Jennie Smith

Combination treatment with GLP-1 agonist and basal insulin helps diabetes patients achieve glycemic control without increasing their risk of hypoglycemia or weight gain, a new meta-analysis has found.

The research, published online Sept. 12 in The Lancet, suggests that glucagon-like peptide-1 (GLP-1) agonists, injectable agents currently used mainly as second- or third-line treatments after oral diabetes therapies have failed, might merit a more prominent role in the treatment pathway in combination with basal insulin.

The authors of the meta-analysis, led by Conrad Eng of Mount Sinai Hospital, Toronto, analyzed results from 15 studies enrolling 4,348 patients with type 2 diabetes. All the studies compared GLP-1 agonists, including exenatide (Byetta), liraglutide (Victoza), and albiglutide (Tanzeum), and basal insulin with other regimens, which included oral agents with or without insulin, and insulin-only regimens.

A GLP-1 agonist plus basal insulin was associated with a reduction of 0.44% in more lowering of hemoglobin A1c and a near doubling in the likelihood of achieving a target HbA1c of 7% or below (relative risk, 1.92), compared with other diabetes treatments. No increased risk of hypoglycemia was seen associated with the GLP-1 and basal insulin regimens, and a mean reduction in weight of 3.22 kg was seen for these compared to the other treatments. Compared with full basal-bolus insulin regimens, a GLP-1 agonist plus basal insulin was seen associated with minimal reduction in HbA1c (–0.1%), but with lower risk of hypoglycemia (RR 0.67) and a reduction in mean weight of 5.66 kg.

The meta-analysis yielded “robust and consistent findings that lend support to the benefits of GLP-1 agonist and basal insulin combination treatment. Indeed, this consistency is apparent despite the fact that these studies differ in several ways, including the antidiabetic treatments assessed, the background oral antidiabetic drugs, the GLP-1 preparation under study, and the sequence of its initiation in relation to that of basal insulin,” Mr. Eng and his colleagues wrote. They acknowledged as limitations of their study the open-label design, industry funding, and short duration of some of the included clinical trials.

The study had no outside funding; one coauthor, Dr. Bernard Zinman, reported financial relationships with Novo Nordisk, Boehringer Ingelheim, Merck, Eli Lilly, AstraZeneca, Jansen, Takeda, and Sanofi-Aventis. Dr. Ravi Retnakaran, corresponding author, disclosed past compensation from Novo Nordisk and Merck.

Combination treatment with GLP-1 agonist and basal insulin helps diabetes patients achieve glycemic control without increasing their risk of hypoglycemia or weight gain, a new meta-analysis has found.

The research, published online Sept. 12 in The Lancet, suggests that glucagon-like peptide-1 (GLP-1) agonists, injectable agents currently used mainly as second- or third-line treatments after oral diabetes therapies have failed, might merit a more prominent role in the treatment pathway in combination with basal insulin.

The authors of the meta-analysis, led by Conrad Eng of Mount Sinai Hospital, Toronto, analyzed results from 15 studies enrolling 4,348 patients with type 2 diabetes. All the studies compared GLP-1 agonists, including exenatide (Byetta), liraglutide (Victoza), and albiglutide (Tanzeum), and basal insulin with other regimens, which included oral agents with or without insulin, and insulin-only regimens.

A GLP-1 agonist plus basal insulin was associated with a reduction of 0.44% in more lowering of hemoglobin A1c and a near doubling in the likelihood of achieving a target HbA1c of 7% or below (relative risk, 1.92), compared with other diabetes treatments. No increased risk of hypoglycemia was seen associated with the GLP-1 and basal insulin regimens, and a mean reduction in weight of 3.22 kg was seen for these compared to the other treatments. Compared with full basal-bolus insulin regimens, a GLP-1 agonist plus basal insulin was seen associated with minimal reduction in HbA1c (–0.1%), but with lower risk of hypoglycemia (RR 0.67) and a reduction in mean weight of 5.66 kg.

The meta-analysis yielded “robust and consistent findings that lend support to the benefits of GLP-1 agonist and basal insulin combination treatment. Indeed, this consistency is apparent despite the fact that these studies differ in several ways, including the antidiabetic treatments assessed, the background oral antidiabetic drugs, the GLP-1 preparation under study, and the sequence of its initiation in relation to that of basal insulin,” Mr. Eng and his colleagues wrote. They acknowledged as limitations of their study the open-label design, industry funding, and short duration of some of the included clinical trials.

The study had no outside funding; one coauthor, Dr. Bernard Zinman, reported financial relationships with Novo Nordisk, Boehringer Ingelheim, Merck, Eli Lilly, AstraZeneca, Jansen, Takeda, and Sanofi-Aventis. Dr. Ravi Retnakaran, corresponding author, disclosed past compensation from Novo Nordisk and Merck.

Combination treatment with GLP-1 agonist and basal insulin helps diabetes patients achieve glycemic control without increasing their risk of hypoglycemia or weight gain, a new meta-analysis has found.

The research, published online Sept. 12 in The Lancet, suggests that glucagon-like peptide-1 (GLP-1) agonists, injectable agents currently used mainly as second- or third-line treatments after oral diabetes therapies have failed, might merit a more prominent role in the treatment pathway in combination with basal insulin.

The authors of the meta-analysis, led by Conrad Eng of Mount Sinai Hospital, Toronto, analyzed results from 15 studies enrolling 4,348 patients with type 2 diabetes. All the studies compared GLP-1 agonists, including exenatide (Byetta), liraglutide (Victoza), and albiglutide (Tanzeum), and basal insulin with other regimens, which included oral agents with or without insulin, and insulin-only regimens.

A GLP-1 agonist plus basal insulin was associated with a reduction of 0.44% in more lowering of hemoglobin A1c and a near doubling in the likelihood of achieving a target HbA1c of 7% or below (relative risk, 1.92), compared with other diabetes treatments. No increased risk of hypoglycemia was seen associated with the GLP-1 and basal insulin regimens, and a mean reduction in weight of 3.22 kg was seen for these compared to the other treatments. Compared with full basal-bolus insulin regimens, a GLP-1 agonist plus basal insulin was seen associated with minimal reduction in HbA1c (–0.1%), but with lower risk of hypoglycemia (RR 0.67) and a reduction in mean weight of 5.66 kg.

The meta-analysis yielded “robust and consistent findings that lend support to the benefits of GLP-1 agonist and basal insulin combination treatment. Indeed, this consistency is apparent despite the fact that these studies differ in several ways, including the antidiabetic treatments assessed, the background oral antidiabetic drugs, the GLP-1 preparation under study, and the sequence of its initiation in relation to that of basal insulin,” Mr. Eng and his colleagues wrote. They acknowledged as limitations of their study the open-label design, industry funding, and short duration of some of the included clinical trials.

The study had no outside funding; one coauthor, Dr. Bernard Zinman, reported financial relationships with Novo Nordisk, Boehringer Ingelheim, Merck, Eli Lilly, AstraZeneca, Jansen, Takeda, and Sanofi-Aventis. Dr. Ravi Retnakaran, corresponding author, disclosed past compensation from Novo Nordisk and Merck.

Redundant combinations of intravenous antibiotics are used in nearly 8 of 10 hospitals, even though they are very infrequently indicated, said a group of researchers working to promote antimicrobial stewardship in hospitals.

In an article published in the October issue of Infection Control and Hospital Epidemiology, Leslie Schultz, R.N., Ph.D., of Premier Safety Institute in Charlotte, N.C., and colleagues reported that a review of cases from more than 500 U.S. hospitals revealed that about 150,000 days of inappropriate antibiotic therapy were prescribed, at an estimated excess cost of more than $12 million over the 4-year study period. Some 78% of hospitals in the study used the unnecessary drug combinations, they said.

©Bhakpong/thinkstockphotos.com

The combination of metronidazole and piperacillin-tazobactam accounted for more than half of the redundant treatments detected in the study, with some 32,500 cases receiving this combination for 2 days or more. Other commonly seen redundant treatments included metronidazole and ampicillin-sulbactam, along with metronidazole and ertapenem, which, together with the metronidazole and piperacillin-tazobactam combination, were seen as responsible for 70% of redundant treatments administered to patients (Infect. Control Hosp. Epidemiol. 2014; 35:1229-35).

In a telephone press conference on Sept. 10, one of Dr. Schultz’s coauthors on the paper, Dr. Arjun Srinivasan of the Centers for Disease Control and Prevention, Atlanta, said that, while concerns about antimicrobial stewardship are not new, the findings came as a surprise. "We would expect the use of these combinations to be vanishingly rare given how often they’re indicated," Dr. Srinivasan said, citing a lack of training in antibiotics as a contributing factor.

"We’ve heard from a lot of clinicians that providers don’t know that piperacillin-tazobactam very effectively kills anaerobic bacteria – but they do know that metronidazole is effective," Dr. Srinivasan said. "People are not as aware as they need to be about what antibiotics kill what bacteria, and we need to make sure people know which antibiotics need to be combined and when – and that with some, you don’t gain anything by adding the second drug. You only increase the risk of side effects."

Another physician taking part in the press conference, Dr. Sara Cosgrove of Johns Hopkins Hospital, Baltimore, agreed. "We have suboptimal training among medical students and house staff about what antibiotics cover what bugs," she said. "We have seen publications suggesting that medical students and residents want more info on antibiotics."

Dr. Cosgrove also noted that changes in hospital work practices may have contributed to the problem. "More people are working in hospitals on shorter shifts, and there are communication issues from one physician to the next. One physician may start an antibiotic and a second physician starts a second. There are many ways we can address the problem of unintended duplicate therapy," she said, including the use of alerts generated when pharmacy receives a request for a redundant drug.

