Bruce Jancin

CHICAGO – Deactivating the renal sympathetic nerves via a catheter-based procedure achieved impressively large and durable reductions in blood pressure in the first randomized, multicenter trial of the novel therapy in patients with resistant hypertension.

The renal sympathetic denervation procedure was straightforward and safe, and the sizeable reduction in blood pressure was maintained throughout the scheduled 6 months of follow-up. In patients treated earlier outside of the clinical trial, blood pressures have continued to drift slightly lower through 2.5 years of follow-up, raising the possibility that this procedure provides once-and-for-all treatment, Dr. Murray D. Esler said at the annual scientific sessions of the American Heart Association.

The primary endpoint in the 106-patient Symplicity HTN-2 trial was office-based blood pressure at 6 months. There was a mean 32/12 mm Hg reduction from a baseline of 178/96 mm Hg in patients in the renal denervation arm, all of whom remained on multidrug therapy. Home and ambulatory blood pressure readings followed suit, although the measured reductions were less robust.

In contrast, blood pressure was unchanged over time in patients in the control arm, even though they remained on optimally dosed multidrug antihypertensive therapy, according to Dr. Esler, associate director of the Baker IDI Heart and Diabetes Institute in Melbourne, Australia.

The encouraging results of Symplicity HTN-2 open the door to an entirely new approach to resistant hypertension, one that sidesteps the expense of lifelong therapy with multiple antihypertensive agents, the inherent limited efficacy of the drugs currently available, and compliance issues that commonly arise with multidrug therapy for a silent disease, he added.

Renal denervation therapy could be widely applicable. Roughly 15%-20% of hypertensive patients have resistant hypertension as defined by blood pressures remaining above target in spite of optimal doses of at least three antihypertensive agents, one of which should be a diuretic. This was the population enrolled in Symplicity HTN-2; in fact, nearly two-thirds of participants were on at least five antihypertensive drugs.

Future trials will evaluate renal denervation in milder forms of essential hypertension, as well as in other diseases involving activation of renal sympathetic outflow, including heart failure, cirrhosis with ascites, and chronic kidney disease.

The denervation procedure entails using standard endovascular technique to pass a proprietary radiofrequency catheter via femoral access into the renal artery lumen. The operator then delivers four to six bursts of low-power radiofrequency energy along the length of each renal artery to ablate the renal nerves, located in the adventitia of the renal artery. This results in decreased whole-body noradrenaline spillover, increased renal blood flow, and reduced plasma renin activity, the investigators noted in a published report released online simultaneously with Dr. Elser’s presentation (Lancet Nov. 17, 2010 [doi: 10.1016/S0140-6736(10)62039-9]).

No serious procedure-related complications occurred. Renal function remained unchanged during follow-up, even in patients who had mild to moderate renal impairment at baseline.

Blood pressure reductions of the magnitude achieved in Symplicity HTN-2 could, in theory, be expected to result in roughly 60% decreases in stroke and MI rates in these sorts of very-high-risk patients, according to Dr. Elser and others.

He said that the inspiration for the development of catheter-based renal denervation came from the earlier success of nonselective surgical sympathetectomy as a means of lowering blood pressure in severe hypertension in the days before modern antihypertensive drugs.

"In the current era, drugs blocking the renin-angiotensin system have moved to the fore and the sympathetic nervous system has kind of been swept into the shadows," he noted.

A U.S. clinical trial of the device therapy will begin early next year. Meanwhile, the therapy is being introduced into clinical practice in Australia and Europe. Dr. Elser said he would not be surprised to see a turf battle between interventional cardiologists and interventional radiologists over who performs the procedure.

Discussant Dr. Suzanne Oparil said, "This is an extremely important study. It has a number of great strengths and the potential to really revolutionize the way we deal with treatment-resistant hypertension."

The absence of adverse events, given the fact that 24 centers were involved in the trial, is a remarkable finding that speaks to the procedure’s safety and ease, observed Dr. Oparil, professor of medicine, physiology, and biophysics and director of the vascular biology and hypertension program at the University of Alabama, Birmingham. However, several limitations of the study were of concern, particularly the fact that only 17% of patients were being treated with aldosterone antagonists, which could be an indication that the patient population was not truly drug resistant.

Dr. Esler disclosed that he has received consulting fees and travel expenses from Ardian, which sponsored the Symplicity HTN-2 trial. Dr. Oparil is a consultant to Amylin, Boehringer-Ingelheim, Daiichi Sankyo, Forest Laboratories, Merck, NicOx, Novartis, and VIVUS.

CHICAGO – Deactivating the renal sympathetic nerves via a catheter-based procedure achieved impressively large and durable reductions in blood pressure in the first randomized, multicenter trial of the novel therapy in patients with resistant hypertension.

The renal sympathetic denervation procedure was straightforward and safe, and the sizeable reduction in blood pressure was maintained throughout the scheduled 6 months of follow-up. In patients treated earlier outside of the clinical trial, blood pressures have continued to drift slightly lower through 2.5 years of follow-up, raising the possibility that this procedure provides once-and-for-all treatment, Dr. Murray D. Esler said at the annual scientific sessions of the American Heart Association.

The primary endpoint in the 106-patient Symplicity HTN-2 trial was office-based blood pressure at 6 months. There was a mean 32/12 mm Hg reduction from a baseline of 178/96 mm Hg in patients in the renal denervation arm, all of whom remained on multidrug therapy. Home and ambulatory blood pressure readings followed suit, although the measured reductions were less robust.

In contrast, blood pressure was unchanged over time in patients in the control arm, even though they remained on optimally dosed multidrug antihypertensive therapy, according to Dr. Esler, associate director of the Baker IDI Heart and Diabetes Institute in Melbourne, Australia.

The encouraging results of Symplicity HTN-2 open the door to an entirely new approach to resistant hypertension, one that sidesteps the expense of lifelong therapy with multiple antihypertensive agents, the inherent limited efficacy of the drugs currently available, and compliance issues that commonly arise with multidrug therapy for a silent disease, he added.

Renal denervation therapy could be widely applicable. Roughly 15%-20% of hypertensive patients have resistant hypertension as defined by blood pressures remaining above target in spite of optimal doses of at least three antihypertensive agents, one of which should be a diuretic. This was the population enrolled in Symplicity HTN-2; in fact, nearly two-thirds of participants were on at least five antihypertensive drugs.

Future trials will evaluate renal denervation in milder forms of essential hypertension, as well as in other diseases involving activation of renal sympathetic outflow, including heart failure, cirrhosis with ascites, and chronic kidney disease.

The denervation procedure entails using standard endovascular technique to pass a proprietary radiofrequency catheter via femoral access into the renal artery lumen. The operator then delivers four to six bursts of low-power radiofrequency energy along the length of each renal artery to ablate the renal nerves, located in the adventitia of the renal artery. This results in decreased whole-body noradrenaline spillover, increased renal blood flow, and reduced plasma renin activity, the investigators noted in a published report released online simultaneously with Dr. Elser’s presentation (Lancet Nov. 17, 2010 [doi: 10.1016/S0140-6736(10)62039-9]).

No serious procedure-related complications occurred. Renal function remained unchanged during follow-up, even in patients who had mild to moderate renal impairment at baseline.

Blood pressure reductions of the magnitude achieved in Symplicity HTN-2 could, in theory, be expected to result in roughly 60% decreases in stroke and MI rates in these sorts of very-high-risk patients, according to Dr. Elser and others.

He said that the inspiration for the development of catheter-based renal denervation came from the earlier success of nonselective surgical sympathetectomy as a means of lowering blood pressure in severe hypertension in the days before modern antihypertensive drugs.

"In the current era, drugs blocking the renin-angiotensin system have moved to the fore and the sympathetic nervous system has kind of been swept into the shadows," he noted.

A U.S. clinical trial of the device therapy will begin early next year. Meanwhile, the therapy is being introduced into clinical practice in Australia and Europe. Dr. Elser said he would not be surprised to see a turf battle between interventional cardiologists and interventional radiologists over who performs the procedure.

Discussant Dr. Suzanne Oparil said, "This is an extremely important study. It has a number of great strengths and the potential to really revolutionize the way we deal with treatment-resistant hypertension."

The absence of adverse events, given the fact that 24 centers were involved in the trial, is a remarkable finding that speaks to the procedure’s safety and ease, observed Dr. Oparil, professor of medicine, physiology, and biophysics and director of the vascular biology and hypertension program at the University of Alabama, Birmingham. However, several limitations of the study were of concern, particularly the fact that only 17% of patients were being treated with aldosterone antagonists, which could be an indication that the patient population was not truly drug resistant.

Dr. Esler disclosed that he has received consulting fees and travel expenses from Ardian, which sponsored the Symplicity HTN-2 trial. Dr. Oparil is a consultant to Amylin, Boehringer-Ingelheim, Daiichi Sankyo, Forest Laboratories, Merck, NicOx, Novartis, and VIVUS.

CHICAGO – Deactivating the renal sympathetic nerves via a catheter-based procedure achieved impressively large and durable reductions in blood pressure in the first randomized, multicenter trial of the novel therapy in patients with resistant hypertension.

The renal sympathetic denervation procedure was straightforward and safe, and the sizeable reduction in blood pressure was maintained throughout the scheduled 6 months of follow-up. In patients treated earlier outside of the clinical trial, blood pressures have continued to drift slightly lower through 2.5 years of follow-up, raising the possibility that this procedure provides once-and-for-all treatment, Dr. Murray D. Esler said at the annual scientific sessions of the American Heart Association.

The primary endpoint in the 106-patient Symplicity HTN-2 trial was office-based blood pressure at 6 months. There was a mean 32/12 mm Hg reduction from a baseline of 178/96 mm Hg in patients in the renal denervation arm, all of whom remained on multidrug therapy. Home and ambulatory blood pressure readings followed suit, although the measured reductions were less robust.

In contrast, blood pressure was unchanged over time in patients in the control arm, even though they remained on optimally dosed multidrug antihypertensive therapy, according to Dr. Esler, associate director of the Baker IDI Heart and Diabetes Institute in Melbourne, Australia.

The encouraging results of Symplicity HTN-2 open the door to an entirely new approach to resistant hypertension, one that sidesteps the expense of lifelong therapy with multiple antihypertensive agents, the inherent limited efficacy of the drugs currently available, and compliance issues that commonly arise with multidrug therapy for a silent disease, he added.

Renal denervation therapy could be widely applicable. Roughly 15%-20% of hypertensive patients have resistant hypertension as defined by blood pressures remaining above target in spite of optimal doses of at least three antihypertensive agents, one of which should be a diuretic. This was the population enrolled in Symplicity HTN-2; in fact, nearly two-thirds of participants were on at least five antihypertensive drugs.

Future trials will evaluate renal denervation in milder forms of essential hypertension, as well as in other diseases involving activation of renal sympathetic outflow, including heart failure, cirrhosis with ascites, and chronic kidney disease.

The denervation procedure entails using standard endovascular technique to pass a proprietary radiofrequency catheter via femoral access into the renal artery lumen. The operator then delivers four to six bursts of low-power radiofrequency energy along the length of each renal artery to ablate the renal nerves, located in the adventitia of the renal artery. This results in decreased whole-body noradrenaline spillover, increased renal blood flow, and reduced plasma renin activity, the investigators noted in a published report released online simultaneously with Dr. Elser’s presentation (Lancet Nov. 17, 2010 [doi: 10.1016/S0140-6736(10)62039-9]).

No serious procedure-related complications occurred. Renal function remained unchanged during follow-up, even in patients who had mild to moderate renal impairment at baseline.

Blood pressure reductions of the magnitude achieved in Symplicity HTN-2 could, in theory, be expected to result in roughly 60% decreases in stroke and MI rates in these sorts of very-high-risk patients, according to Dr. Elser and others.

He said that the inspiration for the development of catheter-based renal denervation came from the earlier success of nonselective surgical sympathetectomy as a means of lowering blood pressure in severe hypertension in the days before modern antihypertensive drugs.

"In the current era, drugs blocking the renin-angiotensin system have moved to the fore and the sympathetic nervous system has kind of been swept into the shadows," he noted.

A U.S. clinical trial of the device therapy will begin early next year. Meanwhile, the therapy is being introduced into clinical practice in Australia and Europe. Dr. Elser said he would not be surprised to see a turf battle between interventional cardiologists and interventional radiologists over who performs the procedure.

Discussant Dr. Suzanne Oparil said, "This is an extremely important study. It has a number of great strengths and the potential to really revolutionize the way we deal with treatment-resistant hypertension."

The absence of adverse events, given the fact that 24 centers were involved in the trial, is a remarkable finding that speaks to the procedure’s safety and ease, observed Dr. Oparil, professor of medicine, physiology, and biophysics and director of the vascular biology and hypertension program at the University of Alabama, Birmingham. However, several limitations of the study were of concern, particularly the fact that only 17% of patients were being treated with aldosterone antagonists, which could be an indication that the patient population was not truly drug resistant.

Dr. Esler disclosed that he has received consulting fees and travel expenses from Ardian, which sponsored the Symplicity HTN-2 trial. Dr. Oparil is a consultant to Amylin, Boehringer-Ingelheim, Daiichi Sankyo, Forest Laboratories, Merck, NicOx, Novartis, and VIVUS.

DENVER – Daily self-administered vaginal danazol effectively decreased pain symptoms caused by rectovaginal endometriosis that persisted despite insertion of a levonorgestrel-releasing IUD, a small, prospective, self-controlled pilot study has shown.

The levonorgestrel-releasing IUD (Mirena) is indicated as a contraceptive, and also to treat heavy periods in women who choose to have an IUD. However, the device is also seeing expanding off-label use as a treatment for endometriosis. Several studies indicate the hormone-releasing IUD is effective at improving endometriosis-related pain symptoms in many women who don’t want to resort to oral or injectable medications (Contraception 2010; 81:117-22). But for the one-quarter to one-third of patients who request device removal after 6 months because of inadequate pain relief, what’s the next option?

