Obese mouse

Immunotherapy that can be effective against tumors in young, thin mice can be lethal to obese ones, according to research published in The Journal of Experimental Medicine.

Investigators conducted experiments in mouse models to determine if there is a subset of cancer patients for whom certain immunotherapies might be especially toxic.

The group found a potential link between body fat and the risk of toxicity from some types of immunotherapy.

“Cancer is primarily considered a disease of the aged, and yet preclinical studies generally use young, lean animal models that may not be reflective of the ‘typical’ cancer patient,” said study author Annie Mirsoian, a PhD candidate at the University of California, Davis in Sacramento.

“Aging is a dynamic process that is characterized by increases in inflammatory factors, as well as a shift in body composition where there is a gradual loss of lean muscle mass and an increase in fat accumulation, which effect how the immune system functions.”

Mirsoian and her colleagues sought to determine if, by adjusting the mouse model to more closely reflect the cancer patient phenotype (advanced age and overweight), they could better understand the discrepancies between animal study outcomes and those in patients in the clinic.

So the team examined aged mice on standard diets and compared those to aged mice that were calorie-restricted throughout their lives.

The investigators found that calorie restriction plays a protective role against toxicity. When aged mice ate their standard diet freely throughout life, they became obese and ultimately experienced lethal adverse reactions after receiving a systemic immunotherapy regimen.

“We know that people who are obese in general are at higher risk for complications from surgery, radiation, and chemotherapy,” said study author Arta Monjazeb, MD, PhD, of the University of California, Davis.

“We know that obese people have higher levels of inflammatory markers in their blood, but there is a lack of data examining the effects of obesity on cancer treatment outcomes.”

In follow-up experiments, the investigators found that young mice that are obese also endure similar toxic consequences, demonstrating that fat is a critical factor in toxic responses to stimulatory anticancer immunotherapy regimens.

“It is important to note, however, that the aged mice on standard diets succumbed to lethality at a quicker rate than young obese mice,” Mirsoian said. “Although our data demonstrate that obesity plays a central role in the development of adverse effects, future studies will focus on examining the aged immune system and cellular characteristics that may have enhanced the sensitivity of these mice to inflammation.”

This study follows an earlier paper, which demonstrated that while young, lean mice tolerate immunotherapy regimens without toxicity, the same regimen for an aged cohort resulted in lethal consequences. The new paper takes a deeper look into how fat deposition throughout aging can be critical in determining treatment tolerance and efficacy.

“Obesity has become an epidemic in our society and is now also affecting younger populations,” Mirsoian said. “Therefore, it’s likely that what the ‘typical’ cancer patient looks like will change. Our findings demonstrate the importance of having preclinical animal models that reflect the clinical scenario.”

“Changing the characteristics of our mouse models allowed for a more accurate determination of possible adverse reactions to therapy and more closely modeled what has been reported in the clinic with stimulatory immunotherapies.”

The investigators said factors like age, fat content, and the types of infections experienced throughout life together shape how the immune system reacts, and they will continue to work on improving their modeling system to reflect these changes.

They project that improvements in mouse modeling may help produce data that can better modulate treatment choices for patients, as well as identify early which patients would benefit from the inclusion of drugs to prevent adverse reactions while maintaining anticancer efficacy.

Obese mouse

Immunotherapy that can be effective against tumors in young, thin mice can be lethal to obese ones, according to research published in The Journal of Experimental Medicine.

Investigators conducted experiments in mouse models to determine if there is a subset of cancer patients for whom certain immunotherapies might be especially toxic.

The group found a potential link between body fat and the risk of toxicity from some types of immunotherapy.

“Cancer is primarily considered a disease of the aged, and yet preclinical studies generally use young, lean animal models that may not be reflective of the ‘typical’ cancer patient,” said study author Annie Mirsoian, a PhD candidate at the University of California, Davis in Sacramento.

“Aging is a dynamic process that is characterized by increases in inflammatory factors, as well as a shift in body composition where there is a gradual loss of lean muscle mass and an increase in fat accumulation, which effect how the immune system functions.”

Mirsoian and her colleagues sought to determine if, by adjusting the mouse model to more closely reflect the cancer patient phenotype (advanced age and overweight), they could better understand the discrepancies between animal study outcomes and those in patients in the clinic.

So the team examined aged mice on standard diets and compared those to aged mice that were calorie-restricted throughout their lives.

The investigators found that calorie restriction plays a protective role against toxicity. When aged mice ate their standard diet freely throughout life, they became obese and ultimately experienced lethal adverse reactions after receiving a systemic immunotherapy regimen.

“We know that people who are obese in general are at higher risk for complications from surgery, radiation, and chemotherapy,” said study author Arta Monjazeb, MD, PhD, of the University of California, Davis.

“We know that obese people have higher levels of inflammatory markers in their blood, but there is a lack of data examining the effects of obesity on cancer treatment outcomes.”

In follow-up experiments, the investigators found that young mice that are obese also endure similar toxic consequences, demonstrating that fat is a critical factor in toxic responses to stimulatory anticancer immunotherapy regimens.

“It is important to note, however, that the aged mice on standard diets succumbed to lethality at a quicker rate than young obese mice,” Mirsoian said. “Although our data demonstrate that obesity plays a central role in the development of adverse effects, future studies will focus on examining the aged immune system and cellular characteristics that may have enhanced the sensitivity of these mice to inflammation.”

This study follows an earlier paper, which demonstrated that while young, lean mice tolerate immunotherapy regimens without toxicity, the same regimen for an aged cohort resulted in lethal consequences. The new paper takes a deeper look into how fat deposition throughout aging can be critical in determining treatment tolerance and efficacy.

“Obesity has become an epidemic in our society and is now also affecting younger populations,” Mirsoian said. “Therefore, it’s likely that what the ‘typical’ cancer patient looks like will change. Our findings demonstrate the importance of having preclinical animal models that reflect the clinical scenario.”

“Changing the characteristics of our mouse models allowed for a more accurate determination of possible adverse reactions to therapy and more closely modeled what has been reported in the clinic with stimulatory immunotherapies.”

The investigators said factors like age, fat content, and the types of infections experienced throughout life together shape how the immune system reacts, and they will continue to work on improving their modeling system to reflect these changes.

They project that improvements in mouse modeling may help produce data that can better modulate treatment choices for patients, as well as identify early which patients would benefit from the inclusion of drugs to prevent adverse reactions while maintaining anticancer efficacy.

Obese mouse

Immunotherapy that can be effective against tumors in young, thin mice can be lethal to obese ones, according to research published in The Journal of Experimental Medicine.

Investigators conducted experiments in mouse models to determine if there is a subset of cancer patients for whom certain immunotherapies might be especially toxic.

The group found a potential link between body fat and the risk of toxicity from some types of immunotherapy.

“Cancer is primarily considered a disease of the aged, and yet preclinical studies generally use young, lean animal models that may not be reflective of the ‘typical’ cancer patient,” said study author Annie Mirsoian, a PhD candidate at the University of California, Davis in Sacramento.

“Aging is a dynamic process that is characterized by increases in inflammatory factors, as well as a shift in body composition where there is a gradual loss of lean muscle mass and an increase in fat accumulation, which effect how the immune system functions.”

Mirsoian and her colleagues sought to determine if, by adjusting the mouse model to more closely reflect the cancer patient phenotype (advanced age and overweight), they could better understand the discrepancies between animal study outcomes and those in patients in the clinic.

So the team examined aged mice on standard diets and compared those to aged mice that were calorie-restricted throughout their lives.

The investigators found that calorie restriction plays a protective role against toxicity. When aged mice ate their standard diet freely throughout life, they became obese and ultimately experienced lethal adverse reactions after receiving a systemic immunotherapy regimen.

“We know that people who are obese in general are at higher risk for complications from surgery, radiation, and chemotherapy,” said study author Arta Monjazeb, MD, PhD, of the University of California, Davis.

“We know that obese people have higher levels of inflammatory markers in their blood, but there is a lack of data examining the effects of obesity on cancer treatment outcomes.”

In follow-up experiments, the investigators found that young mice that are obese also endure similar toxic consequences, demonstrating that fat is a critical factor in toxic responses to stimulatory anticancer immunotherapy regimens.

“It is important to note, however, that the aged mice on standard diets succumbed to lethality at a quicker rate than young obese mice,” Mirsoian said. “Although our data demonstrate that obesity plays a central role in the development of adverse effects, future studies will focus on examining the aged immune system and cellular characteristics that may have enhanced the sensitivity of these mice to inflammation.”

This study follows an earlier paper, which demonstrated that while young, lean mice tolerate immunotherapy regimens without toxicity, the same regimen for an aged cohort resulted in lethal consequences. The new paper takes a deeper look into how fat deposition throughout aging can be critical in determining treatment tolerance and efficacy.

“Obesity has become an epidemic in our society and is now also affecting younger populations,” Mirsoian said. “Therefore, it’s likely that what the ‘typical’ cancer patient looks like will change. Our findings demonstrate the importance of having preclinical animal models that reflect the clinical scenario.”

“Changing the characteristics of our mouse models allowed for a more accurate determination of possible adverse reactions to therapy and more closely modeled what has been reported in the clinic with stimulatory immunotherapies.”

The investigators said factors like age, fat content, and the types of infections experienced throughout life together shape how the immune system reacts, and they will continue to work on improving their modeling system to reflect these changes.

They project that improvements in mouse modeling may help produce data that can better modulate treatment choices for patients, as well as identify early which patients would benefit from the inclusion of drugs to prevent adverse reactions while maintaining anticancer efficacy.

Money

Credit: Petr Kratochvil

New research suggests the low-molecular-weight heparin (LMWH) dalteparin is more cost-effective than unfractionated heparin (UFH) for preventing venous thromboembolism (VTE) in critically ill patients.

The study showed that using dalteparin was the most effective and least costly strategy to prevent all thrombotic events, pulmonary embolism (PE), deep-vein thrombosis (DVT), major bleeding, and heparin-induced thrombocytopenia (HIT).

These results were published in JAMA and presented at the Critical Care Canada Forum in Toronto.

For this study, Robert A. Fowler, MDCM, of the Sunnybrook Health Sciences Centre at the University of Toronto in Ontario, and his colleagues conducted an economic evaluation concurrent with the PROTECT trial.

For PROTECT, researchers compared the effectiveness of dalteparin and UFH as VTE prophylaxis in critically ill patients. The results revealed no difference in the rate of DVT between the two treatment groups, but patients who received dalteparin had lower rates of PE and HIT.

To evaluate the cost-effectiveness of LMWH and UFH, Dr Fowler and his colleagues assessed costs among 2344 patients enrolled on PROTECT. The team evaluated costs in the context of resource use and patient outcomes.

The median post-randomization hospital cost of care was greater for patients who received UFH than for those who received dalteparin—$40,805 vs $39,508—but the difference was not statistically significant (P=0.41).

Subgroup analyses (assessing patients according to such factors as illness severity and body mass index) indicated that dalteparin was the most effective and least costly strategy to prevent all thrombotic events, PE, DVT, major bleeding, and HIT.

Sensitivity analyses indicated that a strategy using LMWH was most effective, least costly 78% of the time, and would remain less costly unless the drug acquisition cost of dalteparin was to increase by more than 20-fold. There was no threshold in which lowering the acquisition cost of UFH favored VTE prophylaxis with UFH.

The researchers said these findings are important for the care of critically ill patients because they provide a cost-minimization rationale that complements clinical effectiveness knowledge from PROTECT.

For example, if an intensive care unit with 1000 medical-surgical admissions per year uses UFH instead of LMWH for VTE prophylaxis, the annual incremental cost would be between $1,000,000 and $1,500,000 with similar or worse clinical outcomes, despite the individual drug cost of UFH being $4 to $5 less per day.

The researchers noted that these findings were driven by lower rates of PE and HIT and the corresponding lower overall use of resources with LMWH.

