M. Alexander Otto

Asian and Hispanic patients with systemic lupus erythematosus have lower all-cause mortality rates than white, black, and Native American patients, according to an analysis of Medicaid claims for 42,221 adult lupus patients published online Jan. 15 in Arthritis & Rheumatology.

As with blacks and Native Americans, previous studies have reported more severe disease among Hispanics, so “our finding of decreased mortality rates and adjusted risks among Hispanic adults with SLE was thus surprising,” said investigators from Brigham and Women’s Hospital, Boston, and the University of Alabama at Birmingham.

The findings don’t necessarily contradict earlier research. It could be that even with more severe disease, Hispanic patients live longer. That’s been found before for cardiovascular disease, and has even been dubbed the “Hispanic paradox.” Perhaps “higher neighborhood social cohesion and family and social support … improve health outcomes” in Hispanic and Asian communities, they said.

The investigators analyzed the patients’ histories over a mean follow-up period of 2.56 years and found that per 1,000 patient-years, there were 5.18 deaths among Asians, 7.12 among Hispanics, 20.17 among whites, 24.13 among blacks, and 27.52 among Native Americans. The analysis included claims filed between 2000 and 2006 from 47 states and the District of Columbia.

Compared with white patients, the risk of all-cause mortality was 52% lower for Hispanic (hazard ratio, 0.48; 95% confidence interval, 0.40-0.59) and 41% lower for Asian patients (HR, 0.59; 95% CI, 0.40-0.86), but 21% higher for black (HR, 1.21; 95% CI, 1.10-1.33) and 40% higher for Native American patients (HR, 1.40; 95% CI, 1.04-1.90). The results were adjusted for comorbidities, demographics, and socioeconomic confounders (Arthritis Rheumatol. 2015 Jan. 15 [doi:10.1002/art.38981]).

Among the 8,191 subjects with lupus nephritis (LN), Hispanic and Asian patients had lower all-cause mortality than did whites. LN mortality was similar between white, black, and Native Americans, maybe due to the smaller LN sample size, the investigators said.

The study suggests future research directions, rather than offering immediate clinical guidance. It’s known that black LN patients generally need higher doses of mycophenolate mofetil and cyclophosphamide than white patients, but how to otherwise handle racial variations in lupus – and other diseases – is not yet clear. A complex dance of genetics and environmental factors is probably at work, said senior investigator Dr. Karen Costenbader, codirector of the lupus center at Brigham and Women’s Hospital.

“Ultimately, the goal is to understand the factors contributing to increased mortality in SLE, in order to modify risk factors and provide tailored therapies to enhance survival.” In the meantime, “clinicians should be aware that among lupus patients, African and Native Americans are doing much more poorly” than others, she said in an interview.

The patients were 18-65 years old, had been enrolled in Medicaid for at least 3 months, and had at least three claims filed for lupus at least 30 days apart. LN patients had at least two additional claims for glomerulonephritis, proteinuria, or renal failure. The study focused on all-cause mortality because the cause of death wasn’t usually reported in the claims data.

Patients’ socioeconomic status was estimated by median household income and other census zip code data.

Dr. Costenbader said she has no relevant disclosures. The work was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, among others.

[email protected]

Asian and Hispanic patients with systemic lupus erythematosus have lower all-cause mortality rates than white, black, and Native American patients, according to an analysis of Medicaid claims for 42,221 adult lupus patients published online Jan. 15 in Arthritis & Rheumatology.

As with blacks and Native Americans, previous studies have reported more severe disease among Hispanics, so “our finding of decreased mortality rates and adjusted risks among Hispanic adults with SLE was thus surprising,” said investigators from Brigham and Women’s Hospital, Boston, and the University of Alabama at Birmingham.

The findings don’t necessarily contradict earlier research. It could be that even with more severe disease, Hispanic patients live longer. That’s been found before for cardiovascular disease, and has even been dubbed the “Hispanic paradox.” Perhaps “higher neighborhood social cohesion and family and social support … improve health outcomes” in Hispanic and Asian communities, they said.

The investigators analyzed the patients’ histories over a mean follow-up period of 2.56 years and found that per 1,000 patient-years, there were 5.18 deaths among Asians, 7.12 among Hispanics, 20.17 among whites, 24.13 among blacks, and 27.52 among Native Americans. The analysis included claims filed between 2000 and 2006 from 47 states and the District of Columbia.

Compared with white patients, the risk of all-cause mortality was 52% lower for Hispanic (hazard ratio, 0.48; 95% confidence interval, 0.40-0.59) and 41% lower for Asian patients (HR, 0.59; 95% CI, 0.40-0.86), but 21% higher for black (HR, 1.21; 95% CI, 1.10-1.33) and 40% higher for Native American patients (HR, 1.40; 95% CI, 1.04-1.90). The results were adjusted for comorbidities, demographics, and socioeconomic confounders (Arthritis Rheumatol. 2015 Jan. 15 [doi:10.1002/art.38981]).

Among the 8,191 subjects with lupus nephritis (LN), Hispanic and Asian patients had lower all-cause mortality than did whites. LN mortality was similar between white, black, and Native Americans, maybe due to the smaller LN sample size, the investigators said.

The study suggests future research directions, rather than offering immediate clinical guidance. It’s known that black LN patients generally need higher doses of mycophenolate mofetil and cyclophosphamide than white patients, but how to otherwise handle racial variations in lupus – and other diseases – is not yet clear. A complex dance of genetics and environmental factors is probably at work, said senior investigator Dr. Karen Costenbader, codirector of the lupus center at Brigham and Women’s Hospital.

“Ultimately, the goal is to understand the factors contributing to increased mortality in SLE, in order to modify risk factors and provide tailored therapies to enhance survival.” In the meantime, “clinicians should be aware that among lupus patients, African and Native Americans are doing much more poorly” than others, she said in an interview.

The patients were 18-65 years old, had been enrolled in Medicaid for at least 3 months, and had at least three claims filed for lupus at least 30 days apart. LN patients had at least two additional claims for glomerulonephritis, proteinuria, or renal failure. The study focused on all-cause mortality because the cause of death wasn’t usually reported in the claims data.

Patients’ socioeconomic status was estimated by median household income and other census zip code data.

Dr. Costenbader said she has no relevant disclosures. The work was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, among others.

[email protected]

Asian and Hispanic patients with systemic lupus erythematosus have lower all-cause mortality rates than white, black, and Native American patients, according to an analysis of Medicaid claims for 42,221 adult lupus patients published online Jan. 15 in Arthritis & Rheumatology.

As with blacks and Native Americans, previous studies have reported more severe disease among Hispanics, so “our finding of decreased mortality rates and adjusted risks among Hispanic adults with SLE was thus surprising,” said investigators from Brigham and Women’s Hospital, Boston, and the University of Alabama at Birmingham.

The findings don’t necessarily contradict earlier research. It could be that even with more severe disease, Hispanic patients live longer. That’s been found before for cardiovascular disease, and has even been dubbed the “Hispanic paradox.” Perhaps “higher neighborhood social cohesion and family and social support … improve health outcomes” in Hispanic and Asian communities, they said.

The investigators analyzed the patients’ histories over a mean follow-up period of 2.56 years and found that per 1,000 patient-years, there were 5.18 deaths among Asians, 7.12 among Hispanics, 20.17 among whites, 24.13 among blacks, and 27.52 among Native Americans. The analysis included claims filed between 2000 and 2006 from 47 states and the District of Columbia.

Compared with white patients, the risk of all-cause mortality was 52% lower for Hispanic (hazard ratio, 0.48; 95% confidence interval, 0.40-0.59) and 41% lower for Asian patients (HR, 0.59; 95% CI, 0.40-0.86), but 21% higher for black (HR, 1.21; 95% CI, 1.10-1.33) and 40% higher for Native American patients (HR, 1.40; 95% CI, 1.04-1.90). The results were adjusted for comorbidities, demographics, and socioeconomic confounders (Arthritis Rheumatol. 2015 Jan. 15 [doi:10.1002/art.38981]).

Among the 8,191 subjects with lupus nephritis (LN), Hispanic and Asian patients had lower all-cause mortality than did whites. LN mortality was similar between white, black, and Native Americans, maybe due to the smaller LN sample size, the investigators said.

The study suggests future research directions, rather than offering immediate clinical guidance. It’s known that black LN patients generally need higher doses of mycophenolate mofetil and cyclophosphamide than white patients, but how to otherwise handle racial variations in lupus – and other diseases – is not yet clear. A complex dance of genetics and environmental factors is probably at work, said senior investigator Dr. Karen Costenbader, codirector of the lupus center at Brigham and Women’s Hospital.

“Ultimately, the goal is to understand the factors contributing to increased mortality in SLE, in order to modify risk factors and provide tailored therapies to enhance survival.” In the meantime, “clinicians should be aware that among lupus patients, African and Native Americans are doing much more poorly” than others, she said in an interview.

The patients were 18-65 years old, had been enrolled in Medicaid for at least 3 months, and had at least three claims filed for lupus at least 30 days apart. LN patients had at least two additional claims for glomerulonephritis, proteinuria, or renal failure. The study focused on all-cause mortality because the cause of death wasn’t usually reported in the claims data.

Patients’ socioeconomic status was estimated by median household income and other census zip code data.

Dr. Costenbader said she has no relevant disclosures. The work was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, among others.

[email protected]

Almost one in five hysterectomies for benign indications were unnecessary, based on 2013 data from 52 Michigan hospitals.

Uterine pathology reports did not match or support the indication for surgery in 18% of the 3,397 hysterectomies reviewed from the Michigan Surgical Quality Collaborative, a state-wide program to improve surgical care. In women under 40 years old, pathology did not support surgery in 38% of hysterectomies for benign indications.

Endometriosis and chronic pain were the most common reasons for unnecessary uterus removal; pathology was unsupportive of surgery in about 40% of those cases. Pathology also was unsupportive in about 14% of women with fibroid or acute uterine bleeding (AUB) and in about 20% of the remaining cases, which were mostly indicated for a blend of bleeding, pain, and other problems (Am. J. Obstet. Gynecol. 2014 Dec 23 [doi:http://dx.doi.org/10.1016/j.ajog.2014.11.031]).

Almost half of the women had no documentation in their charts that alternatives to hysterectomy were tried or even considered. Hormonal management, operative hysteroscopy, endometrial ablation, levonorgestrel intrauterine devices (IUDs), and other approaches were documented in 68% of women under 40 years old, but documentation was less likely in women over 40 years old. Alternatives approaches were more likely in women with larger uteri and in women with endometriosis, but were, overall, “underutilized,” Dr. Daniel Morgan, an associate professor of obstetrics and gynecology at the University of Michigan in Ann Arbor, and his fellow researchers concluded.