Dr. Srinivasan said that hospitals that have implemented alerts have found them effective. Still, both physicians stressed that whatever the methods used, dedicated antimicrobial stewardship teams in hospitals were essential to ensuring the avoidance of redundant treatments.

"Many hospitals report that they are thinking about having an antimicrobial stewardship program. We’d like to nudge them to actually have one," said Dr. Cosgrove, who is chair of the antimicrobial stewardship committee for the Society for Healthcare Epidemiology of America, which publishes Infection Control and Hospital Epidemiology.

Though Johns Hopkins has had an antimicrobial stewardship team since 2002, most hospitals do not have formal groups in place, she said. The Society for Healthcare Epidemiology of America will publish checklists and guidelines in 2015 to help hospitals set up teams, Dr. Cosgrove said, noting that California has recently passed legislation mandating their creation in all hospitals in that state.

All the coauthors of Dr. Schultz’s study except Dr. Srinivasan are employees of Premier Inc., which is a for-profit research corporation. Dr. Srinivasan reported having no conflicts of interest.

Redundant combinations of intravenous antibiotics are used in nearly 8 of 10 hospitals, even though they are very infrequently indicated, said a group of researchers working to promote antimicrobial stewardship in hospitals.

In an article published in the October issue of Infection Control and Hospital Epidemiology, Leslie Schultz, R.N., Ph.D., of Premier Safety Institute in Charlotte, N.C., and colleagues reported that a review of cases from more than 500 U.S. hospitals revealed that about 150,000 days of inappropriate antibiotic therapy were prescribed, at an estimated excess cost of more than $12 million over the 4-year study period. Some 78% of hospitals in the study used the unnecessary drug combinations, they said.

©Bhakpong/thinkstockphotos.com

The combination of metronidazole and piperacillin-tazobactam accounted for more than half of the redundant treatments detected in the study, with some 32,500 cases receiving this combination for 2 days or more. Other commonly seen redundant treatments included metronidazole and ampicillin-sulbactam, along with metronidazole and ertapenem, which, together with the metronidazole and piperacillin-tazobactam combination, were seen as responsible for 70% of redundant treatments administered to patients (Infect. Control Hosp. Epidemiol. 2014; 35:1229-35).

In a telephone press conference on Sept. 10, one of Dr. Schultz’s coauthors on the paper, Dr. Arjun Srinivasan of the Centers for Disease Control and Prevention, Atlanta, said that, while concerns about antimicrobial stewardship are not new, the findings came as a surprise. "We would expect the use of these combinations to be vanishingly rare given how often they’re indicated," Dr. Srinivasan said, citing a lack of training in antibiotics as a contributing factor.

"We’ve heard from a lot of clinicians that providers don’t know that piperacillin-tazobactam very effectively kills anaerobic bacteria – but they do know that metronidazole is effective," Dr. Srinivasan said. "People are not as aware as they need to be about what antibiotics kill what bacteria, and we need to make sure people know which antibiotics need to be combined and when – and that with some, you don’t gain anything by adding the second drug. You only increase the risk of side effects."

Another physician taking part in the press conference, Dr. Sara Cosgrove of Johns Hopkins Hospital, Baltimore, agreed. "We have suboptimal training among medical students and house staff about what antibiotics cover what bugs," she said. "We have seen publications suggesting that medical students and residents want more info on antibiotics."

Dr. Cosgrove also noted that changes in hospital work practices may have contributed to the problem. "More people are working in hospitals on shorter shifts, and there are communication issues from one physician to the next. One physician may start an antibiotic and a second physician starts a second. There are many ways we can address the problem of unintended duplicate therapy," she said, including the use of alerts generated when pharmacy receives a request for a redundant drug.

Dr. Srinivasan said that hospitals that have implemented alerts have found them effective. Still, both physicians stressed that whatever the methods used, dedicated antimicrobial stewardship teams in hospitals were essential to ensuring the avoidance of redundant treatments.

"Many hospitals report that they are thinking about having an antimicrobial stewardship program. We’d like to nudge them to actually have one," said Dr. Cosgrove, who is chair of the antimicrobial stewardship committee for the Society for Healthcare Epidemiology of America, which publishes Infection Control and Hospital Epidemiology.

Though Johns Hopkins has had an antimicrobial stewardship team since 2002, most hospitals do not have formal groups in place, she said. The Society for Healthcare Epidemiology of America will publish checklists and guidelines in 2015 to help hospitals set up teams, Dr. Cosgrove said, noting that California has recently passed legislation mandating their creation in all hospitals in that state.

All the coauthors of Dr. Schultz’s study except Dr. Srinivasan are employees of Premier Inc., which is a for-profit research corporation. Dr. Srinivasan reported having no conflicts of interest.

Redundant combinations of intravenous antibiotics are used in nearly 8 of 10 hospitals, even though they are very infrequently indicated, said a group of researchers working to promote antimicrobial stewardship in hospitals.

In an article published in the October issue of Infection Control and Hospital Epidemiology, Leslie Schultz, R.N., Ph.D., of Premier Safety Institute in Charlotte, N.C., and colleagues reported that a review of cases from more than 500 U.S. hospitals revealed that about 150,000 days of inappropriate antibiotic therapy were prescribed, at an estimated excess cost of more than $12 million over the 4-year study period. Some 78% of hospitals in the study used the unnecessary drug combinations, they said.

©Bhakpong/thinkstockphotos.com

The combination of metronidazole and piperacillin-tazobactam accounted for more than half of the redundant treatments detected in the study, with some 32,500 cases receiving this combination for 2 days or more. Other commonly seen redundant treatments included metronidazole and ampicillin-sulbactam, along with metronidazole and ertapenem, which, together with the metronidazole and piperacillin-tazobactam combination, were seen as responsible for 70% of redundant treatments administered to patients (Infect. Control Hosp. Epidemiol. 2014; 35:1229-35).

In a telephone press conference on Sept. 10, one of Dr. Schultz’s coauthors on the paper, Dr. Arjun Srinivasan of the Centers for Disease Control and Prevention, Atlanta, said that, while concerns about antimicrobial stewardship are not new, the findings came as a surprise. "We would expect the use of these combinations to be vanishingly rare given how often they’re indicated," Dr. Srinivasan said, citing a lack of training in antibiotics as a contributing factor.

"We’ve heard from a lot of clinicians that providers don’t know that piperacillin-tazobactam very effectively kills anaerobic bacteria – but they do know that metronidazole is effective," Dr. Srinivasan said. "People are not as aware as they need to be about what antibiotics kill what bacteria, and we need to make sure people know which antibiotics need to be combined and when – and that with some, you don’t gain anything by adding the second drug. You only increase the risk of side effects."

Another physician taking part in the press conference, Dr. Sara Cosgrove of Johns Hopkins Hospital, Baltimore, agreed. "We have suboptimal training among medical students and house staff about what antibiotics cover what bugs," she said. "We have seen publications suggesting that medical students and residents want more info on antibiotics."

Dr. Cosgrove also noted that changes in hospital work practices may have contributed to the problem. "More people are working in hospitals on shorter shifts, and there are communication issues from one physician to the next. One physician may start an antibiotic and a second physician starts a second. There are many ways we can address the problem of unintended duplicate therapy," she said, including the use of alerts generated when pharmacy receives a request for a redundant drug.

Dr. Srinivasan said that hospitals that have implemented alerts have found them effective. Still, both physicians stressed that whatever the methods used, dedicated antimicrobial stewardship teams in hospitals were essential to ensuring the avoidance of redundant treatments.

"Many hospitals report that they are thinking about having an antimicrobial stewardship program. We’d like to nudge them to actually have one," said Dr. Cosgrove, who is chair of the antimicrobial stewardship committee for the Society for Healthcare Epidemiology of America, which publishes Infection Control and Hospital Epidemiology.

Though Johns Hopkins has had an antimicrobial stewardship team since 2002, most hospitals do not have formal groups in place, she said. The Society for Healthcare Epidemiology of America will publish checklists and guidelines in 2015 to help hospitals set up teams, Dr. Cosgrove said, noting that California has recently passed legislation mandating their creation in all hospitals in that state.

All the coauthors of Dr. Schultz’s study except Dr. Srinivasan are employees of Premier Inc., which is a for-profit research corporation. Dr. Srinivasan reported having no conflicts of interest.

Redundant combinations of intravenous antibiotics are used in nearly 8 of 10 hospitals, even though they are very infrequently indicated, said a group of researchers working to promote antimicrobial stewardship in hospitals.

In an article published in the October issue of Infection Control and Hospital Epidemiology, Leslie Schultz, R.N., Ph.D., of Premier Safety Institute in Charlotte, N.C., and colleagues reported that a review of cases from more than 500 U.S. hospitals revealed that about 150,000 days of inappropriate antibiotic therapy were prescribed, at an estimated excess cost of more than $12 million over the 4-year study period. Some 78% of hospitals in the study used the unnecessary drug combinations, they said.

©Bhakpong/thinkstockphotos.com

The combination of metronidazole and piperacillin-tazobactam accounted for more than half of the redundant treatments detected in the study, with some 32,500 cases receiving this combination for 2 days or more. Other commonly seen redundant treatments included metronidazole and ampicillin-sulbactam, along with metronidazole and ertapenem, which, together with the metronidazole and piperacillin-tazobactam combination, were seen as responsible for 70% of redundant treatments administered to patients (Infect. Control Hosp. Epidemiol. 2014; 35:1229-35).

