SAN DIEGO – Preventive cardiovascular medicine will get “a big boost” from ongoing major randomized controlled trials due to report results during the next several years, Dr. Eric D. Peterson predicted at the annual meeting of the American College of Cardiology.

He presented an overview of eagerly anticipated clinical trials approaching completion in three of the hottest areas of research in general cardiology: new cardiovascular prevention agents and strategies; innovative health policy initiatives; and optimal antithrombotic regimens across the range of chronic coronary artery disease, peripheral vascular disease, patients with atrial fibrillation who’ve undergone percutaneous coronary intervention, and cerebrovascular disease.

Dr. Peterson is executive director of the Duke Clinical Research Institute (DCRI), a major player in some of these studies. To gain additional perspective regarding what’s in store, he consulted a who’s who list of eminent American cardiology clinical trialists as to what’s going to be big in 2016-2017 and shortly beyond.

One thing’s clear looking out at the research horizon: Megatrials enrolling tens of thousands of patients to answer key clinical questions are not a thing of the past.

Far from it.

Cardiovascular prevention

Exciting pivotal phase III cardiovascular prevention trials are well underway in the areas of lipid modification, diabetes, and hypertension. In addition, the possible preventive effect of vitamin D and omega-3 free fatty acid supplementation seen in hypothesis-generating epidemiologic studies is finally being put to a definitive test in a 26,000-subject randomized trial known as VITAL (the Vitamin D and omega-3 trial).

Lipids: All eyes are on ongoing pivotal phase III randomized clinical outcome trials of three monoclonal antibodies that inhibit proprotein convertase subtilisin kexin type 9 (PCSK9): the 22,500-patient FOURIER trial of evolocumab, which includes 9,000 patients older than 65 years; the 18,000-patient ODYSSEY Outcomes trial of alirocumab; and the SPIRE-1 and SPIRE-2 trials of bococizumab totaling 18,300 patients.

In phase II studies, these agents have generated enormous excitement, because they safely achieve unprecedented LDL lowering, with early hints of improved clinical outcomes beyond what’s achievable with today’s drugs, noted Dr. Peterson, professor of medicine at Duke University in Durham, N.C.

CETP inhibitors: The cholesteryl ester transfer protein inhibitors torcetrapib and dalcetrapib flamed out in clinical trials because of safety concerns and lack of clinical benefit. But pivotal phase III trials of two other CETP inhibitors are well underway: anacetrapib, which is the focus of the 30,000-patient REVEAL trial; and evacetrapib, featured in the 11,000-patient ACCELERATE trial. The CETP inhibitors simultaneously boost HDL while reducing LDL.

Diabetes: The search continues for new drugs that not only enhance diabetes control but also improve cardiovascular outcomes, or at the very least are safe in diabetes patients with coronary disease.

Next up is the nearly 15,000-patient Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), coordinated by the DCRI and University of Oxford. It’s due to be presented in June at the annual meeting of the American Diabetes Association in Boston. Trials of other dipeptidyl peptidase-4 inhibitors have shown evidence of an increased risk of heart failure, specifically with saxagliptin in the SAVOR-TIMI 53 trial and alogliptin in EXAMINE, so a lot is riding on TECOS.

The glucagon-like peptide-1 (GLP-1) agonists are under study in cardiovascular event-driven randomized clinical trials collectively totaling more than 33,000 patients with type 2 diabetes. The Exenatide Study of Cardiovascular Event Lowering (EXSCEL), also coordinated by the DCRI and University of Oxford, includes 14,000 randomized patients. Other major trials of GLP-1 agonists are ELIXA (lixisenatide), LEADER (liraglutide), and REWIND (dulaglutide).

In addition, ongoing phase III trials of sodium glucose cotransporter 2 (SGLT-2) inhibitors with cardiovascular endpoints include the Canagliflozin Cardiovascular Assessment Study (CANVAS) and a 7,000-patient study of empagliflozin known as EMPA-REG OUTCOME.

Hypertension: The Systolic Blood Pressure Intervention Trial (SPRINT) is an NIH-funded, randomized trial designed to finally answer a question bothering physicians for years: What’s the right amount of blood pressure lowering?

Nearly 9,400 high-risk patients with clinical or subclinical cardiovascular disease have been randomized to a target systolic blood pressure of less than 120 mm Hg, compared with less than 140 mm Hg. The primary composite endpoint is cardiovascular death, nonfatal MI or stroke, or hospitalization for acute coronary syndrome. Secondary endpoints focus on cognitive impairment, dementia, and rates of progression of chronic kidney disease. Results are expected in 2018.

Vitamin D: The VITAL trial, also sponsored by the NIH, has randomized 25,875 initially healthy men and women to 2,000 IU of vitamin D₃ per day or placebo, and further randomized them to 1 g/day of omega-3 fatty acids or placebo. Key endpoints are total cancers, MI, stroke, and cardiovascular death. Results are coming in 2017.

Optimal antithrombotic therapy

Chronic coronary artery disease: It’s remarkable that physicians still don’t know the right dose of aspirin to use, even though the drug has been around since 1897. The answer is finally on the way. It will come from the ADAPTABLE eTrial, the first comparative effectiveness research project funded by the Patient-Centered Outcomes Research Institute (PCORI).

Twenty thousand U.S. patients with known atherosclerotic cardiovascular disease and at least one extra risk factor will be randomized to daily aspirin at 81 mg or 325 mg and followed for a maximum of 30 months. The primary efficacy endpoint is all-cause mortality, nonfatal MI, or nonfatal stroke. The primary safety endpoint is major bleeding.

This is a groundbreaking innovative study: It’s a 20,000-patient trial budgeted at a mere $10 million – peanuts in the world of megatrials. By comparison, the NIH-funded SPRINT hypertension trial includes less than half as many patients, yet the price tag is $114 million.

The bargain-basement cost of the aspirin trial is possible because follow-up will be via electronic medical records and claims data provided every 3 months by 29 health data networks participating in PCORI’s National Patient-Centered Clinical Research Network (PCORnet). The aspirin study is sort of a shakedown cruise for an exciting new cost-effective approach to conducting comparative effectiveness research.

“This study could be a game changer,” Dr. Peterson declared. “Whether you think the research question is important or not, the ability to utilize electronic health records in long-term patient follow-up in randomized trials will be revolutionary in terms of answering key clinical questions cost effectively.”

Peripheral vascular disease: In search of the antithrombotic regimen that optimizes limb salvage while minimizing vascular event rate, the EUCLID trial has randomized 13,500 patients with symptomatic peripheral artery disease to ticagrelor at 90 mg BID or clopidogrel at 75 mg/day. Follow-up will be for 18 months, with the primary endpoint a composite of cardiovascular death, nonfatal MI, or ischemic stroke.

Atrial fibrillation patients who undergo coronary stent placement: The 2,100-patient PIONEER AF-PCI study, now recruiting, is evaluating different combinations of rivaroxaban in various dosing regimens coupled with clopidogrel, warfarin, and/or aspirin.

Stroke: The SOCRATES trial is recruiting 9,600 patients with acute ischemic stroke or high-risk transient ischemic attack to be randomized within 24 hours to ticagrelor at 90 mg BID or aspirin at 100 mg/day. As with PIONEER, results from SOCRATES are anticipated next year.

Health policy and implementation

The ARTEMIS study poses the question of whether providing a guideline-directed medication gratis will improve patient adherence and/or clinical outcomes.

Some 9,000 high-cardiovascular-risk patients at 300 sites are being randomized to free ticagrelor or clopidogrel – no copay – for 1 year or to usual care. Outcomes include choice of medication, adherence, and major adverse cardiovascular events.

“If this works, there’s the possibility that insurers can be persuaded to pay for medications and basically give them away as a means of ultimately resulting in better outcomes for patients and lower costs,” Dr. Peterson said.

IMPACT AF is an international quality improvement project aimed at improving the use of oral anticoagulation therapy in high-risk patients with atrial fibrillation in Argentina, Brazil, China, India, and Romania. Participating centers will be randomized to receive a provider education and feedback program or not. The primary outcome is a change from baseline through year 1 in the proportion of patients with atrial fibrillation taking an oral anticoagulant.

In summing up the state of research in general cardiology, Dr. Peterson observed, “The way we do trials is changing. The size of the studies is changing. But ultimately, we will find better ways to treat patients, and perhaps we can find better ways to encourage patients to take their medications long term.”

Dr. Peterson reported serving as a consultant to AstraZeneca Boehringer Ingelheim, Genentech, Janssen, and Sanofi, and receiving research funding from Eli Lilly and Janssen.

[email protected]


SAN DIEGO – Preventive cardiovascular medicine will get “a big boost” from ongoing major randomized controlled trials due to report results during the next several years, Dr. Eric D. Peterson predicted at the annual meeting of the American College of Cardiology.

He presented an overview of eagerly anticipated clinical trials approaching completion in three of the hottest areas of research in general cardiology: new cardiovascular prevention agents and strategies; innovative health policy initiatives; and optimal antithrombotic regimens across the range of chronic coronary artery disease, peripheral vascular disease, patients with atrial fibrillation who’ve undergone percutaneous coronary intervention, and cerebrovascular disease.

Dr. Peterson is executive director of the Duke Clinical Research Institute (DCRI), a major player in some of these studies. To gain additional perspective regarding what’s in store, he consulted a who’s who list of eminent American cardiology clinical trialists as to what’s going to be big in 2016-2017 and shortly beyond.

One thing’s clear looking out at the research horizon: Megatrials enrolling tens of thousands of patients to answer key clinical questions are not a thing of the past.

Far from it.

Cardiovascular prevention

Exciting pivotal phase III cardiovascular prevention trials are well underway in the areas of lipid modification, diabetes, and hypertension. In addition, the possible preventive effect of vitamin D and omega-3 free fatty acid supplementation seen in hypothesis-generating epidemiologic studies is finally being put to a definitive test in a 26,000-subject randomized trial known as VITAL (the Vitamin D and omega-3 trial).

Lipids: All eyes are on ongoing pivotal phase III randomized clinical outcome trials of three monoclonal antibodies that inhibit proprotein convertase subtilisin kexin type 9 (PCSK9): the 22,500-patient FOURIER trial of evolocumab, which includes 9,000 patients older than 65 years; the 18,000-patient ODYSSEY Outcomes trial of alirocumab; and the SPIRE-1 and SPIRE-2 trials of bococizumab totaling 18,300 patients.

In phase II studies, these agents have generated enormous excitement, because they safely achieve unprecedented LDL lowering, with early hints of improved clinical outcomes beyond what’s achievable with today’s drugs, noted Dr. Peterson, professor of medicine at Duke University in Durham, N.C.

CETP inhibitors: The cholesteryl ester transfer protein inhibitors torcetrapib and dalcetrapib flamed out in clinical trials because of safety concerns and lack of clinical benefit. But pivotal phase III trials of two other CETP inhibitors are well underway: anacetrapib, which is the focus of the 30,000-patient REVEAL trial; and evacetrapib, featured in the 11,000-patient ACCELERATE trial. The CETP inhibitors simultaneously boost HDL while reducing LDL.

Diabetes: The search continues for new drugs that not only enhance diabetes control but also improve cardiovascular outcomes, or at the very least are safe in diabetes patients with coronary disease.

Next up is the nearly 15,000-patient Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), coordinated by the DCRI and University of Oxford. It’s due to be presented in June at the annual meeting of the American Diabetes Association in Boston. Trials of other dipeptidyl peptidase-4 inhibitors have shown evidence of an increased risk of heart failure, specifically with saxagliptin in the SAVOR-TIMI 53 trial and alogliptin in EXAMINE, so a lot is riding on TECOS.

The glucagon-like peptide-1 (GLP-1) agonists are under study in cardiovascular event-driven randomized clinical trials collectively totaling more than 33,000 patients with type 2 diabetes. The Exenatide Study of Cardiovascular Event Lowering (EXSCEL), also coordinated by the DCRI and University of Oxford, includes 14,000 randomized patients. Other major trials of GLP-1 agonists are ELIXA (lixisenatide), LEADER (liraglutide), and REWIND (dulaglutide).

In addition, ongoing phase III trials of sodium glucose cotransporter 2 (SGLT-2) inhibitors with cardiovascular endpoints include the Canagliflozin Cardiovascular Assessment Study (CANVAS) and a 7,000-patient study of empagliflozin known as EMPA-REG OUTCOME.

Hypertension: The Systolic Blood Pressure Intervention Trial (SPRINT) is an NIH-funded, randomized trial designed to finally answer a question bothering physicians for years: What’s the right amount of blood pressure lowering?