That was the question Dr. Simone Ferrero and his colleagues set out to answer in a study he presented at the annual meeting of the American Society for Reproductive Medicine.

He reported on 15 women with rectovaginal endometriosis and chronic pelvic pain, deep dyspareunia, dysmenorrhea, and difficulty in defecating who remained symptomatic despite insertion of Mirena. At the time of study enrollment, they had been on the levonorgestrel-releasing IUD for a mean of 8.2 months and indicated they were either "dissatisfied" or "very dissatisfied" with it. They were then placed on vaginal danazol (Danocrine) at 100 mg/day.

After 3 months of dual therapy, patients reported a significant progressive decrease in mean pain scores on a visual analog scale for chronic pelvic pain, dysmenorrhea, and dyspareunia compared with baseline, as well as a nonsignificant trend for less intense dyschezia, according to Dr. Ferrero of San Martino Hospital and the University of Genoa (Italy).

After 6 months, the intensity of all of these symptoms was further diminished, and the reduction in difficulty in defecation had achieved significance. The volume of rectovaginal nodules was significantly reduced compared with baseline.

The most common treatment-related adverse events were dermatologic: seborrhea, acne, and/or oily hair in four patients, headache in three, weight gain in excess of 3 kg in two women, and vaginal irritation in two. No adverse effects were noted in lipid profiles, liver function, or clotting factors.

One patient didn’t complete the 6-month study, opting instead for endometriosis surgery at month 5. But 12 of the 15 subjects pronounced themselves satisfied with the dual therapy and opted to continue with it after completing the 6-month study.

The major remaining question unanswered by this or other studies is whether the improvement in pain symptoms will continue for the entire 5-year life of the coil, he noted.

Dr. Ferrero said he had no relevant financial conflicts of interest.

DENVER – Daily self-administered vaginal danazol effectively decreased pain symptoms caused by rectovaginal endometriosis that persisted despite insertion of a levonorgestrel-releasing IUD, a small, prospective, self-controlled pilot study has shown.

The levonorgestrel-releasing IUD (Mirena) is indicated as a contraceptive, and also to treat heavy periods in women who choose to have an IUD. However, the device is also seeing expanding off-label use as a treatment for endometriosis. Several studies indicate the hormone-releasing IUD is effective at improving endometriosis-related pain symptoms in many women who don’t want to resort to oral or injectable medications (Contraception 2010; 81:117-22). But for the one-quarter to one-third of patients who request device removal after 6 months because of inadequate pain relief, what’s the next option?

That was the question Dr. Simone Ferrero and his colleagues set out to answer in a study he presented at the annual meeting of the American Society for Reproductive Medicine.

He reported on 15 women with rectovaginal endometriosis and chronic pelvic pain, deep dyspareunia, dysmenorrhea, and difficulty in defecating who remained symptomatic despite insertion of Mirena. At the time of study enrollment, they had been on the levonorgestrel-releasing IUD for a mean of 8.2 months and indicated they were either "dissatisfied" or "very dissatisfied" with it. They were then placed on vaginal danazol (Danocrine) at 100 mg/day.

After 3 months of dual therapy, patients reported a significant progressive decrease in mean pain scores on a visual analog scale for chronic pelvic pain, dysmenorrhea, and dyspareunia compared with baseline, as well as a nonsignificant trend for less intense dyschezia, according to Dr. Ferrero of San Martino Hospital and the University of Genoa (Italy).

After 6 months, the intensity of all of these symptoms was further diminished, and the reduction in difficulty in defecation had achieved significance. The volume of rectovaginal nodules was significantly reduced compared with baseline.

The most common treatment-related adverse events were dermatologic: seborrhea, acne, and/or oily hair in four patients, headache in three, weight gain in excess of 3 kg in two women, and vaginal irritation in two. No adverse effects were noted in lipid profiles, liver function, or clotting factors.

One patient didn’t complete the 6-month study, opting instead for endometriosis surgery at month 5. But 12 of the 15 subjects pronounced themselves satisfied with the dual therapy and opted to continue with it after completing the 6-month study.

The major remaining question unanswered by this or other studies is whether the improvement in pain symptoms will continue for the entire 5-year life of the coil, he noted.

Dr. Ferrero said he had no relevant financial conflicts of interest.

DENVER – Daily self-administered vaginal danazol effectively decreased pain symptoms caused by rectovaginal endometriosis that persisted despite insertion of a levonorgestrel-releasing IUD, a small, prospective, self-controlled pilot study has shown.

The levonorgestrel-releasing IUD (Mirena) is indicated as a contraceptive, and also to treat heavy periods in women who choose to have an IUD. However, the device is also seeing expanding off-label use as a treatment for endometriosis. Several studies indicate the hormone-releasing IUD is effective at improving endometriosis-related pain symptoms in many women who don’t want to resort to oral or injectable medications (Contraception 2010; 81:117-22). But for the one-quarter to one-third of patients who request device removal after 6 months because of inadequate pain relief, what’s the next option?

That was the question Dr. Simone Ferrero and his colleagues set out to answer in a study he presented at the annual meeting of the American Society for Reproductive Medicine.

He reported on 15 women with rectovaginal endometriosis and chronic pelvic pain, deep dyspareunia, dysmenorrhea, and difficulty in defecating who remained symptomatic despite insertion of Mirena. At the time of study enrollment, they had been on the levonorgestrel-releasing IUD for a mean of 8.2 months and indicated they were either "dissatisfied" or "very dissatisfied" with it. They were then placed on vaginal danazol (Danocrine) at 100 mg/day.

After 3 months of dual therapy, patients reported a significant progressive decrease in mean pain scores on a visual analog scale for chronic pelvic pain, dysmenorrhea, and dyspareunia compared with baseline, as well as a nonsignificant trend for less intense dyschezia, according to Dr. Ferrero of San Martino Hospital and the University of Genoa (Italy).

After 6 months, the intensity of all of these symptoms was further diminished, and the reduction in difficulty in defecation had achieved significance. The volume of rectovaginal nodules was significantly reduced compared with baseline.

The most common treatment-related adverse events were dermatologic: seborrhea, acne, and/or oily hair in four patients, headache in three, weight gain in excess of 3 kg in two women, and vaginal irritation in two. No adverse effects were noted in lipid profiles, liver function, or clotting factors.

One patient didn’t complete the 6-month study, opting instead for endometriosis surgery at month 5. But 12 of the 15 subjects pronounced themselves satisfied with the dual therapy and opted to continue with it after completing the 6-month study.

The major remaining question unanswered by this or other studies is whether the improvement in pain symptoms will continue for the entire 5-year life of the coil, he noted.

Dr. Ferrero said he had no relevant financial conflicts of interest.

CHICAGO – Contrary to conventional wisdom, the use of automated external defibrillators for in-hospital cardiac arrests does not improve survival, a large national study shows.

In fact, just the opposite is true. The use of automated external defibrillators (AEDs) for cardiac arrests occurring on general hospital wards actually proved harmful overall, Dr. Paul S. Chan reported at the annual scientific sessions of the American Heart Association.

The study (JAMA 2010 Nov. 15 [doi:10.1001/jama.2010.1576]), published simultaneously with Dr. Chan’s presentation in Chicago, involved 11,695 patients who experienced cardiac arrest in 204 U.S. hospitals with AEDs, which were utilized in 39% of cases. Survival to hospital discharge occurred in 16.3% of patients in whom an AED was used to assess patients and deliver a shock when indicated compared with 19.3% when it was not. The resultant 15% adjusted lower likelihood of survival with AED use was both statistically and clinically significant.

Moreover, among patients who survived to discharge, AED use had no impact on the rate of major neurologic disability, according to Dr. Chan of Saint Luke’s Mid America Heart Institute, Kansas City, Mo.

The data came from the AHA-sponsored National Registry of Cardiopulmonary Resuscitation, a large prospective quality improvement registry. The study was conducted because even though AEDs have repeatedly been shown to improve survival in certain out-of-hospital settings, there has been a lack of data demonstrating that the devices are beneficial for in-hospital cardiac arrests. Until now, that has been assumed to be the case.

Meanwhile, for the best part of a decade, U.S. hospitals have bought more than 10,000 AEDs per year for placement on general medical wards. Recent industry projections were for 9%-15% annual sales growth to hospitals over the next 5 years.

The explanation for the surprising lack of benefit for AEDS in the in-hospital cardiac arrests probably lies in the very different nature of the initial cardiac arrest rhythms occurring in out-of-hospital versus in-hospital settings. Various studies indicate 45%-71% of patients with out-of-hospital cardiac arrest have a shockable rhythm, such as ventricular fibrillation or pulseless ventricular tachycardia. That was the case in less than 18% of patients with in-hospital cardiac arrest.

In hospitalized patients with a shockable rhythm, the use of AEDs had no effect on survival in the study. In contrast, among the 82% of patients who had an in-hospital cardiac arrest marked by a nonshockable rhythm, such as asystole or pulseless electrical activity, the survival rate was 10.4% with AED use, compared with 15.4% with no AED use.

The AED does not deliver shocks to patients who have an unshockable rhythm, but CPR needs to be temporarily halted while the device’s automated rhythm diagnosis feature is at work. It’s likely that this interruption of chest compressions for up to 45-50 seconds during the first critical minutes of the resuscitation effort provides the mechanistic explanation for the lower survival rate in patients with nonshockable rhythms assessed by AED, according to Dr. Chan.

"While randomized controlled trials are needed to confirm these findings, current use of AEDs in hospitalized patients may warrant reconsideration," he concluded.

"This study probably is a practice changer," session cochair Dr. Karl B. Kern said in an interview.

"We’ve really struggled with how to best reach those patients who are not being monitored when they have a cardiac arrest in the hospital. This study would suggest that the strategy that’s out there right now is not very effective," said Dr. Kern, professor of medicine and interim chief of cardiology at the University of Arizona, Tucson, and vice chair of the AHA Cardiopulmonary, Critical Care, Perioperative and Resuscitation Council.

"I think it’s the same message we’ve been saying for a while now, that chest compressions are king, particularly for nonshockable rhythms, which the majority of in-hospital cardiac arrests are. Chest compressions are what save those patients, and anything that interrupts them comes at a cost," he explained.

The study was funded by the AHA. Dr. Chan declared he has no financial conflicts.

CHICAGO – Contrary to conventional wisdom, the use of automated external defibrillators for in-hospital cardiac arrests does not improve survival, a large national study shows.

In fact, just the opposite is true. The use of automated external defibrillators (AEDs) for cardiac arrests occurring on general hospital wards actually proved harmful overall, Dr. Paul S. Chan reported at the annual scientific sessions of the American Heart Association.

The study (JAMA 2010 Nov. 15 [doi:10.1001/jama.2010.1576]), published simultaneously with Dr. Chan’s presentation in Chicago, involved 11,695 patients who experienced cardiac arrest in 204 U.S. hospitals with AEDs, which were utilized in 39% of cases. Survival to hospital discharge occurred in 16.3% of patients in whom an AED was used to assess patients and deliver a shock when indicated compared with 19.3% when it was not. The resultant 15% adjusted lower likelihood of survival with AED use was both statistically and clinically significant.

Moreover, among patients who survived to discharge, AED use had no impact on the rate of major neurologic disability, according to Dr. Chan of Saint Luke’s Mid America Heart Institute, Kansas City, Mo.

The data came from the AHA-sponsored National Registry of Cardiopulmonary Resuscitation, a large prospective quality improvement registry. The study was conducted because even though AEDs have repeatedly been shown to improve survival in certain out-of-hospital settings, there has been a lack of data demonstrating that the devices are beneficial for in-hospital cardiac arrests. Until now, that has been assumed to be the case.

Meanwhile, for the best part of a decade, U.S. hospitals have bought more than 10,000 AEDs per year for placement on general medical wards. Recent industry projections were for 9%-15% annual sales growth to hospitals over the next 5 years.

The explanation for the surprising lack of benefit for AEDS in the in-hospital cardiac arrests probably lies in the very different nature of the initial cardiac arrest rhythms occurring in out-of-hospital versus in-hospital settings. Various studies indicate 45%-71% of patients with out-of-hospital cardiac arrest have a shockable rhythm, such as ventricular fibrillation or pulseless ventricular tachycardia. That was the case in less than 18% of patients with in-hospital cardiac arrest.

In hospitalized patients with a shockable rhythm, the use of AEDs had no effect on survival in the study. In contrast, among the 82% of patients who had an in-hospital cardiac arrest marked by a nonshockable rhythm, such as asystole or pulseless electrical activity, the survival rate was 10.4% with AED use, compared with 15.4% with no AED use.

The AED does not deliver shocks to patients who have an unshockable rhythm, but CPR needs to be temporarily halted while the device’s automated rhythm diagnosis feature is at work. It’s likely that this interruption of chest compressions for up to 45-50 seconds during the first critical minutes of the resuscitation effort provides the mechanistic explanation for the lower survival rate in patients with nonshockable rhythms assessed by AED, according to Dr. Chan.

"While randomized controlled trials are needed to confirm these findings, current use of AEDs in hospitalized patients may warrant reconsideration," he concluded.

"This study probably is a practice changer," session cochair Dr. Karl B. Kern said in an interview.

"We’ve really struggled with how to best reach those patients who are not being monitored when they have a cardiac arrest in the hospital. This study would suggest that the strategy that’s out there right now is not very effective," said Dr. Kern, professor of medicine and interim chief of cardiology at the University of Arizona, Tucson, and vice chair of the AHA Cardiopulmonary, Critical Care, Perioperative and Resuscitation Council.

"I think it’s the same message we’ve been saying for a while now, that chest compressions are king, particularly for nonshockable rhythms, which the majority of in-hospital cardiac arrests are. Chest compressions are what save those patients, and anything that interrupts them comes at a cost," he explained.

