Robert Finn

Several medical societies have jointly issued new performance measures for cardiac rehabilitation that are expected to greatly increase the number of patients referred to rehabilitation services. The measures also promote a safe exercise environment for those patients, but stop short of holding cardiac rehabilitation centers responsible for meeting individual treatment goals.

Published simultaneously in the Oct. 2 issues of Circulation and the Journal of the American College of Cardiology, the performance measures were developed by the American College of Cardiology, the Association of Cardiovascular and Pulmonary Rehabilitation, and the American Heart Association. The measures were endorsed by nine other medical societies, including the American College of Chest Physicians, the American College of Sports Medicine, and the American Thoracic Society.

“Research continues to show that cardiac rehabilitation services, although very effective and helpful for people with cardiac disease, are still being vastly underutilized,” Dr. Randal J. Thomas said in an interview. Dr. Thomas, director of the Cardiovascular Health Clinic at the Mayo Clinic in Rochester, Minn., chaired the committee that wrote the new cardiac rehabilitation (CR) performance measures.

Despite the fact that CR after cardiac illness has been shown to reduce a patient's mortality risk by 20%–25%, and also to improve physical strength and endurance by 20%–50%, less than 30% of eligible patients participate. There are many reasons for this, but foremost among the correctable causes is that many patients are simply never referred to CR.

Dr. Thomas' committee developed two sets of performance measures after extensive discussion, a public comment period, and revisions. One set of measures is intended to improve the referral of eligible patents to CR, and the other is aimed at improving the services offered by CR programs.

In the first set of measures, the committee specified that all hospitalized patients with eligible conditions should be referred to outpatient CR prior to discharge. In addition, outpatients with a qualifying diagnosis during the prior year should also be referred to CR if they have not yet participated.

The qualifying diagnoses are myocardial infarction, acute coronary syndrome, coronary artery bypass graft surgery, percutaneous coronary artery intervention, cardiac valve surgery, cardiac transplantation, and chronic stable angina. In addition, patients with chronic heart failure and peripheral arterial disease should be considered for CR.

In the second set of measures, the committee specified that all CR programs have a physician medical director, a well-trained emergency response team, and equipment and supplies for emergency resuscitation in the exercise area. All patients should receive individualized assessment of and education about their modifiable cardiovascular risk factors. (See box.)

The committee chose not to hold CR programs responsible for attainment of treatment goals. Dr. Thomas said that while some committee members suggested that CR programs should demonstrate that their patients are achieving LDL-cholesterol levels below 100 mg/dL or 70 mg/dL (for example), ultimately the committee conceded that this was not entirely under the programs' control. Some CR programs do take charge of their patients' prescriptions, but more commonly it's the patients' personal physicians who choose their regimens.

Dr. Thomas acknowledged that existing CR programs could not accommodate the huge influx of new patients that would result if the performance measures were implemented universally.

“We need to work together to establish new models that will help to provide the care necessary for everybody who's not getting the care,” he said. “For example, does everybody need to come into a cardiac rehabilitation center to receive rehabilitation and preventive care? The answer is no. There are a lot of publications showing the benefits of a system where patients would largely carry out their rehabilitation efforts at home or in a local health club, but still under the direction of a nurse and a physician … who will check on them periodically.”

Dr. Thomas said that the insurance industry will have an important role to play if the performance measures are to be implemented. “There is an expectation and a hope, anyway, that the insurance carriers will see the value of some of the novel approaches to rehab and start reimbursing for those models of care, which they're not doing generally now. This is uncharted territory. But I would guess that within the next 3–5 years we'll see a large degree of implementation of these measures.”

The full text of the performance measures is at www.acc.org/qualityandscience/clinical/pdfs/CardiacRehab_PM_sept20.pdf

Risk Assessments Before Rehabilitation

According to the new performance measures, cardiac rehabilitation programs are expected to conduct thorough risk assessments for each patient.

This individualized risk assessment should include:

▸ Assessment of current and past tobacco use.

▸ Assessment of blood pressure control.

▸ Assessment of optimal lipid control.

▸ Assessment of the patient's physical activity habits and exercise level.

▸ Assessment of weight management.

▸ Assessment of diabetes mellitus diagnosis or impaired fasting glucose.

▸ Assessment of the presence or absence of depression.

▸ Assessment of exercise capacity.

▸ Instruction on the importance of adherence to preventive medications.

▸ Communication with the patient's other health care providers.

Several medical societies have jointly issued new performance measures for cardiac rehabilitation that are expected to greatly increase the number of patients referred to rehabilitation services. The measures also promote a safe exercise environment for those patients, but stop short of holding cardiac rehabilitation centers responsible for meeting individual treatment goals.

Published simultaneously in the Oct. 2 issues of Circulation and the Journal of the American College of Cardiology, the performance measures were developed by the American College of Cardiology, the Association of Cardiovascular and Pulmonary Rehabilitation, and the American Heart Association. The measures were endorsed by nine other medical societies, including the American College of Chest Physicians, the American College of Sports Medicine, and the American Thoracic Society.

“Research continues to show that cardiac rehabilitation services, although very effective and helpful for people with cardiac disease, are still being vastly underutilized,” Dr. Randal J. Thomas said in an interview. Dr. Thomas, director of the Cardiovascular Health Clinic at the Mayo Clinic in Rochester, Minn., chaired the committee that wrote the new cardiac rehabilitation (CR) performance measures.

Despite the fact that CR after cardiac illness has been shown to reduce a patient's mortality risk by 20%–25%, and also to improve physical strength and endurance by 20%–50%, less than 30% of eligible patients participate. There are many reasons for this, but foremost among the correctable causes is that many patients are simply never referred to CR.

Dr. Thomas' committee developed two sets of performance measures after extensive discussion, a public comment period, and revisions. One set of measures is intended to improve the referral of eligible patents to CR, and the other is aimed at improving the services offered by CR programs.

In the first set of measures, the committee specified that all hospitalized patients with eligible conditions should be referred to outpatient CR prior to discharge. In addition, outpatients with a qualifying diagnosis during the prior year should also be referred to CR if they have not yet participated.

The qualifying diagnoses are myocardial infarction, acute coronary syndrome, coronary artery bypass graft surgery, percutaneous coronary artery intervention, cardiac valve surgery, cardiac transplantation, and chronic stable angina. In addition, patients with chronic heart failure and peripheral arterial disease should be considered for CR.

In the second set of measures, the committee specified that all CR programs have a physician medical director, a well-trained emergency response team, and equipment and supplies for emergency resuscitation in the exercise area. All patients should receive individualized assessment of and education about their modifiable cardiovascular risk factors. (See box.)

The committee chose not to hold CR programs responsible for attainment of treatment goals. Dr. Thomas said that while some committee members suggested that CR programs should demonstrate that their patients are achieving LDL-cholesterol levels below 100 mg/dL or 70 mg/dL (for example), ultimately the committee conceded that this was not entirely under the programs' control. Some CR programs do take charge of their patients' prescriptions, but more commonly it's the patients' personal physicians who choose their regimens.

Dr. Thomas acknowledged that existing CR programs could not accommodate the huge influx of new patients that would result if the performance measures were implemented universally.

“We need to work together to establish new models that will help to provide the care necessary for everybody who's not getting the care,” he said. “For example, does everybody need to come into a cardiac rehabilitation center to receive rehabilitation and preventive care? The answer is no. There are a lot of publications showing the benefits of a system where patients would largely carry out their rehabilitation efforts at home or in a local health club, but still under the direction of a nurse and a physician … who will check on them periodically.”

Dr. Thomas said that the insurance industry will have an important role to play if the performance measures are to be implemented. “There is an expectation and a hope, anyway, that the insurance carriers will see the value of some of the novel approaches to rehab and start reimbursing for those models of care, which they're not doing generally now. This is uncharted territory. But I would guess that within the next 3–5 years we'll see a large degree of implementation of these measures.”

The full text of the performance measures is at www.acc.org/qualityandscience/clinical/pdfs/CardiacRehab_PM_sept20.pdf

Risk Assessments Before Rehabilitation

According to the new performance measures, cardiac rehabilitation programs are expected to conduct thorough risk assessments for each patient.

This individualized risk assessment should include:

▸ Assessment of current and past tobacco use.

▸ Assessment of blood pressure control.

▸ Assessment of optimal lipid control.

▸ Assessment of the patient's physical activity habits and exercise level.

▸ Assessment of weight management.

▸ Assessment of diabetes mellitus diagnosis or impaired fasting glucose.

▸ Assessment of the presence or absence of depression.

▸ Assessment of exercise capacity.

▸ Instruction on the importance of adherence to preventive medications.

▸ Communication with the patient's other health care providers.

Several medical societies have jointly issued new performance measures for cardiac rehabilitation that are expected to greatly increase the number of patients referred to rehabilitation services. The measures also promote a safe exercise environment for those patients, but stop short of holding cardiac rehabilitation centers responsible for meeting individual treatment goals.

Published simultaneously in the Oct. 2 issues of Circulation and the Journal of the American College of Cardiology, the performance measures were developed by the American College of Cardiology, the Association of Cardiovascular and Pulmonary Rehabilitation, and the American Heart Association. The measures were endorsed by nine other medical societies, including the American College of Chest Physicians, the American College of Sports Medicine, and the American Thoracic Society.

“Research continues to show that cardiac rehabilitation services, although very effective and helpful for people with cardiac disease, are still being vastly underutilized,” Dr. Randal J. Thomas said in an interview. Dr. Thomas, director of the Cardiovascular Health Clinic at the Mayo Clinic in Rochester, Minn., chaired the committee that wrote the new cardiac rehabilitation (CR) performance measures.

Despite the fact that CR after cardiac illness has been shown to reduce a patient's mortality risk by 20%–25%, and also to improve physical strength and endurance by 20%–50%, less than 30% of eligible patients participate. There are many reasons for this, but foremost among the correctable causes is that many patients are simply never referred to CR.

Dr. Thomas' committee developed two sets of performance measures after extensive discussion, a public comment period, and revisions. One set of measures is intended to improve the referral of eligible patents to CR, and the other is aimed at improving the services offered by CR programs.

In the first set of measures, the committee specified that all hospitalized patients with eligible conditions should be referred to outpatient CR prior to discharge. In addition, outpatients with a qualifying diagnosis during the prior year should also be referred to CR if they have not yet participated.

The qualifying diagnoses are myocardial infarction, acute coronary syndrome, coronary artery bypass graft surgery, percutaneous coronary artery intervention, cardiac valve surgery, cardiac transplantation, and chronic stable angina. In addition, patients with chronic heart failure and peripheral arterial disease should be considered for CR.

In the second set of measures, the committee specified that all CR programs have a physician medical director, a well-trained emergency response team, and equipment and supplies for emergency resuscitation in the exercise area. All patients should receive individualized assessment of and education about their modifiable cardiovascular risk factors. (See box.)

The committee chose not to hold CR programs responsible for attainment of treatment goals. Dr. Thomas said that while some committee members suggested that CR programs should demonstrate that their patients are achieving LDL-cholesterol levels below 100 mg/dL or 70 mg/dL (for example), ultimately the committee conceded that this was not entirely under the programs' control. Some CR programs do take charge of their patients' prescriptions, but more commonly it's the patients' personal physicians who choose their regimens.

Dr. Thomas acknowledged that existing CR programs could not accommodate the huge influx of new patients that would result if the performance measures were implemented universally.

“We need to work together to establish new models that will help to provide the care necessary for everybody who's not getting the care,” he said. “For example, does everybody need to come into a cardiac rehabilitation center to receive rehabilitation and preventive care? The answer is no. There are a lot of publications showing the benefits of a system where patients would largely carry out their rehabilitation efforts at home or in a local health club, but still under the direction of a nurse and a physician … who will check on them periodically.”

Dr. Thomas said that the insurance industry will have an important role to play if the performance measures are to be implemented. “There is an expectation and a hope, anyway, that the insurance carriers will see the value of some of the novel approaches to rehab and start reimbursing for those models of care, which they're not doing generally now. This is uncharted territory. But I would guess that within the next 3–5 years we'll see a large degree of implementation of these measures.”