Nearly 9,400 high-risk patients with clinical or subclinical cardiovascular disease have been randomized to a target systolic blood pressure of less than 120 mm Hg, compared with less than 140 mm Hg. The primary composite endpoint is cardiovascular death, nonfatal MI or stroke, or hospitalization for acute coronary syndrome. Secondary endpoints focus on cognitive impairment, dementia, and rates of progression of chronic kidney disease. Results are expected in 2018.

Vitamin D: The VITAL trial, also sponsored by the NIH, has randomized 25,875 initially healthy men and women to 2,000 IU of vitamin D₃ per day or placebo, and further randomized them to 1 g/day of omega-3 fatty acids or placebo. Key endpoints are total cancers, MI, stroke, and cardiovascular death. Results are coming in 2017.

Optimal antithrombotic therapy

Chronic coronary artery disease: It’s remarkable that physicians still don’t know the right dose of aspirin to use, even though the drug has been around since 1897. The answer is finally on the way. It will come from the ADAPTABLE eTrial, the first comparative effectiveness research project funded by the Patient-Centered Outcomes Research Institute (PCORI).

Twenty thousand U.S. patients with known atherosclerotic cardiovascular disease and at least one extra risk factor will be randomized to daily aspirin at 81 mg or 325 mg and followed for a maximum of 30 months. The primary efficacy endpoint is all-cause mortality, nonfatal MI, or nonfatal stroke. The primary safety endpoint is major bleeding.

This is a groundbreaking innovative study: It’s a 20,000-patient trial budgeted at a mere $10 million – peanuts in the world of megatrials. By comparison, the NIH-funded SPRINT hypertension trial includes less than half as many patients, yet the price tag is $114 million.

The bargain-basement cost of the aspirin trial is possible because follow-up will be via electronic medical records and claims data provided every 3 months by 29 health data networks participating in PCORI’s National Patient-Centered Clinical Research Network (PCORnet). The aspirin study is sort of a shakedown cruise for an exciting new cost-effective approach to conducting comparative effectiveness research.

“This study could be a game changer,” Dr. Peterson declared. “Whether you think the research question is important or not, the ability to utilize electronic health records in long-term patient follow-up in randomized trials will be revolutionary in terms of answering key clinical questions cost effectively.”

Peripheral vascular disease: In search of the antithrombotic regimen that optimizes limb salvage while minimizing vascular event rate, the EUCLID trial has randomized 13,500 patients with symptomatic peripheral artery disease to ticagrelor at 90 mg BID or clopidogrel at 75 mg/day. Follow-up will be for 18 months, with the primary endpoint a composite of cardiovascular death, nonfatal MI, or ischemic stroke.

Atrial fibrillation patients who undergo coronary stent placement: The 2,100-patient PIONEER AF-PCI study, now recruiting, is evaluating different combinations of rivaroxaban in various dosing regimens coupled with clopidogrel, warfarin, and/or aspirin.

Stroke: The SOCRATES trial is recruiting 9,600 patients with acute ischemic stroke or high-risk transient ischemic attack to be randomized within 24 hours to ticagrelor at 90 mg BID or aspirin at 100 mg/day. As with PIONEER, results from SOCRATES are anticipated next year.

Health policy and implementation

The ARTEMIS study poses the question of whether providing a guideline-directed medication gratis will improve patient adherence and/or clinical outcomes.

Some 9,000 high-cardiovascular-risk patients at 300 sites are being randomized to free ticagrelor or clopidogrel – no copay – for 1 year or to usual care. Outcomes include choice of medication, adherence, and major adverse cardiovascular events.

“If this works, there’s the possibility that insurers can be persuaded to pay for medications and basically give them away as a means of ultimately resulting in better outcomes for patients and lower costs,” Dr. Peterson said.

IMPACT AF is an international quality improvement project aimed at improving the use of oral anticoagulation therapy in high-risk patients with atrial fibrillation in Argentina, Brazil, China, India, and Romania. Participating centers will be randomized to receive a provider education and feedback program or not. The primary outcome is a change from baseline through year 1 in the proportion of patients with atrial fibrillation taking an oral anticoagulant.

In summing up the state of research in general cardiology, Dr. Peterson observed, “The way we do trials is changing. The size of the studies is changing. But ultimately, we will find better ways to treat patients, and perhaps we can find better ways to encourage patients to take their medications long term.”

Dr. Peterson reported serving as a consultant to AstraZeneca Boehringer Ingelheim, Genentech, Janssen, and Sanofi, and receiving research funding from Eli Lilly and Janssen.

[email protected]


SAN DIEGO – Preventive cardiovascular medicine will get “a big boost” from ongoing major randomized controlled trials due to report results during the next several years, Dr. Eric D. Peterson predicted at the annual meeting of the American College of Cardiology.

He presented an overview of eagerly anticipated clinical trials approaching completion in three of the hottest areas of research in general cardiology: new cardiovascular prevention agents and strategies; innovative health policy initiatives; and optimal antithrombotic regimens across the range of chronic coronary artery disease, peripheral vascular disease, patients with atrial fibrillation who’ve undergone percutaneous coronary intervention, and cerebrovascular disease.

Dr. Peterson is executive director of the Duke Clinical Research Institute (DCRI), a major player in some of these studies. To gain additional perspective regarding what’s in store, he consulted a who’s who list of eminent American cardiology clinical trialists as to what’s going to be big in 2016-2017 and shortly beyond.

One thing’s clear looking out at the research horizon: Megatrials enrolling tens of thousands of patients to answer key clinical questions are not a thing of the past.

Far from it.

Cardiovascular prevention

Exciting pivotal phase III cardiovascular prevention trials are well underway in the areas of lipid modification, diabetes, and hypertension. In addition, the possible preventive effect of vitamin D and omega-3 free fatty acid supplementation seen in hypothesis-generating epidemiologic studies is finally being put to a definitive test in a 26,000-subject randomized trial known as VITAL (the Vitamin D and omega-3 trial).

Lipids: All eyes are on ongoing pivotal phase III randomized clinical outcome trials of three monoclonal antibodies that inhibit proprotein convertase subtilisin kexin type 9 (PCSK9): the 22,500-patient FOURIER trial of evolocumab, which includes 9,000 patients older than 65 years; the 18,000-patient ODYSSEY Outcomes trial of alirocumab; and the SPIRE-1 and SPIRE-2 trials of bococizumab totaling 18,300 patients.

In phase II studies, these agents have generated enormous excitement, because they safely achieve unprecedented LDL lowering, with early hints of improved clinical outcomes beyond what’s achievable with today’s drugs, noted Dr. Peterson, professor of medicine at Duke University in Durham, N.C.

CETP inhibitors: The cholesteryl ester transfer protein inhibitors torcetrapib and dalcetrapib flamed out in clinical trials because of safety concerns and lack of clinical benefit. But pivotal phase III trials of two other CETP inhibitors are well underway: anacetrapib, which is the focus of the 30,000-patient REVEAL trial; and evacetrapib, featured in the 11,000-patient ACCELERATE trial. The CETP inhibitors simultaneously boost HDL while reducing LDL.

Diabetes: The search continues for new drugs that not only enhance diabetes control but also improve cardiovascular outcomes, or at the very least are safe in diabetes patients with coronary disease.

Next up is the nearly 15,000-patient Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), coordinated by the DCRI and University of Oxford. It’s due to be presented in June at the annual meeting of the American Diabetes Association in Boston. Trials of other dipeptidyl peptidase-4 inhibitors have shown evidence of an increased risk of heart failure, specifically with saxagliptin in the SAVOR-TIMI 53 trial and alogliptin in EXAMINE, so a lot is riding on TECOS.

The glucagon-like peptide-1 (GLP-1) agonists are under study in cardiovascular event-driven randomized clinical trials collectively totaling more than 33,000 patients with type 2 diabetes. The Exenatide Study of Cardiovascular Event Lowering (EXSCEL), also coordinated by the DCRI and University of Oxford, includes 14,000 randomized patients. Other major trials of GLP-1 agonists are ELIXA (lixisenatide), LEADER (liraglutide), and REWIND (dulaglutide).

In addition, ongoing phase III trials of sodium glucose cotransporter 2 (SGLT-2) inhibitors with cardiovascular endpoints include the Canagliflozin Cardiovascular Assessment Study (CANVAS) and a 7,000-patient study of empagliflozin known as EMPA-REG OUTCOME.

Hypertension: The Systolic Blood Pressure Intervention Trial (SPRINT) is an NIH-funded, randomized trial designed to finally answer a question bothering physicians for years: What’s the right amount of blood pressure lowering?

Nearly 9,400 high-risk patients with clinical or subclinical cardiovascular disease have been randomized to a target systolic blood pressure of less than 120 mm Hg, compared with less than 140 mm Hg. The primary composite endpoint is cardiovascular death, nonfatal MI or stroke, or hospitalization for acute coronary syndrome. Secondary endpoints focus on cognitive impairment, dementia, and rates of progression of chronic kidney disease. Results are expected in 2018.

Vitamin D: The VITAL trial, also sponsored by the NIH, has randomized 25,875 initially healthy men and women to 2,000 IU of vitamin D₃ per day or placebo, and further randomized them to 1 g/day of omega-3 fatty acids or placebo. Key endpoints are total cancers, MI, stroke, and cardiovascular death. Results are coming in 2017.

Optimal antithrombotic therapy

Chronic coronary artery disease: It’s remarkable that physicians still don’t know the right dose of aspirin to use, even though the drug has been around since 1897. The answer is finally on the way. It will come from the ADAPTABLE eTrial, the first comparative effectiveness research project funded by the Patient-Centered Outcomes Research Institute (PCORI).

Twenty thousand U.S. patients with known atherosclerotic cardiovascular disease and at least one extra risk factor will be randomized to daily aspirin at 81 mg or 325 mg and followed for a maximum of 30 months. The primary efficacy endpoint is all-cause mortality, nonfatal MI, or nonfatal stroke. The primary safety endpoint is major bleeding.

This is a groundbreaking innovative study: It’s a 20,000-patient trial budgeted at a mere $10 million – peanuts in the world of megatrials. By comparison, the NIH-funded SPRINT hypertension trial includes less than half as many patients, yet the price tag is $114 million.

The bargain-basement cost of the aspirin trial is possible because follow-up will be via electronic medical records and claims data provided every 3 months by 29 health data networks participating in PCORI’s National Patient-Centered Clinical Research Network (PCORnet). The aspirin study is sort of a shakedown cruise for an exciting new cost-effective approach to conducting comparative effectiveness research.

“This study could be a game changer,” Dr. Peterson declared. “Whether you think the research question is important or not, the ability to utilize electronic health records in long-term patient follow-up in randomized trials will be revolutionary in terms of answering key clinical questions cost effectively.”

Peripheral vascular disease: In search of the antithrombotic regimen that optimizes limb salvage while minimizing vascular event rate, the EUCLID trial has randomized 13,500 patients with symptomatic peripheral artery disease to ticagrelor at 90 mg BID or clopidogrel at 75 mg/day. Follow-up will be for 18 months, with the primary endpoint a composite of cardiovascular death, nonfatal MI, or ischemic stroke.

Atrial fibrillation patients who undergo coronary stent placement: The 2,100-patient PIONEER AF-PCI study, now recruiting, is evaluating different combinations of rivaroxaban in various dosing regimens coupled with clopidogrel, warfarin, and/or aspirin.

Stroke: The SOCRATES trial is recruiting 9,600 patients with acute ischemic stroke or high-risk transient ischemic attack to be randomized within 24 hours to ticagrelor at 90 mg BID or aspirin at 100 mg/day. As with PIONEER, results from SOCRATES are anticipated next year.

Health policy and implementation

The ARTEMIS study poses the question of whether providing a guideline-directed medication gratis will improve patient adherence and/or clinical outcomes.

Some 9,000 high-cardiovascular-risk patients at 300 sites are being randomized to free ticagrelor or clopidogrel – no copay – for 1 year or to usual care. Outcomes include choice of medication, adherence, and major adverse cardiovascular events.

“If this works, there’s the possibility that insurers can be persuaded to pay for medications and basically give them away as a means of ultimately resulting in better outcomes for patients and lower costs,” Dr. Peterson said.

IMPACT AF is an international quality improvement project aimed at improving the use of oral anticoagulation therapy in high-risk patients with atrial fibrillation in Argentina, Brazil, China, India, and Romania. Participating centers will be randomized to receive a provider education and feedback program or not. The primary outcome is a change from baseline through year 1 in the proportion of patients with atrial fibrillation taking an oral anticoagulant.

