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Mixed findings on iron repletion in HF
NEW ORLEANS – Oral iron supplementation was declared ineffective for the treatment of iron deficiency in patients with heart failure with reduced ejection fraction in one major randomized trial while intravenous ferric carboxymaltose improved exercise capacity and quality of life in another study presented at the American Heart Association scientific sessions.
Iron deficiency is present in roughly half of patients with heart failure with reduced ejection fraction (HFrEF). In affected patients it’s associated with diminished functional capacity and poor quality of life, and is an independent predictor of mortality. Thus, it has emerged as a potential therapeutic target in HFrEF.
The IRONOUT HF (Oral Iron Repletion Effects on Oxygen UpTake in Heart Failure) trial was a multicenter, randomized, double-blind, placebo-controlled clinical trial conducted by the National Heart, Lung, and Blood Institute’s Clinical Heart Failure Network investigators. It included 225 patients with HFrEF and iron deficiency who were randomized to 16 weeks of oral iron polysaccharide at 150 mg b.i.d. or matching placebo.
The primary endpoint was change from baseline to 16 weeks in exercise capacity, as measured via peak oxygen uptake during cardiopulmonary exercise testing. The results were no better in the iron-supplemented group than in placebo-treated controls. Nor was there any benefit for oral iron therapy in terms of quality of life, as assessed by the Kansas City Cardiomyopathy Questionnaire or any of numerous other secondary endpoints, according to Dr. Lewis, head of the heart failure section and director of the cardiopulmonary exercise testing laboratory at Massachusetts General Hospital, Boston.
Participants’ mean baseline hemoglobin level was 12.6 g/dL, but whether patients were anemic at baseline or not made no difference in terms of outcomes. Rates of venous congestion and bleeding were low during the trial.
The problem, the investigators found, was that high-dose oral iron only minimally repleted iron stores. Transferrin saturation increased by a paltry absolute 3% after 16 weeks of twice-daily therapy. Serum ferritin levels increased only 1/20th as much as after intravenous iron ferric carboxymaltose therapy in the earlier positive FAIR-HF (Ferinject Assessment in Patients With Iron Deficiency and Chronic Heart Failure) trial (N Engl J Med. 2009 Dec 17;361:2436-48).
Levels of hepcidin were elevated in study participants. And the higher the level of hepcidin – which Dr. Lewis called “a massive regulator of iron bioavailability and absorption” – the more refractory patients were to oral iron repletion.
“Hepcidin was invented by nature to protect against iron from stimulating growth of bacteria. And when it’s elevated, taking iron orally just has no chance of success,” explained Dr. Anker, professor of cardiology at the University of Gottingen (Germany).
Dr. Anker, who chaired the positive FAIR-HF trial of intravenous iron, said IRONOUT HF was a very well-conducted and definitive clinical trial of oral iron supplementation in HFrEF.
“It’s very simple: Oral iron does not work in patients with chronic heart failure. That’s the take home message. It’s true for peak VO2 [oxygen consumption], for 6-minute walk distance, for symptoms, for quality of life, and even for surrogate markers like NT-proBNP [N-terminal pro b-type natriuretic peptide]. If iron doesn’t get into the body, it’s really difficult to [imagine] that the iron that doesn’t get into the body can exert an effect,” he said.
The primary endpoint in EFFECT-HF was assessor-blinded change in peak VO2 from baseline to week 24. The control group experienced a decrease in peak VO2 over time such that there was a significant difference of 1.0 mL/kg per minute between the two groups.
The ferric carboxymaltose recipients also did significantly better in terms of secondary endpoints including improvement in New York Heart Association functional class, self-reported Patient Global Assessment score, and quality-of-life measures, reported Dr. van Veldhuisen, professor and chairman of cardiology at University Medical Center Groningen (the Netherlands).
Session moderator Clyde Yancy, MD, commented that intravenous iron is not ready for prime time use in clinical practice for several reasons. The open-label EFFECT-HF trial, like the earlier positive double-blind FAIR-HF and CONFIRM-HF IV ferric carboxymaltose trials, was too modest in size to be convincing, especially since this is an expensive and intrusive therapy.
“The endpoint of peak VO2, although a very powerful endpoint, is still one for which there may be some subjectivity, and so we need a more definitive endpoint to be absolutely certain about the potential benefit of the administration of ferric carboxymaltose,” said Dr. Yancy, professor of medicine and chief of cardiology at Northwestern University in Chicago.
Discussant Adrian Hernandez, MD, of the Duke Clinical Research Institute in Durham, N.C., said he considers peak VO2 an important endpoint.
“When you talk to patients, exercise capacity is an outcome that matters to them,” he said. “They often comment that what matters to them is living longer with a better quality of life, free of worsening heart failure, and having improvement in everyday functional status. So the cardiopulmonary exercise test is not just a surrogate endpoint; it’s a measure of functional outcome that matters to patients,” he said.
Still, like Dr. Yancy, Dr. Hernandez said he thinks it’s time to have larger, longer, definitive trials with clinical endpoints in order to understand the role of intravenous iron. Both cardiologists applauded Dr. Anker’s announcement that such a trial, known as FAIR-HF2, is now getting started.
The IRONOUT HF trial was funded by the National Institutes of Health. Dr. Lewis reported receiving research support from a handful of pharmaceutical and medical device companies. Dr. van Velduisen reported serving as a scientific adviser to Vifor Pharma, which sponsored the EFFECT-HF trial. Dr. Anker, who was an EFFECT-HF investigator, serves as a consultant to Vifor and several other companies. Dr. Hernandez was an IRONOUT HF investigator and reported receiving research grants from a handful of pharmaceutical companies.
NEW ORLEANS – Oral iron supplementation was declared ineffective for the treatment of iron deficiency in patients with heart failure with reduced ejection fraction in one major randomized trial while intravenous ferric carboxymaltose improved exercise capacity and quality of life in another study presented at the American Heart Association scientific sessions.
Iron deficiency is present in roughly half of patients with heart failure with reduced ejection fraction (HFrEF). In affected patients it’s associated with diminished functional capacity and poor quality of life, and is an independent predictor of mortality. Thus, it has emerged as a potential therapeutic target in HFrEF.
The IRONOUT HF (Oral Iron Repletion Effects on Oxygen UpTake in Heart Failure) trial was a multicenter, randomized, double-blind, placebo-controlled clinical trial conducted by the National Heart, Lung, and Blood Institute’s Clinical Heart Failure Network investigators. It included 225 patients with HFrEF and iron deficiency who were randomized to 16 weeks of oral iron polysaccharide at 150 mg b.i.d. or matching placebo.
The primary endpoint was change from baseline to 16 weeks in exercise capacity, as measured via peak oxygen uptake during cardiopulmonary exercise testing. The results were no better in the iron-supplemented group than in placebo-treated controls. Nor was there any benefit for oral iron therapy in terms of quality of life, as assessed by the Kansas City Cardiomyopathy Questionnaire or any of numerous other secondary endpoints, according to Dr. Lewis, head of the heart failure section and director of the cardiopulmonary exercise testing laboratory at Massachusetts General Hospital, Boston.
Participants’ mean baseline hemoglobin level was 12.6 g/dL, but whether patients were anemic at baseline or not made no difference in terms of outcomes. Rates of venous congestion and bleeding were low during the trial.
The problem, the investigators found, was that high-dose oral iron only minimally repleted iron stores. Transferrin saturation increased by a paltry absolute 3% after 16 weeks of twice-daily therapy. Serum ferritin levels increased only 1/20th as much as after intravenous iron ferric carboxymaltose therapy in the earlier positive FAIR-HF (Ferinject Assessment in Patients With Iron Deficiency and Chronic Heart Failure) trial (N Engl J Med. 2009 Dec 17;361:2436-48).
Levels of hepcidin were elevated in study participants. And the higher the level of hepcidin – which Dr. Lewis called “a massive regulator of iron bioavailability and absorption” – the more refractory patients were to oral iron repletion.
“Hepcidin was invented by nature to protect against iron from stimulating growth of bacteria. And when it’s elevated, taking iron orally just has no chance of success,” explained Dr. Anker, professor of cardiology at the University of Gottingen (Germany).
Dr. Anker, who chaired the positive FAIR-HF trial of intravenous iron, said IRONOUT HF was a very well-conducted and definitive clinical trial of oral iron supplementation in HFrEF.
“It’s very simple: Oral iron does not work in patients with chronic heart failure. That’s the take home message. It’s true for peak VO2 [oxygen consumption], for 6-minute walk distance, for symptoms, for quality of life, and even for surrogate markers like NT-proBNP [N-terminal pro b-type natriuretic peptide]. If iron doesn’t get into the body, it’s really difficult to [imagine] that the iron that doesn’t get into the body can exert an effect,” he said.
The primary endpoint in EFFECT-HF was assessor-blinded change in peak VO2 from baseline to week 24. The control group experienced a decrease in peak VO2 over time such that there was a significant difference of 1.0 mL/kg per minute between the two groups.
The ferric carboxymaltose recipients also did significantly better in terms of secondary endpoints including improvement in New York Heart Association functional class, self-reported Patient Global Assessment score, and quality-of-life measures, reported Dr. van Veldhuisen, professor and chairman of cardiology at University Medical Center Groningen (the Netherlands).
Session moderator Clyde Yancy, MD, commented that intravenous iron is not ready for prime time use in clinical practice for several reasons. The open-label EFFECT-HF trial, like the earlier positive double-blind FAIR-HF and CONFIRM-HF IV ferric carboxymaltose trials, was too modest in size to be convincing, especially since this is an expensive and intrusive therapy.
“The endpoint of peak VO2, although a very powerful endpoint, is still one for which there may be some subjectivity, and so we need a more definitive endpoint to be absolutely certain about the potential benefit of the administration of ferric carboxymaltose,” said Dr. Yancy, professor of medicine and chief of cardiology at Northwestern University in Chicago.
Discussant Adrian Hernandez, MD, of the Duke Clinical Research Institute in Durham, N.C., said he considers peak VO2 an important endpoint.
“When you talk to patients, exercise capacity is an outcome that matters to them,” he said. “They often comment that what matters to them is living longer with a better quality of life, free of worsening heart failure, and having improvement in everyday functional status. So the cardiopulmonary exercise test is not just a surrogate endpoint; it’s a measure of functional outcome that matters to patients,” he said.
Still, like Dr. Yancy, Dr. Hernandez said he thinks it’s time to have larger, longer, definitive trials with clinical endpoints in order to understand the role of intravenous iron. Both cardiologists applauded Dr. Anker’s announcement that such a trial, known as FAIR-HF2, is now getting started.
The IRONOUT HF trial was funded by the National Institutes of Health. Dr. Lewis reported receiving research support from a handful of pharmaceutical and medical device companies. Dr. van Velduisen reported serving as a scientific adviser to Vifor Pharma, which sponsored the EFFECT-HF trial. Dr. Anker, who was an EFFECT-HF investigator, serves as a consultant to Vifor and several other companies. Dr. Hernandez was an IRONOUT HF investigator and reported receiving research grants from a handful of pharmaceutical companies.
NEW ORLEANS – Oral iron supplementation was declared ineffective for the treatment of iron deficiency in patients with heart failure with reduced ejection fraction in one major randomized trial while intravenous ferric carboxymaltose improved exercise capacity and quality of life in another study presented at the American Heart Association scientific sessions.
Iron deficiency is present in roughly half of patients with heart failure with reduced ejection fraction (HFrEF). In affected patients it’s associated with diminished functional capacity and poor quality of life, and is an independent predictor of mortality. Thus, it has emerged as a potential therapeutic target in HFrEF.
The IRONOUT HF (Oral Iron Repletion Effects on Oxygen UpTake in Heart Failure) trial was a multicenter, randomized, double-blind, placebo-controlled clinical trial conducted by the National Heart, Lung, and Blood Institute’s Clinical Heart Failure Network investigators. It included 225 patients with HFrEF and iron deficiency who were randomized to 16 weeks of oral iron polysaccharide at 150 mg b.i.d. or matching placebo.
The primary endpoint was change from baseline to 16 weeks in exercise capacity, as measured via peak oxygen uptake during cardiopulmonary exercise testing. The results were no better in the iron-supplemented group than in placebo-treated controls. Nor was there any benefit for oral iron therapy in terms of quality of life, as assessed by the Kansas City Cardiomyopathy Questionnaire or any of numerous other secondary endpoints, according to Dr. Lewis, head of the heart failure section and director of the cardiopulmonary exercise testing laboratory at Massachusetts General Hospital, Boston.
Participants’ mean baseline hemoglobin level was 12.6 g/dL, but whether patients were anemic at baseline or not made no difference in terms of outcomes. Rates of venous congestion and bleeding were low during the trial.
The problem, the investigators found, was that high-dose oral iron only minimally repleted iron stores. Transferrin saturation increased by a paltry absolute 3% after 16 weeks of twice-daily therapy. Serum ferritin levels increased only 1/20th as much as after intravenous iron ferric carboxymaltose therapy in the earlier positive FAIR-HF (Ferinject Assessment in Patients With Iron Deficiency and Chronic Heart Failure) trial (N Engl J Med. 2009 Dec 17;361:2436-48).
