Patrice Wendling

Berlin — An investigational agent that targets the BRAF mutation and is present in at least half of melanoma patients has shown impressive results in a second phase I trial.

Response rates with the oral agent PLX4032 reached an unprecedented 70% in metastatic melanoma, signaling a fundamental shift in the way this deadly disease will be treated.

“What's very encouraging is actually that the response rate in nonmutated melanoma is 0%; so we know exactly what we're doing,” European Cancer Organization (ECCO) president Dr. Alexander Eggermont told reporters at the joint congress of ECCO and the European Society for Medical Oncology, where the latest data were presented.

The ability to target therapy based on genetic mutation status is expected to transform the once-bleak field of melanoma, which has seen no improvement in overall survival in the last 30 randomized trials using various chemotherapeutic agents and vaccines. The 5-year survival rate for stage IV melanoma remains at just 18%.

“If I have a young, talented medical oncologist at a cancer center, now I would have no reservations to recommend him to become a melanoma specialist because it's going to become a very exciting field instead of a graveyard,” Dr. Eggermont of Erasmus University in Rotterdam, the Netherlands, said at a press briefing. “One of the fellows here said, 'Wow, this is fantastic; now I will get time to get to know my metastatic melanoma patients.' That's how bad the field was. So this is simply fantastic.”

The phase I extension trial included 31 metastatic melanoma patients who had a BRAF mutation known as V600E and who were treated twice daily with 960 mg of PLX4032. Among 27 evaluable patients, the response rate was 70% by RECIST, including 18 partial responses and 1 complete response. One partial responder subsequently became a complete responder after the data analysis cutoff date.

Progression-free survival is about 8.5 months, although the median has not yet been reached, lead author Dr. Paul Chapman said. Overall survival was not measured. Tumor shrinkage on MRI showed that, after just 15 days of treatment, FDG (

Enthusiasm for the study, which was supported by Plexxicon Inc., was not diminished by the preliminary nature of the data or a string of disappointing late-phase results from other promising melanoma agents.

“My take—and I think it's pretty representative of many in the melanoma academic world—is that this is cataclysmic; this is hugely important,” Dr. David E. Fisher, chief of the dermatology service and director of the cutaneous biology research center at Massachusetts General Hospital, Boston, said in an interview.

Clinicians can predict which patients will respond and which won't, based on the presence of the BRAF

In a previous phase I dose-escalation trial in 55 patients with a variety of cancers, partial responses were reported in 9 of 16 metastatic melanoma patients with the BRAF

Because of the selectivity of the molecule, adverse events have tended to be mild, said Dr. Chapman, an attending physician on the melanoma/sarcoma service at Memorial Sloan-Kettering Cancer Center in New York. Common grade 3 events in the current trial were arthralgia (3%), rash (3%), photosensitivity (3%), and fatigue (7%).

A Disease of Subtypes

Dr. Chapman told reporters that genetic screening will have to become universal in melanoma, just as KRAS testing is essential in treating colorectal cancer. Screening can be completed in 1–2 weeks at active, participating centers.

The BRAF mutation is not the first example of a genetic subtype targeted in metastatic melanoma; Dr. Fisher and his colleagues reported dramatic results last year after targeting the c-KIT mutation with imatinib (Gleevec). Although the armamentarium is not deep for drugs that block BRAF, there are several available agents that target c-KIT, including nilotinib (Tasigna) and sunitinib (Sutent).

Although the signal from the PLX4032 trials is strong, the early data suggest that the single agent is not going to be enough, Dr. Fisher said. Future strategies will likely include combination therapy and the use of agents prior to the development of metastatic disease.

“We need complete remission. We need these tumors to melt away,” he said.

Reporters questioned whether PLX4032 could be used with the monoclonal antibody bevacizumab (Avastin), which increased overall survival by more than 40% when combined with the chemotherapeutic agents carboplatin and paclitaxel in a phase II metastatic melanoma trial that was also presented at the congress.

Dr. Chapman responded, “If you shrink the tumor too much with PLX4032, it may not be as sensitive to VEGF [vascular endothelial growth factor] inhibition, but from a toxicity point of view, I don't think there's any reason why we couldn't combine them.”

Further Trials

A phase II single arm trial (BRIM2) is evaluating 960 mg twice daily of PLX4032 in about 100 BRAF

The randomized, phase III BRIM3 trial is expected to start by the end of 2009 in first-line patients. Plexxicon is codeveloping PLX4032 with Roche.

Dr. Chapman said he had no conflicts of interest.

Melanoma is 'going to become a very exciting field instead of a graveyard.'

Source DR. EGGERMONT

Tumor shrinkage on MRI showed that, after just 15 days of treatment, FDG uptake was essentially shut down.

Source DR. CHAPMAN

Berlin — An investigational agent that targets the BRAF mutation and is present in at least half of melanoma patients has shown impressive results in a second phase I trial.

Response rates with the oral agent PLX4032 reached an unprecedented 70% in metastatic melanoma, signaling a fundamental shift in the way this deadly disease will be treated.

“What's very encouraging is actually that the response rate in nonmutated melanoma is 0%; so we know exactly what we're doing,” European Cancer Organization (ECCO) president Dr. Alexander Eggermont told reporters at the joint congress of ECCO and the European Society for Medical Oncology, where the latest data were presented.

The ability to target therapy based on genetic mutation status is expected to transform the once-bleak field of melanoma, which has seen no improvement in overall survival in the last 30 randomized trials using various chemotherapeutic agents and vaccines. The 5-year survival rate for stage IV melanoma remains at just 18%.

“If I have a young, talented medical oncologist at a cancer center, now I would have no reservations to recommend him to become a melanoma specialist because it's going to become a very exciting field instead of a graveyard,” Dr. Eggermont of Erasmus University in Rotterdam, the Netherlands, said at a press briefing. “One of the fellows here said, 'Wow, this is fantastic; now I will get time to get to know my metastatic melanoma patients.' That's how bad the field was. So this is simply fantastic.”

The phase I extension trial included 31 metastatic melanoma patients who had a BRAF mutation known as V600E and who were treated twice daily with 960 mg of PLX4032. Among 27 evaluable patients, the response rate was 70% by RECIST, including 18 partial responses and 1 complete response. One partial responder subsequently became a complete responder after the data analysis cutoff date.

Progression-free survival is about 8.5 months, although the median has not yet been reached, lead author Dr. Paul Chapman said. Overall survival was not measured. Tumor shrinkage on MRI showed that, after just 15 days of treatment, FDG (

Enthusiasm for the study, which was supported by Plexxicon Inc., was not diminished by the preliminary nature of the data or a string of disappointing late-phase results from other promising melanoma agents.

“My take—and I think it's pretty representative of many in the melanoma academic world—is that this is cataclysmic; this is hugely important,” Dr. David E. Fisher, chief of the dermatology service and director of the cutaneous biology research center at Massachusetts General Hospital, Boston, said in an interview.

Clinicians can predict which patients will respond and which won't, based on the presence of the BRAF

In a previous phase I dose-escalation trial in 55 patients with a variety of cancers, partial responses were reported in 9 of 16 metastatic melanoma patients with the BRAF

Because of the selectivity of the molecule, adverse events have tended to be mild, said Dr. Chapman, an attending physician on the melanoma/sarcoma service at Memorial Sloan-Kettering Cancer Center in New York. Common grade 3 events in the current trial were arthralgia (3%), rash (3%), photosensitivity (3%), and fatigue (7%).

A Disease of Subtypes

Dr. Chapman told reporters that genetic screening will have to become universal in melanoma, just as KRAS testing is essential in treating colorectal cancer. Screening can be completed in 1–2 weeks at active, participating centers.

The BRAF mutation is not the first example of a genetic subtype targeted in metastatic melanoma; Dr. Fisher and his colleagues reported dramatic results last year after targeting the c-KIT mutation with imatinib (Gleevec). Although the armamentarium is not deep for drugs that block BRAF, there are several available agents that target c-KIT, including nilotinib (Tasigna) and sunitinib (Sutent).

Although the signal from the PLX4032 trials is strong, the early data suggest that the single agent is not going to be enough, Dr. Fisher said. Future strategies will likely include combination therapy and the use of agents prior to the development of metastatic disease.

“We need complete remission. We need these tumors to melt away,” he said.

Reporters questioned whether PLX4032 could be used with the monoclonal antibody bevacizumab (Avastin), which increased overall survival by more than 40% when combined with the chemotherapeutic agents carboplatin and paclitaxel in a phase II metastatic melanoma trial that was also presented at the congress.

Dr. Chapman responded, “If you shrink the tumor too much with PLX4032, it may not be as sensitive to VEGF [vascular endothelial growth factor] inhibition, but from a toxicity point of view, I don't think there's any reason why we couldn't combine them.”

Further Trials

A phase II single arm trial (BRIM2) is evaluating 960 mg twice daily of PLX4032 in about 100 BRAF

The randomized, phase III BRIM3 trial is expected to start by the end of 2009 in first-line patients. Plexxicon is codeveloping PLX4032 with Roche.

Dr. Chapman said he had no conflicts of interest.

Melanoma is 'going to become a very exciting field instead of a graveyard.'

Source DR. EGGERMONT

Tumor shrinkage on MRI showed that, after just 15 days of treatment, FDG uptake was essentially shut down.

Source DR. CHAPMAN

Berlin — An investigational agent that targets the BRAF mutation and is present in at least half of melanoma patients has shown impressive results in a second phase I trial.

Response rates with the oral agent PLX4032 reached an unprecedented 70% in metastatic melanoma, signaling a fundamental shift in the way this deadly disease will be treated.

“What's very encouraging is actually that the response rate in nonmutated melanoma is 0%; so we know exactly what we're doing,” European Cancer Organization (ECCO) president Dr. Alexander Eggermont told reporters at the joint congress of ECCO and the European Society for Medical Oncology, where the latest data were presented.

The ability to target therapy based on genetic mutation status is expected to transform the once-bleak field of melanoma, which has seen no improvement in overall survival in the last 30 randomized trials using various chemotherapeutic agents and vaccines. The 5-year survival rate for stage IV melanoma remains at just 18%.

“If I have a young, talented medical oncologist at a cancer center, now I would have no reservations to recommend him to become a melanoma specialist because it's going to become a very exciting field instead of a graveyard,” Dr. Eggermont of Erasmus University in Rotterdam, the Netherlands, said at a press briefing. “One of the fellows here said, 'Wow, this is fantastic; now I will get time to get to know my metastatic melanoma patients.' That's how bad the field was. So this is simply fantastic.”

The phase I extension trial included 31 metastatic melanoma patients who had a BRAF mutation known as V600E and who were treated twice daily with 960 mg of PLX4032. Among 27 evaluable patients, the response rate was 70% by RECIST, including 18 partial responses and 1 complete response. One partial responder subsequently became a complete responder after the data analysis cutoff date.

Progression-free survival is about 8.5 months, although the median has not yet been reached, lead author Dr. Paul Chapman said. Overall survival was not measured. Tumor shrinkage on MRI showed that, after just 15 days of treatment, FDG (

Enthusiasm for the study, which was supported by Plexxicon Inc., was not diminished by the preliminary nature of the data or a string of disappointing late-phase results from other promising melanoma agents.

“My take—and I think it's pretty representative of many in the melanoma academic world—is that this is cataclysmic; this is hugely important,” Dr. David E. Fisher, chief of the dermatology service and director of the cutaneous biology research center at Massachusetts General Hospital, Boston, said in an interview.

Clinicians can predict which patients will respond and which won't, based on the presence of the BRAF

In a previous phase I dose-escalation trial in 55 patients with a variety of cancers, partial responses were reported in 9 of 16 metastatic melanoma patients with the BRAF

Because of the selectivity of the molecule, adverse events have tended to be mild, said Dr. Chapman, an attending physician on the melanoma/sarcoma service at Memorial Sloan-Kettering Cancer Center in New York. Common grade 3 events in the current trial were arthralgia (3%), rash (3%), photosensitivity (3%), and fatigue (7%).