In summing up the state of research in general cardiology, Dr. Peterson observed, “The way we do trials is changing. The size of the studies is changing. But ultimately, we will find better ways to treat patients, and perhaps we can find better ways to encourage patients to take their medications long term.”

Dr. Peterson reported serving as a consultant to AstraZeneca Boehringer Ingelheim, Genentech, Janssen, and Sanofi, and receiving research funding from Eli Lilly and Janssen.

[email protected]


Thrombus

Image by Andre E.X. Brown

A new approach for treating thrombotic thrombocytopenic purpura (TTP) has proven effective in mice, according to a paper published in Blood.

Researchers showed they could “hide” functional recombinant human ADAMTS13 (rADAMTS13) inside mouse platelets to prevent antibodies from impairing ADAMTS13 activity.

These rADAMTS13-expressing platelets were able to inhibit thrombosis and prevent the development of hereditary and acquired TTP in mice.

If a similar technique were to prove effective in humans, it could reduce the amount of plasma transfusions TTP patients require, the researchers said.

They also believe such a method could be used in emergency situations to treat strokes, heart attacks, malignant malaria, and pre-eclampsia, as all of these conditions are associated with relative deficiency of plasma ADAMTS13 activity.

This research began when X. Long Zheng, MD, PhD, of the University of Alabama at Birmingham, had the idea that he could treat TTP by hiding ADAMTS13 inside platelets where autoantibodies can’t see it.

He reasoned that, if he could fill platelets with ADAMTS13, the platelets would then carry the enzyme right to the place it was most needed to dissolve thrombi.

So he and his colleagues developed transgenic mice that expressed rADAMTS13 in their platelets.

The platelets had normal agglutination and aggregation. And they released rADAMTS13 upon stimulation with thrombin and collagen, although they released less when stimulated with 2MesADP.

Mice with rADAMTS13-expressing platelets were significantly protected in a vascular injury model of thrombus formation.

In mice that lacked plasma ADAMTS13 activity due to ADAMTS13 gene deletion and those that had antibody-mediated inhibition of plasma ADAMTS13 activity, rADAMTS13-expressing platelets protected the animals against TTP induced by bacterial toxin or recombinant von Willebrand factor.

These results, the researchers said, “suggest that platelets may be ideal carriers for antithrombic ADAMTS13, allowing its release at high concentrations at the site of thrombus formation without being inactivated by the potential circulating anti-ADAMTS13 inhibitors.”

To employ this treatment method in humans, Dr Zheng said researchers could investigate how to load ADAMTS13 inside donated platelets. They could then test these platelets to learn how many ADAMTS13-loaded platelets need to be transfused to produce antithrombotic and anti-TTP effects in patients with TTP.

Thrombus

Image by Andre E.X. Brown

A new approach for treating thrombotic thrombocytopenic purpura (TTP) has proven effective in mice, according to a paper published in Blood.

Researchers showed they could “hide” functional recombinant human ADAMTS13 (rADAMTS13) inside mouse platelets to prevent antibodies from impairing ADAMTS13 activity.

These rADAMTS13-expressing platelets were able to inhibit thrombosis and prevent the development of hereditary and acquired TTP in mice.

If a similar technique were to prove effective in humans, it could reduce the amount of plasma transfusions TTP patients require, the researchers said.

They also believe such a method could be used in emergency situations to treat strokes, heart attacks, malignant malaria, and pre-eclampsia, as all of these conditions are associated with relative deficiency of plasma ADAMTS13 activity.

This research began when X. Long Zheng, MD, PhD, of the University of Alabama at Birmingham, had the idea that he could treat TTP by hiding ADAMTS13 inside platelets where autoantibodies can’t see it.

He reasoned that, if he could fill platelets with ADAMTS13, the platelets would then carry the enzyme right to the place it was most needed to dissolve thrombi.

So he and his colleagues developed transgenic mice that expressed rADAMTS13 in their platelets.

The platelets had normal agglutination and aggregation. And they released rADAMTS13 upon stimulation with thrombin and collagen, although they released less when stimulated with 2MesADP.

Mice with rADAMTS13-expressing platelets were significantly protected in a vascular injury model of thrombus formation.

In mice that lacked plasma ADAMTS13 activity due to ADAMTS13 gene deletion and those that had antibody-mediated inhibition of plasma ADAMTS13 activity, rADAMTS13-expressing platelets protected the animals against TTP induced by bacterial toxin or recombinant von Willebrand factor.

These results, the researchers said, “suggest that platelets may be ideal carriers for antithrombic ADAMTS13, allowing its release at high concentrations at the site of thrombus formation without being inactivated by the potential circulating anti-ADAMTS13 inhibitors.”

To employ this treatment method in humans, Dr Zheng said researchers could investigate how to load ADAMTS13 inside donated platelets. They could then test these platelets to learn how many ADAMTS13-loaded platelets need to be transfused to produce antithrombotic and anti-TTP effects in patients with TTP.

Thrombus

Image by Andre E.X. Brown

A new approach for treating thrombotic thrombocytopenic purpura (TTP) has proven effective in mice, according to a paper published in Blood.

Researchers showed they could “hide” functional recombinant human ADAMTS13 (rADAMTS13) inside mouse platelets to prevent antibodies from impairing ADAMTS13 activity.

These rADAMTS13-expressing platelets were able to inhibit thrombosis and prevent the development of hereditary and acquired TTP in mice.

If a similar technique were to prove effective in humans, it could reduce the amount of plasma transfusions TTP patients require, the researchers said.

They also believe such a method could be used in emergency situations to treat strokes, heart attacks, malignant malaria, and pre-eclampsia, as all of these conditions are associated with relative deficiency of plasma ADAMTS13 activity.

This research began when X. Long Zheng, MD, PhD, of the University of Alabama at Birmingham, had the idea that he could treat TTP by hiding ADAMTS13 inside platelets where autoantibodies can’t see it.

He reasoned that, if he could fill platelets with ADAMTS13, the platelets would then carry the enzyme right to the place it was most needed to dissolve thrombi.

So he and his colleagues developed transgenic mice that expressed rADAMTS13 in their platelets.

The platelets had normal agglutination and aggregation. And they released rADAMTS13 upon stimulation with thrombin and collagen, although they released less when stimulated with 2MesADP.

Mice with rADAMTS13-expressing platelets were significantly protected in a vascular injury model of thrombus formation.

In mice that lacked plasma ADAMTS13 activity due to ADAMTS13 gene deletion and those that had antibody-mediated inhibition of plasma ADAMTS13 activity, rADAMTS13-expressing platelets protected the animals against TTP induced by bacterial toxin or recombinant von Willebrand factor.

These results, the researchers said, “suggest that platelets may be ideal carriers for antithrombic ADAMTS13, allowing its release at high concentrations at the site of thrombus formation without being inactivated by the potential circulating anti-ADAMTS13 inhibitors.”

To employ this treatment method in humans, Dr Zheng said researchers could investigate how to load ADAMTS13 inside donated platelets. They could then test these platelets to learn how many ADAMTS13-loaded platelets need to be transfused to produce antithrombotic and anti-TTP effects in patients with TTP.

SAN DIEGO – Patients aged 80 years and older benefit from more invasive early treatment after non-ST-elevation myocardial infarction or unstable angina, the After Eighty Trial showed.

After a median follow-up of 1.5 years, an invasive strategy that included coronary angiography significantly reduced the primary endpoint of myocardial infarction (MI), need for urgent revascularization, stroke, and death from 61% with optimal medical treatment to 41% (risk ratio, 0.48; P value < .00001).

That drop was driven primarily by significantly fewer MIs (17% vs. 30%; RR, 0.50; P = .0003) and urgent revascularizations (2% vs. 11%; RR, 0.19; P = .0001), lead author Dr. Nicolai Tegn reported at the American College of Cardiology/Cardiovascular Research Foundation Innovation in Intervention Summit.

There were no significant differences between the invasive and conservative strategy groups in rates of stroke (3% vs. 6%; RR, 0.61; P = .26) or all-cause death (25% vs. 27%; RR, 0.87; P = .53).

The composite of death and MI, however, significantly favored the invasive group (35% vs. 48%; RR, 0.54; P < .0001), he said during a latebreaking clinical trial session.

After Eighty randomly assigned 457 patients, aged 80 years or older, to either optimal medical therapy with no invasive treatments or coronary angiography at a percutaneous coronary intervention (PCI) center the day after inclusion, plus optimal medical therapy after about 4-5 hours if PCI was not performed or about 6-18 hours if it was. Of the 225 patients receiving angiography, 48% went on to balloon angioplasty and/or coronary stenting, and 3% had bypass surgery.

Patients 80 years or older account for roughly one-third of all patients with non-STEMI and unstable angina, but they are underrepresented in clinical trials. As a result, the role of an early invasive strategy, and even an invasive strategy at all, in those elderly patients is still a subject of debate, observed Dr. Tegn, a cardiologist from Rikshospitalet, Oslo University Hospital, Oslo.

The study demonstrated that an invasive strategy is superior to a conservative strategy in patients at least 80 years with NSTEMI or unstable angina, he concluded.

After Eighty is a welcome study because of the under-representation of the elderly in clinical trials, Dr. David Kandzari, director of interventional cardiology at the Piedmont Heart Center in Atlanta, said during a press briefing at the meeting. But it raises the challenge of identifying patients in clinical practice with the same qualifying characteristics, he added, given that the study population represents only 10% of the entire screened population,

There was also a fairly high prevalence of patients who angiographically did not have significant coronary artery disease, yet MI and stroke rates were quite considerable.

That said, “the study in other ways reminds us that the coronary anatomy does not know the age of the patient, meaning that the findings of a benefit of an early invasive strategy seem consistent with previous studies we know across the management of patients with acute coronary syndromes,” Dr. Kandzari said.

After Eighty investigators screened 4,187 elderly patients presenting at 17 community hospitals in Norway with non-STEMI or unstable angina, with or without ST-segment depression in ECG, and normal or elevated troponin T or I levels. Patients had to have no chest pain or other ischemic symptoms after medical treatment and mobilization.

In all, 3,730 patients were excluded for life expectancy less than 12 months because of a serious comorbidity; ongoing or recent bleeding; inability to comply with protocol; clinically unstable including ongoing ischemia; refusal to participate; logistic reasons; or other reasons.

The average age was 84.7 years in the invasive group (range 80-93 years) and 84.9 years in the conservative group (range 80-94 years).

Medical treatment during the index admission included 75 mg aspirin in 97% of both the invasive and conservative groups, clopidogrel (85% vs. 82%), ticagrelor (both 5%), angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blockers (ARB) (43% vs. 50%), beta blocker (83% vs. 85%), statins (90% vs. 85%), loop or thiazide diuretics (41% vs. 33%), calcium channel blocker (20% vs. 21%), nitrates (45% vs. 55%), warfarin (17% vs. 9%), low molecular-weight heparin (both 76% ), and dabigatran in one patient in each group.

Medical therapy at discharge in the invasive and conservative groups was aspirin (both 93%), clopidogrel (both 72%), ticagrelor (both 4%), ACE inhibitor/ARB (52% vs. 54%), beta blockers (both 84%), statins (90% vs. 86%), diuretics (45% vs. 38%), calcium channel blocker (24% vs. 23%), nitrates (34% vs. 48%), warfarin (21% vs. 14%), rivaroxaban (three patients in both groups), and dabigatran (one patient vs. six patients).

There were no differences in bleeding rates between the two groups, Dr. Tegn said. Four major bleeding events were reported in both groups, while 23 patients in the invasive group and 16 patients in the conservative group had minor bleeds.

The Norwegian Health Association sponsored the study. Dr. Tegn reported nothing to disclose. Dr. Kandazari reported research and grant support from Abbott Vascular, Biotronic, Boston Scientific, and Medtronic, and minor consulting honoraria from Boston Scientific and Medtronic.

[email protected]

SAN DIEGO – Patients aged 80 years and older benefit from more invasive early treatment after non-ST-elevation myocardial infarction or unstable angina, the After Eighty Trial showed.

After a median follow-up of 1.5 years, an invasive strategy that included coronary angiography significantly reduced the primary endpoint of myocardial infarction (MI), need for urgent revascularization, stroke, and death from 61% with optimal medical treatment to 41% (risk ratio, 0.48; P value < .00001).