Levels of hepcidin were elevated in study participants. And the higher the level of hepcidin – which Dr. Lewis called “a massive regulator of iron bioavailability and absorption” – the more refractory patients were to oral iron repletion.
“Hepcidin was invented by nature to protect against iron from stimulating growth of bacteria. And when it’s elevated, taking iron orally just has no chance of success,” explained Dr. Anker, professor of cardiology at the University of Gottingen (Germany).
Dr. Anker, who chaired the positive FAIR-HF trial of intravenous iron, said IRONOUT HF was a very well-conducted and definitive clinical trial of oral iron supplementation in HFrEF.
“It’s very simple: Oral iron does not work in patients with chronic heart failure. That’s the take home message. It’s true for peak VO2 [oxygen consumption], for 6-minute walk distance, for symptoms, for quality of life, and even for surrogate markers like NT-proBNP [N-terminal pro b-type natriuretic peptide]. If iron doesn’t get into the body, it’s really difficult to [imagine] that the iron that doesn’t get into the body can exert an effect,” he said.
The primary endpoint in EFFECT-HF was assessor-blinded change in peak VO2 from baseline to week 24. The control group experienced a decrease in peak VO2 over time such that there was a significant difference of 1.0 mL/kg per minute between the two groups.
The ferric carboxymaltose recipients also did significantly better in terms of secondary endpoints including improvement in New York Heart Association functional class, self-reported Patient Global Assessment score, and quality-of-life measures, reported Dr. van Veldhuisen, professor and chairman of cardiology at University Medical Center Groningen (the Netherlands).
Session moderator Clyde Yancy, MD, commented that intravenous iron is not ready for prime time use in clinical practice for several reasons. The open-label EFFECT-HF trial, like the earlier positive double-blind FAIR-HF and CONFIRM-HF IV ferric carboxymaltose trials, was too modest in size to be convincing, especially since this is an expensive and intrusive therapy.
“The endpoint of peak VO2, although a very powerful endpoint, is still one for which there may be some subjectivity, and so we need a more definitive endpoint to be absolutely certain about the potential benefit of the administration of ferric carboxymaltose,” said Dr. Yancy, professor of medicine and chief of cardiology at Northwestern University in Chicago.
Discussant Adrian Hernandez, MD, of the Duke Clinical Research Institute in Durham, N.C., said he considers peak VO2 an important endpoint.
“When you talk to patients, exercise capacity is an outcome that matters to them,” he said. “They often comment that what matters to them is living longer with a better quality of life, free of worsening heart failure, and having improvement in everyday functional status. So the cardiopulmonary exercise test is not just a surrogate endpoint; it’s a measure of functional outcome that matters to patients,” he said.
Still, like Dr. Yancy, Dr. Hernandez said he thinks it’s time to have larger, longer, definitive trials with clinical endpoints in order to understand the role of intravenous iron. Both cardiologists applauded Dr. Anker’s announcement that such a trial, known as FAIR-HF2, is now getting started.
The IRONOUT HF trial was funded by the National Institutes of Health. Dr. Lewis reported receiving research support from a handful of pharmaceutical and medical device companies. Dr. van Velduisen reported serving as a scientific adviser to Vifor Pharma, which sponsored the EFFECT-HF trial. Dr. Anker, who was an EFFECT-HF investigator, serves as a consultant to Vifor and several other companies. Dr. Hernandez was an IRONOUT HF investigator and reported receiving research grants from a handful of pharmaceutical companies.
EXPERT ANALYSIS FROM THE AHA SCIENTIFIC SESSIONS
VIDEO: Appealing DAA denials is worth it for hepatitis C patients
BOSTON – Though criteria for insurance approval for direct-acting antivirals (DAAs) for hepatitis C virus (HCV) are loosening, many patients are still denied by both public and private carriers. Providers and patients should know that it’s worthwhile to appeal these denials; 78.1% (115 of 145) of initial DAA denials were approved on appeal, according to a recent study.
Jane Giang, PharmD, a clinical pharmacist at the University of North Carolina Health System, Chapel Hill, worked with colleagues to conduct a retrospective study of patients at her facility who were prescribed a DAA for HCV between October 2014 and April 2016.
Dr. Giang, in a video interview at the annual meeting of the American Association for the Study of Liver Diseases, said that she works alongside physicians in her clinic to craft appeals, tailoring appeal letters to individual patients’ circumstances.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
In a poster presentation, Dr. Giang and her colleagues presented results from a total of 1,017 patients who were prescribed DAAs for HCV during the study time frame. Of these, three-quarters (n = 794, 78.1%) received initial approval for their medication, while one in five patients (n = 206, 20.2%) had their initial applications denied. The remaining patients either had their cases closed for a variety of reasons, or had pending applications at the time of data analysis.
About half of the patients (n = 496, 48.8%) had commercial insurance. Medicare was the primary insurance for another 207 (n = 20.4%), and Medicaid for 140 (13.8%).
Of the patients whose DAAs were initially denied, 65 (31.6%) of the denials were for fibrosis less than stage F2. Another quarter of patients (n = 57, 27.7%) did not meet approval criteria, and 41 (19.9%) of denials said that the DAA was nonformulary or excluded by the plan. The remaining denials were for missing information or a variety of other reasons.
Half of the patients (n = 504, 49.6%) had F4 fibrosis at the time of application for DAA treatment; 241 (23.7%) had F0 or F1 fibrosis, and the remainder were approximately evenly split between F3 and F4 fibrosis.
When a subset of these denials went through an appeals process, most were eventually approved. Of the 42 denials for less than F2 fibrosis that were appealed, 20 (47.6%) were eventually approved. Of the 40 patients whose applications for DAAs were based on not meeting criteria, 37 (92.5%) were approved on appeal, and of the 32 denials based on plan exclusions or DAAs being nonformulary, 29 (90.6%) were approved on appeal.
When Dr. Giang and her colleagues broke down the numbers by type of insurance, they found that of the 496 patients who had commercial insurance, only 44 (8.9%) eventually received a final denial. Medicare patients had a 3.9% final denial rate, while just one of the 172 patients (0.6%) without insurance who received medication through programs directly from the manufacturer had a final denial.
The largest number of final denials occurred in the group of patients with Medicaid. Of these 140 patients, 25 (17.9%) had a final denial. Dr. Giang said that in North Carolina, providers cannot file appeals for DAA approval on behalf of patients; the paperwork is sent directly to the patient’s home, and patients have to complete and file the forms. She said that she and her colleagues learned to alert these patients to be on the lookout for paperwork, and counseled them to bring the appeal forms into the clinic so that staff could assist them in completing the appeal.
Though Dr. Giang said that her study showed that payer type matters when it comes to reimbursement for HCV care, the “impact of payer type on access to care remains incompletely explored, especially among noninsured patients,” she said.
Dr. Giang reported no outside sources of funding, and no conflicts of interest.
[email protected]
On Twitter@karioakes
BOSTON – Though criteria for insurance approval for direct-acting antivirals (DAAs) for hepatitis C virus (HCV) are loosening, many patients are still denied by both public and private carriers. Providers and patients should know that it’s worthwhile to appeal these denials; 78.1% (115 of 145) of initial DAA denials were approved on appeal, according to a recent study.
Jane Giang, PharmD, a clinical pharmacist at the University of North Carolina Health System, Chapel Hill, worked with colleagues to conduct a retrospective study of patients at her facility who were prescribed a DAA for HCV between October 2014 and April 2016.
Dr. Giang, in a video interview at the annual meeting of the American Association for the Study of Liver Diseases, said that she works alongside physicians in her clinic to craft appeals, tailoring appeal letters to individual patients’ circumstances.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
In a poster presentation, Dr. Giang and her colleagues presented results from a total of 1,017 patients who were prescribed DAAs for HCV during the study time frame. Of these, three-quarters (n = 794, 78.1%) received initial approval for their medication, while one in five patients (n = 206, 20.2%) had their initial applications denied. The remaining patients either had their cases closed for a variety of reasons, or had pending applications at the time of data analysis.
About half of the patients (n = 496, 48.8%) had commercial insurance. Medicare was the primary insurance for another 207 (n = 20.4%), and Medicaid for 140 (13.8%).
Of the patients whose DAAs were initially denied, 65 (31.6%) of the denials were for fibrosis less than stage F2. Another quarter of patients (n = 57, 27.7%) did not meet approval criteria, and 41 (19.9%) of denials said that the DAA was nonformulary or excluded by the plan. The remaining denials were for missing information or a variety of other reasons.
Half of the patients (n = 504, 49.6%) had F4 fibrosis at the time of application for DAA treatment; 241 (23.7%) had F0 or F1 fibrosis, and the remainder were approximately evenly split between F3 and F4 fibrosis.
When a subset of these denials went through an appeals process, most were eventually approved. Of the 42 denials for less than F2 fibrosis that were appealed, 20 (47.6%) were eventually approved. Of the 40 patients whose applications for DAAs were based on not meeting criteria, 37 (92.5%) were approved on appeal, and of the 32 denials based on plan exclusions or DAAs being nonformulary, 29 (90.6%) were approved on appeal.
When Dr. Giang and her colleagues broke down the numbers by type of insurance, they found that of the 496 patients who had commercial insurance, only 44 (8.9%) eventually received a final denial. Medicare patients had a 3.9% final denial rate, while just one of the 172 patients (0.6%) without insurance who received medication through programs directly from the manufacturer had a final denial.
The largest number of final denials occurred in the group of patients with Medicaid. Of these 140 patients, 25 (17.9%) had a final denial. Dr. Giang said that in North Carolina, providers cannot file appeals for DAA approval on behalf of patients; the paperwork is sent directly to the patient’s home, and patients have to complete and file the forms. She said that she and her colleagues learned to alert these patients to be on the lookout for paperwork, and counseled them to bring the appeal forms into the clinic so that staff could assist them in completing the appeal.
Though Dr. Giang said that her study showed that payer type matters when it comes to reimbursement for HCV care, the “impact of payer type on access to care remains incompletely explored, especially among noninsured patients,” she said.
Dr. Giang reported no outside sources of funding, and no conflicts of interest.
[email protected]
On Twitter@karioakes
BOSTON – Though criteria for insurance approval for direct-acting antivirals (DAAs) for hepatitis C virus (HCV) are loosening, many patients are still denied by both public and private carriers. Providers and patients should know that it’s worthwhile to appeal these denials; 78.1% (115 of 145) of initial DAA denials were approved on appeal, according to a recent study.
Jane Giang, PharmD, a clinical pharmacist at the University of North Carolina Health System, Chapel Hill, worked with colleagues to conduct a retrospective study of patients at her facility who were prescribed a DAA for HCV between October 2014 and April 2016.
Dr. Giang, in a video interview at the annual meeting of the American Association for the Study of Liver Diseases, said that she works alongside physicians in her clinic to craft appeals, tailoring appeal letters to individual patients’ circumstances.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
In a poster presentation, Dr. Giang and her colleagues presented results from a total of 1,017 patients who were prescribed DAAs for HCV during the study time frame. Of these, three-quarters (n = 794, 78.1%) received initial approval for their medication, while one in five patients (n = 206, 20.2%) had their initial applications denied. The remaining patients either had their cases closed for a variety of reasons, or had pending applications at the time of data analysis.
About half of the patients (n = 496, 48.8%) had commercial insurance. Medicare was the primary insurance for another 207 (n = 20.4%), and Medicaid for 140 (13.8%).
Of the patients whose DAAs were initially denied, 65 (31.6%) of the denials were for fibrosis less than stage F2. Another quarter of patients (n = 57, 27.7%) did not meet approval criteria, and 41 (19.9%) of denials said that the DAA was nonformulary or excluded by the plan. The remaining denials were for missing information or a variety of other reasons.
Half of the patients (n = 504, 49.6%) had F4 fibrosis at the time of application for DAA treatment; 241 (23.7%) had F0 or F1 fibrosis, and the remainder were approximately evenly split between F3 and F4 fibrosis.
When a subset of these denials went through an appeals process, most were eventually approved. Of the 42 denials for less than F2 fibrosis that were appealed, 20 (47.6%) were eventually approved. Of the 40 patients whose applications for DAAs were based on not meeting criteria, 37 (92.5%) were approved on appeal, and of the 32 denials based on plan exclusions or DAAs being nonformulary, 29 (90.6%) were approved on appeal.
When Dr. Giang and her colleagues broke down the numbers by type of insurance, they found that of the 496 patients who had commercial insurance, only 44 (8.9%) eventually received a final denial. Medicare patients had a 3.9% final denial rate, while just one of the 172 patients (0.6%) without insurance who received medication through programs directly from the manufacturer had a final denial.
The largest number of final denials occurred in the group of patients with Medicaid. Of these 140 patients, 25 (17.9%) had a final denial. Dr. Giang said that in North Carolina, providers cannot file appeals for DAA approval on behalf of patients; the paperwork is sent directly to the patient’s home, and patients have to complete and file the forms. She said that she and her colleagues learned to alert these patients to be on the lookout for paperwork, and counseled them to bring the appeal forms into the clinic so that staff could assist them in completing the appeal.