Parity, body mass index, insurance, and common medical comorbidities did not seem to influence the use of alternatives in the study.

The researchers noted that checklists for preoperative appropriateness have been shown in previous studies to reduce the rate of benign hysterectomies, and increase the likelihood that pathology will support the reason for the operation.

The checklist approach “could help standardize treatment and ensure appropriate uterine-sparing management has been offered. The use of electronic medical records systems could potentially facilitate this type of standardization with relative ease,” the researchers wrote.

Also, the levonorgestrel IUD, “a highly effective, cost-saving intervention for women with acute uterine bleeding and pelvic pain, was considered [in] only 12%” of the Michigan cases. Increasing its use is another “important area for quality improvement and cost savings,” they added.

“We are now in the process of developing institution-specific reports ... on use of alternatives prior to hysterectomy and rates of negative pathology. It is our goal that each institution in the Collaborative will see their data and act on it accordingly. We hope that it will lead to more use (or at least consideration) of alternatives to hysterectomy and lower rates of negative pathology.”

The Michigan Surgical Quality Collaborative is funded by Blue Cross and Blue Shield of Michigan/Blue Care Network. Dr. Morgan reported no conflicts of interest.

[email protected]

Almost one in five hysterectomies for benign indications were unnecessary, based on 2013 data from 52 Michigan hospitals.

Uterine pathology reports did not match or support the indication for surgery in 18% of the 3,397 hysterectomies reviewed from the Michigan Surgical Quality Collaborative, a state-wide program to improve surgical care. In women under 40 years old, pathology did not support surgery in 38% of hysterectomies for benign indications.

Endometriosis and chronic pain were the most common reasons for unnecessary uterus removal; pathology was unsupportive of surgery in about 40% of those cases. Pathology also was unsupportive in about 14% of women with fibroid or acute uterine bleeding (AUB) and in about 20% of the remaining cases, which were mostly indicated for a blend of bleeding, pain, and other problems (Am. J. Obstet. Gynecol. 2014 Dec 23 [doi:http://dx.doi.org/10.1016/j.ajog.2014.11.031]).

Almost half of the women had no documentation in their charts that alternatives to hysterectomy were tried or even considered. Hormonal management, operative hysteroscopy, endometrial ablation, levonorgestrel intrauterine devices (IUDs), and other approaches were documented in 68% of women under 40 years old, but documentation was less likely in women over 40 years old. Alternatives approaches were more likely in women with larger uteri and in women with endometriosis, but were, overall, “underutilized,” Dr. Daniel Morgan, an associate professor of obstetrics and gynecology at the University of Michigan in Ann Arbor, and his fellow researchers concluded.

Parity, body mass index, insurance, and common medical comorbidities did not seem to influence the use of alternatives in the study.

The researchers noted that checklists for preoperative appropriateness have been shown in previous studies to reduce the rate of benign hysterectomies, and increase the likelihood that pathology will support the reason for the operation.

The checklist approach “could help standardize treatment and ensure appropriate uterine-sparing management has been offered. The use of electronic medical records systems could potentially facilitate this type of standardization with relative ease,” the researchers wrote.

Also, the levonorgestrel IUD, “a highly effective, cost-saving intervention for women with acute uterine bleeding and pelvic pain, was considered [in] only 12%” of the Michigan cases. Increasing its use is another “important area for quality improvement and cost savings,” they added.

“We are now in the process of developing institution-specific reports ... on use of alternatives prior to hysterectomy and rates of negative pathology. It is our goal that each institution in the Collaborative will see their data and act on it accordingly. We hope that it will lead to more use (or at least consideration) of alternatives to hysterectomy and lower rates of negative pathology.”

The Michigan Surgical Quality Collaborative is funded by Blue Cross and Blue Shield of Michigan/Blue Care Network. Dr. Morgan reported no conflicts of interest.

[email protected]

Almost one in five hysterectomies for benign indications were unnecessary, based on 2013 data from 52 Michigan hospitals.

Uterine pathology reports did not match or support the indication for surgery in 18% of the 3,397 hysterectomies reviewed from the Michigan Surgical Quality Collaborative, a state-wide program to improve surgical care. In women under 40 years old, pathology did not support surgery in 38% of hysterectomies for benign indications.

Endometriosis and chronic pain were the most common reasons for unnecessary uterus removal; pathology was unsupportive of surgery in about 40% of those cases. Pathology also was unsupportive in about 14% of women with fibroid or acute uterine bleeding (AUB) and in about 20% of the remaining cases, which were mostly indicated for a blend of bleeding, pain, and other problems (Am. J. Obstet. Gynecol. 2014 Dec 23 [doi:http://dx.doi.org/10.1016/j.ajog.2014.11.031]).

Almost half of the women had no documentation in their charts that alternatives to hysterectomy were tried or even considered. Hormonal management, operative hysteroscopy, endometrial ablation, levonorgestrel intrauterine devices (IUDs), and other approaches were documented in 68% of women under 40 years old, but documentation was less likely in women over 40 years old. Alternatives approaches were more likely in women with larger uteri and in women with endometriosis, but were, overall, “underutilized,” Dr. Daniel Morgan, an associate professor of obstetrics and gynecology at the University of Michigan in Ann Arbor, and his fellow researchers concluded.

Parity, body mass index, insurance, and common medical comorbidities did not seem to influence the use of alternatives in the study.

The researchers noted that checklists for preoperative appropriateness have been shown in previous studies to reduce the rate of benign hysterectomies, and increase the likelihood that pathology will support the reason for the operation.

The checklist approach “could help standardize treatment and ensure appropriate uterine-sparing management has been offered. The use of electronic medical records systems could potentially facilitate this type of standardization with relative ease,” the researchers wrote.

Also, the levonorgestrel IUD, “a highly effective, cost-saving intervention for women with acute uterine bleeding and pelvic pain, was considered [in] only 12%” of the Michigan cases. Increasing its use is another “important area for quality improvement and cost savings,” they added.

“We are now in the process of developing institution-specific reports ... on use of alternatives prior to hysterectomy and rates of negative pathology. It is our goal that each institution in the Collaborative will see their data and act on it accordingly. We hope that it will lead to more use (or at least consideration) of alternatives to hysterectomy and lower rates of negative pathology.”

The Michigan Surgical Quality Collaborative is funded by Blue Cross and Blue Shield of Michigan/Blue Care Network. Dr. Morgan reported no conflicts of interest.

[email protected]

VANCOUVER, B.C. – Trendelenburg position does not materially increase ventilator pressures during laparoscopic gynecologic surgery, according to investigators from McMaster University in Hamilton, Ont.

The use of the Trendelenburg position can sometimes cause tension in the operating room. Surgeons need to roll the small bowel out of the pelvis to get access to their gynecologic targets, but anesthesiologists worry that they’ll have to turn up ventilator pressures – and risk barotrauma – if women are placed in a head-down position. It’s unclear from previous studies if pressures really need to be increased when using a moderate Trendelenburg position, Dr. Stephen Bates, a professor of obstetrics and gynecology at McMaster University, said at a meeting sponsored by the AAGL.

To find out, Dr. Bates and his colleagues monitored peak inspiratory pressures (PIP), pneumoperitoneum pressures, degrees of Trendelenburg, and other factors as 100 women underwent laparoscopic hysterectomies performed by a total of seven surgeons. The women were aged 46 years, on average, and had a mean body mass index of 29 kg/m².

The surgeons opted for an average of 10 degrees Trendelenburg, which resulted in a 1.9 cm H₂0 (7%) increase in PIP from horizontal positioning, up from a mean of 26.7 to 28.6 cm H₂0.

“By all anesthesia standards, this is a trivial change and clinically insignificant,” Dr. Bates said in an interview. “The traditional dogma is that if you put patients in Trendelenburg, you’ll increase the difficulty of ventilating them. That was not the case.”

But body mass index, and to a greater degree pneumoperitoneum pressures, did predict increased ventilator pressures among the women.

“The higher pneumoperitoneum pressures are, the harder it is to ventilate,” Dr. Bates said. “There’s [almost] a linear relationship between PnP [pneumoperitoneum pressures] and ventilator pressures.”

When pneumoperitoneum pressures were reduced from 15 to 10 mm Hg, PIP fell by approximately 10%, but the surgeons – all blinded to the reduction in PnP – did not notice any deterioration in their surgical views, he said.

Taken together, the findings suggest a new way to negotiate Trendelenburg positioning in the operating room. “Anesthesiologists and gynecologic surgeons should consider minimizing the pneumoperitoneum pressure rather than reducing the degree of Trendelenburg,” Dr. Bates said.

The researchers also tested an inflatable pillow that lifted women’s buttocks a few inches above the table. The hope was that it would reduce the degree of Trendelenburg needed for their operations, and subsequently reduce PIP. Surgeons were able to decrease Trendelenburg by about 4 degrees with the pillow, but consistent with the study’s overall findings, it made no real difference in PIP. There was a clinically insignificant drop of 0.3 cm H₂0, from a mean of 28.6 to 28.3 cm H₂0, Dr. Bates said.

Dr. Bates reported having no financial disclosures.

[email protected]

VANCOUVER, B.C. – Trendelenburg position does not materially increase ventilator pressures during laparoscopic gynecologic surgery, according to investigators from McMaster University in Hamilton, Ont.

The use of the Trendelenburg position can sometimes cause tension in the operating room. Surgeons need to roll the small bowel out of the pelvis to get access to their gynecologic targets, but anesthesiologists worry that they’ll have to turn up ventilator pressures – and risk barotrauma – if women are placed in a head-down position. It’s unclear from previous studies if pressures really need to be increased when using a moderate Trendelenburg position, Dr. Stephen Bates, a professor of obstetrics and gynecology at McMaster University, said at a meeting sponsored by the AAGL.

To find out, Dr. Bates and his colleagues monitored peak inspiratory pressures (PIP), pneumoperitoneum pressures, degrees of Trendelenburg, and other factors as 100 women underwent laparoscopic hysterectomies performed by a total of seven surgeons. The women were aged 46 years, on average, and had a mean body mass index of 29 kg/m².

The surgeons opted for an average of 10 degrees Trendelenburg, which resulted in a 1.9 cm H₂0 (7%) increase in PIP from horizontal positioning, up from a mean of 26.7 to 28.6 cm H₂0.

“By all anesthesia standards, this is a trivial change and clinically insignificant,” Dr. Bates said in an interview. “The traditional dogma is that if you put patients in Trendelenburg, you’ll increase the difficulty of ventilating them. That was not the case.”

But body mass index, and to a greater degree pneumoperitoneum pressures, did predict increased ventilator pressures among the women.