Money

Credit: Petr Kratochvil

New research suggests the low-molecular-weight heparin (LMWH) dalteparin is more cost-effective than unfractionated heparin (UFH) for preventing venous thromboembolism (VTE) in critically ill patients.

The study showed that using dalteparin was the most effective and least costly strategy to prevent all thrombotic events, pulmonary embolism (PE), deep-vein thrombosis (DVT), major bleeding, and heparin-induced thrombocytopenia (HIT).

These results were published in JAMA and presented at the Critical Care Canada Forum in Toronto.

For this study, Robert A. Fowler, MDCM, of the Sunnybrook Health Sciences Centre at the University of Toronto in Ontario, and his colleagues conducted an economic evaluation concurrent with the PROTECT trial.

For PROTECT, researchers compared the effectiveness of dalteparin and UFH as VTE prophylaxis in critically ill patients. The results revealed no difference in the rate of DVT between the two treatment groups, but patients who received dalteparin had lower rates of PE and HIT.

To evaluate the cost-effectiveness of LMWH and UFH, Dr Fowler and his colleagues assessed costs among 2344 patients enrolled on PROTECT. The team evaluated costs in the context of resource use and patient outcomes.

The median post-randomization hospital cost of care was greater for patients who received UFH than for those who received dalteparin—$40,805 vs $39,508—but the difference was not statistically significant (P=0.41).

Subgroup analyses (assessing patients according to such factors as illness severity and body mass index) indicated that dalteparin was the most effective and least costly strategy to prevent all thrombotic events, PE, DVT, major bleeding, and HIT.

Sensitivity analyses indicated that a strategy using LMWH was most effective, least costly 78% of the time, and would remain less costly unless the drug acquisition cost of dalteparin was to increase by more than 20-fold. There was no threshold in which lowering the acquisition cost of UFH favored VTE prophylaxis with UFH.

The researchers said these findings are important for the care of critically ill patients because they provide a cost-minimization rationale that complements clinical effectiveness knowledge from PROTECT.

For example, if an intensive care unit with 1000 medical-surgical admissions per year uses UFH instead of LMWH for VTE prophylaxis, the annual incremental cost would be between $1,000,000 and $1,500,000 with similar or worse clinical outcomes, despite the individual drug cost of UFH being $4 to $5 less per day.

The researchers noted that these findings were driven by lower rates of PE and HIT and the corresponding lower overall use of resources with LMWH.

Money

Credit: Petr Kratochvil

New research suggests the low-molecular-weight heparin (LMWH) dalteparin is more cost-effective than unfractionated heparin (UFH) for preventing venous thromboembolism (VTE) in critically ill patients.

The study showed that using dalteparin was the most effective and least costly strategy to prevent all thrombotic events, pulmonary embolism (PE), deep-vein thrombosis (DVT), major bleeding, and heparin-induced thrombocytopenia (HIT).

These results were published in JAMA and presented at the Critical Care Canada Forum in Toronto.

For this study, Robert A. Fowler, MDCM, of the Sunnybrook Health Sciences Centre at the University of Toronto in Ontario, and his colleagues conducted an economic evaluation concurrent with the PROTECT trial.

For PROTECT, researchers compared the effectiveness of dalteparin and UFH as VTE prophylaxis in critically ill patients. The results revealed no difference in the rate of DVT between the two treatment groups, but patients who received dalteparin had lower rates of PE and HIT.

To evaluate the cost-effectiveness of LMWH and UFH, Dr Fowler and his colleagues assessed costs among 2344 patients enrolled on PROTECT. The team evaluated costs in the context of resource use and patient outcomes.

The median post-randomization hospital cost of care was greater for patients who received UFH than for those who received dalteparin—$40,805 vs $39,508—but the difference was not statistically significant (P=0.41).

Subgroup analyses (assessing patients according to such factors as illness severity and body mass index) indicated that dalteparin was the most effective and least costly strategy to prevent all thrombotic events, PE, DVT, major bleeding, and HIT.

Sensitivity analyses indicated that a strategy using LMWH was most effective, least costly 78% of the time, and would remain less costly unless the drug acquisition cost of dalteparin was to increase by more than 20-fold. There was no threshold in which lowering the acquisition cost of UFH favored VTE prophylaxis with UFH.

The researchers said these findings are important for the care of critically ill patients because they provide a cost-minimization rationale that complements clinical effectiveness knowledge from PROTECT.

For example, if an intensive care unit with 1000 medical-surgical admissions per year uses UFH instead of LMWH for VTE prophylaxis, the annual incremental cost would be between $1,000,000 and $1,500,000 with similar or worse clinical outcomes, despite the individual drug cost of UFH being $4 to $5 less per day.

The researchers noted that these findings were driven by lower rates of PE and HIT and the corresponding lower overall use of resources with LMWH.

Thrombus

Credit: NHS

The UK’s National Institute for Health and Care Excellence (NICE) has issued a draft guidance recommending dabigatran etexilate (Pradaxa) as an option for treating and preventing recurrent deep-vein thrombosis (DVT) and pulmonary embolism (PE) in adults.

A committee advising NICE concluded that dabigatran is a cost-effective use of resources and a convenient alternative to warfarin, especially for patients who require longer-term anticoagulant therapy.

“For many people, using warfarin can be difficult because of the need for frequent tests to see if the blood is clotting properly and having to adjust the dose of the drug if it is not,” said Carole Longson, NICE Health Technology Evaluation Centre Director.

“The appraisal committee felt that dabigatran represents a potential benefit for many people who have had a DVT or PE, particularly those who have risk factors for recurrence of a blood clot and who therefore need longer-term treatment. We are pleased, therefore, to be able to recommend dabigatran as a cost-effective option for treating DVT and PE and preventing further episodes in adults.”

Dabigatran, made by Boehringer Ingelheim, costs £65.90 for a 60-capsule pack of the 150 mg or 110 mg doses (excluding value-added tax) and costs £2.20 per day of treatment. However, costs may vary in different settings because of negotiated procurement discounts.

The most plausible incremental cost-effectiveness ratio (ICER) for dabigatran compared with warfarin for acute treatment of venous thromboembolism (VTE) was uncertain.

However, both Boehringer Ingelheim’s ICER and an evidence review group’s ICER remained in the range that could be considered a cost-effective use of National Health Service resources. Both were under £20,000 per quality-adjusted life-year (QALY) gained.

Neither Boehringer Ingelheim nor the evidence review group found any significant difference in efficacy between dabigatran and rivaroxaban for acute treatment of VTE in their indirect comparisons, and the costs were very similar between these two treatments.

For combined treatment and secondary prevention of VTE, the committee noted that Boehringer Ingelheim’s base-case ICER for dabigatran compared with warfarin was likely too low (£9973 per QALY gained).

But the evidence review group’s base-case for dabigatran compared with warfarin may have overestimated the ICER (£35,786 per QALY gained). So the committee said the ICER probably falls somewhere between the two estimates.

The committee also noted that dabigatran and rivaroxaban appear to have similar efficacy for combined treatment and secondary prevention of VTE, and their costs are very similar.

For more details, see the draft guidance.

Thrombus

Credit: NHS

The UK’s National Institute for Health and Care Excellence (NICE) has issued a draft guidance recommending dabigatran etexilate (Pradaxa) as an option for treating and preventing recurrent deep-vein thrombosis (DVT) and pulmonary embolism (PE) in adults.

A committee advising NICE concluded that dabigatran is a cost-effective use of resources and a convenient alternative to warfarin, especially for patients who require longer-term anticoagulant therapy.

“For many people, using warfarin can be difficult because of the need for frequent tests to see if the blood is clotting properly and having to adjust the dose of the drug if it is not,” said Carole Longson, NICE Health Technology Evaluation Centre Director.

“The appraisal committee felt that dabigatran represents a potential benefit for many people who have had a DVT or PE, particularly those who have risk factors for recurrence of a blood clot and who therefore need longer-term treatment. We are pleased, therefore, to be able to recommend dabigatran as a cost-effective option for treating DVT and PE and preventing further episodes in adults.”

Dabigatran, made by Boehringer Ingelheim, costs £65.90 for a 60-capsule pack of the 150 mg or 110 mg doses (excluding value-added tax) and costs £2.20 per day of treatment. However, costs may vary in different settings because of negotiated procurement discounts.

The most plausible incremental cost-effectiveness ratio (ICER) for dabigatran compared with warfarin for acute treatment of venous thromboembolism (VTE) was uncertain.

However, both Boehringer Ingelheim’s ICER and an evidence review group’s ICER remained in the range that could be considered a cost-effective use of National Health Service resources. Both were under £20,000 per quality-adjusted life-year (QALY) gained.

Neither Boehringer Ingelheim nor the evidence review group found any significant difference in efficacy between dabigatran and rivaroxaban for acute treatment of VTE in their indirect comparisons, and the costs were very similar between these two treatments.

For combined treatment and secondary prevention of VTE, the committee noted that Boehringer Ingelheim’s base-case ICER for dabigatran compared with warfarin was likely too low (£9973 per QALY gained).

But the evidence review group’s base-case for dabigatran compared with warfarin may have overestimated the ICER (£35,786 per QALY gained). So the committee said the ICER probably falls somewhere between the two estimates.

The committee also noted that dabigatran and rivaroxaban appear to have similar efficacy for combined treatment and secondary prevention of VTE, and their costs are very similar.

For more details, see the draft guidance.

Thrombus

Credit: NHS

The UK’s National Institute for Health and Care Excellence (NICE) has issued a draft guidance recommending dabigatran etexilate (Pradaxa) as an option for treating and preventing recurrent deep-vein thrombosis (DVT) and pulmonary embolism (PE) in adults.

A committee advising NICE concluded that dabigatran is a cost-effective use of resources and a convenient alternative to warfarin, especially for patients who require longer-term anticoagulant therapy.

“For many people, using warfarin can be difficult because of the need for frequent tests to see if the blood is clotting properly and having to adjust the dose of the drug if it is not,” said Carole Longson, NICE Health Technology Evaluation Centre Director.

“The appraisal committee felt that dabigatran represents a potential benefit for many people who have had a DVT or PE, particularly those who have risk factors for recurrence of a blood clot and who therefore need longer-term treatment. We are pleased, therefore, to be able to recommend dabigatran as a cost-effective option for treating DVT and PE and preventing further episodes in adults.”

Dabigatran, made by Boehringer Ingelheim, costs £65.90 for a 60-capsule pack of the 150 mg or 110 mg doses (excluding value-added tax) and costs £2.20 per day of treatment. However, costs may vary in different settings because of negotiated procurement discounts.

The most plausible incremental cost-effectiveness ratio (ICER) for dabigatran compared with warfarin for acute treatment of venous thromboembolism (VTE) was uncertain.

However, both Boehringer Ingelheim’s ICER and an evidence review group’s ICER remained in the range that could be considered a cost-effective use of National Health Service resources. Both were under £20,000 per quality-adjusted life-year (QALY) gained.

Neither Boehringer Ingelheim nor the evidence review group found any significant difference in efficacy between dabigatran and rivaroxaban for acute treatment of VTE in their indirect comparisons, and the costs were very similar between these two treatments.

For combined treatment and secondary prevention of VTE, the committee noted that Boehringer Ingelheim’s base-case ICER for dabigatran compared with warfarin was likely too low (£9973 per QALY gained).

But the evidence review group’s base-case for dabigatran compared with warfarin may have overestimated the ICER (£35,786 per QALY gained). So the committee said the ICER probably falls somewhere between the two estimates.

The committee also noted that dabigatran and rivaroxaban appear to have similar efficacy for combined treatment and secondary prevention of VTE, and their costs are very similar.

For more details, see the draft guidance.