Though Dr. Giang said that her study showed that payer type matters when it comes to reimbursement for HCV care, the “impact of payer type on access to care remains incompletely explored, especially among noninsured patients,” she said.
Dr. Giang reported no outside sources of funding, and no conflicts of interest.
[email protected]
On Twitter@karioakes
AT THE LIVER MEETING 2016
Surgery for bowel obstruction in cancer patients didn’t increase 90-day mortality
CORONADO, CALIF. – Among advanced cancer patients with bowel obstruction, surgery was not an independent predictor of the ability to eat at discharge or survival within 90 days of consultation, results from a long-term retrospective study showed.
“I think this represents the complexity in treating these patients,” lead study author Brian D. Badgwell, MD, said at the annual meeting of the Western Surgical Association. “We need future studies to identify the optimal outcome measures.”
For the current study, the researchers retrospectively reviewed the medical records of 490 patients who required surgical consultation for bowel obstruction at MD Anderson Cancer Center between January 2000 and May 2014. They set out to determine the incidence of obstruction due to intra-abdominal tumor and to identify variables associated with the ability to eat at hospital discharge and 90-day survival. They excluded patients without clinical or radiologic features of mechanical bowel obstruction. Clinical variables of interest included obstruction site, tumor vs. non-tumor cause, laboratory parameters, radiologic extent of malignancy, and the type of treatment performed (surgical, medical, or interventional, defined as interventional radiology or endoscopy). Overall survival was calculated from the date of first surgical evaluation for bowel obstruction to any cause mortality or last follow-up. Univariate and multivariate analyses were performed for ability to eat and a Cox proportional hazards model for 90-day survival.
Dr. Badgwell reported that the most common obstruction site in the 490 patients was the small bowel (64%), followed by large bowel (20%) and gastric outlet (16%). Obstruction etiology was identified as tumor-related in 68% of cases, followed by adhesion-related (20%) and unclear (12%). Nearly half of patients (46%) received chemotherapy within 6 weeks of their surgical consultation, but only 4% were neutropenic. More than half of patients (52%) had an albumin level of less than 3.5 g/dL, 52% had a hemoglobin of 10 g/dL or greater, 36% had lymphadenopathy, 35% had ascites, 34% had peritoneal disease, and 31% had a primary or recurrent tumor in place. In addition, 53% had an abdominal visceral malignancy, 9% had bone metastases, and 14% had lung metastases.
About half of patients (49%) received medical management as their treatment, followed by surgical and procedural treatment (32% and 17%, respectively). Fifteen percent were discharged to in-home hospice or to an inpatient hospice facility. More than two-thirds (68%) were able to eat at the time of discharge, and 43% died within 90 days of surgical consultation.
Multivariate analysis revealed that the following factors were negatively associated with eating at discharge: an intact/primary local recurrence (odds ratio, 0.46), carcinomatosis (OR, 0.34), and albumin level of less than 3.5 g/dL (OR, 0.55). At the same time, variables associated with death within 90 days of consultation included having an intact primary/local recurrence (hazard ratio, 1.75), carcinomatosis (HR, 1.98), and abdominal visceral metastasis (HR, 1.75). Finally, compared with procedural treatment, both medical management and surgical management were negatively associated with death within 90 days (HR of 0.51 and 0.44, respectively).
“There is a high rate of non-mechanical bowel dysfunction in patients undergoing surgical consultation for bowel obstruction,” Dr. Badgwell concluded. “It’s very difficult to categorize these cases preoperatively. They do require a selective approach. Variables associated with outcome measures support caution in patients with carcinomatosis, hypoalbuminemia, and multiple sites of disease on imaging.”
Dr. Badgwell reported having no financial disclosures.
CORONADO, CALIF. – Among advanced cancer patients with bowel obstruction, surgery was not an independent predictor of the ability to eat at discharge or survival within 90 days of consultation, results from a long-term retrospective study showed.
“I think this represents the complexity in treating these patients,” lead study author Brian D. Badgwell, MD, said at the annual meeting of the Western Surgical Association. “We need future studies to identify the optimal outcome measures.”
For the current study, the researchers retrospectively reviewed the medical records of 490 patients who required surgical consultation for bowel obstruction at MD Anderson Cancer Center between January 2000 and May 2014. They set out to determine the incidence of obstruction due to intra-abdominal tumor and to identify variables associated with the ability to eat at hospital discharge and 90-day survival. They excluded patients without clinical or radiologic features of mechanical bowel obstruction. Clinical variables of interest included obstruction site, tumor vs. non-tumor cause, laboratory parameters, radiologic extent of malignancy, and the type of treatment performed (surgical, medical, or interventional, defined as interventional radiology or endoscopy). Overall survival was calculated from the date of first surgical evaluation for bowel obstruction to any cause mortality or last follow-up. Univariate and multivariate analyses were performed for ability to eat and a Cox proportional hazards model for 90-day survival.
Dr. Badgwell reported that the most common obstruction site in the 490 patients was the small bowel (64%), followed by large bowel (20%) and gastric outlet (16%). Obstruction etiology was identified as tumor-related in 68% of cases, followed by adhesion-related (20%) and unclear (12%). Nearly half of patients (46%) received chemotherapy within 6 weeks of their surgical consultation, but only 4% were neutropenic. More than half of patients (52%) had an albumin level of less than 3.5 g/dL, 52% had a hemoglobin of 10 g/dL or greater, 36% had lymphadenopathy, 35% had ascites, 34% had peritoneal disease, and 31% had a primary or recurrent tumor in place. In addition, 53% had an abdominal visceral malignancy, 9% had bone metastases, and 14% had lung metastases.
About half of patients (49%) received medical management as their treatment, followed by surgical and procedural treatment (32% and 17%, respectively). Fifteen percent were discharged to in-home hospice or to an inpatient hospice facility. More than two-thirds (68%) were able to eat at the time of discharge, and 43% died within 90 days of surgical consultation.
Multivariate analysis revealed that the following factors were negatively associated with eating at discharge: an intact/primary local recurrence (odds ratio, 0.46), carcinomatosis (OR, 0.34), and albumin level of less than 3.5 g/dL (OR, 0.55). At the same time, variables associated with death within 90 days of consultation included having an intact primary/local recurrence (hazard ratio, 1.75), carcinomatosis (HR, 1.98), and abdominal visceral metastasis (HR, 1.75). Finally, compared with procedural treatment, both medical management and surgical management were negatively associated with death within 90 days (HR of 0.51 and 0.44, respectively).
“There is a high rate of non-mechanical bowel dysfunction in patients undergoing surgical consultation for bowel obstruction,” Dr. Badgwell concluded. “It’s very difficult to categorize these cases preoperatively. They do require a selective approach. Variables associated with outcome measures support caution in patients with carcinomatosis, hypoalbuminemia, and multiple sites of disease on imaging.”
Dr. Badgwell reported having no financial disclosures.
CORONADO, CALIF. – Among advanced cancer patients with bowel obstruction, surgery was not an independent predictor of the ability to eat at discharge or survival within 90 days of consultation, results from a long-term retrospective study showed.
“I think this represents the complexity in treating these patients,” lead study author Brian D. Badgwell, MD, said at the annual meeting of the Western Surgical Association. “We need future studies to identify the optimal outcome measures.”
For the current study, the researchers retrospectively reviewed the medical records of 490 patients who required surgical consultation for bowel obstruction at MD Anderson Cancer Center between January 2000 and May 2014. They set out to determine the incidence of obstruction due to intra-abdominal tumor and to identify variables associated with the ability to eat at hospital discharge and 90-day survival. They excluded patients without clinical or radiologic features of mechanical bowel obstruction. Clinical variables of interest included obstruction site, tumor vs. non-tumor cause, laboratory parameters, radiologic extent of malignancy, and the type of treatment performed (surgical, medical, or interventional, defined as interventional radiology or endoscopy). Overall survival was calculated from the date of first surgical evaluation for bowel obstruction to any cause mortality or last follow-up. Univariate and multivariate analyses were performed for ability to eat and a Cox proportional hazards model for 90-day survival.
Dr. Badgwell reported that the most common obstruction site in the 490 patients was the small bowel (64%), followed by large bowel (20%) and gastric outlet (16%). Obstruction etiology was identified as tumor-related in 68% of cases, followed by adhesion-related (20%) and unclear (12%). Nearly half of patients (46%) received chemotherapy within 6 weeks of their surgical consultation, but only 4% were neutropenic. More than half of patients (52%) had an albumin level of less than 3.5 g/dL, 52% had a hemoglobin of 10 g/dL or greater, 36% had lymphadenopathy, 35% had ascites, 34% had peritoneal disease, and 31% had a primary or recurrent tumor in place. In addition, 53% had an abdominal visceral malignancy, 9% had bone metastases, and 14% had lung metastases.
About half of patients (49%) received medical management as their treatment, followed by surgical and procedural treatment (32% and 17%, respectively). Fifteen percent were discharged to in-home hospice or to an inpatient hospice facility. More than two-thirds (68%) were able to eat at the time of discharge, and 43% died within 90 days of surgical consultation.
Multivariate analysis revealed that the following factors were negatively associated with eating at discharge: an intact/primary local recurrence (odds ratio, 0.46), carcinomatosis (OR, 0.34), and albumin level of less than 3.5 g/dL (OR, 0.55). At the same time, variables associated with death within 90 days of consultation included having an intact primary/local recurrence (hazard ratio, 1.75), carcinomatosis (HR, 1.98), and abdominal visceral metastasis (HR, 1.75). Finally, compared with procedural treatment, both medical management and surgical management were negatively associated with death within 90 days (HR of 0.51 and 0.44, respectively).
“There is a high rate of non-mechanical bowel dysfunction in patients undergoing surgical consultation for bowel obstruction,” Dr. Badgwell concluded. “It’s very difficult to categorize these cases preoperatively. They do require a selective approach. Variables associated with outcome measures support caution in patients with carcinomatosis, hypoalbuminemia, and multiple sites of disease on imaging.”
Dr. Badgwell reported having no financial disclosures.
AT WSA 2016
Key clinical point:
Major finding: Compared with procedural treatment of bowel obstruction, both medical management and surgical management were negatively associated with death within 90 days (HR of 0.51 and 0.44, respectively).
Data source: A retrospective review of 490 patients with advanced cancer who required surgical consultation for bowel obstruction at MD Anderson Cancer Center, Houston, between January 2000 and May 2014.
Disclosures: Dr. Badgwell reported having no financial disclosures.
Helping patients heal after a bruising election campaign
One of us practices in the “new south” community of Charlotte, N.C., “a red state”; the other is in the “blue bubble” of Washington. In our respective polarized zones, the divergent reactions we heard about the presidential candidates were akin to projective responses to Rorschach tests.
As mental health clinicians, we knew that the country was wounded and in need of healing long before the outcome of the unconventional and acrimonious 2016 American presidential race. So, we were concerned about how patients, clinicians, and divergent communities would go about healing after an 18-month pre-election slugfest that revealed bigotry that persists more than 150 years after the Civil War.
Background of ‘two sides’
None of the nasty rhetoric delivered by our now president-elect or the clearly defensive responses we heard from our former secretary of state were going to be easily forgotten after Nov. 8, 2016. As the process unfolded, however, the voice of psychiatry, with some notable exceptions (the blog of Justin Frank, MD, for example), was absent from the public dialogue. 
Nevertheless, writing in June of this year, Bill Moyers and Michael Winship summed up the private assessment of many professionals and the fears for many of a Trump presidency:
There is a virus infecting our politics and right now it’s flourishing with a scarlet fever. It feeds on fear, paranoia and bigotry. All that was required for it to spread was a timely opportunity – and an opportunist with no scruples. ... There have been stretches of history when this virus lay dormant. ... Today its carrier is Donald Trump, but others came before him: narcissistic demagogues who lie and distort in pursuit of power and self-promotion. Bullies all, swaggering across the landscape with fistfuls of false promises, smears, innuendo and hatred for others, spite and spittle for anyone of a different race, faith, gender, or nationality.1
Alternatively, some had a smoldering fear of the progressive agenda to bring “others” – more women, African Americans, Latinos, the LGBTQ community, Muslims, and the disabled – securely under the tent of American democracy. Others, especially the underemployed cohort in neglected and struggling communities in Middle America, were simply opposed to a continuation of “politics as usual,” a.k.a. Hillary Clinton, and were desperate for change. 
The opposition views were summed up in the innuendo of the slogan: “Make America Great Again.” By the election, the tensions had begun to resemble the aggressive spirit of a sporting event: It’s “us” versus “them.”