In a telephone press conference on Sept. 10, one of Dr. Schultz’s coauthors on the paper, Dr. Arjun Srinivasan of the Centers for Disease Control and Prevention, Atlanta, said that, while concerns about antimicrobial stewardship are not new, the findings came as a surprise. "We would expect the use of these combinations to be vanishingly rare given how often they’re indicated," Dr. Srinivasan said, citing a lack of training in antibiotics as a contributing factor.

"We’ve heard from a lot of clinicians that providers don’t know that piperacillin-tazobactam very effectively kills anaerobic bacteria – but they do know that metronidazole is effective," Dr. Srinivasan said. "People are not as aware as they need to be about what antibiotics kill what bacteria, and we need to make sure people know which antibiotics need to be combined and when – and that with some, you don’t gain anything by adding the second drug. You only increase the risk of side effects."

Another physician taking part in the press conference, Dr. Sara Cosgrove of Johns Hopkins Hospital, Baltimore, agreed. "We have suboptimal training among medical students and house staff about what antibiotics cover what bugs," she said. "We have seen publications suggesting that medical students and residents want more info on antibiotics."

Dr. Cosgrove also noted that changes in hospital work practices may have contributed to the problem. "More people are working in hospitals on shorter shifts, and there are communication issues from one physician to the next. One physician may start an antibiotic and a second physician starts a second. There are many ways we can address the problem of unintended duplicate therapy," she said, including the use of alerts generated when pharmacy receives a request for a redundant drug.

Dr. Srinivasan said that hospitals that have implemented alerts have found them effective. Still, both physicians stressed that whatever the methods used, dedicated antimicrobial stewardship teams in hospitals were essential to ensuring the avoidance of redundant treatments.

"Many hospitals report that they are thinking about having an antimicrobial stewardship program. We’d like to nudge them to actually have one," said Dr. Cosgrove, who is chair of the antimicrobial stewardship committee for the Society for Healthcare Epidemiology of America, which publishes Infection Control and Hospital Epidemiology.

Though Johns Hopkins has had an antimicrobial stewardship team since 2002, most hospitals do not have formal groups in place, she said. The Society for Healthcare Epidemiology of America will publish checklists and guidelines in 2015 to help hospitals set up teams, Dr. Cosgrove said, noting that California has recently passed legislation mandating their creation in all hospitals in that state.

All the coauthors of Dr. Schultz’s study except Dr. Srinivasan are employees of Premier Inc., which is a for-profit research corporation. Dr. Srinivasan reported having no conflicts of interest.

Redundant combinations of intravenous antibiotics are used in nearly 8 of 10 hospitals, even though they are very infrequently indicated, said a group of researchers working to promote antimicrobial stewardship in hospitals.

In an article published in the October issue of Infection Control and Hospital Epidemiology, Leslie Schultz, R.N., Ph.D., of Premier Safety Institute in Charlotte, N.C., and colleagues reported that a review of cases from more than 500 U.S. hospitals revealed that about 150,000 days of inappropriate antibiotic therapy were prescribed, at an estimated excess cost of more than $12 million over the 4-year study period. Some 78% of hospitals in the study used the unnecessary drug combinations, they said.

©Bhakpong/thinkstockphotos.com

The combination of metronidazole and piperacillin-tazobactam accounted for more than half of the redundant treatments detected in the study, with some 32,500 cases receiving this combination for 2 days or more. Other commonly seen redundant treatments included metronidazole and ampicillin-sulbactam, along with metronidazole and ertapenem, which, together with the metronidazole and piperacillin-tazobactam combination, were seen as responsible for 70% of redundant treatments administered to patients (Infect. Control Hosp. Epidemiol. 2014; 35:1229-35).

In a telephone press conference on Sept. 10, one of Dr. Schultz’s coauthors on the paper, Dr. Arjun Srinivasan of the Centers for Disease Control and Prevention, Atlanta, said that, while concerns about antimicrobial stewardship are not new, the findings came as a surprise. "We would expect the use of these combinations to be vanishingly rare given how often they’re indicated," Dr. Srinivasan said, citing a lack of training in antibiotics as a contributing factor.

"We’ve heard from a lot of clinicians that providers don’t know that piperacillin-tazobactam very effectively kills anaerobic bacteria – but they do know that metronidazole is effective," Dr. Srinivasan said. "People are not as aware as they need to be about what antibiotics kill what bacteria, and we need to make sure people know which antibiotics need to be combined and when – and that with some, you don’t gain anything by adding the second drug. You only increase the risk of side effects."

Another physician taking part in the press conference, Dr. Sara Cosgrove of Johns Hopkins Hospital, Baltimore, agreed. "We have suboptimal training among medical students and house staff about what antibiotics cover what bugs," she said. "We have seen publications suggesting that medical students and residents want more info on antibiotics."

Dr. Cosgrove also noted that changes in hospital work practices may have contributed to the problem. "More people are working in hospitals on shorter shifts, and there are communication issues from one physician to the next. One physician may start an antibiotic and a second physician starts a second. There are many ways we can address the problem of unintended duplicate therapy," she said, including the use of alerts generated when pharmacy receives a request for a redundant drug.

Dr. Srinivasan said that hospitals that have implemented alerts have found them effective. Still, both physicians stressed that whatever the methods used, dedicated antimicrobial stewardship teams in hospitals were essential to ensuring the avoidance of redundant treatments.

"Many hospitals report that they are thinking about having an antimicrobial stewardship program. We’d like to nudge them to actually have one," said Dr. Cosgrove, who is chair of the antimicrobial stewardship committee for the Society for Healthcare Epidemiology of America, which publishes Infection Control and Hospital Epidemiology.

Though Johns Hopkins has had an antimicrobial stewardship team since 2002, most hospitals do not have formal groups in place, she said. The Society for Healthcare Epidemiology of America will publish checklists and guidelines in 2015 to help hospitals set up teams, Dr. Cosgrove said, noting that California has recently passed legislation mandating their creation in all hospitals in that state.

All the coauthors of Dr. Schultz’s study except Dr. Srinivasan are employees of Premier Inc., which is a for-profit research corporation. Dr. Srinivasan reported having no conflicts of interest.

Redundant combinations of intravenous antibiotics are used in nearly 8 of 10 hospitals, even though they are very infrequently indicated, said a group of researchers working to promote antimicrobial stewardship in hospitals.

In an article published in the October issue of Infection Control and Hospital Epidemiology, Leslie Schultz, R.N., Ph.D., of Premier Safety Institute in Charlotte, N.C., and colleagues reported that a review of cases from more than 500 U.S. hospitals revealed that about 150,000 days of inappropriate antibiotic therapy were prescribed, at an estimated excess cost of more than $12 million over the 4-year study period. Some 78% of hospitals in the study used the unnecessary drug combinations, they said.

©Bhakpong/thinkstockphotos.com

The combination of metronidazole and piperacillin-tazobactam accounted for more than half of the redundant treatments detected in the study, with some 32,500 cases receiving this combination for 2 days or more. Other commonly seen redundant treatments included metronidazole and ampicillin-sulbactam, along with metronidazole and ertapenem, which, together with the metronidazole and piperacillin-tazobactam combination, were seen as responsible for 70% of redundant treatments administered to patients (Infect. Control Hosp. Epidemiol. 2014; 35:1229-35).

In a telephone press conference on Sept. 10, one of Dr. Schultz’s coauthors on the paper, Dr. Arjun Srinivasan of the Centers for Disease Control and Prevention, Atlanta, said that, while concerns about antimicrobial stewardship are not new, the findings came as a surprise. "We would expect the use of these combinations to be vanishingly rare given how often they’re indicated," Dr. Srinivasan said, citing a lack of training in antibiotics as a contributing factor.

"We’ve heard from a lot of clinicians that providers don’t know that piperacillin-tazobactam very effectively kills anaerobic bacteria – but they do know that metronidazole is effective," Dr. Srinivasan said. "People are not as aware as they need to be about what antibiotics kill what bacteria, and we need to make sure people know which antibiotics need to be combined and when – and that with some, you don’t gain anything by adding the second drug. You only increase the risk of side effects."

Another physician taking part in the press conference, Dr. Sara Cosgrove of Johns Hopkins Hospital, Baltimore, agreed. "We have suboptimal training among medical students and house staff about what antibiotics cover what bugs," she said. "We have seen publications suggesting that medical students and residents want more info on antibiotics."

Dr. Cosgrove also noted that changes in hospital work practices may have contributed to the problem. "More people are working in hospitals on shorter shifts, and there are communication issues from one physician to the next. One physician may start an antibiotic and a second physician starts a second. There are many ways we can address the problem of unintended duplicate therapy," she said, including the use of alerts generated when pharmacy receives a request for a redundant drug.

Dr. Srinivasan said that hospitals that have implemented alerts have found them effective. Still, both physicians stressed that whatever the methods used, dedicated antimicrobial stewardship teams in hospitals were essential to ensuring the avoidance of redundant treatments.

"Many hospitals report that they are thinking about having an antimicrobial stewardship program. We’d like to nudge them to actually have one," said Dr. Cosgrove, who is chair of the antimicrobial stewardship committee for the Society for Healthcare Epidemiology of America, which publishes Infection Control and Hospital Epidemiology.

Though Johns Hopkins has had an antimicrobial stewardship team since 2002, most hospitals do not have formal groups in place, she said. The Society for Healthcare Epidemiology of America will publish checklists and guidelines in 2015 to help hospitals set up teams, Dr. Cosgrove said, noting that California has recently passed legislation mandating their creation in all hospitals in that state.

All the coauthors of Dr. Schultz’s study except Dr. Srinivasan are employees of Premier Inc., which is a for-profit research corporation. Dr. Srinivasan reported having no conflicts of interest.