A Disease of Subtypes

Dr. Chapman told reporters that genetic screening will have to become universal in melanoma, just as KRAS testing is essential in treating colorectal cancer. Screening can be completed in 1–2 weeks at active, participating centers.

The BRAF mutation is not the first example of a genetic subtype targeted in metastatic melanoma; Dr. Fisher and his colleagues reported dramatic results last year after targeting the c-KIT mutation with imatinib (Gleevec). Although the armamentarium is not deep for drugs that block BRAF, there are several available agents that target c-KIT, including nilotinib (Tasigna) and sunitinib (Sutent).

Although the signal from the PLX4032 trials is strong, the early data suggest that the single agent is not going to be enough, Dr. Fisher said. Future strategies will likely include combination therapy and the use of agents prior to the development of metastatic disease.

“We need complete remission. We need these tumors to melt away,” he said.

Reporters questioned whether PLX4032 could be used with the monoclonal antibody bevacizumab (Avastin), which increased overall survival by more than 40% when combined with the chemotherapeutic agents carboplatin and paclitaxel in a phase II metastatic melanoma trial that was also presented at the congress.

Dr. Chapman responded, “If you shrink the tumor too much with PLX4032, it may not be as sensitive to VEGF [vascular endothelial growth factor] inhibition, but from a toxicity point of view, I don't think there's any reason why we couldn't combine them.”

Further Trials

A phase II single arm trial (BRIM2) is evaluating 960 mg twice daily of PLX4032 in about 100 BRAF

The randomized, phase III BRIM3 trial is expected to start by the end of 2009 in first-line patients. Plexxicon is codeveloping PLX4032 with Roche.

Dr. Chapman said he had no conflicts of interest.

Melanoma is 'going to become a very exciting field instead of a graveyard.'

Source DR. EGGERMONT

Tumor shrinkage on MRI showed that, after just 15 days of treatment, FDG uptake was essentially shut down.

Source DR. CHAPMAN

HAMBURG, GERMANY — Transvaginal ultrasound is a useful method for detecting severe pelvic endometriosis and rectosigmoid involvement, according to a study of about 200 women.

Transvaginal ultrasound (TVS) is thought to be reliable for the diagnosis of ovarian endometriosis, but laparoscopy is still the standard for the diagnosis of pelvic endometriosis.

In a prospective, observational study of 201 women examined with TVS before undergoing laparoscopy for evaluation of pelvic pain lasting more than 6 months, 62 (31%) had no endometriosis at laparoscopy according to the revised American Fertility Association classification system, 33 (16%) had minimal disease, 31 (15%) mild, 27 (13%) moderate, and 48 (24%) severe disease, according to data presented at the World Congress on Ultrasound in Obstetrics and Gynecology. Percentages total less than 100% because of rounding.

With laparoscopy as the accepted standard, TVS had a sensitivity of 57% and specificity of 95% to diagnose the absence or presence of endometriosis, reported lead author Dr. Tom Holland of the Early Pregnancy and Gynecology Assessment Unit, University College London Hospitals.

The sensitivity and specificity to diagnosis absent to mild versus moderate to severe disease were 89% and 97%, and 85% and 98% for absent to moderate versus severe endometriosis. The positive and negative likelihood ratios for severe disease were 43.5 and 0.15, respectively.

“TVS performed by experienced operators has a high sensitivity and specificity at detecting severe pelvic endometriosis,” Dr Holland said. “TVS is a good method for triaging women with pelvic endometriosis for optimal surgical care.”

In a separate retrospective, observational study of 72 women, mean age 31 years, who had a bowel resection for presumed deep infiltrating endometriosis, preoperative TVS could detect deep infiltrating endometriosis of the rectosigmoid colon in 79% of cases, Dr. Dominique Van Schoubroeck reported during the same session at the meeting.

Deep endometriosis nodes were recorded by ultrasound as “yes” in 51 women, “possible” in 6, and “no” in 15 cases, with yes and possible cases considered abnormal. Histology reported deep nodes as present in 88% and absent in 12% of cases, said Dr. Van Schoubroeck, obstetrics and gynecology unit, University Hospitals, Catholic University Leuven, Leuven, Belgium. Accurate detection of nodes could help with surgical planning, she said.

Dr. Holland and Dr. Van Schoubroeck disclosed no conflicts of interest.

HAMBURG, GERMANY — Transvaginal ultrasound is a useful method for detecting severe pelvic endometriosis and rectosigmoid involvement, according to a study of about 200 women.

Transvaginal ultrasound (TVS) is thought to be reliable for the diagnosis of ovarian endometriosis, but laparoscopy is still the standard for the diagnosis of pelvic endometriosis.

In a prospective, observational study of 201 women examined with TVS before undergoing laparoscopy for evaluation of pelvic pain lasting more than 6 months, 62 (31%) had no endometriosis at laparoscopy according to the revised American Fertility Association classification system, 33 (16%) had minimal disease, 31 (15%) mild, 27 (13%) moderate, and 48 (24%) severe disease, according to data presented at the World Congress on Ultrasound in Obstetrics and Gynecology. Percentages total less than 100% because of rounding.

With laparoscopy as the accepted standard, TVS had a sensitivity of 57% and specificity of 95% to diagnose the absence or presence of endometriosis, reported lead author Dr. Tom Holland of the Early Pregnancy and Gynecology Assessment Unit, University College London Hospitals.

The sensitivity and specificity to diagnosis absent to mild versus moderate to severe disease were 89% and 97%, and 85% and 98% for absent to moderate versus severe endometriosis. The positive and negative likelihood ratios for severe disease were 43.5 and 0.15, respectively.

“TVS performed by experienced operators has a high sensitivity and specificity at detecting severe pelvic endometriosis,” Dr Holland said. “TVS is a good method for triaging women with pelvic endometriosis for optimal surgical care.”

In a separate retrospective, observational study of 72 women, mean age 31 years, who had a bowel resection for presumed deep infiltrating endometriosis, preoperative TVS could detect deep infiltrating endometriosis of the rectosigmoid colon in 79% of cases, Dr. Dominique Van Schoubroeck reported during the same session at the meeting.

Deep endometriosis nodes were recorded by ultrasound as “yes” in 51 women, “possible” in 6, and “no” in 15 cases, with yes and possible cases considered abnormal. Histology reported deep nodes as present in 88% and absent in 12% of cases, said Dr. Van Schoubroeck, obstetrics and gynecology unit, University Hospitals, Catholic University Leuven, Leuven, Belgium. Accurate detection of nodes could help with surgical planning, she said.

Dr. Holland and Dr. Van Schoubroeck disclosed no conflicts of interest.

HAMBURG, GERMANY — Transvaginal ultrasound is a useful method for detecting severe pelvic endometriosis and rectosigmoid involvement, according to a study of about 200 women.

Transvaginal ultrasound (TVS) is thought to be reliable for the diagnosis of ovarian endometriosis, but laparoscopy is still the standard for the diagnosis of pelvic endometriosis.

In a prospective, observational study of 201 women examined with TVS before undergoing laparoscopy for evaluation of pelvic pain lasting more than 6 months, 62 (31%) had no endometriosis at laparoscopy according to the revised American Fertility Association classification system, 33 (16%) had minimal disease, 31 (15%) mild, 27 (13%) moderate, and 48 (24%) severe disease, according to data presented at the World Congress on Ultrasound in Obstetrics and Gynecology. Percentages total less than 100% because of rounding.

With laparoscopy as the accepted standard, TVS had a sensitivity of 57% and specificity of 95% to diagnose the absence or presence of endometriosis, reported lead author Dr. Tom Holland of the Early Pregnancy and Gynecology Assessment Unit, University College London Hospitals.

The sensitivity and specificity to diagnosis absent to mild versus moderate to severe disease were 89% and 97%, and 85% and 98% for absent to moderate versus severe endometriosis. The positive and negative likelihood ratios for severe disease were 43.5 and 0.15, respectively.

“TVS performed by experienced operators has a high sensitivity and specificity at detecting severe pelvic endometriosis,” Dr Holland said. “TVS is a good method for triaging women with pelvic endometriosis for optimal surgical care.”

In a separate retrospective, observational study of 72 women, mean age 31 years, who had a bowel resection for presumed deep infiltrating endometriosis, preoperative TVS could detect deep infiltrating endometriosis of the rectosigmoid colon in 79% of cases, Dr. Dominique Van Schoubroeck reported during the same session at the meeting.

Deep endometriosis nodes were recorded by ultrasound as “yes” in 51 women, “possible” in 6, and “no” in 15 cases, with yes and possible cases considered abnormal. Histology reported deep nodes as present in 88% and absent in 12% of cases, said Dr. Van Schoubroeck, obstetrics and gynecology unit, University Hospitals, Catholic University Leuven, Leuven, Belgium. Accurate detection of nodes could help with surgical planning, she said.

Dr. Holland and Dr. Van Schoubroeck disclosed no conflicts of interest.

CHICAGO — Two trends are emerging in the development of investigational antihypertensive drugs.

Look for more fixed-dose combinations and agents with beneficial effects beyond blood pressure lowering alone, said Dr. George Bakris, director of the hypertensive diseases unit and professor of medicine at the University of Chicago.

“There's going to be a lot more in the armamentarium of combination therapy,” he said at a meeting sponsored by the International Society on Hypertension in Blacks. “Approximately 76% of all the 75 million hypertensives require two or more antihypertensive agents, and people are sick of taking pills.”

Takeda Pharmaceuticals recently launched a phase III trial of its investigational compound TAK-491, an angiotensin receptor blocker (ARB), combined with the diuretic chlorthalidone in patients with moderate to severe hypertension. Takeda expects TAK-491 to show stronger antihypertensive action and to have a profile in improving insulin resistance and decreasing proteinuria that is superior to existing ARBs. The company also expects that it will succeed its current mainstay product candesartan, also an ARB.

“It's not your mother's ARB,” Dr. Bakris said. “It could be the ARB tailored for the metabolic syndrome.”

Boehringer Ingelheim recently announced effective 24-hour blood pressure control with its investigational combination of the ARB telmisartan and the calcium channel blocker amlodipine in hypertensive patients at risk of cardiovascular events and those not controlled with amlodipine alone.

In April 2009, the Food and Drug Administration approved Exforge HCT, the only antihypertensive agent to include three medications—amlodipine, valsartan, and hydrochlorothiazide—in a single pill.

Neutral Endopeptidase Inhibitors

Neutral endopeptidase (NEP) inhibitors also are being given a second look, this time in combination with ARBs. NEP is the major enzymatic pathway of degradation of natriuretic peptides, which are thought to have such beneficial effects in hypertension as vasodilation, natriuresis, and inhibition of the sympathetic nervous system.

The investigational drug omapatrilat (Vanlev), which combined inhibition of both ACE and NEP, appeared to be a powerhouse, beating such leading agents as losartan and amlodipine. But its new drug application was withdrawn for a second time in 2002 because of reports of life-threatening angioedema.

“Theoretically, the synergy from an ARB/NEP combination should be similar. And because of lesser bradykinin effects, the risk is lower for angioedema, as ARBs have about a 10% incidence of angioedema, compared with ACE inhibitors,” Dr. Bakris explained in an interview. “The role of NEP is unclear since no one knows the mechanism of angioedema, but it is very rare in Caucasians and has an incidence of less than 0.01% in African Americans.”

Several ARB/NEP inhibitors, including MDL 100240 and MDL 100173, are in development, with these combinations expected probably in late 2010-2011, he said.

Endothelin Inhibitors

Finally, researchers are investigating combined ARB and endothelin inhibition. Endothelin (ET-1) is an amino acid peptide produced by the vascular endothelium and increases angiotensin II, aldosterone, antidiuretic hormone, thrombin, and reactive oxygen species. Studies have shown ET-1 is a powerful vasoconstrictor (Radiology 2001;219:419-26) and plays a role in salt retention (Circulation 2001;103:263-8).

