Sherry Boschert

SAN FRANCISCO — When you're seeing patients who are taking bisphosphonate drugs for osteoporosis, don't forget to look in their mouths, Dr. Steven T. Harris said at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.

Osteonecrosis of the jaw recently was added to the precautions section of the prescribing information for all intravenous and oral bisphosphonates, so it is incumbent upon clinicians to look for this very rare complication.

“One of the things I've changed in my clinical practice in the past couple of years is that I laid in a supply of tongue depressors and I've started to look in people's mouths, which I was not routinely doing before,” said Dr. Harris of the university.

Media reports about this side effect of bisphosphonates have caught the attention of patients, some of whom raise concerns about it during visits, he added.

Though no universally accepted definition exists for osteonecrosis of the jaw, a growing consensus characterizes it as an oral cavity lesion with one or more bare bone spots, in the absence of local malignancy or radiation therapy to the head and neck. This is not the same as a patient on bisphosphonate therapy complaining of tooth pain.

“This is a look in the mouth, and there is bone where there should be normal pink mucosa,” Dr. Harris said.

Osteonecrosis of the jaw primarily has been seen in cancer patients receiving high-dose intravenous bisphosphonates therapy, usually monthly. In that population, approximately 0.5%–10% of patients may develop osteonecrosis of the jaw, a range affected by the underlying malignancy.

In patients on oral bisphosphonates, however, rough estimates suggest perhaps 1 patient per 100,000 may develop osteonecrosis of the jaw per year, he said.

The pathophysiology of this disorder is not understood.

Known risk factors for osteonecrosis of the jaw include cancer; concomitant therapies like chemotherapy, radiation, or corticosteroids; poor oral hygiene; and comorbid disorders such as preexisting dental disease, anemia, coagulopathy, or infection.

Be vigilant in patients with poor dental hygiene or procedures such as tooth pulling or teeth implants, Dr. Harris said.

SAN FRANCISCO — When you're seeing patients who are taking bisphosphonate drugs for osteoporosis, don't forget to look in their mouths, Dr. Steven T. Harris said at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.

Osteonecrosis of the jaw recently was added to the precautions section of the prescribing information for all intravenous and oral bisphosphonates, so it is incumbent upon clinicians to look for this very rare complication.

“One of the things I've changed in my clinical practice in the past couple of years is that I laid in a supply of tongue depressors and I've started to look in people's mouths, which I was not routinely doing before,” said Dr. Harris of the university.

Media reports about this side effect of bisphosphonates have caught the attention of patients, some of whom raise concerns about it during visits, he added.

Though no universally accepted definition exists for osteonecrosis of the jaw, a growing consensus characterizes it as an oral cavity lesion with one or more bare bone spots, in the absence of local malignancy or radiation therapy to the head and neck. This is not the same as a patient on bisphosphonate therapy complaining of tooth pain.

“This is a look in the mouth, and there is bone where there should be normal pink mucosa,” Dr. Harris said.

Osteonecrosis of the jaw primarily has been seen in cancer patients receiving high-dose intravenous bisphosphonates therapy, usually monthly. In that population, approximately 0.5%–10% of patients may develop osteonecrosis of the jaw, a range affected by the underlying malignancy.

In patients on oral bisphosphonates, however, rough estimates suggest perhaps 1 patient per 100,000 may develop osteonecrosis of the jaw per year, he said.

The pathophysiology of this disorder is not understood.

Known risk factors for osteonecrosis of the jaw include cancer; concomitant therapies like chemotherapy, radiation, or corticosteroids; poor oral hygiene; and comorbid disorders such as preexisting dental disease, anemia, coagulopathy, or infection.

Be vigilant in patients with poor dental hygiene or procedures such as tooth pulling or teeth implants, Dr. Harris said.

SAN FRANCISCO — When you're seeing patients who are taking bisphosphonate drugs for osteoporosis, don't forget to look in their mouths, Dr. Steven T. Harris said at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.

Osteonecrosis of the jaw recently was added to the precautions section of the prescribing information for all intravenous and oral bisphosphonates, so it is incumbent upon clinicians to look for this very rare complication.

“One of the things I've changed in my clinical practice in the past couple of years is that I laid in a supply of tongue depressors and I've started to look in people's mouths, which I was not routinely doing before,” said Dr. Harris of the university.

Media reports about this side effect of bisphosphonates have caught the attention of patients, some of whom raise concerns about it during visits, he added.

Though no universally accepted definition exists for osteonecrosis of the jaw, a growing consensus characterizes it as an oral cavity lesion with one or more bare bone spots, in the absence of local malignancy or radiation therapy to the head and neck. This is not the same as a patient on bisphosphonate therapy complaining of tooth pain.

“This is a look in the mouth, and there is bone where there should be normal pink mucosa,” Dr. Harris said.

Osteonecrosis of the jaw primarily has been seen in cancer patients receiving high-dose intravenous bisphosphonates therapy, usually monthly. In that population, approximately 0.5%–10% of patients may develop osteonecrosis of the jaw, a range affected by the underlying malignancy.

In patients on oral bisphosphonates, however, rough estimates suggest perhaps 1 patient per 100,000 may develop osteonecrosis of the jaw per year, he said.

The pathophysiology of this disorder is not understood.

Known risk factors for osteonecrosis of the jaw include cancer; concomitant therapies like chemotherapy, radiation, or corticosteroids; poor oral hygiene; and comorbid disorders such as preexisting dental disease, anemia, coagulopathy, or infection.

Be vigilant in patients with poor dental hygiene or procedures such as tooth pulling or teeth implants, Dr. Harris said.

SAN FRANCISCO — Better treatments for posttransplant hypertension or cardiac allograft vasculopathy would help more patients reach 20 years of survival after a heart transplant, Dr. Saleem Haj-Yahia said at the annual meeting of the International Society for Heart and Lung Transplantation.

Little is known about clinical factors associated with long-term survival after a heart transplant. To elucidate such factors, Dr. Haj-Yahia and his associates at Royal Brompton and Harefield Hospital, London, analyzed data on 211 patients who underwent orthotopic heart transplantation between 1980 and 1985. Detailed records also were available for 107 donors in these cases.

Twenty years after their transplants, 53 of the 211 patients (25%) were still alive.

Actuarial survival rates for other times after transplant were 71% at 1 year, 61% at 5 years, 47% at 10 years, and 34% at 15 years. By 25 years posttransplant, 16% of patients remained alive.

Twenty-year survival was more likely in patients who were younger at the time of the transplant, did not develop posttransplant hypertension, and had later development of cardiac allograft vasculopathy (CAV) than did other patients, he reported.

Multivariate analysis showed that older age at transplant nearly doubled the risk of death before 20 years, and the development of posttransplant hypertension increased the risk of death more than fivefold.

A longer interval from transplant to the diagnosis of angiographic CAV increased the odds of long-term survival by about 27%, Dr. Haj-Yahia reported.

“That means more effective treatment of posttransplant hypertension and CAV may improve survival,” he said.

Factors not associated with long-term survival included the gender of the recipient or donor, the donor's age, ischemic time, the indication for transplantation, posttransplant diabetes, renal impairment, human leukocyte antigen levels, recent left ventricular function, frequency of rejection in the first year post transplant, and immunosuppressive regimen.

Cardiac-related events were the main cause of death in this cohort.

SAN FRANCISCO — Better treatments for posttransplant hypertension or cardiac allograft vasculopathy would help more patients reach 20 years of survival after a heart transplant, Dr. Saleem Haj-Yahia said at the annual meeting of the International Society for Heart and Lung Transplantation.

Little is known about clinical factors associated with long-term survival after a heart transplant. To elucidate such factors, Dr. Haj-Yahia and his associates at Royal Brompton and Harefield Hospital, London, analyzed data on 211 patients who underwent orthotopic heart transplantation between 1980 and 1985. Detailed records also were available for 107 donors in these cases.

Twenty years after their transplants, 53 of the 211 patients (25%) were still alive.

Actuarial survival rates for other times after transplant were 71% at 1 year, 61% at 5 years, 47% at 10 years, and 34% at 15 years. By 25 years posttransplant, 16% of patients remained alive.

Twenty-year survival was more likely in patients who were younger at the time of the transplant, did not develop posttransplant hypertension, and had later development of cardiac allograft vasculopathy (CAV) than did other patients, he reported.

Multivariate analysis showed that older age at transplant nearly doubled the risk of death before 20 years, and the development of posttransplant hypertension increased the risk of death more than fivefold.

A longer interval from transplant to the diagnosis of angiographic CAV increased the odds of long-term survival by about 27%, Dr. Haj-Yahia reported.

“That means more effective treatment of posttransplant hypertension and CAV may improve survival,” he said.

Factors not associated with long-term survival included the gender of the recipient or donor, the donor's age, ischemic time, the indication for transplantation, posttransplant diabetes, renal impairment, human leukocyte antigen levels, recent left ventricular function, frequency of rejection in the first year post transplant, and immunosuppressive regimen.

Cardiac-related events were the main cause of death in this cohort.

SAN FRANCISCO — Better treatments for posttransplant hypertension or cardiac allograft vasculopathy would help more patients reach 20 years of survival after a heart transplant, Dr. Saleem Haj-Yahia said at the annual meeting of the International Society for Heart and Lung Transplantation.

