guidelines include one entire section that addresses the nuts and bolts of monitoring. Evidence is cited that affirms the rationale for using computer assistance to adjust dosages based on monitoring data.

▸ Pregnant women. Dr. Hirsh identified new guidelines for pregnancy as among “the most controversial and, I think, the most important” in the document.

Randomized trials are difficult to conduct in this population, so most of the recommendations receive a 2C grade that reflects weak evidence, noted Dr. Shannon M. Bates, who oversaw the chapter on pregnancy issues.

Nonetheless, “a great deal of work has gone into making sure that our recommendations are unbiased and clearly reflect the available data,” said Dr. Bates, director of the adult hematology residency training program at McMaster University Medical Centre in Hamilton, Ont.

“By distilling this information into clear recommendations that include a reflection of the quality of available data, we hope to make it easier for physicians to provide the best evidence-based care to their patients,” she added.

Key elements of the pregnancy guidelines include a recommendation against routine prophylaxis other than early mobilization in patients undergoing cesarean section; a recommendation against testing for inherited hypercoagulable states in women with a history of pregnancy complications; and deletion of a previous recommendation advocating antithrombotic therapy in women with pregnancy complications and a known inherited hypercoagulable state.

Guidelines were eased for patients who have inherited hypercoagulable states because the association of these conditions and pregnancy complications is backed by scant evidence, while screening and interventions are costly, might carry some degree of risk, and might provoke needless anxiety for women, Dr. Bates said.

The new guidelines also provide detailed recommendations for management of women with prosthetic heart valves who are considering pregnancy.

▸ Children. Greatly expanded guidelines “pretty well cover every conceivable thrombotic issue” in neonates and children, Dr. Hirsh noted.

Stroke is one of the 10 leading causes of death in childhood, but it is difficult to diagnose and predict based on risk factors. Therefore, the new guidelines recommend that any child with arterial ischemic stroke receive initial antithrombotic therapy until the underlying causes are understood, followed by maintenance therapy to prevent recurrence.

Detailed sections offer guidelines on the prevention of thrombotic events in children with congenital heart disease, including sections on ventricular assist devices and prosthetic heart valves.

▸ Treatment of DVT. The guidelines offer two options—one monitored and one unmonitored—for subcutaneous heparin administration for acute DVT, Dr. Merli said in an interview.

The first regimen calls for an initial dose of 17,500 U or a weight-adjusted dose of about 250 U/kg every 12 hours, with the dose adjusted to achieve and maintain an activated partial thromboplastin time (aPTT) prolongation that corresponds to plasma heparin levels of 0.3–0.7 IU/mL anti-Xa activity when measured 6 hours after injection (rather than beginning therapy with the smaller initial dose).

The second option is a fixed-dose, unmonitored regimen that calls for an initial dose of 333 U/kg followed by a twice-daily dose of 250 U/kg.

“It's good to have choices,” Dr. Merli said.

The guidelines also suggest for the first time the use of catheter-directed thrombolysis with thrombus fragmentation and/or aspiration in “selected patients with extensive acute proximal DVT who have a low risk of bleeding,” but advocate this pharmacomechanical approach only if “appropriate expertise and resources are available.”

The guidelines also acknowledge the feasibility of reducing international normalized ratio monitoring during anticoagulation therapy in very low risk patients with an unprovoked DVT who have been intensively monitored for 3 months following standard protocols, Dr. Merli noted.

'It's good to have choices' for treatment of acute DVT. DR. MERLI

BEVERLY HILLS, CALIF. — A variety of practical and psychological approaches may be the best medicine for highly active seniors suffering from osteoarthritis and overuse syndromes, speakers said at a multidisciplinary forum at the annual meeting of the American Association for Hand Surgery.

An audience member asked the panel to recommend nonsteroidal anti-inflammatory drugs (NSAIDs) that would be safe for seniors aged 80 years and older who flock to sunny locales each winter to play golf and tennis four times a week, but then come in with aching joints.

“There are no safe nonsteroidals,” replied panelist Steven R. Ytterberg, a rheumatologist at the Mayo Clinic, Rochester, Minn.

Dr. Ytterberg said physicians need to consider “hierarchies” of risk according to side-effect threats. For example, he would rate aspirin as riskiest to the gut, with cyclooxygenase-2 inhibitors “maybe a little safer for the gut, but not nearly as safe for the gut as they were promoted to be.”

Cyclooxygenase-2 inhibitors have cardiac risks of their own, he noted, but may be safer than aspirin for heart-healthy patients with a history of peptic ulcer disease.

When patients absolutely require an NSAID, Dr. Ytterberg said he tends to favor “regular” nonsteroidals.

“For some reason a lot of rheumatologists like naproxen, twice a day,” he said. At this dose, the drug has a “relatively good safety profile … but none are absolutely safe.”

Attention then turned to several certified hand therapists (CHTs), who suggested that active elderly patients can benefit from education about ergonomics and joint protection principles.

They also may need to readjust their expectations and realize they might not be able to match the performance goals they had when they were 20, said Ann Lund, an occupational therapist and CHT at the Mayo Clinic in Rochester.

Paul Brach, a physical therapist, CHT, and director of The Hand Center of Pittsburgh, said referral for an analysis of a patient's grip and/or sporting equipment may be very useful in these patients.

Joint support devices and custom-designed grips can alleviate unnecessary aggravation of osteoarthritis, he said.

“How about paraffin baths? Do they do any good?” asked Dr. Robert Beckenbaugh, professor of orthopedics at the Mayo Clinic.

“They love the paraffin. Once they start the paraffin baths it's almost impossible to get them out of our offices,” Mr. Brach said. Getting serious, he concluded, “Supportive modalities and heat modalities certainly play an important role.”

None of the speakers disclosed ties to manufacturers of drugs or devices.

BEVERLY HILLS, CALIF. — A variety of practical and psychological approaches may be the best medicine for highly active seniors suffering from osteoarthritis and overuse syndromes, speakers said at a multidisciplinary forum at the annual meeting of the American Association for Hand Surgery.

An audience member asked the panel to recommend nonsteroidal anti-inflammatory drugs (NSAIDs) that would be safe for seniors aged 80 years and older who flock to sunny locales each winter to play golf and tennis four times a week, but then come in with aching joints.

“There are no safe nonsteroidals,” replied panelist Steven R. Ytterberg, a rheumatologist at the Mayo Clinic, Rochester, Minn.

Dr. Ytterberg said physicians need to consider “hierarchies” of risk according to side-effect threats. For example, he would rate aspirin as riskiest to the gut, with cyclooxygenase-2 inhibitors “maybe a little safer for the gut, but not nearly as safe for the gut as they were promoted to be.”

Cyclooxygenase-2 inhibitors have cardiac risks of their own, he noted, but may be safer than aspirin for heart-healthy patients with a history of peptic ulcer disease.

When patients absolutely require an NSAID, Dr. Ytterberg said he tends to favor “regular” nonsteroidals.

“For some reason a lot of rheumatologists like naproxen, twice a day,” he said. At this dose, the drug has a “relatively good safety profile … but none are absolutely safe.”

Attention then turned to several certified hand therapists (CHTs), who suggested that active elderly patients can benefit from education about ergonomics and joint protection principles.

They also may need to readjust their expectations and realize they might not be able to match the performance goals they had when they were 20, said Ann Lund, an occupational therapist and CHT at the Mayo Clinic in Rochester.

Paul Brach, a physical therapist, CHT, and director of The Hand Center of Pittsburgh, said referral for an analysis of a patient's grip and/or sporting equipment may be very useful in these patients.

Joint support devices and custom-designed grips can alleviate unnecessary aggravation of osteoarthritis, he said.

“How about paraffin baths? Do they do any good?” asked Dr. Robert Beckenbaugh, professor of orthopedics at the Mayo Clinic.

“They love the paraffin. Once they start the paraffin baths it's almost impossible to get them out of our offices,” Mr. Brach said. Getting serious, he concluded, “Supportive modalities and heat modalities certainly play an important role.”

None of the speakers disclosed ties to manufacturers of drugs or devices.

BEVERLY HILLS, CALIF. — A variety of practical and psychological approaches may be the best medicine for highly active seniors suffering from osteoarthritis and overuse syndromes, speakers said at a multidisciplinary forum at the annual meeting of the American Association for Hand Surgery.

An audience member asked the panel to recommend nonsteroidal anti-inflammatory drugs (NSAIDs) that would be safe for seniors aged 80 years and older who flock to sunny locales each winter to play golf and tennis four times a week, but then come in with aching joints.