Causes of concern
In the months leading up to the election, violent events strained the societal divisions. The police use of force2 resulted in the near-daily deaths of African American men and women and other people of color at the hands of police officers. The events built on a long and growing list of violent acts – the racially motivated shootings of nine men and women in a Charleston, S.C., church, the bombing injuries and deaths at the Boston Marathon, the shooting deaths of 20 children and 6 adults at Sandy Hook Elementary School, the homophobia-motivated shootings in a Florida nightclub – that have heightened levels of fear, anxiety, and concern for personal and family safety. For many, life has felt fragile and out of control, the perfect setup to motivate the electorate to cast their votes for the person they imagined had the most power and most interest in restoring their sense of control over their lives and, ultimately, their sense of safety.
Why the fear? A psychodynamic analysis
As psychiatrists trained in psychodynamic theory, we are quite familiar with the concept of identifying with the aggressor as a means of coping. The classic example is when a child watches his or her parents in an abusive relationship and identifies with the abusive parent in an attempt to avoid identifying with the victimized parent.
This dynamic is one that seems to have played out during this presidential election. By October 2016, Donald J. Trump already reportedly had insulted more than 280 people, places, and things on Twitter.3 Despite the evidence that Mr. Trump verbally bullied not only his opponents, but also the media, Latinos, women, the LGBTQ community, the Republican Party (his claimed party), and Muslims, people came out in numbers high enough to make him America’s president-elect. In the classic process of bullying his perceived enemies, those considered “the other,” he assigned names such as “crooked Hillary,” “little Marco,” and “lyin’ Ted” – just as a bully at school assigns names to the kid he’s decided does not have enough worth to be called by his given name.
He depicted women who accused him of sexual assault as either not being pretty enough to be worthy of assault or self-serving in their public accusations. Mexicans entering this country were referred to as “rapists and thugs.” African Americans were told that their lives are so bad that they “have nothing to lose” if they voted for a candidate who talked about erecting a wall to block out other people of color, and changing immigration laws that would banish an entire religion from entering our country.
The ‘blue bubble’ – Those who voted for Mrs. Clinton
So … this happened. And, in our consulting rooms, we are seeing a stark increase in the numbers of individuals, couples, and families reporting overwhelming anxiety, sadness, and a sense of de-realization (“it’s surreal”). At the core of their anxiety is concern for self, family, and friends as well as concern for the country as a whole.
The post-election notions that families would be immediately broken up, parents deported, the Affordable Care Act immediately dismantled, and countries bombed immediately after Election Day did not become realities. However, there is valid reason to be concerned. The Southern Poverty Law Center has noted a significant increase in post-election hate crimes throughout the nation.4
The new South ‘red states’ – those who voted for Mr. Trump
Trump supporters are feeling victorious because their “underdog” candidate ran an unconventional presidential campaign and won. However, some who voted for Mr. Trump will at some point experience anxiety when the excitement of “winning” wears off. Psychoanalyst Justin Frank speaks to this and more in his Nov. 9, 2016, blog in which he concludes: “While we mourn and blame others and ourselves for our American tragedy, Trump voters must eventually look at themselves in the mirror and exclaim, ‘what have we done?’ ”5
In his Oct. 25, 2016, New York Times article, Michael Barbaro summarized the behaviors that will become increasingly of concern to all as Mr. Trump accepts the oath of office:
The intense ambitions and undisciplined behaviors of Mr. Trump have confounded even those close to him.... In interviews, Mr. Trump makes clear just how difficult it is for him to imagine – let alone accept – defeat....
“I never had a failure,” Mr. Trump said in one of the interviews, despite his repeated corporate bankruptcies and business setbacks, “because I always turned a failure into a success.”6
This fundamental inability to accept responsibility and the attempt to distort reality is something that must concern each of us, regardless of our ideological differences.
Distress tolerance as a model for healing
Even before the outcome of the election, we were hearing from patients who did not feel safe and who reported being “terrified” about what our country might become. This is where a focus on processing the pain and decreasing anxiety is necessary. This is not an anxiety we can medicate with anxiolytics or rationalize by telling ourselves and our patients that the best man won “fair and square.” We have each – by this time – experienced patients who are quite shaken by this turn of events.
Although it has not received much press, many consider Mr. Trump’s victory to be, in part, a “white backlash.” Many supporters of Mr. Trump have felt too ashamed to publicly admit their support for a candidate who at least by innuendo incited fear, anger, and violence. This failure has created an anxiety reminiscent of the daytime anxiety experienced by people who survived nighttime lynchings in small Southern towns. The day after the lynching, it was not unusual for African American men, women, and children to wonder if their grocer, banker, postal carrier, or sheriff had donned a white hood the night before and lynched someone in their community.
The question of survival, how to survive the unimaginable, is what most distresses people. They’ve wondered out loud whether they, their family, and friends would be attacked and/or killed by those who now feel emboldened and authorized to act on their latent aggressive impulses. And, our patients’ fears are legitimate because, unfortunately, studies show that verbal aggression is correlated with increased risk of physical violence and even murder.7
In the dialectical behavioral therapy (DBT) construct developed by Marsha M. Linehan, PhD, the goals of distress tolerance are crisis survival, reality acceptance, and then freedom.8
As we apply our skills, we are uniquely positioned to help our patients and their families survive this crisis, accept that this is our president-elect, and ultimately be free from the anxiety created by the behavior that we all witnessed. We can aid in the navigation through this storm.
Acceptance
We’re already on to reality acceptance. The reality that so many African Americans and people of color have been living is now known and experienced by many who had felt immune to being marginalized. They now understand the loss of security that accompanies overwhelming fear of being the object of verbal, emotional, and physical aggression and violence.
Some are coping by entertaining fantasies that this election outcome will be undone, that the Electoral College will not approve our president-elect when it meets on Dec. 19 or that Mr. Trump will be impeached early in this upcoming term. The results of the presidential election are unlikely to be undone, so having more than 2 months between Election Day and the inauguration to work on acceptance will be helpful. The goal here is to accept the past, be hopeful about the future, and be vigilant in the present.
Freedom
Now, on to freedom. Our goal is to have all of our patients, families, colleagues, and communities able to live without fear that our leaders are not able to apply humanitarian principles to keep all of us safe. The next few months are crucial. Americans must speak out and debride the wound that bullying intentionally causes. Just as with a school bully, Mr. Trump’s behavior has to be called what it is, not sugarcoated or normalized.
History is full of critical moments in time in which, even in our fear, we said nothing. Even the most empathic of us watched the bully at school and felt relief that his behavior was not directed toward us. But we must not avert our gaze.
Bill Moyers and Michael Winship compared Mr. Trump to Sen. Joseph McCarthy, whose reign of terror was ended when journalist Edward R. Murrow courageously spoke out in defiance of the senator. At the end of one of his segments on “See It Now,” Mr. Murrow concluded as he signed off:
We will not walk in fear, one of another. We will not be driven by fear into an age of unreason, if we dig deep in our history and our doctrine, and remember that we are not descended from fearful men — not from men who feared to write, to speak, to associate and to defend causes that were, for the moment, unpopular.9
And, so, how do we cope?
Fortunately, we understand bullying. The bully doesn’t take over the entire school and won’t have the power to take over one’s entire life if the behavior is brought out in the open and openly discussed. But bullies need to accept responsibility, which is what Sen. Harry Reid of Nevada and other legislators urged President-elect Trump to do in days immediately following the election.10 They have called on him to discourage the fear, anger, and violence leading up to and following the election. This action on Mr. Trump’s part would promote a vitally needed national healing process.
Ultimately, this is “the land of the free, the home of the brave …” and we will do what we have always done as psychiatrists and mental health professionals who help to heal wounds. Not all of us will participate in social justice initiatives. However, each of us can listen with intense compassion and interest to those with whom we identify politically and to those whose views diverge from our own. This is our most potent tool in a conflict where we don’t understand the motives of unpredictable leaders or their followers. It is only with this skilled listening that a space is created in which each “other” hears the “other.” This is where real healing begins.
The views expressed in this article are solely those of the authors, and are not meant to represent the views of the American Psychiatric Association, Novant Health, Clinical Psychiatry News, or any other organization.
References
1. http://billposters/story/trump-virus-dark-age-unreason
2. http://blackdoctor.org/495036/national-medical-association-statement-on-police-use-of-force
3. http://www.nytimes.com/interactive/2016/01/28/upshot/donald-trump-twitter-insults.html?_r=0
4. https://www.splcenter.org/hatewatch/2016/11/11/over-200-incidents-hateful-harassment-and-intimidation-election-day
5. http://www.obamaonthecouch.com
6. http://www.nytimes.com/2016/10/26/us/politics/donald-trump-interviews.html
7. “The Nature of Prejudice,” (New York: Perseus Books Publishing, 1979).
8. DBT® Skills Training Handouts and Worksheets, Second Edition (New York: The Guilford Press, 2014).
9. http://billmoyers.com/story/trump-virus-dark-age-unreason
10. http://www.reid.senate.gov/press_releases/2016-11-11-reid-statement-on-the-election-of-donald-trump#.WC0iA6IrKgR
Dr. Dunlap, a psychiatrist and psychoanalyst who practices in Washington, is the immediate past president of the Washington Psychiatric Society, and associate clinical professor of psychiatry and behavioral sciences at George Washington University, Washington. She is interested in the role “difference” – race, culture, and ethnicity – plays in interpersonal relationships and group dynamics. Dr. Ifill-Taylor, a child, adolescent, and adult psychiatrist, is in practice as a medical director in Charlotte, N.C. Previously, she was in private practice in the Washington area and worked as a staff psychiatrist for the Department of Veterans Affairs. She is particularly interested in the effect of our social, political, and occupational environment on mental and physical health.
One of us practices in the “new south” community of Charlotte, N.C., “a red state”; the other is in the “blue bubble” of Washington. In our respective polarized zones, the divergent reactions we heard about the presidential candidates were akin to projective responses to Rorschach tests.
As mental health clinicians, we knew that the country was wounded and in need of healing long before the outcome of the unconventional and acrimonious 2016 American presidential race. So, we were concerned about how patients, clinicians, and divergent communities would go about healing after an 18-month pre-election slugfest that revealed bigotry that persists more than 150 years after the Civil War.
Background of ‘two sides’
None of the nasty rhetoric delivered by our now president-elect or the clearly defensive responses we heard from our former secretary of state were going to be easily forgotten after Nov. 8, 2016. As the process unfolded, however, the voice of psychiatry, with some notable exceptions (the blog of Justin Frank, MD, for example), was absent from the public dialogue.
Nevertheless, writing in June of this year, Bill Moyers and Michael Winship summed up the private assessment of many professionals and the fears for many of a Trump presidency:
There is a virus infecting our politics and right now it’s flourishing with a scarlet fever. It feeds on fear, paranoia and bigotry. All that was required for it to spread was a timely opportunity – and an opportunist with no scruples. ... There have been stretches of history when this virus lay dormant. ... Today its carrier is Donald Trump, but others came before him: narcissistic demagogues who lie and distort in pursuit of power and self-promotion. Bullies all, swaggering across the landscape with fistfuls of false promises, smears, innuendo and hatred for others, spite and spittle for anyone of a different race, faith, gender, or nationality.1
Alternatively, some had a smoldering fear of the progressive agenda to bring “others” – more women, African Americans, Latinos, the LGBTQ community, Muslims, and the disabled – securely under the tent of American democracy. Others, especially the underemployed cohort in neglected and struggling communities in Middle America, were simply opposed to a continuation of “politics as usual,” a.k.a. Hillary Clinton, and were desperate for change.
The opposition views were summed up in the innuendo of the slogan: “Make America Great Again.” By the election, the tensions had begun to resemble the aggressive spirit of a sporting event: It’s “us” versus “them.”
Causes of concern
In the months leading up to the election, violent events strained the societal divisions. The police use of force2 resulted in the near-daily deaths of African American men and women and other people of color at the hands of police officers. The events built on a long and growing list of violent acts – the racially motivated shootings of nine men and women in a Charleston, S.C., church, the bombing injuries and deaths at the Boston Marathon, the shooting deaths of 20 children and 6 adults at Sandy Hook Elementary School, the homophobia-motivated shootings in a Florida nightclub – that have heightened levels of fear, anxiety, and concern for personal and family safety. For many, life has felt fragile and out of control, the perfect setup to motivate the electorate to cast their votes for the person they imagined had the most power and most interest in restoring their sense of control over their lives and, ultimately, their sense of safety.
Why the fear? A psychodynamic analysis
As psychiatrists trained in psychodynamic theory, we are quite familiar with the concept of identifying with the aggressor as a means of coping. The classic example is when a child watches his or her parents in an abusive relationship and identifies with the abusive parent in an attempt to avoid identifying with the victimized parent.
This dynamic is one that seems to have played out during this presidential election. By October 2016, Donald J. Trump already reportedly had insulted more than 280 people, places, and things on Twitter.3 Despite the evidence that Mr. Trump verbally bullied not only his opponents, but also the media, Latinos, women, the LGBTQ community, the Republican Party (his claimed party), and Muslims, people came out in numbers high enough to make him America’s president-elect. In the classic process of bullying his perceived enemies, those considered “the other,” he assigned names such as “crooked Hillary,” “little Marco,” and “lyin’ Ted” – just as a bully at school assigns names to the kid he’s decided does not have enough worth to be called by his given name.