The full text of the performance measures is at www.acc.org/qualityandscience/clinical/pdfs/CardiacRehab_PM_sept20.pdf

Risk Assessments Before Rehabilitation

According to the new performance measures, cardiac rehabilitation programs are expected to conduct thorough risk assessments for each patient.

This individualized risk assessment should include:

▸ Assessment of current and past tobacco use.

▸ Assessment of blood pressure control.

▸ Assessment of optimal lipid control.

▸ Assessment of the patient's physical activity habits and exercise level.

▸ Assessment of weight management.

▸ Assessment of diabetes mellitus diagnosis or impaired fasting glucose.

▸ Assessment of the presence or absence of depression.

▸ Assessment of exercise capacity.

▸ Instruction on the importance of adherence to preventive medications.

▸ Communication with the patient's other health care providers.

Adding a proton pump inhibitor to a nonsteroidal anti-inflammatory drug provides as much protection against NSAID-induced gastropathy as a cyclooxygenase-2 inhibitor (coxib), according to a new study September 2007 issue of the journal Gastroenterology.

Adding a proton pump inhibitor (PPI) to a coxib may provide some additional protection, but in recent years some coxibs have been shown to cause serious cardiovascular disease, wrote Wayne A. Ray, Ph.D., and his colleagues at Vanderbilt University, Nashville, Tenn.

The observational study used data from TennCare, the state of Tennessee's Medicaid program. Patients aged 40 years and older with a new episode of prescribed NSAID or coxib use between 1996 and 2004 were included. After excluding patients with serious illnesses such as cancer, HIV infection, cirrhosis, and chronic alcoholism, and those with less than 2 years of baseline data, the study included 234,010 new episodes of NSAID use and 48,710 new episodes of coxib use, with a total of 363,037 person-years of follow-up.

The investigators adjusted for a large number of demographic variables; prior history of peptic ulcer disease; use of low-dose aspirin, other antiplatelet drugs, anticoagulants, or systemic corticosteroids; new residence in a nursing home; and new nongastrointestinal hospital admission.

They found that the use of NSAIDs without gastroprotective cotherapy was associated with 5.65 peptic ulcer hospitalizations per 1,000 person-years, which is 2.8 times the incidence for comparable patients who were former users of either NSAIDs or coxibs.

Use of a PPI, a double-dose histamine-2 receptor antagonist, or misoprostol along with an NSAID reduced the risk of peptic ulcer hospitalization by 39%. Of the various gastroprotective therapies, PPIs were associated with the greatest risk reduction—54%—among NSAID users.

Unprotected use of a coxib resulted in a 40% reduction in the risk of peptic ulcer hospitalization, compared with unprotected use of an NSAID. Using a gastroprotective therapy in addition to a coxib resulted in a further 10% reduction in risk (for a total of 50%), with no statistically significant advantage for PPIs over other gastroprotective therapies.

In a subanalysis adjusted for dose, naproxen proved to be associated with the highest risk of peptic ulcer hospitalization, with an adjusted rate of 7.8 per 1,000 patient-years. Ibuprofen, rofecoxib, and celecoxib all were associated with significantly lower risks of hospitalization.

Another subgroup analysis showed that an NSAID with gastroprotection was significantly better for several patient groups than an NSAID alone. These groups included patients over the age of 65 years and those with a history of previous ulcers.

In other subgroups with medical comorbidities, those taking low-dose aspirin, and those on antiplatelet or anticoagulant therapy, gastroprotection had no statistically significant improvement over unprotected NSAIDs. The researchers said this was partly because of relatively small numbers of patients in some of the subgroups.

The study was supported by the Agency for Healthcare Research and Quality, and the investigators stated that they received no support from any pharmaceutical company. “[It] is increasingly unlikely that large clinical trials of gastroprotective cotherapy in NSAID users will be conducted,” they wrote. “Proton pump inhibitors are available generically, which limits the incentives for pharmaceutical manufacturers to fund such studies. Furthermore, because NSAID-induced gastropathy is frequent and potentially life threatening, the ethics of randomizing patients to NSAID use without gastroprotective cotherapy are questionable.”

The researchers recommended future trials directly comparing coxibs to NSAIDs with a PPI, and said additional investigation is “urgently needed” to study the benefits of adding a PPI to celecoxib and other coxibs.

Adding a proton pump inhibitor to a nonsteroidal anti-inflammatory drug provides as much protection against NSAID-induced gastropathy as a cyclooxygenase-2 inhibitor (coxib), according to a new study September 2007 issue of the journal Gastroenterology.

Adding a proton pump inhibitor (PPI) to a coxib may provide some additional protection, but in recent years some coxibs have been shown to cause serious cardiovascular disease, wrote Wayne A. Ray, Ph.D., and his colleagues at Vanderbilt University, Nashville, Tenn.

The observational study used data from TennCare, the state of Tennessee's Medicaid program. Patients aged 40 years and older with a new episode of prescribed NSAID or coxib use between 1996 and 2004 were included. After excluding patients with serious illnesses such as cancer, HIV infection, cirrhosis, and chronic alcoholism, and those with less than 2 years of baseline data, the study included 234,010 new episodes of NSAID use and 48,710 new episodes of coxib use, with a total of 363,037 person-years of follow-up.

The investigators adjusted for a large number of demographic variables; prior history of peptic ulcer disease; use of low-dose aspirin, other antiplatelet drugs, anticoagulants, or systemic corticosteroids; new residence in a nursing home; and new nongastrointestinal hospital admission.

They found that the use of NSAIDs without gastroprotective cotherapy was associated with 5.65 peptic ulcer hospitalizations per 1,000 person-years, which is 2.8 times the incidence for comparable patients who were former users of either NSAIDs or coxibs.

Use of a PPI, a double-dose histamine-2 receptor antagonist, or misoprostol along with an NSAID reduced the risk of peptic ulcer hospitalization by 39%. Of the various gastroprotective therapies, PPIs were associated with the greatest risk reduction—54%—among NSAID users.

Unprotected use of a coxib resulted in a 40% reduction in the risk of peptic ulcer hospitalization, compared with unprotected use of an NSAID. Using a gastroprotective therapy in addition to a coxib resulted in a further 10% reduction in risk (for a total of 50%), with no statistically significant advantage for PPIs over other gastroprotective therapies.

In a subanalysis adjusted for dose, naproxen proved to be associated with the highest risk of peptic ulcer hospitalization, with an adjusted rate of 7.8 per 1,000 patient-years. Ibuprofen, rofecoxib, and celecoxib all were associated with significantly lower risks of hospitalization.

Another subgroup analysis showed that an NSAID with gastroprotection was significantly better for several patient groups than an NSAID alone. These groups included patients over the age of 65 years and those with a history of previous ulcers.

In other subgroups with medical comorbidities, those taking low-dose aspirin, and those on antiplatelet or anticoagulant therapy, gastroprotection had no statistically significant improvement over unprotected NSAIDs. The researchers said this was partly because of relatively small numbers of patients in some of the subgroups.

The study was supported by the Agency for Healthcare Research and Quality, and the investigators stated that they received no support from any pharmaceutical company. “[It] is increasingly unlikely that large clinical trials of gastroprotective cotherapy in NSAID users will be conducted,” they wrote. “Proton pump inhibitors are available generically, which limits the incentives for pharmaceutical manufacturers to fund such studies. Furthermore, because NSAID-induced gastropathy is frequent and potentially life threatening, the ethics of randomizing patients to NSAID use without gastroprotective cotherapy are questionable.”

The researchers recommended future trials directly comparing coxibs to NSAIDs with a PPI, and said additional investigation is “urgently needed” to study the benefits of adding a PPI to celecoxib and other coxibs.

Adding a proton pump inhibitor to a nonsteroidal anti-inflammatory drug provides as much protection against NSAID-induced gastropathy as a cyclooxygenase-2 inhibitor (coxib), according to a new study September 2007 issue of the journal Gastroenterology.

Adding a proton pump inhibitor (PPI) to a coxib may provide some additional protection, but in recent years some coxibs have been shown to cause serious cardiovascular disease, wrote Wayne A. Ray, Ph.D., and his colleagues at Vanderbilt University, Nashville, Tenn.

The observational study used data from TennCare, the state of Tennessee's Medicaid program. Patients aged 40 years and older with a new episode of prescribed NSAID or coxib use between 1996 and 2004 were included. After excluding patients with serious illnesses such as cancer, HIV infection, cirrhosis, and chronic alcoholism, and those with less than 2 years of baseline data, the study included 234,010 new episodes of NSAID use and 48,710 new episodes of coxib use, with a total of 363,037 person-years of follow-up.

The investigators adjusted for a large number of demographic variables; prior history of peptic ulcer disease; use of low-dose aspirin, other antiplatelet drugs, anticoagulants, or systemic corticosteroids; new residence in a nursing home; and new nongastrointestinal hospital admission.

They found that the use of NSAIDs without gastroprotective cotherapy was associated with 5.65 peptic ulcer hospitalizations per 1,000 person-years, which is 2.8 times the incidence for comparable patients who were former users of either NSAIDs or coxibs.

Use of a PPI, a double-dose histamine-2 receptor antagonist, or misoprostol along with an NSAID reduced the risk of peptic ulcer hospitalization by 39%. Of the various gastroprotective therapies, PPIs were associated with the greatest risk reduction—54%—among NSAID users.

Unprotected use of a coxib resulted in a 40% reduction in the risk of peptic ulcer hospitalization, compared with unprotected use of an NSAID. Using a gastroprotective therapy in addition to a coxib resulted in a further 10% reduction in risk (for a total of 50%), with no statistically significant advantage for PPIs over other gastroprotective therapies.

In a subanalysis adjusted for dose, naproxen proved to be associated with the highest risk of peptic ulcer hospitalization, with an adjusted rate of 7.8 per 1,000 patient-years. Ibuprofen, rofecoxib, and celecoxib all were associated with significantly lower risks of hospitalization.

Another subgroup analysis showed that an NSAID with gastroprotection was significantly better for several patient groups than an NSAID alone. These groups included patients over the age of 65 years and those with a history of previous ulcers.

In other subgroups with medical comorbidities, those taking low-dose aspirin, and those on antiplatelet or anticoagulant therapy, gastroprotection had no statistically significant improvement over unprotected NSAIDs. The researchers said this was partly because of relatively small numbers of patients in some of the subgroups.

The study was supported by the Agency for Healthcare Research and Quality, and the investigators stated that they received no support from any pharmaceutical company. “[It] is increasingly unlikely that large clinical trials of gastroprotective cotherapy in NSAID users will be conducted,” they wrote. “Proton pump inhibitors are available generically, which limits the incentives for pharmaceutical manufacturers to fund such studies. Furthermore, because NSAID-induced gastropathy is frequent and potentially life threatening, the ethics of randomizing patients to NSAID use without gastroprotective cotherapy are questionable.”

The researchers recommended future trials directly comparing coxibs to NSAIDs with a PPI, and said additional investigation is “urgently needed” to study the benefits of adding a PPI to celecoxib and other coxibs.

SAN FRANCISCO — Several novel treatments for osteoporosis are under investigation, and one might even provide a cure, Dr. Steven R. Cummings said at a meeting sponsored by the University of California, San Francisco.

“Several of these treatments are based on fundamental biology, on biological mechanisms of bone formation and bone resorption,” Dr. Cummings, director of the San Francisco coordinating center of the California Pacific Medical Center Research Institute, said. “[I expect] these to make a big difference in practice within the next 5 years.”

One treatment involves sclerostin, which is produced by osteocytes, the most common and longest-lived cellular component of bone. Residing in microscopic cavities within bones, osteocytes are 100 times more numerous than osteoblasts and osteoclasts combined. Their job appears to be to sense strain in the bone and to communicate the need for bone building to the osteoblasts.

Sclerostin is not found in any other cell. It powerfully inhibits bone formation by interacting with mesenchymal stem cells—the precursors of osteoblasts—and reducing osteoblast formation. Sclerostin is produced by a gene called SOST, and individuals with mutations in that gene have sclerosteosis, a congenital disease characterized by extremely high bone mass, often leading to intracranial pressure and death.

In one study, female rats that were ovariectomized lost 12% of bone mass. But when given a monoclonal antibody to SOST, their vertebral bone mineral density (BMD) rose by 26% and their leg BMD by 16% over 5 weeks.