Infectious diseases have been common topics in the news these past 2 months. Enterovirus EV-D68 and Ebola were the focus of sessions and plenary talks at this year’s American Academy of Pediatrics National Conference and Exposition. The new respiratory syncytial virus prophylaxis guidelines for this winter markedly narrowed the recommended recipient population (Pediatrics 2014;134:415-20). The revision of the 2006 bronchiolitis care guideline was released (Pediatrics 2014 [doi: 10.1542/peds.2014-2742]). And there has been an indictment in an alleged fraud involving HIV vaccine research.

As a moderator of a Listserv for pediatric hospitalists, I am interested in both the content of these discussions and the process by which they occur. Pediatric hospitalists could grouse a bit about the Centers for Disease Control and Prevention (CDC) being a few days slow in disseminating information about the EV-D68 epidemic, but we had no reason to doubt the veracity of that information. Our Listserv had posts from pediatric hospitalists in various cities. We discussed the utility of diagnostic tests; the treatment options and their effectiveness compared with other cases of bronchiolitis; and the impact on emergency department and inpatient census. When the virus 2 weeks later was tenuously associated with a rare paralytic syndrome, the Listserv activity peaked again.

Public reaction to Ebola seems to be at the other extreme. The contagion to two nurses and exposure of a lab supervisor at a Dallas hospital have expanded to impact hundreds of airline passengers and cruise ship passengers. Governors in New York and New Jersey took actions to increase monitoring at airports and establish quarantines. Now Maine is involved. Those actions did not always agree with the suggestions of the CDC. Between the Department of Veterans Affairs scandal, the CDC mishandling of small pox and anthrax in its labs, Wikileaks, and celebrities dissing vaccines, the general public’s trust in health information provided by the U.S. government must be near an all-time low just when credibility is needed most.

Does this sound familiar? George Santayana said, “Those who cannot remember the past are condemned to repeat it.” AIDS in 1981 was a new, lethal contagious disease without an effective treatment. Five cases of unusual pneumonia reported in 1981 have become a million people living with the infection. There were fear, stigmatization, recriminations, political posturing, and many deaths. In response, patient isolation practices changed dramatically. A massive research program ensued that has failed to find a vaccine or cure for HIV, but has developed an expensive ongoing treatment regimen that controls the disease in most people who can afford it. That has left out most people in Africa.

The United States now has an Ebola czar. Ron Klain has no experience with tropical infectious diseases. He was selected because he knows how things get done in Washington, D.C. I don’t see him becoming another C. Everett Koop, credible and comforting. For that status, the New York Times was impressed with the local version of that official.

“People need to feel like they are being given information, that things aren’t being kept from them, that they are being apprised of what’s known, and that we’re being honest. ...”

“Fear is a powerful thing,” she added, “and it’s often not rational. That’s when reliance on science and fact really has to be our North Star.” –Dr. Mary Travis Bassett, New York City Health Commissioner

On the spectrum between these two experiences with EV-D68 and Ebola lie the battles over respiratory syncytial virus prophylaxis and treatment. At the AAP National Conference and Exposition session discussing the 2014 palivizumab recommendations, there was great attention paid to having speakers from the audience identify any conflicts of interest they might have. The new guideline on caring for infants with bronchiolitis has emphasized the methodology of evidence-based medicine. Both these approaches (conflicts of interest and evidence-based medicine) are recent tools in the quest for truth and credibility.

Jack Nicholson said, “You can’t handle the truth!” Woodward and Bernstein, the investigative reporters of Watergate, recently eulogized their editor Ben Bradlee with “His one unbending principle was the quest for the truth and the necessity of that pursuit.”

I can’t add anything at this time to the search for truth in dealing with Ebola and what sort of quarantine policies should be in place. The credibility problem is in the hands of politicos. The balancing of communal safety and individual rights is in the hands of judges. But whatever choices are made, medical ethics requires that they be implemented with respect and with compassion, which includes WiFi access. That is in the hands of nurses and doctors. So I will close with a quote from a meditation written nearly 400 years ago by John Donne, an English poet and cleric, during his own 3-week battle with a near-fatal illness.

“No man is an island, entire of itself; ... any man’s death diminishes me, ... therefore never send to know for whom the bell tolls; it tolls for thee.”

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Dr. Powell said he had no relevant financial disclosures. E-mail him at [email protected].

Infectious diseases have been common topics in the news these past 2 months. Enterovirus EV-D68 and Ebola were the focus of sessions and plenary talks at this year’s American Academy of Pediatrics National Conference and Exposition. The new respiratory syncytial virus prophylaxis guidelines for this winter markedly narrowed the recommended recipient population (Pediatrics 2014;134:415-20). The revision of the 2006 bronchiolitis care guideline was released (Pediatrics 2014 [doi: 10.1542/peds.2014-2742]). And there has been an indictment in an alleged fraud involving HIV vaccine research.

As a moderator of a Listserv for pediatric hospitalists, I am interested in both the content of these discussions and the process by which they occur. Pediatric hospitalists could grouse a bit about the Centers for Disease Control and Prevention (CDC) being a few days slow in disseminating information about the EV-D68 epidemic, but we had no reason to doubt the veracity of that information. Our Listserv had posts from pediatric hospitalists in various cities. We discussed the utility of diagnostic tests; the treatment options and their effectiveness compared with other cases of bronchiolitis; and the impact on emergency department and inpatient census. When the virus 2 weeks later was tenuously associated with a rare paralytic syndrome, the Listserv activity peaked again.

Public reaction to Ebola seems to be at the other extreme. The contagion to two nurses and exposure of a lab supervisor at a Dallas hospital have expanded to impact hundreds of airline passengers and cruise ship passengers. Governors in New York and New Jersey took actions to increase monitoring at airports and establish quarantines. Now Maine is involved. Those actions did not always agree with the suggestions of the CDC. Between the Department of Veterans Affairs scandal, the CDC mishandling of small pox and anthrax in its labs, Wikileaks, and celebrities dissing vaccines, the general public’s trust in health information provided by the U.S. government must be near an all-time low just when credibility is needed most.

Does this sound familiar? George Santayana said, “Those who cannot remember the past are condemned to repeat it.” AIDS in 1981 was a new, lethal contagious disease without an effective treatment. Five cases of unusual pneumonia reported in 1981 have become a million people living with the infection. There were fear, stigmatization, recriminations, political posturing, and many deaths. In response, patient isolation practices changed dramatically. A massive research program ensued that has failed to find a vaccine or cure for HIV, but has developed an expensive ongoing treatment regimen that controls the disease in most people who can afford it. That has left out most people in Africa.

The United States now has an Ebola czar. Ron Klain has no experience with tropical infectious diseases. He was selected because he knows how things get done in Washington, D.C. I don’t see him becoming another C. Everett Koop, credible and comforting. For that status, the New York Times was impressed with the local version of that official.

“People need to feel like they are being given information, that things aren’t being kept from them, that they are being apprised of what’s known, and that we’re being honest. ...”

“Fear is a powerful thing,” she added, “and it’s often not rational. That’s when reliance on science and fact really has to be our North Star.” –Dr. Mary Travis Bassett, New York City Health Commissioner

On the spectrum between these two experiences with EV-D68 and Ebola lie the battles over respiratory syncytial virus prophylaxis and treatment. At the AAP National Conference and Exposition session discussing the 2014 palivizumab recommendations, there was great attention paid to having speakers from the audience identify any conflicts of interest they might have. The new guideline on caring for infants with bronchiolitis has emphasized the methodology of evidence-based medicine. Both these approaches (conflicts of interest and evidence-based medicine) are recent tools in the quest for truth and credibility.

Jack Nicholson said, “You can’t handle the truth!” Woodward and Bernstein, the investigative reporters of Watergate, recently eulogized their editor Ben Bradlee with “His one unbending principle was the quest for the truth and the necessity of that pursuit.”

I can’t add anything at this time to the search for truth in dealing with Ebola and what sort of quarantine policies should be in place. The credibility problem is in the hands of politicos. The balancing of communal safety and individual rights is in the hands of judges. But whatever choices are made, medical ethics requires that they be implemented with respect and with compassion, which includes WiFi access. That is in the hands of nurses and doctors. So I will close with a quote from a meditation written nearly 400 years ago by John Donne, an English poet and cleric, during his own 3-week battle with a near-fatal illness.

“No man is an island, entire of itself; ... any man’s death diminishes me, ... therefore never send to know for whom the bell tolls; it tolls for thee.”

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Dr. Powell said he had no relevant financial disclosures. E-mail him at [email protected].

Infectious diseases have been common topics in the news these past 2 months. Enterovirus EV-D68 and Ebola were the focus of sessions and plenary talks at this year’s American Academy of Pediatrics National Conference and Exposition. The new respiratory syncytial virus prophylaxis guidelines for this winter markedly narrowed the recommended recipient population (Pediatrics 2014;134:415-20). The revision of the 2006 bronchiolitis care guideline was released (Pediatrics 2014 [doi: 10.1542/peds.2014-2742]). And there has been an indictment in an alleged fraud involving HIV vaccine research.

As a moderator of a Listserv for pediatric hospitalists, I am interested in both the content of these discussions and the process by which they occur. Pediatric hospitalists could grouse a bit about the Centers for Disease Control and Prevention (CDC) being a few days slow in disseminating information about the EV-D68 epidemic, but we had no reason to doubt the veracity of that information. Our Listserv had posts from pediatric hospitalists in various cities. We discussed the utility of diagnostic tests; the treatment options and their effectiveness compared with other cases of bronchiolitis; and the impact on emergency department and inpatient census. When the virus 2 weeks later was tenuously associated with a rare paralytic syndrome, the Listserv activity peaked again.

Public reaction to Ebola seems to be at the other extreme. The contagion to two nurses and exposure of a lab supervisor at a Dallas hospital have expanded to impact hundreds of airline passengers and cruise ship passengers. Governors in New York and New Jersey took actions to increase monitoring at airports and establish quarantines. Now Maine is involved. Those actions did not always agree with the suggestions of the CDC. Between the Department of Veterans Affairs scandal, the CDC mishandling of small pox and anthrax in its labs, Wikileaks, and celebrities dissing vaccines, the general public’s trust in health information provided by the U.S. government must be near an all-time low just when credibility is needed most.

Does this sound familiar? George Santayana said, “Those who cannot remember the past are condemned to repeat it.” AIDS in 1981 was a new, lethal contagious disease without an effective treatment. Five cases of unusual pneumonia reported in 1981 have become a million people living with the infection. There were fear, stigmatization, recriminations, political posturing, and many deaths. In response, patient isolation practices changed dramatically. A massive research program ensued that has failed to find a vaccine or cure for HIV, but has developed an expensive ongoing treatment regimen that controls the disease in most people who can afford it. That has left out most people in Africa.

The United States now has an Ebola czar. Ron Klain has no experience with tropical infectious diseases. He was selected because he knows how things get done in Washington, D.C. I don’t see him becoming another C. Everett Koop, credible and comforting. For that status, the New York Times was impressed with the local version of that official.

“People need to feel like they are being given information, that things aren’t being kept from them, that they are being apprised of what’s known, and that we’re being honest. ...”

“Fear is a powerful thing,” she added, “and it’s often not rational. That’s when reliance on science and fact really has to be our North Star.” –Dr. Mary Travis Bassett, New York City Health Commissioner

On the spectrum between these two experiences with EV-D68 and Ebola lie the battles over respiratory syncytial virus prophylaxis and treatment. At the AAP National Conference and Exposition session discussing the 2014 palivizumab recommendations, there was great attention paid to having speakers from the audience identify any conflicts of interest they might have. The new guideline on caring for infants with bronchiolitis has emphasized the methodology of evidence-based medicine. Both these approaches (conflicts of interest and evidence-based medicine) are recent tools in the quest for truth and credibility.

Jack Nicholson said, “You can’t handle the truth!” Woodward and Bernstein, the investigative reporters of Watergate, recently eulogized their editor Ben Bradlee with “His one unbending principle was the quest for the truth and the necessity of that pursuit.”