“The higher pneumoperitoneum pressures are, the harder it is to ventilate,” Dr. Bates said. “There’s [almost] a linear relationship between PnP [pneumoperitoneum pressures] and ventilator pressures.”

When pneumoperitoneum pressures were reduced from 15 to 10 mm Hg, PIP fell by approximately 10%, but the surgeons – all blinded to the reduction in PnP – did not notice any deterioration in their surgical views, he said.

Taken together, the findings suggest a new way to negotiate Trendelenburg positioning in the operating room. “Anesthesiologists and gynecologic surgeons should consider minimizing the pneumoperitoneum pressure rather than reducing the degree of Trendelenburg,” Dr. Bates said.

The researchers also tested an inflatable pillow that lifted women’s buttocks a few inches above the table. The hope was that it would reduce the degree of Trendelenburg needed for their operations, and subsequently reduce PIP. Surgeons were able to decrease Trendelenburg by about 4 degrees with the pillow, but consistent with the study’s overall findings, it made no real difference in PIP. There was a clinically insignificant drop of 0.3 cm H₂0, from a mean of 28.6 to 28.3 cm H₂0, Dr. Bates said.

Dr. Bates reported having no financial disclosures.

[email protected]

VANCOUVER, B.C. – Trendelenburg position does not materially increase ventilator pressures during laparoscopic gynecologic surgery, according to investigators from McMaster University in Hamilton, Ont.

The use of the Trendelenburg position can sometimes cause tension in the operating room. Surgeons need to roll the small bowel out of the pelvis to get access to their gynecologic targets, but anesthesiologists worry that they’ll have to turn up ventilator pressures – and risk barotrauma – if women are placed in a head-down position. It’s unclear from previous studies if pressures really need to be increased when using a moderate Trendelenburg position, Dr. Stephen Bates, a professor of obstetrics and gynecology at McMaster University, said at a meeting sponsored by the AAGL.

To find out, Dr. Bates and his colleagues monitored peak inspiratory pressures (PIP), pneumoperitoneum pressures, degrees of Trendelenburg, and other factors as 100 women underwent laparoscopic hysterectomies performed by a total of seven surgeons. The women were aged 46 years, on average, and had a mean body mass index of 29 kg/m².

The surgeons opted for an average of 10 degrees Trendelenburg, which resulted in a 1.9 cm H₂0 (7%) increase in PIP from horizontal positioning, up from a mean of 26.7 to 28.6 cm H₂0.

“By all anesthesia standards, this is a trivial change and clinically insignificant,” Dr. Bates said in an interview. “The traditional dogma is that if you put patients in Trendelenburg, you’ll increase the difficulty of ventilating them. That was not the case.”

But body mass index, and to a greater degree pneumoperitoneum pressures, did predict increased ventilator pressures among the women.

“The higher pneumoperitoneum pressures are, the harder it is to ventilate,” Dr. Bates said. “There’s [almost] a linear relationship between PnP [pneumoperitoneum pressures] and ventilator pressures.”

When pneumoperitoneum pressures were reduced from 15 to 10 mm Hg, PIP fell by approximately 10%, but the surgeons – all blinded to the reduction in PnP – did not notice any deterioration in their surgical views, he said.

Taken together, the findings suggest a new way to negotiate Trendelenburg positioning in the operating room. “Anesthesiologists and gynecologic surgeons should consider minimizing the pneumoperitoneum pressure rather than reducing the degree of Trendelenburg,” Dr. Bates said.

The researchers also tested an inflatable pillow that lifted women’s buttocks a few inches above the table. The hope was that it would reduce the degree of Trendelenburg needed for their operations, and subsequently reduce PIP. Surgeons were able to decrease Trendelenburg by about 4 degrees with the pillow, but consistent with the study’s overall findings, it made no real difference in PIP. There was a clinically insignificant drop of 0.3 cm H₂0, from a mean of 28.6 to 28.3 cm H₂0, Dr. Bates said.

Dr. Bates reported having no financial disclosures.

[email protected]

MMR-varicella vaccine is about twice as likely to cause febrile seizures in toddlers than separate, same-day MMR and varicella shots, but it’s otherwise just as safe, according to a review of adverse events in children 12-23 months old vaccinated between 2000 and 2012.

The investigators – all from institutions participating in the Centers for Disease Control and Prevention’s Vaccine Safety Datalink project – compared outcomes after 123,200 doses of the MMR-varicella (MMRV) combination vaccine and 584,987 doses of MMR and varicella (MMR+V) vaccines given on the same day (Pediatrics 2015 [doi:10.1542/peds.2014-1822]).

There were no statistically significant difference in the main outcomes: anaphylaxis, immune thrombocytopenia purpura (ITP), ataxia, arthritis, meningitis/encephalitis, acute disseminated encephalomyelitis, and Kawasaki disease. “This study provides reassurance that most of these outcomes are extremely rare and unlikely after either vaccine,” said Dr. Nicola P. Klein of the Kaiser Permanente Vaccine Study Center in Oakland, Calif., and her associates.

For instance, they found 0.86 cases of meningitis/encephalitis per 100,000 doses of MMR+V, and 1.86 per 100,000 doses of MMRV within 3 weeks of vaccination. Similarly, there were 0.52 cases per 100,000 doses of arthritis/arthralgia for MMR+V, and 0.84 cases for MMRV. There were 2.93 Kawasaki cases per 100,000 doses of MMR+V, but no cases in the MMRV group. Such small differences “could be ruled out with 95% confidence,” the investigators said.

Two children had cases of anaphylaxis after MMRV shots, but neither “was confirmed as acute anaphylaxis after chart review; both diagnoses were related to a history of allergic reactions.” Even so, “continued monitoring for anaphylaxis after these vaccines is warranted,” they said. There were no cases of acute disseminated encephalomyelitis in either group.

Continue for additional adverse effects >>

With both vaccines, however, there were around 800 cases of fever per 100,000 doses within 7-10 days of the shots; there were also 52.37 febrile seizures per 100,000 doses of MMR+V, and 101.01 per 100,000 doses of MMRV (relative risk, 1.99 MMRV, compared with MMR+V).

The fever and seizure findings aren’t new; “measles-containing vaccines are” known to be associated with seizure, fever, and ITP, the investigators noted, and MMRV’s higher seizure risk has been reported before.

As expected, both immunization strategies increased the risk of ITP, which peaked 2-4 weeks after vaccination, but the absolute number of cases was small, about 5-10 per 100,000 doses. “To our knowledge, [this is] the first report that MMRV is associated with a similar increased risk of ITP during the same postvaccination risk intervals as MMR,” the investigators said.

MMRV and MMR+V both were associated with a small and surprising decrease in ataxia, but “this observation is more likely due to chance, outcome misclassification, or other unmeasured confounding,” they said.

Dr. Klein, Dr. Roger Baxter, and Allison Naleway, Ph.D., disclosed research funding from Merck, which manufactures the vaccines used in the study, and GlaxoSmithKline, among other industry ties. Dr. Edward A. Belongia reported research support from Medimmune. The remaining authors reported no relevant financial disclosures. The work was funded by the CDC.

MMR-varicella vaccine is about twice as likely to cause febrile seizures in toddlers than separate, same-day MMR and varicella shots, but it’s otherwise just as safe, according to a review of adverse events in children 12-23 months old vaccinated between 2000 and 2012.

The investigators – all from institutions participating in the Centers for Disease Control and Prevention’s Vaccine Safety Datalink project – compared outcomes after 123,200 doses of the MMR-varicella (MMRV) combination vaccine and 584,987 doses of MMR and varicella (MMR+V) vaccines given on the same day (Pediatrics 2015 [doi:10.1542/peds.2014-1822]).

There were no statistically significant difference in the main outcomes: anaphylaxis, immune thrombocytopenia purpura (ITP), ataxia, arthritis, meningitis/encephalitis, acute disseminated encephalomyelitis, and Kawasaki disease. “This study provides reassurance that most of these outcomes are extremely rare and unlikely after either vaccine,” said Dr. Nicola P. Klein of the Kaiser Permanente Vaccine Study Center in Oakland, Calif., and her associates.

For instance, they found 0.86 cases of meningitis/encephalitis per 100,000 doses of MMR+V, and 1.86 per 100,000 doses of MMRV within 3 weeks of vaccination. Similarly, there were 0.52 cases per 100,000 doses of arthritis/arthralgia for MMR+V, and 0.84 cases for MMRV. There were 2.93 Kawasaki cases per 100,000 doses of MMR+V, but no cases in the MMRV group. Such small differences “could be ruled out with 95% confidence,” the investigators said.

Two children had cases of anaphylaxis after MMRV shots, but neither “was confirmed as acute anaphylaxis after chart review; both diagnoses were related to a history of allergic reactions.” Even so, “continued monitoring for anaphylaxis after these vaccines is warranted,” they said. There were no cases of acute disseminated encephalomyelitis in either group.

Continue for additional adverse effects >>

With both vaccines, however, there were around 800 cases of fever per 100,000 doses within 7-10 days of the shots; there were also 52.37 febrile seizures per 100,000 doses of MMR+V, and 101.01 per 100,000 doses of MMRV (relative risk, 1.99 MMRV, compared with MMR+V).

The fever and seizure findings aren’t new; “measles-containing vaccines are” known to be associated with seizure, fever, and ITP, the investigators noted, and MMRV’s higher seizure risk has been reported before.

As expected, both immunization strategies increased the risk of ITP, which peaked 2-4 weeks after vaccination, but the absolute number of cases was small, about 5-10 per 100,000 doses. “To our knowledge, [this is] the first report that MMRV is associated with a similar increased risk of ITP during the same postvaccination risk intervals as MMR,” the investigators said.

MMRV and MMR+V both were associated with a small and surprising decrease in ataxia, but “this observation is more likely due to chance, outcome misclassification, or other unmeasured confounding,” they said.

Dr. Klein, Dr. Roger Baxter, and Allison Naleway, Ph.D., disclosed research funding from Merck, which manufactures the vaccines used in the study, and GlaxoSmithKline, among other industry ties. Dr. Edward A. Belongia reported research support from Medimmune. The remaining authors reported no relevant financial disclosures. The work was funded by the CDC.

MMR-varicella vaccine is about twice as likely to cause febrile seizures in toddlers than separate, same-day MMR and varicella shots, but it’s otherwise just as safe, according to a review of adverse events in children 12-23 months old vaccinated between 2000 and 2012.

The investigators – all from institutions participating in the Centers for Disease Control and Prevention’s Vaccine Safety Datalink project – compared outcomes after 123,200 doses of the MMR-varicella (MMRV) combination vaccine and 584,987 doses of MMR and varicella (MMR+V) vaccines given on the same day (Pediatrics 2015 [doi:10.1542/peds.2014-1822]).