“There are no safe nonsteroidals,” replied panelist Steven R. Ytterberg, a rheumatologist at the Mayo Clinic, Rochester, Minn.

Dr. Ytterberg said physicians need to consider “hierarchies” of risk according to side-effect threats. For example, he would rate aspirin as riskiest to the gut, with cyclooxygenase-2 inhibitors “maybe a little safer for the gut, but not nearly as safe for the gut as they were promoted to be.”

Cyclooxygenase-2 inhibitors have cardiac risks of their own, he noted, but may be safer than aspirin for heart-healthy patients with a history of peptic ulcer disease.

When patients absolutely require an NSAID, Dr. Ytterberg said he tends to favor “regular” nonsteroidals.

“For some reason a lot of rheumatologists like naproxen, twice a day,” he said. At this dose, the drug has a “relatively good safety profile … but none are absolutely safe.”

Attention then turned to several certified hand therapists (CHTs), who suggested that active elderly patients can benefit from education about ergonomics and joint protection principles.

They also may need to readjust their expectations and realize they might not be able to match the performance goals they had when they were 20, said Ann Lund, an occupational therapist and CHT at the Mayo Clinic in Rochester.

Paul Brach, a physical therapist, CHT, and director of The Hand Center of Pittsburgh, said referral for an analysis of a patient's grip and/or sporting equipment may be very useful in these patients.

Joint support devices and custom-designed grips can alleviate unnecessary aggravation of osteoarthritis, he said.

“How about paraffin baths? Do they do any good?” asked Dr. Robert Beckenbaugh, professor of orthopedics at the Mayo Clinic.

“They love the paraffin. Once they start the paraffin baths it's almost impossible to get them out of our offices,” Mr. Brach said. Getting serious, he concluded, “Supportive modalities and heat modalities certainly play an important role.”

None of the speakers disclosed ties to manufacturers of drugs or devices.

VANCOUVER, B.C. — More than a third of primary care patients with health insurance reported delaying or foregoing recommended medical care because they could not afford copays or deductibles in a study that was conducted in 37 clinics in Colorado.

Of 1,133 English- and Spanish-speaking patients who attended family medicine and internal medicine clinics, 30% were underinsured; of these patients, 10% had no health insurance at all, reported Dr. Kent Voorhees of the department of family medicine at the University of Colorado Health Sciences Center in Denver.

Underinsurance was defined as being unable to comply with medical advice at any time in the previous 12 months by patients who have medical insurance but who cannot manage to absorb the financial burden of copayments or deductibles.

The patients included newborns and those aged up to 89 years.

Among 90% of patients with some form of health insurance, 36% were underinsured.

“Even patients with Medicare and Medicaid—groups excluded from previous underinsurance studies—reported being underinsured at a rate of 19.2% and 34.6%, respectively,” Dr. Voorhees and his associates reported in a poster at the annual meeting of the North American Primary Care Research Group.

Half of all underinsured patients said they felt their health had suffered because they could not afford to follow physicians' advice to obtain tests, specialist care, or prescriptions.

An equal percentage of patients with no insurance coverage said their health had suffered for the same reason.

The underinsurance phenomenon is symptomatic of a creeping pattern of cost shifting from payers to patients, which is resulting in hidden compromises in health care, Dr. Voorhees said in an interview at the meeting.

“If patients are healthy, they may not even know they're underinsured,” he added.

The issue lurks under the radar in health policy research, as well as in studies of compliance, yet the Colorado findings are likely to be generalizable to much of the country, according to Dr. Voorhees.

“To adequately meet the health care needs in the [United States], we need to look beyond the problem of the uninsured to create a system that also solves the problem of underinsurance,” the authors said.

“This will improve overall health and health-related outcomes to an acceptable level,” they concluded.

VANCOUVER, B.C. — More than a third of primary care patients with health insurance reported delaying or foregoing recommended medical care because they could not afford copays or deductibles in a study that was conducted in 37 clinics in Colorado.

Of 1,133 English- and Spanish-speaking patients who attended family medicine and internal medicine clinics, 30% were underinsured; of these patients, 10% had no health insurance at all, reported Dr. Kent Voorhees of the department of family medicine at the University of Colorado Health Sciences Center in Denver.

Underinsurance was defined as being unable to comply with medical advice at any time in the previous 12 months by patients who have medical insurance but who cannot manage to absorb the financial burden of copayments or deductibles.

The patients included newborns and those aged up to 89 years.

Among 90% of patients with some form of health insurance, 36% were underinsured.

“Even patients with Medicare and Medicaid—groups excluded from previous underinsurance studies—reported being underinsured at a rate of 19.2% and 34.6%, respectively,” Dr. Voorhees and his associates reported in a poster at the annual meeting of the North American Primary Care Research Group.

Half of all underinsured patients said they felt their health had suffered because they could not afford to follow physicians' advice to obtain tests, specialist care, or prescriptions.

An equal percentage of patients with no insurance coverage said their health had suffered for the same reason.

The underinsurance phenomenon is symptomatic of a creeping pattern of cost shifting from payers to patients, which is resulting in hidden compromises in health care, Dr. Voorhees said in an interview at the meeting.

“If patients are healthy, they may not even know they're underinsured,” he added.

The issue lurks under the radar in health policy research, as well as in studies of compliance, yet the Colorado findings are likely to be generalizable to much of the country, according to Dr. Voorhees.

“To adequately meet the health care needs in the [United States], we need to look beyond the problem of the uninsured to create a system that also solves the problem of underinsurance,” the authors said.

“This will improve overall health and health-related outcomes to an acceptable level,” they concluded.

VANCOUVER, B.C. — More than a third of primary care patients with health insurance reported delaying or foregoing recommended medical care because they could not afford copays or deductibles in a study that was conducted in 37 clinics in Colorado.

Of 1,133 English- and Spanish-speaking patients who attended family medicine and internal medicine clinics, 30% were underinsured; of these patients, 10% had no health insurance at all, reported Dr. Kent Voorhees of the department of family medicine at the University of Colorado Health Sciences Center in Denver.

Underinsurance was defined as being unable to comply with medical advice at any time in the previous 12 months by patients who have medical insurance but who cannot manage to absorb the financial burden of copayments or deductibles.

The patients included newborns and those aged up to 89 years.

Among 90% of patients with some form of health insurance, 36% were underinsured.

“Even patients with Medicare and Medicaid—groups excluded from previous underinsurance studies—reported being underinsured at a rate of 19.2% and 34.6%, respectively,” Dr. Voorhees and his associates reported in a poster at the annual meeting of the North American Primary Care Research Group.

Half of all underinsured patients said they felt their health had suffered because they could not afford to follow physicians' advice to obtain tests, specialist care, or prescriptions.

An equal percentage of patients with no insurance coverage said their health had suffered for the same reason.

The underinsurance phenomenon is symptomatic of a creeping pattern of cost shifting from payers to patients, which is resulting in hidden compromises in health care, Dr. Voorhees said in an interview at the meeting.

“If patients are healthy, they may not even know they're underinsured,” he added.

The issue lurks under the radar in health policy research, as well as in studies of compliance, yet the Colorado findings are likely to be generalizable to much of the country, according to Dr. Voorhees.

“To adequately meet the health care needs in the [United States], we need to look beyond the problem of the uninsured to create a system that also solves the problem of underinsurance,” the authors said.

“This will improve overall health and health-related outcomes to an acceptable level,” they concluded.

SAN DIEGO — Resistance to gonorrhea drugs is climbing just as treatment options are dwindling, making for a potential public health crisis if more drug choices are not brought to market soon.

“The situation is really not good. We're hanging by a thread, with a very serious resistance problem. If we lose cephalosporins [to resistance], we will really be up a creek,” Dr. Jeanne Marrazzo said at Perspectives in Women's Health, sponsored by FAMILY PRACTICE NEWS, OB.GYN. NEWS, and INTERNAL MEDICINE NEWS.

Practically speaking, ceftriaxone (125 mg intramuscularly, in a single dose) remains the only available regimen recommended by the Centers for Disease Control and Prevention for treating gonorrhea, the second-most commonly reported infectious disease in the United States.

After years of decline or stability, U.S. rates of gonorrhea rose for the second straight year in 2006, with about 358,000 new cases reported, according to CDC surveillance statistics.

Many infectious disease specialists are wary of dependence on a single drug to treat a widespread infectious disease because of the threat of resistance, and gonorrhea seems particularly susceptible.