I can’t add anything at this time to the search for truth in dealing with Ebola and what sort of quarantine policies should be in place. The credibility problem is in the hands of politicos. The balancing of communal safety and individual rights is in the hands of judges. But whatever choices are made, medical ethics requires that they be implemented with respect and with compassion, which includes WiFi access. That is in the hands of nurses and doctors. So I will close with a quote from a meditation written nearly 400 years ago by John Donne, an English poet and cleric, during his own 3-week battle with a near-fatal illness.

“No man is an island, entire of itself; ... any man’s death diminishes me, ... therefore never send to know for whom the bell tolls; it tolls for thee.”

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Dr. Powell said he had no relevant financial disclosures. E-mail him at [email protected].

Atrial fibrillation is associated with a more than twofold increase in the risk of silent cerebral infarctions, even in patients with no history of symptomatic stroke, a systematic review and meta-analysis has found.

The analysis of 11 studies involving 5,317 adults with atrial fibrillation (AF) but no history of stroke or prosthetic valves showed a significant increase in the risk of silent cerebral infarctions (odds ratio, 2.62), independent of whether their atrial fibrillation was paroxysmal or persistent, according to meta-analysis published online Nov. 3 in the Annals of Internal Medicine [doi:10.7326/M14-0538].

“Although SCIs [silent cerebral infarctions] do not present with acute stroke symptoms, they have been reported to be associated with more than three- and twofold increases in the risk for symptomatic stroke and dementia, respectively,” wrote Dr. Shadi Kalantarian and colleagues from the Institute for Heart Vascular and Stroke Care and Massachusetts General Hospital.

“Consequently, the higher prevalence of SCI in patients with AF may put this population at a greater risk for cognitive impairment, future stroke, and disability.”

The study was funded by the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, Massachusetts General Hospital, and the Harvard Catalyst and the Harvard Clinical and Translational Science Center. Two authors declared grants and personal fees from private industry.

Atrial fibrillation is associated with a more than twofold increase in the risk of silent cerebral infarctions, even in patients with no history of symptomatic stroke, a systematic review and meta-analysis has found.

The analysis of 11 studies involving 5,317 adults with atrial fibrillation (AF) but no history of stroke or prosthetic valves showed a significant increase in the risk of silent cerebral infarctions (odds ratio, 2.62), independent of whether their atrial fibrillation was paroxysmal or persistent, according to meta-analysis published online Nov. 3 in the Annals of Internal Medicine [doi:10.7326/M14-0538].

“Although SCIs [silent cerebral infarctions] do not present with acute stroke symptoms, they have been reported to be associated with more than three- and twofold increases in the risk for symptomatic stroke and dementia, respectively,” wrote Dr. Shadi Kalantarian and colleagues from the Institute for Heart Vascular and Stroke Care and Massachusetts General Hospital.

“Consequently, the higher prevalence of SCI in patients with AF may put this population at a greater risk for cognitive impairment, future stroke, and disability.”

The study was funded by the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, Massachusetts General Hospital, and the Harvard Catalyst and the Harvard Clinical and Translational Science Center. Two authors declared grants and personal fees from private industry.

Atrial fibrillation is associated with a more than twofold increase in the risk of silent cerebral infarctions, even in patients with no history of symptomatic stroke, a systematic review and meta-analysis has found.

The analysis of 11 studies involving 5,317 adults with atrial fibrillation (AF) but no history of stroke or prosthetic valves showed a significant increase in the risk of silent cerebral infarctions (odds ratio, 2.62), independent of whether their atrial fibrillation was paroxysmal or persistent, according to meta-analysis published online Nov. 3 in the Annals of Internal Medicine [doi:10.7326/M14-0538].

“Although SCIs [silent cerebral infarctions] do not present with acute stroke symptoms, they have been reported to be associated with more than three- and twofold increases in the risk for symptomatic stroke and dementia, respectively,” wrote Dr. Shadi Kalantarian and colleagues from the Institute for Heart Vascular and Stroke Care and Massachusetts General Hospital.

“Consequently, the higher prevalence of SCI in patients with AF may put this population at a greater risk for cognitive impairment, future stroke, and disability.”

The study was funded by the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, Massachusetts General Hospital, and the Harvard Catalyst and the Harvard Clinical and Translational Science Center. Two authors declared grants and personal fees from private industry.

Dabigatran significantly raises the risk of major bleeding and gastrointestinal bleeding across all subgroups of patients with atrial fibrillation, and particularly in African Americans and patients with chronic kidney disease, according to a report published online Nov. 3 in JAMA Internal Medicine.

Physicians should only prescribe dabigatran with caution, and should fully explain to patients who do take the drug how to identify abnormal bleeding so that it can be detected and controlled as early as possible, said Inmaculada Hernandez, Pharm.D., of the department of health policy and management, University of Pittsburgh, and her associates.

The FDA approved dabigatran in 2010 via an accelerated pathway after only 6 months of review, based largely on findings from a single clinical study, the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, which did not adjust for patient characteristics (N. Engl. J. Med. 2009;361:1139-51). That study reported lower bleeding risks with dabigatran than with warfarin. Several months later, the agency’s Adverse Event Reporting System received “a large number” of reports of severe bleeding associated with dabigatran; and the relative bleeding risk associated with the two drugs is still unclear.

Dr. Hernandez and her colleagues examined the issue using data from a nationally representative random sample of 9,404 Medicare beneficiaries newly diagnosed as having nonvalvular atrial fibrillation during a 1-year period and treated in real-world practice. A total of 1,302 patients were given dabigatran and 8,102 were given warfarin to prevent stroke and systemic embolism. They were followed for a median of about 200 days, until discontinuing or switching their anticoagulant, dying, or reaching the study’s cutoff date. Nine categories of bleeding were assessed, and the data were adjusted to account for numerous demographic and clinical characteristics known to affect bleeding risk.

Compared with warfarin, dabigatran was associated with a significantly higher risk of major bleeding (9.0% vs 5.9%), with a hazard ratio of 1.58. Dabigatran also was associated with a significantly higher risk of GI bleeding (HR, 1.85), hematuria (HR, 1.41), vaginal bleeding (HR, 2.27), hemarthrosis (HR, 2.78), and hemoptysis (HR, 1.49). In contrast, dabigatran was associated with a slightly lower (0.6%) rate of intracranial bleeding, and also with lower rates of epistaxis and nonspecified bleeding, the investigators reported (JAMA Intern. Med. 2014 Nov. 3 [doi: 10.1001/jamainternmed.2014.5398]).

These differences were consistent across numerous subgroups of patients assessed, and were especially strong among African Americans and patients with chronic kidney disease.

This study was supported by the Commonwealth Foundation and the U.S. Agency for Healthcare Research and Quality. Dr. Hernandez and her associates reported having no financial conflicts of interest.

Dabigatran significantly raises the risk of major bleeding and gastrointestinal bleeding across all subgroups of patients with atrial fibrillation, and particularly in African Americans and patients with chronic kidney disease, according to a report published online Nov. 3 in JAMA Internal Medicine.

Physicians should only prescribe dabigatran with caution, and should fully explain to patients who do take the drug how to identify abnormal bleeding so that it can be detected and controlled as early as possible, said Inmaculada Hernandez, Pharm.D., of the department of health policy and management, University of Pittsburgh, and her associates.

The FDA approved dabigatran in 2010 via an accelerated pathway after only 6 months of review, based largely on findings from a single clinical study, the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, which did not adjust for patient characteristics (N. Engl. J. Med. 2009;361:1139-51). That study reported lower bleeding risks with dabigatran than with warfarin. Several months later, the agency’s Adverse Event Reporting System received “a large number” of reports of severe bleeding associated with dabigatran; and the relative bleeding risk associated with the two drugs is still unclear.

Dr. Hernandez and her colleagues examined the issue using data from a nationally representative random sample of 9,404 Medicare beneficiaries newly diagnosed as having nonvalvular atrial fibrillation during a 1-year period and treated in real-world practice. A total of 1,302 patients were given dabigatran and 8,102 were given warfarin to prevent stroke and systemic embolism. They were followed for a median of about 200 days, until discontinuing or switching their anticoagulant, dying, or reaching the study’s cutoff date. Nine categories of bleeding were assessed, and the data were adjusted to account for numerous demographic and clinical characteristics known to affect bleeding risk.

Compared with warfarin, dabigatran was associated with a significantly higher risk of major bleeding (9.0% vs 5.9%), with a hazard ratio of 1.58. Dabigatran also was associated with a significantly higher risk of GI bleeding (HR, 1.85), hematuria (HR, 1.41), vaginal bleeding (HR, 2.27), hemarthrosis (HR, 2.78), and hemoptysis (HR, 1.49). In contrast, dabigatran was associated with a slightly lower (0.6%) rate of intracranial bleeding, and also with lower rates of epistaxis and nonspecified bleeding, the investigators reported (JAMA Intern. Med. 2014 Nov. 3 [doi: 10.1001/jamainternmed.2014.5398]).

These differences were consistent across numerous subgroups of patients assessed, and were especially strong among African Americans and patients with chronic kidney disease.

This study was supported by the Commonwealth Foundation and the U.S. Agency for Healthcare Research and Quality. Dr. Hernandez and her associates reported having no financial conflicts of interest.

Dabigatran significantly raises the risk of major bleeding and gastrointestinal bleeding across all subgroups of patients with atrial fibrillation, and particularly in African Americans and patients with chronic kidney disease, according to a report published online Nov. 3 in JAMA Internal Medicine.

Physicians should only prescribe dabigatran with caution, and should fully explain to patients who do take the drug how to identify abnormal bleeding so that it can be detected and controlled as early as possible, said Inmaculada Hernandez, Pharm.D., of the department of health policy and management, University of Pittsburgh, and her associates.

The FDA approved dabigatran in 2010 via an accelerated pathway after only 6 months of review, based largely on findings from a single clinical study, the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, which did not adjust for patient characteristics (N. Engl. J. Med. 2009;361:1139-51). That study reported lower bleeding risks with dabigatran than with warfarin. Several months later, the agency’s Adverse Event Reporting System received “a large number” of reports of severe bleeding associated with dabigatran; and the relative bleeding risk associated with the two drugs is still unclear.

Dr. Hernandez and her colleagues examined the issue using data from a nationally representative random sample of 9,404 Medicare beneficiaries newly diagnosed as having nonvalvular atrial fibrillation during a 1-year period and treated in real-world practice. A total of 1,302 patients were given dabigatran and 8,102 were given warfarin to prevent stroke and systemic embolism. They were followed for a median of about 200 days, until discontinuing or switching their anticoagulant, dying, or reaching the study’s cutoff date. Nine categories of bleeding were assessed, and the data were adjusted to account for numerous demographic and clinical characteristics known to affect bleeding risk.

Compared with warfarin, dabigatran was associated with a significantly higher risk of major bleeding (9.0% vs 5.9%), with a hazard ratio of 1.58. Dabigatran also was associated with a significantly higher risk of GI bleeding (HR, 1.85), hematuria (HR, 1.41), vaginal bleeding (HR, 2.27), hemarthrosis (HR, 2.78), and hemoptysis (HR, 1.49). In contrast, dabigatran was associated with a slightly lower (0.6%) rate of intracranial bleeding, and also with lower rates of epistaxis and nonspecified bleeding, the investigators reported (JAMA Intern. Med. 2014 Nov. 3 [doi: 10.1001/jamainternmed.2014.5398]).

These differences were consistent across numerous subgroups of patients assessed, and were especially strong among African Americans and patients with chronic kidney disease.

This study was supported by the Commonwealth Foundation and the U.S. Agency for Healthcare Research and Quality. Dr. Hernandez and her associates reported having no financial conflicts of interest.

When administered as a nasal spray, t-PA may improve functional recovery in patients with less severe forms of traumatic brain injury (TBI), according to a study published September 3 in PLoS One.