Benzodiazepine use for 3 months or more is associated with a significantly increased likelihood of developing Alzheimer’s disease, and longer exposure is associated with greater odds, according to results from a case-control study published in BMJ.

The authors, led by Sophie Billioti de Gage of Université de Bordeaux (France), conducted a nested case-control study of 1,796 members of a public drug plan in Quebec aged 66 years and older who had been diagnosed with Alzheimer’s disease at least 6 years prior, and more than 7,000 non-Alzheimer’s controls matched for age and sex.

Ms. Billioti de Gage and her colleagues found a cumulative dose-effect association between exposure to benzodiazepines at least 5 years before diagnosis and the odds of developing Alzheimer’s disease, with a significantly greater likelihood observed with benzodiazepine use of 90 or more consecutive days (adjusted odds ratio, 1.51; 95% confidence interval, 1.36-1.69) and daily exposure to benzodiazepines for 180 or more days (adjusted OR, 1.84; 95% CI, 1.62-2.08).

The researchers also found that the type of benzodiazepine prescribed affected risk. Drugs with longer half-life, such as diazepam and clonazepam, were associated with greater likelihood of Alzheimer’s disease (OR, 1.70; 95% CI, 1.46-1.98), compared with shorter-acting drugs, such as lorazepam and alprazolam (OR, 1.43; 95% CI, 1.27-1.61). The association between benzodiazepine use and Alzheimer’s persisted even after researchers adjusted for symptoms that could be indicative of a future dementia diagnosis, including depression, anxiety, and insomnia (BMJ 2014 Sept. 9 [doi:10.1136/bmj.g5205]).

While the study authors acknowledged that they could not rule out that anxiety and sleep disorders, two of the main indications for benzodiazepines, “could be associated with early beta amyloid lesions in brain, and persistent mid-life anxiety could be associated with a greater risk of dementia in older people,” they also noted that their study was designed to reduce the possibility of reverse causation bias “and to provide additional arguments linking benzodiazepine use with Alzheimer’s disease, such as a dose-effect relation.”

The findings, Ms. Billioti de Gage and her colleagues added, argue for “carefully evaluating the indications for use of this drug class … especially considering the prevalence and chronicity of benzodiazepine use in older people and the high and increasing incidence of dementia in developed countries.”

The study was funded by INSERM (Institut National de la Santé et de la Recherche Médicale) and the University of Bordeaux, as well as by unconditional grants from IRESP (Institut de Recherche en Santé Publique), the French Ministry of Health, and the Funding Agency for Health Research of Quebec. One of the study’s coauthors, Dr. Tobias Kurth, declared payment from BMJ and Cephalalgia; another co-author, Marie Tournier, declared receiving honoraria from AstraZeneca, Bristol-Myers Squibb, and Janssen.

Benzodiazepine use for 3 months or more is associated with a significantly increased likelihood of developing Alzheimer’s disease, and longer exposure is associated with greater odds, according to results from a case-control study published in BMJ.

The authors, led by Sophie Billioti de Gage of Université de Bordeaux (France), conducted a nested case-control study of 1,796 members of a public drug plan in Quebec aged 66 years and older who had been diagnosed with Alzheimer’s disease at least 6 years prior, and more than 7,000 non-Alzheimer’s controls matched for age and sex.

Ms. Billioti de Gage and her colleagues found a cumulative dose-effect association between exposure to benzodiazepines at least 5 years before diagnosis and the odds of developing Alzheimer’s disease, with a significantly greater likelihood observed with benzodiazepine use of 90 or more consecutive days (adjusted odds ratio, 1.51; 95% confidence interval, 1.36-1.69) and daily exposure to benzodiazepines for 180 or more days (adjusted OR, 1.84; 95% CI, 1.62-2.08).

The researchers also found that the type of benzodiazepine prescribed affected risk. Drugs with longer half-life, such as diazepam and clonazepam, were associated with greater likelihood of Alzheimer’s disease (OR, 1.70; 95% CI, 1.46-1.98), compared with shorter-acting drugs, such as lorazepam and alprazolam (OR, 1.43; 95% CI, 1.27-1.61). The association between benzodiazepine use and Alzheimer’s persisted even after researchers adjusted for symptoms that could be indicative of a future dementia diagnosis, including depression, anxiety, and insomnia (BMJ 2014 Sept. 9 [doi:10.1136/bmj.g5205]).

While the study authors acknowledged that they could not rule out that anxiety and sleep disorders, two of the main indications for benzodiazepines, “could be associated with early beta amyloid lesions in brain, and persistent mid-life anxiety could be associated with a greater risk of dementia in older people,” they also noted that their study was designed to reduce the possibility of reverse causation bias “and to provide additional arguments linking benzodiazepine use with Alzheimer’s disease, such as a dose-effect relation.”

The findings, Ms. Billioti de Gage and her colleagues added, argue for “carefully evaluating the indications for use of this drug class … especially considering the prevalence and chronicity of benzodiazepine use in older people and the high and increasing incidence of dementia in developed countries.”

The study was funded by INSERM (Institut National de la Santé et de la Recherche Médicale) and the University of Bordeaux, as well as by unconditional grants from IRESP (Institut de Recherche en Santé Publique), the French Ministry of Health, and the Funding Agency for Health Research of Quebec. One of the study’s coauthors, Dr. Tobias Kurth, declared payment from BMJ and Cephalalgia; another co-author, Marie Tournier, declared receiving honoraria from AstraZeneca, Bristol-Myers Squibb, and Janssen.

Benzodiazepine use for 3 months or more is associated with a significantly increased likelihood of developing Alzheimer’s disease, and longer exposure is associated with greater odds, according to results from a case-control study published in BMJ.

The authors, led by Sophie Billioti de Gage of Université de Bordeaux (France), conducted a nested case-control study of 1,796 members of a public drug plan in Quebec aged 66 years and older who had been diagnosed with Alzheimer’s disease at least 6 years prior, and more than 7,000 non-Alzheimer’s controls matched for age and sex.

Ms. Billioti de Gage and her colleagues found a cumulative dose-effect association between exposure to benzodiazepines at least 5 years before diagnosis and the odds of developing Alzheimer’s disease, with a significantly greater likelihood observed with benzodiazepine use of 90 or more consecutive days (adjusted odds ratio, 1.51; 95% confidence interval, 1.36-1.69) and daily exposure to benzodiazepines for 180 or more days (adjusted OR, 1.84; 95% CI, 1.62-2.08).

The researchers also found that the type of benzodiazepine prescribed affected risk. Drugs with longer half-life, such as diazepam and clonazepam, were associated with greater likelihood of Alzheimer’s disease (OR, 1.70; 95% CI, 1.46-1.98), compared with shorter-acting drugs, such as lorazepam and alprazolam (OR, 1.43; 95% CI, 1.27-1.61). The association between benzodiazepine use and Alzheimer’s persisted even after researchers adjusted for symptoms that could be indicative of a future dementia diagnosis, including depression, anxiety, and insomnia (BMJ 2014 Sept. 9 [doi:10.1136/bmj.g5205]).

While the study authors acknowledged that they could not rule out that anxiety and sleep disorders, two of the main indications for benzodiazepines, “could be associated with early beta amyloid lesions in brain, and persistent mid-life anxiety could be associated with a greater risk of dementia in older people,” they also noted that their study was designed to reduce the possibility of reverse causation bias “and to provide additional arguments linking benzodiazepine use with Alzheimer’s disease, such as a dose-effect relation.”

The findings, Ms. Billioti de Gage and her colleagues added, argue for “carefully evaluating the indications for use of this drug class … especially considering the prevalence and chronicity of benzodiazepine use in older people and the high and increasing incidence of dementia in developed countries.”

The study was funded by INSERM (Institut National de la Santé et de la Recherche Médicale) and the University of Bordeaux, as well as by unconditional grants from IRESP (Institut de Recherche en Santé Publique), the French Ministry of Health, and the Funding Agency for Health Research of Quebec. One of the study’s coauthors, Dr. Tobias Kurth, declared payment from BMJ and Cephalalgia; another co-author, Marie Tournier, declared receiving honoraria from AstraZeneca, Bristol-Myers Squibb, and Janssen.

Benzodiazepine use for 3 months or more is associated with a significantly increased likelihood of developing Alzheimer’s disease, and longer exposure is associated with greater odds, according to results from a case-control study published Sept. 9 in BMJ.

The authors, led by Sophie Billioti de Gage of Université de Bordeaux (France), conducted a nested case-control study of 1,796 members of a public drug plan in Quebec, Canada, aged 66 years and older who had been diagnosed with Alzheimer’s disease at least 6 years prior, and more than 7,000 non-Alzheimer’s controls matched for age and sex.

Ms. Billioti de Gage and her colleagues found a cumulative dose-effect association between exposure to benzodiazepines at least 5 years before diagnosis and the odds of developing Alzheimer’s disease, with a significantly greater likelihood observed with benzodiazepine use of 90 or more consecutive days (adjusted odds ratio, 1.51; 95% confidence interval, 1.36-1.69) and daily exposure to benzodiazepines for 180 or more days (adjusted OR, 1.84; 95% CI, 1.62-2.08).

The researchers also found that the type of benzodiazepine prescribed affected risk. Drugs with longer half-life, such as diazepam and clonazepam, were associated with greater likelihood of Alzheimer’s disease (OR, 1.70; 95% CI, 1.46-1.98), compared with shorter-acting drugs, such as lorazepam and alprazolam (OR, 1.43; 95% CI, 1.27-1.61). The association between benzodiazepine use and Alzheimer’s persisted even after researchers adjusted for symptoms that could be indicative of a future dementia diagnosis, including depression, anxiety, and insomnia (BMJ 2014 Sept. 9 [doi:10.1136/bmj.g5205]).