Widespread resistance long ago took penicillins, sulfa drugs, tetracycline, and spectinomycin off the table for gonococcal infections; by April of last year, fluoroquinolones, including ciprofloxacin, ofloxacin, and levofloxacin, also lost their “recommended” status because of resistance documented in sites in the United States and other countries.

Cefixime remains on the CDC's recommended list; it is currently unavailable in the United States, except in a liquid pediatric formula approved last year. A problem with the pediatric formula is that it has a limited shelf life once reconstituted.

Dr. Marrazzo explained that Wyeth Pharmaceuticals discontinued manufacture of cefixime tablets, once marketed as Suprax, when the patent for the medication expired in 2002.

Exclusive rights to the drug are now held by a company based in India, which is rumored to be working with the Food and Drug Administration to obtain approval to market 400-mg tablets in the United States.

Alternative regimens suggested by the CDC include spectinomycin, which is also no longer being manufactured in the United States, and single-dose cephalosporin regimens.

All patients with gonorrhea should be cotreated for chlamydia unless it is ruled out with a highly sensitive test.

The lack of availability of spectinomycin complicates management of patients allergic to cephalosporins, according to Dr. Marrazzo of the Seattle STD/HIV Prevention Training Center and the University of Washington, Seattle. The CDC “cluelessly” recommends desensitizing patients, a suggestion she considers impractical in a busy clinic.

Such cases might call for special consideration of high-dose azithromycin, but the 2-g dose required can cause gastrointestinal problems, even with split doses administered several hours apart. In any case, resistance to azithromycin is likely increasing, so “that's going to be a short-term fix.”

If fluoroquinolones are the only remaining option in cephalosporin-allergic patients, Dr. Marrazzo recommends obtaining a culture before treatment to ensure sensitivity, or obtaining a test of cure in 3–5 days by culture or 3 weeks if a nucleic acid amplification test is used.

Dr. Marrazzo disclosed that she is a consultant to Mission Pharmacal, and serves on the speakers bureaus of 3M and Merck & Co. INTERNAL MEDICINE NEWS is published by International Medical News Group, a division of Elsevier.

A cervical smear photomicrograph shows extracellular diplococci determined to be Neisseria gonorrhoeae bacteria. CDC/Joe Miller

SAN DIEGO — Resistance to gonorrhea drugs is climbing just as treatment options are dwindling, making for a potential public health crisis if more drug choices are not brought to market soon.

“The situation is really not good. We're hanging by a thread, with a very serious resistance problem. If we lose cephalosporins [to resistance], we will really be up a creek,” Dr. Jeanne Marrazzo said at Perspectives in Women's Health, sponsored by FAMILY PRACTICE NEWS, OB.GYN. NEWS, and INTERNAL MEDICINE NEWS.

Practically speaking, ceftriaxone (125 mg intramuscularly, in a single dose) remains the only available regimen recommended by the Centers for Disease Control and Prevention for treating gonorrhea, the second-most commonly reported infectious disease in the United States.

After years of decline or stability, U.S. rates of gonorrhea rose for the second straight year in 2006, with about 358,000 new cases reported, according to CDC surveillance statistics.

Many infectious disease specialists are wary of dependence on a single drug to treat a widespread infectious disease because of the threat of resistance, and gonorrhea seems particularly susceptible.

Widespread resistance long ago took penicillins, sulfa drugs, tetracycline, and spectinomycin off the table for gonococcal infections; by April of last year, fluoroquinolones, including ciprofloxacin, ofloxacin, and levofloxacin, also lost their “recommended” status because of resistance documented in sites in the United States and other countries.

Cefixime remains on the CDC's recommended list; it is currently unavailable in the United States, except in a liquid pediatric formula approved last year. A problem with the pediatric formula is that it has a limited shelf life once reconstituted.

Dr. Marrazzo explained that Wyeth Pharmaceuticals discontinued manufacture of cefixime tablets, once marketed as Suprax, when the patent for the medication expired in 2002.

Exclusive rights to the drug are now held by a company based in India, which is rumored to be working with the Food and Drug Administration to obtain approval to market 400-mg tablets in the United States.

Alternative regimens suggested by the CDC include spectinomycin, which is also no longer being manufactured in the United States, and single-dose cephalosporin regimens.

All patients with gonorrhea should be cotreated for chlamydia unless it is ruled out with a highly sensitive test.

The lack of availability of spectinomycin complicates management of patients allergic to cephalosporins, according to Dr. Marrazzo of the Seattle STD/HIV Prevention Training Center and the University of Washington, Seattle. The CDC “cluelessly” recommends desensitizing patients, a suggestion she considers impractical in a busy clinic.

Such cases might call for special consideration of high-dose azithromycin, but the 2-g dose required can cause gastrointestinal problems, even with split doses administered several hours apart. In any case, resistance to azithromycin is likely increasing, so “that's going to be a short-term fix.”

If fluoroquinolones are the only remaining option in cephalosporin-allergic patients, Dr. Marrazzo recommends obtaining a culture before treatment to ensure sensitivity, or obtaining a test of cure in 3–5 days by culture or 3 weeks if a nucleic acid amplification test is used.

Dr. Marrazzo disclosed that she is a consultant to Mission Pharmacal, and serves on the speakers bureaus of 3M and Merck & Co. INTERNAL MEDICINE NEWS is published by International Medical News Group, a division of Elsevier.

A cervical smear photomicrograph shows extracellular diplococci determined to be Neisseria gonorrhoeae bacteria. CDC/Joe Miller

SAN DIEGO — Resistance to gonorrhea drugs is climbing just as treatment options are dwindling, making for a potential public health crisis if more drug choices are not brought to market soon.

“The situation is really not good. We're hanging by a thread, with a very serious resistance problem. If we lose cephalosporins [to resistance], we will really be up a creek,” Dr. Jeanne Marrazzo said at Perspectives in Women's Health, sponsored by FAMILY PRACTICE NEWS, OB.GYN. NEWS, and INTERNAL MEDICINE NEWS.

Practically speaking, ceftriaxone (125 mg intramuscularly, in a single dose) remains the only available regimen recommended by the Centers for Disease Control and Prevention for treating gonorrhea, the second-most commonly reported infectious disease in the United States.

After years of decline or stability, U.S. rates of gonorrhea rose for the second straight year in 2006, with about 358,000 new cases reported, according to CDC surveillance statistics.

Many infectious disease specialists are wary of dependence on a single drug to treat a widespread infectious disease because of the threat of resistance, and gonorrhea seems particularly susceptible.

Widespread resistance long ago took penicillins, sulfa drugs, tetracycline, and spectinomycin off the table for gonococcal infections; by April of last year, fluoroquinolones, including ciprofloxacin, ofloxacin, and levofloxacin, also lost their “recommended” status because of resistance documented in sites in the United States and other countries.

Cefixime remains on the CDC's recommended list; it is currently unavailable in the United States, except in a liquid pediatric formula approved last year. A problem with the pediatric formula is that it has a limited shelf life once reconstituted.

Dr. Marrazzo explained that Wyeth Pharmaceuticals discontinued manufacture of cefixime tablets, once marketed as Suprax, when the patent for the medication expired in 2002.

Exclusive rights to the drug are now held by a company based in India, which is rumored to be working with the Food and Drug Administration to obtain approval to market 400-mg tablets in the United States.

Alternative regimens suggested by the CDC include spectinomycin, which is also no longer being manufactured in the United States, and single-dose cephalosporin regimens.

All patients with gonorrhea should be cotreated for chlamydia unless it is ruled out with a highly sensitive test.

The lack of availability of spectinomycin complicates management of patients allergic to cephalosporins, according to Dr. Marrazzo of the Seattle STD/HIV Prevention Training Center and the University of Washington, Seattle. The CDC “cluelessly” recommends desensitizing patients, a suggestion she considers impractical in a busy clinic.

Such cases might call for special consideration of high-dose azithromycin, but the 2-g dose required can cause gastrointestinal problems, even with split doses administered several hours apart. In any case, resistance to azithromycin is likely increasing, so “that's going to be a short-term fix.”

If fluoroquinolones are the only remaining option in cephalosporin-allergic patients, Dr. Marrazzo recommends obtaining a culture before treatment to ensure sensitivity, or obtaining a test of cure in 3–5 days by culture or 3 weeks if a nucleic acid amplification test is used.

Dr. Marrazzo disclosed that she is a consultant to Mission Pharmacal, and serves on the speakers bureaus of 3M and Merck & Co. INTERNAL MEDICINE NEWS is published by International Medical News Group, a division of Elsevier.