Seven days after laboratory rats withstood TBI, investigators treated them intranasally with saline or t-PA. Compared with saline treatment, subacute intranasal t-PA treatment significantly improved the animals’ cognitive and sensorimotor functional recovery, reduced the cortical stimulation threshold evoking ipsilateral forelimb movement, enhanced neurogenesis in the dentate gyrus and axonal sprouting of the corticospinal tract originating from the contralesional cortex into the denervated side of the cervical gray matter, and increased the level of mature brain-derived neurotrophic factor.

“Using this novel procedure in our earlier stroke studies, we found significant improvement in neurologic function,” said Michael Chopp, PhD, Scientific Director of the Henry Ford Neuroscience Institute in Detroit. “We essentially repeated the experiment on laboratory rats with subacute TBI with similarly remarkable results. As in stroke treated intranasally with t-PA, our subjects showed greatly improved functional outcome and rewiring of the cortical spinal tract.”

Although the damage resulting from stroke can be reduced if t-PA is administered intravenously within 4.5 hours, IV t-PA also has potentially harmful side effects, including swelling of the brain and hemorrhage. Researchers at Henry Ford Hospital found that the effective treatment window could be extended to as long as two weeks for laboratory rats dosed with t-PA in a nasal spray, which avoids the harmful side effects of IV injection.

Previous research has indicated that drugs administered through the nose directly target the brain and spinal cord, although researchers do not yet fully understand how this targeting occurs. Although the new study offers hope that a drug treatment will emerge, no effective pharmacologic therapy is available yet.

These most recent findings suggest that t-PA has the potential to be a noninvasive treatment for subacute TBI, thus helping the brain restore function to damaged cells. The investigators noted that further animal studies will be required to determine the best dose and the appropriate time window for optimal intranasal treatment.

When administered as a nasal spray, t-PA may improve functional recovery in patients with less severe forms of traumatic brain injury (TBI), according to a study published September 3 in PLoS One.

Seven days after laboratory rats withstood TBI, investigators treated them intranasally with saline or t-PA. Compared with saline treatment, subacute intranasal t-PA treatment significantly improved the animals’ cognitive and sensorimotor functional recovery, reduced the cortical stimulation threshold evoking ipsilateral forelimb movement, enhanced neurogenesis in the dentate gyrus and axonal sprouting of the corticospinal tract originating from the contralesional cortex into the denervated side of the cervical gray matter, and increased the level of mature brain-derived neurotrophic factor.

“Using this novel procedure in our earlier stroke studies, we found significant improvement in neurologic function,” said Michael Chopp, PhD, Scientific Director of the Henry Ford Neuroscience Institute in Detroit. “We essentially repeated the experiment on laboratory rats with subacute TBI with similarly remarkable results. As in stroke treated intranasally with t-PA, our subjects showed greatly improved functional outcome and rewiring of the cortical spinal tract.”

Although the damage resulting from stroke can be reduced if t-PA is administered intravenously within 4.5 hours, IV t-PA also has potentially harmful side effects, including swelling of the brain and hemorrhage. Researchers at Henry Ford Hospital found that the effective treatment window could be extended to as long as two weeks for laboratory rats dosed with t-PA in a nasal spray, which avoids the harmful side effects of IV injection.

Previous research has indicated that drugs administered through the nose directly target the brain and spinal cord, although researchers do not yet fully understand how this targeting occurs. Although the new study offers hope that a drug treatment will emerge, no effective pharmacologic therapy is available yet.

These most recent findings suggest that t-PA has the potential to be a noninvasive treatment for subacute TBI, thus helping the brain restore function to damaged cells. The investigators noted that further animal studies will be required to determine the best dose and the appropriate time window for optimal intranasal treatment.

When administered as a nasal spray, t-PA may improve functional recovery in patients with less severe forms of traumatic brain injury (TBI), according to a study published September 3 in PLoS One.

Seven days after laboratory rats withstood TBI, investigators treated them intranasally with saline or t-PA. Compared with saline treatment, subacute intranasal t-PA treatment significantly improved the animals’ cognitive and sensorimotor functional recovery, reduced the cortical stimulation threshold evoking ipsilateral forelimb movement, enhanced neurogenesis in the dentate gyrus and axonal sprouting of the corticospinal tract originating from the contralesional cortex into the denervated side of the cervical gray matter, and increased the level of mature brain-derived neurotrophic factor.

“Using this novel procedure in our earlier stroke studies, we found significant improvement in neurologic function,” said Michael Chopp, PhD, Scientific Director of the Henry Ford Neuroscience Institute in Detroit. “We essentially repeated the experiment on laboratory rats with subacute TBI with similarly remarkable results. As in stroke treated intranasally with t-PA, our subjects showed greatly improved functional outcome and rewiring of the cortical spinal tract.”

Although the damage resulting from stroke can be reduced if t-PA is administered intravenously within 4.5 hours, IV t-PA also has potentially harmful side effects, including swelling of the brain and hemorrhage. Researchers at Henry Ford Hospital found that the effective treatment window could be extended to as long as two weeks for laboratory rats dosed with t-PA in a nasal spray, which avoids the harmful side effects of IV injection.

Previous research has indicated that drugs administered through the nose directly target the brain and spinal cord, although researchers do not yet fully understand how this targeting occurs. Although the new study offers hope that a drug treatment will emerge, no effective pharmacologic therapy is available yet.

These most recent findings suggest that t-PA has the potential to be a noninvasive treatment for subacute TBI, thus helping the brain restore function to damaged cells. The investigators noted that further animal studies will be required to determine the best dose and the appropriate time window for optimal intranasal treatment.

Traumatic brain injury (TBI) appears to be associated with an increased risk of dementia in adults 55 and older, researchers reported online ahead of print October 27 in JAMA Neurology.

Controversy exists about whether there is a link between a single TBI and the risk of developing dementia. According to the CDC, Americans 55 and older account for more than 60% of all hospitalizations for TBI, with the highest rates of TBI-related emergency department visits, inpatient stays, and deaths happening among patients age 75 and older. Therefore, understanding the effects of a TBI and the development of dementia among middle-aged or older adults has important public health implications.

Raquel C. Gardner, MD, Clinical Instructor and Behavioral Neurology Fellow at the University of California, San Francisco, and colleagues examined the risk of dementia among adults age 55 and older with recent TBI, compared with adults with non-TBI body trauma (NTT), which was defined as fractures but not of the head or neck. The study included 164,661 patients identified in a statewide California administrative health database.

A total of 51,799 patients with trauma (31.5%) had TBI. Of those, 4,361 patients (8.4%) developed dementia, compared with 6,610 patients (5.9%) with NTT. The average time from trauma to dementia diagnosis was 3.2 years, and it was shorter in the TBI group, compared with the NTT group (3.1 vs 3.3 years). Moderate to severe TBI was associated with increased risk of dementia in persons age 55 or older, and mild TBI at age 65 or older increased the dementia risk.

“Whether a person with TBI recovers cognitively or develops dementia, however, is likely dependent on multiple additional risk and protective factors, ranging from genetics and medical comorbidities to environmental exposures and specific characteristics of the TBI itself,” the authors noted.

In a related editorial, Steven T. DeKosky, MD, Professor and Chair, Department of Neurology, University of Pittsburgh School of Medicine, stated that “Judicious use of data by skilled researchers who are familiar with the entire range of dementia research from pathobiology to health care needs will enable us to ask important questions, evolve new or more informed queries, and both lead and complement the translational questions that are before us. Dementia is both a global problem and a pathological conundrum; thus, the complementary use of big data and basic neuroscience analyses offers the most promise.”

Traumatic brain injury (TBI) appears to be associated with an increased risk of dementia in adults 55 and older, researchers reported online ahead of print October 27 in JAMA Neurology.

Controversy exists about whether there is a link between a single TBI and the risk of developing dementia. According to the CDC, Americans 55 and older account for more than 60% of all hospitalizations for TBI, with the highest rates of TBI-related emergency department visits, inpatient stays, and deaths happening among patients age 75 and older. Therefore, understanding the effects of a TBI and the development of dementia among middle-aged or older adults has important public health implications.

Raquel C. Gardner, MD, Clinical Instructor and Behavioral Neurology Fellow at the University of California, San Francisco, and colleagues examined the risk of dementia among adults age 55 and older with recent TBI, compared with adults with non-TBI body trauma (NTT), which was defined as fractures but not of the head or neck. The study included 164,661 patients identified in a statewide California administrative health database.

A total of 51,799 patients with trauma (31.5%) had TBI. Of those, 4,361 patients (8.4%) developed dementia, compared with 6,610 patients (5.9%) with NTT. The average time from trauma to dementia diagnosis was 3.2 years, and it was shorter in the TBI group, compared with the NTT group (3.1 vs 3.3 years). Moderate to severe TBI was associated with increased risk of dementia in persons age 55 or older, and mild TBI at age 65 or older increased the dementia risk.

“Whether a person with TBI recovers cognitively or develops dementia, however, is likely dependent on multiple additional risk and protective factors, ranging from genetics and medical comorbidities to environmental exposures and specific characteristics of the TBI itself,” the authors noted.

In a related editorial, Steven T. DeKosky, MD, Professor and Chair, Department of Neurology, University of Pittsburgh School of Medicine, stated that “Judicious use of data by skilled researchers who are familiar with the entire range of dementia research from pathobiology to health care needs will enable us to ask important questions, evolve new or more informed queries, and both lead and complement the translational questions that are before us. Dementia is both a global problem and a pathological conundrum; thus, the complementary use of big data and basic neuroscience analyses offers the most promise.”

Traumatic brain injury (TBI) appears to be associated with an increased risk of dementia in adults 55 and older, researchers reported online ahead of print October 27 in JAMA Neurology.

Controversy exists about whether there is a link between a single TBI and the risk of developing dementia. According to the CDC, Americans 55 and older account for more than 60% of all hospitalizations for TBI, with the highest rates of TBI-related emergency department visits, inpatient stays, and deaths happening among patients age 75 and older. Therefore, understanding the effects of a TBI and the development of dementia among middle-aged or older adults has important public health implications.

Raquel C. Gardner, MD, Clinical Instructor and Behavioral Neurology Fellow at the University of California, San Francisco, and colleagues examined the risk of dementia among adults age 55 and older with recent TBI, compared with adults with non-TBI body trauma (NTT), which was defined as fractures but not of the head or neck. The study included 164,661 patients identified in a statewide California administrative health database.

A total of 51,799 patients with trauma (31.5%) had TBI. Of those, 4,361 patients (8.4%) developed dementia, compared with 6,610 patients (5.9%) with NTT. The average time from trauma to dementia diagnosis was 3.2 years, and it was shorter in the TBI group, compared with the NTT group (3.1 vs 3.3 years). Moderate to severe TBI was associated with increased risk of dementia in persons age 55 or older, and mild TBI at age 65 or older increased the dementia risk.

“Whether a person with TBI recovers cognitively or develops dementia, however, is likely dependent on multiple additional risk and protective factors, ranging from genetics and medical comorbidities to environmental exposures and specific characteristics of the TBI itself,” the authors noted.

In a related editorial, Steven T. DeKosky, MD, Professor and Chair, Department of Neurology, University of Pittsburgh School of Medicine, stated that “Judicious use of data by skilled researchers who are familiar with the entire range of dementia research from pathobiology to health care needs will enable us to ask important questions, evolve new or more informed queries, and both lead and complement the translational questions that are before us. Dementia is both a global problem and a pathological conundrum; thus, the complementary use of big data and basic neuroscience analyses offers the most promise.”

Sulforaphane, a chemical derived from broccoli sprouts, may ease classic behavioral symptoms in patients with autism spectrum disorders (ASDs), according to a study published online ahead of print October 13 in the Proceedings of the National Academy of Sciences.

The study involved 40 males, ages 13 to 27, with moderate to severe autism. Many participants who received a daily dose of sulforaphane experienced substantial improvements in their social interaction and verbal communication, along with decreases in repetitive, ritualistic behaviors, compared with those who received a placebo, according to the researchers.