“This is a promising treatment, extremely potent, very specific to bone that has, I think, the potential to be a cure for osteoporosis,” Dr. Cummings said. “Human data might be available in the course of the next year.”

Then there is denosumab, an antibody that binds to the RankL receptor on the surface of osteoclasts. Blocking those receptors inhibits the development and activity of osteoclasts and decreases bone resorption.

Given by injection every 6 months, denosumab significantly increased spine and hip BMD, compared with alendronate and placebo in human phase II trials. Phase III trials are underway.

A third potential treatment is to be found in b-blockers. Osteoblasts have been observed in close proximity to sympathetic nerves, and they also possess beta-2 receptors. b-Blockers increase osteoblast activity in vivo. Mice treated with propranolol show increased bone mass. In one study, women taking b-blockers experienced a 28% reduction in the risk of hip fracture.

“Observational data, especially in the case of b-blockers, is difficult to believe enthusiastically,” Dr. Cummings said. “I don't think right now you should alter your clinical decisions about when you use b-blockers.”

Finally, high levels of the amino acid homocysteine appear to result in cardiovascular disease, dementia, blindness, and osteoporosis. Homocysteine appears to bind to and alter cross-links between collagen fibers. Even high-normal levels have been associated with an increased risk of fracture. Treatment with folic acid and vitamin B₁₂ reduces homocysteine levels.

At least one study has shown a large effect of the supplements in reducing fracture risk post stroke. In a randomized controlled trial, 628 patients were given daily doses of 5 mg folate and 1,500 mcg mecobalamin (a vitamin B₁₂ analog) or placebo for 2 years. After adjustment, the patients taking supplements experienced an 80% reduction in the risk of hip fracture (JAMA 2005;293:1082–8).

“This is so dramatic that it's hard to believe,” said Dr. Cummings. He added that he eagerly awaits further research.

Dr. Cummings receives research support and consulting fees from Eli Lilly & Co., Pfizer, and Novartis, and is a consultant to Merck.

Given by injection every 6 months, denosumab significantly increased spine and hip BMD. DR. CUMMINGS

SAN FRANCISCO — Several novel treatments for osteoporosis are under investigation, and one might even provide a cure, Dr. Steven R. Cummings said at a meeting sponsored by the University of California, San Francisco.

“Several of these treatments are based on fundamental biology, on biological mechanisms of bone formation and bone resorption,” Dr. Cummings, director of the San Francisco coordinating center of the California Pacific Medical Center Research Institute, said. “[I expect] these to make a big difference in practice within the next 5 years.”

One treatment involves sclerostin, which is produced by osteocytes, the most common and longest-lived cellular component of bone. Residing in microscopic cavities within bones, osteocytes are 100 times more numerous than osteoblasts and osteoclasts combined. Their job appears to be to sense strain in the bone and to communicate the need for bone building to the osteoblasts.

Sclerostin is not found in any other cell. It powerfully inhibits bone formation by interacting with mesenchymal stem cells—the precursors of osteoblasts—and reducing osteoblast formation. Sclerostin is produced by a gene called SOST, and individuals with mutations in that gene have sclerosteosis, a congenital disease characterized by extremely high bone mass, often leading to intracranial pressure and death.

In one study, female rats that were ovariectomized lost 12% of bone mass. But when given a monoclonal antibody to SOST, their vertebral bone mineral density (BMD) rose by 26% and their leg BMD by 16% over 5 weeks.

“This is a promising treatment, extremely potent, very specific to bone that has, I think, the potential to be a cure for osteoporosis,” Dr. Cummings said. “Human data might be available in the course of the next year.”

Then there is denosumab, an antibody that binds to the RankL receptor on the surface of osteoclasts. Blocking those receptors inhibits the development and activity of osteoclasts and decreases bone resorption.

Given by injection every 6 months, denosumab significantly increased spine and hip BMD, compared with alendronate and placebo in human phase II trials. Phase III trials are underway.

A third potential treatment is to be found in b-blockers. Osteoblasts have been observed in close proximity to sympathetic nerves, and they also possess beta-2 receptors. b-Blockers increase osteoblast activity in vivo. Mice treated with propranolol show increased bone mass. In one study, women taking b-blockers experienced a 28% reduction in the risk of hip fracture.

“Observational data, especially in the case of b-blockers, is difficult to believe enthusiastically,” Dr. Cummings said. “I don't think right now you should alter your clinical decisions about when you use b-blockers.”

Finally, high levels of the amino acid homocysteine appear to result in cardiovascular disease, dementia, blindness, and osteoporosis. Homocysteine appears to bind to and alter cross-links between collagen fibers. Even high-normal levels have been associated with an increased risk of fracture. Treatment with folic acid and vitamin B₁₂ reduces homocysteine levels.

At least one study has shown a large effect of the supplements in reducing fracture risk post stroke. In a randomized controlled trial, 628 patients were given daily doses of 5 mg folate and 1,500 mcg mecobalamin (a vitamin B₁₂ analog) or placebo for 2 years. After adjustment, the patients taking supplements experienced an 80% reduction in the risk of hip fracture (JAMA 2005;293:1082–8).

“This is so dramatic that it's hard to believe,” said Dr. Cummings. He added that he eagerly awaits further research.

Dr. Cummings receives research support and consulting fees from Eli Lilly & Co., Pfizer, and Novartis, and is a consultant to Merck.

Given by injection every 6 months, denosumab significantly increased spine and hip BMD. DR. CUMMINGS

SAN FRANCISCO — Several novel treatments for osteoporosis are under investigation, and one might even provide a cure, Dr. Steven R. Cummings said at a meeting sponsored by the University of California, San Francisco.

“Several of these treatments are based on fundamental biology, on biological mechanisms of bone formation and bone resorption,” Dr. Cummings, director of the San Francisco coordinating center of the California Pacific Medical Center Research Institute, said. “[I expect] these to make a big difference in practice within the next 5 years.”

One treatment involves sclerostin, which is produced by osteocytes, the most common and longest-lived cellular component of bone. Residing in microscopic cavities within bones, osteocytes are 100 times more numerous than osteoblasts and osteoclasts combined. Their job appears to be to sense strain in the bone and to communicate the need for bone building to the osteoblasts.

Sclerostin is not found in any other cell. It powerfully inhibits bone formation by interacting with mesenchymal stem cells—the precursors of osteoblasts—and reducing osteoblast formation. Sclerostin is produced by a gene called SOST, and individuals with mutations in that gene have sclerosteosis, a congenital disease characterized by extremely high bone mass, often leading to intracranial pressure and death.

In one study, female rats that were ovariectomized lost 12% of bone mass. But when given a monoclonal antibody to SOST, their vertebral bone mineral density (BMD) rose by 26% and their leg BMD by 16% over 5 weeks.

“This is a promising treatment, extremely potent, very specific to bone that has, I think, the potential to be a cure for osteoporosis,” Dr. Cummings said. “Human data might be available in the course of the next year.”

Then there is denosumab, an antibody that binds to the RankL receptor on the surface of osteoclasts. Blocking those receptors inhibits the development and activity of osteoclasts and decreases bone resorption.

Given by injection every 6 months, denosumab significantly increased spine and hip BMD, compared with alendronate and placebo in human phase II trials. Phase III trials are underway.

A third potential treatment is to be found in b-blockers. Osteoblasts have been observed in close proximity to sympathetic nerves, and they also possess beta-2 receptors. b-Blockers increase osteoblast activity in vivo. Mice treated with propranolol show increased bone mass. In one study, women taking b-blockers experienced a 28% reduction in the risk of hip fracture.

“Observational data, especially in the case of b-blockers, is difficult to believe enthusiastically,” Dr. Cummings said. “I don't think right now you should alter your clinical decisions about when you use b-blockers.”

Finally, high levels of the amino acid homocysteine appear to result in cardiovascular disease, dementia, blindness, and osteoporosis. Homocysteine appears to bind to and alter cross-links between collagen fibers. Even high-normal levels have been associated with an increased risk of fracture. Treatment with folic acid and vitamin B₁₂ reduces homocysteine levels.

At least one study has shown a large effect of the supplements in reducing fracture risk post stroke. In a randomized controlled trial, 628 patients were given daily doses of 5 mg folate and 1,500 mcg mecobalamin (a vitamin B₁₂ analog) or placebo for 2 years. After adjustment, the patients taking supplements experienced an 80% reduction in the risk of hip fracture (JAMA 2005;293:1082–8).

“This is so dramatic that it's hard to believe,” said Dr. Cummings. He added that he eagerly awaits further research.

Dr. Cummings receives research support and consulting fees from Eli Lilly & Co., Pfizer, and Novartis, and is a consultant to Merck.

Given by injection every 6 months, denosumab significantly increased spine and hip BMD. DR. CUMMINGS

In a controversial move, the American College of Chest Physicians has formally recommended against the use of low-dose helical CT scanning for general lung cancer screening, even in high-risk populations, except in the context of clinical trials.

The ACCP also recommended against the use of serial chest radiographs and sputum cytologic evaluation to screen for the presence of lung cancer.

“The evidence isn't available to show that low-dose CT screening provides a mortality benefit,” Dr. W. Michael Alberts said in an interview. Dr. Alberts, the chief medical officer of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla., chaired the ACCP committee that developed the guidelines. “Because there's a very real potential for harm, it's going to be important to prove or show a mortality benefit prior to recommending screening with a low-dose CT scan.”

The second edition of the college's “Diagnosis and Management of Lung Cancer” includes 260 guidelines, three of which involve lung cancer screening. It was published as a supplement to the September 2007 issue of the journal Chest (2007;132[suppl.]:1S–422S). This edition updates the original version of the guidelines, published in January 2003.

The screening guidelines were developed by a subcommittee headed by Dr. Peter B. Bach of the Memorial Sloan-Kettering Cancer Center, New York. Although acknowledging that low-dose CT scanning remains the most promising of the lung cancer screening techniques, the guideline authors maintain that—even though the existing data do suggest that low-dose CT increases the rate of detection of early-stage lung cancers—such CT screening fails to reduce the number of late-stage lung cancers or the risk of dying from lung cancer. They suggest that this may be because many of the additional cancers detected are small, indolent cancers, which leads to unnecessary invasive procedures that carry a cost in morbidity and mortality.

The subcommittee's analysis includes a theoretical model of the time it takes for a given nodule to double in size. They estimated that the doubling time of lung tumors resulting in deaths is approximately 40–70 days, whereas research shows that the doubling time of early cancers identified by CT screening ranges from 149 to 813 days.

“As best I know, this is the first time that anyone has tried to make a public health policy statement against screening based upon theoretical considerations of nodule doubling time,” said Dr. James L. Mulshine of Rush University Medical Center, Chicago, in an interview. “This is a totally unvalidated tool, and really not the grist for evidence-based analysis of the screening service.”

“The recommendations weren't based on that at all,” Dr. Bach responded in an interview. Instead, he said, the model was intended to provide one possible explanation for the fact that studies have so far failed to demonstrate that screening results in demonstrable improvements in mortality.

Dr. Mulshine said that some studies were omitted from the analysis unfairly, and that the guideline authors interpreted other studies selectively. He is on the board of directors of the Lung Cancer Alliance (www.lungcanceralliance.org

Dr. Mulshine acknowledged the lack of persuasive evidence from double-blind studies showing reduced mortality related to lung cancer screening. One such study may be completed as early as 2009, but possibly not until 2011. Data from another study won't be available for another 2 years or so after that.

“We all hope that the randomized, controlled trials will show a mortality benefit,” Dr. Alberts said. “We'd like to have that outcome, at which time maybe low-dose CT scanning should be recommended. But at this time, the evidence is not available, and there is potential evidence that it may be harmful. As a result, we can't in all good conscience recommend CT scanning at this point.”

But Dr. Mulshine noted that while waiting for the results of those randomized trials, 160,000 Americans die every year from lung cancer, in part because most lung cancer is not diagnosed until it's stage III or IV. And he pointed to data showing that morbidity and mortality from diagnostic procedures conducted as a result of screening are extraordinarily low in “centers of excellence.” Furthermore, the last 5 years have seen a significant improvement in noninvasive procedures, improvements that are likely to continue if more research is done in this area.

