Clinical question: Are patients able to select health-care providers based on price of service?

Background: With health-care costs rising, patients are encouraged to take a more active role in cost containment. Many initiatives call for greater pricing transparency in the health-care system. This study evaluated price availability for a common surgical procedure.

Study design: Telephone inquiries with standardized interview script.

Setting: Twenty top-ranked orthopedic hospitals and 102 non-top-ranked U.S. hospitals.

Synopsis: Hospitals were contacted by phone with a standardized, scripted request for the price of an elective total hip arthroplasty. The script described the patient as a 62-year-old grandmother without insurance who is able to pay out of pocket and wishes to compare hospital prices. On the first or second attempt, 40% of top-ranked and 32% of non-top-ranked hospitals were able to provide their price; after five attempts, authors were unable to obtain full pricing information (both hospital and physician fee) from 40% of top-ranked and 37% of non-top-ranked hospitals. Neither fee was made available by 15% of top-ranked and 16% of non-top-ranked hospitals. Wide variation in pricing was found across hospitals. The authors commented on the difficulties they encountered, such as the transfer of calls between departments and the uncertainty of representatives on how to assist.

Bottom line: For individual patients, applying basic economic principles as a consumer might be tiresome and often impossible, with no major differences between top-ranked and non-top-ranked hospitals.

Citation: Rosenthal JA, Lu X, Cram P. Availability of consumer prices from US hospitals for a common surgical procedure. JAMA Intern Med. 2013;173(6):427-432.

Visit our website for more physician reviews of recent HM-relevant literature.

Clinical question: Are patients able to select health-care providers based on price of service?

Background: With health-care costs rising, patients are encouraged to take a more active role in cost containment. Many initiatives call for greater pricing transparency in the health-care system. This study evaluated price availability for a common surgical procedure.

Study design: Telephone inquiries with standardized interview script.

Setting: Twenty top-ranked orthopedic hospitals and 102 non-top-ranked U.S. hospitals.

Synopsis: Hospitals were contacted by phone with a standardized, scripted request for the price of an elective total hip arthroplasty. The script described the patient as a 62-year-old grandmother without insurance who is able to pay out of pocket and wishes to compare hospital prices. On the first or second attempt, 40% of top-ranked and 32% of non-top-ranked hospitals were able to provide their price; after five attempts, authors were unable to obtain full pricing information (both hospital and physician fee) from 40% of top-ranked and 37% of non-top-ranked hospitals. Neither fee was made available by 15% of top-ranked and 16% of non-top-ranked hospitals. Wide variation in pricing was found across hospitals. The authors commented on the difficulties they encountered, such as the transfer of calls between departments and the uncertainty of representatives on how to assist.

Bottom line: For individual patients, applying basic economic principles as a consumer might be tiresome and often impossible, with no major differences between top-ranked and non-top-ranked hospitals.

Citation: Rosenthal JA, Lu X, Cram P. Availability of consumer prices from US hospitals for a common surgical procedure. JAMA Intern Med. 2013;173(6):427-432.

Visit our website for more physician reviews of recent HM-relevant literature.

Clinical question: Are patients able to select health-care providers based on price of service?

Background: With health-care costs rising, patients are encouraged to take a more active role in cost containment. Many initiatives call for greater pricing transparency in the health-care system. This study evaluated price availability for a common surgical procedure.

Study design: Telephone inquiries with standardized interview script.

Setting: Twenty top-ranked orthopedic hospitals and 102 non-top-ranked U.S. hospitals.

Synopsis: Hospitals were contacted by phone with a standardized, scripted request for the price of an elective total hip arthroplasty. The script described the patient as a 62-year-old grandmother without insurance who is able to pay out of pocket and wishes to compare hospital prices. On the first or second attempt, 40% of top-ranked and 32% of non-top-ranked hospitals were able to provide their price; after five attempts, authors were unable to obtain full pricing information (both hospital and physician fee) from 40% of top-ranked and 37% of non-top-ranked hospitals. Neither fee was made available by 15% of top-ranked and 16% of non-top-ranked hospitals. Wide variation in pricing was found across hospitals. The authors commented on the difficulties they encountered, such as the transfer of calls between departments and the uncertainty of representatives on how to assist.

Bottom line: For individual patients, applying basic economic principles as a consumer might be tiresome and often impossible, with no major differences between top-ranked and non-top-ranked hospitals.

Citation: Rosenthal JA, Lu X, Cram P. Availability of consumer prices from US hospitals for a common surgical procedure. JAMA Intern Med. 2013;173(6):427-432.

Visit our website for more physician reviews of recent HM-relevant literature.

SAN FRANCISCO – Postoperative troponin elevation and myocardial infarction both impact 5-year survival following vascular surgery procedures, the results of a large long-term study showed.

In fact, troponin elevation increased the hazard of death by 50% while myocardial infarction increased the hazard of death by nearly threefold, Dr. Jessica P. Simons reported at the annual meeting of the Society for Vascular Surgery. "Future studies are needed to assess the nature of this association as well as the utility of routine postoperative screening for myocardial ischemia," said Dr. Simons of the division of vascular and endovascular surgery at the University of Massachusetts, Worcester.

In a study that she presented on behalf of the Vascular Study Group of New England (VSGNE), Dr. Simons and her associates set out to determine the association of postoperative troponin elevation with long-term survival in patients undergoing vascular surgical procedures. "Postoperative myocardial infarction has been shown to impact short- and long-term mortality," she said. "In addition, troponin elevations have also been shown to negatively impact survival for a wide range of diagnoses. This has been seen in critical care medical literature and also in the general surgical population."

The researchers identified 16,363 VSGNE patients who underwent carotid revascularization, open AAA repair, endovascular AAA repair, or lower-extremity bypass between 2003 and 2011. The exposure variable of interest was postoperative myocardial ischemia, which was categorized as either no ischemia, troponin elevation, or myocardial infarction. The primary end point was survival during the first 5 years postoperatively. They used Kaplan-Meier analyses and Cox proportional hazards models to evaluate the effect of postoperative troponin elevation and myocardial infarction.

Of the 16,363 patients, 15,888 (97.1%) had no ischemia, 211 (1.3%) had troponin elevation, and 264 (1.6%) had myocardial infarction. When this was broken down by procedure type, open AAA had the highest rates of postoperative myocardial ischemia (9%), troponin elevation (3.9%), and myocardial infarction (5.1%), compared with carotid revascularization, endovascular aneurysm repair, and lower-extremity bypass.

The rate of 5-year survival for all procedures was 73% among those with no ischemia, 54% among those with troponin elevation, and 33% among those with myocardial infarction. This difference reached statistical significance with a P value of less than .0001. After adjusting for covariates, the researchers found a similar trend. In this analysis the rate of 5-year survival was 78% among those with no ischemia, 48% among those with troponin elevation, and 35% among those with myocardial infarction. This also reached statistical significance with a P value of less than .0001.

"We performed a subgroup analysis by procedure type, and the trend was the same across all procedure types," Dr. Simons said.

In Cox modeling the researchers found that postoperative ischemia in the form of a troponin elevation increased the hazard of death at 5 years by 45% (HR, 1.45; P =.01) while myocardial infarction nearly tripled the hazard of death (HR, 2.93; P =.0001).