That drop was driven primarily by significantly fewer MIs (17% vs. 30%; RR, 0.50; P = .0003) and urgent revascularizations (2% vs. 11%; RR, 0.19; P = .0001), lead author Dr. Nicolai Tegn reported at the American College of Cardiology/Cardiovascular Research Foundation Innovation in Intervention Summit.

There were no significant differences between the invasive and conservative strategy groups in rates of stroke (3% vs. 6%; RR, 0.61; P = .26) or all-cause death (25% vs. 27%; RR, 0.87; P = .53).

The composite of death and MI, however, significantly favored the invasive group (35% vs. 48%; RR, 0.54; P < .0001), he said during a latebreaking clinical trial session.

After Eighty randomly assigned 457 patients, aged 80 years or older, to either optimal medical therapy with no invasive treatments or coronary angiography at a percutaneous coronary intervention (PCI) center the day after inclusion, plus optimal medical therapy after about 4-5 hours if PCI was not performed or about 6-18 hours if it was. Of the 225 patients receiving angiography, 48% went on to balloon angioplasty and/or coronary stenting, and 3% had bypass surgery.

Patients 80 years or older account for roughly one-third of all patients with non-STEMI and unstable angina, but they are underrepresented in clinical trials. As a result, the role of an early invasive strategy, and even an invasive strategy at all, in those elderly patients is still a subject of debate, observed Dr. Tegn, a cardiologist from Rikshospitalet, Oslo University Hospital, Oslo.

The study demonstrated that an invasive strategy is superior to a conservative strategy in patients at least 80 years with NSTEMI or unstable angina, he concluded.

After Eighty is a welcome study because of the under-representation of the elderly in clinical trials, Dr. David Kandzari, director of interventional cardiology at the Piedmont Heart Center in Atlanta, said during a press briefing at the meeting. But it raises the challenge of identifying patients in clinical practice with the same qualifying characteristics, he added, given that the study population represents only 10% of the entire screened population,

There was also a fairly high prevalence of patients who angiographically did not have significant coronary artery disease, yet MI and stroke rates were quite considerable.

That said, “the study in other ways reminds us that the coronary anatomy does not know the age of the patient, meaning that the findings of a benefit of an early invasive strategy seem consistent with previous studies we know across the management of patients with acute coronary syndromes,” Dr. Kandzari said.

After Eighty investigators screened 4,187 elderly patients presenting at 17 community hospitals in Norway with non-STEMI or unstable angina, with or without ST-segment depression in ECG, and normal or elevated troponin T or I levels. Patients had to have no chest pain or other ischemic symptoms after medical treatment and mobilization.

In all, 3,730 patients were excluded for life expectancy less than 12 months because of a serious comorbidity; ongoing or recent bleeding; inability to comply with protocol; clinically unstable including ongoing ischemia; refusal to participate; logistic reasons; or other reasons.

The average age was 84.7 years in the invasive group (range 80-93 years) and 84.9 years in the conservative group (range 80-94 years).

Medical treatment during the index admission included 75 mg aspirin in 97% of both the invasive and conservative groups, clopidogrel (85% vs. 82%), ticagrelor (both 5%), angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blockers (ARB) (43% vs. 50%), beta blocker (83% vs. 85%), statins (90% vs. 85%), loop or thiazide diuretics (41% vs. 33%), calcium channel blocker (20% vs. 21%), nitrates (45% vs. 55%), warfarin (17% vs. 9%), low molecular-weight heparin (both 76% ), and dabigatran in one patient in each group.

Medical therapy at discharge in the invasive and conservative groups was aspirin (both 93%), clopidogrel (both 72%), ticagrelor (both 4%), ACE inhibitor/ARB (52% vs. 54%), beta blockers (both 84%), statins (90% vs. 86%), diuretics (45% vs. 38%), calcium channel blocker (24% vs. 23%), nitrates (34% vs. 48%), warfarin (21% vs. 14%), rivaroxaban (three patients in both groups), and dabigatran (one patient vs. six patients).

There were no differences in bleeding rates between the two groups, Dr. Tegn said. Four major bleeding events were reported in both groups, while 23 patients in the invasive group and 16 patients in the conservative group had minor bleeds.

The Norwegian Health Association sponsored the study. Dr. Tegn reported nothing to disclose. Dr. Kandazari reported research and grant support from Abbott Vascular, Biotronic, Boston Scientific, and Medtronic, and minor consulting honoraria from Boston Scientific and Medtronic.

[email protected]

SAN DIEGO – Patients aged 80 years and older benefit from more invasive early treatment after non-ST-elevation myocardial infarction or unstable angina, the After Eighty Trial showed.

After a median follow-up of 1.5 years, an invasive strategy that included coronary angiography significantly reduced the primary endpoint of myocardial infarction (MI), need for urgent revascularization, stroke, and death from 61% with optimal medical treatment to 41% (risk ratio, 0.48; P value < .00001).

That drop was driven primarily by significantly fewer MIs (17% vs. 30%; RR, 0.50; P = .0003) and urgent revascularizations (2% vs. 11%; RR, 0.19; P = .0001), lead author Dr. Nicolai Tegn reported at the American College of Cardiology/Cardiovascular Research Foundation Innovation in Intervention Summit.

There were no significant differences between the invasive and conservative strategy groups in rates of stroke (3% vs. 6%; RR, 0.61; P = .26) or all-cause death (25% vs. 27%; RR, 0.87; P = .53).

The composite of death and MI, however, significantly favored the invasive group (35% vs. 48%; RR, 0.54; P < .0001), he said during a latebreaking clinical trial session.

After Eighty randomly assigned 457 patients, aged 80 years or older, to either optimal medical therapy with no invasive treatments or coronary angiography at a percutaneous coronary intervention (PCI) center the day after inclusion, plus optimal medical therapy after about 4-5 hours if PCI was not performed or about 6-18 hours if it was. Of the 225 patients receiving angiography, 48% went on to balloon angioplasty and/or coronary stenting, and 3% had bypass surgery.

Patients 80 years or older account for roughly one-third of all patients with non-STEMI and unstable angina, but they are underrepresented in clinical trials. As a result, the role of an early invasive strategy, and even an invasive strategy at all, in those elderly patients is still a subject of debate, observed Dr. Tegn, a cardiologist from Rikshospitalet, Oslo University Hospital, Oslo.

The study demonstrated that an invasive strategy is superior to a conservative strategy in patients at least 80 years with NSTEMI or unstable angina, he concluded.

After Eighty is a welcome study because of the under-representation of the elderly in clinical trials, Dr. David Kandzari, director of interventional cardiology at the Piedmont Heart Center in Atlanta, said during a press briefing at the meeting. But it raises the challenge of identifying patients in clinical practice with the same qualifying characteristics, he added, given that the study population represents only 10% of the entire screened population,

There was also a fairly high prevalence of patients who angiographically did not have significant coronary artery disease, yet MI and stroke rates were quite considerable.

That said, “the study in other ways reminds us that the coronary anatomy does not know the age of the patient, meaning that the findings of a benefit of an early invasive strategy seem consistent with previous studies we know across the management of patients with acute coronary syndromes,” Dr. Kandzari said.

After Eighty investigators screened 4,187 elderly patients presenting at 17 community hospitals in Norway with non-STEMI or unstable angina, with or without ST-segment depression in ECG, and normal or elevated troponin T or I levels. Patients had to have no chest pain or other ischemic symptoms after medical treatment and mobilization.

In all, 3,730 patients were excluded for life expectancy less than 12 months because of a serious comorbidity; ongoing or recent bleeding; inability to comply with protocol; clinically unstable including ongoing ischemia; refusal to participate; logistic reasons; or other reasons.

The average age was 84.7 years in the invasive group (range 80-93 years) and 84.9 years in the conservative group (range 80-94 years).

Medical treatment during the index admission included 75 mg aspirin in 97% of both the invasive and conservative groups, clopidogrel (85% vs. 82%), ticagrelor (both 5%), angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blockers (ARB) (43% vs. 50%), beta blocker (83% vs. 85%), statins (90% vs. 85%), loop or thiazide diuretics (41% vs. 33%), calcium channel blocker (20% vs. 21%), nitrates (45% vs. 55%), warfarin (17% vs. 9%), low molecular-weight heparin (both 76% ), and dabigatran in one patient in each group.

Medical therapy at discharge in the invasive and conservative groups was aspirin (both 93%), clopidogrel (both 72%), ticagrelor (both 4%), ACE inhibitor/ARB (52% vs. 54%), beta blockers (both 84%), statins (90% vs. 86%), diuretics (45% vs. 38%), calcium channel blocker (24% vs. 23%), nitrates (34% vs. 48%), warfarin (21% vs. 14%), rivaroxaban (three patients in both groups), and dabigatran (one patient vs. six patients).

There were no differences in bleeding rates between the two groups, Dr. Tegn said. Four major bleeding events were reported in both groups, while 23 patients in the invasive group and 16 patients in the conservative group had minor bleeds.

The Norwegian Health Association sponsored the study. Dr. Tegn reported nothing to disclose. Dr. Kandazari reported research and grant support from Abbott Vascular, Biotronic, Boston Scientific, and Medtronic, and minor consulting honoraria from Boston Scientific and Medtronic.

[email protected]

Earlier this week, an airplane headed from Barcelona to Dusseldorf crashed into the French Alps, leaving 150 people dead. The black box recorder indicated that the copilot was left alone in the cockpit, the pilot was locked out and attempted to gain re-entry, and the flight was reprogrammed to cruise at an altitude of 100 feet, causing the plane to crash after an 8-minute descent. The evidence indicates a deliberate action on the part of the 27-year-old co-pilot, Andreas Lubitz.

With nothing to point to terrorism at this point, the investigation will include the question of whether or not the copilot suffered from a mental illness as a way of explaining his unexplainable actions. In short, was this a combination mass murder/suicide? Was there any way to predict that such an atrocity might happen? Are there measures that can be taken to ensure that it doesn’t happen again?

In the United States, treatment with any psychotropic medication has been a reason to ground a pilot permanently. In April 2010, the Federal Aviation Administration’s rules changed such that a pilot could fly if he’d been treated for mild to moderate depression with a selective serotonin reuptake inhibitor after 12 months. At that time, the FAA announced a 6-month amnesty period where a pilot could come forward about a diagnosis of depression that he had not previously felt comfortable disclosing. Presumably, other countries also have rules that ground pilots for mental illness.

So far, some reports in the media indicate that the copilot was not obviously suffering from a psychiatric disorder; all those who have been interviewed for these reports have expressed shock that Lubitz might have deliberately crashed the plane.

There also has been speculation in the media that a break in the copilot’s training 6 years ago was due to depression, and the mother of a school mate reportedly said that Lubitz had been treated for depression. Finally, investigators found a doctor’s note excusing Lubitz from work. At this point, the Wall Street Journal is reporting that he was being treated for depression. Apparently, he had shredded the note and flew on Tuesday, despite the written work excuse.

Still, all discussion of the copilot’s mental state is purely speculation. The media is noted for sensationalist reporting – and in efforts to get information out quickly, the details are often confused or simply wrong, sometimes to a remarkable extent. We don’t know if the work excuse was written by a psychiatrist or another type of physician; we don’t know if it was for a psychiatric condition, cancer, or simply strep throat.

What we’ve been told is that a copilot who was cleared to fly did so despite a work excuse from a physician, he did not disclose this condition to his employer, and he crashed a plane killing 150 people.

We might assume that the pilot suffered from some type of psychic distress – whether he met criteria for a mental disorder or not, it’s not normal to kill 150 people. If the pilot did have a history of depression and was being treated at the time of this week’s flight, then we may be left with a very unsatisfactory answer.

The anti-psychiatry activists will say that psychotropic medications caused Lubitz to crash the plane. Psychiatrists will be left with no great answer with such a scenario and will be left to say that whatever treatment he was receiving, it wasn’t enough. Certainly, the physician who told Lubitz to take off from work was right: He didn’t belong in a cockpit that day. Presumably, that physician would have done more had he been aware that the patient was about to commit a mass murder.

If the copilot does have a history of depression, but his current work excuse was for an unrelated condition, we might wonder if an untreated recurrence of depression played some role in his actions. One might speculate that the copilot could have been afraid to seek care at this time, perhaps because of a fear that he would lose his vocation.

Still, major depression can hardly explain such an act, and it is unfortunate that the press has already begun to run headlines linking this man’s alleged psychiatric diagnosis to a catastrophic mass murder. Somehow, “mental illness” gets used as an endpoint explanation for why such things happen; and short of a severe psychotic delusional system, it’s a very unsatisfying answer for an unprecedented act of violence.

