Kerri Wachter

BETHESDA, MD. — Despite the experience from recent epidemics, the search for effective treatments for Clostridium difficile-associated diarrhea continues, Dr. Mark Miller said at an annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

During the 2002–2004 epidemic of C. difficile-associated diarrhea (CDAD) in Quebec, spontaneous improvement was rare and serious disease developed rapidly. “Many of us remember many of the cases where they're fine today, they start getting diarrhea tonight, and tomorrow afternoon they're in the intensive care unit with hypotension and acute respiratory distress syndrome,” said Dr. Miller, head of infectious diseases at Sir Mortimer B. Davis—Jewish General Hospital in Montreal.

Traditional treatment for CDAD has been to stop the offending antibiotic, which may relieve symptoms in about 20% of patients. “This is probably not true any more,” Dr. Miller said.

Traditionally, oral administration of drug therapy is preferred, even if that means using a nasogastric tube. Metronidazole (250–500 mg four times daily) has been preferred over vancomycin (125–500 mg four times daily) because it is considerably cheaper, reduces the risk of vancomycin-resistant mutations, and has comparable efficacy, tolerability, and relapse rates, compared with vancomycin.

In Quebec, it is currently considered unethical to withhold specific CDAD therapy. Almost all patients are started on empiric therapy before the toxin assay comes back from the laboratory, said Dr. Miller, also a professor of microbiology/immunology at McGill University.

There also have been a few anecdotal or small series reports saying that the clinical response is slower or that the relapse rate is higher with metronidazole than with vancomycin.

According to the latest treatment algorithm developed in Quebec, serious cases of CDAD are started on vancomycin, bypassing metronidazole. Likewise, a patient who fails to improve on metronidazole is switched to vancomycin.

The use of metronidazole and vancomycin together is widespread in many institutions, but the effectiveness of the combination has not been studied. Some physicians are adding rifampin to metronidazole, and others are adding rifampin or bacitracin to vancomycin. Likewise, these combinations have not been studied. “As you start getting a number of different recipes, it means that nobody is very happy with any single recipe,” Dr. Miller said.

In addition, there is a host of adjuvant nonantibiotic therapies available or in the pipeline. Dr. Miller discussed the literature on these therapies and gave his comments:

▸ Probiotics. Probiotics have been suggested as bioprophylaxis or biotherapy. However, the few studies that have been done with standardized probiotics have shown no effect on C. difficile. In a metaanalysis, researchers concluded that there is insufficient evidence for the routine use of probiotics to prevent or treat CDAD (CMAJ 2005;173:167–70). In addition, because a substance's intended use determines how it is regulated in the United States, many probiotic products are not standardized and are poorly quantified.

▸ Prebiotics. Last year a group in the United Kingdom described the use of oligofructose—a so-called prebiotic—for the treatment of CDAD along with conventional therapy. In the study, patients were randomized to conventional therapy alone or in conjunction with 30 days of oligofructose consumption (Clin. Gastroenterol. Hepatol. 2005;3:442–8). Patients taking oligofructose had a substantial increase in beneficial bifidobacteria in the gut. There was also a decreased relapse rate for those on oligofructose.

▸ Toxin binders. Toxin binders, such as cholestyramine and tolevamer, are another avenue of treatment under investigation. These compounds bind to toxins produced by C. difficile, which lead to CDAD.

Cholestyramine is indicated to help reduce serum cholesterol levels but is sometimes used off label to treat CDAD. However, small case series have not shown it to be effective. “I find that all it does is give my patients more GI symptoms of bloating and flatulence and pain. I don't find it very useful,” Dr. Miller said.

Tolevamer is an investigational polymer (Genzyme Corp.) that is designed to selectively bind to C. difficile toxins A and B. A phase II study showed that high-dose tolevamer (6 g/day) was equivalent to oral vancomycin for curing mild to moderate CDAD. Phase III trials are underway to compare the drug with vancomycin and metronidazole.

▸ Immunotherapy. Interest in the use of intravenous immunoglobulin to treat CDAD was sparked when researchers noted that patients with multiple relapses appeared to be deficient in their immunoglobulin G (IgG) response to toxins. High-titer antitoxin A was associated with protection from and recurrence of disease (N. Eng. J. Med. 2000;342:390–7).

Several small case series using IV immunoglobulin for severe or recurrent disease have shown marked clinical responses in most patients. Dr. Miller and his colleagues are currently performing their own retrospective analysis of IV immunoglobulin use during the Quebec outbreak.

A spin-off approach is passive immunotherapy using just antibodies to C. difficile toxins. Studies have shown that humans produce large quantities of antitoxin IgG after immunization. Researchers at Acambis are currently investigating a vaccine with antitoxin A and antitoxin B IgG.

Researchers are also investigating animal-derived hyperimmune antitoxin products, such as a whey protein concentrate made from the milk of cows vaccinated with C. difficile toxoids. The product appears to help prevent CDAD relapse, based on data from a pilot study (J. Med. Microbiol. 2005;54:197–205).

▸ Fecal flora restoration. Fecal restoration is also being investigated as an effective—albeit unpleasant—therapy for CDAD. The idea is to use enemas of normal stool to restore normal fecal flora. Anecdotal and small series reports show a good response in patients with recurrent CDAD. One study also showed that it is possible to give donor stool via a nasogastric tube.

Dr. Miller disclosed that he is a consultant for and/or holds research grants from ActivBiotics Inc., Advanced Biologics, Bayer, BD's GeneOhm, Conagra Foods Inc., Genzyme Corporation, GlaxoSmithKline, Janssen-Ortho Inc., LDI

BETHESDA, MD. — Despite the experience from recent epidemics, the search for effective treatments for Clostridium difficile-associated diarrhea continues, Dr. Mark Miller said at an annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

During the 2002–2004 epidemic of C. difficile-associated diarrhea (CDAD) in Quebec, spontaneous improvement was rare and serious disease developed rapidly. “Many of us remember many of the cases where they're fine today, they start getting diarrhea tonight, and tomorrow afternoon they're in the intensive care unit with hypotension and acute respiratory distress syndrome,” said Dr. Miller, head of infectious diseases at Sir Mortimer B. Davis—Jewish General Hospital in Montreal.

Traditional treatment for CDAD has been to stop the offending antibiotic, which may relieve symptoms in about 20% of patients. “This is probably not true any more,” Dr. Miller said.

Traditionally, oral administration of drug therapy is preferred, even if that means using a nasogastric tube. Metronidazole (250–500 mg four times daily) has been preferred over vancomycin (125–500 mg four times daily) because it is considerably cheaper, reduces the risk of vancomycin-resistant mutations, and has comparable efficacy, tolerability, and relapse rates, compared with vancomycin.

In Quebec, it is currently considered unethical to withhold specific CDAD therapy. Almost all patients are started on empiric therapy before the toxin assay comes back from the laboratory, said Dr. Miller, also a professor of microbiology/immunology at McGill University.

There also have been a few anecdotal or small series reports saying that the clinical response is slower or that the relapse rate is higher with metronidazole than with vancomycin.

According to the latest treatment algorithm developed in Quebec, serious cases of CDAD are started on vancomycin, bypassing metronidazole. Likewise, a patient who fails to improve on metronidazole is switched to vancomycin.

The use of metronidazole and vancomycin together is widespread in many institutions, but the effectiveness of the combination has not been studied. Some physicians are adding rifampin to metronidazole, and others are adding rifampin or bacitracin to vancomycin. Likewise, these combinations have not been studied. “As you start getting a number of different recipes, it means that nobody is very happy with any single recipe,” Dr. Miller said.

In addition, there is a host of adjuvant nonantibiotic therapies available or in the pipeline. Dr. Miller discussed the literature on these therapies and gave his comments:

▸ Probiotics. Probiotics have been suggested as bioprophylaxis or biotherapy. However, the few studies that have been done with standardized probiotics have shown no effect on C. difficile. In a metaanalysis, researchers concluded that there is insufficient evidence for the routine use of probiotics to prevent or treat CDAD (CMAJ 2005;173:167–70). In addition, because a substance's intended use determines how it is regulated in the United States, many probiotic products are not standardized and are poorly quantified.

▸ Prebiotics. Last year a group in the United Kingdom described the use of oligofructose—a so-called prebiotic—for the treatment of CDAD along with conventional therapy. In the study, patients were randomized to conventional therapy alone or in conjunction with 30 days of oligofructose consumption (Clin. Gastroenterol. Hepatol. 2005;3:442–8). Patients taking oligofructose had a substantial increase in beneficial bifidobacteria in the gut. There was also a decreased relapse rate for those on oligofructose.

▸ Toxin binders. Toxin binders, such as cholestyramine and tolevamer, are another avenue of treatment under investigation. These compounds bind to toxins produced by C. difficile, which lead to CDAD.

Cholestyramine is indicated to help reduce serum cholesterol levels but is sometimes used off label to treat CDAD. However, small case series have not shown it to be effective. “I find that all it does is give my patients more GI symptoms of bloating and flatulence and pain. I don't find it very useful,” Dr. Miller said.

Tolevamer is an investigational polymer (Genzyme Corp.) that is designed to selectively bind to C. difficile toxins A and B. A phase II study showed that high-dose tolevamer (6 g/day) was equivalent to oral vancomycin for curing mild to moderate CDAD. Phase III trials are underway to compare the drug with vancomycin and metronidazole.

▸ Immunotherapy. Interest in the use of intravenous immunoglobulin to treat CDAD was sparked when researchers noted that patients with multiple relapses appeared to be deficient in their immunoglobulin G (IgG) response to toxins. High-titer antitoxin A was associated with protection from and recurrence of disease (N. Eng. J. Med. 2000;342:390–7).

Several small case series using IV immunoglobulin for severe or recurrent disease have shown marked clinical responses in most patients. Dr. Miller and his colleagues are currently performing their own retrospective analysis of IV immunoglobulin use during the Quebec outbreak.

A spin-off approach is passive immunotherapy using just antibodies to C. difficile toxins. Studies have shown that humans produce large quantities of antitoxin IgG after immunization. Researchers at Acambis are currently investigating a vaccine with antitoxin A and antitoxin B IgG.

Researchers are also investigating animal-derived hyperimmune antitoxin products, such as a whey protein concentrate made from the milk of cows vaccinated with C. difficile toxoids. The product appears to help prevent CDAD relapse, based on data from a pilot study (J. Med. Microbiol. 2005;54:197–205).

▸ Fecal flora restoration. Fecal restoration is also being investigated as an effective—albeit unpleasant—therapy for CDAD. The idea is to use enemas of normal stool to restore normal fecal flora. Anecdotal and small series reports show a good response in patients with recurrent CDAD. One study also showed that it is possible to give donor stool via a nasogastric tube.

Dr. Miller disclosed that he is a consultant for and/or holds research grants from ActivBiotics Inc., Advanced Biologics, Bayer, BD's GeneOhm, Conagra Foods Inc., Genzyme Corporation, GlaxoSmithKline, Janssen-Ortho Inc., LDI

BETHESDA, MD. — Despite the experience from recent epidemics, the search for effective treatments for Clostridium difficile-associated diarrhea continues, Dr. Mark Miller said at an annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

During the 2002–2004 epidemic of C. difficile-associated diarrhea (CDAD) in Quebec, spontaneous improvement was rare and serious disease developed rapidly. “Many of us remember many of the cases where they're fine today, they start getting diarrhea tonight, and tomorrow afternoon they're in the intensive care unit with hypotension and acute respiratory distress syndrome,” said Dr. Miller, head of infectious diseases at Sir Mortimer B. Davis—Jewish General Hospital in Montreal.

Traditional treatment for CDAD has been to stop the offending antibiotic, which may relieve symptoms in about 20% of patients. “This is probably not true any more,” Dr. Miller said.

Traditionally, oral administration of drug therapy is preferred, even if that means using a nasogastric tube. Metronidazole (250–500 mg four times daily) has been preferred over vancomycin (125–500 mg four times daily) because it is considerably cheaper, reduces the risk of vancomycin-resistant mutations, and has comparable efficacy, tolerability, and relapse rates, compared with vancomycin.