Dr. Bakris noted that Gilead Sciences made a splash earlier this year when it released interim results showing dramatic additional blood pressure reductions with its selective endothelin A receptor antagonist darusentan in patients who had resistant hypertension despite maximal doses of a three-drug regimen that included a diuretic.

The phase III DAR-311 trial, also known as DORADO, met its coprimary efficacy end points, reporting that 14 weeks of once-daily oral darusentan 50 mg, 100 mg, and 300 mg significantly reduced mean trough sitting systolic BP by 18 mm Hg at the two higher doses and mean trough sitting diastolic BP by 10 mm Hg at all three doses.

“I helped design this study and none of us thought we would get this kind of effect,” he said. “This is definitely something that will be in the armamentarium for resistant hypertension,” Dr. Bakris said.

He suggested darusentan could be available in 6-9 months, but cautioned that it should not be considered for first-line treatment.

“In case you think this is such a gorilla you should start with it, that is not how these studies were designed and you should not extrapolate to that,” he said. “It would be wrong.”

He noted that treatment-related peripheral edema/fluid retention of about 1 L was an issue in about one-third of patients at each dose.

Dr. Bakris disclosed receiving research support from the Juvenile Diabetes Research Foundation, GlaxoSmithKline, Forest Labs, and CVRx, and serving as a consultant or speaker for GSK, Merck, Novartis, Boehringer Ingelheim, Takeda, Abbott, Walgreens, BMS/Sanofi, Gilead, and Forest.

CHICAGO — Two trends are emerging in the development of investigational antihypertensive drugs.

Look for more fixed-dose combinations and agents with beneficial effects beyond blood pressure lowering alone, said Dr. George Bakris, director of the hypertensive diseases unit and professor of medicine at the University of Chicago.

“There's going to be a lot more in the armamentarium of combination therapy,” he said at a meeting sponsored by the International Society on Hypertension in Blacks. “Approximately 76% of all the 75 million hypertensives require two or more antihypertensive agents, and people are sick of taking pills.”

Takeda Pharmaceuticals recently launched a phase III trial of its investigational compound TAK-491, an angiotensin receptor blocker (ARB), combined with the diuretic chlorthalidone in patients with moderate to severe hypertension. Takeda expects TAK-491 to show stronger antihypertensive action and to have a profile in improving insulin resistance and decreasing proteinuria that is superior to existing ARBs. The company also expects that it will succeed its current mainstay product candesartan, also an ARB.

“It's not your mother's ARB,” Dr. Bakris said. “It could be the ARB tailored for the metabolic syndrome.”

Boehringer Ingelheim recently announced effective 24-hour blood pressure control with its investigational combination of the ARB telmisartan and the calcium channel blocker amlodipine in hypertensive patients at risk of cardiovascular events and those not controlled with amlodipine alone.

In April 2009, the Food and Drug Administration approved Exforge HCT, the only antihypertensive agent to include three medications—amlodipine, valsartan, and hydrochlorothiazide—in a single pill.

Neutral Endopeptidase Inhibitors

Neutral endopeptidase (NEP) inhibitors also are being given a second look, this time in combination with ARBs. NEP is the major enzymatic pathway of degradation of natriuretic peptides, which are thought to have such beneficial effects in hypertension as vasodilation, natriuresis, and inhibition of the sympathetic nervous system.

The investigational drug omapatrilat (Vanlev), which combined inhibition of both ACE and NEP, appeared to be a powerhouse, beating such leading agents as losartan and amlodipine. But its new drug application was withdrawn for a second time in 2002 because of reports of life-threatening angioedema.

“Theoretically, the synergy from an ARB/NEP combination should be similar. And because of lesser bradykinin effects, the risk is lower for angioedema, as ARBs have about a 10% incidence of angioedema, compared with ACE inhibitors,” Dr. Bakris explained in an interview. “The role of NEP is unclear since no one knows the mechanism of angioedema, but it is very rare in Caucasians and has an incidence of less than 0.01% in African Americans.”

Several ARB/NEP inhibitors, including MDL 100240 and MDL 100173, are in development, with these combinations expected probably in late 2010-2011, he said.

Endothelin Inhibitors

Finally, researchers are investigating combined ARB and endothelin inhibition. Endothelin (ET-1) is an amino acid peptide produced by the vascular endothelium and increases angiotensin II, aldosterone, antidiuretic hormone, thrombin, and reactive oxygen species. Studies have shown ET-1 is a powerful vasoconstrictor (Radiology 2001;219:419-26) and plays a role in salt retention (Circulation 2001;103:263-8).

Dr. Bakris noted that Gilead Sciences made a splash earlier this year when it released interim results showing dramatic additional blood pressure reductions with its selective endothelin A receptor antagonist darusentan in patients who had resistant hypertension despite maximal doses of a three-drug regimen that included a diuretic.

The phase III DAR-311 trial, also known as DORADO, met its coprimary efficacy end points, reporting that 14 weeks of once-daily oral darusentan 50 mg, 100 mg, and 300 mg significantly reduced mean trough sitting systolic BP by 18 mm Hg at the two higher doses and mean trough sitting diastolic BP by 10 mm Hg at all three doses.

“I helped design this study and none of us thought we would get this kind of effect,” he said. “This is definitely something that will be in the armamentarium for resistant hypertension,” Dr. Bakris said.

He suggested darusentan could be available in 6-9 months, but cautioned that it should not be considered for first-line treatment.

“In case you think this is such a gorilla you should start with it, that is not how these studies were designed and you should not extrapolate to that,” he said. “It would be wrong.”

He noted that treatment-related peripheral edema/fluid retention of about 1 L was an issue in about one-third of patients at each dose.

Dr. Bakris disclosed receiving research support from the Juvenile Diabetes Research Foundation, GlaxoSmithKline, Forest Labs, and CVRx, and serving as a consultant or speaker for GSK, Merck, Novartis, Boehringer Ingelheim, Takeda, Abbott, Walgreens, BMS/Sanofi, Gilead, and Forest.

CHICAGO — Two trends are emerging in the development of investigational antihypertensive drugs.

Look for more fixed-dose combinations and agents with beneficial effects beyond blood pressure lowering alone, said Dr. George Bakris, director of the hypertensive diseases unit and professor of medicine at the University of Chicago.

“There's going to be a lot more in the armamentarium of combination therapy,” he said at a meeting sponsored by the International Society on Hypertension in Blacks. “Approximately 76% of all the 75 million hypertensives require two or more antihypertensive agents, and people are sick of taking pills.”

Takeda Pharmaceuticals recently launched a phase III trial of its investigational compound TAK-491, an angiotensin receptor blocker (ARB), combined with the diuretic chlorthalidone in patients with moderate to severe hypertension. Takeda expects TAK-491 to show stronger antihypertensive action and to have a profile in improving insulin resistance and decreasing proteinuria that is superior to existing ARBs. The company also expects that it will succeed its current mainstay product candesartan, also an ARB.

“It's not your mother's ARB,” Dr. Bakris said. “It could be the ARB tailored for the metabolic syndrome.”

Boehringer Ingelheim recently announced effective 24-hour blood pressure control with its investigational combination of the ARB telmisartan and the calcium channel blocker amlodipine in hypertensive patients at risk of cardiovascular events and those not controlled with amlodipine alone.

In April 2009, the Food and Drug Administration approved Exforge HCT, the only antihypertensive agent to include three medications—amlodipine, valsartan, and hydrochlorothiazide—in a single pill.

Neutral Endopeptidase Inhibitors

Neutral endopeptidase (NEP) inhibitors also are being given a second look, this time in combination with ARBs. NEP is the major enzymatic pathway of degradation of natriuretic peptides, which are thought to have such beneficial effects in hypertension as vasodilation, natriuresis, and inhibition of the sympathetic nervous system.

The investigational drug omapatrilat (Vanlev), which combined inhibition of both ACE and NEP, appeared to be a powerhouse, beating such leading agents as losartan and amlodipine. But its new drug application was withdrawn for a second time in 2002 because of reports of life-threatening angioedema.

“Theoretically, the synergy from an ARB/NEP combination should be similar. And because of lesser bradykinin effects, the risk is lower for angioedema, as ARBs have about a 10% incidence of angioedema, compared with ACE inhibitors,” Dr. Bakris explained in an interview. “The role of NEP is unclear since no one knows the mechanism of angioedema, but it is very rare in Caucasians and has an incidence of less than 0.01% in African Americans.”

Several ARB/NEP inhibitors, including MDL 100240 and MDL 100173, are in development, with these combinations expected probably in late 2010-2011, he said.

Endothelin Inhibitors

Finally, researchers are investigating combined ARB and endothelin inhibition. Endothelin (ET-1) is an amino acid peptide produced by the vascular endothelium and increases angiotensin II, aldosterone, antidiuretic hormone, thrombin, and reactive oxygen species. Studies have shown ET-1 is a powerful vasoconstrictor (Radiology 2001;219:419-26) and plays a role in salt retention (Circulation 2001;103:263-8).

Dr. Bakris noted that Gilead Sciences made a splash earlier this year when it released interim results showing dramatic additional blood pressure reductions with its selective endothelin A receptor antagonist darusentan in patients who had resistant hypertension despite maximal doses of a three-drug regimen that included a diuretic.

The phase III DAR-311 trial, also known as DORADO, met its coprimary efficacy end points, reporting that 14 weeks of once-daily oral darusentan 50 mg, 100 mg, and 300 mg significantly reduced mean trough sitting systolic BP by 18 mm Hg at the two higher doses and mean trough sitting diastolic BP by 10 mm Hg at all three doses.

“I helped design this study and none of us thought we would get this kind of effect,” he said. “This is definitely something that will be in the armamentarium for resistant hypertension,” Dr. Bakris said.

He suggested darusentan could be available in 6-9 months, but cautioned that it should not be considered for first-line treatment.

“In case you think this is such a gorilla you should start with it, that is not how these studies were designed and you should not extrapolate to that,” he said. “It would be wrong.”

He noted that treatment-related peripheral edema/fluid retention of about 1 L was an issue in about one-third of patients at each dose.

Dr. Bakris disclosed receiving research support from the Juvenile Diabetes Research Foundation, GlaxoSmithKline, Forest Labs, and CVRx, and serving as a consultant or speaker for GSK, Merck, Novartis, Boehringer Ingelheim, Takeda, Abbott, Walgreens, BMS/Sanofi, Gilead, and Forest.

CHICAGO — Nearly one-third of elderly general medicine patients were readmitted within 30 days in a retrospective analysis of 164 patients.

Neither inpatient providers nor a standardized algorithm accurately predicted which patients would be readmitted, Dr. Nazima Allaudeen and her associates reported in a poster at the annual meeting of the Society of Hospital Medicine.

“My take-home from this is [that] all of our patients are at risk,” she said in an interview. “Whatever intervention you're going to put in place—whether it be educating your patients more, making sure they have better social support, better patient medication—you really need to do it for everyone.”

Among 159 patients aged 65 years or older, discharged from the general medicine service at the University of California San Francisco Medical Center during a 5-week period beginning March 17, 2008, 52 (32.7%) were readmitted within 30 days. Five patients died during the 30-day postdischarge period.

The rate is much higher than was identified in a recent Northwestern University study in which nearly 20% of 11,855,702 Medicare beneficiaries were rehospitalized within 30 days (N. Engl. J. Med. 2009;360:1418-28).

The higher rate could be explained by the fact that data on unscheduled readmissions to other hospitals were captured—data often missed in other studies, said Dr. Allaudeen, of the Veterans Affairs Palo Alto (Calif.) Health Care System. The researchers reviewed electronic medical records at the local county hospital as well as their own institution, and telephoned patients or caregivers to determine readmission to outside hospitals. They also excluded patients who died during the 30-day postdischarge period.