But for Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, “the issue isn't diagnostic procedures. It's the morbidity and mortality from subsequent surgery that concerns me.” ACS does not recommend routine CT screening for lung cancer at this time.” However, “understanding that some people will nonetheless want to proceed with screening, they should have a careful discussion with their doctor regarding the potential risks that could result.”

The U.S. Preventive Services Task Force states that there is insufficient evidence to recommend for or against lung cancer screening.

'The evidence isn't available to show that low-dose CT screening provides a mortality benefit.' DR. ALBERTS

Other Points Covered by the Guidelines

In addition to the three recommendations on lung cancer screening, the ACCP has issued 257 recommendations on the prevention, diagnosis, and treatment of lung cancer.

The ACCP classifies its evidence-based guidelines as strong (grade 1) or weak (grade 2) based on a balance of risks, benefits, burdens, and costs. The college also classifies the quality of evidence as high (grade A), moderate (grade B), or low (grade C) based on study design, consistency of results, and directness of the evidence.

The following are among the most notable of the other recommendations:

▸ Fifteen of the guidelines deal with complementary therapies and integrative oncology. The guidelines recommend mind-body modalities to reduce anxiety, mood disturbances, or chronic pain (grade 1B); massage therapy for anxiety or pain (grade 1C), as long as it does not involve deep or intense pressure near cancer lesions or anatomical distortions (grade 2C); and acupuncture for poorly controlled pain or for side effects such as neuropathy or xerostomia (grade 1A) and for nausea and vomiting (grade 1B).

However, the guidelines recommend against therapy based on putative manipulation of bioenergy fields (grade 1C); electrostimulation wristbands for nausea and vomiting (grade 1B); and botanical agents in patients who either fail or decline antitumor therapies except in the context of clinical trials (grade 1C).

In addition, physicians should specifically ask all patients with lung cancer about their use of complementary and alternative therapies (grade 1C).

▸ In terms of lung cancer chemoprevention, the guidelines recommend against supplementation with β-carotene, vitamin D, retinoids, N-acetylcysteine, and aspirin (grade 1A). The guidelines further state that even for individuals at risk of lung cancer or with a history of lung cancer, there are insufficient data to recommend any agent—either alone or in combination—for chemoprevention, except in the context of a clinical trial (grade 1B).

▸ Solitary pulmonary nodules are addressed in 29 guidelines. The guidelines direct physicians to estimate the pretest probability of malignancy (grade 1C), and to perform specific imaging and diagnostic tests based on that probability and other characteristics of the nodule (various grades). They also recommend a number of surgical approaches, including thorascopic wedge resection and lobectomy, depending on the results of these tests and patient preference (various grades).

▸ For the first time, the guidelines address bronchioloalveolar carcinoma. They recommend surgical biopsy for establishing a diagnosis (grade 1C); follow-up diagnostic testing after a negative PET scan (grade 1C); and sublobar resection for patients who are good surgical candidates, provided the CT scan shows a pure ground-glass appearance and there's no evidence of invasive disease (grade 1B).

▸ Palliative care is addressed in 35 guidelines. Patients should be reassured that pain can be treated safely and effectively, and all patients should be questioned regularly about their pain (grade 1A). Patients with mild to moderate pain should be managed first with acetaminophen or an NSAID, and then with an opioid when pain becomes more severe (grade 1B). Those with pain unresponsive to standard methods should be referred to a specialized pain clinic or a palliative care consultant (grade 1C).

External radiation therapy and bisphosphonates are recommended for patients who have pain from bone metastases (grade 1A). Patients with malignant tracheoesophageal or bronchoesophageal fistula should be considered for stenting of the esophagus, airway, or both for symptomatic relief, but attempts at curative resection or esophageal bypass are not recommended (grade 1C).

▸ All patients with lung cancer should be evaluated for the presence of depression and treated appropriately (grade 1C).

In a controversial move, the American College of Chest Physicians has formally recommended against the use of low-dose helical CT scanning for general lung cancer screening, even in high-risk populations, except in the context of clinical trials.

The ACCP also recommended against the use of serial chest radiographs and sputum cytologic evaluation to screen for the presence of lung cancer.

“The evidence isn't available to show that low-dose CT screening provides a mortality benefit,” Dr. W. Michael Alberts said in an interview. Dr. Alberts, the chief medical officer of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla., chaired the ACCP committee that developed the guidelines. “Because there's a very real potential for harm, it's going to be important to prove or show a mortality benefit prior to recommending screening with a low-dose CT scan.”

The second edition of the college's “Diagnosis and Management of Lung Cancer” includes 260 guidelines, three of which involve lung cancer screening. It was published as a supplement to the September 2007 issue of the journal Chest (2007;132[suppl.]:1S–422S). This edition updates the original version of the guidelines, published in January 2003.

The screening guidelines were developed by a subcommittee headed by Dr. Peter B. Bach of the Memorial Sloan-Kettering Cancer Center, New York. Although acknowledging that low-dose CT scanning remains the most promising of the lung cancer screening techniques, the guideline authors maintain that—even though the existing data do suggest that low-dose CT increases the rate of detection of early-stage lung cancers—such CT screening fails to reduce the number of late-stage lung cancers or the risk of dying from lung cancer. They suggest that this may be because many of the additional cancers detected are small, indolent cancers, which leads to unnecessary invasive procedures that carry a cost in morbidity and mortality.

The subcommittee's analysis includes a theoretical model of the time it takes for a given nodule to double in size. They estimated that the doubling time of lung tumors resulting in deaths is approximately 40–70 days, whereas research shows that the doubling time of early cancers identified by CT screening ranges from 149 to 813 days.

“As best I know, this is the first time that anyone has tried to make a public health policy statement against screening based upon theoretical considerations of nodule doubling time,” said Dr. James L. Mulshine of Rush University Medical Center, Chicago, in an interview. “This is a totally unvalidated tool, and really not the grist for evidence-based analysis of the screening service.”

“The recommendations weren't based on that at all,” Dr. Bach responded in an interview. Instead, he said, the model was intended to provide one possible explanation for the fact that studies have so far failed to demonstrate that screening results in demonstrable improvements in mortality.

Dr. Mulshine said that some studies were omitted from the analysis unfairly, and that the guideline authors interpreted other studies selectively. He is on the board of directors of the Lung Cancer Alliance (www.lungcanceralliance.org

Dr. Mulshine acknowledged the lack of persuasive evidence from double-blind studies showing reduced mortality related to lung cancer screening. One such study may be completed as early as 2009, but possibly not until 2011. Data from another study won't be available for another 2 years or so after that.

“We all hope that the randomized, controlled trials will show a mortality benefit,” Dr. Alberts said. “We'd like to have that outcome, at which time maybe low-dose CT scanning should be recommended. But at this time, the evidence is not available, and there is potential evidence that it may be harmful. As a result, we can't in all good conscience recommend CT scanning at this point.”

But Dr. Mulshine noted that while waiting for the results of those randomized trials, 160,000 Americans die every year from lung cancer, in part because most lung cancer is not diagnosed until it's stage III or IV. And he pointed to data showing that morbidity and mortality from diagnostic procedures conducted as a result of screening are extraordinarily low in “centers of excellence.” Furthermore, the last 5 years have seen a significant improvement in noninvasive procedures, improvements that are likely to continue if more research is done in this area.

But for Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, “the issue isn't diagnostic procedures. It's the morbidity and mortality from subsequent surgery that concerns me.” ACS does not recommend routine CT screening for lung cancer at this time.” However, “understanding that some people will nonetheless want to proceed with screening, they should have a careful discussion with their doctor regarding the potential risks that could result.”

The U.S. Preventive Services Task Force states that there is insufficient evidence to recommend for or against lung cancer screening.

'The evidence isn't available to show that low-dose CT screening provides a mortality benefit.' DR. ALBERTS

Other Points Covered by the Guidelines

In addition to the three recommendations on lung cancer screening, the ACCP has issued 257 recommendations on the prevention, diagnosis, and treatment of lung cancer.

The ACCP classifies its evidence-based guidelines as strong (grade 1) or weak (grade 2) based on a balance of risks, benefits, burdens, and costs. The college also classifies the quality of evidence as high (grade A), moderate (grade B), or low (grade C) based on study design, consistency of results, and directness of the evidence.

The following are among the most notable of the other recommendations:

▸ Fifteen of the guidelines deal with complementary therapies and integrative oncology. The guidelines recommend mind-body modalities to reduce anxiety, mood disturbances, or chronic pain (grade 1B); massage therapy for anxiety or pain (grade 1C), as long as it does not involve deep or intense pressure near cancer lesions or anatomical distortions (grade 2C); and acupuncture for poorly controlled pain or for side effects such as neuropathy or xerostomia (grade 1A) and for nausea and vomiting (grade 1B).

However, the guidelines recommend against therapy based on putative manipulation of bioenergy fields (grade 1C); electrostimulation wristbands for nausea and vomiting (grade 1B); and botanical agents in patients who either fail or decline antitumor therapies except in the context of clinical trials (grade 1C).

In addition, physicians should specifically ask all patients with lung cancer about their use of complementary and alternative therapies (grade 1C).

▸ In terms of lung cancer chemoprevention, the guidelines recommend against supplementation with β-carotene, vitamin D, retinoids, N-acetylcysteine, and aspirin (grade 1A). The guidelines further state that even for individuals at risk of lung cancer or with a history of lung cancer, there are insufficient data to recommend any agent—either alone or in combination—for chemoprevention, except in the context of a clinical trial (grade 1B).

▸ Solitary pulmonary nodules are addressed in 29 guidelines. The guidelines direct physicians to estimate the pretest probability of malignancy (grade 1C), and to perform specific imaging and diagnostic tests based on that probability and other characteristics of the nodule (various grades). They also recommend a number of surgical approaches, including thorascopic wedge resection and lobectomy, depending on the results of these tests and patient preference (various grades).

▸ For the first time, the guidelines address bronchioloalveolar carcinoma. They recommend surgical biopsy for establishing a diagnosis (grade 1C); follow-up diagnostic testing after a negative PET scan (grade 1C); and sublobar resection for patients who are good surgical candidates, provided the CT scan shows a pure ground-glass appearance and there's no evidence of invasive disease (grade 1B).

▸ Palliative care is addressed in 35 guidelines. Patients should be reassured that pain can be treated safely and effectively, and all patients should be questioned regularly about their pain (grade 1A). Patients with mild to moderate pain should be managed first with acetaminophen or an NSAID, and then with an opioid when pain becomes more severe (grade 1B). Those with pain unresponsive to standard methods should be referred to a specialized pain clinic or a palliative care consultant (grade 1C).

External radiation therapy and bisphosphonates are recommended for patients who have pain from bone metastases (grade 1A). Patients with malignant tracheoesophageal or bronchoesophageal fistula should be considered for stenting of the esophagus, airway, or both for symptomatic relief, but attempts at curative resection or esophageal bypass are not recommended (grade 1C).

▸ All patients with lung cancer should be evaluated for the presence of depression and treated appropriately (grade 1C).

In a controversial move, the American College of Chest Physicians has formally recommended against the use of low-dose helical CT scanning for general lung cancer screening, even in high-risk populations, except in the context of clinical trials.

The ACCP also recommended against the use of serial chest radiographs and sputum cytologic evaluation to screen for the presence of lung cancer.

“The evidence isn't available to show that low-dose CT screening provides a mortality benefit,” Dr. W. Michael Alberts said in an interview. Dr. Alberts, the chief medical officer of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla., chaired the ACCP committee that developed the guidelines. “Because there's a very real potential for harm, it's going to be important to prove or show a mortality benefit prior to recommending screening with a low-dose CT scan.”

The second edition of the college's “Diagnosis and Management of Lung Cancer” includes 260 guidelines, three of which involve lung cancer screening. It was published as a supplement to the September 2007 issue of the journal Chest (2007;132[suppl.]:1S–422S). This edition updates the original version of the guidelines, published in January 2003.

The screening guidelines were developed by a subcommittee headed by Dr. Peter B. Bach of the Memorial Sloan-Kettering Cancer Center, New York. Although acknowledging that low-dose CT scanning remains the most promising of the lung cancer screening techniques, the guideline authors maintain that—even though the existing data do suggest that low-dose CT increases the rate of detection of early-stage lung cancers—such CT screening fails to reduce the number of late-stage lung cancers or the risk of dying from lung cancer. They suggest that this may be because many of the additional cancers detected are small, indolent cancers, which leads to unnecessary invasive procedures that carry a cost in morbidity and mortality.