In Quebec, it is currently considered unethical to withhold specific CDAD therapy. Almost all patients are started on empiric therapy before the toxin assay comes back from the laboratory, said Dr. Miller, also a professor of microbiology/immunology at McGill University.

There also have been a few anecdotal or small series reports saying that the clinical response is slower or that the relapse rate is higher with metronidazole than with vancomycin.

According to the latest treatment algorithm developed in Quebec, serious cases of CDAD are started on vancomycin, bypassing metronidazole. Likewise, a patient who fails to improve on metronidazole is switched to vancomycin.

The use of metronidazole and vancomycin together is widespread in many institutions, but the effectiveness of the combination has not been studied. Some physicians are adding rifampin to metronidazole, and others are adding rifampin or bacitracin to vancomycin. Likewise, these combinations have not been studied. “As you start getting a number of different recipes, it means that nobody is very happy with any single recipe,” Dr. Miller said.

In addition, there is a host of adjuvant nonantibiotic therapies available or in the pipeline. Dr. Miller discussed the literature on these therapies and gave his comments:

▸ Probiotics. Probiotics have been suggested as bioprophylaxis or biotherapy. However, the few studies that have been done with standardized probiotics have shown no effect on C. difficile. In a metaanalysis, researchers concluded that there is insufficient evidence for the routine use of probiotics to prevent or treat CDAD (CMAJ 2005;173:167–70). In addition, because a substance's intended use determines how it is regulated in the United States, many probiotic products are not standardized and are poorly quantified.

▸ Prebiotics. Last year a group in the United Kingdom described the use of oligofructose—a so-called prebiotic—for the treatment of CDAD along with conventional therapy. In the study, patients were randomized to conventional therapy alone or in conjunction with 30 days of oligofructose consumption (Clin. Gastroenterol. Hepatol. 2005;3:442–8). Patients taking oligofructose had a substantial increase in beneficial bifidobacteria in the gut. There was also a decreased relapse rate for those on oligofructose.

▸ Toxin binders. Toxin binders, such as cholestyramine and tolevamer, are another avenue of treatment under investigation. These compounds bind to toxins produced by C. difficile, which lead to CDAD.

Cholestyramine is indicated to help reduce serum cholesterol levels but is sometimes used off label to treat CDAD. However, small case series have not shown it to be effective. “I find that all it does is give my patients more GI symptoms of bloating and flatulence and pain. I don't find it very useful,” Dr. Miller said.

Tolevamer is an investigational polymer (Genzyme Corp.) that is designed to selectively bind to C. difficile toxins A and B. A phase II study showed that high-dose tolevamer (6 g/day) was equivalent to oral vancomycin for curing mild to moderate CDAD. Phase III trials are underway to compare the drug with vancomycin and metronidazole.

▸ Immunotherapy. Interest in the use of intravenous immunoglobulin to treat CDAD was sparked when researchers noted that patients with multiple relapses appeared to be deficient in their immunoglobulin G (IgG) response to toxins. High-titer antitoxin A was associated with protection from and recurrence of disease (N. Eng. J. Med. 2000;342:390–7).

Several small case series using IV immunoglobulin for severe or recurrent disease have shown marked clinical responses in most patients. Dr. Miller and his colleagues are currently performing their own retrospective analysis of IV immunoglobulin use during the Quebec outbreak.

A spin-off approach is passive immunotherapy using just antibodies to C. difficile toxins. Studies have shown that humans produce large quantities of antitoxin IgG after immunization. Researchers at Acambis are currently investigating a vaccine with antitoxin A and antitoxin B IgG.

Researchers are also investigating animal-derived hyperimmune antitoxin products, such as a whey protein concentrate made from the milk of cows vaccinated with C. difficile toxoids. The product appears to help prevent CDAD relapse, based on data from a pilot study (J. Med. Microbiol. 2005;54:197–205).

▸ Fecal flora restoration. Fecal restoration is also being investigated as an effective—albeit unpleasant—therapy for CDAD. The idea is to use enemas of normal stool to restore normal fecal flora. Anecdotal and small series reports show a good response in patients with recurrent CDAD. One study also showed that it is possible to give donor stool via a nasogastric tube.

Dr. Miller disclosed that he is a consultant for and/or holds research grants from ActivBiotics Inc., Advanced Biologics, Bayer, BD's GeneOhm, Conagra Foods Inc., Genzyme Corporation, GlaxoSmithKline, Janssen-Ortho Inc., LDI

Reports of fatal and nonfatal intracranial hemorrhage among HIV-1 infected patients taking Aptivus (tipranavir) in combination antiretroviral therapy have prompted the manufacturer to issue new safety information.

Boehringer Ingelheim Pharmaceuticals Inc. has identified 14 reports of intracranial hemorrhage, including 8 fatalities, in 6,840 HIV-1 infected individuals receiving Aptivus capsules coadministered with ritonavir (Norvir) (500 mg/200 mg twice daily).

Many of these patients who developed intracranial hemorrhage had other medical conditions—CNS lesions, head trauma, recent neurosurgery, coagulopathy, hypertension, or alcohol abuse—or were receiving concomitant medications, including anticoagulants and antiplatelet agents, that may have caused or contributed to these events.

Several sections of the label have been changed to reflect concerns about using the drug in patients at increased risk of bleeding.

No pattern of abnormal coagulation parameters has been identified in patients receiving Aptivus in general or preceding development of intracranial hemorrhage. For this reason, routine measurement of coagulation parameters is not currently indicated for the management of patients taking the drug.

Aptivus/ritonavir therapy should be used cautiously in patients who may be at risk for increased bleeding from trauma, surgery, or medical conditions, or who are taking other drugs known to increase the risk of bleeding. Of note, patients with advanced HIV disease/AIDS have been observed to have an increased risk of intracranial hemorrhage. Investigations are ongoing to determine the role of Aptivus in the development of intracranial hemorrhage.

For more information or to report adverse reactions, contact Boehringer Ingelheim Pharmaceuticals by calling 800-542-6257 (option 4). Adverse reactions can also be reported to the Food and Drug Administration's MedWatch program by calling 800-332-1088.

Reports of fatal and nonfatal intracranial hemorrhage among HIV-1 infected patients taking Aptivus (tipranavir) in combination antiretroviral therapy have prompted the manufacturer to issue new safety information.

Boehringer Ingelheim Pharmaceuticals Inc. has identified 14 reports of intracranial hemorrhage, including 8 fatalities, in 6,840 HIV-1 infected individuals receiving Aptivus capsules coadministered with ritonavir (Norvir) (500 mg/200 mg twice daily).

Many of these patients who developed intracranial hemorrhage had other medical conditions—CNS lesions, head trauma, recent neurosurgery, coagulopathy, hypertension, or alcohol abuse—or were receiving concomitant medications, including anticoagulants and antiplatelet agents, that may have caused or contributed to these events.

Several sections of the label have been changed to reflect concerns about using the drug in patients at increased risk of bleeding.

No pattern of abnormal coagulation parameters has been identified in patients receiving Aptivus in general or preceding development of intracranial hemorrhage. For this reason, routine measurement of coagulation parameters is not currently indicated for the management of patients taking the drug.

Aptivus/ritonavir therapy should be used cautiously in patients who may be at risk for increased bleeding from trauma, surgery, or medical conditions, or who are taking other drugs known to increase the risk of bleeding. Of note, patients with advanced HIV disease/AIDS have been observed to have an increased risk of intracranial hemorrhage. Investigations are ongoing to determine the role of Aptivus in the development of intracranial hemorrhage.

For more information or to report adverse reactions, contact Boehringer Ingelheim Pharmaceuticals by calling 800-542-6257 (option 4). Adverse reactions can also be reported to the Food and Drug Administration's MedWatch program by calling 800-332-1088.

Reports of fatal and nonfatal intracranial hemorrhage among HIV-1 infected patients taking Aptivus (tipranavir) in combination antiretroviral therapy have prompted the manufacturer to issue new safety information.

Boehringer Ingelheim Pharmaceuticals Inc. has identified 14 reports of intracranial hemorrhage, including 8 fatalities, in 6,840 HIV-1 infected individuals receiving Aptivus capsules coadministered with ritonavir (Norvir) (500 mg/200 mg twice daily).

Many of these patients who developed intracranial hemorrhage had other medical conditions—CNS lesions, head trauma, recent neurosurgery, coagulopathy, hypertension, or alcohol abuse—or were receiving concomitant medications, including anticoagulants and antiplatelet agents, that may have caused or contributed to these events.

Several sections of the label have been changed to reflect concerns about using the drug in patients at increased risk of bleeding.

No pattern of abnormal coagulation parameters has been identified in patients receiving Aptivus in general or preceding development of intracranial hemorrhage. For this reason, routine measurement of coagulation parameters is not currently indicated for the management of patients taking the drug.

Aptivus/ritonavir therapy should be used cautiously in patients who may be at risk for increased bleeding from trauma, surgery, or medical conditions, or who are taking other drugs known to increase the risk of bleeding. Of note, patients with advanced HIV disease/AIDS have been observed to have an increased risk of intracranial hemorrhage. Investigations are ongoing to determine the role of Aptivus in the development of intracranial hemorrhage.

For more information or to report adverse reactions, contact Boehringer Ingelheim Pharmaceuticals by calling 800-542-6257 (option 4). Adverse reactions can also be reported to the Food and Drug Administration's MedWatch program by calling 800-332-1088.

STOCKHOLM — Psoriasis improves considerably for some women during pregnancy, and now there are data pointing to the ratio of estrogen to progesterone as a possible explanation for this improvement, according to the results of a study presented at an international conference on psoriasis and psoriatic arthritis.

For the study, 47 pregnant women with psoriasis had their psoriasis assessed and hormone levels measured at 10, 20, and 30 weeks' gestation and at 6 and 24 weeks post partum, said Stefani Kappel, a fourth-year medical student at the University of California, Irvine. Twenty-seven menstruating psoriasis patients were also recruited as controls. and were assessed at similar intervals over a 54-week period.

During pregnancy, just over half of the women (55%) reported improvement in their psoriasis: 21% reported no change and 23% reported worsening. “This was very similar to findings that were reported in the retrospective studies,” said Ms. Kappel, who collaborated with principal investigator Dr. Jenny E. Murase, a dermatology resident at the university.

In the postpartum period, 65% of the women reported a worsening of their psoriasis, 26% reported no change, and 9% reported an improvement.

Psoriatic body surface area decreased significantly among the pregnant women at 10–20 weeks' gestation, compared with the women in the control group. Psoriatic body surface area increased significantly by 6 weeks post partum among the new mothers, compared with the control women.

“Although two-thirds of the patients reported a worsening of psoriasis in the postpartum period … it was more of a return to baseline,” Ms. Kappel said.

The correlation between progesterone levels and improvement of psoriasis during pregnancy was not significant, nor was the correlation between estrone and improvement of psoriasis during pregnancy. There were moderate correlations between improvement in psoriasis and estriol and estradiol levels during pregnancy.

“Given that progesterone increases so much more than estradiol or estrone [during pregnancy], we hypothesized that it was the ratio of estrogen to progesterone that created an altered immunity,” Ms. Kappel said. The correlation between improvement of psoriasis during pregnancy and the ratio of estrogen to progesterone was the strongest.

One patient in particular had a progesterone level that was six standard deviations above the average of the general population during the pregnancy period but an estriol level that was within the normal range. Her psoriasis body surface area worsened from 52% to 65%. The researchers speculate that her ratio of progesterone to estrogen may have caused her worsening disease.

The study results illustrate that there is a shift from Th1 to Th2 immunity in pregnant patients. “This makes sense because Th1-mediated diseases, such as rheumatoid arthritis, psoriasis, and multiple sclerosis, tend to improve during pregnancy, whereas Th2-mediated diseases such as lupus tend to worsen,” Ms. Kappel explained.

In light of these findings, “estrogen, as a potential therapeutic option in conjunction with other treatment modalities, warrants further investigation,” she added.