"We have shown an association between postoperative myocardial ischemia and worse survival, but does postoperative myocardial ischemia worsen long-term survival, or does postoperative myocardial ischemia simply identify a high-risk subset of patients?" Dr. Simons asked. "If postoperative myocardial ischemia worsens long-term survival, then efforts should focus on better preoperative medical optimization and perioperative prevention of ischemia. If postoperative myocardial ischemia is simply identifying a high-risk subset of patients, then efforts should focus on better preoperative risk stratification and postoperative medical surveillance."

She concluded that postoperative myocardial ischemia, "whether a troponin elevation or a myocardial infarction, is associated with lower survival. This effect is seen across all procedure types and persists out to 5 years postoperatively."

Dr. Simons said she had no relevant financial disclosures.

[email protected]

SAN FRANCISCO – Postoperative troponin elevation and myocardial infarction both impact 5-year survival following vascular surgery procedures, the results of a large long-term study showed.

In fact, troponin elevation increased the hazard of death by 50% while myocardial infarction increased the hazard of death by nearly threefold, Dr. Jessica P. Simons reported at the annual meeting of the Society for Vascular Surgery. "Future studies are needed to assess the nature of this association as well as the utility of routine postoperative screening for myocardial ischemia," said Dr. Simons of the division of vascular and endovascular surgery at the University of Massachusetts, Worcester.

In a study that she presented on behalf of the Vascular Study Group of New England (VSGNE), Dr. Simons and her associates set out to determine the association of postoperative troponin elevation with long-term survival in patients undergoing vascular surgical procedures. "Postoperative myocardial infarction has been shown to impact short- and long-term mortality," she said. "In addition, troponin elevations have also been shown to negatively impact survival for a wide range of diagnoses. This has been seen in critical care medical literature and also in the general surgical population."

The researchers identified 16,363 VSGNE patients who underwent carotid revascularization, open AAA repair, endovascular AAA repair, or lower-extremity bypass between 2003 and 2011. The exposure variable of interest was postoperative myocardial ischemia, which was categorized as either no ischemia, troponin elevation, or myocardial infarction. The primary end point was survival during the first 5 years postoperatively. They used Kaplan-Meier analyses and Cox proportional hazards models to evaluate the effect of postoperative troponin elevation and myocardial infarction.

Of the 16,363 patients, 15,888 (97.1%) had no ischemia, 211 (1.3%) had troponin elevation, and 264 (1.6%) had myocardial infarction. When this was broken down by procedure type, open AAA had the highest rates of postoperative myocardial ischemia (9%), troponin elevation (3.9%), and myocardial infarction (5.1%), compared with carotid revascularization, endovascular aneurysm repair, and lower-extremity bypass.

The rate of 5-year survival for all procedures was 73% among those with no ischemia, 54% among those with troponin elevation, and 33% among those with myocardial infarction. This difference reached statistical significance with a P value of less than .0001. After adjusting for covariates, the researchers found a similar trend. In this analysis the rate of 5-year survival was 78% among those with no ischemia, 48% among those with troponin elevation, and 35% among those with myocardial infarction. This also reached statistical significance with a P value of less than .0001.

"We performed a subgroup analysis by procedure type, and the trend was the same across all procedure types," Dr. Simons said.

In Cox modeling the researchers found that postoperative ischemia in the form of a troponin elevation increased the hazard of death at 5 years by 45% (HR, 1.45; P =.01) while myocardial infarction nearly tripled the hazard of death (HR, 2.93; P =.0001).

"We have shown an association between postoperative myocardial ischemia and worse survival, but does postoperative myocardial ischemia worsen long-term survival, or does postoperative myocardial ischemia simply identify a high-risk subset of patients?" Dr. Simons asked. "If postoperative myocardial ischemia worsens long-term survival, then efforts should focus on better preoperative medical optimization and perioperative prevention of ischemia. If postoperative myocardial ischemia is simply identifying a high-risk subset of patients, then efforts should focus on better preoperative risk stratification and postoperative medical surveillance."

She concluded that postoperative myocardial ischemia, "whether a troponin elevation or a myocardial infarction, is associated with lower survival. This effect is seen across all procedure types and persists out to 5 years postoperatively."

Dr. Simons said she had no relevant financial disclosures.

[email protected]

SAN FRANCISCO – Postoperative troponin elevation and myocardial infarction both impact 5-year survival following vascular surgery procedures, the results of a large long-term study showed.

In fact, troponin elevation increased the hazard of death by 50% while myocardial infarction increased the hazard of death by nearly threefold, Dr. Jessica P. Simons reported at the annual meeting of the Society for Vascular Surgery. "Future studies are needed to assess the nature of this association as well as the utility of routine postoperative screening for myocardial ischemia," said Dr. Simons of the division of vascular and endovascular surgery at the University of Massachusetts, Worcester.

In a study that she presented on behalf of the Vascular Study Group of New England (VSGNE), Dr. Simons and her associates set out to determine the association of postoperative troponin elevation with long-term survival in patients undergoing vascular surgical procedures. "Postoperative myocardial infarction has been shown to impact short- and long-term mortality," she said. "In addition, troponin elevations have also been shown to negatively impact survival for a wide range of diagnoses. This has been seen in critical care medical literature and also in the general surgical population."

The researchers identified 16,363 VSGNE patients who underwent carotid revascularization, open AAA repair, endovascular AAA repair, or lower-extremity bypass between 2003 and 2011. The exposure variable of interest was postoperative myocardial ischemia, which was categorized as either no ischemia, troponin elevation, or myocardial infarction. The primary end point was survival during the first 5 years postoperatively. They used Kaplan-Meier analyses and Cox proportional hazards models to evaluate the effect of postoperative troponin elevation and myocardial infarction.

Of the 16,363 patients, 15,888 (97.1%) had no ischemia, 211 (1.3%) had troponin elevation, and 264 (1.6%) had myocardial infarction. When this was broken down by procedure type, open AAA had the highest rates of postoperative myocardial ischemia (9%), troponin elevation (3.9%), and myocardial infarction (5.1%), compared with carotid revascularization, endovascular aneurysm repair, and lower-extremity bypass.

The rate of 5-year survival for all procedures was 73% among those with no ischemia, 54% among those with troponin elevation, and 33% among those with myocardial infarction. This difference reached statistical significance with a P value of less than .0001. After adjusting for covariates, the researchers found a similar trend. In this analysis the rate of 5-year survival was 78% among those with no ischemia, 48% among those with troponin elevation, and 35% among those with myocardial infarction. This also reached statistical significance with a P value of less than .0001.

"We performed a subgroup analysis by procedure type, and the trend was the same across all procedure types," Dr. Simons said.

In Cox modeling the researchers found that postoperative ischemia in the form of a troponin elevation increased the hazard of death at 5 years by 45% (HR, 1.45; P =.01) while myocardial infarction nearly tripled the hazard of death (HR, 2.93; P =.0001).