The subcommittee's analysis includes a theoretical model of the time it takes for a given nodule to double in size. They estimated that the doubling time of lung tumors resulting in deaths is approximately 40–70 days, whereas research shows that the doubling time of early cancers identified by CT screening ranges from 149 to 813 days.

“As best I know, this is the first time that anyone has tried to make a public health policy statement against screening based upon theoretical considerations of nodule doubling time,” said Dr. James L. Mulshine of Rush University Medical Center, Chicago, in an interview. “This is a totally unvalidated tool, and really not the grist for evidence-based analysis of the screening service.”

“The recommendations weren't based on that at all,” Dr. Bach responded in an interview. Instead, he said, the model was intended to provide one possible explanation for the fact that studies have so far failed to demonstrate that screening results in demonstrable improvements in mortality.

Dr. Mulshine said that some studies were omitted from the analysis unfairly, and that the guideline authors interpreted other studies selectively. He is on the board of directors of the Lung Cancer Alliance (www.lungcanceralliance.org

Dr. Mulshine acknowledged the lack of persuasive evidence from double-blind studies showing reduced mortality related to lung cancer screening. One such study may be completed as early as 2009, but possibly not until 2011. Data from another study won't be available for another 2 years or so after that.

“We all hope that the randomized, controlled trials will show a mortality benefit,” Dr. Alberts said. “We'd like to have that outcome, at which time maybe low-dose CT scanning should be recommended. But at this time, the evidence is not available, and there is potential evidence that it may be harmful. As a result, we can't in all good conscience recommend CT scanning at this point.”

But Dr. Mulshine noted that while waiting for the results of those randomized trials, 160,000 Americans die every year from lung cancer, in part because most lung cancer is not diagnosed until it's stage III or IV. And he pointed to data showing that morbidity and mortality from diagnostic procedures conducted as a result of screening are extraordinarily low in “centers of excellence.” Furthermore, the last 5 years have seen a significant improvement in noninvasive procedures, improvements that are likely to continue if more research is done in this area.

But for Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, “the issue isn't diagnostic procedures. It's the morbidity and mortality from subsequent surgery that concerns me.” ACS does not recommend routine CT screening for lung cancer at this time.” However, “understanding that some people will nonetheless want to proceed with screening, they should have a careful discussion with their doctor regarding the potential risks that could result.”

The U.S. Preventive Services Task Force states that there is insufficient evidence to recommend for or against lung cancer screening.

'The evidence isn't available to show that low-dose CT screening provides a mortality benefit.' DR. ALBERTS

Other Points Covered by the Guidelines

In addition to the three recommendations on lung cancer screening, the ACCP has issued 257 recommendations on the prevention, diagnosis, and treatment of lung cancer.

The ACCP classifies its evidence-based guidelines as strong (grade 1) or weak (grade 2) based on a balance of risks, benefits, burdens, and costs. The college also classifies the quality of evidence as high (grade A), moderate (grade B), or low (grade C) based on study design, consistency of results, and directness of the evidence.

The following are among the most notable of the other recommendations:

▸ Fifteen of the guidelines deal with complementary therapies and integrative oncology. The guidelines recommend mind-body modalities to reduce anxiety, mood disturbances, or chronic pain (grade 1B); massage therapy for anxiety or pain (grade 1C), as long as it does not involve deep or intense pressure near cancer lesions or anatomical distortions (grade 2C); and acupuncture for poorly controlled pain or for side effects such as neuropathy or xerostomia (grade 1A) and for nausea and vomiting (grade 1B).

However, the guidelines recommend against therapy based on putative manipulation of bioenergy fields (grade 1C); electrostimulation wristbands for nausea and vomiting (grade 1B); and botanical agents in patients who either fail or decline antitumor therapies except in the context of clinical trials (grade 1C).

In addition, physicians should specifically ask all patients with lung cancer about their use of complementary and alternative therapies (grade 1C).

▸ In terms of lung cancer chemoprevention, the guidelines recommend against supplementation with β-carotene, vitamin D, retinoids, N-acetylcysteine, and aspirin (grade 1A). The guidelines further state that even for individuals at risk of lung cancer or with a history of lung cancer, there are insufficient data to recommend any agent—either alone or in combination—for chemoprevention, except in the context of a clinical trial (grade 1B).

▸ Solitary pulmonary nodules are addressed in 29 guidelines. The guidelines direct physicians to estimate the pretest probability of malignancy (grade 1C), and to perform specific imaging and diagnostic tests based on that probability and other characteristics of the nodule (various grades). They also recommend a number of surgical approaches, including thorascopic wedge resection and lobectomy, depending on the results of these tests and patient preference (various grades).

▸ For the first time, the guidelines address bronchioloalveolar carcinoma. They recommend surgical biopsy for establishing a diagnosis (grade 1C); follow-up diagnostic testing after a negative PET scan (grade 1C); and sublobar resection for patients who are good surgical candidates, provided the CT scan shows a pure ground-glass appearance and there's no evidence of invasive disease (grade 1B).

▸ Palliative care is addressed in 35 guidelines. Patients should be reassured that pain can be treated safely and effectively, and all patients should be questioned regularly about their pain (grade 1A). Patients with mild to moderate pain should be managed first with acetaminophen or an NSAID, and then with an opioid when pain becomes more severe (grade 1B). Those with pain unresponsive to standard methods should be referred to a specialized pain clinic or a palliative care consultant (grade 1C).

External radiation therapy and bisphosphonates are recommended for patients who have pain from bone metastases (grade 1A). Patients with malignant tracheoesophageal or bronchoesophageal fistula should be considered for stenting of the esophagus, airway, or both for symptomatic relief, but attempts at curative resection or esophageal bypass are not recommended (grade 1C).

▸ All patients with lung cancer should be evaluated for the presence of depression and treated appropriately (grade 1C).

The addition of a proton pump inhibitor to a nonsteroidal anti-inflammatory drug provides as much protection against NSAID-induced gastropathy as does use of a cyclooxygenase-2 inhibitor (coxib), according to a study published in the September 2007 issue of the journal Gastroenterology.

Adding a proton pump inhibitor (PPI) to a coxib may provide some additional protection, but in recent years some coxibs have been shown to cause serious cardiovascular disease, wrote Wayne A. Ray, Ph.D., and his colleagues at Vanderbilt University, Nashville, Tenn.

The observational study used data from TennCare, the state of Tennessee's Medicaid program. Patients aged 40 years and older with a new episode of prescribed NSAID or coxib use between 1996 and 2004 were included. After excluding patients with serious illnesses such as cancer, HIV infection, cirrhosis, and chronic alcoholism, and those with less than 2 years of baseline data, the study included 234,010 new episodes of NSAID use and 48,710 new episodes of coxib use, with a total of 363,037 person-years of follow-up.

The investigators adjusted for a large number of demographic variables; prior history of peptic ulcer disease; use of low-dose aspirin, other antiplatelet drugs, anticoagulants, or systemic corticosteroids; new residence in a nursing home; and new nongastrointestinal hospital admission.

They found that use of NSAIDs without gastroprotective cotherapy was associated with 5.65 peptic ulcer hospitalizations per 1,000 person-years, which is 2.8 times the incidence for comparable patients who were former users of either NSAIDs or coxibs.

Use of a PPI, a double-dose histamine-2 receptor antagonist, or misoprostol along with an NSAID reduced the risk of peptic ulcer hospitalization by 39%. Of the various gastroprotective therapies, PPIs were associated with the greatest degree of risk reduction—54%–-in current NSAID users.

Unprotected use of a coxib resulted in a 40% reduction in the risk of peptic ulcer hospitalization, compared with unprotected use of an NSAID. Using a gastroprotective therapy in addition to a coxib resulted in a further 10% reduction in risk (for a total of 50%), with no statistically significant advantage for PPIs over other gastroprotective therapies.

In a subanalysis adjusted for dose, naproxen proved to be associated with the highest risk of peptic ulcer hospitalization, with an adjusted rate of 7.8 per 1,000 patient-years. Ibuprofen, rofecoxib, and celecoxib all were associated with significantly lower risks of hospitalization.

Another subgroup analysis showed that an NSAID with gastroprotection was significantly better for several patient groups than an NSAID alone. These groups included patients over the age of 65 years and those with a history of previous ulcers.

In other subgroups, including those with medical comorbidities, those taking low-dose aspirin, and those on antiplatelet or anticoagulant therapy, gastroprotection provided no statistically significant improvement over unprotected NSAIDs. The investigators noted this was in part because of relatively small numbers of patients in some of the subgroups.

The study was supported by the Agency for Healthcare Research and Quality. The investigators received no support from any pharmaceutical company.

ELSEVIER GLOBAL MEDICAL NEWS

The addition of a proton pump inhibitor to a nonsteroidal anti-inflammatory drug provides as much protection against NSAID-induced gastropathy as does use of a cyclooxygenase-2 inhibitor (coxib), according to a study published in the September 2007 issue of the journal Gastroenterology.

Adding a proton pump inhibitor (PPI) to a coxib may provide some additional protection, but in recent years some coxibs have been shown to cause serious cardiovascular disease, wrote Wayne A. Ray, Ph.D., and his colleagues at Vanderbilt University, Nashville, Tenn.

The observational study used data from TennCare, the state of Tennessee's Medicaid program. Patients aged 40 years and older with a new episode of prescribed NSAID or coxib use between 1996 and 2004 were included. After excluding patients with serious illnesses such as cancer, HIV infection, cirrhosis, and chronic alcoholism, and those with less than 2 years of baseline data, the study included 234,010 new episodes of NSAID use and 48,710 new episodes of coxib use, with a total of 363,037 person-years of follow-up.

The investigators adjusted for a large number of demographic variables; prior history of peptic ulcer disease; use of low-dose aspirin, other antiplatelet drugs, anticoagulants, or systemic corticosteroids; new residence in a nursing home; and new nongastrointestinal hospital admission.

They found that use of NSAIDs without gastroprotective cotherapy was associated with 5.65 peptic ulcer hospitalizations per 1,000 person-years, which is 2.8 times the incidence for comparable patients who were former users of either NSAIDs or coxibs.

Use of a PPI, a double-dose histamine-2 receptor antagonist, or misoprostol along with an NSAID reduced the risk of peptic ulcer hospitalization by 39%. Of the various gastroprotective therapies, PPIs were associated with the greatest degree of risk reduction—54%–-in current NSAID users.

Unprotected use of a coxib resulted in a 40% reduction in the risk of peptic ulcer hospitalization, compared with unprotected use of an NSAID. Using a gastroprotective therapy in addition to a coxib resulted in a further 10% reduction in risk (for a total of 50%), with no statistically significant advantage for PPIs over other gastroprotective therapies.

In a subanalysis adjusted for dose, naproxen proved to be associated with the highest risk of peptic ulcer hospitalization, with an adjusted rate of 7.8 per 1,000 patient-years. Ibuprofen, rofecoxib, and celecoxib all were associated with significantly lower risks of hospitalization.

Another subgroup analysis showed that an NSAID with gastroprotection was significantly better for several patient groups than an NSAID alone. These groups included patients over the age of 65 years and those with a history of previous ulcers.

In other subgroups, including those with medical comorbidities, those taking low-dose aspirin, and those on antiplatelet or anticoagulant therapy, gastroprotection provided no statistically significant improvement over unprotected NSAIDs. The investigators noted this was in part because of relatively small numbers of patients in some of the subgroups.

The study was supported by the Agency for Healthcare Research and Quality. The investigators received no support from any pharmaceutical company.

ELSEVIER GLOBAL MEDICAL NEWS

The addition of a proton pump inhibitor to a nonsteroidal anti-inflammatory drug provides as much protection against NSAID-induced gastropathy as does use of a cyclooxygenase-2 inhibitor (coxib), according to a study published in the September 2007 issue of the journal Gastroenterology.

Adding a proton pump inhibitor (PPI) to a coxib may provide some additional protection, but in recent years some coxibs have been shown to cause serious cardiovascular disease, wrote Wayne A. Ray, Ph.D., and his colleagues at Vanderbilt University, Nashville, Tenn.