Progesterone is the hormone that increases the most in pregnancy—about 200-fold—and is the key hormone in uterine suppression during pregnancy. Most of the pregnant women in this study had elevated progesterone levels within the normal range for the general population. Estrogen suppresses T-cell immunity but is also known to stimulate B-cell-mediated immunity in pregnancy.

Estradiol increases 24-fold during pregnancy and is the most potent estrogen; estrone increases about 6-fold during pregnancy. Estriol is the least potent and is only produced in significant amounts during pregnancy. Most of the pregnant study patients had normal-range levels of all three estrogens during their pregnancies.

STOCKHOLM — Psoriasis improves considerably for some women during pregnancy, and now there are data pointing to the ratio of estrogen to progesterone as a possible explanation for this improvement, according to the results of a study presented at an international conference on psoriasis and psoriatic arthritis.

For the study, 47 pregnant women with psoriasis had their psoriasis assessed and hormone levels measured at 10, 20, and 30 weeks' gestation and at 6 and 24 weeks post partum, said Stefani Kappel, a fourth-year medical student at the University of California, Irvine. Twenty-seven menstruating psoriasis patients were also recruited as controls. and were assessed at similar intervals over a 54-week period.

During pregnancy, just over half of the women (55%) reported improvement in their psoriasis: 21% reported no change and 23% reported worsening. “This was very similar to findings that were reported in the retrospective studies,” said Ms. Kappel, who collaborated with principal investigator Dr. Jenny E. Murase, a dermatology resident at the university.

In the postpartum period, 65% of the women reported a worsening of their psoriasis, 26% reported no change, and 9% reported an improvement.

Psoriatic body surface area decreased significantly among the pregnant women at 10–20 weeks' gestation, compared with the women in the control group. Psoriatic body surface area increased significantly by 6 weeks post partum among the new mothers, compared with the control women.

“Although two-thirds of the patients reported a worsening of psoriasis in the postpartum period … it was more of a return to baseline,” Ms. Kappel said.

The correlation between progesterone levels and improvement of psoriasis during pregnancy was not significant, nor was the correlation between estrone and improvement of psoriasis during pregnancy. There were moderate correlations between improvement in psoriasis and estriol and estradiol levels during pregnancy.

“Given that progesterone increases so much more than estradiol or estrone [during pregnancy], we hypothesized that it was the ratio of estrogen to progesterone that created an altered immunity,” Ms. Kappel said. The correlation between improvement of psoriasis during pregnancy and the ratio of estrogen to progesterone was the strongest.

One patient in particular had a progesterone level that was six standard deviations above the average of the general population during the pregnancy period but an estriol level that was within the normal range. Her psoriasis body surface area worsened from 52% to 65%. The researchers speculate that her ratio of progesterone to estrogen may have caused her worsening disease.

The study results illustrate that there is a shift from Th1 to Th2 immunity in pregnant patients. “This makes sense because Th1-mediated diseases, such as rheumatoid arthritis, psoriasis, and multiple sclerosis, tend to improve during pregnancy, whereas Th2-mediated diseases such as lupus tend to worsen,” Ms. Kappel explained.

In light of these findings, “estrogen, as a potential therapeutic option in conjunction with other treatment modalities, warrants further investigation,” she added.

Progesterone is the hormone that increases the most in pregnancy—about 200-fold—and is the key hormone in uterine suppression during pregnancy. Most of the pregnant women in this study had elevated progesterone levels within the normal range for the general population. Estrogen suppresses T-cell immunity but is also known to stimulate B-cell-mediated immunity in pregnancy.

Estradiol increases 24-fold during pregnancy and is the most potent estrogen; estrone increases about 6-fold during pregnancy. Estriol is the least potent and is only produced in significant amounts during pregnancy. Most of the pregnant study patients had normal-range levels of all three estrogens during their pregnancies.

STOCKHOLM — Psoriasis improves considerably for some women during pregnancy, and now there are data pointing to the ratio of estrogen to progesterone as a possible explanation for this improvement, according to the results of a study presented at an international conference on psoriasis and psoriatic arthritis.

For the study, 47 pregnant women with psoriasis had their psoriasis assessed and hormone levels measured at 10, 20, and 30 weeks' gestation and at 6 and 24 weeks post partum, said Stefani Kappel, a fourth-year medical student at the University of California, Irvine. Twenty-seven menstruating psoriasis patients were also recruited as controls. and were assessed at similar intervals over a 54-week period.

During pregnancy, just over half of the women (55%) reported improvement in their psoriasis: 21% reported no change and 23% reported worsening. “This was very similar to findings that were reported in the retrospective studies,” said Ms. Kappel, who collaborated with principal investigator Dr. Jenny E. Murase, a dermatology resident at the university.

In the postpartum period, 65% of the women reported a worsening of their psoriasis, 26% reported no change, and 9% reported an improvement.

Psoriatic body surface area decreased significantly among the pregnant women at 10–20 weeks' gestation, compared with the women in the control group. Psoriatic body surface area increased significantly by 6 weeks post partum among the new mothers, compared with the control women.

“Although two-thirds of the patients reported a worsening of psoriasis in the postpartum period … it was more of a return to baseline,” Ms. Kappel said.

The correlation between progesterone levels and improvement of psoriasis during pregnancy was not significant, nor was the correlation between estrone and improvement of psoriasis during pregnancy. There were moderate correlations between improvement in psoriasis and estriol and estradiol levels during pregnancy.

“Given that progesterone increases so much more than estradiol or estrone [during pregnancy], we hypothesized that it was the ratio of estrogen to progesterone that created an altered immunity,” Ms. Kappel said. The correlation between improvement of psoriasis during pregnancy and the ratio of estrogen to progesterone was the strongest.

One patient in particular had a progesterone level that was six standard deviations above the average of the general population during the pregnancy period but an estriol level that was within the normal range. Her psoriasis body surface area worsened from 52% to 65%. The researchers speculate that her ratio of progesterone to estrogen may have caused her worsening disease.

The study results illustrate that there is a shift from Th1 to Th2 immunity in pregnant patients. “This makes sense because Th1-mediated diseases, such as rheumatoid arthritis, psoriasis, and multiple sclerosis, tend to improve during pregnancy, whereas Th2-mediated diseases such as lupus tend to worsen,” Ms. Kappel explained.

In light of these findings, “estrogen, as a potential therapeutic option in conjunction with other treatment modalities, warrants further investigation,” she added.

Progesterone is the hormone that increases the most in pregnancy—about 200-fold—and is the key hormone in uterine suppression during pregnancy. Most of the pregnant women in this study had elevated progesterone levels within the normal range for the general population. Estrogen suppresses T-cell immunity but is also known to stimulate B-cell-mediated immunity in pregnancy.

Estradiol increases 24-fold during pregnancy and is the most potent estrogen; estrone increases about 6-fold during pregnancy. Estriol is the least potent and is only produced in significant amounts during pregnancy. Most of the pregnant study patients had normal-range levels of all three estrogens during their pregnancies.

The patient underwent initial precontrast computed tomography (CT) in the emergency department. This scan demonstrated a roughly 3-cm hyperdense mass that was centered on the right cavernous sinus. Associated vasogenic edema surrounded the mass. Additional foci of hypodensity were seen in the right centrum semiovale, said Dr. Gautam R. Mirchandani, director of neuroradiology at New York Methodist Hospital.

Pre- and postcontrast magnetic resonance imaging (MRI) on the next day demonstrated a heterogeneously—but avidly enhancing—extra-axial mass that corresponded with the CT finding. Regions of hypodensity seen on CT matched areas of restricted diffusion on diffusion-weighted imaging—representing acute infarction.

Magnetic resonance angiography (MRA) did not show the middle cerebral artery in that region because of the surrounding hypervascular lesion, which degrades the signal from that region. Flow-related enhancement was seen in more distal branches, suggesting that the middle cerebral artery was not occluded within the mass, but its branches were compromised. Of note, the regions of acute infarction correspond to the vascular territory of perforating vessels that arise from the proximal middle cerebral artery.

Further assessment of the mass was performed with CT angiography (CTA) to evaluate the relationship of the middle cerebral artery to the mass and to the regions of infarction. CTA demonstrated that the middle cerebral artery was not occluded within the lesion, although it was narrowed somewhat. Perforating vessels arising from the middle cerebral artery were also narrowed, likely causing her symptoms.

Based on the imaging characteristics, the clinical team was fairly confident that the avidly enhancing, extra-axial mass represented a meningioma, and surgical resection was planned.

Intraoperatively, frozen sections revealed histology consistent with adenocarcinoma, not with meningioma. Several specimens were sent to confirm this unexpected finding.

On postoperative review of the images, the two in-house neuroradiologists separately concurred that the imaging findings were still most consistent with a meningioma. “Even on re-review, I think it was reasonable to say that this looks like a meningioma,” said Dr. Mirchandani.

This conclusion was primarily based upon the extra-axial location and the avid enhancement. In addition, the tumor mass encased the near-by vessels, rather than occluding them. There was also no evidence of local osseous erosion, which is sometimes seen with other, more aggressive tumors. The absence of a known primary tumor made the possibility of a dural-based metastasis yet less likely.

Afterward, the patient was found to have a primary lung carcinoma, which had metastatically spread to the brain.

The patient arrested during the resection and underwent a prolonged resuscitation effort. She is currently intubated and on a ventilator. The patient is receiving supportive care, as she is still too ill for removal of the lung mass or undergo chemotherapy, said Dr. Susanna Horvath, director of the stroke program at New York Methodist Hospital.

“I think the teaching point in all this is that you have to look at the whole clinical scenario,” said Dr. Horvath.

By a large margin, enhancing, extra-axial masses represent meningiomas. Dural-based metastatic deposits, while possible, are seen much less often. Angiographic imaging can be very helpful in the evaluation of ischemic disease within the brain.

Precontrast CT shows a 3-cm mass near the right cavernous sinus.

Postcontrast T MRI shows the mass to be extra-axial and avidly enhancing. White matter hyperintensity corresponds to the hypodensity on CT.

DWI shows two foci of acute infarct on the right that are also visible on CT.

CTA demonstrates that the MCA within the mass is narrowed. Photos courtesy Dr. Gautam R. Mirchandani

The patient underwent initial precontrast computed tomography (CT) in the emergency department. This scan demonstrated a roughly 3-cm hyperdense mass that was centered on the right cavernous sinus. Associated vasogenic edema surrounded the mass. Additional foci of hypodensity were seen in the right centrum semiovale, said Dr. Gautam R. Mirchandani, director of neuroradiology at New York Methodist Hospital.

Pre- and postcontrast magnetic resonance imaging (MRI) on the next day demonstrated a heterogeneously—but avidly enhancing—extra-axial mass that corresponded with the CT finding. Regions of hypodensity seen on CT matched areas of restricted diffusion on diffusion-weighted imaging—representing acute infarction.

Magnetic resonance angiography (MRA) did not show the middle cerebral artery in that region because of the surrounding hypervascular lesion, which degrades the signal from that region. Flow-related enhancement was seen in more distal branches, suggesting that the middle cerebral artery was not occluded within the mass, but its branches were compromised. Of note, the regions of acute infarction correspond to the vascular territory of perforating vessels that arise from the proximal middle cerebral artery.

Further assessment of the mass was performed with CT angiography (CTA) to evaluate the relationship of the middle cerebral artery to the mass and to the regions of infarction. CTA demonstrated that the middle cerebral artery was not occluded within the lesion, although it was narrowed somewhat. Perforating vessels arising from the middle cerebral artery were also narrowed, likely causing her symptoms.

Based on the imaging characteristics, the clinical team was fairly confident that the avidly enhancing, extra-axial mass represented a meningioma, and surgical resection was planned.

Intraoperatively, frozen sections revealed histology consistent with adenocarcinoma, not with meningioma. Several specimens were sent to confirm this unexpected finding.

On postoperative review of the images, the two in-house neuroradiologists separately concurred that the imaging findings were still most consistent with a meningioma. “Even on re-review, I think it was reasonable to say that this looks like a meningioma,” said Dr. Mirchandani.