“We believe that this may be preliminary evidence for the first treatment for autism that improves symptoms by apparently correcting some of the underlying cellular problems,” said Paul Talalay, MD, Professor of Pharmacology and Molecular Sciences at Johns Hopkins University in Baltimore.

“We are far from being able to declare a victory over autism, but this gives us important insights into what might help,” said coinvestigator Andrew Zimmerman, MD, Professor of Pediatric Neurology at UMass Memorial Medical Center in Worcester.

Cause of Autism Is Elusive
Researchers estimate that ASD affects 1% to 2% of the world’s population, with a much higher incidence in boys than in girls. Its behavioral symptoms, such as poor social interaction and verbal communication, are well known and were first described 70 years ago by Leo Kanner, MD.

Unfortunately, its root causes remain elusive, though progress has been made, Dr. Talalay said, in describing some of the biochemical and molecular abnormalities that tend to accompany ASD. Many of these are related to the efficiency of energy generation in cells. Studies show that the cells of patients with ASD often have high levels of oxidative stress, the buildup of harmful, unintended byproducts from the cell’s use of oxygen that can cause inflammation, damage DNA, and lead to cancer and other chronic diseases.

In 1992, Dr. Talalay’s research group found that sulforaphane can bolster the body’s natural defenses against oxidative stress, inflammation, and DNA damage. In addition, the chemical later was found to improve the body’s heat-shock response, a cascade of events used to protect cells from the stress caused by high temperatures, including those experienced when people have fever.

About one-half of parents report that their children’s autistic behavior improves noticeably when they have a fever, then reverts back when the fever is gone. In 2007, Dr. Zimmerman tested this anecdotal trend clinically and found it to be true, though a mechanism for the fever effect was not identified. Because fevers, similar to sulforaphane, initiate the body’s heat-shock response, Drs. Zimmerman and Talalay wondered if sulforaphane could cause the same temporary improvement in autism that fevers do.

Improvement Linked to Sulforaphane
Before the start of the trial, the patients’ caregivers and physicians filled out three standard behavioral assessments—the Aberrant Behavior Checklist (ABC), the Social Responsiveness Scale (SRS), and the Clinical Global Impressions-Improvement scale (CGI-I). The assessments measure sensory sensitivities, ability to relate to others, verbal communication skills, social interactions, and other behaviors related to autism. Twenty-six participants were randomly selected to receive, based on their weight, 9 to 27 mg of sulforaphane daily, and 14 received placebo. Behavioral assessments were again completed at four, 10, and 18 weeks while treatment continued. A final assessment was completed for most of the participants four weeks after the treatment had stopped.

Most subjects who responded to sulforaphane showed significant improvements by the first measurement at four weeks and continued to improve during the rest of the treatment. After 18 weeks of treatment, the average ABC and SRS scores of those who received sulforaphane had decreased 34% and 17%, respectively, with improvements in bouts of irritability, lethargy, repetitive movements, hyperactivity, awareness, communication, motivation, and mannerisms.

After 18 weeks of treatment, according to the CGI-I scale, 46%, 54%, and 42% of sulforaphane recipients experienced noticeable improvements in social interaction, aberrant behaviors, and verbal communication, respectively.

Dr. Talalay noted that the scores of those who took sulforaphane trended back toward their original values after they stopped taking the chemical, similar to what happens to those who experience improvements during a fever. “It seems like sulforaphane is temporarily helping cells to cope with their handicaps,” he said.

Dr. Zimmerman added that before his group learned which subjects received the sulforaphane or placebo, the impressions of the clinical team, including parents, were that 13 participants noticeably improved. For example, some treated subjects looked them in the eye and shook their hands, which they had not done before. They found out later that all 13 had been taking sulforaphane, which is half of the treatment group. Dr. Talalay cautioned that the levels of sulforaphane precursors present in different varieties of broccoli are highly variable. Furthermore, the capacity of individuals to convert these precursors to active sulforaphane also varies greatly. It would be difficult, he noted, to achieve the levels of sulforaphane used in this study by eating large amounts of broccoli or other cruciferous vegetables.

Sulforaphane, a chemical derived from broccoli sprouts, may ease classic behavioral symptoms in patients with autism spectrum disorders (ASDs), according to a study published online ahead of print October 13 in the Proceedings of the National Academy of Sciences.

The study involved 40 males, ages 13 to 27, with moderate to severe autism. Many participants who received a daily dose of sulforaphane experienced substantial improvements in their social interaction and verbal communication, along with decreases in repetitive, ritualistic behaviors, compared with those who received a placebo, according to the researchers.

“We believe that this may be preliminary evidence for the first treatment for autism that improves symptoms by apparently correcting some of the underlying cellular problems,” said Paul Talalay, MD, Professor of Pharmacology and Molecular Sciences at Johns Hopkins University in Baltimore.

“We are far from being able to declare a victory over autism, but this gives us important insights into what might help,” said coinvestigator Andrew Zimmerman, MD, Professor of Pediatric Neurology at UMass Memorial Medical Center in Worcester.

Cause of Autism Is Elusive
Researchers estimate that ASD affects 1% to 2% of the world’s population, with a much higher incidence in boys than in girls. Its behavioral symptoms, such as poor social interaction and verbal communication, are well known and were first described 70 years ago by Leo Kanner, MD.

Unfortunately, its root causes remain elusive, though progress has been made, Dr. Talalay said, in describing some of the biochemical and molecular abnormalities that tend to accompany ASD. Many of these are related to the efficiency of energy generation in cells. Studies show that the cells of patients with ASD often have high levels of oxidative stress, the buildup of harmful, unintended byproducts from the cell’s use of oxygen that can cause inflammation, damage DNA, and lead to cancer and other chronic diseases.

In 1992, Dr. Talalay’s research group found that sulforaphane can bolster the body’s natural defenses against oxidative stress, inflammation, and DNA damage. In addition, the chemical later was found to improve the body’s heat-shock response, a cascade of events used to protect cells from the stress caused by high temperatures, including those experienced when people have fever.

About one-half of parents report that their children’s autistic behavior improves noticeably when they have a fever, then reverts back when the fever is gone. In 2007, Dr. Zimmerman tested this anecdotal trend clinically and found it to be true, though a mechanism for the fever effect was not identified. Because fevers, similar to sulforaphane, initiate the body’s heat-shock response, Drs. Zimmerman and Talalay wondered if sulforaphane could cause the same temporary improvement in autism that fevers do.

Improvement Linked to Sulforaphane
Before the start of the trial, the patients’ caregivers and physicians filled out three standard behavioral assessments—the Aberrant Behavior Checklist (ABC), the Social Responsiveness Scale (SRS), and the Clinical Global Impressions-Improvement scale (CGI-I). The assessments measure sensory sensitivities, ability to relate to others, verbal communication skills, social interactions, and other behaviors related to autism. Twenty-six participants were randomly selected to receive, based on their weight, 9 to 27 mg of sulforaphane daily, and 14 received placebo. Behavioral assessments were again completed at four, 10, and 18 weeks while treatment continued. A final assessment was completed for most of the participants four weeks after the treatment had stopped.

Most subjects who responded to sulforaphane showed significant improvements by the first measurement at four weeks and continued to improve during the rest of the treatment. After 18 weeks of treatment, the average ABC and SRS scores of those who received sulforaphane had decreased 34% and 17%, respectively, with improvements in bouts of irritability, lethargy, repetitive movements, hyperactivity, awareness, communication, motivation, and mannerisms.

After 18 weeks of treatment, according to the CGI-I scale, 46%, 54%, and 42% of sulforaphane recipients experienced noticeable improvements in social interaction, aberrant behaviors, and verbal communication, respectively.

Dr. Talalay noted that the scores of those who took sulforaphane trended back toward their original values after they stopped taking the chemical, similar to what happens to those who experience improvements during a fever. “It seems like sulforaphane is temporarily helping cells to cope with their handicaps,” he said.

Dr. Zimmerman added that before his group learned which subjects received the sulforaphane or placebo, the impressions of the clinical team, including parents, were that 13 participants noticeably improved. For example, some treated subjects looked them in the eye and shook their hands, which they had not done before. They found out later that all 13 had been taking sulforaphane, which is half of the treatment group. Dr. Talalay cautioned that the levels of sulforaphane precursors present in different varieties of broccoli are highly variable. Furthermore, the capacity of individuals to convert these precursors to active sulforaphane also varies greatly. It would be difficult, he noted, to achieve the levels of sulforaphane used in this study by eating large amounts of broccoli or other cruciferous vegetables.

Sulforaphane, a chemical derived from broccoli sprouts, may ease classic behavioral symptoms in patients with autism spectrum disorders (ASDs), according to a study published online ahead of print October 13 in the Proceedings of the National Academy of Sciences.

The study involved 40 males, ages 13 to 27, with moderate to severe autism. Many participants who received a daily dose of sulforaphane experienced substantial improvements in their social interaction and verbal communication, along with decreases in repetitive, ritualistic behaviors, compared with those who received a placebo, according to the researchers.

“We believe that this may be preliminary evidence for the first treatment for autism that improves symptoms by apparently correcting some of the underlying cellular problems,” said Paul Talalay, MD, Professor of Pharmacology and Molecular Sciences at Johns Hopkins University in Baltimore.

“We are far from being able to declare a victory over autism, but this gives us important insights into what might help,” said coinvestigator Andrew Zimmerman, MD, Professor of Pediatric Neurology at UMass Memorial Medical Center in Worcester.

Cause of Autism Is Elusive
Researchers estimate that ASD affects 1% to 2% of the world’s population, with a much higher incidence in boys than in girls. Its behavioral symptoms, such as poor social interaction and verbal communication, are well known and were first described 70 years ago by Leo Kanner, MD.

Unfortunately, its root causes remain elusive, though progress has been made, Dr. Talalay said, in describing some of the biochemical and molecular abnormalities that tend to accompany ASD. Many of these are related to the efficiency of energy generation in cells. Studies show that the cells of patients with ASD often have high levels of oxidative stress, the buildup of harmful, unintended byproducts from the cell’s use of oxygen that can cause inflammation, damage DNA, and lead to cancer and other chronic diseases.

In 1992, Dr. Talalay’s research group found that sulforaphane can bolster the body’s natural defenses against oxidative stress, inflammation, and DNA damage. In addition, the chemical later was found to improve the body’s heat-shock response, a cascade of events used to protect cells from the stress caused by high temperatures, including those experienced when people have fever.

About one-half of parents report that their children’s autistic behavior improves noticeably when they have a fever, then reverts back when the fever is gone. In 2007, Dr. Zimmerman tested this anecdotal trend clinically and found it to be true, though a mechanism for the fever effect was not identified. Because fevers, similar to sulforaphane, initiate the body’s heat-shock response, Drs. Zimmerman and Talalay wondered if sulforaphane could cause the same temporary improvement in autism that fevers do.

Improvement Linked to Sulforaphane
Before the start of the trial, the patients’ caregivers and physicians filled out three standard behavioral assessments—the Aberrant Behavior Checklist (ABC), the Social Responsiveness Scale (SRS), and the Clinical Global Impressions-Improvement scale (CGI-I). The assessments measure sensory sensitivities, ability to relate to others, verbal communication skills, social interactions, and other behaviors related to autism. Twenty-six participants were randomly selected to receive, based on their weight, 9 to 27 mg of sulforaphane daily, and 14 received placebo. Behavioral assessments were again completed at four, 10, and 18 weeks while treatment continued. A final assessment was completed for most of the participants four weeks after the treatment had stopped.

Most subjects who responded to sulforaphane showed significant improvements by the first measurement at four weeks and continued to improve during the rest of the treatment. After 18 weeks of treatment, the average ABC and SRS scores of those who received sulforaphane had decreased 34% and 17%, respectively, with improvements in bouts of irritability, lethargy, repetitive movements, hyperactivity, awareness, communication, motivation, and mannerisms.