The observational study used data from TennCare, the state of Tennessee's Medicaid program. Patients aged 40 years and older with a new episode of prescribed NSAID or coxib use between 1996 and 2004 were included. After excluding patients with serious illnesses such as cancer, HIV infection, cirrhosis, and chronic alcoholism, and those with less than 2 years of baseline data, the study included 234,010 new episodes of NSAID use and 48,710 new episodes of coxib use, with a total of 363,037 person-years of follow-up.

The investigators adjusted for a large number of demographic variables; prior history of peptic ulcer disease; use of low-dose aspirin, other antiplatelet drugs, anticoagulants, or systemic corticosteroids; new residence in a nursing home; and new nongastrointestinal hospital admission.

They found that use of NSAIDs without gastroprotective cotherapy was associated with 5.65 peptic ulcer hospitalizations per 1,000 person-years, which is 2.8 times the incidence for comparable patients who were former users of either NSAIDs or coxibs.

Use of a PPI, a double-dose histamine-2 receptor antagonist, or misoprostol along with an NSAID reduced the risk of peptic ulcer hospitalization by 39%. Of the various gastroprotective therapies, PPIs were associated with the greatest degree of risk reduction—54%–-in current NSAID users.

Unprotected use of a coxib resulted in a 40% reduction in the risk of peptic ulcer hospitalization, compared with unprotected use of an NSAID. Using a gastroprotective therapy in addition to a coxib resulted in a further 10% reduction in risk (for a total of 50%), with no statistically significant advantage for PPIs over other gastroprotective therapies.

In a subanalysis adjusted for dose, naproxen proved to be associated with the highest risk of peptic ulcer hospitalization, with an adjusted rate of 7.8 per 1,000 patient-years. Ibuprofen, rofecoxib, and celecoxib all were associated with significantly lower risks of hospitalization.

Another subgroup analysis showed that an NSAID with gastroprotection was significantly better for several patient groups than an NSAID alone. These groups included patients over the age of 65 years and those with a history of previous ulcers.

In other subgroups, including those with medical comorbidities, those taking low-dose aspirin, and those on antiplatelet or anticoagulant therapy, gastroprotection provided no statistically significant improvement over unprotected NSAIDs. The investigators noted this was in part because of relatively small numbers of patients in some of the subgroups.

The study was supported by the Agency for Healthcare Research and Quality. The investigators received no support from any pharmaceutical company.

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — Patients with moderate to severe asthma experience fewer exacerbations and use adjunctive and rescue medications for shorter periods when taking combined budesonide and formoterol, compared with those taking budesonide alone, according to a poster presentation at the International Conference of the American Thoracic Society.

These results contradict three previous meta-analyses that failed to find pronounced reductions in asthma exacerbations in patients taking both long-acting β-2 agonists and inhaled steroids, compared with those taking inhaled steroids alone, wrote Dr. Christopher D. O'Brien of AstraZeneca and his coauthors. AstraZeneca, which manufactures combination budesonide and formoterol under the brand name Symbicort, supported the study.

Included in the multicenter randomized study were 708 adolescent and adult patients (mean age 40 years) who had received a diagnosis of asthma and reported consistent daily use of inhaled corticosteroids for at least 4 weeks before screening.

After a 2-week run-in period on budesonide alone (320 mcg twice daily), patients were randomized to receive a higher dose of budesonide alone (640 mcg twice daily), a high dose of budesonide and formoterol (640 mcg/18 mcg twice daily), or a low-dose of budesonide and formoterol (320 mcg/9 mcg twice daily).

Patients on both combined regimens experienced significantly fewer asthma exacerbations over the following 52 weeks. Those on the higher dose of budesonide and formoterol had a 45% reduction in exacerbations, and those on the lower dose had a 41% reduction, compared with patients taking budesonide alone.

Patients on both combined regimens also needed oral corticosteroids for fewer total days than did patients taking budesonide alone, with decreases of 51% for the higher combined dose and 42% for the lower combined dose. Conversely, there were no differences in the groups on several other measures of resource use, such as the number of days of hospitalization because of asthma, the number of emergency department visits, and number of unscheduled visits to a specialist or primary care physician.

SAN FRANCISCO — Patients with moderate to severe asthma experience fewer exacerbations and use adjunctive and rescue medications for shorter periods when taking combined budesonide and formoterol, compared with those taking budesonide alone, according to a poster presentation at the International Conference of the American Thoracic Society.

These results contradict three previous meta-analyses that failed to find pronounced reductions in asthma exacerbations in patients taking both long-acting β-2 agonists and inhaled steroids, compared with those taking inhaled steroids alone, wrote Dr. Christopher D. O'Brien of AstraZeneca and his coauthors. AstraZeneca, which manufactures combination budesonide and formoterol under the brand name Symbicort, supported the study.

Included in the multicenter randomized study were 708 adolescent and adult patients (mean age 40 years) who had received a diagnosis of asthma and reported consistent daily use of inhaled corticosteroids for at least 4 weeks before screening.

After a 2-week run-in period on budesonide alone (320 mcg twice daily), patients were randomized to receive a higher dose of budesonide alone (640 mcg twice daily), a high dose of budesonide and formoterol (640 mcg/18 mcg twice daily), or a low-dose of budesonide and formoterol (320 mcg/9 mcg twice daily).

Patients on both combined regimens experienced significantly fewer asthma exacerbations over the following 52 weeks. Those on the higher dose of budesonide and formoterol had a 45% reduction in exacerbations, and those on the lower dose had a 41% reduction, compared with patients taking budesonide alone.

Patients on both combined regimens also needed oral corticosteroids for fewer total days than did patients taking budesonide alone, with decreases of 51% for the higher combined dose and 42% for the lower combined dose. Conversely, there were no differences in the groups on several other measures of resource use, such as the number of days of hospitalization because of asthma, the number of emergency department visits, and number of unscheduled visits to a specialist or primary care physician.

SAN FRANCISCO — Patients with moderate to severe asthma experience fewer exacerbations and use adjunctive and rescue medications for shorter periods when taking combined budesonide and formoterol, compared with those taking budesonide alone, according to a poster presentation at the International Conference of the American Thoracic Society.

These results contradict three previous meta-analyses that failed to find pronounced reductions in asthma exacerbations in patients taking both long-acting β-2 agonists and inhaled steroids, compared with those taking inhaled steroids alone, wrote Dr. Christopher D. O'Brien of AstraZeneca and his coauthors. AstraZeneca, which manufactures combination budesonide and formoterol under the brand name Symbicort, supported the study.

Included in the multicenter randomized study were 708 adolescent and adult patients (mean age 40 years) who had received a diagnosis of asthma and reported consistent daily use of inhaled corticosteroids for at least 4 weeks before screening.

After a 2-week run-in period on budesonide alone (320 mcg twice daily), patients were randomized to receive a higher dose of budesonide alone (640 mcg twice daily), a high dose of budesonide and formoterol (640 mcg/18 mcg twice daily), or a low-dose of budesonide and formoterol (320 mcg/9 mcg twice daily).

Patients on both combined regimens experienced significantly fewer asthma exacerbations over the following 52 weeks. Those on the higher dose of budesonide and formoterol had a 45% reduction in exacerbations, and those on the lower dose had a 41% reduction, compared with patients taking budesonide alone.

Patients on both combined regimens also needed oral corticosteroids for fewer total days than did patients taking budesonide alone, with decreases of 51% for the higher combined dose and 42% for the lower combined dose. Conversely, there were no differences in the groups on several other measures of resource use, such as the number of days of hospitalization because of asthma, the number of emergency department visits, and number of unscheduled visits to a specialist or primary care physician.

SAN FRANCISCO — Men who are overweight or obese have poorer outcomes following robotic radical prostatectomy, according to a poster presentation by Dr. Jay D. Raman and colleagues at the annual meeting of the Society of Laparoendoscopic Surgeons.

Overweight and obese men had a longer operative time, greater blood loss, and longer hospitalizations, compared with men who had normal body mass index (BMI) values.

The study involved 132 patients with clinically localized prostate cancer. Dr. Raman of New York-Presbyterian Hospital, New York, and his colleagues divided the patients into three cohorts, based on BMI, in which 38 patients had a normal BMI (18–24.9 kg/m

The groups had no significant preoperative differences in age, prostate-specific antigen level, or biopsy Gleason score. Obese patients had a significantly higher percentage of clinical T1c cancers (84%), compared with overweight (67%) and normal-weight (55%) patients. Obese patients also had a significantly lower percentage of T2 cancers (16%), compared with overweight (31%) and normal-weight (45%) patients.

The surgery took an average of 304 minutes in obese men, significantly longer than the 235 minutes among overweight men and 238 minutes among normal-weight men.

Normal-weight men lost an estimated 234 mL of blood on average, significantly less than the 318 mL among overweight men and 316 mL among obese men.

Men of normal weight also had significantly shorter hospitalizations: 1.1 days on average, compared with 1.6 days for overweight men and 1.7 days for obese men.

There were no significant differences among the groups in bilateral nerve-sparing (90% overall), open conversion (2% overall), and positive margins (17% overall). Nor did the investigators find significant differences in the complication rate, which was 8% among normal-weight men, 5% among overweight men, and 6% among obese men.

Robotic radical prostatectomies are “technically more challenging” in men with elevated BMI, the authors said.

SAN FRANCISCO — Men who are overweight or obese have poorer outcomes following robotic radical prostatectomy, according to a poster presentation by Dr. Jay D. Raman and colleagues at the annual meeting of the Society of Laparoendoscopic Surgeons.

Overweight and obese men had a longer operative time, greater blood loss, and longer hospitalizations, compared with men who had normal body mass index (BMI) values.

The study involved 132 patients with clinically localized prostate cancer. Dr. Raman of New York-Presbyterian Hospital, New York, and his colleagues divided the patients into three cohorts, based on BMI, in which 38 patients had a normal BMI (18–24.9 kg/m

The groups had no significant preoperative differences in age, prostate-specific antigen level, or biopsy Gleason score. Obese patients had a significantly higher percentage of clinical T1c cancers (84%), compared with overweight (67%) and normal-weight (55%) patients. Obese patients also had a significantly lower percentage of T2 cancers (16%), compared with overweight (31%) and normal-weight (45%) patients.

The surgery took an average of 304 minutes in obese men, significantly longer than the 235 minutes among overweight men and 238 minutes among normal-weight men.

Normal-weight men lost an estimated 234 mL of blood on average, significantly less than the 318 mL among overweight men and 316 mL among obese men.

Men of normal weight also had significantly shorter hospitalizations: 1.1 days on average, compared with 1.6 days for overweight men and 1.7 days for obese men.

There were no significant differences among the groups in bilateral nerve-sparing (90% overall), open conversion (2% overall), and positive margins (17% overall). Nor did the investigators find significant differences in the complication rate, which was 8% among normal-weight men, 5% among overweight men, and 6% among obese men.

Robotic radical prostatectomies are “technically more challenging” in men with elevated BMI, the authors said.

SAN FRANCISCO — Men who are overweight or obese have poorer outcomes following robotic radical prostatectomy, according to a poster presentation by Dr. Jay D. Raman and colleagues at the annual meeting of the Society of Laparoendoscopic Surgeons.

Overweight and obese men had a longer operative time, greater blood loss, and longer hospitalizations, compared with men who had normal body mass index (BMI) values.

The study involved 132 patients with clinically localized prostate cancer. Dr. Raman of New York-Presbyterian Hospital, New York, and his colleagues divided the patients into three cohorts, based on BMI, in which 38 patients had a normal BMI (18–24.9 kg/m

The groups had no significant preoperative differences in age, prostate-specific antigen level, or biopsy Gleason score. Obese patients had a significantly higher percentage of clinical T1c cancers (84%), compared with overweight (67%) and normal-weight (55%) patients. Obese patients also had a significantly lower percentage of T2 cancers (16%), compared with overweight (31%) and normal-weight (45%) patients.

The surgery took an average of 304 minutes in obese men, significantly longer than the 235 minutes among overweight men and 238 minutes among normal-weight men.

Normal-weight men lost an estimated 234 mL of blood on average, significantly less than the 318 mL among overweight men and 316 mL among obese men.