Little is known about clinical factors associated with long-term survival after a heart transplant. To elucidate such factors, Dr. Haj-Yahia and his associates at Royal Brompton and Harefield Hospital, London, analyzed data on 211 patients who underwent orthotopic heart transplantation between 1980 and 1985. Detailed records also were available for 107 donors in these cases.

Twenty years after their transplants, 53 of the 211 patients (25%) were still alive.

Actuarial survival rates for other times after transplant were 71% at 1 year, 61% at 5 years, 47% at 10 years, and 34% at 15 years. By 25 years posttransplant, 16% of patients remained alive.

Twenty-year survival was more likely in patients who were younger at the time of the transplant, did not develop posttransplant hypertension, and had later development of cardiac allograft vasculopathy (CAV) than did other patients, he reported.

Multivariate analysis showed that older age at transplant nearly doubled the risk of death before 20 years, and the development of posttransplant hypertension increased the risk of death more than fivefold.

A longer interval from transplant to the diagnosis of angiographic CAV increased the odds of long-term survival by about 27%, Dr. Haj-Yahia reported.

“That means more effective treatment of posttransplant hypertension and CAV may improve survival,” he said.

Factors not associated with long-term survival included the gender of the recipient or donor, the donor's age, ischemic time, the indication for transplantation, posttransplant diabetes, renal impairment, human leukocyte antigen levels, recent left ventricular function, frequency of rejection in the first year post transplant, and immunosuppressive regimen.

Cardiac-related events were the main cause of death in this cohort.

SAN FRANCISCO — Long-term use of adenosine diphosphate receptor blockade therapy may be beneficial to patients with non-ST-segment elevation myocardial infarction who have had prior MI, stroke, or peripheral artery disease, Dr. Marc Sabatine said at a meeting sponsored by the California chapter of the American College of Cardiology.

In the few years since the ADP receptor blocker clopidogrel entered the medical armamentarium, studies have shown that acute therapy significantly reduces the risk of death, MI, or stroke in patients with non-ST-elevation acute coronary syndrome or ST-segment elevation MI (STEMI), and that the benefits appear within 24 hours. Other data show that this treatment is not useful for primary prevention of coronary syndromes and that there is variability in patient responses to clopidogrel.

A secondary analysis of the large Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial, which established clopidogrel's efficacy for non-ST-elevation acute coronary syndrome in 2001, found that a greater reduction in cardiovascular death, MI, or stroke seen initially in patients randomized to clopidogrel instead of placebo continued to be significant up to nearly 1 year (Circulation 2003;107:966–72).

“This suggests that the benefit continues to accrue over time, and that treatment out to at least a year makes sense,” said Dr. Sabatine of Brigham and Women's Hospital, Boston. He is on advisory boards for and has received research funds and honoraria from the companies that market clopidogrel, Bristol-Myers Squibb and Sanofi-Aventis.

In the large Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) study, patients who had a history of atherothrombosis or risk factors for it and were on daily aspirin therapy were randomized to dual-platelet therapy with the addition of clopidogrel or placebo. Follow-up to an average of 2.5 years showed no difference in the risk for cardiovascular death, MI, or stroke between groups, however (Am. Heart J. 2004;148:263–8).

That's because the results with clopidogrel affected two subgroups in opposite ways. The drug significantly reduced risk in patients with a history of atherothrombosis but increased overall risk in patients with no more than risk factors for atherothrombosis such as diabetes or hypertension (N. Engl. J. Med. 2006;354:1706–17). A 1%–2% increase in moderate to severe bleeding with long-term clopidogrel use was not offset by reductions in death, MI, or stroke in the latter subgroup.

Subgroup analyses are not definitive, but this “does start to fit with our prior notion that dual-antiplatelet therapy is most efficacious in those with an acute thrombus, either a complete occlusion as in STEMI or subtotal occlusion as in non-ST-elevation acute coronary syndromes,” he said at the meeting, also sponsored by the University of California, San Francisco. “If you just have risk factors but never manifested atherothrombosis, there's no benefit.”

There are no data yet on long-term use of clopidogrel for STEMI. The pivotal trials lasted only weeks, he noted.

'This suggests that [clopidogrel's] benefit continues to accrue over time, and that treatment out to at least a year makes sense.' DR. SABATINE

SAN FRANCISCO — Long-term use of adenosine diphosphate receptor blockade therapy may be beneficial to patients with non-ST-segment elevation myocardial infarction who have had prior MI, stroke, or peripheral artery disease, Dr. Marc Sabatine said at a meeting sponsored by the California chapter of the American College of Cardiology.

In the few years since the ADP receptor blocker clopidogrel entered the medical armamentarium, studies have shown that acute therapy significantly reduces the risk of death, MI, or stroke in patients with non-ST-elevation acute coronary syndrome or ST-segment elevation MI (STEMI), and that the benefits appear within 24 hours. Other data show that this treatment is not useful for primary prevention of coronary syndromes and that there is variability in patient responses to clopidogrel.

A secondary analysis of the large Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial, which established clopidogrel's efficacy for non-ST-elevation acute coronary syndrome in 2001, found that a greater reduction in cardiovascular death, MI, or stroke seen initially in patients randomized to clopidogrel instead of placebo continued to be significant up to nearly 1 year (Circulation 2003;107:966–72).

“This suggests that the benefit continues to accrue over time, and that treatment out to at least a year makes sense,” said Dr. Sabatine of Brigham and Women's Hospital, Boston. He is on advisory boards for and has received research funds and honoraria from the companies that market clopidogrel, Bristol-Myers Squibb and Sanofi-Aventis.

In the large Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) study, patients who had a history of atherothrombosis or risk factors for it and were on daily aspirin therapy were randomized to dual-platelet therapy with the addition of clopidogrel or placebo. Follow-up to an average of 2.5 years showed no difference in the risk for cardiovascular death, MI, or stroke between groups, however (Am. Heart J. 2004;148:263–8).

That's because the results with clopidogrel affected two subgroups in opposite ways. The drug significantly reduced risk in patients with a history of atherothrombosis but increased overall risk in patients with no more than risk factors for atherothrombosis such as diabetes or hypertension (N. Engl. J. Med. 2006;354:1706–17). A 1%–2% increase in moderate to severe bleeding with long-term clopidogrel use was not offset by reductions in death, MI, or stroke in the latter subgroup.

Subgroup analyses are not definitive, but this “does start to fit with our prior notion that dual-antiplatelet therapy is most efficacious in those with an acute thrombus, either a complete occlusion as in STEMI or subtotal occlusion as in non-ST-elevation acute coronary syndromes,” he said at the meeting, also sponsored by the University of California, San Francisco. “If you just have risk factors but never manifested atherothrombosis, there's no benefit.”

There are no data yet on long-term use of clopidogrel for STEMI. The pivotal trials lasted only weeks, he noted.

'This suggests that [clopidogrel's] benefit continues to accrue over time, and that treatment out to at least a year makes sense.' DR. SABATINE

SAN FRANCISCO — Long-term use of adenosine diphosphate receptor blockade therapy may be beneficial to patients with non-ST-segment elevation myocardial infarction who have had prior MI, stroke, or peripheral artery disease, Dr. Marc Sabatine said at a meeting sponsored by the California chapter of the American College of Cardiology.

In the few years since the ADP receptor blocker clopidogrel entered the medical armamentarium, studies have shown that acute therapy significantly reduces the risk of death, MI, or stroke in patients with non-ST-elevation acute coronary syndrome or ST-segment elevation MI (STEMI), and that the benefits appear within 24 hours. Other data show that this treatment is not useful for primary prevention of coronary syndromes and that there is variability in patient responses to clopidogrel.

A secondary analysis of the large Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial, which established clopidogrel's efficacy for non-ST-elevation acute coronary syndrome in 2001, found that a greater reduction in cardiovascular death, MI, or stroke seen initially in patients randomized to clopidogrel instead of placebo continued to be significant up to nearly 1 year (Circulation 2003;107:966–72).

“This suggests that the benefit continues to accrue over time, and that treatment out to at least a year makes sense,” said Dr. Sabatine of Brigham and Women's Hospital, Boston. He is on advisory boards for and has received research funds and honoraria from the companies that market clopidogrel, Bristol-Myers Squibb and Sanofi-Aventis.

In the large Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) study, patients who had a history of atherothrombosis or risk factors for it and were on daily aspirin therapy were randomized to dual-platelet therapy with the addition of clopidogrel or placebo. Follow-up to an average of 2.5 years showed no difference in the risk for cardiovascular death, MI, or stroke between groups, however (Am. Heart J. 2004;148:263–8).

That's because the results with clopidogrel affected two subgroups in opposite ways. The drug significantly reduced risk in patients with a history of atherothrombosis but increased overall risk in patients with no more than risk factors for atherothrombosis such as diabetes or hypertension (N. Engl. J. Med. 2006;354:1706–17). A 1%–2% increase in moderate to severe bleeding with long-term clopidogrel use was not offset by reductions in death, MI, or stroke in the latter subgroup.