This conclusion was primarily based upon the extra-axial location and the avid enhancement. In addition, the tumor mass encased the near-by vessels, rather than occluding them. There was also no evidence of local osseous erosion, which is sometimes seen with other, more aggressive tumors. The absence of a known primary tumor made the possibility of a dural-based metastasis yet less likely.

Afterward, the patient was found to have a primary lung carcinoma, which had metastatically spread to the brain.

The patient arrested during the resection and underwent a prolonged resuscitation effort. She is currently intubated and on a ventilator. The patient is receiving supportive care, as she is still too ill for removal of the lung mass or undergo chemotherapy, said Dr. Susanna Horvath, director of the stroke program at New York Methodist Hospital.

“I think the teaching point in all this is that you have to look at the whole clinical scenario,” said Dr. Horvath.

By a large margin, enhancing, extra-axial masses represent meningiomas. Dural-based metastatic deposits, while possible, are seen much less often. Angiographic imaging can be very helpful in the evaluation of ischemic disease within the brain.

Precontrast CT shows a 3-cm mass near the right cavernous sinus.

Postcontrast T MRI shows the mass to be extra-axial and avidly enhancing. White matter hyperintensity corresponds to the hypodensity on CT.

DWI shows two foci of acute infarct on the right that are also visible on CT.

CTA demonstrates that the MCA within the mass is narrowed. Photos courtesy Dr. Gautam R. Mirchandani

The patient underwent initial precontrast computed tomography (CT) in the emergency department. This scan demonstrated a roughly 3-cm hyperdense mass that was centered on the right cavernous sinus. Associated vasogenic edema surrounded the mass. Additional foci of hypodensity were seen in the right centrum semiovale, said Dr. Gautam R. Mirchandani, director of neuroradiology at New York Methodist Hospital.

Pre- and postcontrast magnetic resonance imaging (MRI) on the next day demonstrated a heterogeneously—but avidly enhancing—extra-axial mass that corresponded with the CT finding. Regions of hypodensity seen on CT matched areas of restricted diffusion on diffusion-weighted imaging—representing acute infarction.

Magnetic resonance angiography (MRA) did not show the middle cerebral artery in that region because of the surrounding hypervascular lesion, which degrades the signal from that region. Flow-related enhancement was seen in more distal branches, suggesting that the middle cerebral artery was not occluded within the mass, but its branches were compromised. Of note, the regions of acute infarction correspond to the vascular territory of perforating vessels that arise from the proximal middle cerebral artery.

Further assessment of the mass was performed with CT angiography (CTA) to evaluate the relationship of the middle cerebral artery to the mass and to the regions of infarction. CTA demonstrated that the middle cerebral artery was not occluded within the lesion, although it was narrowed somewhat. Perforating vessels arising from the middle cerebral artery were also narrowed, likely causing her symptoms.

Based on the imaging characteristics, the clinical team was fairly confident that the avidly enhancing, extra-axial mass represented a meningioma, and surgical resection was planned.

Intraoperatively, frozen sections revealed histology consistent with adenocarcinoma, not with meningioma. Several specimens were sent to confirm this unexpected finding.

On postoperative review of the images, the two in-house neuroradiologists separately concurred that the imaging findings were still most consistent with a meningioma. “Even on re-review, I think it was reasonable to say that this looks like a meningioma,” said Dr. Mirchandani.

This conclusion was primarily based upon the extra-axial location and the avid enhancement. In addition, the tumor mass encased the near-by vessels, rather than occluding them. There was also no evidence of local osseous erosion, which is sometimes seen with other, more aggressive tumors. The absence of a known primary tumor made the possibility of a dural-based metastasis yet less likely.

Afterward, the patient was found to have a primary lung carcinoma, which had metastatically spread to the brain.

The patient arrested during the resection and underwent a prolonged resuscitation effort. She is currently intubated and on a ventilator. The patient is receiving supportive care, as she is still too ill for removal of the lung mass or undergo chemotherapy, said Dr. Susanna Horvath, director of the stroke program at New York Methodist Hospital.

“I think the teaching point in all this is that you have to look at the whole clinical scenario,” said Dr. Horvath.

By a large margin, enhancing, extra-axial masses represent meningiomas. Dural-based metastatic deposits, while possible, are seen much less often. Angiographic imaging can be very helpful in the evaluation of ischemic disease within the brain.

Precontrast CT shows a 3-cm mass near the right cavernous sinus.

Postcontrast T MRI shows the mass to be extra-axial and avidly enhancing. White matter hyperintensity corresponds to the hypodensity on CT.

DWI shows two foci of acute infarct on the right that are also visible on CT.

CTA demonstrates that the MCA within the mass is narrowed. Photos courtesy Dr. Gautam R. Mirchandani

ARLINGTON, VA. — Although the treatment of left main coronary artery lesions remains in the realm of cardiac surgery, some data suggest that there may be a role for drug-eluting stents, said Dr. Samin K. Sharma at a meeting sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

Between 5% and 7% of patients undergoing cardiac catheterization have unprotected left main coronary artery (LMCA) lesions, and almost two-thirds of these patients have distal bifurcation lesions. “The key is that the distal bifurcation is the most common lesion of the left main,” said Dr. Sharma, who is director of the cardiac catheterization laboratory at Mount Sinai Medical Center in New York.

Significant LMCA lesions have been considered primarily a surgical disease. Even the most recent update of percutaneous intervention guidelines (American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions 2005 Guideline Update for Percutaneous Intervention) categorized unprotected left main intervention as a class III indication.

Caution in using stents for LMCA is not without good reason, as there are several problems associated with stenting a left main lesion, compared with surgery, including lower rates of procedural success and higher rates of complications, stent thrombosis, restenosis and target lesion revascularization (TLR), and sudden death.

Several studies suggest a 10% rate of cardiac death at follow-up and a 22% restenosis rate for LMCA treated with bare metal stents. The patient's baseline clinical status and left ventricle function appear to be important predictors of outcome, on the basis of these trials, said Dr. Sharma.

However, results with drug-eluting stents (DESs) appear promising. In one study, patients with LMCA stenosis who were treated with the Cypher sirolimus-eluting stent had a 1-year major adverse cardiovascular event-free survival rate of 98%, compared with 81% for those treated with bare metal stents (J. Am. Coll. Cardiol. 2005;45:351–6).

In one analysis of data from Mount Sinai Medical Center, the TLR rate was 30% for 27 patients who received bare metal stents for unprotected LMCA bifurcation lesions, compared with 8% for 50 patients who received sirolimus-eluting stents, said Dr. Sharma, who is also codirector of the Cardiovascular Institute at Mount Sinai. In most of the procedures performed there, the simultaneous kissing stent technique was used. This technique involves advancing a stent to the side branch, followed by one to the main vessel. The two stents are then simultaneously pulled back to the bifurcation and then into the proximal part of the main vessel, configuring a Y (with the stem of the Y in the main vessel, completely covering the proximal end of the lesion, one arm in the distal main vessel, and one arm in the side branch).

The cutting balloon technique has also been used on the ostial circumflex for the majority of patients. Cutting balloon angioplasty uses atherotomes (microsurgical blades), which are attached to a balloon, expand radially, and cut longitudinal incisions in the plaque and vessel, relieving its hoop stress. The cutting balloon is engineered to protect the vessel from the edges of the atherotomes when it is deflated, minimizing the risk of trauma to the vessel as the balloon is passed to and from the target lesion.

Every patient in the analysis had angiographic follow-up 4 months and 1 year after the procedure. None of the patients had delayed thrombosis, said Dr. Sharma.

Of the 180 patients treated with DESs for unprotected LMCA at Mount Sinai, the 78 patients with ostial lesions and the 38 patients with more distal lesions had no restenosis (0% TLR rate), but the 64 patients with bifurcations had a 9% TLR rate.

Dr. Sharma noted that in one recent study of patients with unprotected LMCA disease, mortality was greater at 1 year among the 123 patients who underwent coronary artery bypass grafting (CABG) (15%), compared with the 50 patients who received DESs (4%). However, tricuspid valve replacement at 1 year was more common in the percutaneous coronary intervention group: 13% for DES, compared with 5% for CABG (J. Am. Coll. Cardiol. 2006;47:864–70).

The SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trial, which began enrollment last year, will hopefully provide a clearer picture. The trial will compare the performance of DES with that of CABG in the most complex patient subsets: those with coronary artery disease in all three coronary arteries, in the LMCA, or both.

Dr. Sharma had no significant financial relationships to disclose, he said.

A coronary angiogram taken before stenting reveals occlusion of the left main coronary artery.

This angiogram, taken after stent placement, shows that flow in the LMCA was restored. Photos courtesy Dr. Samin K. Sharma

ARLINGTON, VA. — Although the treatment of left main coronary artery lesions remains in the realm of cardiac surgery, some data suggest that there may be a role for drug-eluting stents, said Dr. Samin K. Sharma at a meeting sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

Between 5% and 7% of patients undergoing cardiac catheterization have unprotected left main coronary artery (LMCA) lesions, and almost two-thirds of these patients have distal bifurcation lesions. “The key is that the distal bifurcation is the most common lesion of the left main,” said Dr. Sharma, who is director of the cardiac catheterization laboratory at Mount Sinai Medical Center in New York.

Significant LMCA lesions have been considered primarily a surgical disease. Even the most recent update of percutaneous intervention guidelines (American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions 2005 Guideline Update for Percutaneous Intervention) categorized unprotected left main intervention as a class III indication.

Caution in using stents for LMCA is not without good reason, as there are several problems associated with stenting a left main lesion, compared with surgery, including lower rates of procedural success and higher rates of complications, stent thrombosis, restenosis and target lesion revascularization (TLR), and sudden death.

Several studies suggest a 10% rate of cardiac death at follow-up and a 22% restenosis rate for LMCA treated with bare metal stents. The patient's baseline clinical status and left ventricle function appear to be important predictors of outcome, on the basis of these trials, said Dr. Sharma.

However, results with drug-eluting stents (DESs) appear promising. In one study, patients with LMCA stenosis who were treated with the Cypher sirolimus-eluting stent had a 1-year major adverse cardiovascular event-free survival rate of 98%, compared with 81% for those treated with bare metal stents (J. Am. Coll. Cardiol. 2005;45:351–6).

In one analysis of data from Mount Sinai Medical Center, the TLR rate was 30% for 27 patients who received bare metal stents for unprotected LMCA bifurcation lesions, compared with 8% for 50 patients who received sirolimus-eluting stents, said Dr. Sharma, who is also codirector of the Cardiovascular Institute at Mount Sinai. In most of the procedures performed there, the simultaneous kissing stent technique was used. This technique involves advancing a stent to the side branch, followed by one to the main vessel. The two stents are then simultaneously pulled back to the bifurcation and then into the proximal part of the main vessel, configuring a Y (with the stem of the Y in the main vessel, completely covering the proximal end of the lesion, one arm in the distal main vessel, and one arm in the side branch).

The cutting balloon technique has also been used on the ostial circumflex for the majority of patients. Cutting balloon angioplasty uses atherotomes (microsurgical blades), which are attached to a balloon, expand radially, and cut longitudinal incisions in the plaque and vessel, relieving its hoop stress. The cutting balloon is engineered to protect the vessel from the edges of the atherotomes when it is deflated, minimizing the risk of trauma to the vessel as the balloon is passed to and from the target lesion.

Every patient in the analysis had angiographic follow-up 4 months and 1 year after the procedure. None of the patients had delayed thrombosis, said Dr. Sharma.

Of the 180 patients treated with DESs for unprotected LMCA at Mount Sinai, the 78 patients with ostial lesions and the 38 patients with more distal lesions had no restenosis (0% TLR rate), but the 64 patients with bifurcations had a 9% TLR rate.

Dr. Sharma noted that in one recent study of patients with unprotected LMCA disease, mortality was greater at 1 year among the 123 patients who underwent coronary artery bypass grafting (CABG) (15%), compared with the 50 patients who received DESs (4%). However, tricuspid valve replacement at 1 year was more common in the percutaneous coronary intervention group: 13% for DES, compared with 5% for CABG (J. Am. Coll. Cardiol. 2006;47:864–70).

The SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trial, which began enrollment last year, will hopefully provide a clearer picture. The trial will compare the performance of DES with that of CABG in the most complex patient subsets: those with coronary artery disease in all three coronary arteries, in the LMCA, or both.

Dr. Sharma had no significant financial relationships to disclose, he said.

A coronary angiogram taken before stenting reveals occlusion of the left main coronary artery.

This angiogram, taken after stent placement, shows that flow in the LMCA was restored. Photos courtesy Dr. Samin K. Sharma

ARLINGTON, VA. — Although the treatment of left main coronary artery lesions remains in the realm of cardiac surgery, some data suggest that there may be a role for drug-eluting stents, said Dr. Samin K. Sharma at a meeting sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

Between 5% and 7% of patients undergoing cardiac catheterization have unprotected left main coronary artery (LMCA) lesions, and almost two-thirds of these patients have distal bifurcation lesions. “The key is that the distal bifurcation is the most common lesion of the left main,” said Dr. Sharma, who is director of the cardiac catheterization laboratory at Mount Sinai Medical Center in New York.

Significant LMCA lesions have been considered primarily a surgical disease. Even the most recent update of percutaneous intervention guidelines (American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions 2005 Guideline Update for Percutaneous Intervention) categorized unprotected left main intervention as a class III indication.

Caution in using stents for LMCA is not without good reason, as there are several problems associated with stenting a left main lesion, compared with surgery, including lower rates of procedural success and higher rates of complications, stent thrombosis, restenosis and target lesion revascularization (TLR), and sudden death.

Several studies suggest a 10% rate of cardiac death at follow-up and a 22% restenosis rate for LMCA treated with bare metal stents. The patient's baseline clinical status and left ventricle function appear to be important predictors of outcome, on the basis of these trials, said Dr. Sharma.

However, results with drug-eluting stents (DESs) appear promising. In one study, patients with LMCA stenosis who were treated with the Cypher sirolimus-eluting stent had a 1-year major adverse cardiovascular event-free survival rate of 98%, compared with 81% for those treated with bare metal stents (J. Am. Coll. Cardiol. 2005;45:351–6).

In one analysis of data from Mount Sinai Medical Center, the TLR rate was 30% for 27 patients who received bare metal stents for unprotected LMCA bifurcation lesions, compared with 8% for 50 patients who received sirolimus-eluting stents, said Dr. Sharma, who is also codirector of the Cardiovascular Institute at Mount Sinai. In most of the procedures performed there, the simultaneous kissing stent technique was used. This technique involves advancing a stent to the side branch, followed by one to the main vessel. The two stents are then simultaneously pulled back to the bifurcation and then into the proximal part of the main vessel, configuring a Y (with the stem of the Y in the main vessel, completely covering the proximal end of the lesion, one arm in the distal main vessel, and one arm in the side branch).

The cutting balloon technique has also been used on the ostial circumflex for the majority of patients. Cutting balloon angioplasty uses atherotomes (microsurgical blades), which are attached to a balloon, expand radially, and cut longitudinal incisions in the plaque and vessel, relieving its hoop stress. The cutting balloon is engineered to protect the vessel from the edges of the atherotomes when it is deflated, minimizing the risk of trauma to the vessel as the balloon is passed to and from the target lesion.

Every patient in the analysis had angiographic follow-up 4 months and 1 year after the procedure. None of the patients had delayed thrombosis, said Dr. Sharma.

Of the 180 patients treated with DESs for unprotected LMCA at Mount Sinai, the 78 patients with ostial lesions and the 38 patients with more distal lesions had no restenosis (0% TLR rate), but the 64 patients with bifurcations had a 9% TLR rate.

Dr. Sharma noted that in one recent study of patients with unprotected LMCA disease, mortality was greater at 1 year among the 123 patients who underwent coronary artery bypass grafting (CABG) (15%), compared with the 50 patients who received DESs (4%). However, tricuspid valve replacement at 1 year was more common in the percutaneous coronary intervention group: 13% for DES, compared with 5% for CABG (J. Am. Coll. Cardiol. 2006;47:864–70).

The SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trial, which began enrollment last year, will hopefully provide a clearer picture. The trial will compare the performance of DES with that of CABG in the most complex patient subsets: those with coronary artery disease in all three coronary arteries, in the LMCA, or both.

Dr. Sharma had no significant financial relationships to disclose, he said.

A coronary angiogram taken before stenting reveals occlusion of the left main coronary artery.

This angiogram, taken after stent placement, shows that flow in the LMCA was restored. Photos courtesy Dr. Samin K. Sharma

SAN JUAN, P.R. — Dementia and depression appear to be quite common among residents in assisted living facilities, based on two analyses of facilities in Maryland that were presented at the annual meeting of the American Association for Geriatric Psychiatry.

Both analyses used data from the Maryland Assisted Living Study that included 22 facilities—10 large facilities (more than 15 beds) and 12 small (15 beds or fewer). Assisted living facilities are regulated by each state, and levels of regulation vary widely.

For the Maryland Assisted Living Study, residents of assisted living facilities were evaluated by a geriatric psychiatrist, a nurse (who was experienced with dementia evaluation), and a research assistant specializing in psychometrics. Comprehensive evaluations of residents included information from caregivers and family members, a clinical exam and history, assessment with quantitative scales (function, behavior, depression, medical comorbidity, quality of life, caregiver activity/burden), and neuropsychological battery.

A consensus conference specialist determined diagnoses for residents and assessed whether residents had been worked up and whether they were being treated appropriately. In particular, participants were assessed using the Cornell Scale for Depression in Dementia (CSDD), a 19-item clinician-administered instrument that uses information from interviews with both the patient and a nursing staff member. Those with scores greater than 7 were considered clinically depressed. The General Medical Health Rating was used to describe comorbidity and health status.

In the first analysis, researchers looked at levels of depression among 196 residents of assisted living facilities. “This is an important study for several reasons, but it is the first comprehensive assessment of psychiatric disease in the assisted living industry,” said Dr. Lea C. Watson, professor of psychiatry at the University of North Carolina at Chapel Hill. Subjects were an average of 86 years old, and were primarily women (79%) and white (84%).

Overall, 24% (47 subjects) met the criteria for clinical depression and 8% (15 subjects) met the criteria for severe depression (CSDD score greater than 12). Roughly two-thirds (67%) had dementia. The third of the participants who did not have dementia—those with Mini-Mental State Examination scores greater than 22—were evaluated with the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID IV). Of those, 13 met the criteria for depression.

Bivariate analysis revealed no differences between depressed and nondepressed individuals based on age, gender, number of social visits, or facility size. However, depressed individuals did have a greater number of comorbid conditions, required more assistance with activities of daily living, spent a greater number of days in bed per month, and participated in organized activities less frequently than did nondepressed individuals.

After controlling for several factors, (global health, supervision of activities of daily living, and social interaction), assistance with activities of daily living alone remained significantly associated with depression (odds ratio 3.8), while medical comorbidity trended toward significance (odds ratio 1.9).

Only 43% of those who were currently depressed were being treated with antidepressants. Likewise, only 40% of those who were severely depressed were being treated with antidepressants. Those with depression were more likely to be treated with antidepressants if they lived in a larger facility (51 % vs. 17%).

In the second analysis, researchers looked for any differences between large and small facilities for dementia frequency, detection, and management.

“Large facilities have most commonly arisen out of the hospitality industry and are more likely to be part of a chain,” said Quincy M. Samus, a graduate student at Johns Hopkins University in Baltimore, who presented a paper for Dr. Iracema Leroi of the University of Manchester (England). “Small facilities have evolved from the traditional board-and-care homes or group homes,” Ms. Samus said.

This analysis included 198 residents (150 from large facilities and 48 from small). Residents in smaller facilities were younger than were those in larger facilities—average age 82 years vs. 87 years. Residents in both types of facilities were admitted primarily because of functional limitations. Those in large facilities were significantly more likely to be admitted for medical reasons than were those in small facilities.

Significantly more residents in small facilities had dementia than did those in large facilities. Residents in small facilities also were slightly more likely to be diagnosed with Alzheimer's disease, though not significantly so.

Almost all residents (98%) in small facilities had either dementia or some other psychiatric diagnosis vs. 74% of those in large facilities. Likewise, residents in small facilities had more cognitive difficulties as measured by the Mini- Mental State Examination, with an average score of 13 compared with 20 for those in large facilities.

Residents in small facilities also had a greater number of behavioral symptoms, as measured by the Neuropsychiatric Inventory (17 vs. 10). More residents living in small facilities had psychotic disorders as well (10% vs. 1%). There were no differences in mood or anxiety disorders between the two facility sizes.

Of the 39 residents with dementia in small facilities, the caregiver was slightly more likely to recognize dementia symptoms than were family members. The opposite was true for the 95 residents with dementia in large facilities.

In terms of treatment, small and large facilities were comparable in the percentage of patients considered completely treated (around 50%).

“Residents who are living in large facilities actually were more likely to have a private duty [caregiver] stay with them,” Ms. Samus said. Residents in large facilities also were more likely to undergo physical therapy. Large facilities offered more activities for residents. Small facilities were more likely to use restraints and bedrails.

“Small care providers were actually spending more than 400 minutes a day caring, supervising, or doing activities of daily living with their residents, compared with a little over 100 minutes for the large facilities,” Ms. Samus said. The difference may be partly explained by the higher likelihood of having a private-duty caregiver at large facilities.

Residents at small facilities had fewer falls per month (0.13, compared with 0.33). No difference was found in emergency department visits in the last month.

ELSEVIER GLOBAL MEDICAL NEWS

SAN JUAN, P.R. — Dementia and depression appear to be quite common among residents in assisted living facilities, based on two analyses of facilities in Maryland that were presented at the annual meeting of the American Association for Geriatric Psychiatry.

Both analyses used data from the Maryland Assisted Living Study that included 22 facilities—10 large facilities (more than 15 beds) and 12 small (15 beds or fewer). Assisted living facilities are regulated by each state, and levels of regulation vary widely.

For the Maryland Assisted Living Study, residents of assisted living facilities were evaluated by a geriatric psychiatrist, a nurse (who was experienced with dementia evaluation), and a research assistant specializing in psychometrics. Comprehensive evaluations of residents included information from caregivers and family members, a clinical exam and history, assessment with quantitative scales (function, behavior, depression, medical comorbidity, quality of life, caregiver activity/burden), and neuropsychological battery.

A consensus conference specialist determined diagnoses for residents and assessed whether residents had been worked up and whether they were being treated appropriately. In particular, participants were assessed using the Cornell Scale for Depression in Dementia (CSDD), a 19-item clinician-administered instrument that uses information from interviews with both the patient and a nursing staff member. Those with scores greater than 7 were considered clinically depressed. The General Medical Health Rating was used to describe comorbidity and health status.

In the first analysis, researchers looked at levels of depression among 196 residents of assisted living facilities. “This is an important study for several reasons, but it is the first comprehensive assessment of psychiatric disease in the assisted living industry,” said Dr. Lea C. Watson, professor of psychiatry at the University of North Carolina at Chapel Hill. Subjects were an average of 86 years old, and were primarily women (79%) and white (84%).

Overall, 24% (47 subjects) met the criteria for clinical depression and 8% (15 subjects) met the criteria for severe depression (CSDD score greater than 12). Roughly two-thirds (67%) had dementia. The third of the participants who did not have dementia—those with Mini-Mental State Examination scores greater than 22—were evaluated with the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID IV). Of those, 13 met the criteria for depression.

Bivariate analysis revealed no differences between depressed and nondepressed individuals based on age, gender, number of social visits, or facility size. However, depressed individuals did have a greater number of comorbid conditions, required more assistance with activities of daily living, spent a greater number of days in bed per month, and participated in organized activities less frequently than did nondepressed individuals.

After controlling for several factors, (global health, supervision of activities of daily living, and social interaction), assistance with activities of daily living alone remained significantly associated with depression (odds ratio 3.8), while medical comorbidity trended toward significance (odds ratio 1.9).