While the study authors acknowledged that they could not rule out that anxiety and sleep disorders, two of the main indications for benzodiazepines, "could be associated with early beta amyloid lesions in brain, and persistent mid-life anxiety could be associated with a greater risk of dementia in older people," they also noted that their study was designed to reduce the possibility of reverse causation bias "and to provide additional arguments linking benzodiazepine use with Alzheimer’s disease, such as a dose-effect relation."

The findings, Ms. Billioti de Gage and her colleagues added, argue for "carefully evaluating the indications for use of this drug class ... especially considering the prevalence and chronicity of benzodiazepine use in older people and the high and increasing incidence of dementia in developed countries."

The study was funded by INSERM (Institut National de la Santé et de la Recherche Médicale) and the University of Bordeaux, as well as by unconditional grants from IRESP (Institut de Recherche en Santé Publique), the French Ministry of Health (Direction Générale de la Santé), and the Funding Agency for Health Research of Quebec (Fonds de la Recherche en Santé du Québec). One of the study’s coauthors, Dr. Tobias Kurth, declared payment from BMJ and Cephalalgia; another co-author, Marie Tournier, declared receiving honoraria from AstraZeneca, Bristol-Myers Squibb, and Janssen.

Benzodiazepine use for 3 months or more is associated with a significantly increased likelihood of developing Alzheimer’s disease, and longer exposure is associated with greater odds, according to results from a case-control study published Sept. 9 in BMJ.

The authors, led by Sophie Billioti de Gage of Université de Bordeaux (France), conducted a nested case-control study of 1,796 members of a public drug plan in Quebec, Canada, aged 66 years and older who had been diagnosed with Alzheimer’s disease at least 6 years prior, and more than 7,000 non-Alzheimer’s controls matched for age and sex.

Ms. Billioti de Gage and her colleagues found a cumulative dose-effect association between exposure to benzodiazepines at least 5 years before diagnosis and the odds of developing Alzheimer’s disease, with a significantly greater likelihood observed with benzodiazepine use of 90 or more consecutive days (adjusted odds ratio, 1.51; 95% confidence interval, 1.36-1.69) and daily exposure to benzodiazepines for 180 or more days (adjusted OR, 1.84; 95% CI, 1.62-2.08).

The researchers also found that the type of benzodiazepine prescribed affected risk. Drugs with longer half-life, such as diazepam and clonazepam, were associated with greater likelihood of Alzheimer’s disease (OR, 1.70; 95% CI, 1.46-1.98), compared with shorter-acting drugs, such as lorazepam and alprazolam (OR, 1.43; 95% CI, 1.27-1.61). The association between benzodiazepine use and Alzheimer’s persisted even after researchers adjusted for symptoms that could be indicative of a future dementia diagnosis, including depression, anxiety, and insomnia (BMJ 2014 Sept. 9 [doi:10.1136/bmj.g5205]).

While the study authors acknowledged that they could not rule out that anxiety and sleep disorders, two of the main indications for benzodiazepines, "could be associated with early beta amyloid lesions in brain, and persistent mid-life anxiety could be associated with a greater risk of dementia in older people," they also noted that their study was designed to reduce the possibility of reverse causation bias "and to provide additional arguments linking benzodiazepine use with Alzheimer’s disease, such as a dose-effect relation."

The findings, Ms. Billioti de Gage and her colleagues added, argue for "carefully evaluating the indications for use of this drug class ... especially considering the prevalence and chronicity of benzodiazepine use in older people and the high and increasing incidence of dementia in developed countries."

The study was funded by INSERM (Institut National de la Santé et de la Recherche Médicale) and the University of Bordeaux, as well as by unconditional grants from IRESP (Institut de Recherche en Santé Publique), the French Ministry of Health (Direction Générale de la Santé), and the Funding Agency for Health Research of Quebec (Fonds de la Recherche en Santé du Québec). One of the study’s coauthors, Dr. Tobias Kurth, declared payment from BMJ and Cephalalgia; another co-author, Marie Tournier, declared receiving honoraria from AstraZeneca, Bristol-Myers Squibb, and Janssen.

Benzodiazepine use for 3 months or more is associated with a significantly increased likelihood of developing Alzheimer’s disease, and longer exposure is associated with greater odds, according to results from a case-control study published Sept. 9 in BMJ.

The authors, led by Sophie Billioti de Gage of Université de Bordeaux (France), conducted a nested case-control study of 1,796 members of a public drug plan in Quebec, Canada, aged 66 years and older who had been diagnosed with Alzheimer’s disease at least 6 years prior, and more than 7,000 non-Alzheimer’s controls matched for age and sex.

Ms. Billioti de Gage and her colleagues found a cumulative dose-effect association between exposure to benzodiazepines at least 5 years before diagnosis and the odds of developing Alzheimer’s disease, with a significantly greater likelihood observed with benzodiazepine use of 90 or more consecutive days (adjusted odds ratio, 1.51; 95% confidence interval, 1.36-1.69) and daily exposure to benzodiazepines for 180 or more days (adjusted OR, 1.84; 95% CI, 1.62-2.08).

The researchers also found that the type of benzodiazepine prescribed affected risk. Drugs with longer half-life, such as diazepam and clonazepam, were associated with greater likelihood of Alzheimer’s disease (OR, 1.70; 95% CI, 1.46-1.98), compared with shorter-acting drugs, such as lorazepam and alprazolam (OR, 1.43; 95% CI, 1.27-1.61). The association between benzodiazepine use and Alzheimer’s persisted even after researchers adjusted for symptoms that could be indicative of a future dementia diagnosis, including depression, anxiety, and insomnia (BMJ 2014 Sept. 9 [doi:10.1136/bmj.g5205]).

While the study authors acknowledged that they could not rule out that anxiety and sleep disorders, two of the main indications for benzodiazepines, "could be associated with early beta amyloid lesions in brain, and persistent mid-life anxiety could be associated with a greater risk of dementia in older people," they also noted that their study was designed to reduce the possibility of reverse causation bias "and to provide additional arguments linking benzodiazepine use with Alzheimer’s disease, such as a dose-effect relation."

The findings, Ms. Billioti de Gage and her colleagues added, argue for "carefully evaluating the indications for use of this drug class ... especially considering the prevalence and chronicity of benzodiazepine use in older people and the high and increasing incidence of dementia in developed countries."

The study was funded by INSERM (Institut National de la Santé et de la Recherche Médicale) and the University of Bordeaux, as well as by unconditional grants from IRESP (Institut de Recherche en Santé Publique), the French Ministry of Health (Direction Générale de la Santé), and the Funding Agency for Health Research of Quebec (Fonds de la Recherche en Santé du Québec). One of the study’s coauthors, Dr. Tobias Kurth, declared payment from BMJ and Cephalalgia; another co-author, Marie Tournier, declared receiving honoraria from AstraZeneca, Bristol-Myers Squibb, and Janssen.

Benzodiazepine use for 3 months or more is associated with a significantly increased likelihood of developing Alzheimer’s disease, and longer exposure is associated with greater odds, according to results from a case-control study published Sept. 9 in BMJ.

The authors, led by Sophie Billioti de Gage of Université de Bordeaux (France), conducted a nested case-control study of 1,796 members of a public drug plan in Quebec, Canada, aged 66 years and older who had been diagnosed with Alzheimer’s disease at least 6 years prior, and more than 7,000 non-Alzheimer’s controls matched for age and sex.

Ms. Billioti de Gage and her colleagues found a cumulative dose-effect association between exposure to benzodiazepines at least 5 years before diagnosis and the odds of developing Alzheimer’s disease, with a significantly greater likelihood observed with benzodiazepine use of 90 or more consecutive days (adjusted odds ratio, 1.51; 95% confidence interval, 1.36-1.69) and daily exposure to benzodiazepines for 180 or more days (adjusted OR, 1.84; 95% CI, 1.62-2.08).

The researchers also found that the type of benzodiazepine prescribed affected risk. Drugs with longer half-life, such as diazepam and clonazepam, were associated with greater likelihood of Alzheimer’s disease (OR, 1.70; 95% CI, 1.46-1.98), compared with shorter-acting drugs, such as lorazepam and alprazolam (OR, 1.43; 95% CI, 1.27-1.61). The association between benzodiazepine use and Alzheimer’s persisted even after researchers adjusted for symptoms that could be indicative of a future dementia diagnosis, including depression, anxiety, and insomnia (BMJ 2014 Sept. 9 [doi:10.1136/bmj.g5205]).

While the study authors acknowledged that they could not rule out that anxiety and sleep disorders, two of the main indications for benzodiazepines, "could be associated with early beta amyloid lesions in brain, and persistent mid-life anxiety could be associated with a greater risk of dementia in older people," they also noted that their study was designed to reduce the possibility of reverse causation bias "and to provide additional arguments linking benzodiazepine use with Alzheimer’s disease, such as a dose-effect relation."

The findings, Ms. Billioti de Gage and her colleagues added, argue for "carefully evaluating the indications for use of this drug class ... especially considering the prevalence and chronicity of benzodiazepine use in older people and the high and increasing incidence of dementia in developed countries."

The study was funded by INSERM (Institut National de la Santé et de la Recherche Médicale) and the University of Bordeaux, as well as by unconditional grants from IRESP (Institut de Recherche en Santé Publique), the French Ministry of Health (Direction Générale de la Santé), and the Funding Agency for Health Research of Quebec (Fonds de la Recherche en Santé du Québec). One of the study’s coauthors, Dr. Tobias Kurth, declared payment from BMJ and Cephalalgia; another co-author, Marie Tournier, declared receiving honoraria from AstraZeneca, Bristol-Myers Squibb, and Janssen.