The facts will unfold and perhaps we’ll learn a little more. We’ll find out what condition the copilot was being treated for and whether there were other stresses going on in his personal life. But people get depressed, take antidepressants, and deal with stress all the time.

It’s possible, if not likely, that we’ll never understand why this copilot decided to end the lives of so many people along with his own.

Dr. Miller is a coauthor of “Shrink Rap: Three Psychiatrists Explain Their Work (Baltimore: The Johns Hopkins University, 2011).

Earlier this week, an airplane headed from Barcelona to Dusseldorf crashed into the French Alps, leaving 150 people dead. The black box recorder indicated that the copilot was left alone in the cockpit, the pilot was locked out and attempted to gain re-entry, and the flight was reprogrammed to cruise at an altitude of 100 feet, causing the plane to crash after an 8-minute descent. The evidence indicates a deliberate action on the part of the 27-year-old co-pilot, Andreas Lubitz.

With nothing to point to terrorism at this point, the investigation will include the question of whether or not the copilot suffered from a mental illness as a way of explaining his unexplainable actions. In short, was this a combination mass murder/suicide? Was there any way to predict that such an atrocity might happen? Are there measures that can be taken to ensure that it doesn’t happen again?

In the United States, treatment with any psychotropic medication has been a reason to ground a pilot permanently. In April 2010, the Federal Aviation Administration’s rules changed such that a pilot could fly if he’d been treated for mild to moderate depression with a selective serotonin reuptake inhibitor after 12 months. At that time, the FAA announced a 6-month amnesty period where a pilot could come forward about a diagnosis of depression that he had not previously felt comfortable disclosing. Presumably, other countries also have rules that ground pilots for mental illness.

So far, some reports in the media indicate that the copilot was not obviously suffering from a psychiatric disorder; all those who have been interviewed for these reports have expressed shock that Lubitz might have deliberately crashed the plane.

There also has been speculation in the media that a break in the copilot’s training 6 years ago was due to depression, and the mother of a school mate reportedly said that Lubitz had been treated for depression. Finally, investigators found a doctor’s note excusing Lubitz from work. At this point, the Wall Street Journal is reporting that he was being treated for depression. Apparently, he had shredded the note and flew on Tuesday, despite the written work excuse.

Still, all discussion of the copilot’s mental state is purely speculation. The media is noted for sensationalist reporting – and in efforts to get information out quickly, the details are often confused or simply wrong, sometimes to a remarkable extent. We don’t know if the work excuse was written by a psychiatrist or another type of physician; we don’t know if it was for a psychiatric condition, cancer, or simply strep throat.

What we’ve been told is that a copilot who was cleared to fly did so despite a work excuse from a physician, he did not disclose this condition to his employer, and he crashed a plane killing 150 people.

We might assume that the pilot suffered from some type of psychic distress – whether he met criteria for a mental disorder or not, it’s not normal to kill 150 people. If the pilot did have a history of depression and was being treated at the time of this week’s flight, then we may be left with a very unsatisfactory answer.

The anti-psychiatry activists will say that psychotropic medications caused Lubitz to crash the plane. Psychiatrists will be left with no great answer with such a scenario and will be left to say that whatever treatment he was receiving, it wasn’t enough. Certainly, the physician who told Lubitz to take off from work was right: He didn’t belong in a cockpit that day. Presumably, that physician would have done more had he been aware that the patient was about to commit a mass murder.

If the copilot does have a history of depression, but his current work excuse was for an unrelated condition, we might wonder if an untreated recurrence of depression played some role in his actions. One might speculate that the copilot could have been afraid to seek care at this time, perhaps because of a fear that he would lose his vocation.

Still, major depression can hardly explain such an act, and it is unfortunate that the press has already begun to run headlines linking this man’s alleged psychiatric diagnosis to a catastrophic mass murder. Somehow, “mental illness” gets used as an endpoint explanation for why such things happen; and short of a severe psychotic delusional system, it’s a very unsatisfying answer for an unprecedented act of violence.

The facts will unfold and perhaps we’ll learn a little more. We’ll find out what condition the copilot was being treated for and whether there were other stresses going on in his personal life. But people get depressed, take antidepressants, and deal with stress all the time.

It’s possible, if not likely, that we’ll never understand why this copilot decided to end the lives of so many people along with his own.

Dr. Miller is a coauthor of “Shrink Rap: Three Psychiatrists Explain Their Work (Baltimore: The Johns Hopkins University, 2011).

Earlier this week, an airplane headed from Barcelona to Dusseldorf crashed into the French Alps, leaving 150 people dead. The black box recorder indicated that the copilot was left alone in the cockpit, the pilot was locked out and attempted to gain re-entry, and the flight was reprogrammed to cruise at an altitude of 100 feet, causing the plane to crash after an 8-minute descent. The evidence indicates a deliberate action on the part of the 27-year-old co-pilot, Andreas Lubitz.

With nothing to point to terrorism at this point, the investigation will include the question of whether or not the copilot suffered from a mental illness as a way of explaining his unexplainable actions. In short, was this a combination mass murder/suicide? Was there any way to predict that such an atrocity might happen? Are there measures that can be taken to ensure that it doesn’t happen again?

In the United States, treatment with any psychotropic medication has been a reason to ground a pilot permanently. In April 2010, the Federal Aviation Administration’s rules changed such that a pilot could fly if he’d been treated for mild to moderate depression with a selective serotonin reuptake inhibitor after 12 months. At that time, the FAA announced a 6-month amnesty period where a pilot could come forward about a diagnosis of depression that he had not previously felt comfortable disclosing. Presumably, other countries also have rules that ground pilots for mental illness.

So far, some reports in the media indicate that the copilot was not obviously suffering from a psychiatric disorder; all those who have been interviewed for these reports have expressed shock that Lubitz might have deliberately crashed the plane.

There also has been speculation in the media that a break in the copilot’s training 6 years ago was due to depression, and the mother of a school mate reportedly said that Lubitz had been treated for depression. Finally, investigators found a doctor’s note excusing Lubitz from work. At this point, the Wall Street Journal is reporting that he was being treated for depression. Apparently, he had shredded the note and flew on Tuesday, despite the written work excuse.

Still, all discussion of the copilot’s mental state is purely speculation. The media is noted for sensationalist reporting – and in efforts to get information out quickly, the details are often confused or simply wrong, sometimes to a remarkable extent. We don’t know if the work excuse was written by a psychiatrist or another type of physician; we don’t know if it was for a psychiatric condition, cancer, or simply strep throat.

What we’ve been told is that a copilot who was cleared to fly did so despite a work excuse from a physician, he did not disclose this condition to his employer, and he crashed a plane killing 150 people.

We might assume that the pilot suffered from some type of psychic distress – whether he met criteria for a mental disorder or not, it’s not normal to kill 150 people. If the pilot did have a history of depression and was being treated at the time of this week’s flight, then we may be left with a very unsatisfactory answer.

The anti-psychiatry activists will say that psychotropic medications caused Lubitz to crash the plane. Psychiatrists will be left with no great answer with such a scenario and will be left to say that whatever treatment he was receiving, it wasn’t enough. Certainly, the physician who told Lubitz to take off from work was right: He didn’t belong in a cockpit that day. Presumably, that physician would have done more had he been aware that the patient was about to commit a mass murder.

If the copilot does have a history of depression, but his current work excuse was for an unrelated condition, we might wonder if an untreated recurrence of depression played some role in his actions. One might speculate that the copilot could have been afraid to seek care at this time, perhaps because of a fear that he would lose his vocation.

Still, major depression can hardly explain such an act, and it is unfortunate that the press has already begun to run headlines linking this man’s alleged psychiatric diagnosis to a catastrophic mass murder. Somehow, “mental illness” gets used as an endpoint explanation for why such things happen; and short of a severe psychotic delusional system, it’s a very unsatisfying answer for an unprecedented act of violence.

The facts will unfold and perhaps we’ll learn a little more. We’ll find out what condition the copilot was being treated for and whether there were other stresses going on in his personal life. But people get depressed, take antidepressants, and deal with stress all the time.

It’s possible, if not likely, that we’ll never understand why this copilot decided to end the lives of so many people along with his own.

Dr. Miller is a coauthor of “Shrink Rap: Three Psychiatrists Explain Their Work (Baltimore: The Johns Hopkins University, 2011).

Red blood cells

Image courtesy of NHLBI

The US Food and Drug Administration (FDA) has granted orphan drug designation to AG-348 for the treatment of pyruvate kinase deficiency (PKD), a rare form of hemolytic anemia.

AG-348 is a small molecule allosteric activator of pyruvate kinase-R enzymes that directly targets the underlying metabolic defect in PKD.

The orphan designation will provide Agios Pharmaceuticals, the company developing AG-348, with certain benefits. These include market exclusivity upon regulatory approval and exemption from FDA application fees and tax credits for qualified clinical trials.

According to Agios, AG-348 exhibited favorable safety and pharmacokinetic profiles in a pair of phase 1 studies conducted in healthy volunteers.

Study investigators also observed dose-dependent changes in adenosine triphosphate (ATP) and 2,3-DPG blood levels, which are consistent with increased activity of the glycolytic pathway, the expected pharmacodynamic effect of AG-348.

Results from both studies were presented in a poster at the 2014 ASH Annual Meeting (abstract 4007*). One of the studies was a single ascending dose (SAD) study, and the other was a multiple ascending dose (MAD) study.

SAD study

In this study, healthy volunteers were randomized to receive AG-348 (n=36) or placebo (n=12). Patients were divided into 6 dosing cohorts: 30 mg, 120 mg, 360 mg, 700 mg, 1400 mg, and 2500 mg.

The maximum-tolerated dose of AG-348 was not reached, and there were no serious adverse events (AEs) or early withdrawals among AG-348-treated subjects. Overall, the rate of AEs was 33.3% in the placebo arm and 44.4% in the AG-348 arm.

The rate of AEs that were considered possibly treatment-related was 16.7% in the placebo arm and 30.6% in the AG-348 arm. The most common treatment-related AEs were headache (occurring in 16.7% and 11.1% of patients, respectively), nausea (0% and 13.9%, respectively), and vomiting (0% and 5.6%, respectively).

Exposure to AG-348, as measured by area under the concentration × time curve (AUC), increased in a dose-proportional manner after a single dose. And absorption was rapid (median T_max ranged from 0.77 to 4.07 hours), although T_max increased and there was a less-than-proportional increase in C_max at higher doses.

When AG-348 was administered from 30 mg to 360 mg, there was a dose-dependent decrease in blood 2,3-DPG levels over 24 hours—up to a 49% mean decrease. Increasing the dose beyond 360 mg did not result in additional decreases in 2,3-DPG levels. And levels returned to placebo levels after about 72 hours.

There were minimal increases in blood ATP levels after AG-348 treatment at any dose.

MAD study

At the time of the presentation, 2 cohorts of 8 subjects each (6 receiving AG-348 and 2 receiving placebo) had completed treatment in the MAD study. One cohort received drug or placebo at 120 mg BID, and the other received 360 mg BID.

The pharmacokinetic results for day 1 of this study were consistent with those of the SAD study. However, the C_max and AUC_0-Ʈ were lower on day 14 than day 1. Investigators said this suggests that multiple doses of AG-348 increase the rate of its own metabolism.

They also said the decrease in exposure observed on day 14 is consistent with preclinical data that suggest AG-348 is a moderate inducer of CYP3A4, which is the major route of the oxidative metabolism of AG-348.

As in the SAD study, the investigators observed decreases in 2,3-DPG blood levels after the first dose in cohorts 1 and 2—up to a 48% mean decrease from baseline for both doses. Concentrations returned to placebo levels between 48 and 72 hours after the last dose.

Unlike in the SAD study, patients in this study had increases in ATP—up to a 52% mean increase from baseline in both dosing cohorts. ATP levels remained elevated through 72 hours after the last dose.

The investigators said the results of these 2 studies have informed dose selection for the planned phase 2 study of AG-348 in PKD patients, which is expected to begin soon.

*Information in the abstract differs from that presented at the meeting.

Red blood cells

Image courtesy of NHLBI

The US Food and Drug Administration (FDA) has granted orphan drug designation to AG-348 for the treatment of pyruvate kinase deficiency (PKD), a rare form of hemolytic anemia.

AG-348 is a small molecule allosteric activator of pyruvate kinase-R enzymes that directly targets the underlying metabolic defect in PKD.