A cervical smear photomicrograph shows extracellular diplococci determined to be Neisseria gonorrhoeae bacteria. CDC/Joe Miller

SAN DIEGO — Resistance to gonorrhea drugs is climbing just as treatment options are dwindling, making for a potential public health crisis if more drug choices are not brought to market soon.

“The situation is really not good. We're hanging by a thread, with a very serious resistance problem. If we lose cephalosporins [to resistance], we will really be up a creek,” Dr. Jeanne Marrazzo said at Perspectives in Women's Health, sponsored by OB.GYN. NEWS, FAMILY PRACTICE NEWS, and INTERNAL MEDICINE NEWS.

Practically speaking, ceftriaxone (125 mg intramuscularly, in a single dose) remains the only available regimen recommended by the Centers for Disease Control and Prevention for treating gonorrhea, the second-most commonly reported infectious disease in the United States.

After years of decline or stability, U.S. rates of gonorrhea rose for the second straight year in 2006, with about 358,000 new cases reported, according to CDC surveillance statistics. Many infectious disease specialists are wary of dependence on a single drug to treat a widespread infectious disease because of the threat of resistance, and gonorrhea seems particularly susceptible.

Widespread resistance long ago took penicillins, sulfa drugs, tetracycline, and spectinomycin off the table for gonococcal infections; last year fluoroquinolones, including ciprofloxacin, ofloxacin, and levofloxacin, also lost their “recommended” status because of resistance documented in the United States and other countries.

Cefixime remains on the CDC's recommended list; however, it is currently unavailable in the United States except in a liquid pediatric formula that has a limited shelf life once reconstituted.

Dr. Marrazzo explained that Wyeth Pharmaceuticals discontinued manufacture of cefixime tablets, once marketed as Suprax, when the drug's patent expired in 2002.

Exclusive rights to the drug are now held by a company based in India, which is rumored to be working with the Food and Drug Administration to obtain approval to market 400-mg tablets in the United States.

Alternative regimens suggested by the CDC include spectinomycin, which is also no longer being manufactured in the United States, and single-dose cephalosporin regimens.

All patients with gonorrhea should be cotreated for chlamydia unless it is ruled out with a highly sensitive test.

The lack of availability of spectinomycin complicates management of patients allergic to cephalosporins, according to Dr. Marrazzo of the Seattle STD/HIV Prevention Training Center and the University of Washington, Seattle.

The CDC “cluelessly” recommends desensitizing patients, a suggestion she considers impractical in a busy clinic.

Such cases might call for special consideration of high-dose azithromycin, but the 2-g dose required can cause gastrointestinal problems, even with split doses administered several hours apart. In any case, resistance to azithromycin is likely increasing, so “that's going to be a short-term fix.”

If fluoroquinolones are the only remaining option in cephalosporin-allergic patients, Dr. Marrazzo recommends obtaining a culture before treatment to ensure sensitivity, or obtaining a test of cure in 3–5 days by culture or 3 weeks if a nucleic acid amplification test is used.

Dr. Marrazzo disclosed that she is a consultant to Mission Pharmacal and is on the speakers bureaus of 3M and Merck & Co.

OB.GYN. NEWS, FAMILY PRACTICE NEWS, and INTERNAL MEDICINE NEWS are Elsevier publications.

This cervical smear photomicrograph shows extracellular diplococci determined to be Neisseria gonorrhoeae. CDC/Joe Miller

SAN DIEGO — Resistance to gonorrhea drugs is climbing just as treatment options are dwindling, making for a potential public health crisis if more drug choices are not brought to market soon.

“The situation is really not good. We're hanging by a thread, with a very serious resistance problem. If we lose cephalosporins [to resistance], we will really be up a creek,” Dr. Jeanne Marrazzo said at Perspectives in Women's Health, sponsored by OB.GYN. NEWS, FAMILY PRACTICE NEWS, and INTERNAL MEDICINE NEWS.

Practically speaking, ceftriaxone (125 mg intramuscularly, in a single dose) remains the only available regimen recommended by the Centers for Disease Control and Prevention for treating gonorrhea, the second-most commonly reported infectious disease in the United States.

After years of decline or stability, U.S. rates of gonorrhea rose for the second straight year in 2006, with about 358,000 new cases reported, according to CDC surveillance statistics. Many infectious disease specialists are wary of dependence on a single drug to treat a widespread infectious disease because of the threat of resistance, and gonorrhea seems particularly susceptible.

Widespread resistance long ago took penicillins, sulfa drugs, tetracycline, and spectinomycin off the table for gonococcal infections; last year fluoroquinolones, including ciprofloxacin, ofloxacin, and levofloxacin, also lost their “recommended” status because of resistance documented in the United States and other countries.

Cefixime remains on the CDC's recommended list; however, it is currently unavailable in the United States except in a liquid pediatric formula that has a limited shelf life once reconstituted.

Dr. Marrazzo explained that Wyeth Pharmaceuticals discontinued manufacture of cefixime tablets, once marketed as Suprax, when the drug's patent expired in 2002.

Exclusive rights to the drug are now held by a company based in India, which is rumored to be working with the Food and Drug Administration to obtain approval to market 400-mg tablets in the United States.

Alternative regimens suggested by the CDC include spectinomycin, which is also no longer being manufactured in the United States, and single-dose cephalosporin regimens.

All patients with gonorrhea should be cotreated for chlamydia unless it is ruled out with a highly sensitive test.

The lack of availability of spectinomycin complicates management of patients allergic to cephalosporins, according to Dr. Marrazzo of the Seattle STD/HIV Prevention Training Center and the University of Washington, Seattle.

The CDC “cluelessly” recommends desensitizing patients, a suggestion she considers impractical in a busy clinic.

Such cases might call for special consideration of high-dose azithromycin, but the 2-g dose required can cause gastrointestinal problems, even with split doses administered several hours apart. In any case, resistance to azithromycin is likely increasing, so “that's going to be a short-term fix.”

If fluoroquinolones are the only remaining option in cephalosporin-allergic patients, Dr. Marrazzo recommends obtaining a culture before treatment to ensure sensitivity, or obtaining a test of cure in 3–5 days by culture or 3 weeks if a nucleic acid amplification test is used.

Dr. Marrazzo disclosed that she is a consultant to Mission Pharmacal and is on the speakers bureaus of 3M and Merck & Co.

OB.GYN. NEWS, FAMILY PRACTICE NEWS, and INTERNAL MEDICINE NEWS are Elsevier publications.

This cervical smear photomicrograph shows extracellular diplococci determined to be Neisseria gonorrhoeae. CDC/Joe Miller

SAN DIEGO — Resistance to gonorrhea drugs is climbing just as treatment options are dwindling, making for a potential public health crisis if more drug choices are not brought to market soon.

“The situation is really not good. We're hanging by a thread, with a very serious resistance problem. If we lose cephalosporins [to resistance], we will really be up a creek,” Dr. Jeanne Marrazzo said at Perspectives in Women's Health, sponsored by OB.GYN. NEWS, FAMILY PRACTICE NEWS, and INTERNAL MEDICINE NEWS.

Practically speaking, ceftriaxone (125 mg intramuscularly, in a single dose) remains the only available regimen recommended by the Centers for Disease Control and Prevention for treating gonorrhea, the second-most commonly reported infectious disease in the United States.

After years of decline or stability, U.S. rates of gonorrhea rose for the second straight year in 2006, with about 358,000 new cases reported, according to CDC surveillance statistics. Many infectious disease specialists are wary of dependence on a single drug to treat a widespread infectious disease because of the threat of resistance, and gonorrhea seems particularly susceptible.

Widespread resistance long ago took penicillins, sulfa drugs, tetracycline, and spectinomycin off the table for gonococcal infections; last year fluoroquinolones, including ciprofloxacin, ofloxacin, and levofloxacin, also lost their “recommended” status because of resistance documented in the United States and other countries.

Cefixime remains on the CDC's recommended list; however, it is currently unavailable in the United States except in a liquid pediatric formula that has a limited shelf life once reconstituted.

Dr. Marrazzo explained that Wyeth Pharmaceuticals discontinued manufacture of cefixime tablets, once marketed as Suprax, when the drug's patent expired in 2002.

Exclusive rights to the drug are now held by a company based in India, which is rumored to be working with the Food and Drug Administration to obtain approval to market 400-mg tablets in the United States.