"We have shown an association between postoperative myocardial ischemia and worse survival, but does postoperative myocardial ischemia worsen long-term survival, or does postoperative myocardial ischemia simply identify a high-risk subset of patients?" Dr. Simons asked. "If postoperative myocardial ischemia worsens long-term survival, then efforts should focus on better preoperative medical optimization and perioperative prevention of ischemia. If postoperative myocardial ischemia is simply identifying a high-risk subset of patients, then efforts should focus on better preoperative risk stratification and postoperative medical surveillance."

She concluded that postoperative myocardial ischemia, "whether a troponin elevation or a myocardial infarction, is associated with lower survival. This effect is seen across all procedure types and persists out to 5 years postoperatively."

Dr. Simons said she had no relevant financial disclosures.

[email protected]

SAN FRANCISCO – Outcomes of forearm and upper arm hemodialysis arteriovenous grafts are similar despite the fact that large caliber outflow veins are often encountered in the upper arm, results from a large trial showed.

"To preserve a maximal number of access sites, forearm location should always be considered before resorting to an upper arm graft," Dr. Alik Farber said at the Society for Vascular Surgery Annual Meeting.

The incidence and prevalence of end-stage renal disease in the United States has grown exponentially in the past 25 years, said Dr. Farber, chief of vascular and endovascular surgery at Boston University Medical Center. "In fact, in 2010 almost 400,000 patients were undergoing hemodialysis," he said. "At the same time, there has been a steady increase in the percent of AV fistulas placed and an associated decline in the percent of AV grafts placed in the United States. In 2010, 20% of patients were undergoing hemodialysis through AV grafts."

Most grafts in the upper extremity are based on the brachial artery. Some are in the forearm while others are in the upper arm. "In the forearm most grafts are looped," Dr. Farber said. "In the upper arm some are looped and some are straight. As it turns out, the optimal graft configuration is unknown. The optimal venous outflow in the upper extremity is unknown. And the optimal location of the first-time AV graft is controversial."

He went on to note that the forearm AV graft "saves the upper arm for a future graft site and has a potential advantage of increasing the suitability of upper arm veins for future native fistula. On the other hand, there is some evidence in the literature that forearm grafts have lower patency rates. The upper arm graft may have higher patency rates because they are ‘sawn into’ large caliber veins. However, surgeons who preferentially place upper arm grafts tend to skip potential distal access sites."

Given the dearth of information on this topic, Dr. Farber and his associates set out to compare outcomes of forearm and upper arm grafts and to evaluate the association between upper extremity AV graft configuration, location, venous outflow, and patency in 649 patients from a multicenter trial conducted by the Dialysis Access Consortium (DAC). This was a randomized, controlled trial of dipyridamole versus placebo in patients with new AV grafts. It found that dipyridamole increased primary unassisted graft patency (N. Engl. J. Med. 2009;360:2191-201). "The important thing for us was that this is the largest randomized, controlled trial of AV grafts conducted to date," Dr. Farber said.

He presented results from 522 patients with AV grafts that were based on the brachial artery. Of the 522 patients, 269 had a forearm graft (fAVG) and 253 had an upper arm graft (uAVG). The primary outcome was loss of primary unassisted patency. "This was defined as a first occurrence of graft thrombosis, an access procedure to correct a greater than 50% stenosis, or other surgical graft modification," Dr. Farber explained. The secondary outcome was cumulative graft failure, "which was defined as the time from randomization to complete loss of access site for dialysis." Kaplan-Meier curves and Cox models were used to examine the effects of access location and configuration on study outcomes.

Compared with patients in the fAVG group, those in the uAVG group were more likely to be male (43% vs. 34%), to be African-American (78% vs. 62%), to have a lower body mass index (mean of 29 kg/m² vs. a mean of 32 kg/m²), to have a lower baseline systolic blood pressure (139 mm Hg vs. 146 mm Hg), to have hemodialysis initiated before graft placement (80% vs. 64%), and to be on dialysis for a longer period of time (a mean of 2.59 years vs. a mean of 2.51 years).

Unadjusted analyses showed that there was no significant difference in the loss of primary unassisted graft patency or cumulative graft failure between the fAVG and uAVG groups.

Multivariate analyses of outcomes controlled for covariates revealed that the risk of loss of primary unassisted graft patency was not significantly higher in the uAVG group, compared with the fAVG group (hazard ratio of 1.24; P = .15). However, there was a suggestion of an association of increased risk of cumulative graft failure among upper arm grafts (HR 1.37; P = .09).

In a comparison of straight vs. looped grafts, straight configuration grafts "appeared to have a lower risk of primary and secondary failure, compared with looped figuration grafts, [but] this difference was not statistically significant," he said.

When compared to forearm looped grafts, which were used as a reference, there was no significant difference in the risk of primary and secondary failure among straight fAVGs, straight uAVGs, and looped uAVGs. There was a suggestion of increased risk of failure among upper arm looped grafts (HR 1.47; P = .06). There were also no significant differences between the two groups in adverse events and complications at 30 days.

Dr. Farber acknowledged certain limitations of the study. "Like any observational comparison of treatment groups, analysis was susceptible to uncontrolled confounding [variables]," he said. "We did a post hoc analysis of a randomized trial which did not answer the questions that we posed. Preoperative artery and vein diameters were not recorded and the reasons for graft selection are not known. Lastly, access interventions were followed for only 30 days beyond the occurrence of the primary endpoint, so we couldn’t really use access intervention to thoroughly evaluate the determinants of cumulative graft failure."

Dr. Farber said that he had no disclosures.

[email protected]

SAN FRANCISCO – Outcomes of forearm and upper arm hemodialysis arteriovenous grafts are similar despite the fact that large caliber outflow veins are often encountered in the upper arm, results from a large trial showed.

"To preserve a maximal number of access sites, forearm location should always be considered before resorting to an upper arm graft," Dr. Alik Farber said at the Society for Vascular Surgery Annual Meeting.

The incidence and prevalence of end-stage renal disease in the United States has grown exponentially in the past 25 years, said Dr. Farber, chief of vascular and endovascular surgery at Boston University Medical Center. "In fact, in 2010 almost 400,000 patients were undergoing hemodialysis," he said. "At the same time, there has been a steady increase in the percent of AV fistulas placed and an associated decline in the percent of AV grafts placed in the United States. In 2010, 20% of patients were undergoing hemodialysis through AV grafts."

Most grafts in the upper extremity are based on the brachial artery. Some are in the forearm while others are in the upper arm. "In the forearm most grafts are looped," Dr. Farber said. "In the upper arm some are looped and some are straight. As it turns out, the optimal graft configuration is unknown. The optimal venous outflow in the upper extremity is unknown. And the optimal location of the first-time AV graft is controversial."

He went on to note that the forearm AV graft "saves the upper arm for a future graft site and has a potential advantage of increasing the suitability of upper arm veins for future native fistula. On the other hand, there is some evidence in the literature that forearm grafts have lower patency rates. The upper arm graft may have higher patency rates because they are ‘sawn into’ large caliber veins. However, surgeons who preferentially place upper arm grafts tend to skip potential distal access sites."