Only 43% of those who were currently depressed were being treated with antidepressants. Likewise, only 40% of those who were severely depressed were being treated with antidepressants. Those with depression were more likely to be treated with antidepressants if they lived in a larger facility (51 % vs. 17%).

In the second analysis, researchers looked for any differences between large and small facilities for dementia frequency, detection, and management.

“Large facilities have most commonly arisen out of the hospitality industry and are more likely to be part of a chain,” said Quincy M. Samus, a graduate student at Johns Hopkins University in Baltimore, who presented a paper for Dr. Iracema Leroi of the University of Manchester (England). “Small facilities have evolved from the traditional board-and-care homes or group homes,” Ms. Samus said.

This analysis included 198 residents (150 from large facilities and 48 from small). Residents in smaller facilities were younger than were those in larger facilities—average age 82 years vs. 87 years. Residents in both types of facilities were admitted primarily because of functional limitations. Those in large facilities were significantly more likely to be admitted for medical reasons than were those in small facilities.

Significantly more residents in small facilities had dementia than did those in large facilities. Residents in small facilities also were slightly more likely to be diagnosed with Alzheimer's disease, though not significantly so.

Almost all residents (98%) in small facilities had either dementia or some other psychiatric diagnosis vs. 74% of those in large facilities. Likewise, residents in small facilities had more cognitive difficulties as measured by the Mini- Mental State Examination, with an average score of 13 compared with 20 for those in large facilities.

Residents in small facilities also had a greater number of behavioral symptoms, as measured by the Neuropsychiatric Inventory (17 vs. 10). More residents living in small facilities had psychotic disorders as well (10% vs. 1%). There were no differences in mood or anxiety disorders between the two facility sizes.

Of the 39 residents with dementia in small facilities, the caregiver was slightly more likely to recognize dementia symptoms than were family members. The opposite was true for the 95 residents with dementia in large facilities.

In terms of treatment, small and large facilities were comparable in the percentage of patients considered completely treated (around 50%).

“Residents who are living in large facilities actually were more likely to have a private duty [caregiver] stay with them,” Ms. Samus said. Residents in large facilities also were more likely to undergo physical therapy. Large facilities offered more activities for residents. Small facilities were more likely to use restraints and bedrails.

“Small care providers were actually spending more than 400 minutes a day caring, supervising, or doing activities of daily living with their residents, compared with a little over 100 minutes for the large facilities,” Ms. Samus said. The difference may be partly explained by the higher likelihood of having a private-duty caregiver at large facilities.

Residents at small facilities had fewer falls per month (0.13, compared with 0.33). No difference was found in emergency department visits in the last month.

ELSEVIER GLOBAL MEDICAL NEWS

SAN JUAN, P.R. — Dementia and depression appear to be quite common among residents in assisted living facilities, based on two analyses of facilities in Maryland that were presented at the annual meeting of the American Association for Geriatric Psychiatry.

Both analyses used data from the Maryland Assisted Living Study that included 22 facilities—10 large facilities (more than 15 beds) and 12 small (15 beds or fewer). Assisted living facilities are regulated by each state, and levels of regulation vary widely.

For the Maryland Assisted Living Study, residents of assisted living facilities were evaluated by a geriatric psychiatrist, a nurse (who was experienced with dementia evaluation), and a research assistant specializing in psychometrics. Comprehensive evaluations of residents included information from caregivers and family members, a clinical exam and history, assessment with quantitative scales (function, behavior, depression, medical comorbidity, quality of life, caregiver activity/burden), and neuropsychological battery.

A consensus conference specialist determined diagnoses for residents and assessed whether residents had been worked up and whether they were being treated appropriately. In particular, participants were assessed using the Cornell Scale for Depression in Dementia (CSDD), a 19-item clinician-administered instrument that uses information from interviews with both the patient and a nursing staff member. Those with scores greater than 7 were considered clinically depressed. The General Medical Health Rating was used to describe comorbidity and health status.

In the first analysis, researchers looked at levels of depression among 196 residents of assisted living facilities. “This is an important study for several reasons, but it is the first comprehensive assessment of psychiatric disease in the assisted living industry,” said Dr. Lea C. Watson, professor of psychiatry at the University of North Carolina at Chapel Hill. Subjects were an average of 86 years old, and were primarily women (79%) and white (84%).

Overall, 24% (47 subjects) met the criteria for clinical depression and 8% (15 subjects) met the criteria for severe depression (CSDD score greater than 12). Roughly two-thirds (67%) had dementia. The third of the participants who did not have dementia—those with Mini-Mental State Examination scores greater than 22—were evaluated with the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID IV). Of those, 13 met the criteria for depression.

Bivariate analysis revealed no differences between depressed and nondepressed individuals based on age, gender, number of social visits, or facility size. However, depressed individuals did have a greater number of comorbid conditions, required more assistance with activities of daily living, spent a greater number of days in bed per month, and participated in organized activities less frequently than did nondepressed individuals.

After controlling for several factors, (global health, supervision of activities of daily living, and social interaction), assistance with activities of daily living alone remained significantly associated with depression (odds ratio 3.8), while medical comorbidity trended toward significance (odds ratio 1.9).

Only 43% of those who were currently depressed were being treated with antidepressants. Likewise, only 40% of those who were severely depressed were being treated with antidepressants. Those with depression were more likely to be treated with antidepressants if they lived in a larger facility (51 % vs. 17%).

In the second analysis, researchers looked for any differences between large and small facilities for dementia frequency, detection, and management.

“Large facilities have most commonly arisen out of the hospitality industry and are more likely to be part of a chain,” said Quincy M. Samus, a graduate student at Johns Hopkins University in Baltimore, who presented a paper for Dr. Iracema Leroi of the University of Manchester (England). “Small facilities have evolved from the traditional board-and-care homes or group homes,” Ms. Samus said.

This analysis included 198 residents (150 from large facilities and 48 from small). Residents in smaller facilities were younger than were those in larger facilities—average age 82 years vs. 87 years. Residents in both types of facilities were admitted primarily because of functional limitations. Those in large facilities were significantly more likely to be admitted for medical reasons than were those in small facilities.

Significantly more residents in small facilities had dementia than did those in large facilities. Residents in small facilities also were slightly more likely to be diagnosed with Alzheimer's disease, though not significantly so.

Almost all residents (98%) in small facilities had either dementia or some other psychiatric diagnosis vs. 74% of those in large facilities. Likewise, residents in small facilities had more cognitive difficulties as measured by the Mini- Mental State Examination, with an average score of 13 compared with 20 for those in large facilities.

Residents in small facilities also had a greater number of behavioral symptoms, as measured by the Neuropsychiatric Inventory (17 vs. 10). More residents living in small facilities had psychotic disorders as well (10% vs. 1%). There were no differences in mood or anxiety disorders between the two facility sizes.

Of the 39 residents with dementia in small facilities, the caregiver was slightly more likely to recognize dementia symptoms than were family members. The opposite was true for the 95 residents with dementia in large facilities.

In terms of treatment, small and large facilities were comparable in the percentage of patients considered completely treated (around 50%).

“Residents who are living in large facilities actually were more likely to have a private duty [caregiver] stay with them,” Ms. Samus said. Residents in large facilities also were more likely to undergo physical therapy. Large facilities offered more activities for residents. Small facilities were more likely to use restraints and bedrails.

“Small care providers were actually spending more than 400 minutes a day caring, supervising, or doing activities of daily living with their residents, compared with a little over 100 minutes for the large facilities,” Ms. Samus said. The difference may be partly explained by the higher likelihood of having a private-duty caregiver at large facilities.

Residents at small facilities had fewer falls per month (0.13, compared with 0.33). No difference was found in emergency department visits in the last month.

ELSEVIER GLOBAL MEDICAL NEWS

The Food and Drug Administration has approved the first generic versions of Mobic (meloxicam) for the treatment of osteoarthritis.

The new approvals of 13 generic meloxicam applications stem from the agency's cluster review approach, aimed at increasing efficiency and decreasing review time for generic drugs.

The agency has begun to review groups of applications that are typically submitted at the end of 5-year new-chemical-entity exclusivity.

In the case of meloxicam, an NSAID, the FDA received more than 20 abbreviated new drug applications. The new approvals took the review team about 9 months to complete.

The Food and Drug Administration has approved the first generic versions of Mobic (meloxicam) for the treatment of osteoarthritis.

The new approvals of 13 generic meloxicam applications stem from the agency's cluster review approach, aimed at increasing efficiency and decreasing review time for generic drugs.

The agency has begun to review groups of applications that are typically submitted at the end of 5-year new-chemical-entity exclusivity.

In the case of meloxicam, an NSAID, the FDA received more than 20 abbreviated new drug applications. The new approvals took the review team about 9 months to complete.

The Food and Drug Administration has approved the first generic versions of Mobic (meloxicam) for the treatment of osteoarthritis.

The new approvals of 13 generic meloxicam applications stem from the agency's cluster review approach, aimed at increasing efficiency and decreasing review time for generic drugs.

The agency has begun to review groups of applications that are typically submitted at the end of 5-year new-chemical-entity exclusivity.

In the case of meloxicam, an NSAID, the FDA received more than 20 abbreviated new drug applications. The new approvals took the review team about 9 months to complete.

Reports of fatal and nonfatal intracranial hemorrhage among HIV-1 infected patients taking Aptivus (tipranavir) in combination antiretroviral therapy have prompted the manufacturer to issue new safety information.

Boehringer Ingelheim Pharmaceuticals Inc. has identified 14 reports of intracranial hemorrhage, including eight fatalities, in 6,840 HIV-1 infected individuals receiving Aptivus capsules coadministered with ritonavir (Norvir) (500 mg/200 mg twice daily).

Many of these patients who developed intracranial hemorrhage had other medical conditions—CNS lesions, head trauma, recent neurosurgery, coagulopathy, hypertension, or alcohol abuse—or were receiving concomitant medications, including anticoagulants and antiplatelet agents, that may have caused or contributed to these events.

The Boxed Warnings, Indications and Usage, Warnings, Precautions, Adverse Reactions, and Animal Pharmacology sections of the label have been changed to reflect concerns about using the drug in patients at increased risk of bleeding.

No pattern of abnormal coagulation parameters has been identified in patients receiving Aptivus in general or preceding the development of intracranial hemorrhage. For this reason, routine measurement of coagulation parameters is not currently indicated for the management of patients taking the drug.

Aptivus/ritonavir therapy should be used cautiously in patients who may be at risk for increased bleeding from trauma, surgery, or other medical conditions, or who are taking other medications known to increase the risk of bleeding.

Of note, patients with advanced HIV-1 disease/AIDS have been observed to have an increased risk of intracranial hemorrhage. Investigations are ongoing to determine the role of Aptivus in the development of intracranial hemorrhage.

For more information or to report adverse reactions, contact Boehringer Ingelheim Pharmaceuticals by calling 800-542-6257 (option 4). Adverse reactions can also be reported to the Food and Drug Administration's MedWatch program by calling 800-332-1088.

Reports of fatal and nonfatal intracranial hemorrhage among HIV-1 infected patients taking Aptivus (tipranavir) in combination antiretroviral therapy have prompted the manufacturer to issue new safety information.

Boehringer Ingelheim Pharmaceuticals Inc. has identified 14 reports of intracranial hemorrhage, including eight fatalities, in 6,840 HIV-1 infected individuals receiving Aptivus capsules coadministered with ritonavir (Norvir) (500 mg/200 mg twice daily).

Many of these patients who developed intracranial hemorrhage had other medical conditions—CNS lesions, head trauma, recent neurosurgery, coagulopathy, hypertension, or alcohol abuse—or were receiving concomitant medications, including anticoagulants and antiplatelet agents, that may have caused or contributed to these events.

The Boxed Warnings, Indications and Usage, Warnings, Precautions, Adverse Reactions, and Animal Pharmacology sections of the label have been changed to reflect concerns about using the drug in patients at increased risk of bleeding.

No pattern of abnormal coagulation parameters has been identified in patients receiving Aptivus in general or preceding the development of intracranial hemorrhage. For this reason, routine measurement of coagulation parameters is not currently indicated for the management of patients taking the drug.