Alternative regimens suggested by the CDC include spectinomycin, which is also no longer being manufactured in the United States, and single-dose cephalosporin regimens.

All patients with gonorrhea should be cotreated for chlamydia unless it is ruled out with a highly sensitive test.

The lack of availability of spectinomycin complicates management of patients allergic to cephalosporins, according to Dr. Marrazzo of the Seattle STD/HIV Prevention Training Center and the University of Washington, Seattle.

The CDC “cluelessly” recommends desensitizing patients, a suggestion she considers impractical in a busy clinic.

Such cases might call for special consideration of high-dose azithromycin, but the 2-g dose required can cause gastrointestinal problems, even with split doses administered several hours apart. In any case, resistance to azithromycin is likely increasing, so “that's going to be a short-term fix.”

If fluoroquinolones are the only remaining option in cephalosporin-allergic patients, Dr. Marrazzo recommends obtaining a culture before treatment to ensure sensitivity, or obtaining a test of cure in 3–5 days by culture or 3 weeks if a nucleic acid amplification test is used.

Dr. Marrazzo disclosed that she is a consultant to Mission Pharmacal and is on the speakers bureaus of 3M and Merck & Co.

OB.GYN. NEWS, FAMILY PRACTICE NEWS, and INTERNAL MEDICINE NEWS are Elsevier publications.

This cervical smear photomicrograph shows extracellular diplococci determined to be Neisseria gonorrhoeae. CDC/Joe Miller

HONOLULU — Disappointing clinical trial results should not suggest that outcomes cannot be improved in traumatic brain injury, only that study methodologies may need to be refined, Dr. D. James Cooper said during a plenary address at the annual congress of the Society of Critical Care Medicine.

To be sure, various interventions have had hopeful improvements in animal models, but not in human trials.

But the heterogeneity of the traumatic brain injury (TBI) population and “huge differences” in the specific trauma suffered may make study results look unfairly pessimistic, said Dr. Cooper, deputy director of the intensive care unit at Alfred Hospital, Melbourne.

Experimental treatments may be initiated too late because of logistical and informed-consent dilemmas, and older patients may be so unlikely to benefit that they skew results. And follow-up assessment periods may be too brief, because it appears that Glasgow Outcome Scale scores improve greatly over time, but very slowly, he said.

A number of lessons have indeed been learned, even from negative clinical trials, and several promising approaches are currently under review.

Serious doubt has been cast on the efficacy of early high-dose steroids, for example, following the curtailment of the 10,000-patient randomized controlled MRC-CRASH (Corticosteroid Randomisation After Significant Head Injury) trial in the United Kingdom after excess deaths were reported in the steroid arm.

“It seems clear from the study that the use of an agent that has been very widely used, particularly in the developing world, clearly and unambiguously increases mortality, accounting for an absolute number of 3% excess deaths. I think it's abundantly clear … [that the] use of high-dose steroids should cease,” said Dr. Cooper, associate director for Australia's National Trauma Research Institute.

Because they lower vasopressor requirements in TBI patients, lower-dose steroids are used commonly in the intensive care environment, he noted. “There are no randomized controlled trials at all in this area, and it's clear to me, [based on the MRC-CRASH results,] there needs to be … a reevaluation” of this practice, said Dr. Cooper.

Another unexpected finding stemmed from the Australian SAFE-TBI (Saline Versus Albumin Fluid Evaluation-Traumatic Brain Injury) study, in which Dr. Cooper participated. That study of nearly 500 patients confirmed that albumin is independently tied to mortality in TBI patients when it is used for intravascular fluid resuscitation in the first 28 days. In contrast, saline was associated with lower mortality and better neurologic outcomes in patients with moderate to severe TBI.

The reasons remain unclear, although Dr. Cooper hypothesized that albumin may increase brain edema, prompting the use of other agents that could contribute to mortality; that it may increase bleeding or cause more coagulopathy; or that it may be the result of hemodilution.

The possibility remains that albumin's negative effect on survival may be a class effect of colloids, he said.

A recent analysis of data from both the SAFE-TBI study and the earlier ATBIS (Australasian Traumatic Brain Injury Study) “[adds] to our strong feeling that saline alone might be worthwhile,” he said.

As a final note, Dr. Cooper outlined two ongoing international clinical trials of early decompressive craniectomy to reduce intracranial pressure.

The absolute risk of mortality was halved with early decompressive craniectomy versus medical therapy alone in a recent, 38-patient French study; but the trial was concluded early because of slow recruitment.

Dr. Cooper's DECRA (Early Decompression Craniectomy in Patients With Severe Traumatic Brain Injury) trial at 21 sites is enrolling only patients younger than 60 years with blunt diffuse brain injuries—strict criteria that may be more conducive to interpreting results, he said.

So far, 112 patients have been enrolled of 165 anticipated, already more than the largest study ever conducted of early decompressive craniectomy, Dr. Cooper noted.

Among the first 42 patients who received surgery, the complication rate has been less than 10%, he said.

HONOLULU — Disappointing clinical trial results should not suggest that outcomes cannot be improved in traumatic brain injury, only that study methodologies may need to be refined, Dr. D. James Cooper said during a plenary address at the annual congress of the Society of Critical Care Medicine.

To be sure, various interventions have had hopeful improvements in animal models, but not in human trials.

But the heterogeneity of the traumatic brain injury (TBI) population and “huge differences” in the specific trauma suffered may make study results look unfairly pessimistic, said Dr. Cooper, deputy director of the intensive care unit at Alfred Hospital, Melbourne.

Experimental treatments may be initiated too late because of logistical and informed-consent dilemmas, and older patients may be so unlikely to benefit that they skew results. And follow-up assessment periods may be too brief, because it appears that Glasgow Outcome Scale scores improve greatly over time, but very slowly, he said.

A number of lessons have indeed been learned, even from negative clinical trials, and several promising approaches are currently under review.

Serious doubt has been cast on the efficacy of early high-dose steroids, for example, following the curtailment of the 10,000-patient randomized controlled MRC-CRASH (Corticosteroid Randomisation After Significant Head Injury) trial in the United Kingdom after excess deaths were reported in the steroid arm.

“It seems clear from the study that the use of an agent that has been very widely used, particularly in the developing world, clearly and unambiguously increases mortality, accounting for an absolute number of 3% excess deaths. I think it's abundantly clear … [that the] use of high-dose steroids should cease,” said Dr. Cooper, associate director for Australia's National Trauma Research Institute.

Because they lower vasopressor requirements in TBI patients, lower-dose steroids are used commonly in the intensive care environment, he noted. “There are no randomized controlled trials at all in this area, and it's clear to me, [based on the MRC-CRASH results,] there needs to be … a reevaluation” of this practice, said Dr. Cooper.

Another unexpected finding stemmed from the Australian SAFE-TBI (Saline Versus Albumin Fluid Evaluation-Traumatic Brain Injury) study, in which Dr. Cooper participated. That study of nearly 500 patients confirmed that albumin is independently tied to mortality in TBI patients when it is used for intravascular fluid resuscitation in the first 28 days. In contrast, saline was associated with lower mortality and better neurologic outcomes in patients with moderate to severe TBI.

The reasons remain unclear, although Dr. Cooper hypothesized that albumin may increase brain edema, prompting the use of other agents that could contribute to mortality; that it may increase bleeding or cause more coagulopathy; or that it may be the result of hemodilution.

The possibility remains that albumin's negative effect on survival may be a class effect of colloids, he said.

A recent analysis of data from both the SAFE-TBI study and the earlier ATBIS (Australasian Traumatic Brain Injury Study) “[adds] to our strong feeling that saline alone might be worthwhile,” he said.

As a final note, Dr. Cooper outlined two ongoing international clinical trials of early decompressive craniectomy to reduce intracranial pressure.

The absolute risk of mortality was halved with early decompressive craniectomy versus medical therapy alone in a recent, 38-patient French study; but the trial was concluded early because of slow recruitment.

Dr. Cooper's DECRA (Early Decompression Craniectomy in Patients With Severe Traumatic Brain Injury) trial at 21 sites is enrolling only patients younger than 60 years with blunt diffuse brain injuries—strict criteria that may be more conducive to interpreting results, he said.

So far, 112 patients have been enrolled of 165 anticipated, already more than the largest study ever conducted of early decompressive craniectomy, Dr. Cooper noted.

Among the first 42 patients who received surgery, the complication rate has been less than 10%, he said.