In the current study, attending physicians did the best job of predicting who would be readmitted. Their mean predicted readmission rate of 32.5% fell just shy of the actual 32.7% rate. The predicted readmission rate was 41.5% using the probability of repeat admission (Pra) algorithm, which was calculated using eight variables extracted during chart review.

Readmissions cause significant distress to patients and caregivers, and are associated with considerable financial costs. The authors contend that it is especially critical for hospitals to have in place systematic interventions targeting general medicine patients now that Medicare may be changing reimbursement policies for hospital readmissions.

The authors disclosed no conflicts of interest.

CHICAGO — Nearly one-third of elderly general medicine patients were readmitted within 30 days in a retrospective analysis of 164 patients.

Neither inpatient providers nor a standardized algorithm accurately predicted which patients would be readmitted, Dr. Nazima Allaudeen and her associates reported in a poster at the annual meeting of the Society of Hospital Medicine.

“My take-home from this is [that] all of our patients are at risk,” she said in an interview. “Whatever intervention you're going to put in place—whether it be educating your patients more, making sure they have better social support, better patient medication—you really need to do it for everyone.”

Among 159 patients aged 65 years or older, discharged from the general medicine service at the University of California San Francisco Medical Center during a 5-week period beginning March 17, 2008, 52 (32.7%) were readmitted within 30 days. Five patients died during the 30-day postdischarge period.

The rate is much higher than was identified in a recent Northwestern University study in which nearly 20% of 11,855,702 Medicare beneficiaries were rehospitalized within 30 days (N. Engl. J. Med. 2009;360:1418-28).

The higher rate could be explained by the fact that data on unscheduled readmissions to other hospitals were captured—data often missed in other studies, said Dr. Allaudeen, of the Veterans Affairs Palo Alto (Calif.) Health Care System. The researchers reviewed electronic medical records at the local county hospital as well as their own institution, and telephoned patients or caregivers to determine readmission to outside hospitals. They also excluded patients who died during the 30-day postdischarge period.

In the current study, attending physicians did the best job of predicting who would be readmitted. Their mean predicted readmission rate of 32.5% fell just shy of the actual 32.7% rate. The predicted readmission rate was 41.5% using the probability of repeat admission (Pra) algorithm, which was calculated using eight variables extracted during chart review.

Readmissions cause significant distress to patients and caregivers, and are associated with considerable financial costs. The authors contend that it is especially critical for hospitals to have in place systematic interventions targeting general medicine patients now that Medicare may be changing reimbursement policies for hospital readmissions.

The authors disclosed no conflicts of interest.

CHICAGO — Nearly one-third of elderly general medicine patients were readmitted within 30 days in a retrospective analysis of 164 patients.

Neither inpatient providers nor a standardized algorithm accurately predicted which patients would be readmitted, Dr. Nazima Allaudeen and her associates reported in a poster at the annual meeting of the Society of Hospital Medicine.

“My take-home from this is [that] all of our patients are at risk,” she said in an interview. “Whatever intervention you're going to put in place—whether it be educating your patients more, making sure they have better social support, better patient medication—you really need to do it for everyone.”

Among 159 patients aged 65 years or older, discharged from the general medicine service at the University of California San Francisco Medical Center during a 5-week period beginning March 17, 2008, 52 (32.7%) were readmitted within 30 days. Five patients died during the 30-day postdischarge period.

The rate is much higher than was identified in a recent Northwestern University study in which nearly 20% of 11,855,702 Medicare beneficiaries were rehospitalized within 30 days (N. Engl. J. Med. 2009;360:1418-28).

The higher rate could be explained by the fact that data on unscheduled readmissions to other hospitals were captured—data often missed in other studies, said Dr. Allaudeen, of the Veterans Affairs Palo Alto (Calif.) Health Care System. The researchers reviewed electronic medical records at the local county hospital as well as their own institution, and telephoned patients or caregivers to determine readmission to outside hospitals. They also excluded patients who died during the 30-day postdischarge period.

In the current study, attending physicians did the best job of predicting who would be readmitted. Their mean predicted readmission rate of 32.5% fell just shy of the actual 32.7% rate. The predicted readmission rate was 41.5% using the probability of repeat admission (Pra) algorithm, which was calculated using eight variables extracted during chart review.

Readmissions cause significant distress to patients and caregivers, and are associated with considerable financial costs. The authors contend that it is especially critical for hospitals to have in place systematic interventions targeting general medicine patients now that Medicare may be changing reimbursement policies for hospital readmissions.

The authors disclosed no conflicts of interest.

CHICAGO — A short, structured nurse-led educational intervention for patients with irritable bowel syndrome appeared to be as effective in reducing symptoms as a longer, multidisciplinary program, suggest findings from a small randomized trial.

The study evenly randomized 74 patients to six, 2-hour sessions led by a specialist nurse, gastroenterologist, dietician, physiotherapist, and a psychologist or to three, 2-hour sessions led by a specialist nurse using the same content as in the multidisciplinary education.

Knowledge of irritable bowel syndrome (IBS) significantly improved in both groups as measured using a visual analog scale, with no between-group differences observed at 3 and 6 months follow-up, Gisela Ringström, R.N., Ph.D., and her colleagues reported in a poster at meeting on neurogastroenterology and motility.

The score on the IBS Severity Scoring System was reduced in a similar way in both groups, with 33% of the patients in the nurse-led group and 32% in the multidisciplinary group achieving a clinically significant improvement in symptoms, as demonstrated by a reduction of at least 50 points.

Significant improvements were also observed in GI-specific anxiety on the Visceral Sensitivity Index and in several of the nine dimensions on the IBS Quality of Life Questionnaire, according to the investigators from the gastroenterology and hepatology section of the Sahlgrenska University Hospital in Göteborg, Sweden.

The findings are clinically important because approximately 10%-20% of the population in western countries suffer from functional GI disorders, Dr. Ringström said in an interview.

In a separate study, led by Dr. Ringström, 80% of 86 IBS patients referred to a gastroenterologist from primary care had knowledge about IBS, but only 15% felt they had received enough information (Gastroenterol. Nurs. 2009;32:284-92).

In the current study, each patient stated an individual goal before they were included in the study, with 59% of patients in both groups reporting they had met their individual goal, Dr. Ringström and her colleagues reported at the meeting, which was hosted by the Functional Brain-Gut Research Group. Patient evaluation of the content and organization of the intervention on a 7-point scale did not differ between the two groups, reaching a median score of 6-7.

The mean age was 38 years in the nurse-led group and 36 years in the multidisciplinary group, with 92% and 81% female, respectively.

The study was supported by grants from the Swedish Medical Research Council and the Health and Medical Care Committee of the Region of Västra Götaland. The authors disclosed no conflicts of interest.

CHICAGO — A short, structured nurse-led educational intervention for patients with irritable bowel syndrome appeared to be as effective in reducing symptoms as a longer, multidisciplinary program, suggest findings from a small randomized trial.

The study evenly randomized 74 patients to six, 2-hour sessions led by a specialist nurse, gastroenterologist, dietician, physiotherapist, and a psychologist or to three, 2-hour sessions led by a specialist nurse using the same content as in the multidisciplinary education.

Knowledge of irritable bowel syndrome (IBS) significantly improved in both groups as measured using a visual analog scale, with no between-group differences observed at 3 and 6 months follow-up, Gisela Ringström, R.N., Ph.D., and her colleagues reported in a poster at meeting on neurogastroenterology and motility.

The score on the IBS Severity Scoring System was reduced in a similar way in both groups, with 33% of the patients in the nurse-led group and 32% in the multidisciplinary group achieving a clinically significant improvement in symptoms, as demonstrated by a reduction of at least 50 points.

Significant improvements were also observed in GI-specific anxiety on the Visceral Sensitivity Index and in several of the nine dimensions on the IBS Quality of Life Questionnaire, according to the investigators from the gastroenterology and hepatology section of the Sahlgrenska University Hospital in Göteborg, Sweden.

The findings are clinically important because approximately 10%-20% of the population in western countries suffer from functional GI disorders, Dr. Ringström said in an interview.

In a separate study, led by Dr. Ringström, 80% of 86 IBS patients referred to a gastroenterologist from primary care had knowledge about IBS, but only 15% felt they had received enough information (Gastroenterol. Nurs. 2009;32:284-92).

In the current study, each patient stated an individual goal before they were included in the study, with 59% of patients in both groups reporting they had met their individual goal, Dr. Ringström and her colleagues reported at the meeting, which was hosted by the Functional Brain-Gut Research Group. Patient evaluation of the content and organization of the intervention on a 7-point scale did not differ between the two groups, reaching a median score of 6-7.

The mean age was 38 years in the nurse-led group and 36 years in the multidisciplinary group, with 92% and 81% female, respectively.

The study was supported by grants from the Swedish Medical Research Council and the Health and Medical Care Committee of the Region of Västra Götaland. The authors disclosed no conflicts of interest.

CHICAGO — A short, structured nurse-led educational intervention for patients with irritable bowel syndrome appeared to be as effective in reducing symptoms as a longer, multidisciplinary program, suggest findings from a small randomized trial.

The study evenly randomized 74 patients to six, 2-hour sessions led by a specialist nurse, gastroenterologist, dietician, physiotherapist, and a psychologist or to three, 2-hour sessions led by a specialist nurse using the same content as in the multidisciplinary education.

Knowledge of irritable bowel syndrome (IBS) significantly improved in both groups as measured using a visual analog scale, with no between-group differences observed at 3 and 6 months follow-up, Gisela Ringström, R.N., Ph.D., and her colleagues reported in a poster at meeting on neurogastroenterology and motility.

The score on the IBS Severity Scoring System was reduced in a similar way in both groups, with 33% of the patients in the nurse-led group and 32% in the multidisciplinary group achieving a clinically significant improvement in symptoms, as demonstrated by a reduction of at least 50 points.

Significant improvements were also observed in GI-specific anxiety on the Visceral Sensitivity Index and in several of the nine dimensions on the IBS Quality of Life Questionnaire, according to the investigators from the gastroenterology and hepatology section of the Sahlgrenska University Hospital in Göteborg, Sweden.

The findings are clinically important because approximately 10%-20% of the population in western countries suffer from functional GI disorders, Dr. Ringström said in an interview.

In a separate study, led by Dr. Ringström, 80% of 86 IBS patients referred to a gastroenterologist from primary care had knowledge about IBS, but only 15% felt they had received enough information (Gastroenterol. Nurs. 2009;32:284-92).

In the current study, each patient stated an individual goal before they were included in the study, with 59% of patients in both groups reporting they had met their individual goal, Dr. Ringström and her colleagues reported at the meeting, which was hosted by the Functional Brain-Gut Research Group. Patient evaluation of the content and organization of the intervention on a 7-point scale did not differ between the two groups, reaching a median score of 6-7.

The mean age was 38 years in the nurse-led group and 36 years in the multidisciplinary group, with 92% and 81% female, respectively.

The study was supported by grants from the Swedish Medical Research Council and the Health and Medical Care Committee of the Region of Västra Götaland. The authors disclosed no conflicts of interest.

CHICAGO — Screening patients with irritable bowel syndrome for restless legs syndrome may lead to greater identification of RLS and improved treatment for both conditions, new research suggests.

In a single, community-based gastroenterology center, 29% of 90 patients with irritable bowel syndrome (IBS) based on Rome III criteria were also diagnosed with RLS. The prevalence of RLS in the general population is 1%-10%.

All patients with both IBS and RLS had alterations in the initiation and maintenance of sleep, lead author Dr. P. Patrick Basu and his associates reported in a poster at a meeting on neurogastroenterology and motility. Involuntary jerks and wakefulness during more than 30% of sleep time occurred in 75% and 63% of patients, respectively.

Of the 26 patients with RLS, 62% had diarrhea-predominant IBS, while 4% had constipation-predominant IBS and 33% had mixed IBS, suggesting that the specific pathophysiology of diarrhea-predominant IBS may contribute to or relate to RLS. Previous research has identified an association between small intestinal bacterial overgrowth, a factor that may contribute to IBS, and several sensory disorders including fibromyalgia, interstitial cystitis, and RLS.