The study was funded by the AHA. Dr. Chan declared he has no financial conflicts.

CHICAGO – Contrary to conventional wisdom, the use of automated external defibrillators for in-hospital cardiac arrests does not improve survival, a large national study shows.

In fact, just the opposite is true. The use of automated external defibrillators (AEDs) for cardiac arrests occurring on general hospital wards actually proved harmful overall, Dr. Paul S. Chan reported at the annual scientific sessions of the American Heart Association.

The study (JAMA 2010 Nov. 15 [doi:10.1001/jama.2010.1576]), published simultaneously with Dr. Chan’s presentation in Chicago, involved 11,695 patients who experienced cardiac arrest in 204 U.S. hospitals with AEDs, which were utilized in 39% of cases. Survival to hospital discharge occurred in 16.3% of patients in whom an AED was used to assess patients and deliver a shock when indicated compared with 19.3% when it was not. The resultant 15% adjusted lower likelihood of survival with AED use was both statistically and clinically significant.

Moreover, among patients who survived to discharge, AED use had no impact on the rate of major neurologic disability, according to Dr. Chan of Saint Luke’s Mid America Heart Institute, Kansas City, Mo.

The data came from the AHA-sponsored National Registry of Cardiopulmonary Resuscitation, a large prospective quality improvement registry. The study was conducted because even though AEDs have repeatedly been shown to improve survival in certain out-of-hospital settings, there has been a lack of data demonstrating that the devices are beneficial for in-hospital cardiac arrests. Until now, that has been assumed to be the case.

Meanwhile, for the best part of a decade, U.S. hospitals have bought more than 10,000 AEDs per year for placement on general medical wards. Recent industry projections were for 9%-15% annual sales growth to hospitals over the next 5 years.

The explanation for the surprising lack of benefit for AEDS in the in-hospital cardiac arrests probably lies in the very different nature of the initial cardiac arrest rhythms occurring in out-of-hospital versus in-hospital settings. Various studies indicate 45%-71% of patients with out-of-hospital cardiac arrest have a shockable rhythm, such as ventricular fibrillation or pulseless ventricular tachycardia. That was the case in less than 18% of patients with in-hospital cardiac arrest.

In hospitalized patients with a shockable rhythm, the use of AEDs had no effect on survival in the study. In contrast, among the 82% of patients who had an in-hospital cardiac arrest marked by a nonshockable rhythm, such as asystole or pulseless electrical activity, the survival rate was 10.4% with AED use, compared with 15.4% with no AED use.

The AED does not deliver shocks to patients who have an unshockable rhythm, but CPR needs to be temporarily halted while the device’s automated rhythm diagnosis feature is at work. It’s likely that this interruption of chest compressions for up to 45-50 seconds during the first critical minutes of the resuscitation effort provides the mechanistic explanation for the lower survival rate in patients with nonshockable rhythms assessed by AED, according to Dr. Chan.

"While randomized controlled trials are needed to confirm these findings, current use of AEDs in hospitalized patients may warrant reconsideration," he concluded.

"This study probably is a practice changer," session cochair Dr. Karl B. Kern said in an interview.

"We’ve really struggled with how to best reach those patients who are not being monitored when they have a cardiac arrest in the hospital. This study would suggest that the strategy that’s out there right now is not very effective," said Dr. Kern, professor of medicine and interim chief of cardiology at the University of Arizona, Tucson, and vice chair of the AHA Cardiopulmonary, Critical Care, Perioperative and Resuscitation Council.

"I think it’s the same message we’ve been saying for a while now, that chest compressions are king, particularly for nonshockable rhythms, which the majority of in-hospital cardiac arrests are. Chest compressions are what save those patients, and anything that interrupts them comes at a cost," he explained.

The study was funded by the AHA. Dr. Chan declared he has no financial conflicts.

CHICAGO – Contrary to conventional wisdom, the use of automated external defibrillators for in-hospital cardiac arrests does not improve survival, a large national study shows.

In fact, just the opposite is true. The use of automated external defibrillators (AEDs) for cardiac arrests occurring on general hospital wards actually proved harmful overall, Dr. Paul S. Chan reported at the annual scientific sessions of the American Heart Association.

The study (JAMA 2010 Nov. 15 [doi:10.1001/jama.2010.1576]), published simultaneously with Dr. Chan’s presentation in Chicago, involved 11,695 patients who experienced cardiac arrest in 204 U.S. hospitals with AEDs, which were utilized in 39% of cases. Survival to hospital discharge occurred in 16.3% of patients in whom an AED was used to assess patients and deliver a shock when indicated compared with 19.3% when it was not. The resultant 15% adjusted lower likelihood of survival with AED use was both statistically and clinically significant.

Moreover, among patients who survived to discharge, AED use had no impact on the rate of major neurologic disability, according to Dr. Chan of Saint Luke’s Mid America Heart Institute, Kansas City, Mo.

The data came from the AHA-sponsored National Registry of Cardiopulmonary Resuscitation, a large prospective quality improvement registry. The study was conducted because even though AEDs have repeatedly been shown to improve survival in certain out-of-hospital settings, there has been a lack of data demonstrating that the devices are beneficial for in-hospital cardiac arrests. Until now, that has been assumed to be the case.

Meanwhile, for the best part of a decade, U.S. hospitals have bought more than 10,000 AEDs per year for placement on general medical wards. Recent industry projections were for 9%-15% annual sales growth to hospitals over the next 5 years.

The explanation for the surprising lack of benefit for AEDS in the in-hospital cardiac arrests probably lies in the very different nature of the initial cardiac arrest rhythms occurring in out-of-hospital versus in-hospital settings. Various studies indicate 45%-71% of patients with out-of-hospital cardiac arrest have a shockable rhythm, such as ventricular fibrillation or pulseless ventricular tachycardia. That was the case in less than 18% of patients with in-hospital cardiac arrest.

In hospitalized patients with a shockable rhythm, the use of AEDs had no effect on survival in the study. In contrast, among the 82% of patients who had an in-hospital cardiac arrest marked by a nonshockable rhythm, such as asystole or pulseless electrical activity, the survival rate was 10.4% with AED use, compared with 15.4% with no AED use.

The AED does not deliver shocks to patients who have an unshockable rhythm, but CPR needs to be temporarily halted while the device’s automated rhythm diagnosis feature is at work. It’s likely that this interruption of chest compressions for up to 45-50 seconds during the first critical minutes of the resuscitation effort provides the mechanistic explanation for the lower survival rate in patients with nonshockable rhythms assessed by AED, according to Dr. Chan.

"While randomized controlled trials are needed to confirm these findings, current use of AEDs in hospitalized patients may warrant reconsideration," he concluded.

"This study probably is a practice changer," session cochair Dr. Karl B. Kern said in an interview.

"We’ve really struggled with how to best reach those patients who are not being monitored when they have a cardiac arrest in the hospital. This study would suggest that the strategy that’s out there right now is not very effective," said Dr. Kern, professor of medicine and interim chief of cardiology at the University of Arizona, Tucson, and vice chair of the AHA Cardiopulmonary, Critical Care, Perioperative and Resuscitation Council.

"I think it’s the same message we’ve been saying for a while now, that chest compressions are king, particularly for nonshockable rhythms, which the majority of in-hospital cardiac arrests are. Chest compressions are what save those patients, and anything that interrupts them comes at a cost," he explained.

The study was funded by the AHA. Dr. Chan declared he has no financial conflicts.

CHICAGO – Contrary to conventional wisdom, the use of automated external defibrillators for in-hospital cardiac arrests does not improve survival, a large national study shows.

In fact, just the opposite is true. The use of automated external defibrillators (AEDs) for cardiac arrests occurring on general hospital wards actually proved harmful overall, Dr. Paul S. Chan reported at the annual scientific sessions of the American Heart Association.

The study (JAMA 2010 Nov. 15 [doi:10.1001/jama.2010.1576]), published simultaneously with Dr. Chan’s presentation in Chicago, involved 11,695 patients who experienced cardiac arrest in 204 U.S. hospitals with AEDs, which were utilized in 39% of cases. Survival to hospital discharge occurred in 16.3% of patients in whom an AED was used to assess patients and deliver a shock when indicated compared with 19.3% when it was not. The resultant 15% adjusted lower likelihood of survival with AED use was both statistically and clinically significant.

Moreover, among patients who survived to discharge, AED use had no impact on the rate of major neurologic disability, according to Dr. Chan of Saint Luke’s Mid America Heart Institute, Kansas City, Mo.

The data came from the AHA-sponsored National Registry of Cardiopulmonary Resuscitation, a large prospective quality improvement registry. The study was conducted because even though AEDs have repeatedly been shown to improve survival in certain out-of-hospital settings, there has been a lack of data demonstrating that the devices are beneficial for in-hospital cardiac arrests. Until now, that has been assumed to be the case.

Meanwhile, for the best part of a decade, U.S. hospitals have bought more than 10,000 AEDs per year for placement on general medical wards. Recent industry projections were for 9%-15% annual sales growth to hospitals over the next 5 years.

The explanation for the surprising lack of benefit for AEDS in the in-hospital cardiac arrests probably lies in the very different nature of the initial cardiac arrest rhythms occurring in out-of-hospital versus in-hospital settings. Various studies indicate 45%-71% of patients with out-of-hospital cardiac arrest have a shockable rhythm, such as ventricular fibrillation or pulseless ventricular tachycardia. That was the case in less than 18% of patients with in-hospital cardiac arrest.

In hospitalized patients with a shockable rhythm, the use of AEDs had no effect on survival in the study. In contrast, among the 82% of patients who had an in-hospital cardiac arrest marked by a nonshockable rhythm, such as asystole or pulseless electrical activity, the survival rate was 10.4% with AED use, compared with 15.4% with no AED use.

The AED does not deliver shocks to patients who have an unshockable rhythm, but CPR needs to be temporarily halted while the device’s automated rhythm diagnosis feature is at work. It’s likely that this interruption of chest compressions for up to 45-50 seconds during the first critical minutes of the resuscitation effort provides the mechanistic explanation for the lower survival rate in patients with nonshockable rhythms assessed by AED, according to Dr. Chan.

"While randomized controlled trials are needed to confirm these findings, current use of AEDs in hospitalized patients may warrant reconsideration," he concluded.

"This study probably is a practice changer," session cochair Dr. Karl B. Kern said in an interview.

"We’ve really struggled with how to best reach those patients who are not being monitored when they have a cardiac arrest in the hospital. This study would suggest that the strategy that’s out there right now is not very effective," said Dr. Kern, professor of medicine and interim chief of cardiology at the University of Arizona, Tucson, and vice chair of the AHA Cardiopulmonary, Critical Care, Perioperative and Resuscitation Council.

"I think it’s the same message we’ve been saying for a while now, that chest compressions are king, particularly for nonshockable rhythms, which the majority of in-hospital cardiac arrests are. Chest compressions are what save those patients, and anything that interrupts them comes at a cost," he explained.

The study was funded by the AHA. Dr. Chan declared he has no financial conflicts.

CHICAGO – Contrary to conventional wisdom, the use of automated external defibrillators for in-hospital cardiac arrests does not improve survival, a large national study shows.

In fact, just the opposite is true. The use of automated external defibrillators (AEDs) for cardiac arrests occurring on general hospital wards actually proved harmful overall, Dr. Paul S. Chan reported at the annual scientific sessions of the American Heart Association.

The study (JAMA 2010 Nov. 15 [doi:10.1001/jama.2010.1576]), published simultaneously with Dr. Chan’s presentation in Chicago, involved 11,695 patients who experienced cardiac arrest in 204 U.S. hospitals with AEDs, which were utilized in 39% of cases. Survival to hospital discharge occurred in 16.3% of patients in whom an AED was used to assess patients and deliver a shock when indicated compared with 19.3% when it was not. The resultant 15% adjusted lower likelihood of survival with AED use was both statistically and clinically significant.

Moreover, among patients who survived to discharge, AED use had no impact on the rate of major neurologic disability, according to Dr. Chan of Saint Luke’s Mid America Heart Institute, Kansas City, Mo.

The data came from the AHA-sponsored National Registry of Cardiopulmonary Resuscitation, a large prospective quality improvement registry. The study was conducted because even though AEDs have repeatedly been shown to improve survival in certain out-of-hospital settings, there has been a lack of data demonstrating that the devices are beneficial for in-hospital cardiac arrests. Until now, that has been assumed to be the case.

Meanwhile, for the best part of a decade, U.S. hospitals have bought more than 10,000 AEDs per year for placement on general medical wards. Recent industry projections were for 9%-15% annual sales growth to hospitals over the next 5 years.

The explanation for the surprising lack of benefit for AEDS in the in-hospital cardiac arrests probably lies in the very different nature of the initial cardiac arrest rhythms occurring in out-of-hospital versus in-hospital settings. Various studies indicate 45%-71% of patients with out-of-hospital cardiac arrest have a shockable rhythm, such as ventricular fibrillation or pulseless ventricular tachycardia. That was the case in less than 18% of patients with in-hospital cardiac arrest.

In hospitalized patients with a shockable rhythm, the use of AEDs had no effect on survival in the study. In contrast, among the 82% of patients who had an in-hospital cardiac arrest marked by a nonshockable rhythm, such as asystole or pulseless electrical activity, the survival rate was 10.4% with AED use, compared with 15.4% with no AED use.

The AED does not deliver shocks to patients who have an unshockable rhythm, but CPR needs to be temporarily halted while the device’s automated rhythm diagnosis feature is at work. It’s likely that this interruption of chest compressions for up to 45-50 seconds during the first critical minutes of the resuscitation effort provides the mechanistic explanation for the lower survival rate in patients with nonshockable rhythms assessed by AED, according to Dr. Chan.