HONOLULU — Disappointing clinical trial results should not suggest that outcomes cannot be improved in traumatic brain injury, only that study methodologies may need to be refined, Dr. D. James Cooper said during a plenary address at the annual congress of the Society of Critical Care Medicine.

To be sure, various interventions have had hopeful improvements in animal models, but not in human trials.

But the heterogeneity of the traumatic brain injury (TBI) population and “huge differences” in the specific trauma suffered may make study results look unfairly pessimistic, said Dr. Cooper, deputy director of the intensive care unit at Alfred Hospital, Melbourne.

Experimental treatments may be initiated too late because of logistical and informed-consent dilemmas, and older patients may be so unlikely to benefit that they skew results. And follow-up assessment periods may be too brief, because it appears that Glasgow Outcome Scale scores improve greatly over time, but very slowly, he said.

A number of lessons have indeed been learned, even from negative clinical trials, and several promising approaches are currently under review.

Serious doubt has been cast on the efficacy of early high-dose steroids, for example, following the curtailment of the 10,000-patient randomized controlled MRC-CRASH (Corticosteroid Randomisation After Significant Head Injury) trial in the United Kingdom after excess deaths were reported in the steroid arm.

“It seems clear from the study that the use of an agent that has been very widely used, particularly in the developing world, clearly and unambiguously increases mortality, accounting for an absolute number of 3% excess deaths. I think it's abundantly clear … [that the] use of high-dose steroids should cease,” said Dr. Cooper, associate director for Australia's National Trauma Research Institute.

Because they lower vasopressor requirements in TBI patients, lower-dose steroids are used commonly in the intensive care environment, he noted. “There are no randomized controlled trials at all in this area, and it's clear to me, [based on the MRC-CRASH results,] there needs to be … a reevaluation” of this practice, said Dr. Cooper.

Another unexpected finding stemmed from the Australian SAFE-TBI (Saline Versus Albumin Fluid Evaluation-Traumatic Brain Injury) study, in which Dr. Cooper participated. That study of nearly 500 patients confirmed that albumin is independently tied to mortality in TBI patients when it is used for intravascular fluid resuscitation in the first 28 days. In contrast, saline was associated with lower mortality and better neurologic outcomes in patients with moderate to severe TBI.

The reasons remain unclear, although Dr. Cooper hypothesized that albumin may increase brain edema, prompting the use of other agents that could contribute to mortality; that it may increase bleeding or cause more coagulopathy; or that it may be the result of hemodilution.

The possibility remains that albumin's negative effect on survival may be a class effect of colloids, he said.

A recent analysis of data from both the SAFE-TBI study and the earlier ATBIS (Australasian Traumatic Brain Injury Study) “[adds] to our strong feeling that saline alone might be worthwhile,” he said.

As a final note, Dr. Cooper outlined two ongoing international clinical trials of early decompressive craniectomy to reduce intracranial pressure.

The absolute risk of mortality was halved with early decompressive craniectomy versus medical therapy alone in a recent, 38-patient French study; but the trial was concluded early because of slow recruitment.

Dr. Cooper's DECRA (Early Decompression Craniectomy in Patients With Severe Traumatic Brain Injury) trial at 21 sites is enrolling only patients younger than 60 years with blunt diffuse brain injuries—strict criteria that may be more conducive to interpreting results, he said.

So far, 112 patients have been enrolled of 165 anticipated, already more than the largest study ever conducted of early decompressive craniectomy, Dr. Cooper noted.

Among the first 42 patients who received surgery, the complication rate has been less than 10%, he said.

VANCOUVER, B.C. – Measuring a patient's height during routine primary care visits may be one of the simplest and least expensive ways to predict osteoporosis risk and to guide screening, according to a study at Virginia Commonwealth University, Richmond.

Height loss of 1.5 inches (about 4 cm) or more over 3 years was associated with almost a doubling of osteoporosis risk in patients aged 50 years or older in the study of 1,039 primary care patients, reported Dr. Emmeline Gasink at the annual meeting of the North American Primary Care Research Group.

Mean height loss in the study population was 0.596 inches, said Dr. Gasink, currently a resident in the family medicine program at Riverside Healthcare System in Carrollton, Va.

Among the 16% of patients who had a height loss of at least 1.5 inches, 3% had a diagnosis of osteoporosis (odds ratio, 1.8) of developing the disease.

Some patients (13%) had significant height loss but were not diagnosed with osteoporosis. Another 8% did not have significant height loss but had osteoporosis, perhaps representing osteoporosis in a nonvertebral site, said Dr. Gasink in an interview at the meeting.

Nonetheless, a height loss of 1.5 inches or greater over 3 years provided a positive predictive value of 21% for osteoporosis, she said.

The study population was 71% female, so the risk may be slightly less for males. Also, people with low bone density tend to lose height more rapidly than do those with greater bone density.

Still, the overall conclusion of the study, together with findings from five longitudinal trials reviewed by Dr. Gasink, suggest a “strong relationship” between height loss and a new vertebral fracture, lending strength to her findings.

“Height measurement should definitely be a part of a yearly physical for patients 50 and older, as recommended by the U.S. Preventive Health Task Force,” noted Dr. Gasink after the meeting. “As a family physician who follows these people over a period of years, [I suggest that] it would be an easy piece of data to help determine early risk factors for osteoporosis.”

VANCOUVER, B.C. – Measuring a patient's height during routine primary care visits may be one of the simplest and least expensive ways to predict osteoporosis risk and to guide screening, according to a study at Virginia Commonwealth University, Richmond.

Height loss of 1.5 inches (about 4 cm) or more over 3 years was associated with almost a doubling of osteoporosis risk in patients aged 50 years or older in the study of 1,039 primary care patients, reported Dr. Emmeline Gasink at the annual meeting of the North American Primary Care Research Group.

Mean height loss in the study population was 0.596 inches, said Dr. Gasink, currently a resident in the family medicine program at Riverside Healthcare System in Carrollton, Va.

Among the 16% of patients who had a height loss of at least 1.5 inches, 3% had a diagnosis of osteoporosis (odds ratio, 1.8) of developing the disease.

Some patients (13%) had significant height loss but were not diagnosed with osteoporosis. Another 8% did not have significant height loss but had osteoporosis, perhaps representing osteoporosis in a nonvertebral site, said Dr. Gasink in an interview at the meeting.

Nonetheless, a height loss of 1.5 inches or greater over 3 years provided a positive predictive value of 21% for osteoporosis, she said.

The study population was 71% female, so the risk may be slightly less for males. Also, people with low bone density tend to lose height more rapidly than do those with greater bone density.

Still, the overall conclusion of the study, together with findings from five longitudinal trials reviewed by Dr. Gasink, suggest a “strong relationship” between height loss and a new vertebral fracture, lending strength to her findings.

“Height measurement should definitely be a part of a yearly physical for patients 50 and older, as recommended by the U.S. Preventive Health Task Force,” noted Dr. Gasink after the meeting. “As a family physician who follows these people over a period of years, [I suggest that] it would be an easy piece of data to help determine early risk factors for osteoporosis.”

VANCOUVER, B.C. – Measuring a patient's height during routine primary care visits may be one of the simplest and least expensive ways to predict osteoporosis risk and to guide screening, according to a study at Virginia Commonwealth University, Richmond.

Height loss of 1.5 inches (about 4 cm) or more over 3 years was associated with almost a doubling of osteoporosis risk in patients aged 50 years or older in the study of 1,039 primary care patients, reported Dr. Emmeline Gasink at the annual meeting of the North American Primary Care Research Group.

Mean height loss in the study population was 0.596 inches, said Dr. Gasink, currently a resident in the family medicine program at Riverside Healthcare System in Carrollton, Va.

Among the 16% of patients who had a height loss of at least 1.5 inches, 3% had a diagnosis of osteoporosis (odds ratio, 1.8) of developing the disease.

Some patients (13%) had significant height loss but were not diagnosed with osteoporosis. Another 8% did not have significant height loss but had osteoporosis, perhaps representing osteoporosis in a nonvertebral site, said Dr. Gasink in an interview at the meeting.

Nonetheless, a height loss of 1.5 inches or greater over 3 years provided a positive predictive value of 21% for osteoporosis, she said.

The study population was 71% female, so the risk may be slightly less for males. Also, people with low bone density tend to lose height more rapidly than do those with greater bone density.

Still, the overall conclusion of the study, together with findings from five longitudinal trials reviewed by Dr. Gasink, suggest a “strong relationship” between height loss and a new vertebral fracture, lending strength to her findings.