He depicted women who accused him of sexual assault as either not being pretty enough to be worthy of assault or self-serving in their public accusations. Mexicans entering this country were referred to as “rapists and thugs.” African Americans were told that their lives are so bad that they “have nothing to lose” if they voted for a candidate who talked about erecting a wall to block out other people of color, and changing immigration laws that would banish an entire religion from entering our country.
The ‘blue bubble’ – Those who voted for Mrs. Clinton
So … this happened. And, in our consulting rooms, we are seeing a stark increase in the numbers of individuals, couples, and families reporting overwhelming anxiety, sadness, and a sense of de-realization (“it’s surreal”). At the core of their anxiety is concern for self, family, and friends as well as concern for the country as a whole.
The post-election notions that families would be immediately broken up, parents deported, the Affordable Care Act immediately dismantled, and countries bombed immediately after Election Day did not become realities. However, there is valid reason to be concerned. The Southern Poverty Law Center has noted a significant increase in post-election hate crimes throughout the nation.4
The new South ‘red states’ – those who voted for Mr. Trump
Trump supporters are feeling victorious because their “underdog” candidate ran an unconventional presidential campaign and won. However, some who voted for Mr. Trump will at some point experience anxiety when the excitement of “winning” wears off. Psychoanalyst Justin Frank speaks to this and more in his Nov. 9, 2016, blog in which he concludes: “While we mourn and blame others and ourselves for our American tragedy, Trump voters must eventually look at themselves in the mirror and exclaim, ‘what have we done?’ ”5
In his Oct. 25, 2016, New York Times article, Michael Barbaro summarized the behaviors that will become increasingly of concern to all as Mr. Trump accepts the oath of office:
The intense ambitions and undisciplined behaviors of Mr. Trump have confounded even those close to him.... In interviews, Mr. Trump makes clear just how difficult it is for him to imagine – let alone accept – defeat....
“I never had a failure,” Mr. Trump said in one of the interviews, despite his repeated corporate bankruptcies and business setbacks, “because I always turned a failure into a success.”6
This fundamental inability to accept responsibility and the attempt to distort reality is something that must concern each of us, regardless of our ideological differences.
Distress tolerance as a model for healing
Even before the outcome of the election, we were hearing from patients who did not feel safe and who reported being “terrified” about what our country might become. This is where a focus on processing the pain and decreasing anxiety is necessary. This is not an anxiety we can medicate with anxiolytics or rationalize by telling ourselves and our patients that the best man won “fair and square.” We have each – by this time – experienced patients who are quite shaken by this turn of events.
Although it has not received much press, many consider Mr. Trump’s victory to be, in part, a “white backlash.” Many supporters of Mr. Trump have felt too ashamed to publicly admit their support for a candidate who at least by innuendo incited fear, anger, and violence. This failure has created an anxiety reminiscent of the daytime anxiety experienced by people who survived nighttime lynchings in small Southern towns. The day after the lynching, it was not unusual for African American men, women, and children to wonder if their grocer, banker, postal carrier, or sheriff had donned a white hood the night before and lynched someone in their community.
The question of survival, how to survive the unimaginable, is what most distresses people. They’ve wondered out loud whether they, their family, and friends would be attacked and/or killed by those who now feel emboldened and authorized to act on their latent aggressive impulses. And, our patients’ fears are legitimate because, unfortunately, studies show that verbal aggression is correlated with increased risk of physical violence and even murder.7
In the dialectical behavioral therapy (DBT) construct developed by Marsha M. Linehan, PhD, the goals of distress tolerance are crisis survival, reality acceptance, and then freedom.8
As we apply our skills, we are uniquely positioned to help our patients and their families survive this crisis, accept that this is our president-elect, and ultimately be free from the anxiety created by the behavior that we all witnessed. We can aid in the navigation through this storm.
Acceptance
We’re already on to reality acceptance. The reality that so many African Americans and people of color have been living is now known and experienced by many who had felt immune to being marginalized. They now understand the loss of security that accompanies overwhelming fear of being the object of verbal, emotional, and physical aggression and violence.
Some are coping by entertaining fantasies that this election outcome will be undone, that the Electoral College will not approve our president-elect when it meets on Dec. 19 or that Mr. Trump will be impeached early in this upcoming term. The results of the presidential election are unlikely to be undone, so having more than 2 months between Election Day and the inauguration to work on acceptance will be helpful. The goal here is to accept the past, be hopeful about the future, and be vigilant in the present.
Freedom
Now, on to freedom. Our goal is to have all of our patients, families, colleagues, and communities able to live without fear that our leaders are not able to apply humanitarian principles to keep all of us safe. The next few months are crucial. Americans must speak out and debride the wound that bullying intentionally causes. Just as with a school bully, Mr. Trump’s behavior has to be called what it is, not sugarcoated or normalized.
History is full of critical moments in time in which, even in our fear, we said nothing. Even the most empathic of us watched the bully at school and felt relief that his behavior was not directed toward us. But we must not avert our gaze.
Bill Moyers and Michael Winship compared Mr. Trump to Sen. Joseph McCarthy, whose reign of terror was ended when journalist Edward R. Murrow courageously spoke out in defiance of the senator. At the end of one of his segments on “See It Now,” Mr. Murrow concluded as he signed off:
We will not walk in fear, one of another. We will not be driven by fear into an age of unreason, if we dig deep in our history and our doctrine, and remember that we are not descended from fearful men — not from men who feared to write, to speak, to associate and to defend causes that were, for the moment, unpopular.9
And, so, how do we cope?
Fortunately, we understand bullying. The bully doesn’t take over the entire school and won’t have the power to take over one’s entire life if the behavior is brought out in the open and openly discussed. But bullies need to accept responsibility, which is what Sen. Harry Reid of Nevada and other legislators urged President-elect Trump to do in days immediately following the election.10 They have called on him to discourage the fear, anger, and violence leading up to and following the election. This action on Mr. Trump’s part would promote a vitally needed national healing process.
Ultimately, this is “the land of the free, the home of the brave …” and we will do what we have always done as psychiatrists and mental health professionals who help to heal wounds. Not all of us will participate in social justice initiatives. However, each of us can listen with intense compassion and interest to those with whom we identify politically and to those whose views diverge from our own. This is our most potent tool in a conflict where we don’t understand the motives of unpredictable leaders or their followers. It is only with this skilled listening that a space is created in which each “other” hears the “other.” This is where real healing begins.
The views expressed in this article are solely those of the authors, and are not meant to represent the views of the American Psychiatric Association, Novant Health, Clinical Psychiatry News, or any other organization.
References
1. http://billposters/story/trump-virus-dark-age-unreason
2. http://blackdoctor.org/495036/national-medical-association-statement-on-police-use-of-force
3. http://www.nytimes.com/interactive/2016/01/28/upshot/donald-trump-twitter-insults.html?_r=0
4. https://www.splcenter.org/hatewatch/2016/11/11/over-200-incidents-hateful-harassment-and-intimidation-election-day
5. http://www.obamaonthecouch.com
6. http://www.nytimes.com/2016/10/26/us/politics/donald-trump-interviews.html
7. “The Nature of Prejudice,” (New York: Perseus Books Publishing, 1979).
8. DBT® Skills Training Handouts and Worksheets, Second Edition (New York: The Guilford Press, 2014).
9. http://billmoyers.com/story/trump-virus-dark-age-unreason
10. http://www.reid.senate.gov/press_releases/2016-11-11-reid-statement-on-the-election-of-donald-trump#.WC0iA6IrKgR
Dr. Dunlap, a psychiatrist and psychoanalyst who practices in Washington, is the immediate past president of the Washington Psychiatric Society, and associate clinical professor of psychiatry and behavioral sciences at George Washington University, Washington. She is interested in the role “difference” – race, culture, and ethnicity – plays in interpersonal relationships and group dynamics. Dr. Ifill-Taylor, a child, adolescent, and adult psychiatrist, is in practice as a medical director in Charlotte, N.C. Previously, she was in private practice in the Washington area and worked as a staff psychiatrist for the Department of Veterans Affairs. She is particularly interested in the effect of our social, political, and occupational environment on mental and physical health.
One of us practices in the “new south” community of Charlotte, N.C., “a red state”; the other is in the “blue bubble” of Washington. In our respective polarized zones, the divergent reactions we heard about the presidential candidates were akin to projective responses to Rorschach tests.
As mental health clinicians, we knew that the country was wounded and in need of healing long before the outcome of the unconventional and acrimonious 2016 American presidential race. So, we were concerned about how patients, clinicians, and divergent communities would go about healing after an 18-month pre-election slugfest that revealed bigotry that persists more than 150 years after the Civil War.
Background of ‘two sides’
None of the nasty rhetoric delivered by our now president-elect or the clearly defensive responses we heard from our former secretary of state were going to be easily forgotten after Nov. 8, 2016. As the process unfolded, however, the voice of psychiatry, with some notable exceptions (the blog of Justin Frank, MD, for example), was absent from the public dialogue.
Nevertheless, writing in June of this year, Bill Moyers and Michael Winship summed up the private assessment of many professionals and the fears for many of a Trump presidency:
There is a virus infecting our politics and right now it’s flourishing with a scarlet fever. It feeds on fear, paranoia and bigotry. All that was required for it to spread was a timely opportunity – and an opportunist with no scruples. ... There have been stretches of history when this virus lay dormant. ... Today its carrier is Donald Trump, but others came before him: narcissistic demagogues who lie and distort in pursuit of power and self-promotion. Bullies all, swaggering across the landscape with fistfuls of false promises, smears, innuendo and hatred for others, spite and spittle for anyone of a different race, faith, gender, or nationality.1
Alternatively, some had a smoldering fear of the progressive agenda to bring “others” – more women, African Americans, Latinos, the LGBTQ community, Muslims, and the disabled – securely under the tent of American democracy. Others, especially the underemployed cohort in neglected and struggling communities in Middle America, were simply opposed to a continuation of “politics as usual,” a.k.a. Hillary Clinton, and were desperate for change.
The opposition views were summed up in the innuendo of the slogan: “Make America Great Again.” By the election, the tensions had begun to resemble the aggressive spirit of a sporting event: It’s “us” versus “them.”
Causes of concern
In the months leading up to the election, violent events strained the societal divisions. The police use of force2 resulted in the near-daily deaths of African American men and women and other people of color at the hands of police officers. The events built on a long and growing list of violent acts – the racially motivated shootings of nine men and women in a Charleston, S.C., church, the bombing injuries and deaths at the Boston Marathon, the shooting deaths of 20 children and 6 adults at Sandy Hook Elementary School, the homophobia-motivated shootings in a Florida nightclub – that have heightened levels of fear, anxiety, and concern for personal and family safety. For many, life has felt fragile and out of control, the perfect setup to motivate the electorate to cast their votes for the person they imagined had the most power and most interest in restoring their sense of control over their lives and, ultimately, their sense of safety.
Why the fear? A psychodynamic analysis
As psychiatrists trained in psychodynamic theory, we are quite familiar with the concept of identifying with the aggressor as a means of coping. The classic example is when a child watches his or her parents in an abusive relationship and identifies with the abusive parent in an attempt to avoid identifying with the victimized parent.
This dynamic is one that seems to have played out during this presidential election. By October 2016, Donald J. Trump already reportedly had insulted more than 280 people, places, and things on Twitter.3 Despite the evidence that Mr. Trump verbally bullied not only his opponents, but also the media, Latinos, women, the LGBTQ community, the Republican Party (his claimed party), and Muslims, people came out in numbers high enough to make him America’s president-elect. In the classic process of bullying his perceived enemies, those considered “the other,” he assigned names such as “crooked Hillary,” “little Marco,” and “lyin’ Ted” – just as a bully at school assigns names to the kid he’s decided does not have enough worth to be called by his given name.
He depicted women who accused him of sexual assault as either not being pretty enough to be worthy of assault or self-serving in their public accusations. Mexicans entering this country were referred to as “rapists and thugs.” African Americans were told that their lives are so bad that they “have nothing to lose” if they voted for a candidate who talked about erecting a wall to block out other people of color, and changing immigration laws that would banish an entire religion from entering our country.
The ‘blue bubble’ – Those who voted for Mrs. Clinton
So … this happened. And, in our consulting rooms, we are seeing a stark increase in the numbers of individuals, couples, and families reporting overwhelming anxiety, sadness, and a sense of de-realization (“it’s surreal”). At the core of their anxiety is concern for self, family, and friends as well as concern for the country as a whole.
The post-election notions that families would be immediately broken up, parents deported, the Affordable Care Act immediately dismantled, and countries bombed immediately after Election Day did not become realities. However, there is valid reason to be concerned. The Southern Poverty Law Center has noted a significant increase in post-election hate crimes throughout the nation.4
The new South ‘red states’ – those who voted for Mr. Trump
Trump supporters are feeling victorious because their “underdog” candidate ran an unconventional presidential campaign and won. However, some who voted for Mr. Trump will at some point experience anxiety when the excitement of “winning” wears off. Psychoanalyst Justin Frank speaks to this and more in his Nov. 9, 2016, blog in which he concludes: “While we mourn and blame others and ourselves for our American tragedy, Trump voters must eventually look at themselves in the mirror and exclaim, ‘what have we done?’ ”5
In his Oct. 25, 2016, New York Times article, Michael Barbaro summarized the behaviors that will become increasingly of concern to all as Mr. Trump accepts the oath of office:
The intense ambitions and undisciplined behaviors of Mr. Trump have confounded even those close to him.... In interviews, Mr. Trump makes clear just how difficult it is for him to imagine – let alone accept – defeat....