Benzodiazepine use for 3 months or more is associated with a significantly increased likelihood of developing Alzheimer’s disease, and longer exposure is associated with greater odds, according to results from a case-control study published Sept. 9 in BMJ.

The authors, led by Sophie Billioti de Gage of Université de Bordeaux (France), conducted a nested case-control study of 1,796 members of a public drug plan in Quebec, Canada, aged 66 years and older who had been diagnosed with Alzheimer’s disease at least 6 years prior, and more than 7,000 non-Alzheimer’s controls matched for age and sex.

Ms. Billioti de Gage and her colleagues found a cumulative dose-effect association between exposure to benzodiazepines at least 5 years before diagnosis and the odds of developing Alzheimer’s disease, with a significantly greater likelihood observed with benzodiazepine use of 90 or more consecutive days (adjusted odds ratio, 1.51; 95% confidence interval, 1.36-1.69) and daily exposure to benzodiazepines for 180 or more days (adjusted OR, 1.84; 95% CI, 1.62-2.08).

The researchers also found that the type of benzodiazepine prescribed affected risk. Drugs with longer half-life, such as diazepam and clonazepam, were associated with greater likelihood of Alzheimer’s disease (OR, 1.70; 95% CI, 1.46-1.98), compared with shorter-acting drugs, such as lorazepam and alprazolam (OR, 1.43; 95% CI, 1.27-1.61). The association between benzodiazepine use and Alzheimer’s persisted even after researchers adjusted for symptoms that could be indicative of a future dementia diagnosis, including depression, anxiety, and insomnia (BMJ 2014 Sept. 9 [doi:10.1136/bmj.g5205]).

While the study authors acknowledged that they could not rule out that anxiety and sleep disorders, two of the main indications for benzodiazepines, "could be associated with early beta amyloid lesions in brain, and persistent mid-life anxiety could be associated with a greater risk of dementia in older people," they also noted that their study was designed to reduce the possibility of reverse causation bias "and to provide additional arguments linking benzodiazepine use with Alzheimer’s disease, such as a dose-effect relation."

The findings, Ms. Billioti de Gage and her colleagues added, argue for "carefully evaluating the indications for use of this drug class ... especially considering the prevalence and chronicity of benzodiazepine use in older people and the high and increasing incidence of dementia in developed countries."

The study was funded by INSERM (Institut National de la Santé et de la Recherche Médicale) and the University of Bordeaux, as well as by unconditional grants from IRESP (Institut de Recherche en Santé Publique), the French Ministry of Health (Direction Générale de la Santé), and the Funding Agency for Health Research of Quebec (Fonds de la Recherche en Santé du Québec). One of the study’s coauthors, Dr. Tobias Kurth, declared payment from BMJ and Cephalalgia; another co-author, Marie Tournier, declared receiving honoraria from AstraZeneca, Bristol-Myers Squibb, and Janssen.

Benzodiazepine use for 3 months or more is associated with a significantly increased likelihood of developing Alzheimer’s disease, and longer exposure is associated with greater odds, according to results from a case-control study published Sept. 9 in BMJ.

The authors, led by Sophie Billioti de Gage of Université de Bordeaux (France), conducted a nested case-control study of 1,796 members of a public drug plan in Quebec, Canada, aged 66 years and older who had been diagnosed with Alzheimer’s disease at least 6 years prior, and more than 7,000 non-Alzheimer’s controls matched for age and sex.

Ms. Billioti de Gage and her colleagues found a cumulative dose-effect association between exposure to benzodiazepines at least 5 years before diagnosis and the odds of developing Alzheimer’s disease, with a significantly greater likelihood observed with benzodiazepine use of 90 or more consecutive days (adjusted odds ratio, 1.51; 95% confidence interval, 1.36-1.69) and daily exposure to benzodiazepines for 180 or more days (adjusted OR, 1.84; 95% CI, 1.62-2.08).

The researchers also found that the type of benzodiazepine prescribed affected risk. Drugs with longer half-life, such as diazepam and clonazepam, were associated with greater likelihood of Alzheimer’s disease (OR, 1.70; 95% CI, 1.46-1.98), compared with shorter-acting drugs, such as lorazepam and alprazolam (OR, 1.43; 95% CI, 1.27-1.61). The association between benzodiazepine use and Alzheimer’s persisted even after researchers adjusted for symptoms that could be indicative of a future dementia diagnosis, including depression, anxiety, and insomnia (BMJ 2014 Sept. 9 [doi:10.1136/bmj.g5205]).

While the study authors acknowledged that they could not rule out that anxiety and sleep disorders, two of the main indications for benzodiazepines, "could be associated with early beta amyloid lesions in brain, and persistent mid-life anxiety could be associated with a greater risk of dementia in older people," they also noted that their study was designed to reduce the possibility of reverse causation bias "and to provide additional arguments linking benzodiazepine use with Alzheimer’s disease, such as a dose-effect relation."

The findings, Ms. Billioti de Gage and her colleagues added, argue for "carefully evaluating the indications for use of this drug class ... especially considering the prevalence and chronicity of benzodiazepine use in older people and the high and increasing incidence of dementia in developed countries."

The study was funded by INSERM (Institut National de la Santé et de la Recherche Médicale) and the University of Bordeaux, as well as by unconditional grants from IRESP (Institut de Recherche en Santé Publique), the French Ministry of Health (Direction Générale de la Santé), and the Funding Agency for Health Research of Quebec (Fonds de la Recherche en Santé du Québec). One of the study’s coauthors, Dr. Tobias Kurth, declared payment from BMJ and Cephalalgia; another co-author, Marie Tournier, declared receiving honoraria from AstraZeneca, Bristol-Myers Squibb, and Janssen.

Addressing ethical challenges regarding quarantine, payment of health care workers, and the proper use of personal protective equipment could contribute significantly to the containment of the Ebola outbreak in West Africa, according to experts from Johns Hopkins University, Baltimore.

Citing reports of health care workers fleeing clinics, Nancy Kass, Sc.D., said that the international community is in good position to make sure that doctors, nurses, and other staff members at Ebola treatment centers are properly and regularly paid, noting that many are not.

CDC/Daniel J. DeNoon

Even before Ebola, "there were so many things going on in these environments that were unethical" in terms of pay and staffing practices, Dr. Kass, deputy director for bioethics and public health at the JHU Berman Institute of Bioethics, said at a forum held by the university.

The international community needs to provide personal protective equipment and training to all involved, she said, "including the person who cleans the floor."

Survivors of Ebola infection could be safely recruited to perform community outreach "and get a ton of money for doing it," Dr. Kass said.

Raising pay as well as service and staffing standards at clinics could also improve compliance with quarantine demands, she said, while also making quarantine fairer to patients and families.

"In a vacuum, we can think of the most ethical ways to manage quarantine," such as allowing family members to hold the patient’s hand through a barrier, Dr. Kass said. But when resources are tight, quarantine can mean a patient is isolated to the point of being deprived of food and water.

Tim Roberton, a fourth-year doctoral student at the university’s Bloomberg School of Public Health returned from Guinea in July. He said that he found that achieving compliance with quarantine could be a delicate matter, particularly in remote villages.

"To tell someone that you have to get to a treatment center when you get sick, that’s serious business. Do we expect people to comply knowing they’ll never see their families again?"

Even pushing for essential changes in burial practices to avoid infection "is really complicated," he said, and requires cooperation from local officials and religious leaders.

Mr. Roberton’s trip was part of a collaboration between the university and the International Foundation for the Red Cross, which has hundreds of volunteers working in Ebola-affected communities to communicate information about the outbreak, manage dead bodies, and disinfect sites.

"What will stop this is working with communities at the village level to help themselves not spread the disease," Mr. Roberton said, noting that resources should not be directed to research at the expense of controlling the outbreak.

Others at the forum, including panelist Dr. Trish Perl, a clinical epidemiologist with the Johns Hopkins Health System, disagreed with the idea that research and outbreak control goals needed to be in conflict.

"Whatever is done, it is incumbent upon all of us to make sure transparency and scientific rigor is inserted into the process," Dr. Perl said. With SARS (Severe Acute Respiratory Syndrome), "many people got steroids – this ended up hurting people, and there was not so much accountability with how that happened. We have to not do harm."

A number of attendees at the forum pressed the presenters on whether current containment strategies needed to be harder-edged or more coercive to be effective. "There is perhaps a time when coercion is necessary, Mr. Roberton acknowledged.

Dr. Perl alluded to a proposed role for the U.S. military in the Ebola crisis, though she stressed that she did not know what specific approach would be employed.

"I am far from the kind of person who would normally advocate" such a response, she said, but with the outbreak maturing and so many affected, "a command and control structure may be what is needed."

With smallpox, Dr. Perl added, "some pretty draconian things were required."

Addressing ethical challenges regarding quarantine, payment of health care workers, and the proper use of personal protective equipment could contribute significantly to the containment of the Ebola outbreak in West Africa, according to experts from Johns Hopkins University, Baltimore.

Citing reports of health care workers fleeing clinics, Nancy Kass, Sc.D., said that the international community is in good position to make sure that doctors, nurses, and other staff members at Ebola treatment centers are properly and regularly paid, noting that many are not.

CDC/Daniel J. DeNoon

Even before Ebola, "there were so many things going on in these environments that were unethical" in terms of pay and staffing practices, Dr. Kass, deputy director for bioethics and public health at the JHU Berman Institute of Bioethics, said at a forum held by the university.