Given the dearth of information on this topic, Dr. Farber and his associates set out to compare outcomes of forearm and upper arm grafts and to evaluate the association between upper extremity AV graft configuration, location, venous outflow, and patency in 649 patients from a multicenter trial conducted by the Dialysis Access Consortium (DAC). This was a randomized, controlled trial of dipyridamole versus placebo in patients with new AV grafts. It found that dipyridamole increased primary unassisted graft patency (N. Engl. J. Med. 2009;360:2191-201). "The important thing for us was that this is the largest randomized, controlled trial of AV grafts conducted to date," Dr. Farber said.

He presented results from 522 patients with AV grafts that were based on the brachial artery. Of the 522 patients, 269 had a forearm graft (fAVG) and 253 had an upper arm graft (uAVG). The primary outcome was loss of primary unassisted patency. "This was defined as a first occurrence of graft thrombosis, an access procedure to correct a greater than 50% stenosis, or other surgical graft modification," Dr. Farber explained. The secondary outcome was cumulative graft failure, "which was defined as the time from randomization to complete loss of access site for dialysis." Kaplan-Meier curves and Cox models were used to examine the effects of access location and configuration on study outcomes.

Compared with patients in the fAVG group, those in the uAVG group were more likely to be male (43% vs. 34%), to be African-American (78% vs. 62%), to have a lower body mass index (mean of 29 kg/m² vs. a mean of 32 kg/m²), to have a lower baseline systolic blood pressure (139 mm Hg vs. 146 mm Hg), to have hemodialysis initiated before graft placement (80% vs. 64%), and to be on dialysis for a longer period of time (a mean of 2.59 years vs. a mean of 2.51 years).

Unadjusted analyses showed that there was no significant difference in the loss of primary unassisted graft patency or cumulative graft failure between the fAVG and uAVG groups.

Multivariate analyses of outcomes controlled for covariates revealed that the risk of loss of primary unassisted graft patency was not significantly higher in the uAVG group, compared with the fAVG group (hazard ratio of 1.24; P = .15). However, there was a suggestion of an association of increased risk of cumulative graft failure among upper arm grafts (HR 1.37; P = .09).

In a comparison of straight vs. looped grafts, straight configuration grafts "appeared to have a lower risk of primary and secondary failure, compared with looped figuration grafts, [but] this difference was not statistically significant," he said.

When compared to forearm looped grafts, which were used as a reference, there was no significant difference in the risk of primary and secondary failure among straight fAVGs, straight uAVGs, and looped uAVGs. There was a suggestion of increased risk of failure among upper arm looped grafts (HR 1.47; P = .06). There were also no significant differences between the two groups in adverse events and complications at 30 days.

Dr. Farber acknowledged certain limitations of the study. "Like any observational comparison of treatment groups, analysis was susceptible to uncontrolled confounding [variables]," he said. "We did a post hoc analysis of a randomized trial which did not answer the questions that we posed. Preoperative artery and vein diameters were not recorded and the reasons for graft selection are not known. Lastly, access interventions were followed for only 30 days beyond the occurrence of the primary endpoint, so we couldn’t really use access intervention to thoroughly evaluate the determinants of cumulative graft failure."

Dr. Farber said that he had no disclosures.

[email protected]

SAN FRANCISCO – Outcomes of forearm and upper arm hemodialysis arteriovenous grafts are similar despite the fact that large caliber outflow veins are often encountered in the upper arm, results from a large trial showed.

"To preserve a maximal number of access sites, forearm location should always be considered before resorting to an upper arm graft," Dr. Alik Farber said at the Society for Vascular Surgery Annual Meeting.

The incidence and prevalence of end-stage renal disease in the United States has grown exponentially in the past 25 years, said Dr. Farber, chief of vascular and endovascular surgery at Boston University Medical Center. "In fact, in 2010 almost 400,000 patients were undergoing hemodialysis," he said. "At the same time, there has been a steady increase in the percent of AV fistulas placed and an associated decline in the percent of AV grafts placed in the United States. In 2010, 20% of patients were undergoing hemodialysis through AV grafts."

Most grafts in the upper extremity are based on the brachial artery. Some are in the forearm while others are in the upper arm. "In the forearm most grafts are looped," Dr. Farber said. "In the upper arm some are looped and some are straight. As it turns out, the optimal graft configuration is unknown. The optimal venous outflow in the upper extremity is unknown. And the optimal location of the first-time AV graft is controversial."

He went on to note that the forearm AV graft "saves the upper arm for a future graft site and has a potential advantage of increasing the suitability of upper arm veins for future native fistula. On the other hand, there is some evidence in the literature that forearm grafts have lower patency rates. The upper arm graft may have higher patency rates because they are ‘sawn into’ large caliber veins. However, surgeons who preferentially place upper arm grafts tend to skip potential distal access sites."

Given the dearth of information on this topic, Dr. Farber and his associates set out to compare outcomes of forearm and upper arm grafts and to evaluate the association between upper extremity AV graft configuration, location, venous outflow, and patency in 649 patients from a multicenter trial conducted by the Dialysis Access Consortium (DAC). This was a randomized, controlled trial of dipyridamole versus placebo in patients with new AV grafts. It found that dipyridamole increased primary unassisted graft patency (N. Engl. J. Med. 2009;360:2191-201). "The important thing for us was that this is the largest randomized, controlled trial of AV grafts conducted to date," Dr. Farber said.

He presented results from 522 patients with AV grafts that were based on the brachial artery. Of the 522 patients, 269 had a forearm graft (fAVG) and 253 had an upper arm graft (uAVG). The primary outcome was loss of primary unassisted patency. "This was defined as a first occurrence of graft thrombosis, an access procedure to correct a greater than 50% stenosis, or other surgical graft modification," Dr. Farber explained. The secondary outcome was cumulative graft failure, "which was defined as the time from randomization to complete loss of access site for dialysis." Kaplan-Meier curves and Cox models were used to examine the effects of access location and configuration on study outcomes.

Compared with patients in the fAVG group, those in the uAVG group were more likely to be male (43% vs. 34%), to be African-American (78% vs. 62%), to have a lower body mass index (mean of 29 kg/m² vs. a mean of 32 kg/m²), to have a lower baseline systolic blood pressure (139 mm Hg vs. 146 mm Hg), to have hemodialysis initiated before graft placement (80% vs. 64%), and to be on dialysis for a longer period of time (a mean of 2.59 years vs. a mean of 2.51 years).

Unadjusted analyses showed that there was no significant difference in the loss of primary unassisted graft patency or cumulative graft failure between the fAVG and uAVG groups.

Multivariate analyses of outcomes controlled for covariates revealed that the risk of loss of primary unassisted graft patency was not significantly higher in the uAVG group, compared with the fAVG group (hazard ratio of 1.24; P = .15). However, there was a suggestion of an association of increased risk of cumulative graft failure among upper arm grafts (HR 1.37; P = .09).

In a comparison of straight vs. looped grafts, straight configuration grafts "appeared to have a lower risk of primary and secondary failure, compared with looped figuration grafts, [but] this difference was not statistically significant," he said.

When compared to forearm looped grafts, which were used as a reference, there was no significant difference in the risk of primary and secondary failure among straight fAVGs, straight uAVGs, and looped uAVGs. There was a suggestion of increased risk of failure among upper arm looped grafts (HR 1.47; P = .06). There were also no significant differences between the two groups in adverse events and complications at 30 days.