“Diagnosis of simultaneous IBS and RLS may provide enhanced therapeutic efficacy for these patients, as some medications, i.e., rifaximin, may provide relief for both conditions,” wrote Dr. Basu, director of gastroenterology, North Shore–Long Island Jewish Health System at Forest Hills, N.Y., and his associates.

Although the data were not included in the poster, 19 of the 26 IBS patients with RLS were treated with the antibiotic rifaximin, with 9 reporting relief of their RLS symptoms, Dr. Basu said. The diagnosis of RLS was made using a standard questionnaire formulated by the International Restless Legs Syndrome Study Group and was confirmed by polysomnography.

Dr. Basu's decision to use rifaximin was prompted by an independent study in 13 patients with IBS and a positive lactulose breath test, an indicator of small intestinal bacterial overgrowth, in which rifaximin 1,200 mg/day for 10 days was associated with at least an 80% improvement from baseline in RLS symptoms in 10 patients and a “great” or “moderate” global GI symptom improvement in 11 patients (Dig. Dis. Sci. 2008;53:1252-6). Five of the 10 patients followed long term (mean 139 days) maintained complete resolution of their RLS symptoms.

Dr. Basu uses rifaximin plus probiotics in his own practice for patients with both RLS and IBS, and is planning to evaluate its efficacy at doses up to 1,400 mg/day in combination with probiotics in 75 IBS patients with RLS.

Two recent studies from Washington University School of Medicine, St. Louis, examined whether RLS is associated with celiac disease and Crohn's disease, because all three conditions are associated with iron deficiency. The incidence of RLS was 35% among 85 patients with celiac disease (Dig. Dis. Sci. 2009 Sept. 3 [Epub ahead of print]) and 43% among 272 consecutive patients with Crohn's disease (Inflammatory Bowel Dis. 2009 July 2 [doi:10.1002/ibd.21001]). The rate of iron deficiency was significantly higher among celiac patients with active RLS versus those without RLS, but there was no difference between Crohn's patients with and without RLS with respect to current iron deficiency.

Dr. Basu and associates reported no conflicts of interest. Support for preparation of the poster was provided by Salix Pharmaceuticals, which markets rifaximin as Xifaxan.

CHICAGO — Screening patients with irritable bowel syndrome for restless legs syndrome may lead to greater identification of RLS and improved treatment for both conditions, new research suggests.

In a single, community-based gastroenterology center, 29% of 90 patients with irritable bowel syndrome (IBS) based on Rome III criteria were also diagnosed with RLS. The prevalence of RLS in the general population is 1%-10%.

All patients with both IBS and RLS had alterations in the initiation and maintenance of sleep, lead author Dr. P. Patrick Basu and his associates reported in a poster at a meeting on neurogastroenterology and motility. Involuntary jerks and wakefulness during more than 30% of sleep time occurred in 75% and 63% of patients, respectively.

Of the 26 patients with RLS, 62% had diarrhea-predominant IBS, while 4% had constipation-predominant IBS and 33% had mixed IBS, suggesting that the specific pathophysiology of diarrhea-predominant IBS may contribute to or relate to RLS. Previous research has identified an association between small intestinal bacterial overgrowth, a factor that may contribute to IBS, and several sensory disorders including fibromyalgia, interstitial cystitis, and RLS.

“Diagnosis of simultaneous IBS and RLS may provide enhanced therapeutic efficacy for these patients, as some medications, i.e., rifaximin, may provide relief for both conditions,” wrote Dr. Basu, director of gastroenterology, North Shore–Long Island Jewish Health System at Forest Hills, N.Y., and his associates.

Although the data were not included in the poster, 19 of the 26 IBS patients with RLS were treated with the antibiotic rifaximin, with 9 reporting relief of their RLS symptoms, Dr. Basu said. The diagnosis of RLS was made using a standard questionnaire formulated by the International Restless Legs Syndrome Study Group and was confirmed by polysomnography.

Dr. Basu's decision to use rifaximin was prompted by an independent study in 13 patients with IBS and a positive lactulose breath test, an indicator of small intestinal bacterial overgrowth, in which rifaximin 1,200 mg/day for 10 days was associated with at least an 80% improvement from baseline in RLS symptoms in 10 patients and a “great” or “moderate” global GI symptom improvement in 11 patients (Dig. Dis. Sci. 2008;53:1252-6). Five of the 10 patients followed long term (mean 139 days) maintained complete resolution of their RLS symptoms.

Dr. Basu uses rifaximin plus probiotics in his own practice for patients with both RLS and IBS, and is planning to evaluate its efficacy at doses up to 1,400 mg/day in combination with probiotics in 75 IBS patients with RLS.

Two recent studies from Washington University School of Medicine, St. Louis, examined whether RLS is associated with celiac disease and Crohn's disease, because all three conditions are associated with iron deficiency. The incidence of RLS was 35% among 85 patients with celiac disease (Dig. Dis. Sci. 2009 Sept. 3 [Epub ahead of print]) and 43% among 272 consecutive patients with Crohn's disease (Inflammatory Bowel Dis. 2009 July 2 [doi:10.1002/ibd.21001]). The rate of iron deficiency was significantly higher among celiac patients with active RLS versus those without RLS, but there was no difference between Crohn's patients with and without RLS with respect to current iron deficiency.

Dr. Basu and associates reported no conflicts of interest. Support for preparation of the poster was provided by Salix Pharmaceuticals, which markets rifaximin as Xifaxan.

CHICAGO — Screening patients with irritable bowel syndrome for restless legs syndrome may lead to greater identification of RLS and improved treatment for both conditions, new research suggests.

In a single, community-based gastroenterology center, 29% of 90 patients with irritable bowel syndrome (IBS) based on Rome III criteria were also diagnosed with RLS. The prevalence of RLS in the general population is 1%-10%.

All patients with both IBS and RLS had alterations in the initiation and maintenance of sleep, lead author Dr. P. Patrick Basu and his associates reported in a poster at a meeting on neurogastroenterology and motility. Involuntary jerks and wakefulness during more than 30% of sleep time occurred in 75% and 63% of patients, respectively.

Of the 26 patients with RLS, 62% had diarrhea-predominant IBS, while 4% had constipation-predominant IBS and 33% had mixed IBS, suggesting that the specific pathophysiology of diarrhea-predominant IBS may contribute to or relate to RLS. Previous research has identified an association between small intestinal bacterial overgrowth, a factor that may contribute to IBS, and several sensory disorders including fibromyalgia, interstitial cystitis, and RLS.

“Diagnosis of simultaneous IBS and RLS may provide enhanced therapeutic efficacy for these patients, as some medications, i.e., rifaximin, may provide relief for both conditions,” wrote Dr. Basu, director of gastroenterology, North Shore–Long Island Jewish Health System at Forest Hills, N.Y., and his associates.

Although the data were not included in the poster, 19 of the 26 IBS patients with RLS were treated with the antibiotic rifaximin, with 9 reporting relief of their RLS symptoms, Dr. Basu said. The diagnosis of RLS was made using a standard questionnaire formulated by the International Restless Legs Syndrome Study Group and was confirmed by polysomnography.

Dr. Basu's decision to use rifaximin was prompted by an independent study in 13 patients with IBS and a positive lactulose breath test, an indicator of small intestinal bacterial overgrowth, in which rifaximin 1,200 mg/day for 10 days was associated with at least an 80% improvement from baseline in RLS symptoms in 10 patients and a “great” or “moderate” global GI symptom improvement in 11 patients (Dig. Dis. Sci. 2008;53:1252-6). Five of the 10 patients followed long term (mean 139 days) maintained complete resolution of their RLS symptoms.

Dr. Basu uses rifaximin plus probiotics in his own practice for patients with both RLS and IBS, and is planning to evaluate its efficacy at doses up to 1,400 mg/day in combination with probiotics in 75 IBS patients with RLS.

Two recent studies from Washington University School of Medicine, St. Louis, examined whether RLS is associated with celiac disease and Crohn's disease, because all three conditions are associated with iron deficiency. The incidence of RLS was 35% among 85 patients with celiac disease (Dig. Dis. Sci. 2009 Sept. 3 [Epub ahead of print]) and 43% among 272 consecutive patients with Crohn's disease (Inflammatory Bowel Dis. 2009 July 2 [doi:10.1002/ibd.21001]). The rate of iron deficiency was significantly higher among celiac patients with active RLS versus those without RLS, but there was no difference between Crohn's patients with and without RLS with respect to current iron deficiency.

Dr. Basu and associates reported no conflicts of interest. Support for preparation of the poster was provided by Salix Pharmaceuticals, which markets rifaximin as Xifaxan.

CHICAGO — Screening patients with irritable bowel syndrome for restless legs syndrome may lead to greater identification of RLS and improved treatment for both conditions, new research suggests.

In a single, community-based gastroenterology center, 29% of 90 patients with IBS based on Rome III criteria were also diagnosed with RLS. The prevalence of RLS in the general population is 1%-10%.

All patients with both IBS and RLS had alterations in the initiation and maintenance of sleep, lead author Dr. P. Patrick Basu and his associates reported in a poster at a meeting on neurogastroenterology and motility. Involuntary jerks occurred in 75% of patients and wakefulness occurred in 63% for more than 30% of sleep time

Of the 26 patients with both RLS and IBS, 62% had diarrhea-predominant IBS, while 4% had constipation-predominant IBS and 33% had mixed IBS, suggesting that the specific pathophysiology of diarrhea-predominant IBS may contribute to or relate to RLS. Previous research has identified an association between small intestinal bacterial overgrowth, a factor that may contribute to IBS, and several sensory disorders including fibromyalgia, interstitial cystitis, and RLS.

“Diagnosis of simultaneous IBS and RLS may provide enhanced therapeutic efficacy for these patients, as some medications, i.e., rifaximin, may provide relief for both conditions,” wrote Dr. Basu, director of gastroenterology, North Shore–Long Island Jewish Health System at Forest Hills, N.Y., and his associates.

Although the data were not included in the poster, 19 of the 26 patients with both IBS and RLS were treated with the antibiotic rifaximin, with 9 reporting relief of their RLS symptoms, Dr. Basu said in an interview. The diagnosis of RLS was made using a standard questionnaire formulated by the International Restless Legs Syndrome Study Group and was confirmed by polysomnography.

Dr. Basu's decision to use rifaximin was prompted by an independent study in 13 patients with IBS and a positive lactulose breath test, an indicator of small intestinal bacterial overgrowth, in which rifaximin 1,200 mg/day for 10 days was associated with at least an 80% improvement from baseline in RLS symptoms in 10 patients and a “great” or “moderate” global GI symptom improvement in 11 patients (Dig. Dis. Sci. 2008;53:1252–6). Five of the 10 patients followed long term (mean 139 days) maintained complete resolution of their RLS symptoms.

Dr. Basu uses rifaximin plus probiotics in his own practice for patients with both RLS and IBS, and is planning to evaluate its efficacy at doses up to 1,400 mg/day in combination with probiotics in 75 IBS patients with RLS.

Two recent studies from Washington University, St. Louis, examined whether RLS is associated with celiac disease and Crohn's disease, because all three conditions are associated with iron deficiency. The incidence of RLS was 35% among 85 patients with celiac disease (Dig. Dis. Sci. 2009 Sept. 3 [Epub ahead of print]) and 43% among 272 consecutive patients with Crohn's disease (Inflamm. Bowel Dis. 2009 July 2 [doi:10.1002/ibd.21001

Dr. Basu noted that screening IBS patients for RLS may allow greater identification and subsequent treatment of RLS, which is thought to be underdiagnosed, even in the general population.

“I have a large population of IBS patients at my main office in Queens, which is an interesting cauldron of all populations, and I just started asking casually and more than 60% of patients had symptoms,” he said.