The orphan designation will provide Agios Pharmaceuticals, the company developing AG-348, with certain benefits. These include market exclusivity upon regulatory approval and exemption from FDA application fees and tax credits for qualified clinical trials.

According to Agios, AG-348 exhibited favorable safety and pharmacokinetic profiles in a pair of phase 1 studies conducted in healthy volunteers.

Study investigators also observed dose-dependent changes in adenosine triphosphate (ATP) and 2,3-DPG blood levels, which are consistent with increased activity of the glycolytic pathway, the expected pharmacodynamic effect of AG-348.

Results from both studies were presented in a poster at the 2014 ASH Annual Meeting (abstract 4007*). One of the studies was a single ascending dose (SAD) study, and the other was a multiple ascending dose (MAD) study.

SAD study

In this study, healthy volunteers were randomized to receive AG-348 (n=36) or placebo (n=12). Patients were divided into 6 dosing cohorts: 30 mg, 120 mg, 360 mg, 700 mg, 1400 mg, and 2500 mg.

The maximum-tolerated dose of AG-348 was not reached, and there were no serious adverse events (AEs) or early withdrawals among AG-348-treated subjects. Overall, the rate of AEs was 33.3% in the placebo arm and 44.4% in the AG-348 arm.

The rate of AEs that were considered possibly treatment-related was 16.7% in the placebo arm and 30.6% in the AG-348 arm. The most common treatment-related AEs were headache (occurring in 16.7% and 11.1% of patients, respectively), nausea (0% and 13.9%, respectively), and vomiting (0% and 5.6%, respectively).

Exposure to AG-348, as measured by area under the concentration × time curve (AUC), increased in a dose-proportional manner after a single dose. And absorption was rapid (median T_max ranged from 0.77 to 4.07 hours), although T_max increased and there was a less-than-proportional increase in C_max at higher doses.

When AG-348 was administered from 30 mg to 360 mg, there was a dose-dependent decrease in blood 2,3-DPG levels over 24 hours—up to a 49% mean decrease. Increasing the dose beyond 360 mg did not result in additional decreases in 2,3-DPG levels. And levels returned to placebo levels after about 72 hours.

There were minimal increases in blood ATP levels after AG-348 treatment at any dose.

MAD study

At the time of the presentation, 2 cohorts of 8 subjects each (6 receiving AG-348 and 2 receiving placebo) had completed treatment in the MAD study. One cohort received drug or placebo at 120 mg BID, and the other received 360 mg BID.

The pharmacokinetic results for day 1 of this study were consistent with those of the SAD study. However, the C_max and AUC_0-Ʈ were lower on day 14 than day 1. Investigators said this suggests that multiple doses of AG-348 increase the rate of its own metabolism.

They also said the decrease in exposure observed on day 14 is consistent with preclinical data that suggest AG-348 is a moderate inducer of CYP3A4, which is the major route of the oxidative metabolism of AG-348.

As in the SAD study, the investigators observed decreases in 2,3-DPG blood levels after the first dose in cohorts 1 and 2—up to a 48% mean decrease from baseline for both doses. Concentrations returned to placebo levels between 48 and 72 hours after the last dose.

Unlike in the SAD study, patients in this study had increases in ATP—up to a 52% mean increase from baseline in both dosing cohorts. ATP levels remained elevated through 72 hours after the last dose.

The investigators said the results of these 2 studies have informed dose selection for the planned phase 2 study of AG-348 in PKD patients, which is expected to begin soon.

*Information in the abstract differs from that presented at the meeting.

Red blood cells

Image courtesy of NHLBI

The US Food and Drug Administration (FDA) has granted orphan drug designation to AG-348 for the treatment of pyruvate kinase deficiency (PKD), a rare form of hemolytic anemia.

AG-348 is a small molecule allosteric activator of pyruvate kinase-R enzymes that directly targets the underlying metabolic defect in PKD.

The orphan designation will provide Agios Pharmaceuticals, the company developing AG-348, with certain benefits. These include market exclusivity upon regulatory approval and exemption from FDA application fees and tax credits for qualified clinical trials.

According to Agios, AG-348 exhibited favorable safety and pharmacokinetic profiles in a pair of phase 1 studies conducted in healthy volunteers.

Study investigators also observed dose-dependent changes in adenosine triphosphate (ATP) and 2,3-DPG blood levels, which are consistent with increased activity of the glycolytic pathway, the expected pharmacodynamic effect of AG-348.

Results from both studies were presented in a poster at the 2014 ASH Annual Meeting (abstract 4007*). One of the studies was a single ascending dose (SAD) study, and the other was a multiple ascending dose (MAD) study.

SAD study

In this study, healthy volunteers were randomized to receive AG-348 (n=36) or placebo (n=12). Patients were divided into 6 dosing cohorts: 30 mg, 120 mg, 360 mg, 700 mg, 1400 mg, and 2500 mg.

The maximum-tolerated dose of AG-348 was not reached, and there were no serious adverse events (AEs) or early withdrawals among AG-348-treated subjects. Overall, the rate of AEs was 33.3% in the placebo arm and 44.4% in the AG-348 arm.

The rate of AEs that were considered possibly treatment-related was 16.7% in the placebo arm and 30.6% in the AG-348 arm. The most common treatment-related AEs were headache (occurring in 16.7% and 11.1% of patients, respectively), nausea (0% and 13.9%, respectively), and vomiting (0% and 5.6%, respectively).

Exposure to AG-348, as measured by area under the concentration × time curve (AUC), increased in a dose-proportional manner after a single dose. And absorption was rapid (median T_max ranged from 0.77 to 4.07 hours), although T_max increased and there was a less-than-proportional increase in C_max at higher doses.

When AG-348 was administered from 30 mg to 360 mg, there was a dose-dependent decrease in blood 2,3-DPG levels over 24 hours—up to a 49% mean decrease. Increasing the dose beyond 360 mg did not result in additional decreases in 2,3-DPG levels. And levels returned to placebo levels after about 72 hours.

There were minimal increases in blood ATP levels after AG-348 treatment at any dose.

MAD study

At the time of the presentation, 2 cohorts of 8 subjects each (6 receiving AG-348 and 2 receiving placebo) had completed treatment in the MAD study. One cohort received drug or placebo at 120 mg BID, and the other received 360 mg BID.

The pharmacokinetic results for day 1 of this study were consistent with those of the SAD study. However, the C_max and AUC_0-Ʈ were lower on day 14 than day 1. Investigators said this suggests that multiple doses of AG-348 increase the rate of its own metabolism.

They also said the decrease in exposure observed on day 14 is consistent with preclinical data that suggest AG-348 is a moderate inducer of CYP3A4, which is the major route of the oxidative metabolism of AG-348.

As in the SAD study, the investigators observed decreases in 2,3-DPG blood levels after the first dose in cohorts 1 and 2—up to a 48% mean decrease from baseline for both doses. Concentrations returned to placebo levels between 48 and 72 hours after the last dose.

Unlike in the SAD study, patients in this study had increases in ATP—up to a 52% mean increase from baseline in both dosing cohorts. ATP levels remained elevated through 72 hours after the last dose.

The investigators said the results of these 2 studies have informed dose selection for the planned phase 2 study of AG-348 in PKD patients, which is expected to begin soon.

*Information in the abstract differs from that presented at the meeting.

Olympus, the manufacturer of the TJF-Q180V duodenoscope, has issued new, validated instructions for reprocessing this particular model, as part of the response to recent reports of a possible association between multidrug-resistant bacterial infections and improperly processed duodenoscopes, according to the Food and Drug Administration.

The new instructions, which replace the manual reprocessing instructions included in the original labeling, and validation data have been reviewed by the FDA as part of its ongoing review of the device. The agency “recommends that any facilities that are using Olympus’ TJF-Q180V duodenoscope train staff on the new instructions and implement them as soon as possible,” according to an FDA statement. The instructions are provided in letters sent by Olympus to health care and other facilities that use this particular model.

“Key changes” have been made to the procedures for precleaning, manual cleaning, and manual high-level disinfection reprocessing procedures, the FDA said.

The TJF-Q180 V duodenoscope was the model used in four patients who had undergone an endoscopic retrograde cholangiopancreatography (ERCP) procedure between August 2014 and January 2015 with the same duodenoscope at Cedars-Sinai Medical Center in Los Angeles and had been infected with carbapenem-resistant Enterobacteriaceae (CRE). This outbreak was announced by the medical center in early March in a statement that said the infections occurred “despite the fact that Cedars-Sinai meticulously followed the disinfection procedure for duodenoscopes” recommended in instructions provided by Olympus and the FDA.

In February, the FDA first announced that the agency had received reports of multidrug-resistant bacterial infections in patients who had undergone ERCP procedures with duodenoscopes, despite proper cleaning and disinfection of the devices and that the “complex design of ERCP endoscopes (also called duodenoscopes) may impede effective reprocessing.”

In the latest statement, the FDA said it “is closely monitoring the possible association between reprocessed duodenoscopes and the transmission of infectious agents,” including multidrug-resistant bacterial infections caused by CRE. If they are not properly reprocessed, the statement adds, “residual body fluids and organic debris may remain in microscopic crevices of the device following an attempted cleaning and high-level disinfection. If these residual fluids contain microbial contamination, subsequent patients may be exposed to serious infections.”

Adverse events associated with duodenoscopes should be reported to the FDA’s MedWatch Program at 800-332-1088 or www.accessdata.fda.gov/scripts/medwatch.

AGA Resource
Read more about AGA’s efforts and recommendations to stop duodenoscope infections here.

[email protected]

Olympus, the manufacturer of the TJF-Q180V duodenoscope, has issued new, validated instructions for reprocessing this particular model, as part of the response to recent reports of a possible association between multidrug-resistant bacterial infections and improperly processed duodenoscopes, according to the Food and Drug Administration.

The new instructions, which replace the manual reprocessing instructions included in the original labeling, and validation data have been reviewed by the FDA as part of its ongoing review of the device. The agency “recommends that any facilities that are using Olympus’ TJF-Q180V duodenoscope train staff on the new instructions and implement them as soon as possible,” according to an FDA statement. The instructions are provided in letters sent by Olympus to health care and other facilities that use this particular model.

“Key changes” have been made to the procedures for precleaning, manual cleaning, and manual high-level disinfection reprocessing procedures, the FDA said.

The TJF-Q180 V duodenoscope was the model used in four patients who had undergone an endoscopic retrograde cholangiopancreatography (ERCP) procedure between August 2014 and January 2015 with the same duodenoscope at Cedars-Sinai Medical Center in Los Angeles and had been infected with carbapenem-resistant Enterobacteriaceae (CRE). This outbreak was announced by the medical center in early March in a statement that said the infections occurred “despite the fact that Cedars-Sinai meticulously followed the disinfection procedure for duodenoscopes” recommended in instructions provided by Olympus and the FDA.

In February, the FDA first announced that the agency had received reports of multidrug-resistant bacterial infections in patients who had undergone ERCP procedures with duodenoscopes, despite proper cleaning and disinfection of the devices and that the “complex design of ERCP endoscopes (also called duodenoscopes) may impede effective reprocessing.”

In the latest statement, the FDA said it “is closely monitoring the possible association between reprocessed duodenoscopes and the transmission of infectious agents,” including multidrug-resistant bacterial infections caused by CRE. If they are not properly reprocessed, the statement adds, “residual body fluids and organic debris may remain in microscopic crevices of the device following an attempted cleaning and high-level disinfection. If these residual fluids contain microbial contamination, subsequent patients may be exposed to serious infections.”

Adverse events associated with duodenoscopes should be reported to the FDA’s MedWatch Program at 800-332-1088 or www.accessdata.fda.gov/scripts/medwatch.

AGA Resource
Read more about AGA’s efforts and recommendations to stop duodenoscope infections here.

[email protected]

Olympus, the manufacturer of the TJF-Q180V duodenoscope, has issued new, validated instructions for reprocessing this particular model, as part of the response to recent reports of a possible association between multidrug-resistant bacterial infections and improperly processed duodenoscopes, according to the Food and Drug Administration.

The new instructions, which replace the manual reprocessing instructions included in the original labeling, and validation data have been reviewed by the FDA as part of its ongoing review of the device. The agency “recommends that any facilities that are using Olympus’ TJF-Q180V duodenoscope train staff on the new instructions and implement them as soon as possible,” according to an FDA statement. The instructions are provided in letters sent by Olympus to health care and other facilities that use this particular model.

“Key changes” have been made to the procedures for precleaning, manual cleaning, and manual high-level disinfection reprocessing procedures, the FDA said.