"While randomized controlled trials are needed to confirm these findings, current use of AEDs in hospitalized patients may warrant reconsideration," he concluded.

"This study probably is a practice changer," session cochair Dr. Karl B. Kern said in an interview.

"We’ve really struggled with how to best reach those patients who are not being monitored when they have a cardiac arrest in the hospital. This study would suggest that the strategy that’s out there right now is not very effective," said Dr. Kern, professor of medicine and interim chief of cardiology at the University of Arizona, Tucson, and vice chair of the AHA Cardiopulmonary, Critical Care, Perioperative and Resuscitation Council.

"I think it’s the same message we’ve been saying for a while now, that chest compressions are king, particularly for nonshockable rhythms, which the majority of in-hospital cardiac arrests are. Chest compressions are what save those patients, and anything that interrupts them comes at a cost," he explained.

The study was funded by the AHA. Dr. Chan declared he has no financial conflicts.

DENVER – Marijuana use may be associated with a markedly decreased risk of diabetes.

A provocative new analysis of data from the Third National Health and Nutrition Examination Survey (NHANES III) indicates marijuana users had 66% lower odds of having diabetes after adjustment for numerous potential confounding factors, Dr. Magda Shaheen reported at the annual meeting of the American Public Health Association.

This robust observed benefit has a biologically plausible mechanism, she noted.

In addition to defects in pancreatic beta cell function and insulin sensitivity, the pathogenesis of diabetes is thought to involve systemic inflammation. Marijuana contains bioactive cannabinoids that have been shown to have an anti-inflammatory effect. This was borne out in the NHANES III analysis, where the prevalence of an elevated C-reactive protein level in excess of 0.5 mg/dL was significantly higher in nonusers of marijuana, at 18.9%, than in past users, with a 13% prevalence of elevated CRP, current light users (16%), or current heavy users of the illicit drug (9%), according to Dr. Shaheen of Charles R. Drew University of Medicine and Science, Los Angeles.

The study population consisted of 10,896 NHANES III participants aged 20-59 years; they constituted a statistically representative sample of the broader U.S. civilian population in 1988-94, when the survey was conducted.

The majority of subjects – 55% – reported never having used marijuana. Another 37% were past users, meaning they hadn’t used marijuana during the previous month. The 6% of subjects who reported currently using the drug 1-4 days per month were categorized as current light users, while 3.3% of subjects were current heavier users.

The age-adjusted prevalence of diabetes in this cross-sectional study was 4% in nonusers and significantly lower at 3% in marijuana users.

Current and past users of marijuana were significantly younger, had a lower body mass index, and were more physically active than were nonusers. They were also more likely to smoke cigarettes, drink alcohol, and use cocaine. In addition, they were more likely to have an HDL level greater than 40 mg/dL and had lower mean total cholesterol, LDL, and triglyceride levels.

In a multiple logistic regression analysis adjusted for socio-demographic factors, comorbid conditions, laboratory values, and inflammatory markers, marijuana users had a 66% lower likelihood of having diabetes. This benefit was confined to the 41- to 59-year-old age group, where the reduction in diabetes risk associated with marijuana use was 67%. In contrast, the 7% reduction in risk among 20- to 40-year-olds was not statistically significant. These findings could be the result of the markedly higher occurrence of diabetes in middle age.

Unlike in diabetes, marijuana use was not associated with a lower prevalence of the other chronic diseases that Dr. Shaheen and coworkers looked at in which systemic inflammation also plays a role: myocardial infarction, heart failure, stroke, and hypertension.

"This was probably due to the lower prevalence of these diseases in this age group," she commented.

Dr. Shaheen noted that the lowest prevalence of diabetes was found in current light users of marijuana, although past users and current heavy users also had lower rates than did nonusers.

"This finding in light marijuana users is similar to the effect of alcohol on diabetes mellitus and the metabolic syndrome. Studies have shown that mild alcohol use was associated with a lower prevalence of diabetes and metabolic syndrome, and higher use was associated with a higher prevalence," she observed.

Dr. Shaheen stressed that as this was a cross-sectional study, it can’t establish causality. The findings, while provocative, ought to be interpreted cautiously.

"Prospective studies need to be performed in rodents and humans to determine a causal relationship between cannabinoid receptor activation and diabetes. Until those studies are performed, we do not advocate the use of marijuana in patients at risk for diabetes mellitus," the investigator stressed.

The study was funded by Omics Biotechnology, which is pursuing potential medical applications for nonpsychotropic cannabinoid receptor agonists. Dr. Shaheen declared she has no relevant financial relationships.

DENVER – Marijuana use may be associated with a markedly decreased risk of diabetes.

A provocative new analysis of data from the Third National Health and Nutrition Examination Survey (NHANES III) indicates marijuana users had 66% lower odds of having diabetes after adjustment for numerous potential confounding factors, Dr. Magda Shaheen reported at the annual meeting of the American Public Health Association.

This robust observed benefit has a biologically plausible mechanism, she noted.

In addition to defects in pancreatic beta cell function and insulin sensitivity, the pathogenesis of diabetes is thought to involve systemic inflammation. Marijuana contains bioactive cannabinoids that have been shown to have an anti-inflammatory effect. This was borne out in the NHANES III analysis, where the prevalence of an elevated C-reactive protein level in excess of 0.5 mg/dL was significantly higher in nonusers of marijuana, at 18.9%, than in past users, with a 13% prevalence of elevated CRP, current light users (16%), or current heavy users of the illicit drug (9%), according to Dr. Shaheen of Charles R. Drew University of Medicine and Science, Los Angeles.

The study population consisted of 10,896 NHANES III participants aged 20-59 years; they constituted a statistically representative sample of the broader U.S. civilian population in 1988-94, when the survey was conducted.

The majority of subjects – 55% – reported never having used marijuana. Another 37% were past users, meaning they hadn’t used marijuana during the previous month. The 6% of subjects who reported currently using the drug 1-4 days per month were categorized as current light users, while 3.3% of subjects were current heavier users.

The age-adjusted prevalence of diabetes in this cross-sectional study was 4% in nonusers and significantly lower at 3% in marijuana users.

Current and past users of marijuana were significantly younger, had a lower body mass index, and were more physically active than were nonusers. They were also more likely to smoke cigarettes, drink alcohol, and use cocaine. In addition, they were more likely to have an HDL level greater than 40 mg/dL and had lower mean total cholesterol, LDL, and triglyceride levels.

In a multiple logistic regression analysis adjusted for socio-demographic factors, comorbid conditions, laboratory values, and inflammatory markers, marijuana users had a 66% lower likelihood of having diabetes. This benefit was confined to the 41- to 59-year-old age group, where the reduction in diabetes risk associated with marijuana use was 67%. In contrast, the 7% reduction in risk among 20- to 40-year-olds was not statistically significant. These findings could be the result of the markedly higher occurrence of diabetes in middle age.

Unlike in diabetes, marijuana use was not associated with a lower prevalence of the other chronic diseases that Dr. Shaheen and coworkers looked at in which systemic inflammation also plays a role: myocardial infarction, heart failure, stroke, and hypertension.

"This was probably due to the lower prevalence of these diseases in this age group," she commented.

Dr. Shaheen noted that the lowest prevalence of diabetes was found in current light users of marijuana, although past users and current heavy users also had lower rates than did nonusers.

"This finding in light marijuana users is similar to the effect of alcohol on diabetes mellitus and the metabolic syndrome. Studies have shown that mild alcohol use was associated with a lower prevalence of diabetes and metabolic syndrome, and higher use was associated with a higher prevalence," she observed.

Dr. Shaheen stressed that as this was a cross-sectional study, it can’t establish causality. The findings, while provocative, ought to be interpreted cautiously.

"Prospective studies need to be performed in rodents and humans to determine a causal relationship between cannabinoid receptor activation and diabetes. Until those studies are performed, we do not advocate the use of marijuana in patients at risk for diabetes mellitus," the investigator stressed.

The study was funded by Omics Biotechnology, which is pursuing potential medical applications for nonpsychotropic cannabinoid receptor agonists. Dr. Shaheen declared she has no relevant financial relationships.

DENVER – Marijuana use may be associated with a markedly decreased risk of diabetes.

A provocative new analysis of data from the Third National Health and Nutrition Examination Survey (NHANES III) indicates marijuana users had 66% lower odds of having diabetes after adjustment for numerous potential confounding factors, Dr. Magda Shaheen reported at the annual meeting of the American Public Health Association.

This robust observed benefit has a biologically plausible mechanism, she noted.

In addition to defects in pancreatic beta cell function and insulin sensitivity, the pathogenesis of diabetes is thought to involve systemic inflammation. Marijuana contains bioactive cannabinoids that have been shown to have an anti-inflammatory effect. This was borne out in the NHANES III analysis, where the prevalence of an elevated C-reactive protein level in excess of 0.5 mg/dL was significantly higher in nonusers of marijuana, at 18.9%, than in past users, with a 13% prevalence of elevated CRP, current light users (16%), or current heavy users of the illicit drug (9%), according to Dr. Shaheen of Charles R. Drew University of Medicine and Science, Los Angeles.

The study population consisted of 10,896 NHANES III participants aged 20-59 years; they constituted a statistically representative sample of the broader U.S. civilian population in 1988-94, when the survey was conducted.

The majority of subjects – 55% – reported never having used marijuana. Another 37% were past users, meaning they hadn’t used marijuana during the previous month. The 6% of subjects who reported currently using the drug 1-4 days per month were categorized as current light users, while 3.3% of subjects were current heavier users.

The age-adjusted prevalence of diabetes in this cross-sectional study was 4% in nonusers and significantly lower at 3% in marijuana users.

Current and past users of marijuana were significantly younger, had a lower body mass index, and were more physically active than were nonusers. They were also more likely to smoke cigarettes, drink alcohol, and use cocaine. In addition, they were more likely to have an HDL level greater than 40 mg/dL and had lower mean total cholesterol, LDL, and triglyceride levels.

In a multiple logistic regression analysis adjusted for socio-demographic factors, comorbid conditions, laboratory values, and inflammatory markers, marijuana users had a 66% lower likelihood of having diabetes. This benefit was confined to the 41- to 59-year-old age group, where the reduction in diabetes risk associated with marijuana use was 67%. In contrast, the 7% reduction in risk among 20- to 40-year-olds was not statistically significant. These findings could be the result of the markedly higher occurrence of diabetes in middle age.

Unlike in diabetes, marijuana use was not associated with a lower prevalence of the other chronic diseases that Dr. Shaheen and coworkers looked at in which systemic inflammation also plays a role: myocardial infarction, heart failure, stroke, and hypertension.

"This was probably due to the lower prevalence of these diseases in this age group," she commented.

Dr. Shaheen noted that the lowest prevalence of diabetes was found in current light users of marijuana, although past users and current heavy users also had lower rates than did nonusers.

"This finding in light marijuana users is similar to the effect of alcohol on diabetes mellitus and the metabolic syndrome. Studies have shown that mild alcohol use was associated with a lower prevalence of diabetes and metabolic syndrome, and higher use was associated with a higher prevalence," she observed.

Dr. Shaheen stressed that as this was a cross-sectional study, it can’t establish causality. The findings, while provocative, ought to be interpreted cautiously.

"Prospective studies need to be performed in rodents and humans to determine a causal relationship between cannabinoid receptor activation and diabetes. Until those studies are performed, we do not advocate the use of marijuana in patients at risk for diabetes mellitus," the investigator stressed.

The study was funded by Omics Biotechnology, which is pursuing potential medical applications for nonpsychotropic cannabinoid receptor agonists. Dr. Shaheen declared she has no relevant financial relationships.

DENVER – Doubling the currently low alcohol tax would result in roughly a 35% reduction in direct alcohol-related mortality as well as substantial benefits across a range of other important public health outcomes, a meta-analysis has shown.

Photo credit: Copyright dethchimo/Fotolia.com

"We have a lot of literature. This is probably the most studied preventive health policy issue. The magnitude of the observed effects is larger and more consistent than for most other preventive efforts that’ve been studied," Alexander C. Wagenaar, Ph.D., said at the annual meeting of the American Public Health Association.

He presented a meta-analysis based on what he described as "an exhaustive search" of the past 50 years of published studies on the effects of alcohol tax pricing policies on a whole range of public health outcomes.

In summary, a 10% increase in the alcohol tax and a commensurate price increase would result in an across-the-board 5% reduction in drinking across all groups: underage teens as well as adults, moderate as well as heavy drinkers. The meta-analysis of 50 studies showed that doubling the alcohol tax would be associated on average with a 35% reduction in deaths due to cirrhosis, some cancers, and other directly alcohol-related causes; an 11% drop in traffic crash morbidity and mortality; a 6% decrease in sexually transmitted infections; a 2% reduction in violence; and a 1% decrease in crime and delinquent misbehavior. All of these effects were statistically significant, according to Dr. Wagenaar, professor of epidemiology and health policy at the University of Florida, Gainesville.

"This is a policy that applies at the population level. It’s not just for the high-risk group, it’s not only for the people that get into treatment. When a tax change is implemented, it changes the environment slightly across the entire population such that there’s a reduction in drinking, and that effect ripples across these whole sets of alcohol-related outcomes," explained the researcher, whose prior health policy studies have been credited as playing a key role in establishing the uniform nationwide drinking age of 21.

Suicide was the only outcome the investigators studied that didn’t show a significant decrease in response to an increased tax on alcohol. Most of the 11 relevant studies have been conducted by only two research groups.

"There’s not enough evidence yet to determine conclusively whether change in alcohol taxes influences suicide rates," Dr. Wagenaar said.

He pointed out several practical advantages to raising the alcohol tax, beyond the striking public health benefits. An alcohol tax increase would generate additional revenues that could be used to fund other public health objectives or to bolster the general fund. No costly new bureaucratic infrastructure is required to implement an alcohol tax increase; the tax structures are already present. And alcohol tax rates are now at historic lows because they’re volume-based and aren’t adjusted for inflation.