The mean age of the 90-patient cohort was 33 years; 60 were female, 38 were Hispanic, 26 white, 24 Asian, and 2 black.

Dr. Basu and associates reported no conflicts of interest. Support for preparation of the poster was provided by Salix Pharmaceuticals, which markets rifaximin as Xifaxan.

CHICAGO — Screening patients with irritable bowel syndrome for restless legs syndrome may lead to greater identification of RLS and improved treatment for both conditions, new research suggests.

In a single, community-based gastroenterology center, 29% of 90 patients with IBS based on Rome III criteria were also diagnosed with RLS. The prevalence of RLS in the general population is 1%-10%.

All patients with both IBS and RLS had alterations in the initiation and maintenance of sleep, lead author Dr. P. Patrick Basu and his associates reported in a poster at a meeting on neurogastroenterology and motility. Involuntary jerks occurred in 75% of patients and wakefulness occurred in 63% for more than 30% of sleep time

Of the 26 patients with both RLS and IBS, 62% had diarrhea-predominant IBS, while 4% had constipation-predominant IBS and 33% had mixed IBS, suggesting that the specific pathophysiology of diarrhea-predominant IBS may contribute to or relate to RLS. Previous research has identified an association between small intestinal bacterial overgrowth, a factor that may contribute to IBS, and several sensory disorders including fibromyalgia, interstitial cystitis, and RLS.

“Diagnosis of simultaneous IBS and RLS may provide enhanced therapeutic efficacy for these patients, as some medications, i.e., rifaximin, may provide relief for both conditions,” wrote Dr. Basu, director of gastroenterology, North Shore–Long Island Jewish Health System at Forest Hills, N.Y., and his associates.

Although the data were not included in the poster, 19 of the 26 patients with both IBS and RLS were treated with the antibiotic rifaximin, with 9 reporting relief of their RLS symptoms, Dr. Basu said in an interview. The diagnosis of RLS was made using a standard questionnaire formulated by the International Restless Legs Syndrome Study Group and was confirmed by polysomnography.

Dr. Basu's decision to use rifaximin was prompted by an independent study in 13 patients with IBS and a positive lactulose breath test, an indicator of small intestinal bacterial overgrowth, in which rifaximin 1,200 mg/day for 10 days was associated with at least an 80% improvement from baseline in RLS symptoms in 10 patients and a “great” or “moderate” global GI symptom improvement in 11 patients (Dig. Dis. Sci. 2008;53:1252–6). Five of the 10 patients followed long term (mean 139 days) maintained complete resolution of their RLS symptoms.

Dr. Basu uses rifaximin plus probiotics in his own practice for patients with both RLS and IBS, and is planning to evaluate its efficacy at doses up to 1,400 mg/day in combination with probiotics in 75 IBS patients with RLS.

Two recent studies from Washington University, St. Louis, examined whether RLS is associated with celiac disease and Crohn's disease, because all three conditions are associated with iron deficiency. The incidence of RLS was 35% among 85 patients with celiac disease (Dig. Dis. Sci. 2009 Sept. 3 [Epub ahead of print]) and 43% among 272 consecutive patients with Crohn's disease (Inflamm. Bowel Dis. 2009 July 2 [doi:10.1002/ibd.21001

Dr. Basu noted that screening IBS patients for RLS may allow greater identification and subsequent treatment of RLS, which is thought to be underdiagnosed, even in the general population.

“I have a large population of IBS patients at my main office in Queens, which is an interesting cauldron of all populations, and I just started asking casually and more than 60% of patients had symptoms,” he said.

The mean age of the 90-patient cohort was 33 years; 60 were female, 38 were Hispanic, 26 white, 24 Asian, and 2 black.

Dr. Basu and associates reported no conflicts of interest. Support for preparation of the poster was provided by Salix Pharmaceuticals, which markets rifaximin as Xifaxan.

CHICAGO — Screening patients with irritable bowel syndrome for restless legs syndrome may lead to greater identification of RLS and improved treatment for both conditions, new research suggests.

In a single, community-based gastroenterology center, 29% of 90 patients with IBS based on Rome III criteria were also diagnosed with RLS. The prevalence of RLS in the general population is 1%-10%.

All patients with both IBS and RLS had alterations in the initiation and maintenance of sleep, lead author Dr. P. Patrick Basu and his associates reported in a poster at a meeting on neurogastroenterology and motility. Involuntary jerks occurred in 75% of patients and wakefulness occurred in 63% for more than 30% of sleep time

Of the 26 patients with both RLS and IBS, 62% had diarrhea-predominant IBS, while 4% had constipation-predominant IBS and 33% had mixed IBS, suggesting that the specific pathophysiology of diarrhea-predominant IBS may contribute to or relate to RLS. Previous research has identified an association between small intestinal bacterial overgrowth, a factor that may contribute to IBS, and several sensory disorders including fibromyalgia, interstitial cystitis, and RLS.

“Diagnosis of simultaneous IBS and RLS may provide enhanced therapeutic efficacy for these patients, as some medications, i.e., rifaximin, may provide relief for both conditions,” wrote Dr. Basu, director of gastroenterology, North Shore–Long Island Jewish Health System at Forest Hills, N.Y., and his associates.

Although the data were not included in the poster, 19 of the 26 patients with both IBS and RLS were treated with the antibiotic rifaximin, with 9 reporting relief of their RLS symptoms, Dr. Basu said in an interview. The diagnosis of RLS was made using a standard questionnaire formulated by the International Restless Legs Syndrome Study Group and was confirmed by polysomnography.

Dr. Basu's decision to use rifaximin was prompted by an independent study in 13 patients with IBS and a positive lactulose breath test, an indicator of small intestinal bacterial overgrowth, in which rifaximin 1,200 mg/day for 10 days was associated with at least an 80% improvement from baseline in RLS symptoms in 10 patients and a “great” or “moderate” global GI symptom improvement in 11 patients (Dig. Dis. Sci. 2008;53:1252–6). Five of the 10 patients followed long term (mean 139 days) maintained complete resolution of their RLS symptoms.

Dr. Basu uses rifaximin plus probiotics in his own practice for patients with both RLS and IBS, and is planning to evaluate its efficacy at doses up to 1,400 mg/day in combination with probiotics in 75 IBS patients with RLS.

Two recent studies from Washington University, St. Louis, examined whether RLS is associated with celiac disease and Crohn's disease, because all three conditions are associated with iron deficiency. The incidence of RLS was 35% among 85 patients with celiac disease (Dig. Dis. Sci. 2009 Sept. 3 [Epub ahead of print]) and 43% among 272 consecutive patients with Crohn's disease (Inflamm. Bowel Dis. 2009 July 2 [doi:10.1002/ibd.21001

Dr. Basu noted that screening IBS patients for RLS may allow greater identification and subsequent treatment of RLS, which is thought to be underdiagnosed, even in the general population.

“I have a large population of IBS patients at my main office in Queens, which is an interesting cauldron of all populations, and I just started asking casually and more than 60% of patients had symptoms,” he said.

The mean age of the 90-patient cohort was 33 years; 60 were female, 38 were Hispanic, 26 white, 24 Asian, and 2 black.

Dr. Basu and associates reported no conflicts of interest. Support for preparation of the poster was provided by Salix Pharmaceuticals, which markets rifaximin as Xifaxan.

Soldiers and their families are being offered free access to psychotherapy across the country.

The Soldiers Project is providing confidential psychotherapy to address the growing need for comprehensive mental health care for military personnel and their families and to stop the transmission of trauma to future generations, according to project founder and director Dr. Judith Broder.

“We know that when people are traumatized and it's not treated that the trauma gets carried on to their children and their children's children, but if there's early intervention and treatment then the traumatized person is less likely to be a transmitter,” said Dr. Broder, a psychiatrist and psychoanalyst. “That's the basic impetus—to get in there early and as intensive as possible, and that's a fundamental difference from the services the VA [Veterans Administration] can provide.

“We see soldiers and their families for as long as they need—sometimes for up to 2½ years—for free.”

Started in 2004 under the aegis of the Los Angeles Institute and Society of Psychoanalytic Studies, The Soldiers Project now has chapters in the cities of Chicago, Seattle, and Sacramento, and in New York, New Jersey, and southern California. At least 350 soldiers or veterans have been treated. Patients access services via the project's Web site (www.thesoldiersproject.org

The project stresses the need for psychological support and education for military families and children, because it can provide a framework for families to understand and talk about deployment, reunions, and transitions during multiple deployments, Dr. Broder said. Soldiers returning home may be changed by combat-related medical conditions or become impatient or withdrawn, while family dynamics can change as children and spouses adapt to fill the void of the missing parent. The uncertainty of whether a soldier will be redeployed is unique to this war and particularly stressful for children and spouses, with many soldiers shutting down as a way to cope with the uncertainty.

If the slow, painstaking work of psychoanalysis, which Sigmund Freud once likened to archaeological excavation, sounds like an odd match for tight-lipped, action-oriented soldiers, Dr. Broder said the approach is actually well suited. She suggests that in some fundamental way the basic character of many of the young men and women who have served has been shattered, and that this type of wound may be difficult to reach by the more widely used cognitive-behavioral therapy (CBT) with its systematic, goal-oriented approach to influencing dysfunctional behaviors and emotions.

In some cases, the volunteer physicians opt to prescribe medication to the returning soldiers. They do this in addition to providing psychotherapy, she said.

The specific credentials of the therapists tend to be less of an issue than the “proximity of the volunteer's office to the referral request and the time availability,” she said.

“We pride ourselves on finding therapists who are close to the people making the request,” she said. “Many of the traumatized veterans cannot drive freeways or be in a car or bus for extended periods, as serving in Iraq often exposed them to hidden explosives or rocket-propelled grenades.”

In addition, the volunteer therapists try to help the soldiers obtain medications through the VA, since the soldiers must pay for the medication out of pocket if they get them privately.

'We see soldiers and their families for as long as they need—sometimes for up to 2½ years—for free.'

Source DR. BRODER

Soldiers and their families are being offered free access to psychotherapy across the country.

The Soldiers Project is providing confidential psychotherapy to address the growing need for comprehensive mental health care for military personnel and their families and to stop the transmission of trauma to future generations, according to project founder and director Dr. Judith Broder.

“We know that when people are traumatized and it's not treated that the trauma gets carried on to their children and their children's children, but if there's early intervention and treatment then the traumatized person is less likely to be a transmitter,” said Dr. Broder, a psychiatrist and psychoanalyst. “That's the basic impetus—to get in there early and as intensive as possible, and that's a fundamental difference from the services the VA [Veterans Administration] can provide.

“We see soldiers and their families for as long as they need—sometimes for up to 2½ years—for free.”

Started in 2004 under the aegis of the Los Angeles Institute and Society of Psychoanalytic Studies, The Soldiers Project now has chapters in the cities of Chicago, Seattle, and Sacramento, and in New York, New Jersey, and southern California. At least 350 soldiers or veterans have been treated. Patients access services via the project's Web site (www.thesoldiersproject.org

The project stresses the need for psychological support and education for military families and children, because it can provide a framework for families to understand and talk about deployment, reunions, and transitions during multiple deployments, Dr. Broder said. Soldiers returning home may be changed by combat-related medical conditions or become impatient or withdrawn, while family dynamics can change as children and spouses adapt to fill the void of the missing parent. The uncertainty of whether a soldier will be redeployed is unique to this war and particularly stressful for children and spouses, with many soldiers shutting down as a way to cope with the uncertainty.

If the slow, painstaking work of psychoanalysis, which Sigmund Freud once likened to archaeological excavation, sounds like an odd match for tight-lipped, action-oriented soldiers, Dr. Broder said the approach is actually well suited. She suggests that in some fundamental way the basic character of many of the young men and women who have served has been shattered, and that this type of wound may be difficult to reach by the more widely used cognitive-behavioral therapy (CBT) with its systematic, goal-oriented approach to influencing dysfunctional behaviors and emotions.