Dr. Farber acknowledged certain limitations of the study. "Like any observational comparison of treatment groups, analysis was susceptible to uncontrolled confounding [variables]," he said. "We did a post hoc analysis of a randomized trial which did not answer the questions that we posed. Preoperative artery and vein diameters were not recorded and the reasons for graft selection are not known. Lastly, access interventions were followed for only 30 days beyond the occurrence of the primary endpoint, so we couldn’t really use access intervention to thoroughly evaluate the determinants of cumulative graft failure."

Dr. Farber said that he had no disclosures.

[email protected]

Living in the stroke belt as an adolescent is significantly associated with a high risk of stroke, according to research published online ahead of print April 24 in Neurology. Researchers examined data for 24,544 stroke-free participants in the Reasons for Geographic and Racial Differences in Stroke study. Stroke belt exposure was calculated by combinations of stroke belt birthplace, current residence, and proportion of years in the stroke belt during discrete age categories. Risk of stroke was significantly associated with proportion of life in the stroke belt and with all other exposure periods except birth, ages 31 to 45, and current residence. After adjustment for risk factors, the risk of stroke remained significantly associated only with proportion of residence in the stroke belt during adolescence.

Increased levels of trimethylamine-N-oxide (TMAO), a proatherosclerotic metabolite, are associated with an increased risk of stroke, myocardial infarction, or death, according to research published in the April 25 New England Journal of Medicine. Investigators measured TMAO, choline, and betaine levels in patients who had eaten two hard-boiled eggs and deuterium [d9]-labeled phosphatidylcholine before and after suppressing intestinal microbiota with antibiotics. They also examined the relationship between fasting plasma levels of TMAO and major adverse cardiovascular events during three years of follow-up. Increased plasma levels of TMAO were associated with an increased risk of a major adverse cardiovascular event. An elevated TMAO level predicted an increased risk of major adverse cardiovascular events after adjustment for traditional risk factors, as well as in lower-risk subgroups.

A single-nucleotide polymorphism (SNP) in the ABCA7 gene was significantly linked with an increased risk of Alzheimer’s disease among African Americans, according to research published in the April 10 JAMA. African Americans with this mutation have nearly double the risk of Alzheimer’s disease, but the SNP is not associated with the disease among Europeans. The effect size for the SNP in ABCA7 was comparable with that of the APOE ε4–determining SNP rs429358. Investigators examined data for 5,896 African Americans (1,968 with Alzheimer’s disease and 3,928 controls) who were 60 or older. Data were collected between 1989 and 2011 at multiple sites. The team assessed the association of Alzheimer’s disease with genotyped and imputed SNPs in case–control and in family-based data sets.

The FDA has approved the Precision Spectra Spinal Cord Stimulator (SCS) System, which is designed to provide improved pain relief to patients with chronic pain. The system, manufactured by Boston Scientific (Natick, Massachusetts), includes Illumina 3D software intended to improve physicians’ control of the stimulation field. It is based on a proprietary computer model that takes into account 3-D anatomical structures, including the conductivity of the spinal cord and surrounding tissue. The physician can select a desired location on the spinal cord and prompt the programming software to create a customized stimulation field to mask the patient’s pain. Previous SCS systems included 16 contacts, but the Precision Spectra system includes 32 contacts and is designed to offer more coverage of the spinal cord.

Framingham risk scores may be better than a dementia risk score for assessing individuals’ risk of cognitive decline and targeting modifiable risk factors, according to research published in the April 2 Neurology. Researchers examined data for participants in the Whitehall II longitudinal cohort study. Subjects’ mean age at baseline was 55.6. The investigators compared the Framingham general cardiovascular disease risk score and the Framingham stroke risk score with the Cardiovascular Risk Factors, Aging, and Dementia risk score. Patients underwent cognitive tests of reasoning, memory, verbal fluency, vocabulary, and global cognition three times over 10 years. Compared with the dementia risk score, cardiovascular and stroke risk scores showed slightly stronger associations with 10-year cognitive decline. The differences were statistically significant for semantic fluency and global cognitive scores.

Children born to women who used valproate during pregnancy may have a significantly increased risk of autism spectrum disorder and childhood autism, according to research published in the April 24 JAMA. Investigators used national registers to identify Danish children exposed to valproate during pregnancy and diagnosed with autism spectrum disorders. The researchers analyzed the risks associated with all autism spectrum disorders, as well as childhood autism, and adjusted for potential confounders. The estimated absolute risk after 14 years of follow-up was 1.53% for autism spectrum disorder and 0.48% for childhood autism. The 508 children exposed to valproate had an absolute risk of 4.42% for autism spectrum disorder and an absolute risk of 2.50% for childhood autism. Results changed slightly after considering only the children born to women with epilepsy.

The antisense oligonucleotide ISIS 333611 is a safe treatment for amyotrophic lateral sclerosis (ALS), according to a trial published online ahead of print March 29 in Lancet Neurology. Investigators studied 32 patients with SOD1-positive ALS in a randomized, placebo-controlled, phase I trial. The researchers delivered the drug by intrathecal infusion using an external pump over 11.5 hours at increasing doses (0.15 mg, 0.50 mg, 1.50 mg, and 3.00 mg). Approximately 88% of patients in the placebo group had adverse events, compared with 83% in the active group. The most common events were post-lumbar puncture syndrome, back pain, and nausea. The investigators found no dose-limiting toxic effects or safety or tolerability concerns related to ISIS 333611. No serious adverse events occurred in patients given ISIS 333611.

Thalamic atrophy in patients with clinically isolated syndrome (CIS) is associated with the development of clinically definite multiple sclerosis (MS), according to a study published online ahead of print April 23 in Radiology. Using MRI, researchers assessed 216 patients with CIS at baseline, six months, one year, and two years. MRI measures of progression included new and enlarged T2 lesions and changes in whole-brain, tissue-specific global, and regional gray matter volumes. In mixed-effect model analysis, the lateral ventricle volume, accumulation of new total T2 and new enlarging T2 lesions increase, and thalamic and whole-brain volume decrease were associated with development of clinically definite MS. In multivariate regression analysis, decrease in thalamic volumes and increase in lateral ventricle volumes were associated with the development of clinically definite MS.

Functional MRI (fMRI) can identify pain caused by heat in healthy persons, according to research published in the April 11 New England Journal of Medicine. In four studies of 114 participants, investigators developed an fMRI-based measure that predicts pain intensity, tested its sensitivity and specificity to pain versus warmth, assessed its specificity relative to social pain, and assessed the responsiveness of the measure to the analgesic remifentanil. The neurologic signature distinguished painful heat from nonpainful warmth, pain anticipation, and pain recall with sensitivity and specificity of 94% or more. The signature discriminated between painful heat and nonpainful warmth with 93% sensitivity and specificity. It also distinguished between physical pain and social pain with 85% sensitivity and 73% specificity. The strength of the signature response was substantially reduced after remifentanil administration.