There were no statistically significant difference in the main outcomes: anaphylaxis, immune thrombocytopenia purpura (ITP), ataxia, arthritis, meningitis/encephalitis, acute disseminated encephalomyelitis, and Kawasaki disease. “This study provides reassurance that most of these outcomes are extremely rare and unlikely after either vaccine,” said Dr. Nicola P. Klein of the Kaiser Permanente Vaccine Study Center in Oakland, Calif., and her associates.

For instance, they found 0.86 cases of meningitis/encephalitis per 100,000 doses of MMR+V, and 1.86 per 100,000 doses of MMRV within 3 weeks of vaccination. Similarly, there were 0.52 cases per 100,000 doses of arthritis/arthralgia for MMR+V, and 0.84 cases for MMRV. There were 2.93 Kawasaki cases per 100,000 doses of MMR+V, but no cases in the MMRV group. Such small differences “could be ruled out with 95% confidence,” the investigators said.

Two children had cases of anaphylaxis after MMRV shots, but neither “was confirmed as acute anaphylaxis after chart review; both diagnoses were related to a history of allergic reactions.” Even so, “continued monitoring for anaphylaxis after these vaccines is warranted,” they said. There were no cases of acute disseminated encephalomyelitis in either group.

Continue for additional adverse effects >>

With both vaccines, however, there were around 800 cases of fever per 100,000 doses within 7-10 days of the shots; there were also 52.37 febrile seizures per 100,000 doses of MMR+V, and 101.01 per 100,000 doses of MMRV (relative risk, 1.99 MMRV, compared with MMR+V).

The fever and seizure findings aren’t new; “measles-containing vaccines are” known to be associated with seizure, fever, and ITP, the investigators noted, and MMRV’s higher seizure risk has been reported before.

As expected, both immunization strategies increased the risk of ITP, which peaked 2-4 weeks after vaccination, but the absolute number of cases was small, about 5-10 per 100,000 doses. “To our knowledge, [this is] the first report that MMRV is associated with a similar increased risk of ITP during the same postvaccination risk intervals as MMR,” the investigators said.

MMRV and MMR+V both were associated with a small and surprising decrease in ataxia, but “this observation is more likely due to chance, outcome misclassification, or other unmeasured confounding,” they said.

Dr. Klein, Dr. Roger Baxter, and Allison Naleway, Ph.D., disclosed research funding from Merck, which manufactures the vaccines used in the study, and GlaxoSmithKline, among other industry ties. Dr. Edward A. Belongia reported research support from Medimmune. The remaining authors reported no relevant financial disclosures. The work was funded by the CDC.

MMR-varicella vaccine is about twice as likely to cause febrile seizures in toddlers than separate, same-day MMR and varicella shots, but it’s otherwise just as safe, according to a review of adverse events in children 12-23 months old vaccinated between 2000 and 2012.

The investigators – all from institutions participating in the Centers for Disease Control and Prevention’s Vaccine Safety Datalink project – compared outcomes after 123,200 doses of the MMR-varicella (MMRV) combination vaccine and 584,987 doses of MMR and varicella (MMR+V) vaccines given on the same day (Pediatrics 2015 [doi:10.1542/peds.2014-1822]).

There were no statistically significant difference in the main outcomes: anaphylaxis, immune thrombocytopenia purpura (ITP), ataxia, arthritis, meningitis/encephalitis, acute disseminated encephalomyelitis, and Kawasaki disease. “This study provides reassurance that most of these outcomes are extremely rare and unlikely after either vaccine,” said Dr. Nicola P. Klein of the Kaiser Permanente Vaccine Study Center in Oakland, Calif., and her associates.

© Sean Locke/iStockphoto.com

For instance, they found 0.86 cases of meningitis/encephalitis per 100,000 doses of MMR+V, and 1.86 per 100,000 doses of MMRV within 3 weeks of vaccination. Similarly, there were 0.52 cases per 100,000 doses of arthritis/arthralgia for MMR+V, and 0.84 cases for MMRV. There were 2.93 Kawasaki cases per 100,000 doses of MMR+V, but no cases in the MMRV group. Such small differences “could be ruled out with 95% confidence,” the investigators said.

Two children had cases of anaphylaxis after MMRV shots, but neither “was confirmed as acute anaphylaxis after chart review; both diagnoses were related to a history of allergic reactions.” Even so, “continued monitoring for anaphylaxis after these vaccines is warranted,” they said. There were no cases of acute disseminated encephalomyelitis in either group.

With both vaccines, however, there were around 800 cases of fever per 100,000 doses within 7-10 days of the shots; there were also 52.37 febrile seizures per 100,000 doses of MMR+V, and 101.01 per 100,000 doses of MMRV (relative risk, 1.99 MMRV, compared with MMR+V).

The fever and seizure findings aren’t new; “measles-containing vaccines are” known to be associated with seizure, fever, and ITP, the investigators noted, and MMRV’s higher seizure risk has been reported before.

As expected, both immunization strategies increased the risk of ITP, which peaked 2-4 weeks after vaccination, but the absolute number of cases was small, about 5-10 per 100,000 doses. “To our knowledge, [this is] the first report that MMRV is associated with a similar increased risk of ITP during the same postvaccination risk intervals as MMR,” the investigators said.

MMRV and MMR+V both were associated with a small and surprising decrease in ataxia, but “this observation is more likely due to chance, outcome misclassification, or other unmeasured confounding,” they said.

Dr. Klein, Dr. Roger Baxter, and Allison Naleway, Ph.D., disclosed research funding from Merck, which manufactures the vaccines used in the study, and GlaxoSmithKline, among other industry ties. Dr. Edward A. Belongia reported research support from Medimmune. The remaining authors reported no relevant financial disclosures. The work was funded by the CDC.

[email protected]

MMR-varicella vaccine is about twice as likely to cause febrile seizures in toddlers than separate, same-day MMR and varicella shots, but it’s otherwise just as safe, according to a review of adverse events in children 12-23 months old vaccinated between 2000 and 2012.

The investigators – all from institutions participating in the Centers for Disease Control and Prevention’s Vaccine Safety Datalink project – compared outcomes after 123,200 doses of the MMR-varicella (MMRV) combination vaccine and 584,987 doses of MMR and varicella (MMR+V) vaccines given on the same day (Pediatrics 2015 [doi:10.1542/peds.2014-1822]).

There were no statistically significant difference in the main outcomes: anaphylaxis, immune thrombocytopenia purpura (ITP), ataxia, arthritis, meningitis/encephalitis, acute disseminated encephalomyelitis, and Kawasaki disease. “This study provides reassurance that most of these outcomes are extremely rare and unlikely after either vaccine,” said Dr. Nicola P. Klein of the Kaiser Permanente Vaccine Study Center in Oakland, Calif., and her associates.

© Sean Locke/iStockphoto.com

For instance, they found 0.86 cases of meningitis/encephalitis per 100,000 doses of MMR+V, and 1.86 per 100,000 doses of MMRV within 3 weeks of vaccination. Similarly, there were 0.52 cases per 100,000 doses of arthritis/arthralgia for MMR+V, and 0.84 cases for MMRV. There were 2.93 Kawasaki cases per 100,000 doses of MMR+V, but no cases in the MMRV group. Such small differences “could be ruled out with 95% confidence,” the investigators said.

Two children had cases of anaphylaxis after MMRV shots, but neither “was confirmed as acute anaphylaxis after chart review; both diagnoses were related to a history of allergic reactions.” Even so, “continued monitoring for anaphylaxis after these vaccines is warranted,” they said. There were no cases of acute disseminated encephalomyelitis in either group.

With both vaccines, however, there were around 800 cases of fever per 100,000 doses within 7-10 days of the shots; there were also 52.37 febrile seizures per 100,000 doses of MMR+V, and 101.01 per 100,000 doses of MMRV (relative risk, 1.99 MMRV, compared with MMR+V).

The fever and seizure findings aren’t new; “measles-containing vaccines are” known to be associated with seizure, fever, and ITP, the investigators noted, and MMRV’s higher seizure risk has been reported before.

As expected, both immunization strategies increased the risk of ITP, which peaked 2-4 weeks after vaccination, but the absolute number of cases was small, about 5-10 per 100,000 doses. “To our knowledge, [this is] the first report that MMRV is associated with a similar increased risk of ITP during the same postvaccination risk intervals as MMR,” the investigators said.

MMRV and MMR+V both were associated with a small and surprising decrease in ataxia, but “this observation is more likely due to chance, outcome misclassification, or other unmeasured confounding,” they said.

Dr. Klein, Dr. Roger Baxter, and Allison Naleway, Ph.D., disclosed research funding from Merck, which manufactures the vaccines used in the study, and GlaxoSmithKline, among other industry ties. Dr. Edward A. Belongia reported research support from Medimmune. The remaining authors reported no relevant financial disclosures. The work was funded by the CDC.

[email protected]

MMR-varicella vaccine is about twice as likely to cause febrile seizures in toddlers than separate, same-day MMR and varicella shots, but it’s otherwise just as safe, according to a review of adverse events in children 12-23 months old vaccinated between 2000 and 2012.

The investigators – all from institutions participating in the Centers for Disease Control and Prevention’s Vaccine Safety Datalink project – compared outcomes after 123,200 doses of the MMR-varicella (MMRV) combination vaccine and 584,987 doses of MMR and varicella (MMR+V) vaccines given on the same day (Pediatrics 2015 [doi:10.1542/peds.2014-1822]).

There were no statistically significant difference in the main outcomes: anaphylaxis, immune thrombocytopenia purpura (ITP), ataxia, arthritis, meningitis/encephalitis, acute disseminated encephalomyelitis, and Kawasaki disease. “This study provides reassurance that most of these outcomes are extremely rare and unlikely after either vaccine,” said Dr. Nicola P. Klein of the Kaiser Permanente Vaccine Study Center in Oakland, Calif., and her associates.

© Sean Locke/iStockphoto.com

For instance, they found 0.86 cases of meningitis/encephalitis per 100,000 doses of MMR+V, and 1.86 per 100,000 doses of MMRV within 3 weeks of vaccination. Similarly, there were 0.52 cases per 100,000 doses of arthritis/arthralgia for MMR+V, and 0.84 cases for MMRV. There were 2.93 Kawasaki cases per 100,000 doses of MMR+V, but no cases in the MMRV group. Such small differences “could be ruled out with 95% confidence,” the investigators said.

Two children had cases of anaphylaxis after MMRV shots, but neither “was confirmed as acute anaphylaxis after chart review; both diagnoses were related to a history of allergic reactions.” Even so, “continued monitoring for anaphylaxis after these vaccines is warranted,” they said. There were no cases of acute disseminated encephalomyelitis in either group.