In some cases, the volunteer physicians opt to prescribe medication to the returning soldiers. They do this in addition to providing psychotherapy, she said.

The specific credentials of the therapists tend to be less of an issue than the “proximity of the volunteer's office to the referral request and the time availability,” she said.

“We pride ourselves on finding therapists who are close to the people making the request,” she said. “Many of the traumatized veterans cannot drive freeways or be in a car or bus for extended periods, as serving in Iraq often exposed them to hidden explosives or rocket-propelled grenades.”

In addition, the volunteer therapists try to help the soldiers obtain medications through the VA, since the soldiers must pay for the medication out of pocket if they get them privately.

'We see soldiers and their families for as long as they need—sometimes for up to 2½ years—for free.'

Source DR. BRODER

Soldiers and their families are being offered free access to psychotherapy across the country.

The Soldiers Project is providing confidential psychotherapy to address the growing need for comprehensive mental health care for military personnel and their families and to stop the transmission of trauma to future generations, according to project founder and director Dr. Judith Broder.

“We know that when people are traumatized and it's not treated that the trauma gets carried on to their children and their children's children, but if there's early intervention and treatment then the traumatized person is less likely to be a transmitter,” said Dr. Broder, a psychiatrist and psychoanalyst. “That's the basic impetus—to get in there early and as intensive as possible, and that's a fundamental difference from the services the VA [Veterans Administration] can provide.

“We see soldiers and their families for as long as they need—sometimes for up to 2½ years—for free.”

Started in 2004 under the aegis of the Los Angeles Institute and Society of Psychoanalytic Studies, The Soldiers Project now has chapters in the cities of Chicago, Seattle, and Sacramento, and in New York, New Jersey, and southern California. At least 350 soldiers or veterans have been treated. Patients access services via the project's Web site (www.thesoldiersproject.org

The project stresses the need for psychological support and education for military families and children, because it can provide a framework for families to understand and talk about deployment, reunions, and transitions during multiple deployments, Dr. Broder said. Soldiers returning home may be changed by combat-related medical conditions or become impatient or withdrawn, while family dynamics can change as children and spouses adapt to fill the void of the missing parent. The uncertainty of whether a soldier will be redeployed is unique to this war and particularly stressful for children and spouses, with many soldiers shutting down as a way to cope with the uncertainty.

If the slow, painstaking work of psychoanalysis, which Sigmund Freud once likened to archaeological excavation, sounds like an odd match for tight-lipped, action-oriented soldiers, Dr. Broder said the approach is actually well suited. She suggests that in some fundamental way the basic character of many of the young men and women who have served has been shattered, and that this type of wound may be difficult to reach by the more widely used cognitive-behavioral therapy (CBT) with its systematic, goal-oriented approach to influencing dysfunctional behaviors and emotions.

In some cases, the volunteer physicians opt to prescribe medication to the returning soldiers. They do this in addition to providing psychotherapy, she said.

The specific credentials of the therapists tend to be less of an issue than the “proximity of the volunteer's office to the referral request and the time availability,” she said.

“We pride ourselves on finding therapists who are close to the people making the request,” she said. “Many of the traumatized veterans cannot drive freeways or be in a car or bus for extended periods, as serving in Iraq often exposed them to hidden explosives or rocket-propelled grenades.”

In addition, the volunteer therapists try to help the soldiers obtain medications through the VA, since the soldiers must pay for the medication out of pocket if they get them privately.

'We see soldiers and their families for as long as they need—sometimes for up to 2½ years—for free.'

Source DR. BRODER

CHICAGO — Ethnic differences in dyslipidemia should be factored into screening programs for metabolic syndrome, Dr. Anne E. Sumner said at a meeting sponsored by the International Society on Hypertension in Blacks.

Atherogenic dyslipidemia, one of the key criteria used to identify metabolic syndrome, is present more often in whites and Hispanics than in blacks, who tend to have normal triglycerides and low HDL cholesterol levels.

“This challenges the conventional thinking about the interrelationship of triglycerides and HDL,” she said.

A recent unpublished study using National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 showed that the frequency of increased triglycerides was significantly lower in blacks than whites and Hispanics, even after adjustment for sex and body mass index, said Dr. Sumner of the National Institute of Diabetes and Digestive and Kidney Diseases.

An earlier study she published showed that blacks are more likely than whites or Mexican Americans to be insulin resistant and to have triglyceride levels below threshold values used to define enlarged-waist elevated-triglyceride syndrome, overweight lipid syndrome, or hyper-triglyceridemic waist syndrome (Atherosclerosis 2008;196:696–703).

The three syndromes—proposed as better predictors of the onset of coronary artery disease and type 2 diabetes, compared with metabolic syndrome—were defined based on data from populations that were predominantly non-Hispanic white.

“From a public health point of view, the absence of elevated triglycerides in blacks does not mean the absence of risk,” she said. “We need then to beware of screening programs that use triglycerides to diagnose risk.

“Isolated low HDL is a manifestation of insulin resistance and represents a cardiovascular disease risk and therefore should be treated.”

She noted that three studies have shown the benefits of treating low HDL—the Helsinki Heart Study; the Veterans Affairs High-Density Lipoprotein Intervention Trial, which had excellent representation of African Americans; and the INTERHEART Africa Study, conducted in sub-Saharan Africa.

Still, the latest report from the American Heart Association shows that death rates from cardiovascular disease are highest among blacks, despite an overall decline of 26.4% from 1995 to 2005. The death rate from CVD in 2005 was 278.9 per 100,000 persons overall, but was 438.4/100,000 in black men and 319.7/100,000 in black women (Circulation 2009;119:e21–181).

Several factors may contribute to the dyslipidemia pattern seen in blacks, explained Dr. Sumner, who stressed that her views are not those of the U.S. government or the National Institutes of Health. Blacks have higher lipoprotein lipase levels and lower apolipoprotein CIII levels, which promotes elevated triglycerides. Blacks also have less visceral adipose tissue and intrahepatic fat, which results in less production of very-low-density lipoprotein, a major carrier of triglycerides.

Dr. Sumner noted that there is a push underway worldwide to use hyper-triglyceridemic waist syndrome to predict cardiovascular risk. The test is cheaper to perform than the metabolic triad, requiring only the simple variables of waist circumference of 90 cm or more in men and at least 85 cm in women and a plasma triglyceride level of 177 mg/dL or more.

This approach works in whites, but not in blacks, Dr. Sumner said. She cited unpublished results from ongoing research in 120 overweight, obese, or prediabetic African Americans showing that 40 had the metabolic triad, but only 3 had a triglyceride level over 177 mg/dL. She suggested that prospective studies are needed to explore whether a reformulation of metabolic syndrome parameter thresholds might optimize risk identification in populations of African ancestry.

Dr. Sumner disclosed no conflicts of interest or study support.

CHICAGO — Ethnic differences in dyslipidemia should be factored into screening programs for metabolic syndrome, Dr. Anne E. Sumner said at a meeting sponsored by the International Society on Hypertension in Blacks.

Atherogenic dyslipidemia, one of the key criteria used to identify metabolic syndrome, is present more often in whites and Hispanics than in blacks, who tend to have normal triglycerides and low HDL cholesterol levels.

“This challenges the conventional thinking about the interrelationship of triglycerides and HDL,” she said.

A recent unpublished study using National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 showed that the frequency of increased triglycerides was significantly lower in blacks than whites and Hispanics, even after adjustment for sex and body mass index, said Dr. Sumner of the National Institute of Diabetes and Digestive and Kidney Diseases.

An earlier study she published showed that blacks are more likely than whites or Mexican Americans to be insulin resistant and to have triglyceride levels below threshold values used to define enlarged-waist elevated-triglyceride syndrome, overweight lipid syndrome, or hyper-triglyceridemic waist syndrome (Atherosclerosis 2008;196:696–703).

The three syndromes—proposed as better predictors of the onset of coronary artery disease and type 2 diabetes, compared with metabolic syndrome—were defined based on data from populations that were predominantly non-Hispanic white.

“From a public health point of view, the absence of elevated triglycerides in blacks does not mean the absence of risk,” she said. “We need then to beware of screening programs that use triglycerides to diagnose risk.

“Isolated low HDL is a manifestation of insulin resistance and represents a cardiovascular disease risk and therefore should be treated.”

She noted that three studies have shown the benefits of treating low HDL—the Helsinki Heart Study; the Veterans Affairs High-Density Lipoprotein Intervention Trial, which had excellent representation of African Americans; and the INTERHEART Africa Study, conducted in sub-Saharan Africa.

Still, the latest report from the American Heart Association shows that death rates from cardiovascular disease are highest among blacks, despite an overall decline of 26.4% from 1995 to 2005. The death rate from CVD in 2005 was 278.9 per 100,000 persons overall, but was 438.4/100,000 in black men and 319.7/100,000 in black women (Circulation 2009;119:e21–181).

Several factors may contribute to the dyslipidemia pattern seen in blacks, explained Dr. Sumner, who stressed that her views are not those of the U.S. government or the National Institutes of Health. Blacks have higher lipoprotein lipase levels and lower apolipoprotein CIII levels, which promotes elevated triglycerides. Blacks also have less visceral adipose tissue and intrahepatic fat, which results in less production of very-low-density lipoprotein, a major carrier of triglycerides.

Dr. Sumner noted that there is a push underway worldwide to use hyper-triglyceridemic waist syndrome to predict cardiovascular risk. The test is cheaper to perform than the metabolic triad, requiring only the simple variables of waist circumference of 90 cm or more in men and at least 85 cm in women and a plasma triglyceride level of 177 mg/dL or more.

This approach works in whites, but not in blacks, Dr. Sumner said. She cited unpublished results from ongoing research in 120 overweight, obese, or prediabetic African Americans showing that 40 had the metabolic triad, but only 3 had a triglyceride level over 177 mg/dL. She suggested that prospective studies are needed to explore whether a reformulation of metabolic syndrome parameter thresholds might optimize risk identification in populations of African ancestry.

Dr. Sumner disclosed no conflicts of interest or study support.

CHICAGO — Ethnic differences in dyslipidemia should be factored into screening programs for metabolic syndrome, Dr. Anne E. Sumner said at a meeting sponsored by the International Society on Hypertension in Blacks.

Atherogenic dyslipidemia, one of the key criteria used to identify metabolic syndrome, is present more often in whites and Hispanics than in blacks, who tend to have normal triglycerides and low HDL cholesterol levels.

“This challenges the conventional thinking about the interrelationship of triglycerides and HDL,” she said.

A recent unpublished study using National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 showed that the frequency of increased triglycerides was significantly lower in blacks than whites and Hispanics, even after adjustment for sex and body mass index, said Dr. Sumner of the National Institute of Diabetes and Digestive and Kidney Diseases.

An earlier study she published showed that blacks are more likely than whites or Mexican Americans to be insulin resistant and to have triglyceride levels below threshold values used to define enlarged-waist elevated-triglyceride syndrome, overweight lipid syndrome, or hyper-triglyceridemic waist syndrome (Atherosclerosis 2008;196:696–703).

The three syndromes—proposed as better predictors of the onset of coronary artery disease and type 2 diabetes, compared with metabolic syndrome—were defined based on data from populations that were predominantly non-Hispanic white.

“From a public health point of view, the absence of elevated triglycerides in blacks does not mean the absence of risk,” she said. “We need then to beware of screening programs that use triglycerides to diagnose risk.

“Isolated low HDL is a manifestation of insulin resistance and represents a cardiovascular disease risk and therefore should be treated.”

She noted that three studies have shown the benefits of treating low HDL—the Helsinki Heart Study; the Veterans Affairs High-Density Lipoprotein Intervention Trial, which had excellent representation of African Americans; and the INTERHEART Africa Study, conducted in sub-Saharan Africa.