Family history of late-onset Alzheimer’s disease is associated with an increased prevalence of an abnormal cerebral beta-amyloid and tau protein phenotype in patients with mild cognitive impairment (MCI), according to a study published on April 17 in PLOS One. Investigators studied 257 participants (ages 55 to 89) in the Alzheimer’s Disease Neuroimaging Initiative. Subjects were categorized as cognitively normal, having MCI, or having Alzheimer’s disease. Among patients with MCI, CSF Ab42 was lower, t-tau was higher, and t-tau–Ab42 ratio was higher in patients with a family history of Alzheimer’s disease than in patients without. A significant residual effect of family history on pathologic markers in MCI remained after adjusting for APOE e4. The effect of family history was not significant in patients with Alzheimer’s disease.

Most potential migraine triggers are so variable that it may not be possible to identify them without formal experimentation, according to a study published in the April issue of Headache. Investigators examined the similarity of day-to-day weather conditions over four years, as well as the similarity of ovarian hormones and perceived stress over a median of 89 days in nine patients with headache and regular menstrual cycles. A threshold of 90% similarity using Gower’s index identified similar days for comparison. The day-to-day variability in the three headache triggers was substantial enough that finding two naturally similar days for which to contrast the effect of a fourth trigger (eg, drinking wine) occurred infrequently. Fluctuations in weather patterns resulted in a median of 2.3 similar days each year.

Elevated low-density lipoprotein (LDL) cholesterol and altered cholesterol homeostasis may promote neurodegeneration, atherosclerosis, and Alzheimer’s disease by disrupting chromosome segregation, according to research published on April 12 in PLOS One. In a study of mice, investigators observed that high dietary cholesterol induced aneuploidy. In a separate study, the accumulation of intracellular cholesterol was associated with the accumulation of aneuploid fibroblasts, neurons, and glia in patients with Niemann-Pick C1. The researchers also observed that oxidized LDL, LDL, and cholesterol, but not high-density lipoprotein (HDL), induced chromosome mis-segregation and aneuploidy in cultured cells, including neuronal precursors. LDL-induced aneuploidy required the LDL receptor, but not Ab. Cholesterol treatment disrupted the structure of the mitotic spindle, providing a cell biologic mechanism for its aneugenic activity, and ethanol or calcium chelation attenuated lipoprotein-induced chromosome mis-segregation.

The incidence of dementia in central Stockholm may have decreased from the late 1980s to the early 2000s, according to research published online ahead of print April 17 in Neurology. Investigators analyzed data from two cross-sectional surveys of people ages 75 or older. One study was conducted from 1987 to 1989 and included 1,700 participants; the other was conducted from 2001 to 2004 and included 1,575 subjects. The team inferred the incidence of dementia according to its relationship with prevalence and survival. The adjusted odds ratio of dementia in the later study versus the earlier study was 1.17. The multiadjusted hazard ratio of death in the later study versus the earlier study was 0.71 in subjects with dementia, 0.68 in those without dementia, and 0.66 in all participants.

—Erik Greb
Senior Associate Editor

Living in the stroke belt as an adolescent is significantly associated with a high risk of stroke, according to research published online ahead of print April 24 in Neurology. Researchers examined data for 24,544 stroke-free participants in the Reasons for Geographic and Racial Differences in Stroke study. Stroke belt exposure was calculated by combinations of stroke belt birthplace, current residence, and proportion of years in the stroke belt during discrete age categories. Risk of stroke was significantly associated with proportion of life in the stroke belt and with all other exposure periods except birth, ages 31 to 45, and current residence. After adjustment for risk factors, the risk of stroke remained significantly associated only with proportion of residence in the stroke belt during adolescence.

Increased levels of trimethylamine-N-oxide (TMAO), a proatherosclerotic metabolite, are associated with an increased risk of stroke, myocardial infarction, or death, according to research published in the April 25 New England Journal of Medicine. Investigators measured TMAO, choline, and betaine levels in patients who had eaten two hard-boiled eggs and deuterium [d9]-labeled phosphatidylcholine before and after suppressing intestinal microbiota with antibiotics. They also examined the relationship between fasting plasma levels of TMAO and major adverse cardiovascular events during three years of follow-up. Increased plasma levels of TMAO were associated with an increased risk of a major adverse cardiovascular event. An elevated TMAO level predicted an increased risk of major adverse cardiovascular events after adjustment for traditional risk factors, as well as in lower-risk subgroups.

A single-nucleotide polymorphism (SNP) in the ABCA7 gene was significantly linked with an increased risk of Alzheimer’s disease among African Americans, according to research published in the April 10 JAMA. African Americans with this mutation have nearly double the risk of Alzheimer’s disease, but the SNP is not associated with the disease among Europeans. The effect size for the SNP in ABCA7 was comparable with that of the APOE ε4–determining SNP rs429358. Investigators examined data for 5,896 African Americans (1,968 with Alzheimer’s disease and 3,928 controls) who were 60 or older. Data were collected between 1989 and 2011 at multiple sites. The team assessed the association of Alzheimer’s disease with genotyped and imputed SNPs in case–control and in family-based data sets.

The FDA has approved the Precision Spectra Spinal Cord Stimulator (SCS) System, which is designed to provide improved pain relief to patients with chronic pain. The system, manufactured by Boston Scientific (Natick, Massachusetts), includes Illumina 3D software intended to improve physicians’ control of the stimulation field. It is based on a proprietary computer model that takes into account 3-D anatomical structures, including the conductivity of the spinal cord and surrounding tissue. The physician can select a desired location on the spinal cord and prompt the programming software to create a customized stimulation field to mask the patient’s pain. Previous SCS systems included 16 contacts, but the Precision Spectra system includes 32 contacts and is designed to offer more coverage of the spinal cord.

Framingham risk scores may be better than a dementia risk score for assessing individuals’ risk of cognitive decline and targeting modifiable risk factors, according to research published in the April 2 Neurology. Researchers examined data for participants in the Whitehall II longitudinal cohort study. Subjects’ mean age at baseline was 55.6. The investigators compared the Framingham general cardiovascular disease risk score and the Framingham stroke risk score with the Cardiovascular Risk Factors, Aging, and Dementia risk score. Patients underwent cognitive tests of reasoning, memory, verbal fluency, vocabulary, and global cognition three times over 10 years. Compared with the dementia risk score, cardiovascular and stroke risk scores showed slightly stronger associations with 10-year cognitive decline. The differences were statistically significant for semantic fluency and global cognitive scores.

Children born to women who used valproate during pregnancy may have a significantly increased risk of autism spectrum disorder and childhood autism, according to research published in the April 24 JAMA. Investigators used national registers to identify Danish children exposed to valproate during pregnancy and diagnosed with autism spectrum disorders. The researchers analyzed the risks associated with all autism spectrum disorders, as well as childhood autism, and adjusted for potential confounders. The estimated absolute risk after 14 years of follow-up was 1.53% for autism spectrum disorder and 0.48% for childhood autism. The 508 children exposed to valproate had an absolute risk of 4.42% for autism spectrum disorder and an absolute risk of 2.50% for childhood autism. Results changed slightly after considering only the children born to women with epilepsy.