The international community needs to provide personal protective equipment and training to all involved, she said, "including the person who cleans the floor."

Survivors of Ebola infection could be safely recruited to perform community outreach "and get a ton of money for doing it," Dr. Kass said.

Raising pay as well as service and staffing standards at clinics could also improve compliance with quarantine demands, she said, while also making quarantine fairer to patients and families.

"In a vacuum, we can think of the most ethical ways to manage quarantine," such as allowing family members to hold the patient’s hand through a barrier, Dr. Kass said. But when resources are tight, quarantine can mean a patient is isolated to the point of being deprived of food and water.

Tim Roberton, a fourth-year doctoral student at the university’s Bloomberg School of Public Health returned from Guinea in July. He said that he found that achieving compliance with quarantine could be a delicate matter, particularly in remote villages.

"To tell someone that you have to get to a treatment center when you get sick, that’s serious business. Do we expect people to comply knowing they’ll never see their families again?"

Even pushing for essential changes in burial practices to avoid infection "is really complicated," he said, and requires cooperation from local officials and religious leaders.

Mr. Roberton’s trip was part of a collaboration between the university and the International Foundation for the Red Cross, which has hundreds of volunteers working in Ebola-affected communities to communicate information about the outbreak, manage dead bodies, and disinfect sites.

"What will stop this is working with communities at the village level to help themselves not spread the disease," Mr. Roberton said, noting that resources should not be directed to research at the expense of controlling the outbreak.

Others at the forum, including panelist Dr. Trish Perl, a clinical epidemiologist with the Johns Hopkins Health System, disagreed with the idea that research and outbreak control goals needed to be in conflict.

"Whatever is done, it is incumbent upon all of us to make sure transparency and scientific rigor is inserted into the process," Dr. Perl said. With SARS (Severe Acute Respiratory Syndrome), "many people got steroids – this ended up hurting people, and there was not so much accountability with how that happened. We have to not do harm."

A number of attendees at the forum pressed the presenters on whether current containment strategies needed to be harder-edged or more coercive to be effective. "There is perhaps a time when coercion is necessary, Mr. Roberton acknowledged.

Dr. Perl alluded to a proposed role for the U.S. military in the Ebola crisis, though she stressed that she did not know what specific approach would be employed.

"I am far from the kind of person who would normally advocate" such a response, she said, but with the outbreak maturing and so many affected, "a command and control structure may be what is needed."

With smallpox, Dr. Perl added, "some pretty draconian things were required."

Addressing ethical challenges regarding quarantine, payment of health care workers, and the proper use of personal protective equipment could contribute significantly to the containment of the Ebola outbreak in West Africa, according to experts from Johns Hopkins University, Baltimore.

Citing reports of health care workers fleeing clinics, Nancy Kass, Sc.D., said that the international community is in good position to make sure that doctors, nurses, and other staff members at Ebola treatment centers are properly and regularly paid, noting that many are not.

CDC/Daniel J. DeNoon

Even before Ebola, "there were so many things going on in these environments that were unethical" in terms of pay and staffing practices, Dr. Kass, deputy director for bioethics and public health at the JHU Berman Institute of Bioethics, said at a forum held by the university.

The international community needs to provide personal protective equipment and training to all involved, she said, "including the person who cleans the floor."

Survivors of Ebola infection could be safely recruited to perform community outreach "and get a ton of money for doing it," Dr. Kass said.

Raising pay as well as service and staffing standards at clinics could also improve compliance with quarantine demands, she said, while also making quarantine fairer to patients and families.

"In a vacuum, we can think of the most ethical ways to manage quarantine," such as allowing family members to hold the patient’s hand through a barrier, Dr. Kass said. But when resources are tight, quarantine can mean a patient is isolated to the point of being deprived of food and water.

Tim Roberton, a fourth-year doctoral student at the university’s Bloomberg School of Public Health returned from Guinea in July. He said that he found that achieving compliance with quarantine could be a delicate matter, particularly in remote villages.

"To tell someone that you have to get to a treatment center when you get sick, that’s serious business. Do we expect people to comply knowing they’ll never see their families again?"

Even pushing for essential changes in burial practices to avoid infection "is really complicated," he said, and requires cooperation from local officials and religious leaders.

Mr. Roberton’s trip was part of a collaboration between the university and the International Foundation for the Red Cross, which has hundreds of volunteers working in Ebola-affected communities to communicate information about the outbreak, manage dead bodies, and disinfect sites.

"What will stop this is working with communities at the village level to help themselves not spread the disease," Mr. Roberton said, noting that resources should not be directed to research at the expense of controlling the outbreak.

Others at the forum, including panelist Dr. Trish Perl, a clinical epidemiologist with the Johns Hopkins Health System, disagreed with the idea that research and outbreak control goals needed to be in conflict.

"Whatever is done, it is incumbent upon all of us to make sure transparency and scientific rigor is inserted into the process," Dr. Perl said. With SARS (Severe Acute Respiratory Syndrome), "many people got steroids – this ended up hurting people, and there was not so much accountability with how that happened. We have to not do harm."

A number of attendees at the forum pressed the presenters on whether current containment strategies needed to be harder-edged or more coercive to be effective. "There is perhaps a time when coercion is necessary, Mr. Roberton acknowledged.

Dr. Perl alluded to a proposed role for the U.S. military in the Ebola crisis, though she stressed that she did not know what specific approach would be employed.

"I am far from the kind of person who would normally advocate" such a response, she said, but with the outbreak maturing and so many affected, "a command and control structure may be what is needed."

With smallpox, Dr. Perl added, "some pretty draconian things were required."

The rate of secondary transmission to household members of patients with Middle East respiratory syndrome coronavirus (MERS-CoV) is 4%, a study has shown.

The researchers studied 26 symptomatic index patients in Saudi Arabia along with 280 of their household contacts, and found only 12 with laboratory evidence of infection. The report was published online Aug. 27 in the New England Journal of Medicine.

Courtesy of Maureen Metcalfe/Azaibi Tamin

Dr. Christian Drosten of the University of Bonn (Germany) Medical Center and colleagues found the 12 contacts to have laboratory evidence of MERS-CoV infection a median of 17.5 days from onset of symptoms in the index patients they lived with. Two of the infected household contacts reported having had contact with camels. All 280 contacts were screened via RT-PCR assays on RNA from throat swabs along with serologic testing that included enzyme-linked immunosorbent assays (ELISAs), and immunofluorescence assays.

Of the 12 with evidence of infection, 7 carried MERS-CoV in their upper respiratory tract, generally in low levels. Nonetheless, "positive RT-PCR findings in persons with subclinical infection who are tested soon after exposure should be complemented by serologic analysis," the investigators wrote.

The median age of the household contacts in the study was 29, and of the 12 infected, only one developed symptoms, which were mild. "Persons in the first few decades of life without coexisting illnesses may be able to carry low levels of MERS-CoV RNA without obvious symptoms," the researchers wrote (N. Engl. J. Med. 2014 Aug. 27 [doi:10.1056/NEJMoa1405858]).

The investigators cited as a weakness of their study the fact that only 44 of the 280 contacts originally tested provided follow-up samples. This was because the first round of testing was obligatory in Saudi Arabia, and the second, voluntary. The lack of follow-up testing meant that "we cannot determine whether we may have missed contacts who had delayed seroconversion," they wrote.

Dr. Drosten’s research was funded by the European Commission and German government grants. One coauthor reported receiving payment from the Institute for Experimental Immunology affiliated with EuroIMMUN, a maker of reagents for diagnostics, and another reported support from EuroIMMUN as well as a pending patent related to human betacoronavirus lineage.

The rate of secondary transmission to household members of patients with Middle East respiratory syndrome coronavirus (MERS-CoV) is 4%, a study has shown.

The researchers studied 26 symptomatic index patients in Saudi Arabia along with 280 of their household contacts, and found only 12 with laboratory evidence of infection. The report was published online Aug. 27 in the New England Journal of Medicine.

Courtesy of Maureen Metcalfe/Azaibi Tamin

Dr. Christian Drosten of the University of Bonn (Germany) Medical Center and colleagues found the 12 contacts to have laboratory evidence of MERS-CoV infection a median of 17.5 days from onset of symptoms in the index patients they lived with. Two of the infected household contacts reported having had contact with camels. All 280 contacts were screened via RT-PCR assays on RNA from throat swabs along with serologic testing that included enzyme-linked immunosorbent assays (ELISAs), and immunofluorescence assays.

Of the 12 with evidence of infection, 7 carried MERS-CoV in their upper respiratory tract, generally in low levels. Nonetheless, "positive RT-PCR findings in persons with subclinical infection who are tested soon after exposure should be complemented by serologic analysis," the investigators wrote.

The median age of the household contacts in the study was 29, and of the 12 infected, only one developed symptoms, which were mild. "Persons in the first few decades of life without coexisting illnesses may be able to carry low levels of MERS-CoV RNA without obvious symptoms," the researchers wrote (N. Engl. J. Med. 2014 Aug. 27 [doi:10.1056/NEJMoa1405858]).

The investigators cited as a weakness of their study the fact that only 44 of the 280 contacts originally tested provided follow-up samples. This was because the first round of testing was obligatory in Saudi Arabia, and the second, voluntary. The lack of follow-up testing meant that "we cannot determine whether we may have missed contacts who had delayed seroconversion," they wrote.

Dr. Drosten’s research was funded by the European Commission and German government grants. One coauthor reported receiving payment from the Institute for Experimental Immunology affiliated with EuroIMMUN, a maker of reagents for diagnostics, and another reported support from EuroIMMUN as well as a pending patent related to human betacoronavirus lineage.