“Height measurement should definitely be a part of a yearly physical for patients 50 and older, as recommended by the U.S. Preventive Health Task Force,” noted Dr. Gasink after the meeting. “As a family physician who follows these people over a period of years, [I suggest that] it would be an easy piece of data to help determine early risk factors for osteoporosis.”

SAN DIEGO – Osteoporosis management is about to undergo some changes, including a new international focus on assessing fracture risk in clinical practice and an emphasis on vitamin D, Dr. Stuart L. Silverman predicted at the Perspectives in Women's Health conference, sponsored by FAMILY PRACTICE NEWS, OB.GYN. NEWS, and INTERNAL MEDICINE NEWS.

“We're changing the whole way we approach osteoporosis in 2008,” said Dr. Silverman, with the International Working Group on Fracture Risk Assessment for the World Health Organization.

New guidelines will encourage the calculation of fracture risk based not only on their bone mineral density and T score, but also on age, body mass index, family history, and other factors, he explained.

This composite fracture score, expected to be incorporated into software linked with dual-energy x-ray absorptiometry (DXA) equipment by late 2008, will provide a much more comprehensive and easy-to-understand risk profile, he said.

“You will get a printout that says your patient has, [for example], a 10-year risk of hip fracture of 3%,” said Dr. Silverman, of the division of rheumatology at Cedars-Sinai Medical Center in Los Angeles.

The calculated 10-year risk for clinical fracture of the shoulder, forearm, or vertebra will be included in a separate score.

Factors in the 10-year predictions of fracture risk include:

▸ Age, which can change the 10-year risk for a woman with a T score of −2.5 at the femoral neck from 2% at age 50 to 12.5% at age 80.

▸ History of prior fragility fracture, which increases fracture risk fivefold.

▸ Low body weight/BMI.

▸ History of a hip fracture in the patient's mother or father.

▸ Lifetime history of ever using corticosteroids at a dose of 5 mg/day or greater for 3 months or longer.

▸ Current smoking.

▸ Consumption of more than two alcoholic drinks per day.

▸ Secondary osteoporosis caused by a disease process or a drug.

“Your goal is not to reduce risk of osteoporosis, but to reduce the risk of fracture,” Dr. Silverman said.

One way that risk can be reduced is through vitamin D supplementation recommendations, which are also likely to change soon, according to Dr. Silverman.

“Recently we've all come to appreciate that we really need much more vitamin D,” he said. “We're pushing for 800 to 1,000 IU day, and I will tell you that a lot of us in the field … are actually taking more than that,” he added.

New studies show vitamin D is useful not only for bones, but for balance and for reducing overall cancer risk, he noted.

RHEUMATOLOGY NEWS, like FAMILY PRACTICE NEWS, OB.GYN. NEWS, and INTERNAL MEDICINE NEWS, is published by the International Medical News Group, a division of Elsevier.

SAN DIEGO – Osteoporosis management is about to undergo some changes, including a new international focus on assessing fracture risk in clinical practice and an emphasis on vitamin D, Dr. Stuart L. Silverman predicted at the Perspectives in Women's Health conference, sponsored by FAMILY PRACTICE NEWS, OB.GYN. NEWS, and INTERNAL MEDICINE NEWS.

“We're changing the whole way we approach osteoporosis in 2008,” said Dr. Silverman, with the International Working Group on Fracture Risk Assessment for the World Health Organization.

New guidelines will encourage the calculation of fracture risk based not only on their bone mineral density and T score, but also on age, body mass index, family history, and other factors, he explained.

This composite fracture score, expected to be incorporated into software linked with dual-energy x-ray absorptiometry (DXA) equipment by late 2008, will provide a much more comprehensive and easy-to-understand risk profile, he said.

“You will get a printout that says your patient has, [for example], a 10-year risk of hip fracture of 3%,” said Dr. Silverman, of the division of rheumatology at Cedars-Sinai Medical Center in Los Angeles.

The calculated 10-year risk for clinical fracture of the shoulder, forearm, or vertebra will be included in a separate score.

Factors in the 10-year predictions of fracture risk include:

▸ Age, which can change the 10-year risk for a woman with a T score of −2.5 at the femoral neck from 2% at age 50 to 12.5% at age 80.

▸ History of prior fragility fracture, which increases fracture risk fivefold.

▸ Low body weight/BMI.

▸ History of a hip fracture in the patient's mother or father.

▸ Lifetime history of ever using corticosteroids at a dose of 5 mg/day or greater for 3 months or longer.

▸ Current smoking.

▸ Consumption of more than two alcoholic drinks per day.

▸ Secondary osteoporosis caused by a disease process or a drug.

“Your goal is not to reduce risk of osteoporosis, but to reduce the risk of fracture,” Dr. Silverman said.

One way that risk can be reduced is through vitamin D supplementation recommendations, which are also likely to change soon, according to Dr. Silverman.

“Recently we've all come to appreciate that we really need much more vitamin D,” he said. “We're pushing for 800 to 1,000 IU day, and I will tell you that a lot of us in the field … are actually taking more than that,” he added.

New studies show vitamin D is useful not only for bones, but for balance and for reducing overall cancer risk, he noted.

RHEUMATOLOGY NEWS, like FAMILY PRACTICE NEWS, OB.GYN. NEWS, and INTERNAL MEDICINE NEWS, is published by the International Medical News Group, a division of Elsevier.

SAN DIEGO – Osteoporosis management is about to undergo some changes, including a new international focus on assessing fracture risk in clinical practice and an emphasis on vitamin D, Dr. Stuart L. Silverman predicted at the Perspectives in Women's Health conference, sponsored by FAMILY PRACTICE NEWS, OB.GYN. NEWS, and INTERNAL MEDICINE NEWS.

“We're changing the whole way we approach osteoporosis in 2008,” said Dr. Silverman, with the International Working Group on Fracture Risk Assessment for the World Health Organization.

New guidelines will encourage the calculation of fracture risk based not only on their bone mineral density and T score, but also on age, body mass index, family history, and other factors, he explained.

This composite fracture score, expected to be incorporated into software linked with dual-energy x-ray absorptiometry (DXA) equipment by late 2008, will provide a much more comprehensive and easy-to-understand risk profile, he said.

“You will get a printout that says your patient has, [for example], a 10-year risk of hip fracture of 3%,” said Dr. Silverman, of the division of rheumatology at Cedars-Sinai Medical Center in Los Angeles.

The calculated 10-year risk for clinical fracture of the shoulder, forearm, or vertebra will be included in a separate score.

Factors in the 10-year predictions of fracture risk include:

▸ Age, which can change the 10-year risk for a woman with a T score of −2.5 at the femoral neck from 2% at age 50 to 12.5% at age 80.

▸ History of prior fragility fracture, which increases fracture risk fivefold.

▸ Low body weight/BMI.

▸ History of a hip fracture in the patient's mother or father.

▸ Lifetime history of ever using corticosteroids at a dose of 5 mg/day or greater for 3 months or longer.

▸ Current smoking.

▸ Consumption of more than two alcoholic drinks per day.

▸ Secondary osteoporosis caused by a disease process or a drug.

“Your goal is not to reduce risk of osteoporosis, but to reduce the risk of fracture,” Dr. Silverman said.

One way that risk can be reduced is through vitamin D supplementation recommendations, which are also likely to change soon, according to Dr. Silverman.

“Recently we've all come to appreciate that we really need much more vitamin D,” he said. “We're pushing for 800 to 1,000 IU day, and I will tell you that a lot of us in the field … are actually taking more than that,” he added.

New studies show vitamin D is useful not only for bones, but for balance and for reducing overall cancer risk, he noted.

RHEUMATOLOGY NEWS, like FAMILY PRACTICE NEWS, OB.GYN. NEWS, and INTERNAL MEDICINE NEWS, is published by the International Medical News Group, a division of Elsevier.

SAN DIEGO — Resistance to gonorrhea drugs is climbing just as treatment options are dwindling, making for a potential public health crisis if more drug choices are not brought to market soon.

"The situation is really not good. We're hanging by a thread, with a very serious resistance problem. If we lose cephalosporins [to resistance], we will really be up a creek," Dr. Jeanne Marrazzo said at Perspectives in Women's Health, sponsored by FAMILY PRACTICE NEWS, OB.GYN. NEWS, and INTERNAL MEDICINE NEWS.

Practically speaking, ceftriaxone (125 mg intramuscularly, in a single dose) remains the only available regimen recommended by the Centers for Disease Control and Prevention for treating gonorrhea, the second-most commonly reported infectious disease in the United States. After years of decline or stability, U.S. gonorrhea rates rose for the second straight year in 2006, with about 358,000 new cases reported, according to CDC surveillance statistics.