Aptivus/ritonavir therapy should be used cautiously in patients who may be at risk for increased bleeding from trauma, surgery, or other medical conditions, or who are taking other medications known to increase the risk of bleeding.

Of note, patients with advanced HIV-1 disease/AIDS have been observed to have an increased risk of intracranial hemorrhage. Investigations are ongoing to determine the role of Aptivus in the development of intracranial hemorrhage.

For more information or to report adverse reactions, contact Boehringer Ingelheim Pharmaceuticals by calling 800-542-6257 (option 4). Adverse reactions can also be reported to the Food and Drug Administration's MedWatch program by calling 800-332-1088.

Reports of fatal and nonfatal intracranial hemorrhage among HIV-1 infected patients taking Aptivus (tipranavir) in combination antiretroviral therapy have prompted the manufacturer to issue new safety information.

Boehringer Ingelheim Pharmaceuticals Inc. has identified 14 reports of intracranial hemorrhage, including eight fatalities, in 6,840 HIV-1 infected individuals receiving Aptivus capsules coadministered with ritonavir (Norvir) (500 mg/200 mg twice daily).

Many of these patients who developed intracranial hemorrhage had other medical conditions—CNS lesions, head trauma, recent neurosurgery, coagulopathy, hypertension, or alcohol abuse—or were receiving concomitant medications, including anticoagulants and antiplatelet agents, that may have caused or contributed to these events.

The Boxed Warnings, Indications and Usage, Warnings, Precautions, Adverse Reactions, and Animal Pharmacology sections of the label have been changed to reflect concerns about using the drug in patients at increased risk of bleeding.

No pattern of abnormal coagulation parameters has been identified in patients receiving Aptivus in general or preceding the development of intracranial hemorrhage. For this reason, routine measurement of coagulation parameters is not currently indicated for the management of patients taking the drug.

Aptivus/ritonavir therapy should be used cautiously in patients who may be at risk for increased bleeding from trauma, surgery, or other medical conditions, or who are taking other medications known to increase the risk of bleeding.

Of note, patients with advanced HIV-1 disease/AIDS have been observed to have an increased risk of intracranial hemorrhage. Investigations are ongoing to determine the role of Aptivus in the development of intracranial hemorrhage.

For more information or to report adverse reactions, contact Boehringer Ingelheim Pharmaceuticals by calling 800-542-6257 (option 4). Adverse reactions can also be reported to the Food and Drug Administration's MedWatch program by calling 800-332-1088.

WASHINGTON – Cognitive changes in Parkinson's disease can be seen on positron emission tomography imaging and correlate well with psychological tests, according to data reported in a poster at the World Parkinson Congress.

Dr. David Eidelberg, director of the Center for Neurosciences, and his colleagues at the Feinstein Institute for Medical Research at the North Shore-Long Island Jewish Health System in Manhasset, New York, studied 47 Parkinson's disease (PD) patients (31 men and 16 women) using

In addition to affect, four domains–memory/verbal learning, attention/executive function, visuospatial function, and general cognitive function–were assessed with neuropsychological testing.

“We looked for patterns in the brain that correlated with their psychologic performance,” Dr. Eidelberg said.

The patients were an average age of 58 years and had PD for an average of 12 years. General cognitive function was assessed using the Mini-Mental State Examination.

Scans were analyzed using network analysis that isolates different aspects of neural circuits that correlate with cognitive function. Analysis revealed a significant pattern of covarying metabolic reductions in the parietal cortex, anterior cingulate area, and medical frontal lobe. This pattern correlated negatively with performance on the California Verbal Learning test, Stroop test, digit symbol test, and Hooper Visual Organization test, and positively with the Trail Making test, but not with affect.

The researchers also validated this PD cognitive-related pattern (PDCP) in 21 patients with PD who were scanned twice over a 2-month period. Comparison of the test-retest results showed that PDCP was highly reliable as a predictor of psychological performance.

“What makes this appealing is that there is a way to measure cognitive function indirectly,” Dr. Eidelberg said.

The researchers also investigated two clinical applications for the technique. First, they computed the PD-related pattern (motor function) and PDCP in 15 early-stage patients scanned at baseline and at 2 and 4 years. PDCP expression was significantly elevated at the third time point with respect to both baseline and the second time point. “The motor pattern is higher typically and progresses like a straight line. The PDCP starts slower and may not be a straight line in terms of its evolution,” he said.

In PD the motor and cognitive changes have different time courses. Cognitive changes have a later evolution in the course of the disease. “Treating the motor component of Parkinson's disease, which is what we all do, does not appear to really do much for cognition and at times makes it worse,” Dr. Eidelberg said.

The findings validate PDCP as a stable and reproducible imaging marker of cognitive function in PD. Unlike the PD motor-related pattern, the nonmotor pattern evolves slowly over time and its expression is not altered by therapeutic interventions targeting the motor manifestation of PD.

Metabolic decreases in the prefrontal/frontal cortex (in green; Brodmann areas 9 and 46) and parietal cortex (Brodmann 7, 39, and 40) typify PDCP for mild/moderate cognitive impairment. Courtesy Dr. David Eidelberg

WASHINGTON – Cognitive changes in Parkinson's disease can be seen on positron emission tomography imaging and correlate well with psychological tests, according to data reported in a poster at the World Parkinson Congress.

Dr. David Eidelberg, director of the Center for Neurosciences, and his colleagues at the Feinstein Institute for Medical Research at the North Shore-Long Island Jewish Health System in Manhasset, New York, studied 47 Parkinson's disease (PD) patients (31 men and 16 women) using

In addition to affect, four domains–memory/verbal learning, attention/executive function, visuospatial function, and general cognitive function–were assessed with neuropsychological testing.

“We looked for patterns in the brain that correlated with their psychologic performance,” Dr. Eidelberg said.

The patients were an average age of 58 years and had PD for an average of 12 years. General cognitive function was assessed using the Mini-Mental State Examination.

Scans were analyzed using network analysis that isolates different aspects of neural circuits that correlate with cognitive function. Analysis revealed a significant pattern of covarying metabolic reductions in the parietal cortex, anterior cingulate area, and medical frontal lobe. This pattern correlated negatively with performance on the California Verbal Learning test, Stroop test, digit symbol test, and Hooper Visual Organization test, and positively with the Trail Making test, but not with affect.

The researchers also validated this PD cognitive-related pattern (PDCP) in 21 patients with PD who were scanned twice over a 2-month period. Comparison of the test-retest results showed that PDCP was highly reliable as a predictor of psychological performance.

“What makes this appealing is that there is a way to measure cognitive function indirectly,” Dr. Eidelberg said.

The researchers also investigated two clinical applications for the technique. First, they computed the PD-related pattern (motor function) and PDCP in 15 early-stage patients scanned at baseline and at 2 and 4 years. PDCP expression was significantly elevated at the third time point with respect to both baseline and the second time point. “The motor pattern is higher typically and progresses like a straight line. The PDCP starts slower and may not be a straight line in terms of its evolution,” he said.

In PD the motor and cognitive changes have different time courses. Cognitive changes have a later evolution in the course of the disease. “Treating the motor component of Parkinson's disease, which is what we all do, does not appear to really do much for cognition and at times makes it worse,” Dr. Eidelberg said.

The findings validate PDCP as a stable and reproducible imaging marker of cognitive function in PD. Unlike the PD motor-related pattern, the nonmotor pattern evolves slowly over time and its expression is not altered by therapeutic interventions targeting the motor manifestation of PD.

Metabolic decreases in the prefrontal/frontal cortex (in green; Brodmann areas 9 and 46) and parietal cortex (Brodmann 7, 39, and 40) typify PDCP for mild/moderate cognitive impairment. Courtesy Dr. David Eidelberg

WASHINGTON – Cognitive changes in Parkinson's disease can be seen on positron emission tomography imaging and correlate well with psychological tests, according to data reported in a poster at the World Parkinson Congress.

Dr. David Eidelberg, director of the Center for Neurosciences, and his colleagues at the Feinstein Institute for Medical Research at the North Shore-Long Island Jewish Health System in Manhasset, New York, studied 47 Parkinson's disease (PD) patients (31 men and 16 women) using

In addition to affect, four domains–memory/verbal learning, attention/executive function, visuospatial function, and general cognitive function–were assessed with neuropsychological testing.

“We looked for patterns in the brain that correlated with their psychologic performance,” Dr. Eidelberg said.

The patients were an average age of 58 years and had PD for an average of 12 years. General cognitive function was assessed using the Mini-Mental State Examination.

Scans were analyzed using network analysis that isolates different aspects of neural circuits that correlate with cognitive function. Analysis revealed a significant pattern of covarying metabolic reductions in the parietal cortex, anterior cingulate area, and medical frontal lobe. This pattern correlated negatively with performance on the California Verbal Learning test, Stroop test, digit symbol test, and Hooper Visual Organization test, and positively with the Trail Making test, but not with affect.

The researchers also validated this PD cognitive-related pattern (PDCP) in 21 patients with PD who were scanned twice over a 2-month period. Comparison of the test-retest results showed that PDCP was highly reliable as a predictor of psychological performance.

“What makes this appealing is that there is a way to measure cognitive function indirectly,” Dr. Eidelberg said.

The researchers also investigated two clinical applications for the technique. First, they computed the PD-related pattern (motor function) and PDCP in 15 early-stage patients scanned at baseline and at 2 and 4 years. PDCP expression was significantly elevated at the third time point with respect to both baseline and the second time point. “The motor pattern is higher typically and progresses like a straight line. The PDCP starts slower and may not be a straight line in terms of its evolution,” he said.

In PD the motor and cognitive changes have different time courses. Cognitive changes have a later evolution in the course of the disease. “Treating the motor component of Parkinson's disease, which is what we all do, does not appear to really do much for cognition and at times makes it worse,” Dr. Eidelberg said.

The findings validate PDCP as a stable and reproducible imaging marker of cognitive function in PD. Unlike the PD motor-related pattern, the nonmotor pattern evolves slowly over time and its expression is not altered by therapeutic interventions targeting the motor manifestation of PD.

Metabolic decreases in the prefrontal/frontal cortex (in green; Brodmann areas 9 and 46) and parietal cortex (Brodmann 7, 39, and 40) typify PDCP for mild/moderate cognitive impairment. Courtesy Dr. David Eidelberg

WASHINGTON — Improvements in technology and technique are helping to overcome some of the limitations of CT colonography, and this may ultimately lead to its widespread use in screening for colorectal cancer, Dr. Jay P. Heiken said at the International Union Against Cancer Conference.

CT colonography—also known as virtual colonoscopy—allows physicians to look for abnormalities in the colon wall using either the standard 2-D format or a 3-D approach. The 3-D view allows the physician to see the colon in much the same way that an endoscopist would—navigating the colon forward or backward, said Dr. Heiken, a professor of radiology at the Mallinckrodt Institute of Radiology at Washington University, St. Louis.

The advantages of this technique over optical colonoscopy include:

▸ A noninvasive technique that requires no sedation.

▸ Rapid image acquisition.

▸ Accurate localization of lesions.

▸ The elimination of blind spots.

▸ Extracolonic findings.

The technique is not without disadvantages, however. The first problem is the radiation dose. “I think this really is not a significant problem,” Dr. Heiken said. Several studies have shown that CT colonography can be performed with a radiation dose substantially lower than that of an aircontrast barium enema.

With virtual colonoscopy, it can be difficult to distinguish polyps from residual stool. Stool tagging can be used to overcome this obstacle. Small amounts of barium are administered orally the day before the examination. The barium is ingested during the bowel cleansing process and is incorporated into any residual stool in the colon, allowing that stool to be clearly differentiated from a polyp on a 2-D image.

A similar technique can be used to help distinguish polyps from residual fluid, which many bowel preparations can leave behind. Fluid tagging involves administering a small amount of oral iodine the night before the examination. Residual fluid then appears high in density on a 2-D image.

The landmark study for virtual colonoscopy involved 1,233 asymptomatic adults who underwent virtual and optical scans on the same day (N. Engl. J. Med. 2003;349:2191–200). The researchers concluded that virtual colonoscopy was comparable to optical colonoscopy for the detection of clinically relevant polyps.