Still, the latest report from the American Heart Association shows that death rates from cardiovascular disease are highest among blacks, despite an overall decline of 26.4% from 1995 to 2005. The death rate from CVD in 2005 was 278.9 per 100,000 persons overall, but was 438.4/100,000 in black men and 319.7/100,000 in black women (Circulation 2009;119:e21–181).

Several factors may contribute to the dyslipidemia pattern seen in blacks, explained Dr. Sumner, who stressed that her views are not those of the U.S. government or the National Institutes of Health. Blacks have higher lipoprotein lipase levels and lower apolipoprotein CIII levels, which promotes elevated triglycerides. Blacks also have less visceral adipose tissue and intrahepatic fat, which results in less production of very-low-density lipoprotein, a major carrier of triglycerides.

Dr. Sumner noted that there is a push underway worldwide to use hyper-triglyceridemic waist syndrome to predict cardiovascular risk. The test is cheaper to perform than the metabolic triad, requiring only the simple variables of waist circumference of 90 cm or more in men and at least 85 cm in women and a plasma triglyceride level of 177 mg/dL or more.

This approach works in whites, but not in blacks, Dr. Sumner said. She cited unpublished results from ongoing research in 120 overweight, obese, or prediabetic African Americans showing that 40 had the metabolic triad, but only 3 had a triglyceride level over 177 mg/dL. She suggested that prospective studies are needed to explore whether a reformulation of metabolic syndrome parameter thresholds might optimize risk identification in populations of African ancestry.

Dr. Sumner disclosed no conflicts of interest or study support.

CHICAGO — Although Hispanics are grossly underrepresented in heart failure trials, emerging evidence suggests they have unique risk factors and heart failure outcomes that should be taken into clinical consideration.

The evidence also underscores the importance of recognizing the vast heterogeneity of Hispanics, Dr. Ileana Piña said at a meeting sponsored by the International Society on Hypertension in Blacks.

“Hispanics represent a cultural group, not a racially identifiable group,” the Cuban-born cardiologist said. “You can't lump them all together.”

But that's exactly what has happened. Until the Medicare enrollment files were changed in 1994, Hispanics or Native Americans were simply classified as either “white” or “black.” It wasn't until the 2000 U.S. census that the term “Hispanic” was changed to “Spanish, Hispanic, or Latino” to describe persons of Cuban, Mexican, Puerto Rican, South or Central American, or other Spanish culture or origin, regardless of race.

Several studies have made the observation—dubbed the “Hispanic paradox”—that Hispanics have lower all-cause and cardiovascular mortality, despite increased obesity and diabetes, and lower socioeconomic status, said Dr. Piña, professor of medicine at Case Western Reserve University in Cleveland, and a Veterans Affairs National Quality Scholar.

In a study of Medicare enrollees aged 65 years or older, Hispanics were 1.2 times more likely to be hospitalized for heart failure than were whites, while blacks were 1.5 times more likely. But after adjustment for sex and age, in-hospital mortality was significantly lower among Hispanics and blacks than among whites (Am. Heart J. 2005;150:448-54). A California study also showed that blacks and “Latinos” initially hospitalized with heart failure in 1991 or 1992 were more likely to be rehospitalized than were Asians and whites, but were less likely to die during the 12-month follow-up period (Am. Heart J. 1999;137:919-27).

Sociocultural factors are often used to explain the Hispanic paradox, but more recent data are causing some to rethink the paradox or at least to differentiate Hispanics by birthplace. Among diabetics in the San Antonio Heart Study, age- and sex-adjusted hazard ratios indicated that U.S.-born Mexican Americans have a 66% greater risk of all-cause mortality and of cardiovascular mortality, compared with non-Hispanic whites, while Mexico-born Mexican Americans appeared to be at similar risk (Diabetes Care 2002;25:1557-63).

A recent “state-of-the-art” paper on the subject notes that Hispanic ethnicity is marked by a disproportionate cardiometabolic risk burden, largely because of exceedingly high rates of insulin resistance. The authors hypothesize that “the central concept of insulin resistance—compounded by inflammation and neuroendocrine overactivity—may be a predominant etiologic factor for cardiomyopathy in Hispanics” (J. Am. Coll. Cardiol. 2009;53;1167-75).

The authors go on to call for greater representation in patient registries, research studies, and clinical trials, a call echoed by Dr. Piña. Hispanic or Latino patients made up just 3% of HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), she noted, yet they make up about 15% of the total U.S. population. Still, among nine recent major heart failure trials, HF-ACTION was the only trial that specifically differentiated Hispanics, instead of lumping them together with other ethnicities as “nonwhites” or “other.”

“If you think the inclusion of women in heart failure trials is poor, inclusion of Hispanics is horrendous,” she said.

Greater elucidation of heart failure risk factors and outcomes in Hispanic populations could lead to more targeted therapies and risk modification. With one in three U.S. residents expected to be Hispanic by 2050, there is great urgency to act, Dr. Piña said.

Dr. Piña disclosed serving as a speaker for AstraZeneca, Novartis, and Merck, and as a consultant for the Food and Drug Administration.

CHICAGO — Although Hispanics are grossly underrepresented in heart failure trials, emerging evidence suggests they have unique risk factors and heart failure outcomes that should be taken into clinical consideration.

The evidence also underscores the importance of recognizing the vast heterogeneity of Hispanics, Dr. Ileana Piña said at a meeting sponsored by the International Society on Hypertension in Blacks.

“Hispanics represent a cultural group, not a racially identifiable group,” the Cuban-born cardiologist said. “You can't lump them all together.”

But that's exactly what has happened. Until the Medicare enrollment files were changed in 1994, Hispanics or Native Americans were simply classified as either “white” or “black.” It wasn't until the 2000 U.S. census that the term “Hispanic” was changed to “Spanish, Hispanic, or Latino” to describe persons of Cuban, Mexican, Puerto Rican, South or Central American, or other Spanish culture or origin, regardless of race.

Several studies have made the observation—dubbed the “Hispanic paradox”—that Hispanics have lower all-cause and cardiovascular mortality, despite increased obesity and diabetes, and lower socioeconomic status, said Dr. Piña, professor of medicine at Case Western Reserve University in Cleveland, and a Veterans Affairs National Quality Scholar.

In a study of Medicare enrollees aged 65 years or older, Hispanics were 1.2 times more likely to be hospitalized for heart failure than were whites, while blacks were 1.5 times more likely. But after adjustment for sex and age, in-hospital mortality was significantly lower among Hispanics and blacks than among whites (Am. Heart J. 2005;150:448-54). A California study also showed that blacks and “Latinos” initially hospitalized with heart failure in 1991 or 1992 were more likely to be rehospitalized than were Asians and whites, but were less likely to die during the 12-month follow-up period (Am. Heart J. 1999;137:919-27).

Sociocultural factors are often used to explain the Hispanic paradox, but more recent data are causing some to rethink the paradox or at least to differentiate Hispanics by birthplace. Among diabetics in the San Antonio Heart Study, age- and sex-adjusted hazard ratios indicated that U.S.-born Mexican Americans have a 66% greater risk of all-cause mortality and of cardiovascular mortality, compared with non-Hispanic whites, while Mexico-born Mexican Americans appeared to be at similar risk (Diabetes Care 2002;25:1557-63).

A recent “state-of-the-art” paper on the subject notes that Hispanic ethnicity is marked by a disproportionate cardiometabolic risk burden, largely because of exceedingly high rates of insulin resistance. The authors hypothesize that “the central concept of insulin resistance—compounded by inflammation and neuroendocrine overactivity—may be a predominant etiologic factor for cardiomyopathy in Hispanics” (J. Am. Coll. Cardiol. 2009;53;1167-75).

The authors go on to call for greater representation in patient registries, research studies, and clinical trials, a call echoed by Dr. Piña. Hispanic or Latino patients made up just 3% of HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), she noted, yet they make up about 15% of the total U.S. population. Still, among nine recent major heart failure trials, HF-ACTION was the only trial that specifically differentiated Hispanics, instead of lumping them together with other ethnicities as “nonwhites” or “other.”

“If you think the inclusion of women in heart failure trials is poor, inclusion of Hispanics is horrendous,” she said.

Greater elucidation of heart failure risk factors and outcomes in Hispanic populations could lead to more targeted therapies and risk modification. With one in three U.S. residents expected to be Hispanic by 2050, there is great urgency to act, Dr. Piña said.

Dr. Piña disclosed serving as a speaker for AstraZeneca, Novartis, and Merck, and as a consultant for the Food and Drug Administration.

CHICAGO — Although Hispanics are grossly underrepresented in heart failure trials, emerging evidence suggests they have unique risk factors and heart failure outcomes that should be taken into clinical consideration.

The evidence also underscores the importance of recognizing the vast heterogeneity of Hispanics, Dr. Ileana Piña said at a meeting sponsored by the International Society on Hypertension in Blacks.

“Hispanics represent a cultural group, not a racially identifiable group,” the Cuban-born cardiologist said. “You can't lump them all together.”

But that's exactly what has happened. Until the Medicare enrollment files were changed in 1994, Hispanics or Native Americans were simply classified as either “white” or “black.” It wasn't until the 2000 U.S. census that the term “Hispanic” was changed to “Spanish, Hispanic, or Latino” to describe persons of Cuban, Mexican, Puerto Rican, South or Central American, or other Spanish culture or origin, regardless of race.

Several studies have made the observation—dubbed the “Hispanic paradox”—that Hispanics have lower all-cause and cardiovascular mortality, despite increased obesity and diabetes, and lower socioeconomic status, said Dr. Piña, professor of medicine at Case Western Reserve University in Cleveland, and a Veterans Affairs National Quality Scholar.

In a study of Medicare enrollees aged 65 years or older, Hispanics were 1.2 times more likely to be hospitalized for heart failure than were whites, while blacks were 1.5 times more likely. But after adjustment for sex and age, in-hospital mortality was significantly lower among Hispanics and blacks than among whites (Am. Heart J. 2005;150:448-54). A California study also showed that blacks and “Latinos” initially hospitalized with heart failure in 1991 or 1992 were more likely to be rehospitalized than were Asians and whites, but were less likely to die during the 12-month follow-up period (Am. Heart J. 1999;137:919-27).

Sociocultural factors are often used to explain the Hispanic paradox, but more recent data are causing some to rethink the paradox or at least to differentiate Hispanics by birthplace. Among diabetics in the San Antonio Heart Study, age- and sex-adjusted hazard ratios indicated that U.S.-born Mexican Americans have a 66% greater risk of all-cause mortality and of cardiovascular mortality, compared with non-Hispanic whites, while Mexico-born Mexican Americans appeared to be at similar risk (Diabetes Care 2002;25:1557-63).

A recent “state-of-the-art” paper on the subject notes that Hispanic ethnicity is marked by a disproportionate cardiometabolic risk burden, largely because of exceedingly high rates of insulin resistance. The authors hypothesize that “the central concept of insulin resistance—compounded by inflammation and neuroendocrine overactivity—may be a predominant etiologic factor for cardiomyopathy in Hispanics” (J. Am. Coll. Cardiol. 2009;53;1167-75).

The authors go on to call for greater representation in patient registries, research studies, and clinical trials, a call echoed by Dr. Piña. Hispanic or Latino patients made up just 3% of HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), she noted, yet they make up about 15% of the total U.S. population. Still, among nine recent major heart failure trials, HF-ACTION was the only trial that specifically differentiated Hispanics, instead of lumping them together with other ethnicities as “nonwhites” or “other.”

“If you think the inclusion of women in heart failure trials is poor, inclusion of Hispanics is horrendous,” she said.

Greater elucidation of heart failure risk factors and outcomes in Hispanic populations could lead to more targeted therapies and risk modification. With one in three U.S. residents expected to be Hispanic by 2050, there is great urgency to act, Dr. Piña said.

Dr. Piña disclosed serving as a speaker for AstraZeneca, Novartis, and Merck, and as a consultant for the Food and Drug Administration.