"That’s how we’ve gotten into this situation where the tax rates now are only a fraction of what they were in the 1950s, ’60s, and ’70s. If we were to simply return the tax rates in most jurisdictions to the rates that were in place in the ’60s and ’70s, we would see the kinds of effects that we’re seeing in the meta-analysis, because in many areas that would involve a doubling of the tax rates," Dr. Wagenaar said.

In response to an audience question, he said the available evidence indicates there is no threshold effect for the relationship between alcohol tax increases and public health benefits. In other words, if the alcohol tax is increased by, say, one-quarter, public health benefits will accrue, albeit not with the same large effect sizes as with a doubling of the tax.

Dr. Wagenaar’s study was funded by the Robert Wood Johnson Foundation. He said he has no relevant financial conflicts of interest.

DENVER – Doubling the currently low alcohol tax would result in roughly a 35% reduction in direct alcohol-related mortality as well as substantial benefits across a range of other important public health outcomes, a meta-analysis has shown.

Photo credit: Copyright dethchimo/Fotolia.com

"We have a lot of literature. This is probably the most studied preventive health policy issue. The magnitude of the observed effects is larger and more consistent than for most other preventive efforts that’ve been studied," Alexander C. Wagenaar, Ph.D., said at the annual meeting of the American Public Health Association.

He presented a meta-analysis based on what he described as "an exhaustive search" of the past 50 years of published studies on the effects of alcohol tax pricing policies on a whole range of public health outcomes.

In summary, a 10% increase in the alcohol tax and a commensurate price increase would result in an across-the-board 5% reduction in drinking across all groups: underage teens as well as adults, moderate as well as heavy drinkers. The meta-analysis of 50 studies showed that doubling the alcohol tax would be associated on average with a 35% reduction in deaths due to cirrhosis, some cancers, and other directly alcohol-related causes; an 11% drop in traffic crash morbidity and mortality; a 6% decrease in sexually transmitted infections; a 2% reduction in violence; and a 1% decrease in crime and delinquent misbehavior. All of these effects were statistically significant, according to Dr. Wagenaar, professor of epidemiology and health policy at the University of Florida, Gainesville.

"This is a policy that applies at the population level. It’s not just for the high-risk group, it’s not only for the people that get into treatment. When a tax change is implemented, it changes the environment slightly across the entire population such that there’s a reduction in drinking, and that effect ripples across these whole sets of alcohol-related outcomes," explained the researcher, whose prior health policy studies have been credited as playing a key role in establishing the uniform nationwide drinking age of 21.

Suicide was the only outcome the investigators studied that didn’t show a significant decrease in response to an increased tax on alcohol. Most of the 11 relevant studies have been conducted by only two research groups.

"There’s not enough evidence yet to determine conclusively whether change in alcohol taxes influences suicide rates," Dr. Wagenaar said.

He pointed out several practical advantages to raising the alcohol tax, beyond the striking public health benefits. An alcohol tax increase would generate additional revenues that could be used to fund other public health objectives or to bolster the general fund. No costly new bureaucratic infrastructure is required to implement an alcohol tax increase; the tax structures are already present. And alcohol tax rates are now at historic lows because they’re volume-based and aren’t adjusted for inflation.

"That’s how we’ve gotten into this situation where the tax rates now are only a fraction of what they were in the 1950s, ’60s, and ’70s. If we were to simply return the tax rates in most jurisdictions to the rates that were in place in the ’60s and ’70s, we would see the kinds of effects that we’re seeing in the meta-analysis, because in many areas that would involve a doubling of the tax rates," Dr. Wagenaar said.

In response to an audience question, he said the available evidence indicates there is no threshold effect for the relationship between alcohol tax increases and public health benefits. In other words, if the alcohol tax is increased by, say, one-quarter, public health benefits will accrue, albeit not with the same large effect sizes as with a doubling of the tax.

Dr. Wagenaar’s study was funded by the Robert Wood Johnson Foundation. He said he has no relevant financial conflicts of interest.

DENVER – Doubling the currently low alcohol tax would result in roughly a 35% reduction in direct alcohol-related mortality as well as substantial benefits across a range of other important public health outcomes, a meta-analysis has shown.

Photo credit: Copyright dethchimo/Fotolia.com

"We have a lot of literature. This is probably the most studied preventive health policy issue. The magnitude of the observed effects is larger and more consistent than for most other preventive efforts that’ve been studied," Alexander C. Wagenaar, Ph.D., said at the annual meeting of the American Public Health Association.

He presented a meta-analysis based on what he described as "an exhaustive search" of the past 50 years of published studies on the effects of alcohol tax pricing policies on a whole range of public health outcomes.

In summary, a 10% increase in the alcohol tax and a commensurate price increase would result in an across-the-board 5% reduction in drinking across all groups: underage teens as well as adults, moderate as well as heavy drinkers. The meta-analysis of 50 studies showed that doubling the alcohol tax would be associated on average with a 35% reduction in deaths due to cirrhosis, some cancers, and other directly alcohol-related causes; an 11% drop in traffic crash morbidity and mortality; a 6% decrease in sexually transmitted infections; a 2% reduction in violence; and a 1% decrease in crime and delinquent misbehavior. All of these effects were statistically significant, according to Dr. Wagenaar, professor of epidemiology and health policy at the University of Florida, Gainesville.

"This is a policy that applies at the population level. It’s not just for the high-risk group, it’s not only for the people that get into treatment. When a tax change is implemented, it changes the environment slightly across the entire population such that there’s a reduction in drinking, and that effect ripples across these whole sets of alcohol-related outcomes," explained the researcher, whose prior health policy studies have been credited as playing a key role in establishing the uniform nationwide drinking age of 21.

Suicide was the only outcome the investigators studied that didn’t show a significant decrease in response to an increased tax on alcohol. Most of the 11 relevant studies have been conducted by only two research groups.

"There’s not enough evidence yet to determine conclusively whether change in alcohol taxes influences suicide rates," Dr. Wagenaar said.

He pointed out several practical advantages to raising the alcohol tax, beyond the striking public health benefits. An alcohol tax increase would generate additional revenues that could be used to fund other public health objectives or to bolster the general fund. No costly new bureaucratic infrastructure is required to implement an alcohol tax increase; the tax structures are already present. And alcohol tax rates are now at historic lows because they’re volume-based and aren’t adjusted for inflation.

"That’s how we’ve gotten into this situation where the tax rates now are only a fraction of what they were in the 1950s, ’60s, and ’70s. If we were to simply return the tax rates in most jurisdictions to the rates that were in place in the ’60s and ’70s, we would see the kinds of effects that we’re seeing in the meta-analysis, because in many areas that would involve a doubling of the tax rates," Dr. Wagenaar said.

In response to an audience question, he said the available evidence indicates there is no threshold effect for the relationship between alcohol tax increases and public health benefits. In other words, if the alcohol tax is increased by, say, one-quarter, public health benefits will accrue, albeit not with the same large effect sizes as with a doubling of the tax.

Dr. Wagenaar’s study was funded by the Robert Wood Johnson Foundation. He said he has no relevant financial conflicts of interest.

DENVER – Preimplantation genetic diagnosis using a novel 24-chromosome screen for aneuploidy on day 5 of embryonic development resulted in significantly increased rates of implantation and clinical pregnancy in a randomized controlled trial.

The implantation rate was 76% in fresh embryos transferred after day-5 trophectoderm biopsy showed them to be euploid, compared with 52% in embryos that didn’t undergo aneuploidy screening. That’s an absolute 24% difference in the primary study end point, Dr. Richard T. Scott Jr., noted at the annual meeting of the American Society for Reproductive Medicine.

"We believe this is a highly clinically important difference," added Dr. Scott of Reproductive Medicine Associates of New Jersey, Morristown, and the Robert Wood Johnson Medical School, New Brunswick.

He reported on 80 women randomized to 24-chromosome aneuploidy screening utilizing quantitative polymerase chain reaction (PCR) and copy number analysis followed by fresh embryo transfer or to day-5 blastocyst transfer without aneuploidy screening. The group of patients had a relatively good prognosis, with a mean age of 33 years (none over age 42 years), and not more than one prior failed cycle of in vitro fertilization. The mean number of embryos transferred per patient was 1.8 in the aneuploidy screening group, significantly less than the 2.0 in controls.

Sustained implantation occurred in 54 of 71 (76%) transferred embryos in the aneuploidy screening group, compared with 42 of 81 (52%) in the control arm.

The results were especially impressive in the group of 28 women aged 35 or older: a 74% implantation rate with aneuploidy screening, nearly double the 40% rate in controls, Dr. Scott continued.

Clinical pregnancy occurred in 37 of 39 women in the aneuploidy screening group, for a 95% success rate, compared with 78% in 41 controls. The ongoing or delivered pregnancy rate was 87% in the aneuploidy screening group, significantly better than the 68% rate in unscreened women.

The 24-chromosome aneuploidy screening technique Dr. Scott and coworkers have developed over the last 4-plus years provides reliable results within 4 hours, permitting same-day or next-morning embryo transfer without embryo freezing.

The rationale for developing this aneuploidy screening technique lies in the steep age-related rise in the prevalence of aneuploidy. For women aged 36-41 years, the prevalence of aneuploidy, including monosomies as well as trisomies, is 70%-80% among embryos deemed suitable for transfer based on conventional morphologic analysis.

A day-5 screening test had to be developed, because it’s impossible to tell aneuploid from euploid embryos on day 3. Besides, biopsy on day 3 is more stressful for the embryo, which is only eight cells in size at that point.

"We believe day-3 biopsy lowers implantation rates by as much as 15%-20%," Dr. Scott explained.

Just how reliable is the genetic screening test? In various studies to date, the investigators have transferred more than 970 embryos identified as euploid, with more than 650 resultant implantations. Three embryos identified as euploid on the screening test resulted in abnormal gestations: one tetraploidy, one Turner’s syndrome, and one trisomy 13. But the Turner’s syndrome and trisomy turned out to be mosaics on genetic analysis of the products of conception.

"The only clear diagnostic error was the tetraploid embryo. I should point out that our technology does not accurately evaluate for tetraploidy. Therefore the error rate attributable to the test itself is probably about 1 per 1,000," according to the fertility specialist.

The study presented at the ASRM meeting provides level I evidence that 24-chromosome aneuploidy screening enhances embryo selection and improves clinical outcomes, the final step in validation of the test. In the next few weeks, the test will be introduced at a select handful of fertility clinics around the country. Eventually it will become much more widely available. Although more than 100 clinics have inquired about offering the test, at present most don’t have the capability of doing day-5 biopsy, which is a prerequisite, Dr. Scott said in an interview.

"It’s a fairly complex methodology to do this. It’s extremely labor intensive, and you need a lot of expensive toys. The cost of the test is about $2,500 – that’s what we charge, the true cost with no markup," he added.

In an interview, session co-chair Dr. Eric Levens called Dr. Scott’s study one of the clear highlights of the meeting, an assessment later confirmed by the announcement that Dr. Scott tied for first place in the ASRM Scientific Program Prize Paper Awards.

This new ability to do a day-5 embryo biopsy and get the results back so fast that there’s no need to undertake a frozen embryo transfer is a significant advance, Dr. Levens said.

"Biopsy on day 5 at the blastocyst stage is potentially less invasive to the embryo than the standard day-3 biopsy used in preimplantation genetic diagnosis. Day-5 biopsy allows for the natural selection process to occur from day 3 to the day-5 transition, where the embryo starts to rely on its own machinery. And it also allows the benefits of aneuploidy screening," observed Dr. Levens of Shady Grove Fertility in Annandale, Va.

Dr. Scott noted that the ongoing twin gestation rate in the aneuploidy screening group was twice that in controls, reflecting the higher implantation rates achieved through preimplantation genetic diagnosis. A goal in future studies will be to further reduce the embryo transfer number from the mean 1.8 in the latest study in order to attain very high elective single-embryo transfer rates while maintaining high implantation and delivery rates. The eventual goal, he stressed, is to minimize IVF multiple gestations.

"The total cost of IVF probably represents only 10%-15% of the true cost. It’s the obstetrical and pediatric care downstream that’s really expensive, and the bulk of that is for twins and triplets," Dr. Scott explained.

"The economic implications of avoiding multiple gestations are enormous. If we could identify which embryos will make babies before we have to make transfer decisions, we could reduce the number of transfers and avoid all triplets and almost all twins. That would reduce the obstetrical and pediatric costs such that as a society we could provide free care for infertility for everyone in this country – and still save money," he asserted.

Dr. Scott said he and his coworkers have self-funded the development of the 24-chromosome aneuploidy screening system without commercial support.

DENVER – Preimplantation genetic diagnosis using a novel 24-chromosome screen for aneuploidy on day 5 of embryonic development resulted in significantly increased rates of implantation and clinical pregnancy in a randomized controlled trial.

The implantation rate was 76% in fresh embryos transferred after day-5 trophectoderm biopsy showed them to be euploid, compared with 52% in embryos that didn’t undergo aneuploidy screening. That’s an absolute 24% difference in the primary study end point, Dr. Richard T. Scott Jr., noted at the annual meeting of the American Society for Reproductive Medicine.

"We believe this is a highly clinically important difference," added Dr. Scott of Reproductive Medicine Associates of New Jersey, Morristown, and the Robert Wood Johnson Medical School, New Brunswick.

He reported on 80 women randomized to 24-chromosome aneuploidy screening utilizing quantitative polymerase chain reaction (PCR) and copy number analysis followed by fresh embryo transfer or to day-5 blastocyst transfer without aneuploidy screening. The group of patients had a relatively good prognosis, with a mean age of 33 years (none over age 42 years), and not more than one prior failed cycle of in vitro fertilization. The mean number of embryos transferred per patient was 1.8 in the aneuploidy screening group, significantly less than the 2.0 in controls.