The antisense oligonucleotide ISIS 333611 is a safe treatment for amyotrophic lateral sclerosis (ALS), according to a trial published online ahead of print March 29 in Lancet Neurology. Investigators studied 32 patients with SOD1-positive ALS in a randomized, placebo-controlled, phase I trial. The researchers delivered the drug by intrathecal infusion using an external pump over 11.5 hours at increasing doses (0.15 mg, 0.50 mg, 1.50 mg, and 3.00 mg). Approximately 88% of patients in the placebo group had adverse events, compared with 83% in the active group. The most common events were post-lumbar puncture syndrome, back pain, and nausea. The investigators found no dose-limiting toxic effects or safety or tolerability concerns related to ISIS 333611. No serious adverse events occurred in patients given ISIS 333611.

Thalamic atrophy in patients with clinically isolated syndrome (CIS) is associated with the development of clinically definite multiple sclerosis (MS), according to a study published online ahead of print April 23 in Radiology. Using MRI, researchers assessed 216 patients with CIS at baseline, six months, one year, and two years. MRI measures of progression included new and enlarged T2 lesions and changes in whole-brain, tissue-specific global, and regional gray matter volumes. In mixed-effect model analysis, the lateral ventricle volume, accumulation of new total T2 and new enlarging T2 lesions increase, and thalamic and whole-brain volume decrease were associated with development of clinically definite MS. In multivariate regression analysis, decrease in thalamic volumes and increase in lateral ventricle volumes were associated with the development of clinically definite MS.

Functional MRI (fMRI) can identify pain caused by heat in healthy persons, according to research published in the April 11 New England Journal of Medicine. In four studies of 114 participants, investigators developed an fMRI-based measure that predicts pain intensity, tested its sensitivity and specificity to pain versus warmth, assessed its specificity relative to social pain, and assessed the responsiveness of the measure to the analgesic remifentanil. The neurologic signature distinguished painful heat from nonpainful warmth, pain anticipation, and pain recall with sensitivity and specificity of 94% or more. The signature discriminated between painful heat and nonpainful warmth with 93% sensitivity and specificity. It also distinguished between physical pain and social pain with 85% sensitivity and 73% specificity. The strength of the signature response was substantially reduced after remifentanil administration.

Family history of late-onset Alzheimer’s disease is associated with an increased prevalence of an abnormal cerebral beta-amyloid and tau protein phenotype in patients with mild cognitive impairment (MCI), according to a study published on April 17 in PLOS One. Investigators studied 257 participants (ages 55 to 89) in the Alzheimer’s Disease Neuroimaging Initiative. Subjects were categorized as cognitively normal, having MCI, or having Alzheimer’s disease. Among patients with MCI, CSF Ab42 was lower, t-tau was higher, and t-tau–Ab42 ratio was higher in patients with a family history of Alzheimer’s disease than in patients without. A significant residual effect of family history on pathologic markers in MCI remained after adjusting for APOE e4. The effect of family history was not significant in patients with Alzheimer’s disease.

Most potential migraine triggers are so variable that it may not be possible to identify them without formal experimentation, according to a study published in the April issue of Headache. Investigators examined the similarity of day-to-day weather conditions over four years, as well as the similarity of ovarian hormones and perceived stress over a median of 89 days in nine patients with headache and regular menstrual cycles. A threshold of 90% similarity using Gower’s index identified similar days for comparison. The day-to-day variability in the three headache triggers was substantial enough that finding two naturally similar days for which to contrast the effect of a fourth trigger (eg, drinking wine) occurred infrequently. Fluctuations in weather patterns resulted in a median of 2.3 similar days each year.

Elevated low-density lipoprotein (LDL) cholesterol and altered cholesterol homeostasis may promote neurodegeneration, atherosclerosis, and Alzheimer’s disease by disrupting chromosome segregation, according to research published on April 12 in PLOS One. In a study of mice, investigators observed that high dietary cholesterol induced aneuploidy. In a separate study, the accumulation of intracellular cholesterol was associated with the accumulation of aneuploid fibroblasts, neurons, and glia in patients with Niemann-Pick C1. The researchers also observed that oxidized LDL, LDL, and cholesterol, but not high-density lipoprotein (HDL), induced chromosome mis-segregation and aneuploidy in cultured cells, including neuronal precursors. LDL-induced aneuploidy required the LDL receptor, but not Ab. Cholesterol treatment disrupted the structure of the mitotic spindle, providing a cell biologic mechanism for its aneugenic activity, and ethanol or calcium chelation attenuated lipoprotein-induced chromosome mis-segregation.

The incidence of dementia in central Stockholm may have decreased from the late 1980s to the early 2000s, according to research published online ahead of print April 17 in Neurology. Investigators analyzed data from two cross-sectional surveys of people ages 75 or older. One study was conducted from 1987 to 1989 and included 1,700 participants; the other was conducted from 2001 to 2004 and included 1,575 subjects. The team inferred the incidence of dementia according to its relationship with prevalence and survival. The adjusted odds ratio of dementia in the later study versus the earlier study was 1.17. The multiadjusted hazard ratio of death in the later study versus the earlier study was 0.71 in subjects with dementia, 0.68 in those without dementia, and 0.66 in all participants.

—Erik Greb
Senior Associate Editor

Living in the stroke belt as an adolescent is significantly associated with a high risk of stroke, according to research published online ahead of print April 24 in Neurology. Researchers examined data for 24,544 stroke-free participants in the Reasons for Geographic and Racial Differences in Stroke study. Stroke belt exposure was calculated by combinations of stroke belt birthplace, current residence, and proportion of years in the stroke belt during discrete age categories. Risk of stroke was significantly associated with proportion of life in the stroke belt and with all other exposure periods except birth, ages 31 to 45, and current residence. After adjustment for risk factors, the risk of stroke remained significantly associated only with proportion of residence in the stroke belt during adolescence.

Increased levels of trimethylamine-N-oxide (TMAO), a proatherosclerotic metabolite, are associated with an increased risk of stroke, myocardial infarction, or death, according to research published in the April 25 New England Journal of Medicine. Investigators measured TMAO, choline, and betaine levels in patients who had eaten two hard-boiled eggs and deuterium [d9]-labeled phosphatidylcholine before and after suppressing intestinal microbiota with antibiotics. They also examined the relationship between fasting plasma levels of TMAO and major adverse cardiovascular events during three years of follow-up. Increased plasma levels of TMAO were associated with an increased risk of a major adverse cardiovascular event. An elevated TMAO level predicted an increased risk of major adverse cardiovascular events after adjustment for traditional risk factors, as well as in lower-risk subgroups.

A single-nucleotide polymorphism (SNP) in the ABCA7 gene was significantly linked with an increased risk of Alzheimer’s disease among African Americans, according to research published in the April 10 JAMA. African Americans with this mutation have nearly double the risk of Alzheimer’s disease, but the SNP is not associated with the disease among Europeans. The effect size for the SNP in ABCA7 was comparable with that of the APOE ε4–determining SNP rs429358. Investigators examined data for 5,896 African Americans (1,968 with Alzheimer’s disease and 3,928 controls) who were 60 or older. Data were collected between 1989 and 2011 at multiple sites. The team assessed the association of Alzheimer’s disease with genotyped and imputed SNPs in case–control and in family-based data sets.