The TJF-Q180 V duodenoscope was the model used in four patients who had undergone an endoscopic retrograde cholangiopancreatography (ERCP) procedure between August 2014 and January 2015 with the same duodenoscope at Cedars-Sinai Medical Center in Los Angeles and had been infected with carbapenem-resistant Enterobacteriaceae (CRE). This outbreak was announced by the medical center in early March in a statement that said the infections occurred “despite the fact that Cedars-Sinai meticulously followed the disinfection procedure for duodenoscopes” recommended in instructions provided by Olympus and the FDA.

In February, the FDA first announced that the agency had received reports of multidrug-resistant bacterial infections in patients who had undergone ERCP procedures with duodenoscopes, despite proper cleaning and disinfection of the devices and that the “complex design of ERCP endoscopes (also called duodenoscopes) may impede effective reprocessing.”

In the latest statement, the FDA said it “is closely monitoring the possible association between reprocessed duodenoscopes and the transmission of infectious agents,” including multidrug-resistant bacterial infections caused by CRE. If they are not properly reprocessed, the statement adds, “residual body fluids and organic debris may remain in microscopic crevices of the device following an attempted cleaning and high-level disinfection. If these residual fluids contain microbial contamination, subsequent patients may be exposed to serious infections.”

Adverse events associated with duodenoscopes should be reported to the FDA’s MedWatch Program at 800-332-1088 or www.accessdata.fda.gov/scripts/medwatch.

AGA Resource
Read more about AGA’s efforts and recommendations to stop duodenoscope infections here.

[email protected]

Hip replacement is becoming more common among middle-aged Americans at the same time as the number of surgeons who perform the procedure is declining, Dr. Alexander S. McLawhorn said at the annual meeting of the American Academy of Orthopaedic Surgeons in Las Vegas.

In 2011, patients aged 45-64 years underwent 42.3% of the hip replacements performed, compared with 33.9% in 2002. The number of replacements performed rose from approximately 68,000 in 2002 to 128,000 in 2011, an increase of 89.2%, compared with an increase of 37.0% among those aged 65 years and older, according to data from the Nationwide Inpatient Sample.

This “observed growth was best explained by an expansion of the middle-aged population in the United States. This particular age group is projected to continue expanding, and as such the demand for [hip replacement] in this active group of patients will likely continue to rise as well,” Dr. McLawhorn of the Hospital for Special Surgery, New York, said in a written statement.

According to membership data from the AAOS, however, the number of physicians performing hip replacements declined by almost 29% from 2002 to 2011, which will “increase the future revision burden” on those surgeons who are still doing the procedure, the investigators said.

Dr. McLawhorn had no conflicts to report, but one of his associates disclosed relationships with Ethicon, the Knee Society, Medtronic, Mekanika, and Zimmer.

[email protected]

Hip replacement is becoming more common among middle-aged Americans at the same time as the number of surgeons who perform the procedure is declining, Dr. Alexander S. McLawhorn said at the annual meeting of the American Academy of Orthopaedic Surgeons in Las Vegas.

In 2011, patients aged 45-64 years underwent 42.3% of the hip replacements performed, compared with 33.9% in 2002. The number of replacements performed rose from approximately 68,000 in 2002 to 128,000 in 2011, an increase of 89.2%, compared with an increase of 37.0% among those aged 65 years and older, according to data from the Nationwide Inpatient Sample.

This “observed growth was best explained by an expansion of the middle-aged population in the United States. This particular age group is projected to continue expanding, and as such the demand for [hip replacement] in this active group of patients will likely continue to rise as well,” Dr. McLawhorn of the Hospital for Special Surgery, New York, said in a written statement.

According to membership data from the AAOS, however, the number of physicians performing hip replacements declined by almost 29% from 2002 to 2011, which will “increase the future revision burden” on those surgeons who are still doing the procedure, the investigators said.

Dr. McLawhorn had no conflicts to report, but one of his associates disclosed relationships with Ethicon, the Knee Society, Medtronic, Mekanika, and Zimmer.

[email protected]

Hip replacement is becoming more common among middle-aged Americans at the same time as the number of surgeons who perform the procedure is declining, Dr. Alexander S. McLawhorn said at the annual meeting of the American Academy of Orthopaedic Surgeons in Las Vegas.

In 2011, patients aged 45-64 years underwent 42.3% of the hip replacements performed, compared with 33.9% in 2002. The number of replacements performed rose from approximately 68,000 in 2002 to 128,000 in 2011, an increase of 89.2%, compared with an increase of 37.0% among those aged 65 years and older, according to data from the Nationwide Inpatient Sample.

This “observed growth was best explained by an expansion of the middle-aged population in the United States. This particular age group is projected to continue expanding, and as such the demand for [hip replacement] in this active group of patients will likely continue to rise as well,” Dr. McLawhorn of the Hospital for Special Surgery, New York, said in a written statement.

According to membership data from the AAOS, however, the number of physicians performing hip replacements declined by almost 29% from 2002 to 2011, which will “increase the future revision burden” on those surgeons who are still doing the procedure, the investigators said.

Dr. McLawhorn had no conflicts to report, but one of his associates disclosed relationships with Ethicon, the Knee Society, Medtronic, Mekanika, and Zimmer.

[email protected]

LAS VEGAS—While women may have their first total joint replacement (TJR) at an older age, they are less likely to have complications related to their surgery or require revision surgery, according to a study presented at the 2015 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS). The findings contradict the theory that TJR is underutilized in female patients because they have worse outcomes than men.

Researchers reviewed patient databases from an Ontario hospital for first-time primary total hip replacement (THR) and total knee replacement (TKR) patients between 2002 and 2009. There were 37,881 THR surgeries (53.8% female) and 59,564 TKR surgeries (60.5% female). Women who underwent THR were significantly older than males (70 years vs. 65 years); however, there was no difference in age between male and female patients undergoing TKR (median age 68 years for both). A greater proportion of female patients undergoing TJR were defined as frail (6.6% vs. 3.5% for THR; and, 6.7% vs. 4% for TKR).

Following surgery, men were:

• 15% more likely to return to the emergency department within 30 days of hospital discharge following either THR or TKR.

• 60% and 70% more likely to have an acute myocardial infarction within 3 months following THR and TKR, respectively.

• 50% more likely to require a revision arthroplasty within 2 years of TKR.

• 25% more likely to be readmitted to the hospital and 70% more likely to experience an infection or revision surgery within 2 years of TKR, compared to women.

“Despite the fact that women have a higher prevalence of advanced hip and knee arthritis, prior research indicates that North American women with arthritis are less likely to receive joint replacement than men,” said lead study author Bheeshma Ravi, MD, PhD, an orthopedic surgery resident at the University of Toronto. “One possible explanation is that women are less often offered or accept surgery because their risk of serious complications following surgery is greater than that of men.

“In this study, we found that while overall rates of serious complications were low for both groups, they were lower for women than for men for both hip and knee replacement, particularly the latter” said Dr. Ravi. “Thus, the previously documented sex difference utilization of TJR cannot be explained by differential risks of complications following surgery.”

LAS VEGAS—While women may have their first total joint replacement (TJR) at an older age, they are less likely to have complications related to their surgery or require revision surgery, according to a study presented at the 2015 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS). The findings contradict the theory that TJR is underutilized in female patients because they have worse outcomes than men.

Researchers reviewed patient databases from an Ontario hospital for first-time primary total hip replacement (THR) and total knee replacement (TKR) patients between 2002 and 2009. There were 37,881 THR surgeries (53.8% female) and 59,564 TKR surgeries (60.5% female). Women who underwent THR were significantly older than males (70 years vs. 65 years); however, there was no difference in age between male and female patients undergoing TKR (median age 68 years for both). A greater proportion of female patients undergoing TJR were defined as frail (6.6% vs. 3.5% for THR; and, 6.7% vs. 4% for TKR).

Following surgery, men were:

• 15% more likely to return to the emergency department within 30 days of hospital discharge following either THR or TKR.

• 60% and 70% more likely to have an acute myocardial infarction within 3 months following THR and TKR, respectively.

• 50% more likely to require a revision arthroplasty within 2 years of TKR.

• 25% more likely to be readmitted to the hospital and 70% more likely to experience an infection or revision surgery within 2 years of TKR, compared to women.

“Despite the fact that women have a higher prevalence of advanced hip and knee arthritis, prior research indicates that North American women with arthritis are less likely to receive joint replacement than men,” said lead study author Bheeshma Ravi, MD, PhD, an orthopedic surgery resident at the University of Toronto. “One possible explanation is that women are less often offered or accept surgery because their risk of serious complications following surgery is greater than that of men.

“In this study, we found that while overall rates of serious complications were low for both groups, they were lower for women than for men for both hip and knee replacement, particularly the latter” said Dr. Ravi. “Thus, the previously documented sex difference utilization of TJR cannot be explained by differential risks of complications following surgery.”

LAS VEGAS—While women may have their first total joint replacement (TJR) at an older age, they are less likely to have complications related to their surgery or require revision surgery, according to a study presented at the 2015 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS). The findings contradict the theory that TJR is underutilized in female patients because they have worse outcomes than men.

Researchers reviewed patient databases from an Ontario hospital for first-time primary total hip replacement (THR) and total knee replacement (TKR) patients between 2002 and 2009. There were 37,881 THR surgeries (53.8% female) and 59,564 TKR surgeries (60.5% female). Women who underwent THR were significantly older than males (70 years vs. 65 years); however, there was no difference in age between male and female patients undergoing TKR (median age 68 years for both). A greater proportion of female patients undergoing TJR were defined as frail (6.6% vs. 3.5% for THR; and, 6.7% vs. 4% for TKR).

Following surgery, men were:

• 15% more likely to return to the emergency department within 30 days of hospital discharge following either THR or TKR.

• 60% and 70% more likely to have an acute myocardial infarction within 3 months following THR and TKR, respectively.

• 50% more likely to require a revision arthroplasty within 2 years of TKR.

• 25% more likely to be readmitted to the hospital and 70% more likely to experience an infection or revision surgery within 2 years of TKR, compared to women.

“Despite the fact that women have a higher prevalence of advanced hip and knee arthritis, prior research indicates that North American women with arthritis are less likely to receive joint replacement than men,” said lead study author Bheeshma Ravi, MD, PhD, an orthopedic surgery resident at the University of Toronto. “One possible explanation is that women are less often offered or accept surgery because their risk of serious complications following surgery is greater than that of men.

“In this study, we found that while overall rates of serious complications were low for both groups, they were lower for women than for men for both hip and knee replacement, particularly the latter” said Dr. Ravi. “Thus, the previously documented sex difference utilization of TJR cannot be explained by differential risks of complications following surgery.”

LAS VEGAS—Black and Hispanic patients were 62% and 50%, respectively, more likely to be readmitted to the hospital within 30 days after total joint replacement (TJR) surgery compared to white patients, according to a study presented at the 2015 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS). In addition, Medicaid patients were 40% more likely to be readmitted to the hospital than patients with private insurance. Poorer outcomes, due in part to patient comorbidities, may reflect limited access to primary care, insufficient patient-doctor communication, researchers suggest.

Disparities in the provision of health care services have long been documented, including that black patients utilize hip and total knee replacement at rates nearly 40% less than white patients, despite having comparable or higher rates of osteoarthritis.

In this study, researchers analyzed 5 years of data—demographic (including race/ethnicity), clinical, and billing—on nearly 53,000 patients admitted to Connecticut hospitals for TJR from 2008 to 2012. The average patient age was 67 years, and the vast majority of patients were white (87%), covered by Medicare (56.7%), and female (61%).

The overall 30-day readmission rate for patients was 5.2%. The most common reasons for readmission were postoperative infection (8%), infection and inflammatory reaction due to internal joint prosthesis (6%), hematoma complications during a procedure (3%), and dislocation of a prosthetic joint (3%). Among the other study findings:

• Readmission rates were 83.5 per thousand for black patients, 78.9 for Hispanic patients, and 53.3 for white patients.

• Longer length of hospital stay was significantly associated with increased odds of readmission.

• When controlling for comorbidities and type of insurance coverage, the readmission rate for Hispanic patients dropped 44%, and for black patients, 38%. Black patients remained significantly more likely than white patients to be readmitted following surgery, after controlling for comorbidities.

• Patients covered by Medicare were 30% more likely to be readmitted within 30 days following discharge compared to patients covered by private insurance, and Medicaid patients were 40% more likely.