Sustained implantation occurred in 54 of 71 (76%) transferred embryos in the aneuploidy screening group, compared with 42 of 81 (52%) in the control arm.

The results were especially impressive in the group of 28 women aged 35 or older: a 74% implantation rate with aneuploidy screening, nearly double the 40% rate in controls, Dr. Scott continued.

Clinical pregnancy occurred in 37 of 39 women in the aneuploidy screening group, for a 95% success rate, compared with 78% in 41 controls. The ongoing or delivered pregnancy rate was 87% in the aneuploidy screening group, significantly better than the 68% rate in unscreened women.

The 24-chromosome aneuploidy screening technique Dr. Scott and coworkers have developed over the last 4-plus years provides reliable results within 4 hours, permitting same-day or next-morning embryo transfer without embryo freezing.

The rationale for developing this aneuploidy screening technique lies in the steep age-related rise in the prevalence of aneuploidy. For women aged 36-41 years, the prevalence of aneuploidy, including monosomies as well as trisomies, is 70%-80% among embryos deemed suitable for transfer based on conventional morphologic analysis.

A day-5 screening test had to be developed, because it’s impossible to tell aneuploid from euploid embryos on day 3. Besides, biopsy on day 3 is more stressful for the embryo, which is only eight cells in size at that point.

"We believe day-3 biopsy lowers implantation rates by as much as 15%-20%," Dr. Scott explained.

Just how reliable is the genetic screening test? In various studies to date, the investigators have transferred more than 970 embryos identified as euploid, with more than 650 resultant implantations. Three embryos identified as euploid on the screening test resulted in abnormal gestations: one tetraploidy, one Turner’s syndrome, and one trisomy 13. But the Turner’s syndrome and trisomy turned out to be mosaics on genetic analysis of the products of conception.

"The only clear diagnostic error was the tetraploid embryo. I should point out that our technology does not accurately evaluate for tetraploidy. Therefore the error rate attributable to the test itself is probably about 1 per 1,000," according to the fertility specialist.

The study presented at the ASRM meeting provides level I evidence that 24-chromosome aneuploidy screening enhances embryo selection and improves clinical outcomes, the final step in validation of the test. In the next few weeks, the test will be introduced at a select handful of fertility clinics around the country. Eventually it will become much more widely available. Although more than 100 clinics have inquired about offering the test, at present most don’t have the capability of doing day-5 biopsy, which is a prerequisite, Dr. Scott said in an interview.

"It’s a fairly complex methodology to do this. It’s extremely labor intensive, and you need a lot of expensive toys. The cost of the test is about $2,500 – that’s what we charge, the true cost with no markup," he added.

In an interview, session co-chair Dr. Eric Levens called Dr. Scott’s study one of the clear highlights of the meeting, an assessment later confirmed by the announcement that Dr. Scott tied for first place in the ASRM Scientific Program Prize Paper Awards.

This new ability to do a day-5 embryo biopsy and get the results back so fast that there’s no need to undertake a frozen embryo transfer is a significant advance, Dr. Levens said.

"Biopsy on day 5 at the blastocyst stage is potentially less invasive to the embryo than the standard day-3 biopsy used in preimplantation genetic diagnosis. Day-5 biopsy allows for the natural selection process to occur from day 3 to the day-5 transition, where the embryo starts to rely on its own machinery. And it also allows the benefits of aneuploidy screening," observed Dr. Levens of Shady Grove Fertility in Annandale, Va.

Dr. Scott noted that the ongoing twin gestation rate in the aneuploidy screening group was twice that in controls, reflecting the higher implantation rates achieved through preimplantation genetic diagnosis. A goal in future studies will be to further reduce the embryo transfer number from the mean 1.8 in the latest study in order to attain very high elective single-embryo transfer rates while maintaining high implantation and delivery rates. The eventual goal, he stressed, is to minimize IVF multiple gestations.

"The total cost of IVF probably represents only 10%-15% of the true cost. It’s the obstetrical and pediatric care downstream that’s really expensive, and the bulk of that is for twins and triplets," Dr. Scott explained.

"The economic implications of avoiding multiple gestations are enormous. If we could identify which embryos will make babies before we have to make transfer decisions, we could reduce the number of transfers and avoid all triplets and almost all twins. That would reduce the obstetrical and pediatric costs such that as a society we could provide free care for infertility for everyone in this country – and still save money," he asserted.

Dr. Scott said he and his coworkers have self-funded the development of the 24-chromosome aneuploidy screening system without commercial support.

DENVER – Preimplantation genetic diagnosis using a novel 24-chromosome screen for aneuploidy on day 5 of embryonic development resulted in significantly increased rates of implantation and clinical pregnancy in a randomized controlled trial.

The implantation rate was 76% in fresh embryos transferred after day-5 trophectoderm biopsy showed them to be euploid, compared with 52% in embryos that didn’t undergo aneuploidy screening. That’s an absolute 24% difference in the primary study end point, Dr. Richard T. Scott Jr., noted at the annual meeting of the American Society for Reproductive Medicine.

"We believe this is a highly clinically important difference," added Dr. Scott of Reproductive Medicine Associates of New Jersey, Morristown, and the Robert Wood Johnson Medical School, New Brunswick.

He reported on 80 women randomized to 24-chromosome aneuploidy screening utilizing quantitative polymerase chain reaction (PCR) and copy number analysis followed by fresh embryo transfer or to day-5 blastocyst transfer without aneuploidy screening. The group of patients had a relatively good prognosis, with a mean age of 33 years (none over age 42 years), and not more than one prior failed cycle of in vitro fertilization. The mean number of embryos transferred per patient was 1.8 in the aneuploidy screening group, significantly less than the 2.0 in controls.

Sustained implantation occurred in 54 of 71 (76%) transferred embryos in the aneuploidy screening group, compared with 42 of 81 (52%) in the control arm.

The results were especially impressive in the group of 28 women aged 35 or older: a 74% implantation rate with aneuploidy screening, nearly double the 40% rate in controls, Dr. Scott continued.

Clinical pregnancy occurred in 37 of 39 women in the aneuploidy screening group, for a 95% success rate, compared with 78% in 41 controls. The ongoing or delivered pregnancy rate was 87% in the aneuploidy screening group, significantly better than the 68% rate in unscreened women.

The 24-chromosome aneuploidy screening technique Dr. Scott and coworkers have developed over the last 4-plus years provides reliable results within 4 hours, permitting same-day or next-morning embryo transfer without embryo freezing.

The rationale for developing this aneuploidy screening technique lies in the steep age-related rise in the prevalence of aneuploidy. For women aged 36-41 years, the prevalence of aneuploidy, including monosomies as well as trisomies, is 70%-80% among embryos deemed suitable for transfer based on conventional morphologic analysis.

A day-5 screening test had to be developed, because it’s impossible to tell aneuploid from euploid embryos on day 3. Besides, biopsy on day 3 is more stressful for the embryo, which is only eight cells in size at that point.

"We believe day-3 biopsy lowers implantation rates by as much as 15%-20%," Dr. Scott explained.

Just how reliable is the genetic screening test? In various studies to date, the investigators have transferred more than 970 embryos identified as euploid, with more than 650 resultant implantations. Three embryos identified as euploid on the screening test resulted in abnormal gestations: one tetraploidy, one Turner’s syndrome, and one trisomy 13. But the Turner’s syndrome and trisomy turned out to be mosaics on genetic analysis of the products of conception.

"The only clear diagnostic error was the tetraploid embryo. I should point out that our technology does not accurately evaluate for tetraploidy. Therefore the error rate attributable to the test itself is probably about 1 per 1,000," according to the fertility specialist.

The study presented at the ASRM meeting provides level I evidence that 24-chromosome aneuploidy screening enhances embryo selection and improves clinical outcomes, the final step in validation of the test. In the next few weeks, the test will be introduced at a select handful of fertility clinics around the country. Eventually it will become much more widely available. Although more than 100 clinics have inquired about offering the test, at present most don’t have the capability of doing day-5 biopsy, which is a prerequisite, Dr. Scott said in an interview.

"It’s a fairly complex methodology to do this. It’s extremely labor intensive, and you need a lot of expensive toys. The cost of the test is about $2,500 – that’s what we charge, the true cost with no markup," he added.

In an interview, session co-chair Dr. Eric Levens called Dr. Scott’s study one of the clear highlights of the meeting, an assessment later confirmed by the announcement that Dr. Scott tied for first place in the ASRM Scientific Program Prize Paper Awards.

This new ability to do a day-5 embryo biopsy and get the results back so fast that there’s no need to undertake a frozen embryo transfer is a significant advance, Dr. Levens said.

"Biopsy on day 5 at the blastocyst stage is potentially less invasive to the embryo than the standard day-3 biopsy used in preimplantation genetic diagnosis. Day-5 biopsy allows for the natural selection process to occur from day 3 to the day-5 transition, where the embryo starts to rely on its own machinery. And it also allows the benefits of aneuploidy screening," observed Dr. Levens of Shady Grove Fertility in Annandale, Va.

Dr. Scott noted that the ongoing twin gestation rate in the aneuploidy screening group was twice that in controls, reflecting the higher implantation rates achieved through preimplantation genetic diagnosis. A goal in future studies will be to further reduce the embryo transfer number from the mean 1.8 in the latest study in order to attain very high elective single-embryo transfer rates while maintaining high implantation and delivery rates. The eventual goal, he stressed, is to minimize IVF multiple gestations.

"The total cost of IVF probably represents only 10%-15% of the true cost. It’s the obstetrical and pediatric care downstream that’s really expensive, and the bulk of that is for twins and triplets," Dr. Scott explained.

"The economic implications of avoiding multiple gestations are enormous. If we could identify which embryos will make babies before we have to make transfer decisions, we could reduce the number of transfers and avoid all triplets and almost all twins. That would reduce the obstetrical and pediatric costs such that as a society we could provide free care for infertility for everyone in this country – and still save money," he asserted.

Dr. Scott said he and his coworkers have self-funded the development of the 24-chromosome aneuploidy screening system without commercial support.

KEYSTONE, COLO. – Right now, Diamyd Medical's GAD vaccine is in the sweet spot in the developmental pipeline – an interim period of enormous optimism that this novel autoantigen-based immunotherapy will safely prevent many cases of type 1 diabetes.

The results of three phase II studies look quite promising. Two large phase III clinical trials are well underway in Europe and the United States. The safety experience with the 65-kD isoform of GAD (glutamic acid decarboxylase-65) vaccine has been outstanding. The subcutaneous two-injection series is easy to administer. Acceptance of the vaccine by patients and their families is high.

The vaccine targets a serious disease whose incidence is steadily climbing by 3%-5% per year in developed countries. And most patients with recently diagnosed type 1 diabetes possess GAD autoantibodies, so the Diamyd vaccine would be widely applicable.

All of that was good enough for Johnson & Johnson, which in June inked a huge development and marketing deal for the GAD vaccine with small Swedish biotech company Diamyd Medical. Under the deal, Diamyd receives $45 million upfront, milestone payments of up to $580 million, and tiered royalties after that. The Federal Trade Commission's antitrust division has approved the deal.

But during this blissful interlude, one key question remains: Is the Diamyd vaccine effective?

“It's too early to say if this works. Absolutely too early. We have a phase III trial in Europe with results due next spring. And the TrialNet study [is] going on here in the U.S. So we will know in a year or 2,” Dr. Johnny L. Ludvigsson said at the conference, which was sponsored by the Children's Diabetes Foundation at Denver.

Dr. Ludvigsson, professor of pediatrics at the University of Linkoping (Sweden), led the phase III European trial evaluating whether the GAD vaccine preserves beta-cell function and residual insulin secretion in patients with type 1 diabetes diagnosed within 3 months of starting treatment. He also headed a phase II study that caused a favorable buzz within the diabetes research community (N. Engl. J. Med. 2008;359:1909-20) and for which he is now analyzing 5-year follow-up data.

And while the forthcoming phase III trial results will tell the tale as to clinical efficacy, at this time some useful interim observations can be made about the GAD vaccine, according to Dr. Ludvigsson:

▸ The vaccine has demonstrated excellent safety. Experience with the vaccine to date totals 850 patient-years in adults and 350 patient-years in children, with no adverse events reported. This is enormously reassuring because GAD transforms glutamate into GABA, an important neurotransmitter. Lack of GAD in the CNS leads to muscle rigidity and convulsions, while stimulation of CNS GAD results in inhibition of neurotransmission. The absence of any such adverse events indicates the vaccine is working, as designed, to affect only the activated T cells that have targeted pancreatic beta cells for destruction, Dr. Ludvigsson said.

▸ The vaccine has demonstrated prolonged immunologic effects. The immunologic response to the Diamyd vaccine lasts surprisingly long – approaching 5 years and still counting. It's a GAD-specific, cell-mediated, and humoral immune response characterized by increased GAD autoantibodies, a Th2 shift marked by reduction in activated T cells and an increase in regulatory T cells, a sharp and sustained rise in levels of interleukins−2,−5, −10, −13, and −17, and GAD tolerance.

▸ “The earlier we treat, the better the outcome.” That's why the phase III European trial is restricted to patients diagnosed with type 1 diabetes within the past 3 months. It's also the impetus for ongoing prevention trials in individuals at very high genetic risk for type 1 diabetes who have GAD autoantibodies but have not developed overt disease.

For the future, the GAD vaccine alone probably is not the solution to type 1 diabetes, Dr. Ludvigsson said candidly.

“I believe this opens the door to using different antigens, like in allergy. Allergists don't use just cat antigen in patients who have cat, dog, and house dust mite allergies. I suppose we may also learn to combine autoantigens, together with possible stimulation of beta cells in combination with drugs that promote beta-cell regeneration,” he continued.