Two subsequent studies found much lower sensitivities for CT colonography, at about 50% (JAMA 2004;291:1713–9; Lancet 2005;365:305–11). Neither of the studies involved screening populations, and both used somewhat outdated techniques and 2-D images. “We're now using multidetector scanners that have 4, 16, or 64 detector rows,” Dr. Heiken said. “Our spatial resolution is much greater, so we can identify much smaller polyps.”

Moreover, readers involved in the JAMA study were not trained in reading virtual colonoscopy images. All of these aspects help to account for the low sensitivities.

Importantly, results should be available in 2007 from the U.S. CT Colonography Screening Trial involving virtual and optical colonoscopy of 2,600 asymptomatic adults with average risk for colon cancer. None of the 15 participating institutions has used less than 16-row CT, and most have been using 64-row CT. In addition, stool and fluid tagging is being used, and all readers have been trained. The trial is organized by the American College of Radiology Imaging Network and is funded by the National Cancer Institute.

While most of the obstacles to the widespread use of virtual colonoscopy as a screening tool appear to have been addressed, capacity—particularly adequate reader training—remains an issue. “It takes at least 50–100 examinations to begin to develop the expertise necessary to read these [images] properly and accurately,” Dr. Heiken said. Reader training would have to be ramped up to meet the goal of widespread use.

Perhaps the most important issue is the lack of third-party payment for colorectal screening using CT colonography in the United States.

Still, some innovations on the horizon may hasten the routine use of virtual colonoscopy. The “filet” view opens the colon up electronically to allow it to be viewed like a pathology specimen. “The advantage of that is that it makes it less likely that we'll miss things … around bends,” Dr. Heiken said.

Computer-aided diagnosis also may soon play a part in virtual colonoscopy. Software improvements could help identify potential polyps missed on visual inspection. The final determination would still be made by the physician. “It will be very important for helping us improve our detection rate, decrease interobserver variability, and … make our examination more efficient,” he said.

Virtual colonoscopy examinations involving minimal bowel preparation might even be possible soon. “One of the big obstacles to colorectal cancer screening is that most patients do not want to have to undergo a rigorous, cathartic bowel preparation,” Dr. Heiken said. Consequently, many patients who should be screened forgo this exam. Some studies have shown that it is feasible to perform CT colonography with stool and fluid tagging but without cathartic preparation and get good results.

Greater patient discomfort associated with colon inflation during virtual colonoscopy is another potential limitation. However, discomfort most often arises from the use of room air to insufflate the colon, Dr. Heiken noted. The use of CO2 is more comfortable for the patient and the gas is more quickly reabsorbed by the body.

This sagittal image of a rectosigmoid polyp was made with a 16-row scanner.

The same polyp is displayed in an endoluminal view by using a 3-D format. Photos courtesy Dr. Jay P. Heiken

WASHINGTON — Improvements in technology and technique are helping to overcome some of the limitations of CT colonography, and this may ultimately lead to its widespread use in screening for colorectal cancer, Dr. Jay P. Heiken said at the International Union Against Cancer Conference.

CT colonography—also known as virtual colonoscopy—allows physicians to look for abnormalities in the colon wall using either the standard 2-D format or a 3-D approach. The 3-D view allows the physician to see the colon in much the same way that an endoscopist would—navigating the colon forward or backward, said Dr. Heiken, a professor of radiology at the Mallinckrodt Institute of Radiology at Washington University, St. Louis.

The advantages of this technique over optical colonoscopy include:

▸ A noninvasive technique that requires no sedation.

▸ Rapid image acquisition.

▸ Accurate localization of lesions.

▸ The elimination of blind spots.

▸ Extracolonic findings.

The technique is not without disadvantages, however. The first problem is the radiation dose. “I think this really is not a significant problem,” Dr. Heiken said. Several studies have shown that CT colonography can be performed with a radiation dose substantially lower than that of an aircontrast barium enema.

With virtual colonoscopy, it can be difficult to distinguish polyps from residual stool. Stool tagging can be used to overcome this obstacle. Small amounts of barium are administered orally the day before the examination. The barium is ingested during the bowel cleansing process and is incorporated into any residual stool in the colon, allowing that stool to be clearly differentiated from a polyp on a 2-D image.

A similar technique can be used to help distinguish polyps from residual fluid, which many bowel preparations can leave behind. Fluid tagging involves administering a small amount of oral iodine the night before the examination. Residual fluid then appears high in density on a 2-D image.

The landmark study for virtual colonoscopy involved 1,233 asymptomatic adults who underwent virtual and optical scans on the same day (N. Engl. J. Med. 2003;349:2191–200). The researchers concluded that virtual colonoscopy was comparable to optical colonoscopy for the detection of clinically relevant polyps.

Two subsequent studies found much lower sensitivities for CT colonography, at about 50% (JAMA 2004;291:1713–9; Lancet 2005;365:305–11). Neither of the studies involved screening populations, and both used somewhat outdated techniques and 2-D images. “We're now using multidetector scanners that have 4, 16, or 64 detector rows,” Dr. Heiken said. “Our spatial resolution is much greater, so we can identify much smaller polyps.”

Moreover, readers involved in the JAMA study were not trained in reading virtual colonoscopy images. All of these aspects help to account for the low sensitivities.

Importantly, results should be available in 2007 from the U.S. CT Colonography Screening Trial involving virtual and optical colonoscopy of 2,600 asymptomatic adults with average risk for colon cancer. None of the 15 participating institutions has used less than 16-row CT, and most have been using 64-row CT. In addition, stool and fluid tagging is being used, and all readers have been trained. The trial is organized by the American College of Radiology Imaging Network and is funded by the National Cancer Institute.

While most of the obstacles to the widespread use of virtual colonoscopy as a screening tool appear to have been addressed, capacity—particularly adequate reader training—remains an issue. “It takes at least 50–100 examinations to begin to develop the expertise necessary to read these [images] properly and accurately,” Dr. Heiken said. Reader training would have to be ramped up to meet the goal of widespread use.

Perhaps the most important issue is the lack of third-party payment for colorectal screening using CT colonography in the United States.

Still, some innovations on the horizon may hasten the routine use of virtual colonoscopy. The “filet” view opens the colon up electronically to allow it to be viewed like a pathology specimen. “The advantage of that is that it makes it less likely that we'll miss things … around bends,” Dr. Heiken said.

Computer-aided diagnosis also may soon play a part in virtual colonoscopy. Software improvements could help identify potential polyps missed on visual inspection. The final determination would still be made by the physician. “It will be very important for helping us improve our detection rate, decrease interobserver variability, and … make our examination more efficient,” he said.

Virtual colonoscopy examinations involving minimal bowel preparation might even be possible soon. “One of the big obstacles to colorectal cancer screening is that most patients do not want to have to undergo a rigorous, cathartic bowel preparation,” Dr. Heiken said. Consequently, many patients who should be screened forgo this exam. Some studies have shown that it is feasible to perform CT colonography with stool and fluid tagging but without cathartic preparation and get good results.

Greater patient discomfort associated with colon inflation during virtual colonoscopy is another potential limitation. However, discomfort most often arises from the use of room air to insufflate the colon, Dr. Heiken noted. The use of CO2 is more comfortable for the patient and the gas is more quickly reabsorbed by the body.

This sagittal image of a rectosigmoid polyp was made with a 16-row scanner.

The same polyp is displayed in an endoluminal view by using a 3-D format. Photos courtesy Dr. Jay P. Heiken

WASHINGTON — Improvements in technology and technique are helping to overcome some of the limitations of CT colonography, and this may ultimately lead to its widespread use in screening for colorectal cancer, Dr. Jay P. Heiken said at the International Union Against Cancer Conference.

CT colonography—also known as virtual colonoscopy—allows physicians to look for abnormalities in the colon wall using either the standard 2-D format or a 3-D approach. The 3-D view allows the physician to see the colon in much the same way that an endoscopist would—navigating the colon forward or backward, said Dr. Heiken, a professor of radiology at the Mallinckrodt Institute of Radiology at Washington University, St. Louis.

The advantages of this technique over optical colonoscopy include:

▸ A noninvasive technique that requires no sedation.

▸ Rapid image acquisition.

▸ Accurate localization of lesions.

▸ The elimination of blind spots.

▸ Extracolonic findings.

The technique is not without disadvantages, however. The first problem is the radiation dose. “I think this really is not a significant problem,” Dr. Heiken said. Several studies have shown that CT colonography can be performed with a radiation dose substantially lower than that of an aircontrast barium enema.

With virtual colonoscopy, it can be difficult to distinguish polyps from residual stool. Stool tagging can be used to overcome this obstacle. Small amounts of barium are administered orally the day before the examination. The barium is ingested during the bowel cleansing process and is incorporated into any residual stool in the colon, allowing that stool to be clearly differentiated from a polyp on a 2-D image.

A similar technique can be used to help distinguish polyps from residual fluid, which many bowel preparations can leave behind. Fluid tagging involves administering a small amount of oral iodine the night before the examination. Residual fluid then appears high in density on a 2-D image.

The landmark study for virtual colonoscopy involved 1,233 asymptomatic adults who underwent virtual and optical scans on the same day (N. Engl. J. Med. 2003;349:2191–200). The researchers concluded that virtual colonoscopy was comparable to optical colonoscopy for the detection of clinically relevant polyps.

Two subsequent studies found much lower sensitivities for CT colonography, at about 50% (JAMA 2004;291:1713–9; Lancet 2005;365:305–11). Neither of the studies involved screening populations, and both used somewhat outdated techniques and 2-D images. “We're now using multidetector scanners that have 4, 16, or 64 detector rows,” Dr. Heiken said. “Our spatial resolution is much greater, so we can identify much smaller polyps.”

Moreover, readers involved in the JAMA study were not trained in reading virtual colonoscopy images. All of these aspects help to account for the low sensitivities.

Importantly, results should be available in 2007 from the U.S. CT Colonography Screening Trial involving virtual and optical colonoscopy of 2,600 asymptomatic adults with average risk for colon cancer. None of the 15 participating institutions has used less than 16-row CT, and most have been using 64-row CT. In addition, stool and fluid tagging is being used, and all readers have been trained. The trial is organized by the American College of Radiology Imaging Network and is funded by the National Cancer Institute.

While most of the obstacles to the widespread use of virtual colonoscopy as a screening tool appear to have been addressed, capacity—particularly adequate reader training—remains an issue. “It takes at least 50–100 examinations to begin to develop the expertise necessary to read these [images] properly and accurately,” Dr. Heiken said. Reader training would have to be ramped up to meet the goal of widespread use.

Perhaps the most important issue is the lack of third-party payment for colorectal screening using CT colonography in the United States.

Still, some innovations on the horizon may hasten the routine use of virtual colonoscopy. The “filet” view opens the colon up electronically to allow it to be viewed like a pathology specimen. “The advantage of that is that it makes it less likely that we'll miss things … around bends,” Dr. Heiken said.

Computer-aided diagnosis also may soon play a part in virtual colonoscopy. Software improvements could help identify potential polyps missed on visual inspection. The final determination would still be made by the physician. “It will be very important for helping us improve our detection rate, decrease interobserver variability, and … make our examination more efficient,” he said.

Virtual colonoscopy examinations involving minimal bowel preparation might even be possible soon. “One of the big obstacles to colorectal cancer screening is that most patients do not want to have to undergo a rigorous, cathartic bowel preparation,” Dr. Heiken said. Consequently, many patients who should be screened forgo this exam. Some studies have shown that it is feasible to perform CT colonography with stool and fluid tagging but without cathartic preparation and get good results.

Greater patient discomfort associated with colon inflation during virtual colonoscopy is another potential limitation. However, discomfort most often arises from the use of room air to insufflate the colon, Dr. Heiken noted. The use of CO2 is more comfortable for the patient and the gas is more quickly reabsorbed by the body.

This sagittal image of a rectosigmoid polyp was made with a 16-row scanner.

The same polyp is displayed in an endoluminal view by using a 3-D format. Photos courtesy Dr. Jay P. Heiken