Subgroup analyses are not definitive, but this “does start to fit with our prior notion that dual-antiplatelet therapy is most efficacious in those with an acute thrombus, either a complete occlusion as in STEMI or subtotal occlusion as in non-ST-elevation acute coronary syndromes,” he said at the meeting, also sponsored by the University of California, San Francisco. “If you just have risk factors but never manifested atherothrombosis, there's no benefit.”

There are no data yet on long-term use of clopidogrel for STEMI. The pivotal trials lasted only weeks, he noted.

'This suggests that [clopidogrel's] benefit continues to accrue over time, and that treatment out to at least a year makes sense.' DR. SABATINE

SAN FRANCISCO — Results from three small, foreign trials of an experimental heart pump were good enough to prompt a U.S. feasibility study, and two U.S. trials are planned, Dr. Donald S. Esmore said at the annual meeting of the International Society for Heart and Lung Transplantation.

In the three foreign studies, the VentrAssist left ventricular assist device was implanted either as destination therapy or as a bridge to transplant. In the U.S. feasibility study, which began in 2005, 10 patients out of a planned total of 30 have had the device implanted as a bridge to transplant, he said.

Dr. Esmore is a cardiothoracic surgeon at Alfred Hospital, Melbourne, and a consultant to Ventracor, the company that makes the heart pump. Ventracor plans to begin separate U.S. pivotal trials for destination therapy and for bridge to transplant this year, he said.

The initial pilot trial in Australia found no device-related deaths and a low rate of adverse events in nine patients who received the device, four as destination therapy and five as a bridge to transplant. The mean length of support on the device was 297 days.

A subsequent phase II trial in 33 patients who received the heart pump as a bridge to transplant at multiple centers outside the United States showed that 27 (82%) survived and either underwent heart transplantation within 154 days or were alive and capable of being transplanted, reported Dr. Esmore and his associates.

The median time to transplant for those who got new hearts was 95 days (range 32–306 days). The bridge time on the heart pump was a median of 167 days, reaching 486 days.

Five patients died during the study—two of them (6%) within 30 days of transplantation—for an overall survival rate of 85%.

The rate of serious adverse events was similar to rates seen with other heart pumps, Dr. Esmore said. There were 10 local infections, 8 cases of systemic sepsis, and 6 device malfunctions. Two patients died of a cerebrovascular accident; 14 had neurologic embolic events but experienced no major disability and progressed to successful transplantation.

The third foreign trial has enrolled 12 of an expected 15 patients to get the device as destination therapy. The mean time on the pump has been 378 days. Seven patients remain alive on the pump, and one has had a heart transplant.

The combined results from these studies show that close to 60% of patients survived in the 2 years after getting the pump, he said.

SAN FRANCISCO — Results from three small, foreign trials of an experimental heart pump were good enough to prompt a U.S. feasibility study, and two U.S. trials are planned, Dr. Donald S. Esmore said at the annual meeting of the International Society for Heart and Lung Transplantation.

In the three foreign studies, the VentrAssist left ventricular assist device was implanted either as destination therapy or as a bridge to transplant. In the U.S. feasibility study, which began in 2005, 10 patients out of a planned total of 30 have had the device implanted as a bridge to transplant, he said.

Dr. Esmore is a cardiothoracic surgeon at Alfred Hospital, Melbourne, and a consultant to Ventracor, the company that makes the heart pump. Ventracor plans to begin separate U.S. pivotal trials for destination therapy and for bridge to transplant this year, he said.

The initial pilot trial in Australia found no device-related deaths and a low rate of adverse events in nine patients who received the device, four as destination therapy and five as a bridge to transplant. The mean length of support on the device was 297 days.

A subsequent phase II trial in 33 patients who received the heart pump as a bridge to transplant at multiple centers outside the United States showed that 27 (82%) survived and either underwent heart transplantation within 154 days or were alive and capable of being transplanted, reported Dr. Esmore and his associates.

The median time to transplant for those who got new hearts was 95 days (range 32–306 days). The bridge time on the heart pump was a median of 167 days, reaching 486 days.

Five patients died during the study—two of them (6%) within 30 days of transplantation—for an overall survival rate of 85%.

The rate of serious adverse events was similar to rates seen with other heart pumps, Dr. Esmore said. There were 10 local infections, 8 cases of systemic sepsis, and 6 device malfunctions. Two patients died of a cerebrovascular accident; 14 had neurologic embolic events but experienced no major disability and progressed to successful transplantation.

The third foreign trial has enrolled 12 of an expected 15 patients to get the device as destination therapy. The mean time on the pump has been 378 days. Seven patients remain alive on the pump, and one has had a heart transplant.

The combined results from these studies show that close to 60% of patients survived in the 2 years after getting the pump, he said.

SAN FRANCISCO — Results from three small, foreign trials of an experimental heart pump were good enough to prompt a U.S. feasibility study, and two U.S. trials are planned, Dr. Donald S. Esmore said at the annual meeting of the International Society for Heart and Lung Transplantation.

In the three foreign studies, the VentrAssist left ventricular assist device was implanted either as destination therapy or as a bridge to transplant. In the U.S. feasibility study, which began in 2005, 10 patients out of a planned total of 30 have had the device implanted as a bridge to transplant, he said.

Dr. Esmore is a cardiothoracic surgeon at Alfred Hospital, Melbourne, and a consultant to Ventracor, the company that makes the heart pump. Ventracor plans to begin separate U.S. pivotal trials for destination therapy and for bridge to transplant this year, he said.

The initial pilot trial in Australia found no device-related deaths and a low rate of adverse events in nine patients who received the device, four as destination therapy and five as a bridge to transplant. The mean length of support on the device was 297 days.

A subsequent phase II trial in 33 patients who received the heart pump as a bridge to transplant at multiple centers outside the United States showed that 27 (82%) survived and either underwent heart transplantation within 154 days or were alive and capable of being transplanted, reported Dr. Esmore and his associates.

The median time to transplant for those who got new hearts was 95 days (range 32–306 days). The bridge time on the heart pump was a median of 167 days, reaching 486 days.

Five patients died during the study—two of them (6%) within 30 days of transplantation—for an overall survival rate of 85%.

The rate of serious adverse events was similar to rates seen with other heart pumps, Dr. Esmore said. There were 10 local infections, 8 cases of systemic sepsis, and 6 device malfunctions. Two patients died of a cerebrovascular accident; 14 had neurologic embolic events but experienced no major disability and progressed to successful transplantation.

The third foreign trial has enrolled 12 of an expected 15 patients to get the device as destination therapy. The mean time on the pump has been 378 days. Seven patients remain alive on the pump, and one has had a heart transplant.

The combined results from these studies show that close to 60% of patients survived in the 2 years after getting the pump, he said.

SAN FRANCISCO — Patients with transplanted hearts face a higher risk of sudden cardiac death if they have left ventricular ejection fractions below 40%, a retrospective study of 208 patients found.

The risk for sudden cardiac death is compounded if the patient also has cardiac allograft vasculopathy of any severity, Dr. Michelle Montpetit and her associates reported at the annual meeting of the International Society for Heart and Lung Transplantation.

“It would be reasonable to consider implantation of defibrillators in heart transplant patients with an ejection fraction of less than 40% and cardiac allograft vasculopathy of any severity,” said Dr. Montpetit of Loyola University, Maywood, Ill.

Identifying these patients early is important, she said, because 73% of patients in the study who died of sudden cardiac death did so within the first 5 years after heart transplantation.

Implantable cardioverter defibrillators (ICDs) are recommended for nontransplant patients with heart failure to prevent sudden cardiac death. Previous studies have shown that defibrillators improve survival in nontransplant patients with a history of MI and an ejection fraction below 30%, and in nontransplant patients with cardiomyopathy and an ejection fraction below 35%.

Several previous small studies suggest that 6%–37% of patients after heart transplantation die of sudden cardiac death. The only previous study of ICD use in patients after heart transplant found that 3 of 10 patients were cardioverted appropriately during 13 months of follow-up. They had received ICDs for indications including low ejection fraction and coronary disease, syncope, or symptomatic ventricular tachycardia.

The current study examined data on 208 of 617 patients who underwent heart transplantation at Loyola University Medical Center from 1984 to 2005. The 208 died during those 2 decades, 27% of them from sudden cardiac death, which was defined as a witnessed arrhythmic death or a sudden death at home or in the hospital with no known cause.

Patients with sudden cardiac death were more likely to have undergone heart transplantation for ischemic cardiomyopathy (64%), compared with 46% of patients who died of other causes. Other clinical and demographic characteristics were similar between groups.

The only single factor associated with sudden cardiac death in multivariate analysis was left ventricular ejection fraction. Among the entire cohort, 40% of patients with ejection fractions below 40% died of sudden cardiac death, compared with 22% of patients with greater ejection fractions. Of the 56 patients with sudden cardiac death, 23 (41%) had ejection fractions below 40%.

Cardiac allograft vasculopathy by itself was not associated with risk of sudden cardiac death, but when combined with a low ejection fraction, it increased the risk of sudden cardiac death to 52%, Dr. Montpetit said.

Among a subset of patients who underwent coronary angiography near the time of death, 4 had mild cardiac allograft vasculopathy (defined as any lesion less than 50% of a major vessel) and 13 had severe vasculopathy (lesions greater than 50%). The severity of vasculopathy did not appear to affect the risk of sudden cardiac death.