Many physicians are wary of dependence on a single drug to treat a widespread infectious disease because of possible resistance, and gonorrhea seems particularly susceptible, Dr. Marrazzo said. Widespread resistance long ago took penicillins, sulfa drugs, tetracycline, and spectinomycin off the table for gonococcal infections; by April of last year, fluoroquinolones, including ciprofloxacin, ofloxacin, and levofloxacin, also lost their "recommended" status because of resistance documented in sites in the United States and other countries. Cefixime remains on the CDC's recommended list; however, it is currently unavailable in the United States, except in a liquid pediatric formula approved last year.

Dr. Marrazzo explained that Wyeth Pharmaceuticals discontinued manufacture of cefixime tablets, once marketed as Suprax, when the drug's patent expired in 2002. Exclusive rights to the drug are now held by a company based in India, which is rumored to be working with the Food and Drug Administration to obtain approval to market 400-mg tablets in the United States.

Alternative regimens suggested by the CDC include spectinomycin, which is also no longer being manufactured in the United States, and single-dose cephalosporin regimens.

All patients with gonorrhea should be cotreated for chlamydia unless it is ruled out with a highly sensitive test.

The lack of availability of spectinomycin complicates management of patients allergic to cephalosporins, according to Dr. Marrazzo of the Seattle STD/HIV Prevention Training Center and the University of Washington, Seattle. The CDC "cluelessly" recommends desensitizing patients.

Such cases might call for special consideration of high-dose azithromycin, but the 2-g dose required can cause gastrointestinal problems, even with split doses. In any case, resistance to azithromycin is likely increasing, so "that's going to be a short-term fix," she said. If fluoroquinolones are the only remaining option in cephalosporin-allergic patients, Dr. Marrazzo recommends obtaining a culture before treatment to ensure sensitivity, or obtaining a test of cure in 3–5 days by culture or 3 weeks if a nucleic acid amplification test is used.

Dr. Marrazzo disclosed that she is a consultant to Mission Pharmacal and serves on the speakers bureaus of 3M and Merck & Co. Perspectives in Women's Health and this newspaper are owned by Elsevier.

This cervical smear shows extracellular diplococci that were determined to be Neisseria gonorrhoeae. CDC/Joe Miller

SAN DIEGO — Resistance to gonorrhea drugs is climbing just as treatment options are dwindling, making for a potential public health crisis if more drug choices are not brought to market soon.

"The situation is really not good. We're hanging by a thread, with a very serious resistance problem. If we lose cephalosporins [to resistance], we will really be up a creek," Dr. Jeanne Marrazzo said at Perspectives in Women's Health, sponsored by FAMILY PRACTICE NEWS, OB.GYN. NEWS, and INTERNAL MEDICINE NEWS.

Practically speaking, ceftriaxone (125 mg intramuscularly, in a single dose) remains the only available regimen recommended by the Centers for Disease Control and Prevention for treating gonorrhea, the second-most commonly reported infectious disease in the United States. After years of decline or stability, U.S. gonorrhea rates rose for the second straight year in 2006, with about 358,000 new cases reported, according to CDC surveillance statistics.

Many physicians are wary of dependence on a single drug to treat a widespread infectious disease because of possible resistance, and gonorrhea seems particularly susceptible, Dr. Marrazzo said. Widespread resistance long ago took penicillins, sulfa drugs, tetracycline, and spectinomycin off the table for gonococcal infections; by April of last year, fluoroquinolones, including ciprofloxacin, ofloxacin, and levofloxacin, also lost their "recommended" status because of resistance documented in sites in the United States and other countries. Cefixime remains on the CDC's recommended list; however, it is currently unavailable in the United States, except in a liquid pediatric formula approved last year.

Dr. Marrazzo explained that Wyeth Pharmaceuticals discontinued manufacture of cefixime tablets, once marketed as Suprax, when the drug's patent expired in 2002. Exclusive rights to the drug are now held by a company based in India, which is rumored to be working with the Food and Drug Administration to obtain approval to market 400-mg tablets in the United States.

Alternative regimens suggested by the CDC include spectinomycin, which is also no longer being manufactured in the United States, and single-dose cephalosporin regimens.

All patients with gonorrhea should be cotreated for chlamydia unless it is ruled out with a highly sensitive test.

The lack of availability of spectinomycin complicates management of patients allergic to cephalosporins, according to Dr. Marrazzo of the Seattle STD/HIV Prevention Training Center and the University of Washington, Seattle. The CDC "cluelessly" recommends desensitizing patients.

Such cases might call for special consideration of high-dose azithromycin, but the 2-g dose required can cause gastrointestinal problems, even with split doses. In any case, resistance to azithromycin is likely increasing, so "that's going to be a short-term fix," she said. If fluoroquinolones are the only remaining option in cephalosporin-allergic patients, Dr. Marrazzo recommends obtaining a culture before treatment to ensure sensitivity, or obtaining a test of cure in 3–5 days by culture or 3 weeks if a nucleic acid amplification test is used.

Dr. Marrazzo disclosed that she is a consultant to Mission Pharmacal and serves on the speakers bureaus of 3M and Merck & Co. Perspectives in Women's Health and this newspaper are owned by Elsevier.

This cervical smear shows extracellular diplococci that were determined to be Neisseria gonorrhoeae. CDC/Joe Miller

SAN DIEGO — Resistance to gonorrhea drugs is climbing just as treatment options are dwindling, making for a potential public health crisis if more drug choices are not brought to market soon.

"The situation is really not good. We're hanging by a thread, with a very serious resistance problem. If we lose cephalosporins [to resistance], we will really be up a creek," Dr. Jeanne Marrazzo said at Perspectives in Women's Health, sponsored by FAMILY PRACTICE NEWS, OB.GYN. NEWS, and INTERNAL MEDICINE NEWS.

Practically speaking, ceftriaxone (125 mg intramuscularly, in a single dose) remains the only available regimen recommended by the Centers for Disease Control and Prevention for treating gonorrhea, the second-most commonly reported infectious disease in the United States. After years of decline or stability, U.S. gonorrhea rates rose for the second straight year in 2006, with about 358,000 new cases reported, according to CDC surveillance statistics.

Many physicians are wary of dependence on a single drug to treat a widespread infectious disease because of possible resistance, and gonorrhea seems particularly susceptible, Dr. Marrazzo said. Widespread resistance long ago took penicillins, sulfa drugs, tetracycline, and spectinomycin off the table for gonococcal infections; by April of last year, fluoroquinolones, including ciprofloxacin, ofloxacin, and levofloxacin, also lost their "recommended" status because of resistance documented in sites in the United States and other countries. Cefixime remains on the CDC's recommended list; however, it is currently unavailable in the United States, except in a liquid pediatric formula approved last year.

Dr. Marrazzo explained that Wyeth Pharmaceuticals discontinued manufacture of cefixime tablets, once marketed as Suprax, when the drug's patent expired in 2002. Exclusive rights to the drug are now held by a company based in India, which is rumored to be working with the Food and Drug Administration to obtain approval to market 400-mg tablets in the United States.

Alternative regimens suggested by the CDC include spectinomycin, which is also no longer being manufactured in the United States, and single-dose cephalosporin regimens.

All patients with gonorrhea should be cotreated for chlamydia unless it is ruled out with a highly sensitive test.

The lack of availability of spectinomycin complicates management of patients allergic to cephalosporins, according to Dr. Marrazzo of the Seattle STD/HIV Prevention Training Center and the University of Washington, Seattle. The CDC "cluelessly" recommends desensitizing patients.

Such cases might call for special consideration of high-dose azithromycin, but the 2-g dose required can cause gastrointestinal problems, even with split doses. In any case, resistance to azithromycin is likely increasing, so "that's going to be a short-term fix," she said. If fluoroquinolones are the only remaining option in cephalosporin-allergic patients, Dr. Marrazzo recommends obtaining a culture before treatment to ensure sensitivity, or obtaining a test of cure in 3–5 days by culture or 3 weeks if a nucleic acid amplification test is used.

Dr. Marrazzo disclosed that she is a consultant to Mission Pharmacal and serves on the speakers bureaus of 3M and Merck & Co. Perspectives in Women's Health and this newspaper are owned by Elsevier.

This cervical smear shows extracellular diplococci that were determined to be Neisseria gonorrhoeae. CDC/Joe Miller