Recent research using national data on Medicare suggests that community-based factors, such as availability of general practitioners in the area, may be as or more important than hospital factors in determining readmission rates, and that patients may have few options other than hospital care for both urgent and non-urgent conditions related to their surgery or other conditions.

“Using an all-payer database, our study shows that black patients who undergo total knee replacement may have poorer outcomes,” said lead study author and orthopedic surgeon Courtland Lewis, MD. “After controlling for two key variables implicated in race and ethnic disparities in hospital readmission—preoperative comorbidities and type of insurance coverage—black patients still have a 35% higher likelihood of all-cause, 30-day readmission compared to white patients.

“Our ongoing research in this area is focused on other factors, such as the patient’s connection to primary care and patient-provider communication, that may explain this troubling finding,” said Dr. Lewis.

LAS VEGAS—Black and Hispanic patients were 62% and 50%, respectively, more likely to be readmitted to the hospital within 30 days after total joint replacement (TJR) surgery compared to white patients, according to a study presented at the 2015 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS). In addition, Medicaid patients were 40% more likely to be readmitted to the hospital than patients with private insurance. Poorer outcomes, due in part to patient comorbidities, may reflect limited access to primary care, insufficient patient-doctor communication, researchers suggest.

Disparities in the provision of health care services have long been documented, including that black patients utilize hip and total knee replacement at rates nearly 40% less than white patients, despite having comparable or higher rates of osteoarthritis.

In this study, researchers analyzed 5 years of data—demographic (including race/ethnicity), clinical, and billing—on nearly 53,000 patients admitted to Connecticut hospitals for TJR from 2008 to 2012. The average patient age was 67 years, and the vast majority of patients were white (87%), covered by Medicare (56.7%), and female (61%).

The overall 30-day readmission rate for patients was 5.2%. The most common reasons for readmission were postoperative infection (8%), infection and inflammatory reaction due to internal joint prosthesis (6%), hematoma complications during a procedure (3%), and dislocation of a prosthetic joint (3%). Among the other study findings:

• Readmission rates were 83.5 per thousand for black patients, 78.9 for Hispanic patients, and 53.3 for white patients.

• Longer length of hospital stay was significantly associated with increased odds of readmission.

• When controlling for comorbidities and type of insurance coverage, the readmission rate for Hispanic patients dropped 44%, and for black patients, 38%. Black patients remained significantly more likely than white patients to be readmitted following surgery, after controlling for comorbidities.

• Patients covered by Medicare were 30% more likely to be readmitted within 30 days following discharge compared to patients covered by private insurance, and Medicaid patients were 40% more likely.

Recent research using national data on Medicare suggests that community-based factors, such as availability of general practitioners in the area, may be as or more important than hospital factors in determining readmission rates, and that patients may have few options other than hospital care for both urgent and non-urgent conditions related to their surgery or other conditions.

“Using an all-payer database, our study shows that black patients who undergo total knee replacement may have poorer outcomes,” said lead study author and orthopedic surgeon Courtland Lewis, MD. “After controlling for two key variables implicated in race and ethnic disparities in hospital readmission—preoperative comorbidities and type of insurance coverage—black patients still have a 35% higher likelihood of all-cause, 30-day readmission compared to white patients.

“Our ongoing research in this area is focused on other factors, such as the patient’s connection to primary care and patient-provider communication, that may explain this troubling finding,” said Dr. Lewis.

LAS VEGAS—Black and Hispanic patients were 62% and 50%, respectively, more likely to be readmitted to the hospital within 30 days after total joint replacement (TJR) surgery compared to white patients, according to a study presented at the 2015 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS). In addition, Medicaid patients were 40% more likely to be readmitted to the hospital than patients with private insurance. Poorer outcomes, due in part to patient comorbidities, may reflect limited access to primary care, insufficient patient-doctor communication, researchers suggest.

Disparities in the provision of health care services have long been documented, including that black patients utilize hip and total knee replacement at rates nearly 40% less than white patients, despite having comparable or higher rates of osteoarthritis.

In this study, researchers analyzed 5 years of data—demographic (including race/ethnicity), clinical, and billing—on nearly 53,000 patients admitted to Connecticut hospitals for TJR from 2008 to 2012. The average patient age was 67 years, and the vast majority of patients were white (87%), covered by Medicare (56.7%), and female (61%).

The overall 30-day readmission rate for patients was 5.2%. The most common reasons for readmission were postoperative infection (8%), infection and inflammatory reaction due to internal joint prosthesis (6%), hematoma complications during a procedure (3%), and dislocation of a prosthetic joint (3%). Among the other study findings:

• Readmission rates were 83.5 per thousand for black patients, 78.9 for Hispanic patients, and 53.3 for white patients.

• Longer length of hospital stay was significantly associated with increased odds of readmission.

• When controlling for comorbidities and type of insurance coverage, the readmission rate for Hispanic patients dropped 44%, and for black patients, 38%. Black patients remained significantly more likely than white patients to be readmitted following surgery, after controlling for comorbidities.

• Patients covered by Medicare were 30% more likely to be readmitted within 30 days following discharge compared to patients covered by private insurance, and Medicaid patients were 40% more likely.

Recent research using national data on Medicare suggests that community-based factors, such as availability of general practitioners in the area, may be as or more important than hospital factors in determining readmission rates, and that patients may have few options other than hospital care for both urgent and non-urgent conditions related to their surgery or other conditions.

“Using an all-payer database, our study shows that black patients who undergo total knee replacement may have poorer outcomes,” said lead study author and orthopedic surgeon Courtland Lewis, MD. “After controlling for two key variables implicated in race and ethnic disparities in hospital readmission—preoperative comorbidities and type of insurance coverage—black patients still have a 35% higher likelihood of all-cause, 30-day readmission compared to white patients.

“Our ongoing research in this area is focused on other factors, such as the patient’s connection to primary care and patient-provider communication, that may explain this troubling finding,” said Dr. Lewis.

LAS VEGAS—The number of total hip replacements (THRs) nearly doubled among middle-age patients between 2002 and 2011, primarily due to the expansion of the middle-age population in the United States, according to a study presented at the 2015 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS). Continued growth in utilization of hip replacement surgery in patients ages 45 to 64 years, an increase in revision surgeries for this population as they age, and a nearly 30% decline in the number of surgeons who perform THR could have significant implications for future health care costs, THR demand, and access, researchers said.

The researchers used the Nationwide Inpatient Sample (NIS) to identify primary THRs performed between 2002 and 2011 in patients ages 45 to 64 years, as well as related hospital charges. Population data and projections were obtained from the US Census Bureau and surgeon workforce estimates from the AAOS.

In 2011, 42.3% of THRs were performed in patients ages 45 to 64 years compared to 33.9% in 2002. Utilization of THR in this age group increased 89.2% from 2002 to 2011, from approximately 68,000 THRs in 2002 to 128,000 THRs in 2011. The overall population increased 21.3%. In addition, the authors found that:

• Growth of THR utilization in the 45- to 64-year-old age group grew 2.4 times faster than it did in the Medicare-aged population (age > 65 years).

• A rise in the prevalence of obesity, a known risk factor for hip osteoarthritis, among middle-age Americans was not significantly associated with increased THR utilization.

• Mean hospital charges in the THR 45- to 64-year-old age group declined 5.7% from 2002 to 2011, and declined 2.5% in the Medicare population (age > 65 years).

• Mean physician reimbursement per THR, in 2011 US dollars, declined 26.2% over the same period.

• Concurrently, the number of physicians reporting that they performed THR surgeries declined 28.2%.

“The purpose of this study was to identify potential drivers of THR utilization in the middle-age patient segment,” said lead study author Alexander S. McLawhorn, MD, MBA, an orthopedic surgery resident at the Hospital for Special Surgery in New York City. “Our multivariable statistical model suggested that the observed growth was best explained by an expansion of the middle-age population in the US. This particular age group is projected to continue expanding, and as such the demand for THR in this active group of patients will likely continue to rise as well. Our results underscore concerns about consumption of premium-priced implants in younger patients and the future revision burden this trend implies in the face of a dwindling number of physicians who specialize in hip arthroplasty surgery.”

LAS VEGAS—The number of total hip replacements (THRs) nearly doubled among middle-age patients between 2002 and 2011, primarily due to the expansion of the middle-age population in the United States, according to a study presented at the 2015 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS). Continued growth in utilization of hip replacement surgery in patients ages 45 to 64 years, an increase in revision surgeries for this population as they age, and a nearly 30% decline in the number of surgeons who perform THR could have significant implications for future health care costs, THR demand, and access, researchers said.

The researchers used the Nationwide Inpatient Sample (NIS) to identify primary THRs performed between 2002 and 2011 in patients ages 45 to 64 years, as well as related hospital charges. Population data and projections were obtained from the US Census Bureau and surgeon workforce estimates from the AAOS.

In 2011, 42.3% of THRs were performed in patients ages 45 to 64 years compared to 33.9% in 2002. Utilization of THR in this age group increased 89.2% from 2002 to 2011, from approximately 68,000 THRs in 2002 to 128,000 THRs in 2011. The overall population increased 21.3%. In addition, the authors found that:

• Growth of THR utilization in the 45- to 64-year-old age group grew 2.4 times faster than it did in the Medicare-aged population (age > 65 years).

• A rise in the prevalence of obesity, a known risk factor for hip osteoarthritis, among middle-age Americans was not significantly associated with increased THR utilization.

• Mean hospital charges in the THR 45- to 64-year-old age group declined 5.7% from 2002 to 2011, and declined 2.5% in the Medicare population (age > 65 years).

• Mean physician reimbursement per THR, in 2011 US dollars, declined 26.2% over the same period.

• Concurrently, the number of physicians reporting that they performed THR surgeries declined 28.2%.

“The purpose of this study was to identify potential drivers of THR utilization in the middle-age patient segment,” said lead study author Alexander S. McLawhorn, MD, MBA, an orthopedic surgery resident at the Hospital for Special Surgery in New York City. “Our multivariable statistical model suggested that the observed growth was best explained by an expansion of the middle-age population in the US. This particular age group is projected to continue expanding, and as such the demand for THR in this active group of patients will likely continue to rise as well. Our results underscore concerns about consumption of premium-priced implants in younger patients and the future revision burden this trend implies in the face of a dwindling number of physicians who specialize in hip arthroplasty surgery.”

LAS VEGAS—The number of total hip replacements (THRs) nearly doubled among middle-age patients between 2002 and 2011, primarily due to the expansion of the middle-age population in the United States, according to a study presented at the 2015 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS). Continued growth in utilization of hip replacement surgery in patients ages 45 to 64 years, an increase in revision surgeries for this population as they age, and a nearly 30% decline in the number of surgeons who perform THR could have significant implications for future health care costs, THR demand, and access, researchers said.

The researchers used the Nationwide Inpatient Sample (NIS) to identify primary THRs performed between 2002 and 2011 in patients ages 45 to 64 years, as well as related hospital charges. Population data and projections were obtained from the US Census Bureau and surgeon workforce estimates from the AAOS.

In 2011, 42.3% of THRs were performed in patients ages 45 to 64 years compared to 33.9% in 2002. Utilization of THR in this age group increased 89.2% from 2002 to 2011, from approximately 68,000 THRs in 2002 to 128,000 THRs in 2011. The overall population increased 21.3%. In addition, the authors found that:

• Growth of THR utilization in the 45- to 64-year-old age group grew 2.4 times faster than it did in the Medicare-aged population (age > 65 years).

• A rise in the prevalence of obesity, a known risk factor for hip osteoarthritis, among middle-age Americans was not significantly associated with increased THR utilization.

• Mean hospital charges in the THR 45- to 64-year-old age group declined 5.7% from 2002 to 2011, and declined 2.5% in the Medicare population (age > 65 years).

• Mean physician reimbursement per THR, in 2011 US dollars, declined 26.2% over the same period.

• Concurrently, the number of physicians reporting that they performed THR surgeries declined 28.2%.

“The purpose of this study was to identify potential drivers of THR utilization in the middle-age patient segment,” said lead study author Alexander S. McLawhorn, MD, MBA, an orthopedic surgery resident at the Hospital for Special Surgery in New York City. “Our multivariable statistical model suggested that the observed growth was best explained by an expansion of the middle-age population in the US. This particular age group is projected to continue expanding, and as such the demand for THR in this active group of patients will likely continue to rise as well. Our results underscore concerns about consumption of premium-priced implants in younger patients and the future revision burden this trend implies in the face of a dwindling number of physicians who specialize in hip arthroplasty surgery.”