The findings were limited by the retrospective nature of the study, its small size, and the lack of autopsy data to confirm the cause of death, Dr. Montpetit said. Not all patients had coronary angiography or ejection fraction measurements near the time of death. The records may have been skewed by the fact that “we tend to collect more data on patients with acute rejection,” she said.

A posttransplant history of at least one episode of severe rejection was significantly more common in patients who later died of sudden cardiac death (64%) than in patients who died of other causes (46%).

SAN FRANCISCO — Patients with transplanted hearts face a higher risk of sudden cardiac death if they have left ventricular ejection fractions below 40%, a retrospective study of 208 patients found.

The risk for sudden cardiac death is compounded if the patient also has cardiac allograft vasculopathy of any severity, Dr. Michelle Montpetit and her associates reported at the annual meeting of the International Society for Heart and Lung Transplantation.

“It would be reasonable to consider implantation of defibrillators in heart transplant patients with an ejection fraction of less than 40% and cardiac allograft vasculopathy of any severity,” said Dr. Montpetit of Loyola University, Maywood, Ill.

Identifying these patients early is important, she said, because 73% of patients in the study who died of sudden cardiac death did so within the first 5 years after heart transplantation.

Implantable cardioverter defibrillators (ICDs) are recommended for nontransplant patients with heart failure to prevent sudden cardiac death. Previous studies have shown that defibrillators improve survival in nontransplant patients with a history of MI and an ejection fraction below 30%, and in nontransplant patients with cardiomyopathy and an ejection fraction below 35%.

Several previous small studies suggest that 6%–37% of patients after heart transplantation die of sudden cardiac death. The only previous study of ICD use in patients after heart transplant found that 3 of 10 patients were cardioverted appropriately during 13 months of follow-up. They had received ICDs for indications including low ejection fraction and coronary disease, syncope, or symptomatic ventricular tachycardia.

The current study examined data on 208 of 617 patients who underwent heart transplantation at Loyola University Medical Center from 1984 to 2005. The 208 died during those 2 decades, 27% of them from sudden cardiac death, which was defined as a witnessed arrhythmic death or a sudden death at home or in the hospital with no known cause.

Patients with sudden cardiac death were more likely to have undergone heart transplantation for ischemic cardiomyopathy (64%), compared with 46% of patients who died of other causes. Other clinical and demographic characteristics were similar between groups.

The only single factor associated with sudden cardiac death in multivariate analysis was left ventricular ejection fraction. Among the entire cohort, 40% of patients with ejection fractions below 40% died of sudden cardiac death, compared with 22% of patients with greater ejection fractions. Of the 56 patients with sudden cardiac death, 23 (41%) had ejection fractions below 40%.

Cardiac allograft vasculopathy by itself was not associated with risk of sudden cardiac death, but when combined with a low ejection fraction, it increased the risk of sudden cardiac death to 52%, Dr. Montpetit said.

Among a subset of patients who underwent coronary angiography near the time of death, 4 had mild cardiac allograft vasculopathy (defined as any lesion less than 50% of a major vessel) and 13 had severe vasculopathy (lesions greater than 50%). The severity of vasculopathy did not appear to affect the risk of sudden cardiac death.

The findings were limited by the retrospective nature of the study, its small size, and the lack of autopsy data to confirm the cause of death, Dr. Montpetit said. Not all patients had coronary angiography or ejection fraction measurements near the time of death. The records may have been skewed by the fact that “we tend to collect more data on patients with acute rejection,” she said.

A posttransplant history of at least one episode of severe rejection was significantly more common in patients who later died of sudden cardiac death (64%) than in patients who died of other causes (46%).

SAN FRANCISCO — Patients with transplanted hearts face a higher risk of sudden cardiac death if they have left ventricular ejection fractions below 40%, a retrospective study of 208 patients found.

The risk for sudden cardiac death is compounded if the patient also has cardiac allograft vasculopathy of any severity, Dr. Michelle Montpetit and her associates reported at the annual meeting of the International Society for Heart and Lung Transplantation.

“It would be reasonable to consider implantation of defibrillators in heart transplant patients with an ejection fraction of less than 40% and cardiac allograft vasculopathy of any severity,” said Dr. Montpetit of Loyola University, Maywood, Ill.

Identifying these patients early is important, she said, because 73% of patients in the study who died of sudden cardiac death did so within the first 5 years after heart transplantation.

Implantable cardioverter defibrillators (ICDs) are recommended for nontransplant patients with heart failure to prevent sudden cardiac death. Previous studies have shown that defibrillators improve survival in nontransplant patients with a history of MI and an ejection fraction below 30%, and in nontransplant patients with cardiomyopathy and an ejection fraction below 35%.

Several previous small studies suggest that 6%–37% of patients after heart transplantation die of sudden cardiac death. The only previous study of ICD use in patients after heart transplant found that 3 of 10 patients were cardioverted appropriately during 13 months of follow-up. They had received ICDs for indications including low ejection fraction and coronary disease, syncope, or symptomatic ventricular tachycardia.

The current study examined data on 208 of 617 patients who underwent heart transplantation at Loyola University Medical Center from 1984 to 2005. The 208 died during those 2 decades, 27% of them from sudden cardiac death, which was defined as a witnessed arrhythmic death or a sudden death at home or in the hospital with no known cause.

Patients with sudden cardiac death were more likely to have undergone heart transplantation for ischemic cardiomyopathy (64%), compared with 46% of patients who died of other causes. Other clinical and demographic characteristics were similar between groups.

The only single factor associated with sudden cardiac death in multivariate analysis was left ventricular ejection fraction. Among the entire cohort, 40% of patients with ejection fractions below 40% died of sudden cardiac death, compared with 22% of patients with greater ejection fractions. Of the 56 patients with sudden cardiac death, 23 (41%) had ejection fractions below 40%.

Cardiac allograft vasculopathy by itself was not associated with risk of sudden cardiac death, but when combined with a low ejection fraction, it increased the risk of sudden cardiac death to 52%, Dr. Montpetit said.

Among a subset of patients who underwent coronary angiography near the time of death, 4 had mild cardiac allograft vasculopathy (defined as any lesion less than 50% of a major vessel) and 13 had severe vasculopathy (lesions greater than 50%). The severity of vasculopathy did not appear to affect the risk of sudden cardiac death.

The findings were limited by the retrospective nature of the study, its small size, and the lack of autopsy data to confirm the cause of death, Dr. Montpetit said. Not all patients had coronary angiography or ejection fraction measurements near the time of death. The records may have been skewed by the fact that “we tend to collect more data on patients with acute rejection,” she said.

A posttransplant history of at least one episode of severe rejection was significantly more common in patients who later died of sudden cardiac death (64%) than in patients who died of other causes (46%).

SAN FRANCISCO — A plateau in bone mineral density improvement while on antiresorptive therapy for osteoporosis does not mean the treatment has stopped working, Dr. Steven T. Harris said at a diabetes update sponsored by the University of California, San Francisco.

One should explain this to patients at the start of therapy to avoid disappointment or worse when their T scores stop rising, he said.

The most important clinical objective is to prevent fractures, not to produce changes in surrogate markers like bone mineral density or biochemical markers of bone turnover, he emphasized. The risk of fracture declines significantly despite a slight improvement in T score or even no change in T score in the first year on antiresorptive medication because of improvements in bone quality. The fracture protection continues while the patient is on therapy, despite no further changes in bone mineral density.

Antiresorptive agents such as bisphosphonates, selective estrogen receptor modifiers, calcitonin, and estrogen decrease bone resorption and bone formation.

This typically produces an increase in bone mineral density in the first year of therapy and a smaller increase the second year, which is then followed by a plateau. Despite the plateau, fracture protection continues.

“It is the rule, not the exception, that bone density goes up a little, then stabilizes. That is not nonresponse. That does not mean you have to change the therapy. That does not mean that your patients are not taking their medications. This is physiology in action,” Dr. Harris said.

Many patients logically assume that if a T score of −3.2 won them a diagnosis of osteoporosis, for example, then the goal of therapy is to get the T score back to zero, which is why it is important to explain this possiblity early on.

Findings from studies of the bisphosphonates risedronate and alendronate, for example, show that therapy increases spinal bone density 5%–8% and hip bone density by 3%–5% after 3 years in osteoporotic women. Those are “not terribly impressive” numbers until you look at the fracture protection, he said, noting that the drugs reduced the incidence of vertebral fractures by 40%–65% and the incidence of hip fractures by 40%–60%.

SAN FRANCISCO — A plateau in bone mineral density improvement while on antiresorptive therapy for osteoporosis does not mean the treatment has stopped working, Dr. Steven T. Harris said at a diabetes update sponsored by the University of California, San Francisco.

One should explain this to patients at the start of therapy to avoid disappointment or worse when their T scores stop rising, he said.

The most important clinical objective is to prevent fractures, not to produce changes in surrogate markers like bone mineral density or biochemical markers of bone turnover, he emphasized. The risk of fracture declines significantly despite a slight improvement in T score or even no change in T score in the first year on antiresorptive medication because of improvements in bone quality. The fracture protection continues while the patient is on therapy, despite no further changes in bone mineral density.