With both vaccines, however, there were around 800 cases of fever per 100,000 doses within 7-10 days of the shots; there were also 52.37 febrile seizures per 100,000 doses of MMR+V, and 101.01 per 100,000 doses of MMRV (relative risk, 1.99 MMRV, compared with MMR+V).

The fever and seizure findings aren’t new; “measles-containing vaccines are” known to be associated with seizure, fever, and ITP, the investigators noted, and MMRV’s higher seizure risk has been reported before.

As expected, both immunization strategies increased the risk of ITP, which peaked 2-4 weeks after vaccination, but the absolute number of cases was small, about 5-10 per 100,000 doses. “To our knowledge, [this is] the first report that MMRV is associated with a similar increased risk of ITP during the same postvaccination risk intervals as MMR,” the investigators said.

MMRV and MMR+V both were associated with a small and surprising decrease in ataxia, but “this observation is more likely due to chance, outcome misclassification, or other unmeasured confounding,” they said.

Dr. Klein, Dr. Roger Baxter, and Allison Naleway, Ph.D., disclosed research funding from Merck, which manufactures the vaccines used in the study, and GlaxoSmithKline, among other industry ties. Dr. Edward A. Belongia reported research support from Medimmune. The remaining authors reported no relevant financial disclosures. The work was funded by the CDC.

[email protected]

SEATTLE – UCB will likely submit brivaracetam – its follow-up to levetiracetam – to the Food and Drug Administration for approval in the not-so-distant future.

Brivaracetam is a molecular analog of levetiracetam (Keppra), a widely used epilepsy drug that’s now available as a generic. The company has reported that it binds synaptic vesicle protein 2A with greater affinity than does levetiracetam, which suggests greater potency. However, phase III testing compared brivaracetam to placebo, so it’s unclear if the analog has advantages over the older drug, according to Dr. Pavel Klein, an epileptologist and director of the Mid-Atlantic Epilepsy and Sleep Center in Bethesda, Md.

“Levetiracetam is a great medication, but its psychiatric side effects,” which can include aggression, depression, and even psychosis, are “limiting. If brivaracetam turns out to be a friendlier version of levetiracetam, that would be helpful, but we don’t know that yet,” he said at the annual meeting of the American Epilepsy Society.

Dr. Klein was the principal investigator on brivaracetam’s final phase III trial, and he presented the results at the meeting. With testing complete, UCB said it plans to submit brivaracetam to the FDA in early 2015.

His study randomized 768 adult patients with refractory partial onset seizures to placebo or 100 or 200 mg/day brivaracetam by mouth for 12 weeks as an adjunct; the subjects were also taking one or two other antiepileptic drugs, although not levetiracetam; the trial excluded patients taking levetiracetam and those who had taken it within 3 months. The study group was about 40 years old on average, and evenly split between men and women.

Brivaracetam 100 mg/day reduced 28-day adjusted seizure frequency by 22.8% over placebo, and 200 mg/day reduced it 23.2% over placebo. The responder rate – a reduction of at least 50% in seizure frequency – was 21.6% for placebo, 38.9% for brivaracetam 100 mg, and 37.8% for brivaracetam 200 mg. About 4.5% of brivaracetam patients went the entire 12 weeks without a seizure, versus less than 1% in the placebo group.

“Efficacy was seen in both levetiracetam-naive patients and patients previously exposed to levetiracetam, but there wasn’t really any significant difference in efficacy between the 100- and 200-mg doses. Neither was superior,” Dr. Klein said.

The efficacy outcomes are comparable to levetiracetam’s phase III results against placebo, as described in the older drug’s FDA labeling. However, brivaracetam seems to help some patients at a smaller dose, which is a potential selling point for UCB.

The study dropout rate was 6.5% for placebo patients and about 11% in the brivaracetam group. About two-thirds of brivaracetam patients reported side effects, most commonly – and also similar to levetiracetam – somnolence, dizziness, and fatigue.

Self-reported “irritability occurred relatively little” in the study, perhaps in about 2% of brivaracetam patients and 1% of the placebo group. Postmarketing data shows that irritability occurs in “somewhere around 10%” of levetiracetam patients, Dr. Klein said.

The earlier phase III trials also compared brivaracetam against placebo as an adjunct, but mostly at smaller doses; the results for 100 and 200 mg tended to be more robust.

UCB funded the work. Dr. Klein said he investigated the drug on the company’s behalf. He is also a speaker and adviser for UCB.

[email protected]

SEATTLE – UCB will likely submit brivaracetam – its follow-up to levetiracetam – to the Food and Drug Administration for approval in the not-so-distant future.

Brivaracetam is a molecular analog of levetiracetam (Keppra), a widely used epilepsy drug that’s now available as a generic. The company has reported that it binds synaptic vesicle protein 2A with greater affinity than does levetiracetam, which suggests greater potency. However, phase III testing compared brivaracetam to placebo, so it’s unclear if the analog has advantages over the older drug, according to Dr. Pavel Klein, an epileptologist and director of the Mid-Atlantic Epilepsy and Sleep Center in Bethesda, Md.

“Levetiracetam is a great medication, but its psychiatric side effects,” which can include aggression, depression, and even psychosis, are “limiting. If brivaracetam turns out to be a friendlier version of levetiracetam, that would be helpful, but we don’t know that yet,” he said at the annual meeting of the American Epilepsy Society.

Dr. Klein was the principal investigator on brivaracetam’s final phase III trial, and he presented the results at the meeting. With testing complete, UCB said it plans to submit brivaracetam to the FDA in early 2015.

His study randomized 768 adult patients with refractory partial onset seizures to placebo or 100 or 200 mg/day brivaracetam by mouth for 12 weeks as an adjunct; the subjects were also taking one or two other antiepileptic drugs, although not levetiracetam; the trial excluded patients taking levetiracetam and those who had taken it within 3 months. The study group was about 40 years old on average, and evenly split between men and women.

Brivaracetam 100 mg/day reduced 28-day adjusted seizure frequency by 22.8% over placebo, and 200 mg/day reduced it 23.2% over placebo. The responder rate – a reduction of at least 50% in seizure frequency – was 21.6% for placebo, 38.9% for brivaracetam 100 mg, and 37.8% for brivaracetam 200 mg. About 4.5% of brivaracetam patients went the entire 12 weeks without a seizure, versus less than 1% in the placebo group.

“Efficacy was seen in both levetiracetam-naive patients and patients previously exposed to levetiracetam, but there wasn’t really any significant difference in efficacy between the 100- and 200-mg doses. Neither was superior,” Dr. Klein said.

The efficacy outcomes are comparable to levetiracetam’s phase III results against placebo, as described in the older drug’s FDA labeling. However, brivaracetam seems to help some patients at a smaller dose, which is a potential selling point for UCB.

The study dropout rate was 6.5% for placebo patients and about 11% in the brivaracetam group. About two-thirds of brivaracetam patients reported side effects, most commonly – and also similar to levetiracetam – somnolence, dizziness, and fatigue.

Self-reported “irritability occurred relatively little” in the study, perhaps in about 2% of brivaracetam patients and 1% of the placebo group. Postmarketing data shows that irritability occurs in “somewhere around 10%” of levetiracetam patients, Dr. Klein said.

The earlier phase III trials also compared brivaracetam against placebo as an adjunct, but mostly at smaller doses; the results for 100 and 200 mg tended to be more robust.

UCB funded the work. Dr. Klein said he investigated the drug on the company’s behalf. He is also a speaker and adviser for UCB.

[email protected]

SEATTLE – UCB will likely submit brivaracetam – its follow-up to levetiracetam – to the Food and Drug Administration for approval in the not-so-distant future.

Brivaracetam is a molecular analog of levetiracetam (Keppra), a widely used epilepsy drug that’s now available as a generic. The company has reported that it binds synaptic vesicle protein 2A with greater affinity than does levetiracetam, which suggests greater potency. However, phase III testing compared brivaracetam to placebo, so it’s unclear if the analog has advantages over the older drug, according to Dr. Pavel Klein, an epileptologist and director of the Mid-Atlantic Epilepsy and Sleep Center in Bethesda, Md.

“Levetiracetam is a great medication, but its psychiatric side effects,” which can include aggression, depression, and even psychosis, are “limiting. If brivaracetam turns out to be a friendlier version of levetiracetam, that would be helpful, but we don’t know that yet,” he said at the annual meeting of the American Epilepsy Society.

Dr. Klein was the principal investigator on brivaracetam’s final phase III trial, and he presented the results at the meeting. With testing complete, UCB said it plans to submit brivaracetam to the FDA in early 2015.

His study randomized 768 adult patients with refractory partial onset seizures to placebo or 100 or 200 mg/day brivaracetam by mouth for 12 weeks as an adjunct; the subjects were also taking one or two other antiepileptic drugs, although not levetiracetam; the trial excluded patients taking levetiracetam and those who had taken it within 3 months. The study group was about 40 years old on average, and evenly split between men and women.

Brivaracetam 100 mg/day reduced 28-day adjusted seizure frequency by 22.8% over placebo, and 200 mg/day reduced it 23.2% over placebo. The responder rate – a reduction of at least 50% in seizure frequency – was 21.6% for placebo, 38.9% for brivaracetam 100 mg, and 37.8% for brivaracetam 200 mg. About 4.5% of brivaracetam patients went the entire 12 weeks without a seizure, versus less than 1% in the placebo group.

“Efficacy was seen in both levetiracetam-naive patients and patients previously exposed to levetiracetam, but there wasn’t really any significant difference in efficacy between the 100- and 200-mg doses. Neither was superior,” Dr. Klein said.

The efficacy outcomes are comparable to levetiracetam’s phase III results against placebo, as described in the older drug’s FDA labeling. However, brivaracetam seems to help some patients at a smaller dose, which is a potential selling point for UCB.

The study dropout rate was 6.5% for placebo patients and about 11% in the brivaracetam group. About two-thirds of brivaracetam patients reported side effects, most commonly – and also similar to levetiracetam – somnolence, dizziness, and fatigue.

Self-reported “irritability occurred relatively little” in the study, perhaps in about 2% of brivaracetam patients and 1% of the placebo group. Postmarketing data shows that irritability occurs in “somewhere around 10%” of levetiracetam patients, Dr. Klein said.

The earlier phase III trials also compared brivaracetam against placebo as an adjunct, but mostly at smaller doses; the results for 100 and 200 mg tended to be more robust.

UCB funded the work. Dr. Klein said he investigated the drug on the company’s behalf. He is also a speaker and adviser for UCB.

[email protected]

SEATTLE – Adults want to know about the risk of sudden death when they are diagnosed with epilepsy, or shortly thereafter, and they want to hear the news face-to-face from their diagnosing neurologist, according to surveys of 23 epilepsy patients at McMaster University in Hamilton, Ont.