After 18 weeks of treatment, according to the CGI-I scale, 46%, 54%, and 42% of sulforaphane recipients experienced noticeable improvements in social interaction, aberrant behaviors, and verbal communication, respectively.

Dr. Talalay noted that the scores of those who took sulforaphane trended back toward their original values after they stopped taking the chemical, similar to what happens to those who experience improvements during a fever. “It seems like sulforaphane is temporarily helping cells to cope with their handicaps,” he said.

Dr. Zimmerman added that before his group learned which subjects received the sulforaphane or placebo, the impressions of the clinical team, including parents, were that 13 participants noticeably improved. For example, some treated subjects looked them in the eye and shook their hands, which they had not done before. They found out later that all 13 had been taking sulforaphane, which is half of the treatment group. Dr. Talalay cautioned that the levels of sulforaphane precursors present in different varieties of broccoli are highly variable. Furthermore, the capacity of individuals to convert these precursors to active sulforaphane also varies greatly. It would be difficult, he noted, to achieve the levels of sulforaphane used in this study by eating large amounts of broccoli or other cruciferous vegetables.

Researchers found no long-term association of vaccines with multiple sclerosis (MS) or any other CNS demyelinating syndromes, according to a study published online ahead of print October 20 in JAMA Neurology. The investigators examined the relationship between vaccines and MS or other CNS demyelinating syndromes by using data from Kaiser Permanente Southern California members. The study authors identified 780 cases of CNS demyelinating syndromes and 3,885 controls; 92 cases and 459 controls were females between the ages of 9 and 26, which is the indicated age range for human papillomavirus (HPV) vaccination. The researchers found no associations between HepB vaccinations, HPV vaccination, or any vaccination and the risk of MS or CNS demyelinating syndromes for as long as three years later. Vaccination of any type was associated with increased risk of a CNS demyelinating syndrome onset within the first 30 days after vaccination only in patients younger than 50, but this association was not evident after 30 days.

Bariatric surgery is a potential risk factor for spontaneous intracranial hypotension, according to a study published online ahead of print October 22 in Neurology. Researchers compared a group of 338 patients with spontaneous intracranial hypotension to a control group of 245 people with unruptured intracranial aneurysms. Eleven of the 338 (3.3%) people with spontaneous intracranial hypotension had previously had bariatric surgery, compared with two of the 245 (0.8%) people with intracranial aneurysms. Of the 11 people with bariatric surgery and spontaneous intracranial hypotension, nine had no more symptoms after treatment, while symptoms persisted for two. The symptoms started from three months to 20 years after the bariatric surgery, and participants had lost an average of 116 pounds during that time.

Longitudinal measures of cortical atrophy were widely correlated with sleep quality, according to a study published September 9 in Neurology. The study included 147 adults, ages 20 and 84. Researchers examined the link between sleep difficulties, such as having trouble falling asleep or staying asleep at night, and brain volume. All participants underwent two MRI brain scans, an average of 3.5 years apart, before completing a questionnaire about their sleep habits. A total of 35% of the participants met the criteria for poor sleep quality, scoring an average of 8.5 out of 21 points on the sleep assessment. The researchers found that sleep difficulties were linked with a more rapid decline in brain volume during the course of the study in various brain regions, including within frontal, temporal, and parietal areas. The results were more pronounced in people older than 60.

An international group of researchers has established the first standardized guidelines for the collection of blood to test for early Alzheimer’s disease, as reported online ahead of print September 27 in Alzheimer’s & Dementia. These guidelines will be used in research for blood-based biomarkers of Alzheimer’s disease and will ensure that every laboratory is following the same protocol when collecting blood. The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimer’s disease. Researchers have worked with representatives from the United States, Germany, Australia, England, and other countries to create these standards. “You can create a blood test in the lab, but if you don’t have a systemized way for collecting the blood, the test will never go into practice,” said the investigators.

A new study suggests a cause of amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print October 14 in Proceedings of the National Academy of Sciences. Researchers used advanced biophysical methods to probe how different superoxide dismutase 1(SOD1) gene mutations in a genetic ALS hotspot affect SOD protein stability. Investigators examined how the aggregation dynamics of mutant SOD G93A differed from that of nonmutant SOD. They developed a method for gradually inducing SOD aggregation, which was measured with SAXS, a structural imaging system. The G93-mutant SODs appear to have looser, floppier structures that are more likely to drop their copper ions and are more likely to misfold and stick together in aggregates. “Our work supports a common theme whereby loss of protein stability leads to disease,” investigators said.

Long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis, according to a study published online ahead of print October 14 in the Lancet. Researchers followed 1,713 patients with carotid artery disease, of whom 855 were assigned to stenting and 858 to endarterectomy, for as long as 10 years. The median follow-up was 4.2 years. Both techniques were found to be equally good at preventing fatal and disabling strokes, but stented patients were slightly more likely to have minor strokes without long-term effects. The risk of any stroke in five years was 15.2% in the stenting group, compared with 9.4% in the endarterectomy group, but the additional strokes were minor and had no impact on long-term quality of life.

Researchers have found Class II evidence that serum metabolite profiles accurately distinguish patients with different subtypes and stages of multiple sclerosis (MS), according to a study published October 21 in Neurology. Investigators obtained serum samples from patients with primary progressive MS, secondary-progressive MS, and relapsing-remitting MS, patients with other neurodegenerative conditions, and from age-matched controls. Samples were analyzed by nuclear magnetic resonance, and partial least squares discriminant analysis models were derived to separate disease groups. The partial least squares discriminant analysis models for serum samples from patients with MS enabled reliable differentiation between relapsing-remitting MS and secondary-progressive MS. This approach identified significant differences between the metabolite profiles of each of the MS groups and the healthy controls, as well as predicting disease group membership with high sensitivity and specificity.

Parkinson’s disease pathogenic mutations have an age-dependent penetrance that could be ameliorated or exacerbated by modifier genes or environmental factors in different populations, according to a study published online ahead of print October 20 in JAMA Neurology. The investigators examined 49 previously published studies that included 709 participants and were found in ISI Web of Science and PubMed. They also analyzed extracted information about the number of mutation carriers within families and sporadic cases worldwide for pathogenic mutations in SNCA, LRRK2, VPS35, EIF4G1, and DNAJC13. The end-of-search date was January 31, 2014. In particular, penetrance of SNCA duplications were comparable to point mutations and driven by inclusion of SNCA p.A53T (mean age at onset, 45.9). Each penetrance estimate was given separately with 95% confidence intervals.

Spreading depolarizations can be measured after traumatic brain injury (TBI) by the placement of EEG electrodes on the scalp, according to a study published online ahead of print August 25 in Annals of Neurology. Eighteen patients requiring surgical treatment for TBI were monitored by invasive electrocorticography (ECoG) and noninvasive scalp EEG during intensive care. Spreading depolarizations were first identified in subdural recordings, and EEGs were then examined visually and quantitatively to identify correlates. A total of 455 spreading depolarizations occurred during 65.9 days of simultaneous ECoG and EEG monitoring. For 179 of 455 events (39%), depolarizations caused temporally isolated, transient depressions of spontaneous EEG amplitudes to 57% (median) of baseline power. For 62 of 179 (35%) events, isolated depressions showed a clear spread of depression between EEG channels with delays of 17 minutes (median).

A diet that includes walnuts may have a beneficial effect on reducing the risk, delaying the onset, and slowing the progression of, or preventing, Alzheimer’s disease, according to a study published October 21 in the Journal of Alzheimer’s Disease. The research group examined the effects of dietary supplementation on mice with 6% or 9% walnuts, which is equivalent to 1 ounce and 1.5 ounces per day, respectively, of walnuts in humans. The investigators found significant improvement in learning skills, memory, reducing anxiety, and motor development in mice fed a walnut-enriched diet. “These findings are very promising and help lay the groundwork for future human studies on walnuts and Alzheimer’s disease,” the investigators said.

Dopamine receptor agonist drugs are associated with impulse control disorders, such as pathologic gambling, hypersexuality, and compulsive shopping, according to a study that was published online ahead of print October 20 in JAMA Internal Medicine. Researchers conducted a retrospective disproportionality analysis that was based on the 2.7 million serious domestic and foreign adverse drug event reports between 2003 and 2012 that were extracted from the FDA Adverse Event Reporting System. The investigators identified 1,580 events indicating impulse control disorders from the United States and 21 other countries (710 for dopamine receptor agonist drugs and 870 for other drugs). The dopamine receptor agonist drugs had a strong signal associated with these impulse control disorders. The association was strongest for the dopamine agonists pramipexole and ropinirole, with preferential affinity for the dopamine D3 receptor. A signal was also seen for aripiprazole.

—Kimberly D. Williams

Researchers found no long-term association of vaccines with multiple sclerosis (MS) or any other CNS demyelinating syndromes, according to a study published online ahead of print October 20 in JAMA Neurology. The investigators examined the relationship between vaccines and MS or other CNS demyelinating syndromes by using data from Kaiser Permanente Southern California members. The study authors identified 780 cases of CNS demyelinating syndromes and 3,885 controls; 92 cases and 459 controls were females between the ages of 9 and 26, which is the indicated age range for human papillomavirus (HPV) vaccination. The researchers found no associations between HepB vaccinations, HPV vaccination, or any vaccination and the risk of MS or CNS demyelinating syndromes for as long as three years later. Vaccination of any type was associated with increased risk of a CNS demyelinating syndrome onset within the first 30 days after vaccination only in patients younger than 50, but this association was not evident after 30 days.

Bariatric surgery is a potential risk factor for spontaneous intracranial hypotension, according to a study published online ahead of print October 22 in Neurology. Researchers compared a group of 338 patients with spontaneous intracranial hypotension to a control group of 245 people with unruptured intracranial aneurysms. Eleven of the 338 (3.3%) people with spontaneous intracranial hypotension had previously had bariatric surgery, compared with two of the 245 (0.8%) people with intracranial aneurysms. Of the 11 people with bariatric surgery and spontaneous intracranial hypotension, nine had no more symptoms after treatment, while symptoms persisted for two. The symptoms started from three months to 20 years after the bariatric surgery, and participants had lost an average of 116 pounds during that time.

Longitudinal measures of cortical atrophy were widely correlated with sleep quality, according to a study published September 9 in Neurology. The study included 147 adults, ages 20 and 84. Researchers examined the link between sleep difficulties, such as having trouble falling asleep or staying asleep at night, and brain volume. All participants underwent two MRI brain scans, an average of 3.5 years apart, before completing a questionnaire about their sleep habits. A total of 35% of the participants met the criteria for poor sleep quality, scoring an average of 8.5 out of 21 points on the sleep assessment. The researchers found that sleep difficulties were linked with a more rapid decline in brain volume during the course of the study in various brain regions, including within frontal, temporal, and parietal areas. The results were more pronounced in people older than 60.

An international group of researchers has established the first standardized guidelines for the collection of blood to test for early Alzheimer’s disease, as reported online ahead of print September 27 in Alzheimer’s & Dementia. These guidelines will be used in research for blood-based biomarkers of Alzheimer’s disease and will ensure that every laboratory is following the same protocol when collecting blood. The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimer’s disease. Researchers have worked with representatives from the United States, Germany, Australia, England, and other countries to create these standards. “You can create a blood test in the lab, but if you don’t have a systemized way for collecting the blood, the test will never go into practice,” said the investigators.

A new study suggests a cause of amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print October 14 in Proceedings of the National Academy of Sciences. Researchers used advanced biophysical methods to probe how different superoxide dismutase 1(SOD1) gene mutations in a genetic ALS hotspot affect SOD protein stability. Investigators examined how the aggregation dynamics of mutant SOD G93A differed from that of nonmutant SOD. They developed a method for gradually inducing SOD aggregation, which was measured with SAXS, a structural imaging system. The G93-mutant SODs appear to have looser, floppier structures that are more likely to drop their copper ions and are more likely to misfold and stick together in aggregates. “Our work supports a common theme whereby loss of protein stability leads to disease,” investigators said.