Antiresorptive agents such as bisphosphonates, selective estrogen receptor modifiers, calcitonin, and estrogen decrease bone resorption and bone formation.

This typically produces an increase in bone mineral density in the first year of therapy and a smaller increase the second year, which is then followed by a plateau. Despite the plateau, fracture protection continues.

“It is the rule, not the exception, that bone density goes up a little, then stabilizes. That is not nonresponse. That does not mean you have to change the therapy. That does not mean that your patients are not taking their medications. This is physiology in action,” Dr. Harris said.

Many patients logically assume that if a T score of −3.2 won them a diagnosis of osteoporosis, for example, then the goal of therapy is to get the T score back to zero, which is why it is important to explain this possiblity early on.

Findings from studies of the bisphosphonates risedronate and alendronate, for example, show that therapy increases spinal bone density 5%–8% and hip bone density by 3%–5% after 3 years in osteoporotic women. Those are “not terribly impressive” numbers until you look at the fracture protection, he said, noting that the drugs reduced the incidence of vertebral fractures by 40%–65% and the incidence of hip fractures by 40%–60%.

SAN FRANCISCO — A plateau in bone mineral density improvement while on antiresorptive therapy for osteoporosis does not mean the treatment has stopped working, Dr. Steven T. Harris said at a diabetes update sponsored by the University of California, San Francisco.

One should explain this to patients at the start of therapy to avoid disappointment or worse when their T scores stop rising, he said.

The most important clinical objective is to prevent fractures, not to produce changes in surrogate markers like bone mineral density or biochemical markers of bone turnover, he emphasized. The risk of fracture declines significantly despite a slight improvement in T score or even no change in T score in the first year on antiresorptive medication because of improvements in bone quality. The fracture protection continues while the patient is on therapy, despite no further changes in bone mineral density.

Antiresorptive agents such as bisphosphonates, selective estrogen receptor modifiers, calcitonin, and estrogen decrease bone resorption and bone formation.

This typically produces an increase in bone mineral density in the first year of therapy and a smaller increase the second year, which is then followed by a plateau. Despite the plateau, fracture protection continues.

“It is the rule, not the exception, that bone density goes up a little, then stabilizes. That is not nonresponse. That does not mean you have to change the therapy. That does not mean that your patients are not taking their medications. This is physiology in action,” Dr. Harris said.

Many patients logically assume that if a T score of −3.2 won them a diagnosis of osteoporosis, for example, then the goal of therapy is to get the T score back to zero, which is why it is important to explain this possiblity early on.

Findings from studies of the bisphosphonates risedronate and alendronate, for example, show that therapy increases spinal bone density 5%–8% and hip bone density by 3%–5% after 3 years in osteoporotic women. Those are “not terribly impressive” numbers until you look at the fracture protection, he said, noting that the drugs reduced the incidence of vertebral fractures by 40%–65% and the incidence of hip fractures by 40%–60%.

SAN FRANCISCO — Bisphosphonates remain the prime oral therapies for osteoporosis, but some competing agents might alter medical practice, Dr. Steven T. Harris said at a meeting on diabetes and endocrinology that was sponsored by the University of California, San Francisco.

More liberal use of vitamin D and a new indication for the selective estrogen receptor modifier raloxifene (Evista) give these agents a higher clinical profile, said Dr. Harris of the university. Investigational oral therapies that soon are likely to play a role in osteoporosis treatment include the monoclonal antibody denosumab and the new bisphosphonate zoledronic acid (Reclast).

▸ Vitamin D. Institute of Medicine recommendations in 1997 that adults get 200–600 IU a day of vitamin D (depending on age) now are widely considered to be inadequate. The minimum probably should be 800–1,000 IU a day for adults, and it's almost impossible to overdose on vitamin D, he noted.

Experts have urged clinicians to keep patients' 25-hydroxyvitamin D levels up to 30 ng/mL or higher, so “we ought to be a little more generous in our D supplementation than we have been historically,” he said.

Multiple studies in recent years have reported associations between vitamin D insufficiency and an increase in a variety of immune diseases and malignancies including osteoarthritis, multiple sclerosis, fibromyalgia, type 1 diabetes, and cardiovascular disease.

Dr. Harris changed his practice toward greater emphasis on vitamin D supplementation after a recent study showed that half of osteoporotic patients on prescription therapies had vitamin D insufficiency regardless of where they lived (J. Clin. Endocrinol. Metab. 2005;90:3215–24).

▸ Raloxifene. Approved for the prevention or treatment of osteoporosis, raloxifene has been shown to decrease the incidence of vertebral fractures in women with preexisting vertebral fractures or low bone density. It does not affect the risk of nonvertebral or hip fractures and so “does not compete terribly well with other osteoporosis treatment options,” Dr. Harris said.

Three other studies report that raloxifene decreases the risk of estrogen receptor-positive invasive breast cancer (but not estrogen receptor-negative tumors or ductal carcinoma in situ). “It's almost certain that sometime this year Evista is going to be approved by the Food and Drug Administration to reduce the risk of breast cancer.”

That added indication might boost raloxifene's use for some osteoporotic patients, though that remains to be seen.

▸ Denosumab. One subcutaneous injection of this experimental monoclonal antibody greatly decreases bone resorption almost immediately, a recent study suggests. One injection every 6 months produced bone density improvements similar to gains seen in patients treated weekly with the oral bisphosphonate alendronate (N. Engl. J. Med. 2006;354:821–31).

A large clinical trial is studying denosumab for osteoporosis. No data on fracture prevention are available yet.

▸ Zoledronic acid. A 15-minute intravenous infusion of 5 mg zoledronic acid once yearly for 3 years in lieu of oral therapy significantly reduced vertebral, nonvertebral, and hip fractures in a study of 7,736 postmenopausal women randomized to the drug or placebo, according to preliminary results reported at a 2006 conference. Zoledronic acid is not approved to treat osteoporosis but is indicated for treatment of patients with hypercalcemia of malignancy, multiple myeloma, Paget's disease of bone, or bone metastases from solid tumors. Dr. Harris predicted the drug would win approval for osteoporosis, and he said he believes it is unlikely to prove more effective than oral therapies but could offer an alternative for osteoporotic patients who can't or won't take oral medication.

'We ought to be a little more generous in our D supplementation.' DR. HARRIS

SAN FRANCISCO — Bisphosphonates remain the prime oral therapies for osteoporosis, but some competing agents might alter medical practice, Dr. Steven T. Harris said at a meeting on diabetes and endocrinology that was sponsored by the University of California, San Francisco.

More liberal use of vitamin D and a new indication for the selective estrogen receptor modifier raloxifene (Evista) give these agents a higher clinical profile, said Dr. Harris of the university. Investigational oral therapies that soon are likely to play a role in osteoporosis treatment include the monoclonal antibody denosumab and the new bisphosphonate zoledronic acid (Reclast).

▸ Vitamin D. Institute of Medicine recommendations in 1997 that adults get 200–600 IU a day of vitamin D (depending on age) now are widely considered to be inadequate. The minimum probably should be 800–1,000 IU a day for adults, and it's almost impossible to overdose on vitamin D, he noted.

Experts have urged clinicians to keep patients' 25-hydroxyvitamin D levels up to 30 ng/mL or higher, so “we ought to be a little more generous in our D supplementation than we have been historically,” he said.

Multiple studies in recent years have reported associations between vitamin D insufficiency and an increase in a variety of immune diseases and malignancies including osteoarthritis, multiple sclerosis, fibromyalgia, type 1 diabetes, and cardiovascular disease.

Dr. Harris changed his practice toward greater emphasis on vitamin D supplementation after a recent study showed that half of osteoporotic patients on prescription therapies had vitamin D insufficiency regardless of where they lived (J. Clin. Endocrinol. Metab. 2005;90:3215–24).

▸ Raloxifene. Approved for the prevention or treatment of osteoporosis, raloxifene has been shown to decrease the incidence of vertebral fractures in women with preexisting vertebral fractures or low bone density. It does not affect the risk of nonvertebral or hip fractures and so “does not compete terribly well with other osteoporosis treatment options,” Dr. Harris said.

Three other studies report that raloxifene decreases the risk of estrogen receptor-positive invasive breast cancer (but not estrogen receptor-negative tumors or ductal carcinoma in situ). “It's almost certain that sometime this year Evista is going to be approved by the Food and Drug Administration to reduce the risk of breast cancer.”

That added indication might boost raloxifene's use for some osteoporotic patients, though that remains to be seen.

▸ Denosumab. One subcutaneous injection of this experimental monoclonal antibody greatly decreases bone resorption almost immediately, a recent study suggests. One injection every 6 months produced bone density improvements similar to gains seen in patients treated weekly with the oral bisphosphonate alendronate (N. Engl. J. Med. 2006;354:821–31).

A large clinical trial is studying denosumab for osteoporosis. No data on fracture prevention are available yet.