Men of normal weight also had significantly shorter hospitalizations: 1.1 days on average, compared with 1.6 days for overweight men and 1.7 days for obese men.

There were no significant differences among the groups in bilateral nerve-sparing (90% overall), open conversion (2% overall), and positive margins (17% overall). Nor did the investigators find significant differences in the complication rate, which was 8% among normal-weight men, 5% among overweight men, and 6% among obese men.

Robotic radical prostatectomies are “technically more challenging” in men with elevated BMI, the authors said.

SAN FRANCISCO — Robotic radical prostatectomy had a complication rate of about 5.1% and promising medium-term outcomes, according to a large case series presented in two posters at the annual meeting of the Society of Laparoendoscopic Surgeons.

This complication rate is similar to those reported in large series of open radical prostatectomies and lower than those reported in laparoscopic and other robotic series, wrote Dr. Pankaj P. Dangle and colleagues from The Ohio State University Medical Center, Columbus.

According to the first poster, among 1,256 procedures performed by a single surgeon (Dr. Vipul R. Patel), there were 64 complications: 2 intraoperative, 16 perioperative, and 46 postoperative. No patients died, and no patients had to be converted to open repair.

Four patients had myocardial infarctions, four required blood transfusions, and three had pulmonary emboli.

Anastomotic leakage was the most common complication, occurring in 1.75% of the cases.

Other indicators also pointed to a learning curve with robotic radical prostatectomy. For example, the overall complication rate was 9.33% among the first 300 patients, but 3.37% among the last 300 patients.

In the second poster, the investigators extended the case series to 1,500 patients, with all procedures performed by Dr. Patel over a 56-month period. As in the original series, he used the da Vinci Surgical System, and he performed the procedure transperitoneally using a six-trocar technique.

The patients' average age was 61, and their mean body mass index was 29 kg/m

Overall, 97% of the patients were discharged home on the first postoperative day, and the mean catheter time was 6.3 days. After 3 months, 92% of the patients were completely continent; that number went up to 97% after 6 months and 98% after 12 months.

The investigators, who disclosed that they have no financial relationships related to their presentation, concluded that robotic-assistant laparoscopic radical prostatectomy is a safe, feasible, and minimally invasive alternative for treating clinically localized prostate cancer.

SAN FRANCISCO — Robotic radical prostatectomy had a complication rate of about 5.1% and promising medium-term outcomes, according to a large case series presented in two posters at the annual meeting of the Society of Laparoendoscopic Surgeons.

This complication rate is similar to those reported in large series of open radical prostatectomies and lower than those reported in laparoscopic and other robotic series, wrote Dr. Pankaj P. Dangle and colleagues from The Ohio State University Medical Center, Columbus.

According to the first poster, among 1,256 procedures performed by a single surgeon (Dr. Vipul R. Patel), there were 64 complications: 2 intraoperative, 16 perioperative, and 46 postoperative. No patients died, and no patients had to be converted to open repair.

Four patients had myocardial infarctions, four required blood transfusions, and three had pulmonary emboli.

Anastomotic leakage was the most common complication, occurring in 1.75% of the cases.

Other indicators also pointed to a learning curve with robotic radical prostatectomy. For example, the overall complication rate was 9.33% among the first 300 patients, but 3.37% among the last 300 patients.

In the second poster, the investigators extended the case series to 1,500 patients, with all procedures performed by Dr. Patel over a 56-month period. As in the original series, he used the da Vinci Surgical System, and he performed the procedure transperitoneally using a six-trocar technique.

The patients' average age was 61, and their mean body mass index was 29 kg/m

Overall, 97% of the patients were discharged home on the first postoperative day, and the mean catheter time was 6.3 days. After 3 months, 92% of the patients were completely continent; that number went up to 97% after 6 months and 98% after 12 months.

The investigators, who disclosed that they have no financial relationships related to their presentation, concluded that robotic-assistant laparoscopic radical prostatectomy is a safe, feasible, and minimally invasive alternative for treating clinically localized prostate cancer.

SAN FRANCISCO — Robotic radical prostatectomy had a complication rate of about 5.1% and promising medium-term outcomes, according to a large case series presented in two posters at the annual meeting of the Society of Laparoendoscopic Surgeons.

This complication rate is similar to those reported in large series of open radical prostatectomies and lower than those reported in laparoscopic and other robotic series, wrote Dr. Pankaj P. Dangle and colleagues from The Ohio State University Medical Center, Columbus.

According to the first poster, among 1,256 procedures performed by a single surgeon (Dr. Vipul R. Patel), there were 64 complications: 2 intraoperative, 16 perioperative, and 46 postoperative. No patients died, and no patients had to be converted to open repair.

Four patients had myocardial infarctions, four required blood transfusions, and three had pulmonary emboli.

Anastomotic leakage was the most common complication, occurring in 1.75% of the cases.

Other indicators also pointed to a learning curve with robotic radical prostatectomy. For example, the overall complication rate was 9.33% among the first 300 patients, but 3.37% among the last 300 patients.

In the second poster, the investigators extended the case series to 1,500 patients, with all procedures performed by Dr. Patel over a 56-month period. As in the original series, he used the da Vinci Surgical System, and he performed the procedure transperitoneally using a six-trocar technique.

The patients' average age was 61, and their mean body mass index was 29 kg/m

Overall, 97% of the patients were discharged home on the first postoperative day, and the mean catheter time was 6.3 days. After 3 months, 92% of the patients were completely continent; that number went up to 97% after 6 months and 98% after 12 months.

The investigators, who disclosed that they have no financial relationships related to their presentation, concluded that robotic-assistant laparoscopic radical prostatectomy is a safe, feasible, and minimally invasive alternative for treating clinically localized prostate cancer.

SAN FRANCISCO — Investigational bone imaging techniques hold the promise of providing clinically useful information about bone structure in three dimensions unattainable with dual-energy x-ray absorptiometry, Mary L. Bouxsein, Ph.D., said at a meeting on osteoporosis sponsored by the University of California, San Francisco.

While dual-energy x-ray absorptiometry (DXA) measurements show moderate to strong correlations with whole bone strength, the technique cannot distinguish specific attributes of three-dimensional geometry, cortical versus cancellous density, trabecular architecture, or intrinsic properties of the bone matrix.

However, there are some exciting newer techniques, although they are currently in the research phase, said Dr. Bouxsein of Harvard Medical School, Boston.

She highlighted the advantages and limitations of five promising novel imaging techniques:

▸ Hip strength analysis (HSA). This technique uses image data from 2-D DXA to derive 3-D geometry. Developed in the early 1980s, HSA uses data from the attenuation profile of the x-ray beam to calculate such things as cortical thickness and bone strength. But HSA makes several assumptions, most notably that there is constant mineral density in the bone and that the neck and shaft of bones are circular.

“This makes a lot of sense in measurements of long bone, and that was where it was first developed,” Dr. Bouxsein said. “Now where I think the challenge comes in … applying this exact same technique to measurement of the femoral neck. … It would be a big challenge to extract properties of the cortex using this direct method.”

One attraction of HSA is that it requires no new data collection, since researchers can reanalyze old DXA scans with this new technique. However, there is much more attention currently being focused on techniques that are truly three-dimensional.

▸ Quantitative computed tomography (QCT). With QCT, standard CT images are made with a bone-density “phantom” in the viewing area. This allows a quantitative measure of bone density in the final image and gives a 3-D view of bone geometry as well as an isolated look at the trabecular and cortical compartments.

The technique's precision, currently at about 2%–6%, is a bit worse than DXA, Dr. Bouxsein said. The radiation dose is higher than DXA, although still low enough to be acceptable for longitudinal studies.

The resolution is on the order of 300 mcm by 1 mm, somewhat too low to resolve individual trabecular elements, which measure about 100–300 mcm in the adult spine.

Studies have shown that QCT does show age- and treatment-related effects and is useful at both axial and peripheral sites. On the other hand, there are no prospective fracture data (although some are coming), reference data are limited, analysis methods are not yet standardized, and marrow fat can influence QCT measurements, with an increase in marrow fat resulting in an apparent decrease in trabecular bone mineral density (BMD).

▸ High-resolution peripheral quantitative CT (pQCT). This technique has become available within the past 2 years. It uses specialized equipment and can measure the peripheral skeleton, including the distal radius and distal tibia.

It has a voxel size of just 82 mcm

The technique's precision is quite good, with short-term reproducibility of 0.7%–1.3% for density and 0.9%–5.1% for microarchitecture. Because it's a peripheral technique, the patient receives a relatively low dose of radiation, and because it uses dedicated equipment, measurements are standardized. Using pQCT, researchers have been able to discriminate among osteopenic women with and without a history of fragility fracture, even when their BMDs are quite similar.

On the other hand, pQCT can't be used to measure central sites, and access is quite limited, with only about 10 machines in the world, including three in the United States. Clinical studies have so far been limited.

▸ High-resolution MRI (HR-MRI). This technique for trabecular bone uses standard clinical scanners and allows physicians to conduct virtual bone biopsies. The technique discriminates patients with a history of fragility fracture from controls, uses nonionizing radiation, and may be useful for monitoring response to treatment.

At the moment, HR-MRI can only be used at peripheral sites, although there is some potential for its use at the hip, Dr. Bouxsein noted.

Its resolution is a bit too low, at just about 100–300 mcm, but that is expected to improve with higher magnetic-field strengths.

Its short-term reproducibility, meanwhile, has been measured at a disappointing 3%–8%. Finally, the HR-MRI technique has been the subject of only limited clinical studies.

▸ Finite element analysis (FEA). Dr. Bouxsein said she was particularly excited about this technique, which is a standard engineering technique that has been used for decades to measure the mechanical properties of airliners and other complex structures. FEA for bone can provide multiple strength metrics.

In measuring bone strength, FEA integrates material and structural information from 3-D QCT to create a computer model of an individual patient's bone. That model is then subjected to virtual stresses and strains.

In vitro, FEA has been shown to predict both femoral and vertebral strength better than BMD measurements alone. But only a small number of clinical studies have been conducted.

The overall state of these promising techniques for noninvasive assessment of bone strength are useful “certainly for clinical research, certainly for clinical trials, [but] certainly not for clinical practice,” said Dr. Bouxsein.

“We don't have T scores or an absolute prediction of fracture risk. We don't yet have good evidence that we can use these to monitor therapy. We need several more years to figure out which one of these, if any, will make their way into clinical practice. [But] we've certainly learned a lot about the pathophysiology of this disease,” she added.

SAN FRANCISCO — Investigational bone imaging techniques hold the promise of providing clinically useful information about bone structure in three dimensions unattainable with dual-energy x-ray absorptiometry, Mary L. Bouxsein, Ph.D., said at a meeting on osteoporosis sponsored by the University of California, San Francisco.

While dual-energy x-ray absorptiometry (DXA) measurements show moderate to strong correlations with whole bone strength, the technique cannot distinguish specific attributes of three-dimensional geometry, cortical versus cancellous density, trabecular architecture, or intrinsic properties of the bone matrix.

However, there are some exciting newer techniques, although they are currently in the research phase, said Dr. Bouxsein of Harvard Medical School, Boston.

She highlighted the advantages and limitations of five promising novel imaging techniques:

▸ Hip strength analysis (HSA). This technique uses image data from 2-D DXA to derive 3-D geometry. Developed in the early 1980s, HSA uses data from the attenuation profile of the x-ray beam to calculate such things as cortical thickness and bone strength. But HSA makes several assumptions, most notably that there is constant mineral density in the bone and that the neck and shaft of bones are circular.

“This makes a lot of sense in measurements of long bone, and that was where it was first developed,” Dr. Bouxsein said. “Now where I think the challenge comes in … applying this exact same technique to measurement of the femoral neck. … It would be a big challenge to extract properties of the cortex using this direct method.”

One attraction of HSA is that it requires no new data collection, since researchers can reanalyze old DXA scans with this new technique. However, there is much more attention currently being focused on techniques that are truly three-dimensional.

▸ Quantitative computed tomography (QCT). With QCT, standard CT images are made with a bone-density “phantom” in the viewing area. This allows a quantitative measure of bone density in the final image and gives a 3-D view of bone geometry as well as an isolated look at the trabecular and cortical compartments.