The likely necessity for a combined approach addressing multiple pathways was underscored in a separate presentation by Dr. Jay S. Skyler, chairman of the type 1 Diabetes TrialNet, a National Institutes of Health-funded international network of centers conducting clinical trials of diabetes therapies.

The GAD vaccine appears to have the same limitation as the other immunomodulatory therapies evaluated to date in clinical trials, including the B cell–depleting anti-CD20 agent rituximab, and the anti-CD3 biologics teplizumab and otelixizumab: Namely, they preserve beta-cell function for a while, but the effect is transient. Eventually, fasting C-peptide levels start to fall off in parallel to the placebo group. That's why combination therapy will probably be required in order to cure or prevent type 1 diabetes, according to Dr. Skyler, professor of medicine, pediatrics and psychology at the University of Miami.

Ideally, a combination therapy should be multipronged, with three goals: Stop immune destruction, preserve beta-cell mass, and replace or regenerate beta cells. Such a regimen might start off with a potent anti-inflammatory therapy – perhaps an anti-interleukin-1beta agent or tumor necrosis factor inhibitor – to quell the metabolic stress surrounding the pancreatic islets. This might well need to be given on a continuing basis.

Dr. Ludvigsson reported receiving research grant support from Diamyd. Dr. Skyler has served as a consultant to and/or received research grants from numerous pharmaceutical companies.

'It's too early to say if this works. Absolutely too early.'

Source DR. LUDVIGSSON

Eventually, fasting C-peptide levels start to fall off in parallel to the placebo group.

Source DR. SKYLER

View on the News

More Than One Type of Prevention

Elimination of the environmental agent(s) responsible for type 1 diabetes (T1D) would be the most efficient approach to primary prevention; however, more work is needed to identify the environmental agents and to develop effective interventions.

Blocking progression from islet autoimmunity to clinical diabetes or secondary prevention has been attempted, so far to no avail, by a number of groups, including large randomized trials.

Trials in patients with newly diagnosed T1D aim at tertiary prevention, such as preservation of remaining islet beta cells to induce and prolong partial remission. Unfortunately, most islets have already been destroyed by the time diabetes is diagnosed and complete reversal of diabetes is highly unlikely. Benefits may include a simpler insulin regimen, lower hemoglobin A_1c, and reduced risk of hypoglycemia and microvascular complications. The gain may be even greater if the intervention is applied as soon as the patient shows asymptomatic “dysglycemia.”

While new interventions are often tested first in patients with established diabetes, and, when proven safe, applied to patients with pre-T1D, efficacy after diagnosis of diabetes is not to be a precondition to application in pre-T1D, as there may be a “point of no return” in the destruction of the islets, rendering some interventions effective only at the earlier stages of the process.

Among several approaches to prevention of T1D, “vaccination” using islet autoantigens (intact or altered peptides derived from insulin, GAD₆₅ or other proteins) stands out as potentially inducing long-term tolerance by induction of regulatory T cells that down-regulate immunity to autoantigens. Until recently, trials of insulin administered parenterally, orally, or intranasally have been unsuccessful. Therefore, the initial results from trials of the Diamyd vaccine, as reviewed here, were greeted with huge interest and excitement. The vaccine includes the whole recombinant human GAD₆₅ (rhGAD₆₅) molecule suspended in alum. The protective effect was most pronounced in patients treated within 3 months of diagnosis, and no serious side effects were observed.

Insulin-related molecules continue to attract great interest in vaccine development. Phase I studies have been completed or are nearing completion for a proinsulin peptide C19-A3, an insulin peptide with incomplete Freund adjuvant, and a plasmid encoding proinsulin.

Combination therapies may enhance efficacy while lowering risk of adverse events if utilizing therapies from different treatment pathways. While more targeted therapies are being employed, immunomodulatory agents are still relatively nonspecific and potentially toxic to some of the trial participants.

In the long run, primary prevention will likely be the optimal approach to the prevention of T1D. Once more than one islet autoantibody is present, most individuals progress to diabetes in 5-10 years. The TrialNet consortium (

www.diabetestrialnet.org

MARIAN REWERS, M.D., PH.D., is professor of pediatrics and preventive medicine at the Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver. He is on an advisory board for GlaxoSmithKline and provided medical-legal consultation for AstraZeneca.

KEYSTONE, COLO. – Right now, Diamyd Medical's GAD vaccine is in the sweet spot in the developmental pipeline – an interim period of enormous optimism that this novel autoantigen-based immunotherapy will safely prevent many cases of type 1 diabetes.

The results of three phase II studies look quite promising. Two large phase III clinical trials are well underway in Europe and the United States. The safety experience with the 65-kD isoform of GAD (glutamic acid decarboxylase-65) vaccine has been outstanding. The subcutaneous two-injection series is easy to administer. Acceptance of the vaccine by patients and their families is high.

The vaccine targets a serious disease whose incidence is steadily climbing by 3%-5% per year in developed countries. And most patients with recently diagnosed type 1 diabetes possess GAD autoantibodies, so the Diamyd vaccine would be widely applicable.

All of that was good enough for Johnson & Johnson, which in June inked a huge development and marketing deal for the GAD vaccine with small Swedish biotech company Diamyd Medical. Under the deal, Diamyd receives $45 million upfront, milestone payments of up to $580 million, and tiered royalties after that. The Federal Trade Commission's antitrust division has approved the deal.

But during this blissful interlude, one key question remains: Is the Diamyd vaccine effective?

“It's too early to say if this works. Absolutely too early. We have a phase III trial in Europe with results due next spring. And the TrialNet study [is] going on here in the U.S. So we will know in a year or 2,” Dr. Johnny L. Ludvigsson said at the conference, which was sponsored by the Children's Diabetes Foundation at Denver.

Dr. Ludvigsson, professor of pediatrics at the University of Linkoping (Sweden), led the phase III European trial evaluating whether the GAD vaccine preserves beta-cell function and residual insulin secretion in patients with type 1 diabetes diagnosed within 3 months of starting treatment. He also headed a phase II study that caused a favorable buzz within the diabetes research community (N. Engl. J. Med. 2008;359:1909-20) and for which he is now analyzing 5-year follow-up data.

And while the forthcoming phase III trial results will tell the tale as to clinical efficacy, at this time some useful interim observations can be made about the GAD vaccine, according to Dr. Ludvigsson:

▸ The vaccine has demonstrated excellent safety. Experience with the vaccine to date totals 850 patient-years in adults and 350 patient-years in children, with no adverse events reported. This is enormously reassuring because GAD transforms glutamate into GABA, an important neurotransmitter. Lack of GAD in the CNS leads to muscle rigidity and convulsions, while stimulation of CNS GAD results in inhibition of neurotransmission. The absence of any such adverse events indicates the vaccine is working, as designed, to affect only the activated T cells that have targeted pancreatic beta cells for destruction, Dr. Ludvigsson said.

▸ The vaccine has demonstrated prolonged immunologic effects. The immunologic response to the Diamyd vaccine lasts surprisingly long – approaching 5 years and still counting. It's a GAD-specific, cell-mediated, and humoral immune response characterized by increased GAD autoantibodies, a Th2 shift marked by reduction in activated T cells and an increase in regulatory T cells, a sharp and sustained rise in levels of interleukins−2,−5, −10, −13, and −17, and GAD tolerance.

▸ “The earlier we treat, the better the outcome.” That's why the phase III European trial is restricted to patients diagnosed with type 1 diabetes within the past 3 months. It's also the impetus for ongoing prevention trials in individuals at very high genetic risk for type 1 diabetes who have GAD autoantibodies but have not developed overt disease.

For the future, the GAD vaccine alone probably is not the solution to type 1 diabetes, Dr. Ludvigsson said candidly.

“I believe this opens the door to using different antigens, like in allergy. Allergists don't use just cat antigen in patients who have cat, dog, and house dust mite allergies. I suppose we may also learn to combine autoantigens, together with possible stimulation of beta cells in combination with drugs that promote beta-cell regeneration,” he continued.

The likely necessity for a combined approach addressing multiple pathways was underscored in a separate presentation by Dr. Jay S. Skyler, chairman of the type 1 Diabetes TrialNet, a National Institutes of Health-funded international network of centers conducting clinical trials of diabetes therapies.

The GAD vaccine appears to have the same limitation as the other immunomodulatory therapies evaluated to date in clinical trials, including the B cell–depleting anti-CD20 agent rituximab, and the anti-CD3 biologics teplizumab and otelixizumab: Namely, they preserve beta-cell function for a while, but the effect is transient. Eventually, fasting C-peptide levels start to fall off in parallel to the placebo group. That's why combination therapy will probably be required in order to cure or prevent type 1 diabetes, according to Dr. Skyler, professor of medicine, pediatrics and psychology at the University of Miami.

Ideally, a combination therapy should be multipronged, with three goals: Stop immune destruction, preserve beta-cell mass, and replace or regenerate beta cells. Such a regimen might start off with a potent anti-inflammatory therapy – perhaps an anti-interleukin-1beta agent or tumor necrosis factor inhibitor – to quell the metabolic stress surrounding the pancreatic islets. This might well need to be given on a continuing basis.

Dr. Ludvigsson reported receiving research grant support from Diamyd. Dr. Skyler has served as a consultant to and/or received research grants from numerous pharmaceutical companies.

'It's too early to say if this works. Absolutely too early.'

Source DR. LUDVIGSSON

Eventually, fasting C-peptide levels start to fall off in parallel to the placebo group.

Source DR. SKYLER

View on the News

More Than One Type of Prevention

Elimination of the environmental agent(s) responsible for type 1 diabetes (T1D) would be the most efficient approach to primary prevention; however, more work is needed to identify the environmental agents and to develop effective interventions.

Blocking progression from islet autoimmunity to clinical diabetes or secondary prevention has been attempted, so far to no avail, by a number of groups, including large randomized trials.

Trials in patients with newly diagnosed T1D aim at tertiary prevention, such as preservation of remaining islet beta cells to induce and prolong partial remission. Unfortunately, most islets have already been destroyed by the time diabetes is diagnosed and complete reversal of diabetes is highly unlikely. Benefits may include a simpler insulin regimen, lower hemoglobin A_1c, and reduced risk of hypoglycemia and microvascular complications. The gain may be even greater if the intervention is applied as soon as the patient shows asymptomatic “dysglycemia.”

While new interventions are often tested first in patients with established diabetes, and, when proven safe, applied to patients with pre-T1D, efficacy after diagnosis of diabetes is not to be a precondition to application in pre-T1D, as there may be a “point of no return” in the destruction of the islets, rendering some interventions effective only at the earlier stages of the process.

Among several approaches to prevention of T1D, “vaccination” using islet autoantigens (intact or altered peptides derived from insulin, GAD₆₅ or other proteins) stands out as potentially inducing long-term tolerance by induction of regulatory T cells that down-regulate immunity to autoantigens. Until recently, trials of insulin administered parenterally, orally, or intranasally have been unsuccessful. Therefore, the initial results from trials of the Diamyd vaccine, as reviewed here, were greeted with huge interest and excitement. The vaccine includes the whole recombinant human GAD₆₅ (rhGAD₆₅) molecule suspended in alum. The protective effect was most pronounced in patients treated within 3 months of diagnosis, and no serious side effects were observed.

Insulin-related molecules continue to attract great interest in vaccine development. Phase I studies have been completed or are nearing completion for a proinsulin peptide C19-A3, an insulin peptide with incomplete Freund adjuvant, and a plasmid encoding proinsulin.

Combination therapies may enhance efficacy while lowering risk of adverse events if utilizing therapies from different treatment pathways. While more targeted therapies are being employed, immunomodulatory agents are still relatively nonspecific and potentially toxic to some of the trial participants.

In the long run, primary prevention will likely be the optimal approach to the prevention of T1D. Once more than one islet autoantibody is present, most individuals progress to diabetes in 5-10 years. The TrialNet consortium (

www.diabetestrialnet.org

MARIAN REWERS, M.D., PH.D., is professor of pediatrics and preventive medicine at the Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver. He is on an advisory board for GlaxoSmithKline and provided medical-legal consultation for AstraZeneca.

KEYSTONE, COLO. – Right now, Diamyd Medical's GAD vaccine is in the sweet spot in the developmental pipeline – an interim period of enormous optimism that this novel autoantigen-based immunotherapy will safely prevent many cases of type 1 diabetes.

The results of three phase II studies look quite promising. Two large phase III clinical trials are well underway in Europe and the United States. The safety experience with the 65-kD isoform of GAD (glutamic acid decarboxylase-65) vaccine has been outstanding. The subcutaneous two-injection series is easy to administer. Acceptance of the vaccine by patients and their families is high.

The vaccine targets a serious disease whose incidence is steadily climbing by 3%-5% per year in developed countries. And most patients with recently diagnosed type 1 diabetes possess GAD autoantibodies, so the Diamyd vaccine would be widely applicable.

All of that was good enough for Johnson & Johnson, which in June inked a huge development and marketing deal for the GAD vaccine with small Swedish biotech company Diamyd Medical. Under the deal, Diamyd receives $45 million upfront, milestone payments of up to $580 million, and tiered royalties after that. The Federal Trade Commission's antitrust division has approved the deal.

But during this blissful interlude, one key question remains: Is the Diamyd vaccine effective?

“It's too early to say if this works. Absolutely too early. We have a phase III trial in Europe with results due next spring. And the TrialNet study [is] going on here in the U.S. So we will know in a year or 2,” Dr. Johnny L. Ludvigsson said at the conference, which was sponsored by the Children's Diabetes Foundation at Denver.

Dr. Ludvigsson, professor of pediatrics at the University of Linkoping (Sweden), led the phase III European trial evaluating whether the GAD vaccine preserves beta-cell function and residual insulin secretion in patients with type 1 diabetes diagnosed within 3 months of starting treatment. He also headed a phase II study that caused a favorable buzz within the diabetes research community (N. Engl. J. Med. 2008;359:1909-20) and for which he is now analyzing 5-year follow-up data.