The rate of secondary transmission to household members of patients with Middle East respiratory syndrome coronavirus (MERS-CoV) is 4%, a study has shown.

The researchers studied 26 symptomatic index patients in Saudi Arabia along with 280 of their household contacts, and found only 12 with laboratory evidence of infection. The report was published online Aug. 27 in the New England Journal of Medicine.

Courtesy of Maureen Metcalfe/Azaibi Tamin

Dr. Christian Drosten of the University of Bonn (Germany) Medical Center and colleagues found the 12 contacts to have laboratory evidence of MERS-CoV infection a median of 17.5 days from onset of symptoms in the index patients they lived with. Two of the infected household contacts reported having had contact with camels. All 280 contacts were screened via RT-PCR assays on RNA from throat swabs along with serologic testing that included enzyme-linked immunosorbent assays (ELISAs), and immunofluorescence assays.

Of the 12 with evidence of infection, 7 carried MERS-CoV in their upper respiratory tract, generally in low levels. Nonetheless, "positive RT-PCR findings in persons with subclinical infection who are tested soon after exposure should be complemented by serologic analysis," the investigators wrote.

The median age of the household contacts in the study was 29, and of the 12 infected, only one developed symptoms, which were mild. "Persons in the first few decades of life without coexisting illnesses may be able to carry low levels of MERS-CoV RNA without obvious symptoms," the researchers wrote (N. Engl. J. Med. 2014 Aug. 27 [doi:10.1056/NEJMoa1405858]).

The investigators cited as a weakness of their study the fact that only 44 of the 280 contacts originally tested provided follow-up samples. This was because the first round of testing was obligatory in Saudi Arabia, and the second, voluntary. The lack of follow-up testing meant that "we cannot determine whether we may have missed contacts who had delayed seroconversion," they wrote.

Dr. Drosten’s research was funded by the European Commission and German government grants. One coauthor reported receiving payment from the Institute for Experimental Immunology affiliated with EuroIMMUN, a maker of reagents for diagnostics, and another reported support from EuroIMMUN as well as a pending patent related to human betacoronavirus lineage.

Researchers in Australia have used whole exome sequencing to discover a previously unknown pathogenic allele in a 4-year-old girl with early-onset cerebral systemic lupus erythematosus.

The researchers, led by Julia Ellyard, Ph.D., of Australian National University in Canberra, characterized the allele’s deleterious activity and recommend a personalized course of therapy based on their findings. Whole exome sequencing (WES) of the patient had revealed a rare, homozygous mutation in the three prime repair exonuclease 1 (TREX1) gene. The mutant protein TREX1 R97H was associated with a 20-fold reduction in exonuclease activity and an elevated interferon-alpha signature in the patient, who was deemed a candidate for experimental neutralizing anti-interferon-alpha therapy, which is under investigation in multiple phase II clinical trials, Dr. Ellyard and her colleagues reported (Arthritis Rheumatol. 2014 Aug. 19 [doi:10.1002/art.38824]).

The girl first presented at 3 years of age with arthritis, malar rash, diffuse purpura rashes, episodic fever, chronic headache, and vomiting, but no history of seizures or visual disturbance. Her Lebanese parents were first cousins but had no family history of autoimmunity. Her serology was positive for high-titer antinuclear antibodies, anti-double stranded DNA antibodies, anticardiolipin antibodies, elevated immunoglobulin G and A, and lymphopenia and Coombs’ positive anemia – all of which are consistent with systemic lupus erythematosus (SLE). MRI following her development of right-sided hemiparesis at 4 years revealed occlusion of the left middle cerebral artery and left-sided MCA infarct, and subsequent MR angiography showed "widespread and marked irregularities of the medium sized vessels consistent with vasculitis in the context of cerebral SLE," the authors wrote.

The study is the first to find a homozygous TREX1 variant in a patient with systemic lupus erythematosus. It also is the first study conducted by the university’s Center for Personalized Immunology, which was established to help discover causative genetic variation with the goal of delivering individualized treatment strategies.

The findings demonstrated "the efficacy of WES in identifying the genetic basis of autoimmune disease on an individual, personalized basis. We were able to identify a pathogenic variant in TREX1, which had not been a prime candidate for sequencing, and subsequently confirmed the deleterious effect of the mutation," the researchers wrote. "WES can identify genetic causes of complex autoimmune diseases such as SLE and, through identification of rare and novel deleterious variants, improve therapeutic options."

Dr. Ellyard and her colleagues received grant and fellowship support from Australia’s National Health and Medical Research Council and the Royal Australian College of Physicians. None of the authors reported conflicts of interest.

Researchers in Australia have used whole exome sequencing to discover a previously unknown pathogenic allele in a 4-year-old girl with early-onset cerebral systemic lupus erythematosus.

The researchers, led by Julia Ellyard, Ph.D., of Australian National University in Canberra, characterized the allele’s deleterious activity and recommend a personalized course of therapy based on their findings. Whole exome sequencing (WES) of the patient had revealed a rare, homozygous mutation in the three prime repair exonuclease 1 (TREX1) gene. The mutant protein TREX1 R97H was associated with a 20-fold reduction in exonuclease activity and an elevated interferon-alpha signature in the patient, who was deemed a candidate for experimental neutralizing anti-interferon-alpha therapy, which is under investigation in multiple phase II clinical trials, Dr. Ellyard and her colleagues reported (Arthritis Rheumatol. 2014 Aug. 19 [doi:10.1002/art.38824]).

The girl first presented at 3 years of age with arthritis, malar rash, diffuse purpura rashes, episodic fever, chronic headache, and vomiting, but no history of seizures or visual disturbance. Her Lebanese parents were first cousins but had no family history of autoimmunity. Her serology was positive for high-titer antinuclear antibodies, anti-double stranded DNA antibodies, anticardiolipin antibodies, elevated immunoglobulin G and A, and lymphopenia and Coombs’ positive anemia – all of which are consistent with systemic lupus erythematosus (SLE). MRI following her development of right-sided hemiparesis at 4 years revealed occlusion of the left middle cerebral artery and left-sided MCA infarct, and subsequent MR angiography showed "widespread and marked irregularities of the medium sized vessels consistent with vasculitis in the context of cerebral SLE," the authors wrote.

The study is the first to find a homozygous TREX1 variant in a patient with systemic lupus erythematosus. It also is the first study conducted by the university’s Center for Personalized Immunology, which was established to help discover causative genetic variation with the goal of delivering individualized treatment strategies.

The findings demonstrated "the efficacy of WES in identifying the genetic basis of autoimmune disease on an individual, personalized basis. We were able to identify a pathogenic variant in TREX1, which had not been a prime candidate for sequencing, and subsequently confirmed the deleterious effect of the mutation," the researchers wrote. "WES can identify genetic causes of complex autoimmune diseases such as SLE and, through identification of rare and novel deleterious variants, improve therapeutic options."

Dr. Ellyard and her colleagues received grant and fellowship support from Australia’s National Health and Medical Research Council and the Royal Australian College of Physicians. None of the authors reported conflicts of interest.

Researchers in Australia have used whole exome sequencing to discover a previously unknown pathogenic allele in a 4-year-old girl with early-onset cerebral systemic lupus erythematosus.

The researchers, led by Julia Ellyard, Ph.D., of Australian National University in Canberra, characterized the allele’s deleterious activity and recommend a personalized course of therapy based on their findings. Whole exome sequencing (WES) of the patient had revealed a rare, homozygous mutation in the three prime repair exonuclease 1 (TREX1) gene. The mutant protein TREX1 R97H was associated with a 20-fold reduction in exonuclease activity and an elevated interferon-alpha signature in the patient, who was deemed a candidate for experimental neutralizing anti-interferon-alpha therapy, which is under investigation in multiple phase II clinical trials, Dr. Ellyard and her colleagues reported (Arthritis Rheumatol. 2014 Aug. 19 [doi:10.1002/art.38824]).

The girl first presented at 3 years of age with arthritis, malar rash, diffuse purpura rashes, episodic fever, chronic headache, and vomiting, but no history of seizures or visual disturbance. Her Lebanese parents were first cousins but had no family history of autoimmunity. Her serology was positive for high-titer antinuclear antibodies, anti-double stranded DNA antibodies, anticardiolipin antibodies, elevated immunoglobulin G and A, and lymphopenia and Coombs’ positive anemia – all of which are consistent with systemic lupus erythematosus (SLE). MRI following her development of right-sided hemiparesis at 4 years revealed occlusion of the left middle cerebral artery and left-sided MCA infarct, and subsequent MR angiography showed "widespread and marked irregularities of the medium sized vessels consistent with vasculitis in the context of cerebral SLE," the authors wrote.

The study is the first to find a homozygous TREX1 variant in a patient with systemic lupus erythematosus. It also is the first study conducted by the university’s Center for Personalized Immunology, which was established to help discover causative genetic variation with the goal of delivering individualized treatment strategies.

The findings demonstrated "the efficacy of WES in identifying the genetic basis of autoimmune disease on an individual, personalized basis. We were able to identify a pathogenic variant in TREX1, which had not been a prime candidate for sequencing, and subsequently confirmed the deleterious effect of the mutation," the researchers wrote. "WES can identify genetic causes of complex autoimmune diseases such as SLE and, through identification of rare and novel deleterious variants, improve therapeutic options."

Dr. Ellyard and her colleagues received grant and fellowship support from Australia’s National Health and Medical Research Council and the Royal Australian College of Physicians. None of the authors reported conflicts of interest.