“I never had a failure,” Mr. Trump said in one of the interviews, despite his repeated corporate bankruptcies and business setbacks, “because I always turned a failure into a success.”6
This fundamental inability to accept responsibility and the attempt to distort reality is something that must concern each of us, regardless of our ideological differences.
Distress tolerance as a model for healing
Even before the outcome of the election, we were hearing from patients who did not feel safe and who reported being “terrified” about what our country might become. This is where a focus on processing the pain and decreasing anxiety is necessary. This is not an anxiety we can medicate with anxiolytics or rationalize by telling ourselves and our patients that the best man won “fair and square.” We have each – by this time – experienced patients who are quite shaken by this turn of events.
Although it has not received much press, many consider Mr. Trump’s victory to be, in part, a “white backlash.” Many supporters of Mr. Trump have felt too ashamed to publicly admit their support for a candidate who at least by innuendo incited fear, anger, and violence. This failure has created an anxiety reminiscent of the daytime anxiety experienced by people who survived nighttime lynchings in small Southern towns. The day after the lynching, it was not unusual for African American men, women, and children to wonder if their grocer, banker, postal carrier, or sheriff had donned a white hood the night before and lynched someone in their community.
The question of survival, how to survive the unimaginable, is what most distresses people. They’ve wondered out loud whether they, their family, and friends would be attacked and/or killed by those who now feel emboldened and authorized to act on their latent aggressive impulses. And, our patients’ fears are legitimate because, unfortunately, studies show that verbal aggression is correlated with increased risk of physical violence and even murder.7
In the dialectical behavioral therapy (DBT) construct developed by Marsha M. Linehan, PhD, the goals of distress tolerance are crisis survival, reality acceptance, and then freedom.8
As we apply our skills, we are uniquely positioned to help our patients and their families survive this crisis, accept that this is our president-elect, and ultimately be free from the anxiety created by the behavior that we all witnessed. We can aid in the navigation through this storm.
Acceptance
We’re already on to reality acceptance. The reality that so many African Americans and people of color have been living is now known and experienced by many who had felt immune to being marginalized. They now understand the loss of security that accompanies overwhelming fear of being the object of verbal, emotional, and physical aggression and violence.
Some are coping by entertaining fantasies that this election outcome will be undone, that the Electoral College will not approve our president-elect when it meets on Dec. 19 or that Mr. Trump will be impeached early in this upcoming term. The results of the presidential election are unlikely to be undone, so having more than 2 months between Election Day and the inauguration to work on acceptance will be helpful. The goal here is to accept the past, be hopeful about the future, and be vigilant in the present.
Freedom
Now, on to freedom. Our goal is to have all of our patients, families, colleagues, and communities able to live without fear that our leaders are not able to apply humanitarian principles to keep all of us safe. The next few months are crucial. Americans must speak out and debride the wound that bullying intentionally causes. Just as with a school bully, Mr. Trump’s behavior has to be called what it is, not sugarcoated or normalized.
History is full of critical moments in time in which, even in our fear, we said nothing. Even the most empathic of us watched the bully at school and felt relief that his behavior was not directed toward us. But we must not avert our gaze.
Bill Moyers and Michael Winship compared Mr. Trump to Sen. Joseph McCarthy, whose reign of terror was ended when journalist Edward R. Murrow courageously spoke out in defiance of the senator. At the end of one of his segments on “See It Now,” Mr. Murrow concluded as he signed off:
We will not walk in fear, one of another. We will not be driven by fear into an age of unreason, if we dig deep in our history and our doctrine, and remember that we are not descended from fearful men — not from men who feared to write, to speak, to associate and to defend causes that were, for the moment, unpopular.9
And, so, how do we cope?
Fortunately, we understand bullying. The bully doesn’t take over the entire school and won’t have the power to take over one’s entire life if the behavior is brought out in the open and openly discussed. But bullies need to accept responsibility, which is what Sen. Harry Reid of Nevada and other legislators urged President-elect Trump to do in days immediately following the election.10 They have called on him to discourage the fear, anger, and violence leading up to and following the election. This action on Mr. Trump’s part would promote a vitally needed national healing process.
Ultimately, this is “the land of the free, the home of the brave …” and we will do what we have always done as psychiatrists and mental health professionals who help to heal wounds. Not all of us will participate in social justice initiatives. However, each of us can listen with intense compassion and interest to those with whom we identify politically and to those whose views diverge from our own. This is our most potent tool in a conflict where we don’t understand the motives of unpredictable leaders or their followers. It is only with this skilled listening that a space is created in which each “other” hears the “other.” This is where real healing begins.
The views expressed in this article are solely those of the authors, and are not meant to represent the views of the American Psychiatric Association, Novant Health, Clinical Psychiatry News, or any other organization.
References
1. http://billposters/story/trump-virus-dark-age-unreason
2. http://blackdoctor.org/495036/national-medical-association-statement-on-police-use-of-force
3. http://www.nytimes.com/interactive/2016/01/28/upshot/donald-trump-twitter-insults.html?_r=0
4. https://www.splcenter.org/hatewatch/2016/11/11/over-200-incidents-hateful-harassment-and-intimidation-election-day
5. http://www.obamaonthecouch.com
6. http://www.nytimes.com/2016/10/26/us/politics/donald-trump-interviews.html
7. “The Nature of Prejudice,” (New York: Perseus Books Publishing, 1979).
8. DBT® Skills Training Handouts and Worksheets, Second Edition (New York: The Guilford Press, 2014).
9. http://billmoyers.com/story/trump-virus-dark-age-unreason
10. http://www.reid.senate.gov/press_releases/2016-11-11-reid-statement-on-the-election-of-donald-trump#.WC0iA6IrKgR
Dr. Dunlap, a psychiatrist and psychoanalyst who practices in Washington, is the immediate past president of the Washington Psychiatric Society, and associate clinical professor of psychiatry and behavioral sciences at George Washington University, Washington. She is interested in the role “difference” – race, culture, and ethnicity – plays in interpersonal relationships and group dynamics. Dr. Ifill-Taylor, a child, adolescent, and adult psychiatrist, is in practice as a medical director in Charlotte, N.C. Previously, she was in private practice in the Washington area and worked as a staff psychiatrist for the Department of Veterans Affairs. She is particularly interested in the effect of our social, political, and occupational environment on mental and physical health.
Hospital factors play key role in readmission risk after surgery
CORONADO, CALIF. – Variation in readmission risk across hospitals following certain surgical procedures is more attributable to hospital factors than to patient characteristics, results from a large analysis demonstrated.
Such is the impact of the care delivery macro environment (CDM), which Sarah A. Brownlee and coauthors defined as a series of complex interactions between patient characteristics and imposed hospital attributes than can impact patient outcomes postoperatively.
The purpose of the current study was to determine the relative contribution of various aspects of the CDM to 1-year readmission risk after surgery. Working with colleagues Anai Kothari, MD, and Paul Kuo MD, in the One:MAP Section of Clinical informatics and Analytics in the department of surgery at Loyola University Medical Center, Ms. Brownlee analyzed the Healthcare Cost and Utilization Project State Inpatient Databases from Florida, New York, and Washington between 2009 and 2013, which were linked to the American Hospital Association Annual Survey from that same time period.
The researchers used smoothed hazard estimates to determine all-cause readmission in the year after surgery, and multilevel survival models with shared frailty to determine the relative impact of hospital versus patient characteristics on the heterogeneity of readmission risk between hospitals. They limited the analysis to patients aged 18 years and older who underwent one the following procedures: abdominal aortic aneurysm repair, pancreatectomy, colectomy, coronary artery bypass graft, and total hip arthroplasty.
Ms. Brownlee reported results from 502,157 patients who underwent surgical procedures at 347 hospitals. The 1-year readmission rate was 23.5%, and ranged from 12% to 36% across procedures. After controlling for procedure, the researchers observed a 7.9% variation in readmission risk between hospitals. Staffing accounted for 9.8% of variance, followed by hospital structural characteristics such as teaching status and clinical programs (7.5%), patient ZIP code (3.8%), hospital perioperative resources such as inpatient rehab (2.9%), hospital volume (2.8%), and patient clinical characteristics (2.1%). The following hospital characteristics were significantly associated with a lower risk of 1-year readmission: high physician/bed ratio (hazard ratio 0.85; P = .00017); transplant status (HR 0.87; P = .022); high-income ZIP code (HR 0.89; P less than .001); high nurse bed/bed ratio (HR 0.90; P = .047), and cancer center designation (HR 0.93; P = .021).
“Compared to patient clinical characteristics, hospital factors such as staffing ratios, perioperative resources, and structural elements account for more variation in postoperative outcomes,” Ms. Brownlee concluded. “However, it’s important to note that in the present study, over 70% of variation in readmission rates is not explained by the covariates that we analyzed. It’s possible that there are other factors we need to consider. That’s where the direction of this research is going. Much of the variation in readmission risk across hospitals cannot be characterized with currently utilized administrative data.”
The National Institutes of Health provided funding for the study. Ms. Brownlee reported having no financial disclosures.
CORONADO, CALIF. – Variation in readmission risk across hospitals following certain surgical procedures is more attributable to hospital factors than to patient characteristics, results from a large analysis demonstrated.
Such is the impact of the care delivery macro environment (CDM), which Sarah A. Brownlee and coauthors defined as a series of complex interactions between patient characteristics and imposed hospital attributes than can impact patient outcomes postoperatively.
The purpose of the current study was to determine the relative contribution of various aspects of the CDM to 1-year readmission risk after surgery. Working with colleagues Anai Kothari, MD, and Paul Kuo MD, in the One:MAP Section of Clinical informatics and Analytics in the department of surgery at Loyola University Medical Center, Ms. Brownlee analyzed the Healthcare Cost and Utilization Project State Inpatient Databases from Florida, New York, and Washington between 2009 and 2013, which were linked to the American Hospital Association Annual Survey from that same time period.
The researchers used smoothed hazard estimates to determine all-cause readmission in the year after surgery, and multilevel survival models with shared frailty to determine the relative impact of hospital versus patient characteristics on the heterogeneity of readmission risk between hospitals. They limited the analysis to patients aged 18 years and older who underwent one the following procedures: abdominal aortic aneurysm repair, pancreatectomy, colectomy, coronary artery bypass graft, and total hip arthroplasty.
Ms. Brownlee reported results from 502,157 patients who underwent surgical procedures at 347 hospitals. The 1-year readmission rate was 23.5%, and ranged from 12% to 36% across procedures. After controlling for procedure, the researchers observed a 7.9% variation in readmission risk between hospitals. Staffing accounted for 9.8% of variance, followed by hospital structural characteristics such as teaching status and clinical programs (7.5%), patient ZIP code (3.8%), hospital perioperative resources such as inpatient rehab (2.9%), hospital volume (2.8%), and patient clinical characteristics (2.1%). The following hospital characteristics were significantly associated with a lower risk of 1-year readmission: high physician/bed ratio (hazard ratio 0.85; P = .00017); transplant status (HR 0.87; P = .022); high-income ZIP code (HR 0.89; P less than .001); high nurse bed/bed ratio (HR 0.90; P = .047), and cancer center designation (HR 0.93; P = .021).
“Compared to patient clinical characteristics, hospital factors such as staffing ratios, perioperative resources, and structural elements account for more variation in postoperative outcomes,” Ms. Brownlee concluded. “However, it’s important to note that in the present study, over 70% of variation in readmission rates is not explained by the covariates that we analyzed. It’s possible that there are other factors we need to consider. That’s where the direction of this research is going. Much of the variation in readmission risk across hospitals cannot be characterized with currently utilized administrative data.”
The National Institutes of Health provided funding for the study. Ms. Brownlee reported having no financial disclosures.
CORONADO, CALIF. – Variation in readmission risk across hospitals following certain surgical procedures is more attributable to hospital factors than to patient characteristics, results from a large analysis demonstrated.
Such is the impact of the care delivery macro environment (CDM), which Sarah A. Brownlee and coauthors defined as a series of complex interactions between patient characteristics and imposed hospital attributes than can impact patient outcomes postoperatively.
The purpose of the current study was to determine the relative contribution of various aspects of the CDM to 1-year readmission risk after surgery. Working with colleagues Anai Kothari, MD, and Paul Kuo MD, in the One:MAP Section of Clinical informatics and Analytics in the department of surgery at Loyola University Medical Center, Ms. Brownlee analyzed the Healthcare Cost and Utilization Project State Inpatient Databases from Florida, New York, and Washington between 2009 and 2013, which were linked to the American Hospital Association Annual Survey from that same time period.