The FDA has approved the Precision Spectra Spinal Cord Stimulator (SCS) System, which is designed to provide improved pain relief to patients with chronic pain. The system, manufactured by Boston Scientific (Natick, Massachusetts), includes Illumina 3D software intended to improve physicians’ control of the stimulation field. It is based on a proprietary computer model that takes into account 3-D anatomical structures, including the conductivity of the spinal cord and surrounding tissue. The physician can select a desired location on the spinal cord and prompt the programming software to create a customized stimulation field to mask the patient’s pain. Previous SCS systems included 16 contacts, but the Precision Spectra system includes 32 contacts and is designed to offer more coverage of the spinal cord.

Framingham risk scores may be better than a dementia risk score for assessing individuals’ risk of cognitive decline and targeting modifiable risk factors, according to research published in the April 2 Neurology. Researchers examined data for participants in the Whitehall II longitudinal cohort study. Subjects’ mean age at baseline was 55.6. The investigators compared the Framingham general cardiovascular disease risk score and the Framingham stroke risk score with the Cardiovascular Risk Factors, Aging, and Dementia risk score. Patients underwent cognitive tests of reasoning, memory, verbal fluency, vocabulary, and global cognition three times over 10 years. Compared with the dementia risk score, cardiovascular and stroke risk scores showed slightly stronger associations with 10-year cognitive decline. The differences were statistically significant for semantic fluency and global cognitive scores.

Children born to women who used valproate during pregnancy may have a significantly increased risk of autism spectrum disorder and childhood autism, according to research published in the April 24 JAMA. Investigators used national registers to identify Danish children exposed to valproate during pregnancy and diagnosed with autism spectrum disorders. The researchers analyzed the risks associated with all autism spectrum disorders, as well as childhood autism, and adjusted for potential confounders. The estimated absolute risk after 14 years of follow-up was 1.53% for autism spectrum disorder and 0.48% for childhood autism. The 508 children exposed to valproate had an absolute risk of 4.42% for autism spectrum disorder and an absolute risk of 2.50% for childhood autism. Results changed slightly after considering only the children born to women with epilepsy.

The antisense oligonucleotide ISIS 333611 is a safe treatment for amyotrophic lateral sclerosis (ALS), according to a trial published online ahead of print March 29 in Lancet Neurology. Investigators studied 32 patients with SOD1-positive ALS in a randomized, placebo-controlled, phase I trial. The researchers delivered the drug by intrathecal infusion using an external pump over 11.5 hours at increasing doses (0.15 mg, 0.50 mg, 1.50 mg, and 3.00 mg). Approximately 88% of patients in the placebo group had adverse events, compared with 83% in the active group. The most common events were post-lumbar puncture syndrome, back pain, and nausea. The investigators found no dose-limiting toxic effects or safety or tolerability concerns related to ISIS 333611. No serious adverse events occurred in patients given ISIS 333611.

Thalamic atrophy in patients with clinically isolated syndrome (CIS) is associated with the development of clinically definite multiple sclerosis (MS), according to a study published online ahead of print April 23 in Radiology. Using MRI, researchers assessed 216 patients with CIS at baseline, six months, one year, and two years. MRI measures of progression included new and enlarged T2 lesions and changes in whole-brain, tissue-specific global, and regional gray matter volumes. In mixed-effect model analysis, the lateral ventricle volume, accumulation of new total T2 and new enlarging T2 lesions increase, and thalamic and whole-brain volume decrease were associated with development of clinically definite MS. In multivariate regression analysis, decrease in thalamic volumes and increase in lateral ventricle volumes were associated with the development of clinically definite MS.

Functional MRI (fMRI) can identify pain caused by heat in healthy persons, according to research published in the April 11 New England Journal of Medicine. In four studies of 114 participants, investigators developed an fMRI-based measure that predicts pain intensity, tested its sensitivity and specificity to pain versus warmth, assessed its specificity relative to social pain, and assessed the responsiveness of the measure to the analgesic remifentanil. The neurologic signature distinguished painful heat from nonpainful warmth, pain anticipation, and pain recall with sensitivity and specificity of 94% or more. The signature discriminated between painful heat and nonpainful warmth with 93% sensitivity and specificity. It also distinguished between physical pain and social pain with 85% sensitivity and 73% specificity. The strength of the signature response was substantially reduced after remifentanil administration.

Family history of late-onset Alzheimer’s disease is associated with an increased prevalence of an abnormal cerebral beta-amyloid and tau protein phenotype in patients with mild cognitive impairment (MCI), according to a study published on April 17 in PLOS One. Investigators studied 257 participants (ages 55 to 89) in the Alzheimer’s Disease Neuroimaging Initiative. Subjects were categorized as cognitively normal, having MCI, or having Alzheimer’s disease. Among patients with MCI, CSF Ab42 was lower, t-tau was higher, and t-tau–Ab42 ratio was higher in patients with a family history of Alzheimer’s disease than in patients without. A significant residual effect of family history on pathologic markers in MCI remained after adjusting for APOE e4. The effect of family history was not significant in patients with Alzheimer’s disease.

Most potential migraine triggers are so variable that it may not be possible to identify them without formal experimentation, according to a study published in the April issue of Headache. Investigators examined the similarity of day-to-day weather conditions over four years, as well as the similarity of ovarian hormones and perceived stress over a median of 89 days in nine patients with headache and regular menstrual cycles. A threshold of 90% similarity using Gower’s index identified similar days for comparison. The day-to-day variability in the three headache triggers was substantial enough that finding two naturally similar days for which to contrast the effect of a fourth trigger (eg, drinking wine) occurred infrequently. Fluctuations in weather patterns resulted in a median of 2.3 similar days each year.

Elevated low-density lipoprotein (LDL) cholesterol and altered cholesterol homeostasis may promote neurodegeneration, atherosclerosis, and Alzheimer’s disease by disrupting chromosome segregation, according to research published on April 12 in PLOS One. In a study of mice, investigators observed that high dietary cholesterol induced aneuploidy. In a separate study, the accumulation of intracellular cholesterol was associated with the accumulation of aneuploid fibroblasts, neurons, and glia in patients with Niemann-Pick C1. The researchers also observed that oxidized LDL, LDL, and cholesterol, but not high-density lipoprotein (HDL), induced chromosome mis-segregation and aneuploidy in cultured cells, including neuronal precursors. LDL-induced aneuploidy required the LDL receptor, but not Ab. Cholesterol treatment disrupted the structure of the mitotic spindle, providing a cell biologic mechanism for its aneugenic activity, and ethanol or calcium chelation attenuated lipoprotein-induced chromosome mis-segregation.

The incidence of dementia in central Stockholm may have decreased from the late 1980s to the early 2000s, according to research published online ahead of print April 17 in Neurology. Investigators analyzed data from two cross-sectional surveys of people ages 75 or older. One study was conducted from 1987 to 1989 and included 1,700 participants; the other was conducted from 2001 to 2004 and included 1,575 subjects. The team inferred the incidence of dementia according to its relationship with prevalence and survival. The adjusted odds ratio of dementia in the later study versus the earlier study was 1.17. The multiadjusted hazard ratio of death in the later study versus the earlier study was 0.71 in subjects with dementia, 0.68 in those without dementia, and 0.66 in all participants.

—Erik Greb
Senior Associate Editor