Doctors often struggle about how – or even if – to explain Sudden Unexpected Death in Epilepsy (SUDEP) to patients because the risk of SUDEP is small – perhaps 1 in 1,000 per year overall – but the potential for unwarranted anxiety about sudden death is large. There’s concern that patients will obsess about SUDEP and forget everything they hear about epilepsy management.

Instead of trying to guess what patients want, the investigators turned to “the experts” on how to broach difficult medical issues, the patients themselves, said epileptologist and lead investigator Dr. Rajesh RamachandranNair, an associate professor of pediatrics at McMaster.

They interviewed 19 epilepsy patients aged 18-65 years over the phone for almost an hour, and listened to what four others had to say in a focus group. All of the subjects had focal or generalized convulsive seizures and about half were well controlled with medication. Most had been diagnosed for more than a year, but two patients had been diagnosed within the previous 12 months. Thirteen (57%) hadn’t heard about SUDEP before being invited into the study, the others didn’t know much about the problem; 16 of the 23 patients were women. “There was 100% agreement that all of them wanted to know about SUDEP. Several people actually overestimated the risk, so this could be a positive discussion” for patients, Dr. RamachandranNair said at the American Epilepsy Society annual meeting.

Fifteen (65%) wanted to hear about SUDEP at the time of diagnosis; the rest wanted the discussion shortly thereafter at follow-up. All of the patients wanted to hear the news from a physician, primarily face-to-face from a neurologist who could accurately answer their questions. The patients said the conversation should focus mostly on the actual risk of sudden death, general information about the problem, prevention, and perhaps support group contacts. Most wanted to leave the office with supplmental written materials.

Most thought it was a good idea for all epilepsy patents to know about SUDEP, so that they and their loved ones could prepare for the possibility. Most also wanted a close relative in the room when they learned of SUDEP, and many thought it was a good idea to have a nurse or social worker present for extra support. Fourteen (61%) did not think knowing about SUDEP would change their lives, but a handful said it would make them take better care of themselves and be more compliant with their medications.

The McMaster team had a social worker on standby for their study, “but none of the patients contacted the social worker, which indirectly tell us that patients were probably not [too] worried” about the news, Dr. RamachandranNair said.

Dr. RamachandranNair and his colleagues have been tackling SUDEP awareness for several years. They previously found that parents of children with epilepsy want a similarly frank discussion of the issue.

“One word of caution is that this is a highly selective group.” They agreed to participate in the study, “so that tells us they are probably information seekers who want to know about their health status,” Dr. RamachandranNair said.

The team is planning future work to check the generalizability of their results, and assess how well patients live with the news of SUDEP.

Dr. RamachandranNair said he has no relevant financial disclosures. The work was funded by the Ontario Ministry of Health and Long-Term Care.

[email protected]

SEATTLE – Adults want to know about the risk of sudden death when they are diagnosed with epilepsy, or shortly thereafter, and they want to hear the news face-to-face from their diagnosing neurologist, according to surveys of 23 epilepsy patients at McMaster University in Hamilton, Ont.

Doctors often struggle about how – or even if – to explain Sudden Unexpected Death in Epilepsy (SUDEP) to patients because the risk of SUDEP is small – perhaps 1 in 1,000 per year overall – but the potential for unwarranted anxiety about sudden death is large. There’s concern that patients will obsess about SUDEP and forget everything they hear about epilepsy management.

Instead of trying to guess what patients want, the investigators turned to “the experts” on how to broach difficult medical issues, the patients themselves, said epileptologist and lead investigator Dr. Rajesh RamachandranNair, an associate professor of pediatrics at McMaster.

They interviewed 19 epilepsy patients aged 18-65 years over the phone for almost an hour, and listened to what four others had to say in a focus group. All of the subjects had focal or generalized convulsive seizures and about half were well controlled with medication. Most had been diagnosed for more than a year, but two patients had been diagnosed within the previous 12 months. Thirteen (57%) hadn’t heard about SUDEP before being invited into the study, the others didn’t know much about the problem; 16 of the 23 patients were women. “There was 100% agreement that all of them wanted to know about SUDEP. Several people actually overestimated the risk, so this could be a positive discussion” for patients, Dr. RamachandranNair said at the American Epilepsy Society annual meeting.

Fifteen (65%) wanted to hear about SUDEP at the time of diagnosis; the rest wanted the discussion shortly thereafter at follow-up. All of the patients wanted to hear the news from a physician, primarily face-to-face from a neurologist who could accurately answer their questions. The patients said the conversation should focus mostly on the actual risk of sudden death, general information about the problem, prevention, and perhaps support group contacts. Most wanted to leave the office with supplmental written materials.

Most thought it was a good idea for all epilepsy patents to know about SUDEP, so that they and their loved ones could prepare for the possibility. Most also wanted a close relative in the room when they learned of SUDEP, and many thought it was a good idea to have a nurse or social worker present for extra support. Fourteen (61%) did not think knowing about SUDEP would change their lives, but a handful said it would make them take better care of themselves and be more compliant with their medications.

The McMaster team had a social worker on standby for their study, “but none of the patients contacted the social worker, which indirectly tell us that patients were probably not [too] worried” about the news, Dr. RamachandranNair said.

Dr. RamachandranNair and his colleagues have been tackling SUDEP awareness for several years. They previously found that parents of children with epilepsy want a similarly frank discussion of the issue.

“One word of caution is that this is a highly selective group.” They agreed to participate in the study, “so that tells us they are probably information seekers who want to know about their health status,” Dr. RamachandranNair said.

The team is planning future work to check the generalizability of their results, and assess how well patients live with the news of SUDEP.

Dr. RamachandranNair said he has no relevant financial disclosures. The work was funded by the Ontario Ministry of Health and Long-Term Care.

[email protected]

SEATTLE – Adults want to know about the risk of sudden death when they are diagnosed with epilepsy, or shortly thereafter, and they want to hear the news face-to-face from their diagnosing neurologist, according to surveys of 23 epilepsy patients at McMaster University in Hamilton, Ont.

Doctors often struggle about how – or even if – to explain Sudden Unexpected Death in Epilepsy (SUDEP) to patients because the risk of SUDEP is small – perhaps 1 in 1,000 per year overall – but the potential for unwarranted anxiety about sudden death is large. There’s concern that patients will obsess about SUDEP and forget everything they hear about epilepsy management.

Instead of trying to guess what patients want, the investigators turned to “the experts” on how to broach difficult medical issues, the patients themselves, said epileptologist and lead investigator Dr. Rajesh RamachandranNair, an associate professor of pediatrics at McMaster.

They interviewed 19 epilepsy patients aged 18-65 years over the phone for almost an hour, and listened to what four others had to say in a focus group. All of the subjects had focal or generalized convulsive seizures and about half were well controlled with medication. Most had been diagnosed for more than a year, but two patients had been diagnosed within the previous 12 months. Thirteen (57%) hadn’t heard about SUDEP before being invited into the study, the others didn’t know much about the problem; 16 of the 23 patients were women. “There was 100% agreement that all of them wanted to know about SUDEP. Several people actually overestimated the risk, so this could be a positive discussion” for patients, Dr. RamachandranNair said at the American Epilepsy Society annual meeting.

Fifteen (65%) wanted to hear about SUDEP at the time of diagnosis; the rest wanted the discussion shortly thereafter at follow-up. All of the patients wanted to hear the news from a physician, primarily face-to-face from a neurologist who could accurately answer their questions. The patients said the conversation should focus mostly on the actual risk of sudden death, general information about the problem, prevention, and perhaps support group contacts. Most wanted to leave the office with supplmental written materials.

Most thought it was a good idea for all epilepsy patents to know about SUDEP, so that they and their loved ones could prepare for the possibility. Most also wanted a close relative in the room when they learned of SUDEP, and many thought it was a good idea to have a nurse or social worker present for extra support. Fourteen (61%) did not think knowing about SUDEP would change their lives, but a handful said it would make them take better care of themselves and be more compliant with their medications.

The McMaster team had a social worker on standby for their study, “but none of the patients contacted the social worker, which indirectly tell us that patients were probably not [too] worried” about the news, Dr. RamachandranNair said.

Dr. RamachandranNair and his colleagues have been tackling SUDEP awareness for several years. They previously found that parents of children with epilepsy want a similarly frank discussion of the issue.

“One word of caution is that this is a highly selective group.” They agreed to participate in the study, “so that tells us they are probably information seekers who want to know about their health status,” Dr. RamachandranNair said.

The team is planning future work to check the generalizability of their results, and assess how well patients live with the news of SUDEP.

Dr. RamachandranNair said he has no relevant financial disclosures. The work was funded by the Ontario Ministry of Health and Long-Term Care.

[email protected]

VANCOUVER, B.C. – A medical cocktail of tranexamic acid, gonadotropin-releasing hormone agonist, and an aromatase inhibitor stops bleeding from uterine arteriovenous malformations and eliminates the malformations on Doppler ultrasound within a few months, according to a small case series from Western University in London, Ont.

The finding could be a “game changer,” if it holds up under further testing, since it appears to resolve uterine arteriovenous malformations (AVMs) without compromising fertility, unlike uterine artery embolization or hysterectomy, said Dr. Angelos Vilos of Western University, the study’s lead investigator.

“We believe that we have come up with a novel and advantageous cocktail [that is] accessible to all physicians,” he said. “It eliminates uterine bleeding and AVMs. We know it’s safe, and all these medications are readily available.”

Dr. Vilos said he plans to use the drug cocktail as a first-line therapy in patients with uterine bleeding from AVMs.

The investigators used uterine tamponade, as needed, to control bleeding in nine women, then gave them oral tranexamic acid (Cyklokapron) 1 g three times daily for 5 days to clot AVM bleeders. The women also received gonadotropin-releasing hormone (GnRH) agonist injections to shrink the uterus and its vasculature – usually one shot of leuprolide, but goserelin was used for one woman – plus oral letrozole 2.5 mg/day for 5 days after the first injection to prevent GnRH flare.

The uterine AVMs “disappeared” on Doppler ultrasound within 3 months, Dr. Vilos said.

Four of the women went on to conceive spontaneously and have live births. Four others are on oral contraceptives. The ninth woman opted for a subsequent tubal ligation.

“We were able to preserve fertility and the uterus in all of these women,” he said.

The patients had been bleeding from uterine AVMs for up to 6 months, most following spontaneous or therapeutic abortions. They all had negative beta–human chorionic gonadotropin and Doppler-confirmed AVMs in the myometrium. Retained products were ruled out in all of the patients. Two women had failed embolization with coils and gel foam, and two women required transfusions before treatment. One woman required uterine tamponade before the protocol.