▸ Zoledronic acid. A 15-minute intravenous infusion of 5 mg zoledronic acid once yearly for 3 years in lieu of oral therapy significantly reduced vertebral, nonvertebral, and hip fractures in a study of 7,736 postmenopausal women randomized to the drug or placebo, according to preliminary results reported at a 2006 conference. Zoledronic acid is not approved to treat osteoporosis but is indicated for treatment of patients with hypercalcemia of malignancy, multiple myeloma, Paget's disease of bone, or bone metastases from solid tumors. Dr. Harris predicted the drug would win approval for osteoporosis, and he said he believes it is unlikely to prove more effective than oral therapies but could offer an alternative for osteoporotic patients who can't or won't take oral medication.

'We ought to be a little more generous in our D supplementation.' DR. HARRIS

SAN FRANCISCO — Bisphosphonates remain the prime oral therapies for osteoporosis, but some competing agents might alter medical practice, Dr. Steven T. Harris said at a meeting on diabetes and endocrinology that was sponsored by the University of California, San Francisco.

More liberal use of vitamin D and a new indication for the selective estrogen receptor modifier raloxifene (Evista) give these agents a higher clinical profile, said Dr. Harris of the university. Investigational oral therapies that soon are likely to play a role in osteoporosis treatment include the monoclonal antibody denosumab and the new bisphosphonate zoledronic acid (Reclast).

▸ Vitamin D. Institute of Medicine recommendations in 1997 that adults get 200–600 IU a day of vitamin D (depending on age) now are widely considered to be inadequate. The minimum probably should be 800–1,000 IU a day for adults, and it's almost impossible to overdose on vitamin D, he noted.

Experts have urged clinicians to keep patients' 25-hydroxyvitamin D levels up to 30 ng/mL or higher, so “we ought to be a little more generous in our D supplementation than we have been historically,” he said.

Multiple studies in recent years have reported associations between vitamin D insufficiency and an increase in a variety of immune diseases and malignancies including osteoarthritis, multiple sclerosis, fibromyalgia, type 1 diabetes, and cardiovascular disease.

Dr. Harris changed his practice toward greater emphasis on vitamin D supplementation after a recent study showed that half of osteoporotic patients on prescription therapies had vitamin D insufficiency regardless of where they lived (J. Clin. Endocrinol. Metab. 2005;90:3215–24).

▸ Raloxifene. Approved for the prevention or treatment of osteoporosis, raloxifene has been shown to decrease the incidence of vertebral fractures in women with preexisting vertebral fractures or low bone density. It does not affect the risk of nonvertebral or hip fractures and so “does not compete terribly well with other osteoporosis treatment options,” Dr. Harris said.

Three other studies report that raloxifene decreases the risk of estrogen receptor-positive invasive breast cancer (but not estrogen receptor-negative tumors or ductal carcinoma in situ). “It's almost certain that sometime this year Evista is going to be approved by the Food and Drug Administration to reduce the risk of breast cancer.”

That added indication might boost raloxifene's use for some osteoporotic patients, though that remains to be seen.

▸ Denosumab. One subcutaneous injection of this experimental monoclonal antibody greatly decreases bone resorption almost immediately, a recent study suggests. One injection every 6 months produced bone density improvements similar to gains seen in patients treated weekly with the oral bisphosphonate alendronate (N. Engl. J. Med. 2006;354:821–31).

A large clinical trial is studying denosumab for osteoporosis. No data on fracture prevention are available yet.

▸ Zoledronic acid. A 15-minute intravenous infusion of 5 mg zoledronic acid once yearly for 3 years in lieu of oral therapy significantly reduced vertebral, nonvertebral, and hip fractures in a study of 7,736 postmenopausal women randomized to the drug or placebo, according to preliminary results reported at a 2006 conference. Zoledronic acid is not approved to treat osteoporosis but is indicated for treatment of patients with hypercalcemia of malignancy, multiple myeloma, Paget's disease of bone, or bone metastases from solid tumors. Dr. Harris predicted the drug would win approval for osteoporosis, and he said he believes it is unlikely to prove more effective than oral therapies but could offer an alternative for osteoporotic patients who can't or won't take oral medication.

'We ought to be a little more generous in our D supplementation.' DR. HARRIS

SAN FRANCISCO — A woman's prediction of the number of children she will have in her lifetime often falls short, Dr. Kristie Keeton said in a poster presentation at the annual meeting of the Society for Maternal-Fetal Medicine.

An Internet survey asked women who said they had completed childbearing to look back to their first pregnancy and their thoughts at that time about how many children they planned to have.

Among 458 women who said they had planned on having one or two children, 41% were accurate, 16% had fewer children than they planned, and 42% had more children than expected, reported Dr. Keeton of the University of Michigan, Ann Arbor, and her associates.

Among women who had more children than predicted, 68% had three or more children.

The findings have implications for counseling of women who request cesarean delivery, which is a growing phenomenon, Dr. Keeton said in an interview at the poster.

A recent State of the Science statement by the National Institutes of Health said that “Cesarean delivery on maternal request is not recommended for women desiring several children,” she noted.

The risks of placenta previa, accreta, and surgical complications increase with each C-section.

The current study suggests that at the time of first pregnancy, women are unable to predict their final parity.

This information should be incorporated into counseling of women who desire a primary elective C-section, Dr. Keeton said.

The U.S. C-section rate for 2005 was over 30%, the highest rate ever, according to preliminary data from the National Center for Health Statistics, she noted.

Women in the present study were more likely to accurately predict their parity if they were older at the time of first pregnancy (25 years vs. 21 years) and if they had two siblings instead of three.

One flaw of the study design was that it could not take into account the potential for recall bias affecting respondents' answers. Also, although all women said they had completed childbearing, it is possible that some may have future pregnancies, which would increase the proportion of respondents who underpredicted the number of children they would have.

Perhaps because the survey was conducted over the Internet, the demographics of the respondents were not representative of the general population: 74% of the women were white, 69% had at least some college education, and 70% were married or had a domestic partner. The mean age of respondents was 39 years.

SAN FRANCISCO — A woman's prediction of the number of children she will have in her lifetime often falls short, Dr. Kristie Keeton said in a poster presentation at the annual meeting of the Society for Maternal-Fetal Medicine.

An Internet survey asked women who said they had completed childbearing to look back to their first pregnancy and their thoughts at that time about how many children they planned to have.

Among 458 women who said they had planned on having one or two children, 41% were accurate, 16% had fewer children than they planned, and 42% had more children than expected, reported Dr. Keeton of the University of Michigan, Ann Arbor, and her associates.

Among women who had more children than predicted, 68% had three or more children.

The findings have implications for counseling of women who request cesarean delivery, which is a growing phenomenon, Dr. Keeton said in an interview at the poster.

A recent State of the Science statement by the National Institutes of Health said that “Cesarean delivery on maternal request is not recommended for women desiring several children,” she noted.

The risks of placenta previa, accreta, and surgical complications increase with each C-section.

The current study suggests that at the time of first pregnancy, women are unable to predict their final parity.

This information should be incorporated into counseling of women who desire a primary elective C-section, Dr. Keeton said.

The U.S. C-section rate for 2005 was over 30%, the highest rate ever, according to preliminary data from the National Center for Health Statistics, she noted.

Women in the present study were more likely to accurately predict their parity if they were older at the time of first pregnancy (25 years vs. 21 years) and if they had two siblings instead of three.

One flaw of the study design was that it could not take into account the potential for recall bias affecting respondents' answers. Also, although all women said they had completed childbearing, it is possible that some may have future pregnancies, which would increase the proportion of respondents who underpredicted the number of children they would have.

Perhaps because the survey was conducted over the Internet, the demographics of the respondents were not representative of the general population: 74% of the women were white, 69% had at least some college education, and 70% were married or had a domestic partner. The mean age of respondents was 39 years.

SAN FRANCISCO — A woman's prediction of the number of children she will have in her lifetime often falls short, Dr. Kristie Keeton said in a poster presentation at the annual meeting of the Society for Maternal-Fetal Medicine.

An Internet survey asked women who said they had completed childbearing to look back to their first pregnancy and their thoughts at that time about how many children they planned to have.

Among 458 women who said they had planned on having one or two children, 41% were accurate, 16% had fewer children than they planned, and 42% had more children than expected, reported Dr. Keeton of the University of Michigan, Ann Arbor, and her associates.

Among women who had more children than predicted, 68% had three or more children.

The findings have implications for counseling of women who request cesarean delivery, which is a growing phenomenon, Dr. Keeton said in an interview at the poster.

A recent State of the Science statement by the National Institutes of Health said that “Cesarean delivery on maternal request is not recommended for women desiring several children,” she noted.

The risks of placenta previa, accreta, and surgical complications increase with each C-section.

The current study suggests that at the time of first pregnancy, women are unable to predict their final parity.

This information should be incorporated into counseling of women who desire a primary elective C-section, Dr. Keeton said.

The U.S. C-section rate for 2005 was over 30%, the highest rate ever, according to preliminary data from the National Center for Health Statistics, she noted.

Women in the present study were more likely to accurately predict their parity if they were older at the time of first pregnancy (25 years vs. 21 years) and if they had two siblings instead of three.

One flaw of the study design was that it could not take into account the potential for recall bias affecting respondents' answers. Also, although all women said they had completed childbearing, it is possible that some may have future pregnancies, which would increase the proportion of respondents who underpredicted the number of children they would have.

Perhaps because the survey was conducted over the Internet, the demographics of the respondents were not representative of the general population: 74% of the women were white, 69% had at least some college education, and 70% were married or had a domestic partner. The mean age of respondents was 39 years.