And while the forthcoming phase III trial results will tell the tale as to clinical efficacy, at this time some useful interim observations can be made about the GAD vaccine, according to Dr. Ludvigsson:

▸ The vaccine has demonstrated excellent safety. Experience with the vaccine to date totals 850 patient-years in adults and 350 patient-years in children, with no adverse events reported. This is enormously reassuring because GAD transforms glutamate into GABA, an important neurotransmitter. Lack of GAD in the CNS leads to muscle rigidity and convulsions, while stimulation of CNS GAD results in inhibition of neurotransmission. The absence of any such adverse events indicates the vaccine is working, as designed, to affect only the activated T cells that have targeted pancreatic beta cells for destruction, Dr. Ludvigsson said.

▸ The vaccine has demonstrated prolonged immunologic effects. The immunologic response to the Diamyd vaccine lasts surprisingly long – approaching 5 years and still counting. It's a GAD-specific, cell-mediated, and humoral immune response characterized by increased GAD autoantibodies, a Th2 shift marked by reduction in activated T cells and an increase in regulatory T cells, a sharp and sustained rise in levels of interleukins−2,−5, −10, −13, and −17, and GAD tolerance.

▸ “The earlier we treat, the better the outcome.” That's why the phase III European trial is restricted to patients diagnosed with type 1 diabetes within the past 3 months. It's also the impetus for ongoing prevention trials in individuals at very high genetic risk for type 1 diabetes who have GAD autoantibodies but have not developed overt disease.

For the future, the GAD vaccine alone probably is not the solution to type 1 diabetes, Dr. Ludvigsson said candidly.

“I believe this opens the door to using different antigens, like in allergy. Allergists don't use just cat antigen in patients who have cat, dog, and house dust mite allergies. I suppose we may also learn to combine autoantigens, together with possible stimulation of beta cells in combination with drugs that promote beta-cell regeneration,” he continued.

The likely necessity for a combined approach addressing multiple pathways was underscored in a separate presentation by Dr. Jay S. Skyler, chairman of the type 1 Diabetes TrialNet, a National Institutes of Health-funded international network of centers conducting clinical trials of diabetes therapies.

The GAD vaccine appears to have the same limitation as the other immunomodulatory therapies evaluated to date in clinical trials, including the B cell–depleting anti-CD20 agent rituximab, and the anti-CD3 biologics teplizumab and otelixizumab: Namely, they preserve beta-cell function for a while, but the effect is transient. Eventually, fasting C-peptide levels start to fall off in parallel to the placebo group. That's why combination therapy will probably be required in order to cure or prevent type 1 diabetes, according to Dr. Skyler, professor of medicine, pediatrics and psychology at the University of Miami.

Ideally, a combination therapy should be multipronged, with three goals: Stop immune destruction, preserve beta-cell mass, and replace or regenerate beta cells. Such a regimen might start off with a potent anti-inflammatory therapy – perhaps an anti-interleukin-1beta agent or tumor necrosis factor inhibitor – to quell the metabolic stress surrounding the pancreatic islets. This might well need to be given on a continuing basis.

Dr. Ludvigsson reported receiving research grant support from Diamyd. Dr. Skyler has served as a consultant to and/or received research grants from numerous pharmaceutical companies.

'It's too early to say if this works. Absolutely too early.'

Source DR. LUDVIGSSON

Eventually, fasting C-peptide levels start to fall off in parallel to the placebo group.

Source DR. SKYLER

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More Than One Type of Prevention

Elimination of the environmental agent(s) responsible for type 1 diabetes (T1D) would be the most efficient approach to primary prevention; however, more work is needed to identify the environmental agents and to develop effective interventions.

Blocking progression from islet autoimmunity to clinical diabetes or secondary prevention has been attempted, so far to no avail, by a number of groups, including large randomized trials.

Trials in patients with newly diagnosed T1D aim at tertiary prevention, such as preservation of remaining islet beta cells to induce and prolong partial remission. Unfortunately, most islets have already been destroyed by the time diabetes is diagnosed and complete reversal of diabetes is highly unlikely. Benefits may include a simpler insulin regimen, lower hemoglobin A_1c, and reduced risk of hypoglycemia and microvascular complications. The gain may be even greater if the intervention is applied as soon as the patient shows asymptomatic “dysglycemia.”

While new interventions are often tested first in patients with established diabetes, and, when proven safe, applied to patients with pre-T1D, efficacy after diagnosis of diabetes is not to be a precondition to application in pre-T1D, as there may be a “point of no return” in the destruction of the islets, rendering some interventions effective only at the earlier stages of the process.

Among several approaches to prevention of T1D, “vaccination” using islet autoantigens (intact or altered peptides derived from insulin, GAD₆₅ or other proteins) stands out as potentially inducing long-term tolerance by induction of regulatory T cells that down-regulate immunity to autoantigens. Until recently, trials of insulin administered parenterally, orally, or intranasally have been unsuccessful. Therefore, the initial results from trials of the Diamyd vaccine, as reviewed here, were greeted with huge interest and excitement. The vaccine includes the whole recombinant human GAD₆₅ (rhGAD₆₅) molecule suspended in alum. The protective effect was most pronounced in patients treated within 3 months of diagnosis, and no serious side effects were observed.

Insulin-related molecules continue to attract great interest in vaccine development. Phase I studies have been completed or are nearing completion for a proinsulin peptide C19-A3, an insulin peptide with incomplete Freund adjuvant, and a plasmid encoding proinsulin.

Combination therapies may enhance efficacy while lowering risk of adverse events if utilizing therapies from different treatment pathways. While more targeted therapies are being employed, immunomodulatory agents are still relatively nonspecific and potentially toxic to some of the trial participants.

In the long run, primary prevention will likely be the optimal approach to the prevention of T1D. Once more than one islet autoantibody is present, most individuals progress to diabetes in 5-10 years. The TrialNet consortium (

www.diabetestrialnet.org

MARIAN REWERS, M.D., PH.D., is professor of pediatrics and preventive medicine at the Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver. He is on an advisory board for GlaxoSmithKline and provided medical-legal consultation for AstraZeneca.

SAN ANTONIO – Body mass index is strongly correlated with self-reported days of insufficient sleep per month among U.S. adults, based on a large national study.

The study included 384,020 U.S. adults who participated in the Centers for Disease Control and Prevention's 2008 Behavioral Risk Factor Surveillance System survey, the world's largest telephone health survey. The 2008 version asked: “During the past 30 days, for about how many days have you felt you did not get enough rest or sleep?”

Days of insufficient sleep followed a linear trend across body mass index (BMI) categories. Among the 36.8% of respondents who were normal weight or underweight, the mean number of days of insufficient sleep in the past month was 7.9. The 36.4% of the population who were overweight averaged 8.4 days. For the 17.1% who were obese class I with a BMI of at least 30 and less than 35 kg/m

Twenty-five percent of normal-weight respondents indicated they had 14 or more days of insufficient sleep in the past 30 days. This proportion rose steadily through the BMI categories, reaching 37.1% among individuals who were obese class III, added Ms. Wheaton of the CDC.

In a multivariate regression analysis adjusted for demographic variables, physical activity, and smoking, respondents who were obese class I, II, or III were, respectively, 1.4-fold, 1.6-fold, and 1.8-fold more likely than were normal-weight individuals to have had at least 14 days of insufficient sleep in the past 30 days.

One implication of this study, she said, is that insufficient sleep should be addressed in weight- reduction programs.

This study was supported by a grant from the Association for Prevention Teaching and Research, and the CDC. Ms. Wheaton reported no financial conflicts.

SAN ANTONIO – Body mass index is strongly correlated with self-reported days of insufficient sleep per month among U.S. adults, based on a large national study.

The study included 384,020 U.S. adults who participated in the Centers for Disease Control and Prevention's 2008 Behavioral Risk Factor Surveillance System survey, the world's largest telephone health survey. The 2008 version asked: “During the past 30 days, for about how many days have you felt you did not get enough rest or sleep?”

Days of insufficient sleep followed a linear trend across body mass index (BMI) categories. Among the 36.8% of respondents who were normal weight or underweight, the mean number of days of insufficient sleep in the past month was 7.9. The 36.4% of the population who were overweight averaged 8.4 days. For the 17.1% who were obese class I with a BMI of at least 30 and less than 35 kg/m

Twenty-five percent of normal-weight respondents indicated they had 14 or more days of insufficient sleep in the past 30 days. This proportion rose steadily through the BMI categories, reaching 37.1% among individuals who were obese class III, added Ms. Wheaton of the CDC.

In a multivariate regression analysis adjusted for demographic variables, physical activity, and smoking, respondents who were obese class I, II, or III were, respectively, 1.4-fold, 1.6-fold, and 1.8-fold more likely than were normal-weight individuals to have had at least 14 days of insufficient sleep in the past 30 days.

One implication of this study, she said, is that insufficient sleep should be addressed in weight- reduction programs.

This study was supported by a grant from the Association for Prevention Teaching and Research, and the CDC. Ms. Wheaton reported no financial conflicts.

SAN ANTONIO – Body mass index is strongly correlated with self-reported days of insufficient sleep per month among U.S. adults, based on a large national study.

The study included 384,020 U.S. adults who participated in the Centers for Disease Control and Prevention's 2008 Behavioral Risk Factor Surveillance System survey, the world's largest telephone health survey. The 2008 version asked: “During the past 30 days, for about how many days have you felt you did not get enough rest or sleep?”

Days of insufficient sleep followed a linear trend across body mass index (BMI) categories. Among the 36.8% of respondents who were normal weight or underweight, the mean number of days of insufficient sleep in the past month was 7.9. The 36.4% of the population who were overweight averaged 8.4 days. For the 17.1% who were obese class I with a BMI of at least 30 and less than 35 kg/m

Twenty-five percent of normal-weight respondents indicated they had 14 or more days of insufficient sleep in the past 30 days. This proportion rose steadily through the BMI categories, reaching 37.1% among individuals who were obese class III, added Ms. Wheaton of the CDC.

In a multivariate regression analysis adjusted for demographic variables, physical activity, and smoking, respondents who were obese class I, II, or III were, respectively, 1.4-fold, 1.6-fold, and 1.8-fold more likely than were normal-weight individuals to have had at least 14 days of insufficient sleep in the past 30 days.

One implication of this study, she said, is that insufficient sleep should be addressed in weight- reduction programs.

This study was supported by a grant from the Association for Prevention Teaching and Research, and the CDC. Ms. Wheaton reported no financial conflicts.

GOTHENBURG, SWEDEN – Updosing desloratadine by up to fourfold beyond the standard 5 mg for chronic spontaneous urticaria boosted treatment response with no effect on safety, according to the results of a randomized, double-blind controlled trial.

The findings support the current guidelines of the Global Allergy and Asthma European Network (GA

Dr. Elena Ardelean reported on 29 patients with chronic spontaneous urticaria who were randomized to either 5 or 20 mg of desloratadine (Clarinex) on two separate occasions when they presented with urticaria On another occasion they received no treatment. On all three occasions investigators evaluated them for 5 hours. The main end point was the number of spontaneously occurring wheals present at baseline versus 5 hours post treatment, compared with the spontaneous resolution rate with no treatment.

The reduction in wheals 5 hours after administration of 5 mg of desloratadine compared with baseline was 50% greater than with spontaneous resolution. But 20 mg resulted in a significantly greater 70% reduction, said Dr. Ardelean of Charité University Hospital, Berlin. There were no side effects with either dose of desloratadine

The trial was supported by GA2LEN. Dr. Ardelean said she had no relevant financial conflicts.

GOTHENBURG, SWEDEN – Updosing desloratadine by up to fourfold beyond the standard 5 mg for chronic spontaneous urticaria boosted treatment response with no effect on safety, according to the results of a randomized, double-blind controlled trial.

The findings support the current guidelines of the Global Allergy and Asthma European Network (GA

Dr. Elena Ardelean reported on 29 patients with chronic spontaneous urticaria who were randomized to either 5 or 20 mg of desloratadine (Clarinex) on two separate occasions when they presented with urticaria On another occasion they received no treatment. On all three occasions investigators evaluated them for 5 hours. The main end point was the number of spontaneously occurring wheals present at baseline versus 5 hours post treatment, compared with the spontaneous resolution rate with no treatment.

The reduction in wheals 5 hours after administration of 5 mg of desloratadine compared with baseline was 50% greater than with spontaneous resolution. But 20 mg resulted in a significantly greater 70% reduction, said Dr. Ardelean of Charité University Hospital, Berlin. There were no side effects with either dose of desloratadine

The trial was supported by GA2LEN. Dr. Ardelean said she had no relevant financial conflicts.

GOTHENBURG, SWEDEN – Updosing desloratadine by up to fourfold beyond the standard 5 mg for chronic spontaneous urticaria boosted treatment response with no effect on safety, according to the results of a randomized, double-blind controlled trial.

The findings support the current guidelines of the Global Allergy and Asthma European Network (GA

Dr. Elena Ardelean reported on 29 patients with chronic spontaneous urticaria who were randomized to either 5 or 20 mg of desloratadine (Clarinex) on two separate occasions when they presented with urticaria On another occasion they received no treatment. On all three occasions investigators evaluated them for 5 hours. The main end point was the number of spontaneously occurring wheals present at baseline versus 5 hours post treatment, compared with the spontaneous resolution rate with no treatment.

The reduction in wheals 5 hours after administration of 5 mg of desloratadine compared with baseline was 50% greater than with spontaneous resolution. But 20 mg resulted in a significantly greater 70% reduction, said Dr. Ardelean of Charité University Hospital, Berlin. There were no side effects with either dose of desloratadine

The trial was supported by GA2LEN. Dr. Ardelean said she had no relevant financial conflicts.