The technique's precision, currently at about 2%–6%, is a bit worse than DXA, Dr. Bouxsein said. The radiation dose is higher than DXA, although still low enough to be acceptable for longitudinal studies.

The resolution is on the order of 300 mcm by 1 mm, somewhat too low to resolve individual trabecular elements, which measure about 100–300 mcm in the adult spine.

Studies have shown that QCT does show age- and treatment-related effects and is useful at both axial and peripheral sites. On the other hand, there are no prospective fracture data (although some are coming), reference data are limited, analysis methods are not yet standardized, and marrow fat can influence QCT measurements, with an increase in marrow fat resulting in an apparent decrease in trabecular bone mineral density (BMD).

▸ High-resolution peripheral quantitative CT (pQCT). This technique has become available within the past 2 years. It uses specialized equipment and can measure the peripheral skeleton, including the distal radius and distal tibia.

It has a voxel size of just 82 mcm

The technique's precision is quite good, with short-term reproducibility of 0.7%–1.3% for density and 0.9%–5.1% for microarchitecture. Because it's a peripheral technique, the patient receives a relatively low dose of radiation, and because it uses dedicated equipment, measurements are standardized. Using pQCT, researchers have been able to discriminate among osteopenic women with and without a history of fragility fracture, even when their BMDs are quite similar.

On the other hand, pQCT can't be used to measure central sites, and access is quite limited, with only about 10 machines in the world, including three in the United States. Clinical studies have so far been limited.

▸ High-resolution MRI (HR-MRI). This technique for trabecular bone uses standard clinical scanners and allows physicians to conduct virtual bone biopsies. The technique discriminates patients with a history of fragility fracture from controls, uses nonionizing radiation, and may be useful for monitoring response to treatment.

At the moment, HR-MRI can only be used at peripheral sites, although there is some potential for its use at the hip, Dr. Bouxsein noted.

Its resolution is a bit too low, at just about 100–300 mcm, but that is expected to improve with higher magnetic-field strengths.

Its short-term reproducibility, meanwhile, has been measured at a disappointing 3%–8%. Finally, the HR-MRI technique has been the subject of only limited clinical studies.

▸ Finite element analysis (FEA). Dr. Bouxsein said she was particularly excited about this technique, which is a standard engineering technique that has been used for decades to measure the mechanical properties of airliners and other complex structures. FEA for bone can provide multiple strength metrics.

In measuring bone strength, FEA integrates material and structural information from 3-D QCT to create a computer model of an individual patient's bone. That model is then subjected to virtual stresses and strains.

In vitro, FEA has been shown to predict both femoral and vertebral strength better than BMD measurements alone. But only a small number of clinical studies have been conducted.

The overall state of these promising techniques for noninvasive assessment of bone strength are useful “certainly for clinical research, certainly for clinical trials, [but] certainly not for clinical practice,” said Dr. Bouxsein.

“We don't have T scores or an absolute prediction of fracture risk. We don't yet have good evidence that we can use these to monitor therapy. We need several more years to figure out which one of these, if any, will make their way into clinical practice. [But] we've certainly learned a lot about the pathophysiology of this disease,” she added.

SAN FRANCISCO — Investigational bone imaging techniques hold the promise of providing clinically useful information about bone structure in three dimensions unattainable with dual-energy x-ray absorptiometry, Mary L. Bouxsein, Ph.D., said at a meeting on osteoporosis sponsored by the University of California, San Francisco.

While dual-energy x-ray absorptiometry (DXA) measurements show moderate to strong correlations with whole bone strength, the technique cannot distinguish specific attributes of three-dimensional geometry, cortical versus cancellous density, trabecular architecture, or intrinsic properties of the bone matrix.

However, there are some exciting newer techniques, although they are currently in the research phase, said Dr. Bouxsein of Harvard Medical School, Boston.

She highlighted the advantages and limitations of five promising novel imaging techniques:

▸ Hip strength analysis (HSA). This technique uses image data from 2-D DXA to derive 3-D geometry. Developed in the early 1980s, HSA uses data from the attenuation profile of the x-ray beam to calculate such things as cortical thickness and bone strength. But HSA makes several assumptions, most notably that there is constant mineral density in the bone and that the neck and shaft of bones are circular.

“This makes a lot of sense in measurements of long bone, and that was where it was first developed,” Dr. Bouxsein said. “Now where I think the challenge comes in … applying this exact same technique to measurement of the femoral neck. … It would be a big challenge to extract properties of the cortex using this direct method.”

One attraction of HSA is that it requires no new data collection, since researchers can reanalyze old DXA scans with this new technique. However, there is much more attention currently being focused on techniques that are truly three-dimensional.

▸ Quantitative computed tomography (QCT). With QCT, standard CT images are made with a bone-density “phantom” in the viewing area. This allows a quantitative measure of bone density in the final image and gives a 3-D view of bone geometry as well as an isolated look at the trabecular and cortical compartments.

The technique's precision, currently at about 2%–6%, is a bit worse than DXA, Dr. Bouxsein said. The radiation dose is higher than DXA, although still low enough to be acceptable for longitudinal studies.

The resolution is on the order of 300 mcm by 1 mm, somewhat too low to resolve individual trabecular elements, which measure about 100–300 mcm in the adult spine.

Studies have shown that QCT does show age- and treatment-related effects and is useful at both axial and peripheral sites. On the other hand, there are no prospective fracture data (although some are coming), reference data are limited, analysis methods are not yet standardized, and marrow fat can influence QCT measurements, with an increase in marrow fat resulting in an apparent decrease in trabecular bone mineral density (BMD).

▸ High-resolution peripheral quantitative CT (pQCT). This technique has become available within the past 2 years. It uses specialized equipment and can measure the peripheral skeleton, including the distal radius and distal tibia.

It has a voxel size of just 82 mcm

The technique's precision is quite good, with short-term reproducibility of 0.7%–1.3% for density and 0.9%–5.1% for microarchitecture. Because it's a peripheral technique, the patient receives a relatively low dose of radiation, and because it uses dedicated equipment, measurements are standardized. Using pQCT, researchers have been able to discriminate among osteopenic women with and without a history of fragility fracture, even when their BMDs are quite similar.

On the other hand, pQCT can't be used to measure central sites, and access is quite limited, with only about 10 machines in the world, including three in the United States. Clinical studies have so far been limited.

▸ High-resolution MRI (HR-MRI). This technique for trabecular bone uses standard clinical scanners and allows physicians to conduct virtual bone biopsies. The technique discriminates patients with a history of fragility fracture from controls, uses nonionizing radiation, and may be useful for monitoring response to treatment.

At the moment, HR-MRI can only be used at peripheral sites, although there is some potential for its use at the hip, Dr. Bouxsein noted.

Its resolution is a bit too low, at just about 100–300 mcm, but that is expected to improve with higher magnetic-field strengths.

Its short-term reproducibility, meanwhile, has been measured at a disappointing 3%–8%. Finally, the HR-MRI technique has been the subject of only limited clinical studies.

▸ Finite element analysis (FEA). Dr. Bouxsein said she was particularly excited about this technique, which is a standard engineering technique that has been used for decades to measure the mechanical properties of airliners and other complex structures. FEA for bone can provide multiple strength metrics.

In measuring bone strength, FEA integrates material and structural information from 3-D QCT to create a computer model of an individual patient's bone. That model is then subjected to virtual stresses and strains.

In vitro, FEA has been shown to predict both femoral and vertebral strength better than BMD measurements alone. But only a small number of clinical studies have been conducted.

The overall state of these promising techniques for noninvasive assessment of bone strength are useful “certainly for clinical research, certainly for clinical trials, [but] certainly not for clinical practice,” said Dr. Bouxsein.

“We don't have T scores or an absolute prediction of fracture risk. We don't yet have good evidence that we can use these to monitor therapy. We need several more years to figure out which one of these, if any, will make their way into clinical practice. [But] we've certainly learned a lot about the pathophysiology of this disease,” she added.

Patients with metabolic syndrome are nearly three times as likely to die following coronary artery bypass graft surgery as are patients without the syndrome, according to a large study.

Patients with both metabolic syndrome and diabetes had a 2.7-fold increase in the risk of mortality, and patients with metabolic syndrome but without diabetes had a 2.4-fold increase in risk. In the multivariate analysis, there proved to be no significant increase in the risk of mortality in patients who had diabetes but not metabolic syndrome, wrote Dr. Najmeddine Echahidi of the Centre de Recherche de l'Hôpital Laval, Quebec, and colleagues (J. Am. Coll. Cardiol. 2007;50:843–51).

The retrospective analysis involved 5,304 consecutive patients who underwent an isolated coronary artery bypass graft (CABG) during 2000–2004 at a single institution. An analysis of prospectively collected laboratory and physical data revealed that 46% met criteria for metabolic syndrome as set out by the National Cholesterol Education Program Adult Treatment Panel III.

The study's primary end point was death from any cause, either within 30 days of surgery or after any interval if the patient was not discharged from the hospital. Results were adjusted for gender, peripheral vascular disease, chronic obstructive pulmonary disease, and preoperative renal failure, MI, and stroke.

The overall unadjusted mortality was 1.6%, but was significantly higher (2.4%) among patients with metabolic syndrome, and significantly lower (0.9%) among patients without metabolic syndrome.

Several other factors also increased the risk of mortality after CABG. These included age older than 75 years (relative risk 3.4), BMI less than 18.5 kg/m

Patients with metabolic syndrome are nearly three times as likely to die following coronary artery bypass graft surgery as are patients without the syndrome, according to a large study.

Patients with both metabolic syndrome and diabetes had a 2.7-fold increase in the risk of mortality, and patients with metabolic syndrome but without diabetes had a 2.4-fold increase in risk. In the multivariate analysis, there proved to be no significant increase in the risk of mortality in patients who had diabetes but not metabolic syndrome, wrote Dr. Najmeddine Echahidi of the Centre de Recherche de l'Hôpital Laval, Quebec, and colleagues (J. Am. Coll. Cardiol. 2007;50:843–51).

The retrospective analysis involved 5,304 consecutive patients who underwent an isolated coronary artery bypass graft (CABG) during 2000–2004 at a single institution. An analysis of prospectively collected laboratory and physical data revealed that 46% met criteria for metabolic syndrome as set out by the National Cholesterol Education Program Adult Treatment Panel III.

The study's primary end point was death from any cause, either within 30 days of surgery or after any interval if the patient was not discharged from the hospital. Results were adjusted for gender, peripheral vascular disease, chronic obstructive pulmonary disease, and preoperative renal failure, MI, and stroke.

The overall unadjusted mortality was 1.6%, but was significantly higher (2.4%) among patients with metabolic syndrome, and significantly lower (0.9%) among patients without metabolic syndrome.

Several other factors also increased the risk of mortality after CABG. These included age older than 75 years (relative risk 3.4), BMI less than 18.5 kg/m

Patients with metabolic syndrome are nearly three times as likely to die following coronary artery bypass graft surgery as are patients without the syndrome, according to a large study.

Patients with both metabolic syndrome and diabetes had a 2.7-fold increase in the risk of mortality, and patients with metabolic syndrome but without diabetes had a 2.4-fold increase in risk. In the multivariate analysis, there proved to be no significant increase in the risk of mortality in patients who had diabetes but not metabolic syndrome, wrote Dr. Najmeddine Echahidi of the Centre de Recherche de l'Hôpital Laval, Quebec, and colleagues (J. Am. Coll. Cardiol. 2007;50:843–51).

The retrospective analysis involved 5,304 consecutive patients who underwent an isolated coronary artery bypass graft (CABG) during 2000–2004 at a single institution. An analysis of prospectively collected laboratory and physical data revealed that 46% met criteria for metabolic syndrome as set out by the National Cholesterol Education Program Adult Treatment Panel III.

The study's primary end point was death from any cause, either within 30 days of surgery or after any interval if the patient was not discharged from the hospital. Results were adjusted for gender, peripheral vascular disease, chronic obstructive pulmonary disease, and preoperative renal failure, MI, and stroke.

The overall unadjusted mortality was 1.6%, but was significantly higher (2.4%) among patients with metabolic syndrome, and significantly lower (0.9%) among patients without metabolic syndrome.

Several other factors also increased the risk of mortality after CABG. These included age older than 75 years (relative risk 3.4), BMI less than 18.5 kg/m