SAN FRANCISCO — The first step in preparing a diabetic woman for pregnancy is recognizing that she has diabetes before she conceives.

Women with type 2 diabetes often don't get diagnosed until pregnancy, when it's too late to reduce the risk of congenital anomalies through better glycemic control, Dr. Ingrid Block said at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.

Congenital anomalies in infants of diabetic mothers occur as early as 5 weeks after the mother's last menstrual period (for caudal regression) and as late as 8 weeks after the last period (for cardiac anomalies).

“If you don't sit down with that patient and ensure that she plans her pregnancy and that she has good glycemic control before conception, you run the risk that she'll find out she's 8 weeks pregnant and she has missed the opportunity” to avoid these congenital anomalies, said Dr. Block, of the university.

With any new female patients, pay attention to their obstetric histories, she urged. If a nondiabetic woman has delivered a large baby or had gestational diabetes, she's at increased risk for developing type 2 diabetes and should be screened for it periodically.

Congenital anomalies occur in 6%–10% of pregnancies among diabetic women with uncontrolled hyperglycemia, compared with an incidence of 2% in nondiabetic women. Emphasize effective contraception until diabetes patients achieve stable glycemia, Dr. Block said.

Preconception counseling and care should help women optimize glycemic control before pregnancy, which significantly reduces the risks of anomalies and fetal death, studies have shown. Women with type 2 diabetes should transition before conception from managing their diabetes using diet alone or oral therapies to using insulin, she added. Identification and treatment of long-term complications of diabetes—such as retinopathy, nephropathy, neuropathy, hypertension, and coronary artery disease—will give physicians an opportunity to warn some patients about difficult or nonviable pregnancies.

Diabetic women with early renal failure are unlikely to have viable pregnancies, for example, but renal transplant has allowed some of these women to have successful pregnancies and deliveries. A diabetic woman with preconception hypertension and proteinuria over 500 mg in 24 hours should be informed of her significant risk for preeclampsia and preterm delivery, which could mean weeks in the neonatal intensive care unit.

“That is a very stressful experience for the baby and the parents,” Dr. Block said.

At her institution, women with type 1 or type 2 diabetes who want to become pregnant get tests for hemoglobin HbA_1c and TSH levels, 24-hour urine protein, and serum creatinine. They also get an ECG, and patients at high risk for coronary artery disease undergo noninvasive stress tests. Referrals for ophthalmologic evaluation, nutrition therapy, and a review of diabetes self-care skills are routine. Every patient gets a glucagon emergency kit if she doesn't already have one, and starts prenatal vitamins.

Any women with type 1 diabetes who are on regular insulin are switched to aspart or lispro forms of insulin. Women with type 2 diabetes stop oral hypoglycemics and start insulin. If they are on ACE inhibitor therapy, type 2 diabetes patients stop the drug and switch to labetalol or methyldopa.

It's important to know how much support the woman has at home, and how involved the father is in the pregnancy.

Start these patients on frequent glucose monitoring before meals and 60–90 minutes after eating, with a blood glucose check at 2 a.m., she said. Before pregnancy, aim for a fasting blood glucose less than 105 mg/dL, a 1-hour postprandial level below 155 mg/dL, and a 2 a.m. level below 120 mg/dL. During pregnancy, aim for a fasting blood glucose below 95 mg/dL, a 1-hour postprandial level less than 140 mg/dL, and a 2 a.m. level below 120 mg/dL.

SAN FRANCISCO — The first step in preparing a diabetic woman for pregnancy is recognizing that she has diabetes before she conceives.

Women with type 2 diabetes often don't get diagnosed until pregnancy, when it's too late to reduce the risk of congenital anomalies through better glycemic control, Dr. Ingrid Block said at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.

Congenital anomalies in infants of diabetic mothers occur as early as 5 weeks after the mother's last menstrual period (for caudal regression) and as late as 8 weeks after the last period (for cardiac anomalies).

“If you don't sit down with that patient and ensure that she plans her pregnancy and that she has good glycemic control before conception, you run the risk that she'll find out she's 8 weeks pregnant and she has missed the opportunity” to avoid these congenital anomalies, said Dr. Block, of the university.

With any new female patients, pay attention to their obstetric histories, she urged. If a nondiabetic woman has delivered a large baby or had gestational diabetes, she's at increased risk for developing type 2 diabetes and should be screened for it periodically.

Congenital anomalies occur in 6%–10% of pregnancies among diabetic women with uncontrolled hyperglycemia, compared with an incidence of 2% in nondiabetic women. Emphasize effective contraception until diabetes patients achieve stable glycemia, Dr. Block said.

Preconception counseling and care should help women optimize glycemic control before pregnancy, which significantly reduces the risks of anomalies and fetal death, studies have shown. Women with type 2 diabetes should transition before conception from managing their diabetes using diet alone or oral therapies to using insulin, she added. Identification and treatment of long-term complications of diabetes—such as retinopathy, nephropathy, neuropathy, hypertension, and coronary artery disease—will give physicians an opportunity to warn some patients about difficult or nonviable pregnancies.

Diabetic women with early renal failure are unlikely to have viable pregnancies, for example, but renal transplant has allowed some of these women to have successful pregnancies and deliveries. A diabetic woman with preconception hypertension and proteinuria over 500 mg in 24 hours should be informed of her significant risk for preeclampsia and preterm delivery, which could mean weeks in the neonatal intensive care unit.

“That is a very stressful experience for the baby and the parents,” Dr. Block said.

At her institution, women with type 1 or type 2 diabetes who want to become pregnant get tests for hemoglobin HbA_1c and TSH levels, 24-hour urine protein, and serum creatinine. They also get an ECG, and patients at high risk for coronary artery disease undergo noninvasive stress tests. Referrals for ophthalmologic evaluation, nutrition therapy, and a review of diabetes self-care skills are routine. Every patient gets a glucagon emergency kit if she doesn't already have one, and starts prenatal vitamins.

Any women with type 1 diabetes who are on regular insulin are switched to aspart or lispro forms of insulin. Women with type 2 diabetes stop oral hypoglycemics and start insulin. If they are on ACE inhibitor therapy, type 2 diabetes patients stop the drug and switch to labetalol or methyldopa.

It's important to know how much support the woman has at home, and how involved the father is in the pregnancy.

Start these patients on frequent glucose monitoring before meals and 60–90 minutes after eating, with a blood glucose check at 2 a.m., she said. Before pregnancy, aim for a fasting blood glucose less than 105 mg/dL, a 1-hour postprandial level below 155 mg/dL, and a 2 a.m. level below 120 mg/dL. During pregnancy, aim for a fasting blood glucose below 95 mg/dL, a 1-hour postprandial level less than 140 mg/dL, and a 2 a.m. level below 120 mg/dL.

SAN FRANCISCO — The first step in preparing a diabetic woman for pregnancy is recognizing that she has diabetes before she conceives.

Women with type 2 diabetes often don't get diagnosed until pregnancy, when it's too late to reduce the risk of congenital anomalies through better glycemic control, Dr. Ingrid Block said at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.

Congenital anomalies in infants of diabetic mothers occur as early as 5 weeks after the mother's last menstrual period (for caudal regression) and as late as 8 weeks after the last period (for cardiac anomalies).

“If you don't sit down with that patient and ensure that she plans her pregnancy and that she has good glycemic control before conception, you run the risk that she'll find out she's 8 weeks pregnant and she has missed the opportunity” to avoid these congenital anomalies, said Dr. Block, of the university.

With any new female patients, pay attention to their obstetric histories, she urged. If a nondiabetic woman has delivered a large baby or had gestational diabetes, she's at increased risk for developing type 2 diabetes and should be screened for it periodically.

Congenital anomalies occur in 6%–10% of pregnancies among diabetic women with uncontrolled hyperglycemia, compared with an incidence of 2% in nondiabetic women. Emphasize effective contraception until diabetes patients achieve stable glycemia, Dr. Block said.

Preconception counseling and care should help women optimize glycemic control before pregnancy, which significantly reduces the risks of anomalies and fetal death, studies have shown. Women with type 2 diabetes should transition before conception from managing their diabetes using diet alone or oral therapies to using insulin, she added. Identification and treatment of long-term complications of diabetes—such as retinopathy, nephropathy, neuropathy, hypertension, and coronary artery disease—will give physicians an opportunity to warn some patients about difficult or nonviable pregnancies.

Diabetic women with early renal failure are unlikely to have viable pregnancies, for example, but renal transplant has allowed some of these women to have successful pregnancies and deliveries. A diabetic woman with preconception hypertension and proteinuria over 500 mg in 24 hours should be informed of her significant risk for preeclampsia and preterm delivery, which could mean weeks in the neonatal intensive care unit.

“That is a very stressful experience for the baby and the parents,” Dr. Block said.

At her institution, women with type 1 or type 2 diabetes who want to become pregnant get tests for hemoglobin HbA_1c and TSH levels, 24-hour urine protein, and serum creatinine. They also get an ECG, and patients at high risk for coronary artery disease undergo noninvasive stress tests. Referrals for ophthalmologic evaluation, nutrition therapy, and a review of diabetes self-care skills are routine. Every patient gets a glucagon emergency kit if she doesn't already have one, and starts prenatal vitamins.