Long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis, according to a study published online ahead of print October 14 in the Lancet. Researchers followed 1,713 patients with carotid artery disease, of whom 855 were assigned to stenting and 858 to endarterectomy, for as long as 10 years. The median follow-up was 4.2 years. Both techniques were found to be equally good at preventing fatal and disabling strokes, but stented patients were slightly more likely to have minor strokes without long-term effects. The risk of any stroke in five years was 15.2% in the stenting group, compared with 9.4% in the endarterectomy group, but the additional strokes were minor and had no impact on long-term quality of life.

Researchers have found Class II evidence that serum metabolite profiles accurately distinguish patients with different subtypes and stages of multiple sclerosis (MS), according to a study published October 21 in Neurology. Investigators obtained serum samples from patients with primary progressive MS, secondary-progressive MS, and relapsing-remitting MS, patients with other neurodegenerative conditions, and from age-matched controls. Samples were analyzed by nuclear magnetic resonance, and partial least squares discriminant analysis models were derived to separate disease groups. The partial least squares discriminant analysis models for serum samples from patients with MS enabled reliable differentiation between relapsing-remitting MS and secondary-progressive MS. This approach identified significant differences between the metabolite profiles of each of the MS groups and the healthy controls, as well as predicting disease group membership with high sensitivity and specificity.

Parkinson’s disease pathogenic mutations have an age-dependent penetrance that could be ameliorated or exacerbated by modifier genes or environmental factors in different populations, according to a study published online ahead of print October 20 in JAMA Neurology. The investigators examined 49 previously published studies that included 709 participants and were found in ISI Web of Science and PubMed. They also analyzed extracted information about the number of mutation carriers within families and sporadic cases worldwide for pathogenic mutations in SNCA, LRRK2, VPS35, EIF4G1, and DNAJC13. The end-of-search date was January 31, 2014. In particular, penetrance of SNCA duplications were comparable to point mutations and driven by inclusion of SNCA p.A53T (mean age at onset, 45.9). Each penetrance estimate was given separately with 95% confidence intervals.

Spreading depolarizations can be measured after traumatic brain injury (TBI) by the placement of EEG electrodes on the scalp, according to a study published online ahead of print August 25 in Annals of Neurology. Eighteen patients requiring surgical treatment for TBI were monitored by invasive electrocorticography (ECoG) and noninvasive scalp EEG during intensive care. Spreading depolarizations were first identified in subdural recordings, and EEGs were then examined visually and quantitatively to identify correlates. A total of 455 spreading depolarizations occurred during 65.9 days of simultaneous ECoG and EEG monitoring. For 179 of 455 events (39%), depolarizations caused temporally isolated, transient depressions of spontaneous EEG amplitudes to 57% (median) of baseline power. For 62 of 179 (35%) events, isolated depressions showed a clear spread of depression between EEG channels with delays of 17 minutes (median).

A diet that includes walnuts may have a beneficial effect on reducing the risk, delaying the onset, and slowing the progression of, or preventing, Alzheimer’s disease, according to a study published October 21 in the Journal of Alzheimer’s Disease. The research group examined the effects of dietary supplementation on mice with 6% or 9% walnuts, which is equivalent to 1 ounce and 1.5 ounces per day, respectively, of walnuts in humans. The investigators found significant improvement in learning skills, memory, reducing anxiety, and motor development in mice fed a walnut-enriched diet. “These findings are very promising and help lay the groundwork for future human studies on walnuts and Alzheimer’s disease,” the investigators said.

Dopamine receptor agonist drugs are associated with impulse control disorders, such as pathologic gambling, hypersexuality, and compulsive shopping, according to a study that was published online ahead of print October 20 in JAMA Internal Medicine. Researchers conducted a retrospective disproportionality analysis that was based on the 2.7 million serious domestic and foreign adverse drug event reports between 2003 and 2012 that were extracted from the FDA Adverse Event Reporting System. The investigators identified 1,580 events indicating impulse control disorders from the United States and 21 other countries (710 for dopamine receptor agonist drugs and 870 for other drugs). The dopamine receptor agonist drugs had a strong signal associated with these impulse control disorders. The association was strongest for the dopamine agonists pramipexole and ropinirole, with preferential affinity for the dopamine D3 receptor. A signal was also seen for aripiprazole.

—Kimberly D. Williams

Researchers found no long-term association of vaccines with multiple sclerosis (MS) or any other CNS demyelinating syndromes, according to a study published online ahead of print October 20 in JAMA Neurology. The investigators examined the relationship between vaccines and MS or other CNS demyelinating syndromes by using data from Kaiser Permanente Southern California members. The study authors identified 780 cases of CNS demyelinating syndromes and 3,885 controls; 92 cases and 459 controls were females between the ages of 9 and 26, which is the indicated age range for human papillomavirus (HPV) vaccination. The researchers found no associations between HepB vaccinations, HPV vaccination, or any vaccination and the risk of MS or CNS demyelinating syndromes for as long as three years later. Vaccination of any type was associated with increased risk of a CNS demyelinating syndrome onset within the first 30 days after vaccination only in patients younger than 50, but this association was not evident after 30 days.

Bariatric surgery is a potential risk factor for spontaneous intracranial hypotension, according to a study published online ahead of print October 22 in Neurology. Researchers compared a group of 338 patients with spontaneous intracranial hypotension to a control group of 245 people with unruptured intracranial aneurysms. Eleven of the 338 (3.3%) people with spontaneous intracranial hypotension had previously had bariatric surgery, compared with two of the 245 (0.8%) people with intracranial aneurysms. Of the 11 people with bariatric surgery and spontaneous intracranial hypotension, nine had no more symptoms after treatment, while symptoms persisted for two. The symptoms started from three months to 20 years after the bariatric surgery, and participants had lost an average of 116 pounds during that time.

Longitudinal measures of cortical atrophy were widely correlated with sleep quality, according to a study published September 9 in Neurology. The study included 147 adults, ages 20 and 84. Researchers examined the link between sleep difficulties, such as having trouble falling asleep or staying asleep at night, and brain volume. All participants underwent two MRI brain scans, an average of 3.5 years apart, before completing a questionnaire about their sleep habits. A total of 35% of the participants met the criteria for poor sleep quality, scoring an average of 8.5 out of 21 points on the sleep assessment. The researchers found that sleep difficulties were linked with a more rapid decline in brain volume during the course of the study in various brain regions, including within frontal, temporal, and parietal areas. The results were more pronounced in people older than 60.

An international group of researchers has established the first standardized guidelines for the collection of blood to test for early Alzheimer’s disease, as reported online ahead of print September 27 in Alzheimer’s & Dementia. These guidelines will be used in research for blood-based biomarkers of Alzheimer’s disease and will ensure that every laboratory is following the same protocol when collecting blood. The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimer’s disease. Researchers have worked with representatives from the United States, Germany, Australia, England, and other countries to create these standards. “You can create a blood test in the lab, but if you don’t have a systemized way for collecting the blood, the test will never go into practice,” said the investigators.

A new study suggests a cause of amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print October 14 in Proceedings of the National Academy of Sciences. Researchers used advanced biophysical methods to probe how different superoxide dismutase 1(SOD1) gene mutations in a genetic ALS hotspot affect SOD protein stability. Investigators examined how the aggregation dynamics of mutant SOD G93A differed from that of nonmutant SOD. They developed a method for gradually inducing SOD aggregation, which was measured with SAXS, a structural imaging system. The G93-mutant SODs appear to have looser, floppier structures that are more likely to drop their copper ions and are more likely to misfold and stick together in aggregates. “Our work supports a common theme whereby loss of protein stability leads to disease,” investigators said.

Long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis, according to a study published online ahead of print October 14 in the Lancet. Researchers followed 1,713 patients with carotid artery disease, of whom 855 were assigned to stenting and 858 to endarterectomy, for as long as 10 years. The median follow-up was 4.2 years. Both techniques were found to be equally good at preventing fatal and disabling strokes, but stented patients were slightly more likely to have minor strokes without long-term effects. The risk of any stroke in five years was 15.2% in the stenting group, compared with 9.4% in the endarterectomy group, but the additional strokes were minor and had no impact on long-term quality of life.

Researchers have found Class II evidence that serum metabolite profiles accurately distinguish patients with different subtypes and stages of multiple sclerosis (MS), according to a study published October 21 in Neurology. Investigators obtained serum samples from patients with primary progressive MS, secondary-progressive MS, and relapsing-remitting MS, patients with other neurodegenerative conditions, and from age-matched controls. Samples were analyzed by nuclear magnetic resonance, and partial least squares discriminant analysis models were derived to separate disease groups. The partial least squares discriminant analysis models for serum samples from patients with MS enabled reliable differentiation between relapsing-remitting MS and secondary-progressive MS. This approach identified significant differences between the metabolite profiles of each of the MS groups and the healthy controls, as well as predicting disease group membership with high sensitivity and specificity.

Parkinson’s disease pathogenic mutations have an age-dependent penetrance that could be ameliorated or exacerbated by modifier genes or environmental factors in different populations, according to a study published online ahead of print October 20 in JAMA Neurology. The investigators examined 49 previously published studies that included 709 participants and were found in ISI Web of Science and PubMed. They also analyzed extracted information about the number of mutation carriers within families and sporadic cases worldwide for pathogenic mutations in SNCA, LRRK2, VPS35, EIF4G1, and DNAJC13. The end-of-search date was January 31, 2014. In particular, penetrance of SNCA duplications were comparable to point mutations and driven by inclusion of SNCA p.A53T (mean age at onset, 45.9). Each penetrance estimate was given separately with 95% confidence intervals.

Spreading depolarizations can be measured after traumatic brain injury (TBI) by the placement of EEG electrodes on the scalp, according to a study published online ahead of print August 25 in Annals of Neurology. Eighteen patients requiring surgical treatment for TBI were monitored by invasive electrocorticography (ECoG) and noninvasive scalp EEG during intensive care. Spreading depolarizations were first identified in subdural recordings, and EEGs were then examined visually and quantitatively to identify correlates. A total of 455 spreading depolarizations occurred during 65.9 days of simultaneous ECoG and EEG monitoring. For 179 of 455 events (39%), depolarizations caused temporally isolated, transient depressions of spontaneous EEG amplitudes to 57% (median) of baseline power. For 62 of 179 (35%) events, isolated depressions showed a clear spread of depression between EEG channels with delays of 17 minutes (median).

A diet that includes walnuts may have a beneficial effect on reducing the risk, delaying the onset, and slowing the progression of, or preventing, Alzheimer’s disease, according to a study published October 21 in the Journal of Alzheimer’s Disease. The research group examined the effects of dietary supplementation on mice with 6% or 9% walnuts, which is equivalent to 1 ounce and 1.5 ounces per day, respectively, of walnuts in humans. The investigators found significant improvement in learning skills, memory, reducing anxiety, and motor development in mice fed a walnut-enriched diet. “These findings are very promising and help lay the groundwork for future human studies on walnuts and Alzheimer’s disease,” the investigators said.

Dopamine receptor agonist drugs are associated with impulse control disorders, such as pathologic gambling, hypersexuality, and compulsive shopping, according to a study that was published online ahead of print October 20 in JAMA Internal Medicine. Researchers conducted a retrospective disproportionality analysis that was based on the 2.7 million serious domestic and foreign adverse drug event reports between 2003 and 2012 that were extracted from the FDA Adverse Event Reporting System. The investigators identified 1,580 events indicating impulse control disorders from the United States and 21 other countries (710 for dopamine receptor agonist drugs and 870 for other drugs). The dopamine receptor agonist drugs had a strong signal associated with these impulse control disorders. The association was strongest for the dopamine agonists pramipexole and ropinirole, with preferential affinity for the dopamine D3 receptor. A signal was also seen for aripiprazole.

—Kimberly D. Williams