The researchers used smoothed hazard estimates to determine all-cause readmission in the year after surgery, and multilevel survival models with shared frailty to determine the relative impact of hospital versus patient characteristics on the heterogeneity of readmission risk between hospitals. They limited the analysis to patients aged 18 years and older who underwent one the following procedures: abdominal aortic aneurysm repair, pancreatectomy, colectomy, coronary artery bypass graft, and total hip arthroplasty.
Ms. Brownlee reported results from 502,157 patients who underwent surgical procedures at 347 hospitals. The 1-year readmission rate was 23.5%, and ranged from 12% to 36% across procedures. After controlling for procedure, the researchers observed a 7.9% variation in readmission risk between hospitals. Staffing accounted for 9.8% of variance, followed by hospital structural characteristics such as teaching status and clinical programs (7.5%), patient ZIP code (3.8%), hospital perioperative resources such as inpatient rehab (2.9%), hospital volume (2.8%), and patient clinical characteristics (2.1%). The following hospital characteristics were significantly associated with a lower risk of 1-year readmission: high physician/bed ratio (hazard ratio 0.85; P = .00017); transplant status (HR 0.87; P = .022); high-income ZIP code (HR 0.89; P less than .001); high nurse bed/bed ratio (HR 0.90; P = .047), and cancer center designation (HR 0.93; P = .021).
“Compared to patient clinical characteristics, hospital factors such as staffing ratios, perioperative resources, and structural elements account for more variation in postoperative outcomes,” Ms. Brownlee concluded. “However, it’s important to note that in the present study, over 70% of variation in readmission rates is not explained by the covariates that we analyzed. It’s possible that there are other factors we need to consider. That’s where the direction of this research is going. Much of the variation in readmission risk across hospitals cannot be characterized with currently utilized administrative data.”
The National Institutes of Health provided funding for the study. Ms. Brownlee reported having no financial disclosures.
AT WSA 2016
Key clinical point:
Major finding: Staffing accounted for 9.8% of variance in readmission risk between hospitals, followed by hospital structural characteristics such as teaching status and clinical programs (7.5%).
Data source: Results from 502,157 patients who underwent surgical procedures at 347 hospitals in three states.
Disclosures: The National Institutes of Health provided funding for the study. Ms. Brownlee reported having no financial disclosures.
Recovery path complicated for trauma patients with VTE
CORONADO, CALIF. – Patients who develop a venous thromboembolism (VTE) following severe hemorrhage are more susceptible to complications, compared with their counterparts who do not; they also exhibit hypercoagulability and enhanced platelet function at admission, and have delayed recovery of coagulation and platelet function following injury.
Those are the key findings from a secondary analysis of data from the Pragmatic Randomized Optimal Platelet and Plasma Ratio (PROPPR) trial, which randomized 680 severely injured trauma patients from 12 level I trauma centers to receive 1:1:1 or 1:1:2 ratios of plasma to platelets to red blood cells (JAMA 2015;313[5]:471-82). “The prevention of VTE following traumatic injury is an ongoing challenge,” Belinda H. McCully, PhD, said at the annual meeting of the Western Surgical Association. “Despite prophylaxis, about 25% of patients present with VTE, which is associated with higher complications and an increased risk for mortality. Common risk factors for mortality include age, body mass index, extremity injury, and immobility, but the precise mechanisms that contribute to VTE development are not well understood. We do know that the three main factors contributing to thrombosis include static flow, endothelial injury, and hypercoagulability. Clinically, coagulation is the most feasible factor to assess, mainly through the use of conventional coagulation tests, thromboelastography, platelet levels, and platelet function assays.” 
Dr. McCully of the division of trauma, critical care, and acute care surgery in the department of surgery at Oregon Health & Science University, Portland, and her associates hypothesized that enhanced, earlier recovery of coagulation function is associated with increased VTE risk in severely injured trauma patients. To test this hypothesis, they conducted a secondary analysis of the PROPPR database, excluding patients who received anticoagulants, to rule out any bias against VTE development, as well as patients who died within 24 hours, to reduce the survival bias. This left 558 patients: 475 who did not develop a VTE, and 83 who did (defined as those who developed deep vein thrombosis or pulmonary embolism). Patient characteristics of interest included age, sex, BMI, mechanism of injury, and injury severity, as well as the transfusion group, the type of blood products given, and the percentage of patients given procoagulants. The investigators also assessed length of stay and complication incidence previously defined by the trial. During the trial, blood samples were taken from admission up to 72 hours and were used to asses both whole blood coagulation using thromboelastography and platelet function using the Multiplate assay.
Dr. McCully reported that VTE patients and non-VTE patients demonstrated similar admission platelet function activity and inhibition of all platelet function parameters at 24 hours (P less than .05). The onset of platelet function recovery was delayed in VTE patients, specifically for arachidonic acid, adenosine-5’-diphosphate, and collagen. Changes in thromboelastography, clot time to initiation, formation, rate of formation, and strength and index of platelet function from admission to 2 hours indicated increasing hypocoagulability (P less than .05) but suppressed clot lysis in both groups. Compared with patients in the non-VTE group, the VTE group had lower mortality (4% vs. 13%) but increased total hospital days (a mean of 30 vs. 16; P less than .05).
Adverse outcomes were also more prevalent in the VTE group, compared with the non-VTE group, and included systemic inflammatory response syndrome (82% vs. 72%), acute kidney injury (36% vs. 26%), infection (61% vs. 31%), sepsis (60% vs. 28%), and pneumonia (34% vs. 19%; P less than 0.05 for all associations). Conversely, regression analysis showed that VTE was associated only with total hospital days (odds ratio, 1.12), while adverse events were similar between the two groups. “From this we can conclude that VTE development following trauma may be attributed to hypercoagulable thromboelastography parameters and enhanced platelet function at admission, and compensatory mechanisms in response to a delayed recovery of coagulation and platelet function,” Dr. McCully said.
She acknowledged certain limitations of the study, including the fact that it was a secondary analysis of prospectively collected data. “We also plan to assess plasma markers of clot strength and fibrinolysis, which is an ongoing process,” she said. “Despite excluding patients that died within 24 hours, there was still a survival bias in the VTE group.”
The PROPPR study was supported by the National Heart, Lung, and Blood Institute and by the Department of Defense. Dr. McCully reported having no relevant financial disclosures.
CORONADO, CALIF. – Patients who develop a venous thromboembolism (VTE) following severe hemorrhage are more susceptible to complications, compared with their counterparts who do not; they also exhibit hypercoagulability and enhanced platelet function at admission, and have delayed recovery of coagulation and platelet function following injury.
Those are the key findings from a secondary analysis of data from the Pragmatic Randomized Optimal Platelet and Plasma Ratio (PROPPR) trial, which randomized 680 severely injured trauma patients from 12 level I trauma centers to receive 1:1:1 or 1:1:2 ratios of plasma to platelets to red blood cells (JAMA 2015;313[5]:471-82). “The prevention of VTE following traumatic injury is an ongoing challenge,” Belinda H. McCully, PhD, said at the annual meeting of the Western Surgical Association. “Despite prophylaxis, about 25% of patients present with VTE, which is associated with higher complications and an increased risk for mortality. Common risk factors for mortality include age, body mass index, extremity injury, and immobility, but the precise mechanisms that contribute to VTE development are not well understood. We do know that the three main factors contributing to thrombosis include static flow, endothelial injury, and hypercoagulability. Clinically, coagulation is the most feasible factor to assess, mainly through the use of conventional coagulation tests, thromboelastography, platelet levels, and platelet function assays.”
Dr. McCully of the division of trauma, critical care, and acute care surgery in the department of surgery at Oregon Health & Science University, Portland, and her associates hypothesized that enhanced, earlier recovery of coagulation function is associated with increased VTE risk in severely injured trauma patients. To test this hypothesis, they conducted a secondary analysis of the PROPPR database, excluding patients who received anticoagulants, to rule out any bias against VTE development, as well as patients who died within 24 hours, to reduce the survival bias. This left 558 patients: 475 who did not develop a VTE, and 83 who did (defined as those who developed deep vein thrombosis or pulmonary embolism). Patient characteristics of interest included age, sex, BMI, mechanism of injury, and injury severity, as well as the transfusion group, the type of blood products given, and the percentage of patients given procoagulants. The investigators also assessed length of stay and complication incidence previously defined by the trial. During the trial, blood samples were taken from admission up to 72 hours and were used to asses both whole blood coagulation using thromboelastography and platelet function using the Multiplate assay.
Dr. McCully reported that VTE patients and non-VTE patients demonstrated similar admission platelet function activity and inhibition of all platelet function parameters at 24 hours (P less than .05). The onset of platelet function recovery was delayed in VTE patients, specifically for arachidonic acid, adenosine-5’-diphosphate, and collagen. Changes in thromboelastography, clot time to initiation, formation, rate of formation, and strength and index of platelet function from admission to 2 hours indicated increasing hypocoagulability (P less than .05) but suppressed clot lysis in both groups. Compared with patients in the non-VTE group, the VTE group had lower mortality (4% vs. 13%) but increased total hospital days (a mean of 30 vs. 16; P less than .05).
Adverse outcomes were also more prevalent in the VTE group, compared with the non-VTE group, and included systemic inflammatory response syndrome (82% vs. 72%), acute kidney injury (36% vs. 26%), infection (61% vs. 31%), sepsis (60% vs. 28%), and pneumonia (34% vs. 19%; P less than 0.05 for all associations). Conversely, regression analysis showed that VTE was associated only with total hospital days (odds ratio, 1.12), while adverse events were similar between the two groups. “From this we can conclude that VTE development following trauma may be attributed to hypercoagulable thromboelastography parameters and enhanced platelet function at admission, and compensatory mechanisms in response to a delayed recovery of coagulation and platelet function,” Dr. McCully said.
She acknowledged certain limitations of the study, including the fact that it was a secondary analysis of prospectively collected data. “We also plan to assess plasma markers of clot strength and fibrinolysis, which is an ongoing process,” she said. “Despite excluding patients that died within 24 hours, there was still a survival bias in the VTE group.”
The PROPPR study was supported by the National Heart, Lung, and Blood Institute and by the Department of Defense. Dr. McCully reported having no relevant financial disclosures.
CORONADO, CALIF. – Patients who develop a venous thromboembolism (VTE) following severe hemorrhage are more susceptible to complications, compared with their counterparts who do not; they also exhibit hypercoagulability and enhanced platelet function at admission, and have delayed recovery of coagulation and platelet function following injury.
Those are the key findings from a secondary analysis of data from the Pragmatic Randomized Optimal Platelet and Plasma Ratio (PROPPR) trial, which randomized 680 severely injured trauma patients from 12 level I trauma centers to receive 1:1:1 or 1:1:2 ratios of plasma to platelets to red blood cells (JAMA 2015;313[5]:471-82). “The prevention of VTE following traumatic injury is an ongoing challenge,” Belinda H. McCully, PhD, said at the annual meeting of the Western Surgical Association. “Despite prophylaxis, about 25% of patients present with VTE, which is associated with higher complications and an increased risk for mortality. Common risk factors for mortality include age, body mass index, extremity injury, and immobility, but the precise mechanisms that contribute to VTE development are not well understood. We do know that the three main factors contributing to thrombosis include static flow, endothelial injury, and hypercoagulability. Clinically, coagulation is the most feasible factor to assess, mainly through the use of conventional coagulation tests, thromboelastography, platelet levels, and platelet function assays.”
Dr. McCully of the division of trauma, critical care, and acute care surgery in the department of surgery at Oregon Health & Science University, Portland, and her associates hypothesized that enhanced, earlier recovery of coagulation function is associated with increased VTE risk in severely injured trauma patients. To test this hypothesis, they conducted a secondary analysis of the PROPPR database, excluding patients who received anticoagulants, to rule out any bias against VTE development, as well as patients who died within 24 hours, to reduce the survival bias. This left 558 patients: 475 who did not develop a VTE, and 83 who did (defined as those who developed deep vein thrombosis or pulmonary embolism). Patient characteristics of interest included age, sex, BMI, mechanism of injury, and injury severity, as well as the transfusion group, the type of blood products given, and the percentage of patients given procoagulants. The investigators also assessed length of stay and complication incidence previously defined by the trial. During the trial, blood samples were taken from admission up to 72 hours and were used to asses both whole blood coagulation using thromboelastography and platelet function using the Multiplate assay.
Dr. McCully reported that VTE patients and non-VTE patients demonstrated similar admission platelet function activity and inhibition of all platelet function parameters at 24 hours (P less than .05). The onset of platelet function recovery was delayed in VTE patients, specifically for arachidonic acid, adenosine-5’-diphosphate, and collagen. Changes in thromboelastography, clot time to initiation, formation, rate of formation, and strength and index of platelet function from admission to 2 hours indicated increasing hypocoagulability (P less than .05) but suppressed clot lysis in both groups. Compared with patients in the non-VTE group, the VTE group had lower mortality (4% vs. 13%) but increased total hospital days (a mean of 30 vs. 16; P less than .05).