“These women weren’t resolving on their own,” Dr. Vilos said at the meeting sponsored by AAGL.

Based on previous work, Dr. Vilos said he and his team were comfortable using GnRH agonists and letrozole for endometriosis, and they frequently use tranexamic acid for acute bleeding. “So we kind of put these ideas together,” he said.

Several of the women were hemorrhaging in the middle of the night, and the community hospitals where they were being treated couldn’t do embolization. The hospitals called Western University, a tertiary care center, for assistance. “We initiated the protocol, and they resolved,” Dr. Vilos said. “[It’s] an effective management strategy.”

Dr. Vilos is an advisor for Bayer Healthcare and Actavis. The investigators did not receive outside funding for the work.

[email protected]

VANCOUVER, B.C. – A medical cocktail of tranexamic acid, gonadotropin-releasing hormone agonist, and an aromatase inhibitor stops bleeding from uterine arteriovenous malformations and eliminates the malformations on Doppler ultrasound within a few months, according to a small case series from Western University in London, Ont.

The finding could be a “game changer,” if it holds up under further testing, since it appears to resolve uterine arteriovenous malformations (AVMs) without compromising fertility, unlike uterine artery embolization or hysterectomy, said Dr. Angelos Vilos of Western University, the study’s lead investigator.

“We believe that we have come up with a novel and advantageous cocktail [that is] accessible to all physicians,” he said. “It eliminates uterine bleeding and AVMs. We know it’s safe, and all these medications are readily available.”

Dr. Vilos said he plans to use the drug cocktail as a first-line therapy in patients with uterine bleeding from AVMs.

The investigators used uterine tamponade, as needed, to control bleeding in nine women, then gave them oral tranexamic acid (Cyklokapron) 1 g three times daily for 5 days to clot AVM bleeders. The women also received gonadotropin-releasing hormone (GnRH) agonist injections to shrink the uterus and its vasculature – usually one shot of leuprolide, but goserelin was used for one woman – plus oral letrozole 2.5 mg/day for 5 days after the first injection to prevent GnRH flare.

The uterine AVMs “disappeared” on Doppler ultrasound within 3 months, Dr. Vilos said.

Four of the women went on to conceive spontaneously and have live births. Four others are on oral contraceptives. The ninth woman opted for a subsequent tubal ligation.

“We were able to preserve fertility and the uterus in all of these women,” he said.

The patients had been bleeding from uterine AVMs for up to 6 months, most following spontaneous or therapeutic abortions. They all had negative beta–human chorionic gonadotropin and Doppler-confirmed AVMs in the myometrium. Retained products were ruled out in all of the patients. Two women had failed embolization with coils and gel foam, and two women required transfusions before treatment. One woman required uterine tamponade before the protocol.

“These women weren’t resolving on their own,” Dr. Vilos said at the meeting sponsored by AAGL.

Based on previous work, Dr. Vilos said he and his team were comfortable using GnRH agonists and letrozole for endometriosis, and they frequently use tranexamic acid for acute bleeding. “So we kind of put these ideas together,” he said.

Several of the women were hemorrhaging in the middle of the night, and the community hospitals where they were being treated couldn’t do embolization. The hospitals called Western University, a tertiary care center, for assistance. “We initiated the protocol, and they resolved,” Dr. Vilos said. “[It’s] an effective management strategy.”

Dr. Vilos is an advisor for Bayer Healthcare and Actavis. The investigators did not receive outside funding for the work.

[email protected]

VANCOUVER, B.C. – A medical cocktail of tranexamic acid, gonadotropin-releasing hormone agonist, and an aromatase inhibitor stops bleeding from uterine arteriovenous malformations and eliminates the malformations on Doppler ultrasound within a few months, according to a small case series from Western University in London, Ont.

The finding could be a “game changer,” if it holds up under further testing, since it appears to resolve uterine arteriovenous malformations (AVMs) without compromising fertility, unlike uterine artery embolization or hysterectomy, said Dr. Angelos Vilos of Western University, the study’s lead investigator.

“We believe that we have come up with a novel and advantageous cocktail [that is] accessible to all physicians,” he said. “It eliminates uterine bleeding and AVMs. We know it’s safe, and all these medications are readily available.”

Dr. Vilos said he plans to use the drug cocktail as a first-line therapy in patients with uterine bleeding from AVMs.

The investigators used uterine tamponade, as needed, to control bleeding in nine women, then gave them oral tranexamic acid (Cyklokapron) 1 g three times daily for 5 days to clot AVM bleeders. The women also received gonadotropin-releasing hormone (GnRH) agonist injections to shrink the uterus and its vasculature – usually one shot of leuprolide, but goserelin was used for one woman – plus oral letrozole 2.5 mg/day for 5 days after the first injection to prevent GnRH flare.

The uterine AVMs “disappeared” on Doppler ultrasound within 3 months, Dr. Vilos said.

Four of the women went on to conceive spontaneously and have live births. Four others are on oral contraceptives. The ninth woman opted for a subsequent tubal ligation.

“We were able to preserve fertility and the uterus in all of these women,” he said.

The patients had been bleeding from uterine AVMs for up to 6 months, most following spontaneous or therapeutic abortions. They all had negative beta–human chorionic gonadotropin and Doppler-confirmed AVMs in the myometrium. Retained products were ruled out in all of the patients. Two women had failed embolization with coils and gel foam, and two women required transfusions before treatment. One woman required uterine tamponade before the protocol.

“These women weren’t resolving on their own,” Dr. Vilos said at the meeting sponsored by AAGL.

Based on previous work, Dr. Vilos said he and his team were comfortable using GnRH agonists and letrozole for endometriosis, and they frequently use tranexamic acid for acute bleeding. “So we kind of put these ideas together,” he said.

Several of the women were hemorrhaging in the middle of the night, and the community hospitals where they were being treated couldn’t do embolization. The hospitals called Western University, a tertiary care center, for assistance. “We initiated the protocol, and they resolved,” Dr. Vilos said. “[It’s] an effective management strategy.”

Dr. Vilos is an advisor for Bayer Healthcare and Actavis. The investigators did not receive outside funding for the work.

[email protected]

SEATTLE – Auras don’t keep epilepsy patients safe while driving, according to a Yale University review of 215 medically-refractory epilepsy patients who had seizures behind the wheel.

Patients who have auras before their seizures are just as likely to get into accidents as are those who do not. “Our findings question the assumed protective benefit of reliable auras against motor vehicle accidents,” said Dr. Vineet Punia, a fellow in clinical neurophysiology, EEG, and epilepsy at the Cleveland Clinic.

It’s widely assumed that auras give patients enough time to pull off the road before a seizure. Many states have codified that belief into their driving laws based on advice from the American Academy of Neurology and American Epilepsy Society to use “consistent and prolonged auras” as a favorable factor when deciding if epilepsy patients should be licensed to drive (Epilepsia 1994;35:696-705).

That assumption has led to “a false sense of security,” Dr. Punia said at the annual meeting of the American Epilepsy Society. Even when they last more than a minute, “auras do not decrease the risk of motor vehicle accidents. We need to educate” people about this, he said, and, perhaps, rethink the laws.

He and his team looked for differences between the 141 patients who said their seizures caused car accidents, and the 74 who said they did not. The patients in the study were culled from the Multicenter Study of Epilepsy Surgery database.

If auras kept patients safe, the team reasoned that they would be more common in the accident-free group, but that’s not what they found. About 66% of the accident-free group reported having reliable auras before their attacks, the same as in the group that had seizure-related crashes. About 20% in both groups estimated that their auras lasted more than a minute, and about 41% in both thought that their auras were almost always long enough to prevent accidents.

“The presence of a reliable aura did not differ between the two groups. Having a longer aura did not prevent accidents. This would definitely affect how I counsel patients who want to drive,” Dr. Punia said.

The two groups were evenly matched. In both, about 86% had temporal lobe epilepsy; the majority had complex partial seizures (CPS); 45% were women; and the average age was 40 years.

There were a few factors that increased the odds of being involved in a motor vehicle accident, including having a history of CPS (odds ratio, 2.83; 95% confidence interval, 1.14-7.09; P = .029), at least one CPS per month in the last 3 months (OR, 2.52; 95% CI, 1.22-5.21; P = .01), and postictal periods of a minute or more (OR, 2.53; 95% CI, 1.04-6.19; P = .05) .

“CPS and longer postictal state are the most salient features of seizures” that increase the risk of accidents, suggesting that “impairment of consciousness may be a key factor,” they said.

The work was funded internally, and the investigators said they have no relevant industry disclosures.

[email protected]

SEATTLE – Auras don’t keep epilepsy patients safe while driving, according to a Yale University review of 215 medically-refractory epilepsy patients who had seizures behind the wheel.

Patients who have auras before their seizures are just as likely to get into accidents as are those who do not. “Our findings question the assumed protective benefit of reliable auras against motor vehicle accidents,” said Dr. Vineet Punia, a fellow in clinical neurophysiology, EEG, and epilepsy at the Cleveland Clinic.

It’s widely assumed that auras give patients enough time to pull off the road before a seizure. Many states have codified that belief into their driving laws based on advice from the American Academy of Neurology and American Epilepsy Society to use “consistent and prolonged auras” as a favorable factor when deciding if epilepsy patients should be licensed to drive (Epilepsia 1994;35:696-705).

That assumption has led to “a false sense of security,” Dr. Punia said at the annual meeting of the American Epilepsy Society. Even when they last more than a minute, “auras do not decrease the risk of motor vehicle accidents. We need to educate” people about this, he said, and, perhaps, rethink the laws.

He and his team looked for differences between the 141 patients who said their seizures caused car accidents, and the 74 who said they did not. The patients in the study were culled from the Multicenter Study of Epilepsy Surgery database.

If auras kept patients safe, the team reasoned that they would be more common in the accident-free group, but that’s not what they found. About 66% of the accident-free group reported having reliable auras before their attacks, the same as in the group that had seizure-related crashes. About 20% in both groups estimated that their auras lasted more than a minute, and about 41% in both thought that their auras were almost always long enough to prevent accidents.

“The presence of a reliable aura did not differ between the two groups. Having a longer aura did not prevent accidents. This would definitely affect how I counsel patients who want to drive,” Dr. Punia said.

The two groups were evenly matched. In both, about 86% had temporal lobe epilepsy; the majority had complex partial seizures (CPS); 45% were women; and the average age was 40 years.

There were a few factors that increased the odds of being involved in a motor vehicle accident, including having a history of CPS (odds ratio, 2.83; 95% confidence interval, 1.14-7.09; P = .029), at least one CPS per month in the last 3 months (OR, 2.52; 95% CI, 1.22-5.21; P = .01), and postictal periods of a minute or more (OR, 2.53; 95% CI, 1.04-6.19; P = .05) .