Any women with type 1 diabetes who are on regular insulin are switched to aspart or lispro forms of insulin. Women with type 2 diabetes stop oral hypoglycemics and start insulin. If they are on ACE inhibitor therapy, type 2 diabetes patients stop the drug and switch to labetalol or methyldopa.

It's important to know how much support the woman has at home, and how involved the father is in the pregnancy.

Start these patients on frequent glucose monitoring before meals and 60–90 minutes after eating, with a blood glucose check at 2 a.m., she said. Before pregnancy, aim for a fasting blood glucose less than 105 mg/dL, a 1-hour postprandial level below 155 mg/dL, and a 2 a.m. level below 120 mg/dL. During pregnancy, aim for a fasting blood glucose below 95 mg/dL, a 1-hour postprandial level less than 140 mg/dL, and a 2 a.m. level below 120 mg/dL.

SAN FRANCISCO — Exercise by itself is unlikely to lead to weight loss, but becoming physically fit reduces a person's risk for mortality or cardiovascular death regardless of weight, Dr. Robert Baron said at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.

A 2006 meta-analysis of 43 randomized, controlled studies of exercise to treat obesity in 3,476 patients found small weight losses from exercise alone compared with no intervention. The difference between groups often did not achieve statistical significance (Cochrane Database of Syst. Rev. 2006;DOI:10.1002/14651858.CD003817.pub3). Many of the studies used smaller exercise doses than now would be considered the standard of care, said Dr. Baron, professor of medicine at the university.

The investigators then focused a more formal meta-analysis on a subset of relatively homogenous studies that typically compared exercise plus a weight-loss diet to treatment using the diet alone. They found a statistically significant, modestly better weight loss in the combination group, in which patients lost 1.1 kg more than did the diet group.

Studies that employed a higher frequency, duration, or intensity of exercise, however, produced a 1.5-kg greater weight loss in the exercise-plus-diet group. In those studies, patients in the exercise groups improved their blood pressures, fasting blood glucose measurements, and triglyceride levels regardless of whether they lost weight.

Discussions about “fit versus fat” in recent years largely originated with the 1999 Aerobics Center Longitudinal Study (ACLS), which reported mortality benefits from fitness even in overweight or obese men. In the 14-year observational study of 25,714 men, the relative risk of death in men who were fit was only 10% higher in overweight or obese men compared with normal-weight men. In men who were not fit, however, the risk of death doubled in normal-weight men, was 2.5 times higher in overweight men, and tripled in obese men compared with fit, normal-weight men (JAMA 1999;282:1547–53).

More recent studies have attempted to confirm these findings. An analysis of data on 116,564 women in the Nurses Health Study found less impressive—but still beneficial—effects of fitness in a 24-year observational study. Compared with normal-weight, active women, the relative risk of death was 1.6 in normal-weight, inactive women, 1.9 in overweight, active women, and 2.6 in overweight, inactive women (N. Engl. J. Med. 2004;351:2694–703).

A separate analysis of data on 19,173 men from the ACLS found that fitness decreased the risk of death from cardiovascular disease in patients with metabolic syndrome in any weight group (Diabetes Care 2005;28:391–7). In the normal-weight group, metabolic syndrome doubled the risk of cardiovascular mortality, but the risk was only 1.6-fold higher in fit men with metabolic syndrome compared with fit, healthy controls.

In the overweight group, fitness normalized a slightly higher risk among healthy men as a whole compared with normal-weight men. A 1.8-fold higher risk in men with metabolic syndrome became a 1.2-fold higher risk with fitness. Among obese men with or without metabolic syndrome, a nearly threefold higher risk for cardiovascular death was halved among fit men.

SAN FRANCISCO — Exercise by itself is unlikely to lead to weight loss, but becoming physically fit reduces a person's risk for mortality or cardiovascular death regardless of weight, Dr. Robert Baron said at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.

A 2006 meta-analysis of 43 randomized, controlled studies of exercise to treat obesity in 3,476 patients found small weight losses from exercise alone compared with no intervention. The difference between groups often did not achieve statistical significance (Cochrane Database of Syst. Rev. 2006;DOI:10.1002/14651858.CD003817.pub3). Many of the studies used smaller exercise doses than now would be considered the standard of care, said Dr. Baron, professor of medicine at the university.

The investigators then focused a more formal meta-analysis on a subset of relatively homogenous studies that typically compared exercise plus a weight-loss diet to treatment using the diet alone. They found a statistically significant, modestly better weight loss in the combination group, in which patients lost 1.1 kg more than did the diet group.

Studies that employed a higher frequency, duration, or intensity of exercise, however, produced a 1.5-kg greater weight loss in the exercise-plus-diet group. In those studies, patients in the exercise groups improved their blood pressures, fasting blood glucose measurements, and triglyceride levels regardless of whether they lost weight.

Discussions about “fit versus fat” in recent years largely originated with the 1999 Aerobics Center Longitudinal Study (ACLS), which reported mortality benefits from fitness even in overweight or obese men. In the 14-year observational study of 25,714 men, the relative risk of death in men who were fit was only 10% higher in overweight or obese men compared with normal-weight men. In men who were not fit, however, the risk of death doubled in normal-weight men, was 2.5 times higher in overweight men, and tripled in obese men compared with fit, normal-weight men (JAMA 1999;282:1547–53).

More recent studies have attempted to confirm these findings. An analysis of data on 116,564 women in the Nurses Health Study found less impressive—but still beneficial—effects of fitness in a 24-year observational study. Compared with normal-weight, active women, the relative risk of death was 1.6 in normal-weight, inactive women, 1.9 in overweight, active women, and 2.6 in overweight, inactive women (N. Engl. J. Med. 2004;351:2694–703).

A separate analysis of data on 19,173 men from the ACLS found that fitness decreased the risk of death from cardiovascular disease in patients with metabolic syndrome in any weight group (Diabetes Care 2005;28:391–7). In the normal-weight group, metabolic syndrome doubled the risk of cardiovascular mortality, but the risk was only 1.6-fold higher in fit men with metabolic syndrome compared with fit, healthy controls.

In the overweight group, fitness normalized a slightly higher risk among healthy men as a whole compared with normal-weight men. A 1.8-fold higher risk in men with metabolic syndrome became a 1.2-fold higher risk with fitness. Among obese men with or without metabolic syndrome, a nearly threefold higher risk for cardiovascular death was halved among fit men.

SAN FRANCISCO — Exercise by itself is unlikely to lead to weight loss, but becoming physically fit reduces a person's risk for mortality or cardiovascular death regardless of weight, Dr. Robert Baron said at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.

A 2006 meta-analysis of 43 randomized, controlled studies of exercise to treat obesity in 3,476 patients found small weight losses from exercise alone compared with no intervention. The difference between groups often did not achieve statistical significance (Cochrane Database of Syst. Rev. 2006;DOI:10.1002/14651858.CD003817.pub3). Many of the studies used smaller exercise doses than now would be considered the standard of care, said Dr. Baron, professor of medicine at the university.

The investigators then focused a more formal meta-analysis on a subset of relatively homogenous studies that typically compared exercise plus a weight-loss diet to treatment using the diet alone. They found a statistically significant, modestly better weight loss in the combination group, in which patients lost 1.1 kg more than did the diet group.

Studies that employed a higher frequency, duration, or intensity of exercise, however, produced a 1.5-kg greater weight loss in the exercise-plus-diet group. In those studies, patients in the exercise groups improved their blood pressures, fasting blood glucose measurements, and triglyceride levels regardless of whether they lost weight.

Discussions about “fit versus fat” in recent years largely originated with the 1999 Aerobics Center Longitudinal Study (ACLS), which reported mortality benefits from fitness even in overweight or obese men. In the 14-year observational study of 25,714 men, the relative risk of death in men who were fit was only 10% higher in overweight or obese men compared with normal-weight men. In men who were not fit, however, the risk of death doubled in normal-weight men, was 2.5 times higher in overweight men, and tripled in obese men compared with fit, normal-weight men (JAMA 1999;282:1547–53).

More recent studies have attempted to confirm these findings. An analysis of data on 116,564 women in the Nurses Health Study found less impressive—but still beneficial—effects of fitness in a 24-year observational study. Compared with normal-weight, active women, the relative risk of death was 1.6 in normal-weight, inactive women, 1.9 in overweight, active women, and 2.6 in overweight, inactive women (N. Engl. J. Med. 2004;351:2694–703).

A separate analysis of data on 19,173 men from the ACLS found that fitness decreased the risk of death from cardiovascular disease in patients with metabolic syndrome in any weight group (Diabetes Care 2005;28:391–7). In the normal-weight group, metabolic syndrome doubled the risk of cardiovascular mortality, but the risk was only 1.6-fold higher in fit men with metabolic syndrome compared with fit, healthy controls.

In the overweight group, fitness normalized a slightly higher risk among healthy men as a whole compared with normal-weight men. A 1.8-fold higher risk in men with metabolic syndrome became a 1.2-fold higher risk with fitness. Among obese men with or without metabolic syndrome, a nearly threefold higher risk for cardiovascular death was halved among fit men.