“CPS and longer postictal state are the most salient features of seizures” that increase the risk of accidents, suggesting that “impairment of consciousness may be a key factor,” they said.

The work was funded internally, and the investigators said they have no relevant industry disclosures.

[email protected]

SEATTLE – Auras don’t keep epilepsy patients safe while driving, according to a Yale University review of 215 medically-refractory epilepsy patients who had seizures behind the wheel.

Patients who have auras before their seizures are just as likely to get into accidents as are those who do not. “Our findings question the assumed protective benefit of reliable auras against motor vehicle accidents,” said Dr. Vineet Punia, a fellow in clinical neurophysiology, EEG, and epilepsy at the Cleveland Clinic.

It’s widely assumed that auras give patients enough time to pull off the road before a seizure. Many states have codified that belief into their driving laws based on advice from the American Academy of Neurology and American Epilepsy Society to use “consistent and prolonged auras” as a favorable factor when deciding if epilepsy patients should be licensed to drive (Epilepsia 1994;35:696-705).

That assumption has led to “a false sense of security,” Dr. Punia said at the annual meeting of the American Epilepsy Society. Even when they last more than a minute, “auras do not decrease the risk of motor vehicle accidents. We need to educate” people about this, he said, and, perhaps, rethink the laws.

He and his team looked for differences between the 141 patients who said their seizures caused car accidents, and the 74 who said they did not. The patients in the study were culled from the Multicenter Study of Epilepsy Surgery database.

If auras kept patients safe, the team reasoned that they would be more common in the accident-free group, but that’s not what they found. About 66% of the accident-free group reported having reliable auras before their attacks, the same as in the group that had seizure-related crashes. About 20% in both groups estimated that their auras lasted more than a minute, and about 41% in both thought that their auras were almost always long enough to prevent accidents.

“The presence of a reliable aura did not differ between the two groups. Having a longer aura did not prevent accidents. This would definitely affect how I counsel patients who want to drive,” Dr. Punia said.

The two groups were evenly matched. In both, about 86% had temporal lobe epilepsy; the majority had complex partial seizures (CPS); 45% were women; and the average age was 40 years.

There were a few factors that increased the odds of being involved in a motor vehicle accident, including having a history of CPS (odds ratio, 2.83; 95% confidence interval, 1.14-7.09; P = .029), at least one CPS per month in the last 3 months (OR, 2.52; 95% CI, 1.22-5.21; P = .01), and postictal periods of a minute or more (OR, 2.53; 95% CI, 1.04-6.19; P = .05) .

“CPS and longer postictal state are the most salient features of seizures” that increase the risk of accidents, suggesting that “impairment of consciousness may be a key factor,” they said.

The work was funded internally, and the investigators said they have no relevant industry disclosures.

[email protected]

SEATTLE – When history, physical, and brain MRI fail to find a cause for infantile spasms, genetic studies – not specialized metabolic testing – should be the next diagnostic step, according to investigators from the National Infantile Spasms Consortium.

In a prospective study of 251 children with West syndrome at 21 pediatric epilepsy centers in the United States, they found that genetic studies – especially epilepsy gene panels and array comparative genomic hybridization (aCGH) – were more likely than specialized metabolic tests were to reveal the cause of infantile spasms. They were also a bit less expensive, and sometimes caught genes associated with mitochondrial disorders, glucose transporter deficiencies, and other metabolic issues.

“If your MRI looks normal, you are better off spending your money on genetic studies. Think about doing [an aCGH] microarray and an epilepsy gene panel if the microarray is negative.” If answers are still elusive, metabolic screening is in order, but “you can probably limit it to serum lactate, pyruvate amino acids, and urine organic acids,” said study leader Dr. Elaine Wirrell, director of the pediatric epilepsy fellowship program at the Mayo Clinic in Rochester, Minn.History, physical, and MRI found congenital or acquired structural brain abnormalities or other obvious causes for spasms in 138 children (55%). Three months of follow-up testing identified the cause in another 23 (9%). The kids in the study were an average of 7 months old at presentation and were about evenly split between boys and girls.

Almost all the children in the study had extensive metabolic evaluations of their blood and urine, and about half had cerebrospinal fluid testing. Even so, the diagnostic yield of metabolic workups was “very low” among children with no clear etiology for their spasms after their initial evaluations. “Very rarely did metabolic testing come up with any sort of etiological answer,” Dr. Wirrell said, and in the few times it did, abnormalities were found only on serum lactate, pyruvate amino acids, and urine organic acid testing.

About half of the kids had genetic testing. In the group with no clear etiology, 20 had an epilepsy gene panel; its diagnostic yield was 30%. If the variants of uncertain significance (VUS) were included, the yield rose to more than 50%. Among the 60-plus children screened with aCGH microarray, the diagnostic yield was 10%, but with the VUS, it was 20%. Chromosome 15 abnormalities were found in a number of children.

“We had a significant yield of clear pathogenic changes and variants” with genetic testing. With more widespread use, “I think we would pick up a lot more children who have genetic causes” for infantile spasms, Dr. Wirrell said.

There’s not a lot that can be done for those children at present. “For most cases that have a genetic etiology, we are not at the point where we can say ‘this etiology equals that treatment,’ but I think we’ll get there,” she said.

The study was funded by the American Epilepsy Society and the Pediatric Epilepsy Research Foundation. Dr. Wirrell said she has no industry disclosures.

[email protected]

SEATTLE – When history, physical, and brain MRI fail to find a cause for infantile spasms, genetic studies – not specialized metabolic testing – should be the next diagnostic step, according to investigators from the National Infantile Spasms Consortium.

In a prospective study of 251 children with West syndrome at 21 pediatric epilepsy centers in the United States, they found that genetic studies – especially epilepsy gene panels and array comparative genomic hybridization (aCGH) – were more likely than specialized metabolic tests were to reveal the cause of infantile spasms. They were also a bit less expensive, and sometimes caught genes associated with mitochondrial disorders, glucose transporter deficiencies, and other metabolic issues.

“If your MRI looks normal, you are better off spending your money on genetic studies. Think about doing [an aCGH] microarray and an epilepsy gene panel if the microarray is negative.” If answers are still elusive, metabolic screening is in order, but “you can probably limit it to serum lactate, pyruvate amino acids, and urine organic acids,” said study leader Dr. Elaine Wirrell, director of the pediatric epilepsy fellowship program at the Mayo Clinic in Rochester, Minn.History, physical, and MRI found congenital or acquired structural brain abnormalities or other obvious causes for spasms in 138 children (55%). Three months of follow-up testing identified the cause in another 23 (9%). The kids in the study were an average of 7 months old at presentation and were about evenly split between boys and girls.

Almost all the children in the study had extensive metabolic evaluations of their blood and urine, and about half had cerebrospinal fluid testing. Even so, the diagnostic yield of metabolic workups was “very low” among children with no clear etiology for their spasms after their initial evaluations. “Very rarely did metabolic testing come up with any sort of etiological answer,” Dr. Wirrell said, and in the few times it did, abnormalities were found only on serum lactate, pyruvate amino acids, and urine organic acid testing.

About half of the kids had genetic testing. In the group with no clear etiology, 20 had an epilepsy gene panel; its diagnostic yield was 30%. If the variants of uncertain significance (VUS) were included, the yield rose to more than 50%. Among the 60-plus children screened with aCGH microarray, the diagnostic yield was 10%, but with the VUS, it was 20%. Chromosome 15 abnormalities were found in a number of children.

“We had a significant yield of clear pathogenic changes and variants” with genetic testing. With more widespread use, “I think we would pick up a lot more children who have genetic causes” for infantile spasms, Dr. Wirrell said.

There’s not a lot that can be done for those children at present. “For most cases that have a genetic etiology, we are not at the point where we can say ‘this etiology equals that treatment,’ but I think we’ll get there,” she said.

The study was funded by the American Epilepsy Society and the Pediatric Epilepsy Research Foundation. Dr. Wirrell said she has no industry disclosures.

[email protected]

SEATTLE – When history, physical, and brain MRI fail to find a cause for infantile spasms, genetic studies – not specialized metabolic testing – should be the next diagnostic step, according to investigators from the National Infantile Spasms Consortium.

In a prospective study of 251 children with West syndrome at 21 pediatric epilepsy centers in the United States, they found that genetic studies – especially epilepsy gene panels and array comparative genomic hybridization (aCGH) – were more likely than specialized metabolic tests were to reveal the cause of infantile spasms. They were also a bit less expensive, and sometimes caught genes associated with mitochondrial disorders, glucose transporter deficiencies, and other metabolic issues.

“If your MRI looks normal, you are better off spending your money on genetic studies. Think about doing [an aCGH] microarray and an epilepsy gene panel if the microarray is negative.” If answers are still elusive, metabolic screening is in order, but “you can probably limit it to serum lactate, pyruvate amino acids, and urine organic acids,” said study leader Dr. Elaine Wirrell, director of the pediatric epilepsy fellowship program at the Mayo Clinic in Rochester, Minn.History, physical, and MRI found congenital or acquired structural brain abnormalities or other obvious causes for spasms in 138 children (55%). Three months of follow-up testing identified the cause in another 23 (9%). The kids in the study were an average of 7 months old at presentation and were about evenly split between boys and girls.

Almost all the children in the study had extensive metabolic evaluations of their blood and urine, and about half had cerebrospinal fluid testing. Even so, the diagnostic yield of metabolic workups was “very low” among children with no clear etiology for their spasms after their initial evaluations. “Very rarely did metabolic testing come up with any sort of etiological answer,” Dr. Wirrell said, and in the few times it did, abnormalities were found only on serum lactate, pyruvate amino acids, and urine organic acid testing.

About half of the kids had genetic testing. In the group with no clear etiology, 20 had an epilepsy gene panel; its diagnostic yield was 30%. If the variants of uncertain significance (VUS) were included, the yield rose to more than 50%. Among the 60-plus children screened with aCGH microarray, the diagnostic yield was 10%, but with the VUS, it was 20%. Chromosome 15 abnormalities were found in a number of children.

“We had a significant yield of clear pathogenic changes and variants” with genetic testing. With more widespread use, “I think we would pick up a lot more children who have genetic causes” for infantile spasms, Dr. Wirrell said.

There’s not a lot that can be done for those children at present. “For most cases that have a genetic etiology, we are not at the point where we can say ‘this etiology equals that treatment,’ but I think we’ll get there,” she said.

The study was funded by the American Epilepsy Society and the Pediatric Epilepsy Research Foundation. Dr. Wirrell said she has no industry disclosures.

[email protected]