Adverse outcomes were also more prevalent in the VTE group, compared with the non-VTE group, and included systemic inflammatory response syndrome (82% vs. 72%), acute kidney injury (36% vs. 26%), infection (61% vs. 31%), sepsis (60% vs. 28%), and pneumonia (34% vs. 19%; P less than 0.05 for all associations). Conversely, regression analysis showed that VTE was associated only with total hospital days (odds ratio, 1.12), while adverse events were similar between the two groups. “From this we can conclude that VTE development following trauma may be attributed to hypercoagulable thromboelastography parameters and enhanced platelet function at admission, and compensatory mechanisms in response to a delayed recovery of coagulation and platelet function,” Dr. McCully said.
She acknowledged certain limitations of the study, including the fact that it was a secondary analysis of prospectively collected data. “We also plan to assess plasma markers of clot strength and fibrinolysis, which is an ongoing process,” she said. “Despite excluding patients that died within 24 hours, there was still a survival bias in the VTE group.”
The PROPPR study was supported by the National Heart, Lung, and Blood Institute and by the Department of Defense. Dr. McCully reported having no relevant financial disclosures.
AT WSA 2016
Key clinical point:
Major finding: Compared with patients in the non-VTE group, the VTE group had lower mortality (4% vs. 13%) but increased total hospital days (a mean of 30 vs. 16; P less than .05).
Data source: A secondary analysis of 558 patients from the Pragmatic Randomized Optimal Platelet and Plasma Ratio (PROPPR) trial, which randomized severely injured trauma patients from 12 level I trauma centers to receive 1:1:1 or 1:1:2 ratios of plasma to platelets to red blood cells.
Disclosures: The PROPPR study was supported by the National Heart, Lung, and Blood Institute and by the Department of Defense. Dr. McCully reported having no relevant financial disclosures.
VIDEO: Statins cut mortality in ankylosing spondylitis, psoriatic arthritis
WASHINGTON – Statins lowered all-cause mortality by 32% in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in a retrospective cohort study.
The magnitude of benefit from statins in these two disease states is greater than that found in the general population (estimated 9%-14% reduction in all-cause mortality) and than that reported in patients with rheumatoid arthritis (RA, 21% reduction), said Amar Oza, MD, a second-year rheumatology fellow at Massachusetts General Hospital and Harvard Medical School, both in Boston.
“This is a unique study. The benefit of statins has not been looked at in AS and PsA, specifically,” Dr. Oza explained. “More data are needed” to establish this benefit with certainty, he added.
The data were presented at the annual meeting of the American College of Rheumatology, and Dr. Oza discussed the findings in a video interview.
The study compared 2,904 patients with AS or PsA who initiated statins between 2000 and 2014 with 2,904 propensity-matched AS or PsA patients who did not initiate statins during that period. Patients were drawn from a United Kingdom general population database.
The investigators used a propensity score that accounted for 50 confounding variables to match the two cohorts. These variables included, but were not limited to, disease duration, socioeconomic status, body mass index, lifestyle factors, and medication use.
“This study is the first step in elucidating the benefit of statins in AS and PsA. It is a good step forward. If additional data substantiate that AS and PsA patients have a low threshold for statins, I can envision statins for both primary and secondary prevention in this patient population,” Dr. Oza stated.
The authors had no relevant financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WASHINGTON – Statins lowered all-cause mortality by 32% in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in a retrospective cohort study.
The magnitude of benefit from statins in these two disease states is greater than that found in the general population (estimated 9%-14% reduction in all-cause mortality) and than that reported in patients with rheumatoid arthritis (RA, 21% reduction), said Amar Oza, MD, a second-year rheumatology fellow at Massachusetts General Hospital and Harvard Medical School, both in Boston.
“This is a unique study. The benefit of statins has not been looked at in AS and PsA, specifically,” Dr. Oza explained. “More data are needed” to establish this benefit with certainty, he added.
The data were presented at the annual meeting of the American College of Rheumatology, and Dr. Oza discussed the findings in a video interview.
The study compared 2,904 patients with AS or PsA who initiated statins between 2000 and 2014 with 2,904 propensity-matched AS or PsA patients who did not initiate statins during that period. Patients were drawn from a United Kingdom general population database.
The investigators used a propensity score that accounted for 50 confounding variables to match the two cohorts. These variables included, but were not limited to, disease duration, socioeconomic status, body mass index, lifestyle factors, and medication use.
“This study is the first step in elucidating the benefit of statins in AS and PsA. It is a good step forward. If additional data substantiate that AS and PsA patients have a low threshold for statins, I can envision statins for both primary and secondary prevention in this patient population,” Dr. Oza stated.
The authors had no relevant financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WASHINGTON – Statins lowered all-cause mortality by 32% in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in a retrospective cohort study.
The magnitude of benefit from statins in these two disease states is greater than that found in the general population (estimated 9%-14% reduction in all-cause mortality) and than that reported in patients with rheumatoid arthritis (RA, 21% reduction), said Amar Oza, MD, a second-year rheumatology fellow at Massachusetts General Hospital and Harvard Medical School, both in Boston.
“This is a unique study. The benefit of statins has not been looked at in AS and PsA, specifically,” Dr. Oza explained. “More data are needed” to establish this benefit with certainty, he added.
The data were presented at the annual meeting of the American College of Rheumatology, and Dr. Oza discussed the findings in a video interview.
The study compared 2,904 patients with AS or PsA who initiated statins between 2000 and 2014 with 2,904 propensity-matched AS or PsA patients who did not initiate statins during that period. Patients were drawn from a United Kingdom general population database.
The investigators used a propensity score that accounted for 50 confounding variables to match the two cohorts. These variables included, but were not limited to, disease duration, socioeconomic status, body mass index, lifestyle factors, and medication use.
“This study is the first step in elucidating the benefit of statins in AS and PsA. It is a good step forward. If additional data substantiate that AS and PsA patients have a low threshold for statins, I can envision statins for both primary and secondary prevention in this patient population,” Dr. Oza stated.
The authors had no relevant financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE ACR ANNUAL MEETING
How Does Physical Activity Differ in Mild Alzheimer’s Disease?
People with Alzheimer’s disease have different daily patterns of activity, compared with healthy controls, according to research published online ahead of print October 4 in the Journal of Alzheimer’s Disease. Understanding this different daily pattern in physical activity could be key to designing interventions and improving sleep for people with early Alzheimer’s disease, perhaps by targeting more physical activity in morning, said the researchers.
Too little is known about patterns of activity for people experiencing the early stages of Alzheimer’s disease, according to Amber Watts, PhD, Assistant Professor of Clinical Psychology at the University of Kansas in Lawrence. For instance, researchers have lacked useful data about how the progression of the disease itself plays a role in diminishing day-to-day physical activity.
Vijay R. Varma, PhD, a postdoctoral fellow at the National Institute on Aging, and Dr. Watts analyzed the daily physical activity of 92 volunteers with and without mild Alzheimer’s disease at the University of Kansas’s Alzheimer’s Disease Center in Kansas City. Participants wore Actigraph GT3X+ accelerometers for a week.Mild Alzheimer’s disease was associated with less moderate-intensity physical activity, lower peak activity, and lower physical activity complexity, particularly during the morning. Mild Alzheimer’s disease was not associated with greater sedentary activity or less lower-intensity physical activity across the day after adjusting for noncognitive covariates.
The kinds of physical activity helpful to people with Alzheimer’s disease might be simple activities such as finding time to walk around the neighborhood, said Dr. Watts. “Walking is actually the best thing,” she said. “It is low risk, it is safe, anyone can do it, it doesn’t require specific equipment, it can be done anywhere. There are other light-intensity activities like stretching, tai chi, household chores, gardening, walking around the mall—those are also beneficial. People with Alzheimer’s disease do not have to go to the gym, they just need to do something that keeps them moving and keeps them from sitting continuously.”
Suggested Reading
Varma VR, Watts A. Daily physical activity patterns during the early stage of Alzheimer’s disease. J Alzheimers Dis. 2016 Oct 4 [Epub ahead of print].
People with Alzheimer’s disease have different daily patterns of activity, compared with healthy controls, according to research published online ahead of print October 4 in the Journal of Alzheimer’s Disease. Understanding this different daily pattern in physical activity could be key to designing interventions and improving sleep for people with early Alzheimer’s disease, perhaps by targeting more physical activity in morning, said the researchers.
Too little is known about patterns of activity for people experiencing the early stages of Alzheimer’s disease, according to Amber Watts, PhD, Assistant Professor of Clinical Psychology at the University of Kansas in Lawrence. For instance, researchers have lacked useful data about how the progression of the disease itself plays a role in diminishing day-to-day physical activity.
Vijay R. Varma, PhD, a postdoctoral fellow at the National Institute on Aging, and Dr. Watts analyzed the daily physical activity of 92 volunteers with and without mild Alzheimer’s disease at the University of Kansas’s Alzheimer’s Disease Center in Kansas City. Participants wore Actigraph GT3X+ accelerometers for a week.Mild Alzheimer’s disease was associated with less moderate-intensity physical activity, lower peak activity, and lower physical activity complexity, particularly during the morning. Mild Alzheimer’s disease was not associated with greater sedentary activity or less lower-intensity physical activity across the day after adjusting for noncognitive covariates.
The kinds of physical activity helpful to people with Alzheimer’s disease might be simple activities such as finding time to walk around the neighborhood, said Dr. Watts. “Walking is actually the best thing,” she said. “It is low risk, it is safe, anyone can do it, it doesn’t require specific equipment, it can be done anywhere. There are other light-intensity activities like stretching, tai chi, household chores, gardening, walking around the mall—those are also beneficial. People with Alzheimer’s disease do not have to go to the gym, they just need to do something that keeps them moving and keeps them from sitting continuously.”
Suggested Reading
Varma VR, Watts A. Daily physical activity patterns during the early stage of Alzheimer’s disease. J Alzheimers Dis. 2016 Oct 4 [Epub ahead of print].
People with Alzheimer’s disease have different daily patterns of activity, compared with healthy controls, according to research published online ahead of print October 4 in the Journal of Alzheimer’s Disease. Understanding this different daily pattern in physical activity could be key to designing interventions and improving sleep for people with early Alzheimer’s disease, perhaps by targeting more physical activity in morning, said the researchers.
Too little is known about patterns of activity for people experiencing the early stages of Alzheimer’s disease, according to Amber Watts, PhD, Assistant Professor of Clinical Psychology at the University of Kansas in Lawrence. For instance, researchers have lacked useful data about how the progression of the disease itself plays a role in diminishing day-to-day physical activity.
Vijay R. Varma, PhD, a postdoctoral fellow at the National Institute on Aging, and Dr. Watts analyzed the daily physical activity of 92 volunteers with and without mild Alzheimer’s disease at the University of Kansas’s Alzheimer’s Disease Center in Kansas City. Participants wore Actigraph GT3X+ accelerometers for a week.Mild Alzheimer’s disease was associated with less moderate-intensity physical activity, lower peak activity, and lower physical activity complexity, particularly during the morning. Mild Alzheimer’s disease was not associated with greater sedentary activity or less lower-intensity physical activity across the day after adjusting for noncognitive covariates.
The kinds of physical activity helpful to people with Alzheimer’s disease might be simple activities such as finding time to walk around the neighborhood, said Dr. Watts. “Walking is actually the best thing,” she said. “It is low risk, it is safe, anyone can do it, it doesn’t require specific equipment, it can be done anywhere. There are other light-intensity activities like stretching, tai chi, household chores, gardening, walking around the mall—those are also beneficial. People with Alzheimer’s disease do not have to go to the gym, they just need to do something that keeps them moving and keeps them from sitting continuously.”
Suggested Reading
Varma VR, Watts A. Daily physical activity patterns during the early stage of Alzheimer’s disease. J Alzheimers Dis. 2016 Oct 4 [Epub ahead of print].
REBOA may be a safe alternative to RTACC in the acute care setting
WASHINGTON – Resuscitative endovascular balloon occlusion of the aorta (REBOA) could be an acceptable alternative to thoracotomy in traumatic arrest patients who are hemorrhaging below the diaphragm, according to the results of a small pilot study which were presented by William Teeter, MD, at the annual clinical congress of the American College of Surgeons.
Furthermore, virtual simulation training sufficiently prepares surgeons to safely use the REBOA technique in the acute care setting, a separate study found. Importantly, this training has the potential to allow REBOA to become a widespread tool for surgeons regardless of their endovascular surgical experience.
Dr. Teeter presented the preliminary results of a pilot study involving 19 patients who received RTACC between 2008 and 2013 and 17 patients who received REBOA between 2013 and 2015. All study participants were trauma patients who arrived at the R Adams Cowley Shock Trauma Center in arrest or arrested shortly after arrival.
Age, gender, Glasgow Coma Scale, and injury severity score were the same or similar between the two groups, Dr. Teeter reported. Mean systolic blood pressure at admission was 14 mmHg for the REBOA group and 28 mmHg for the RTACC group; however, the majority of patients (82% of REBOA patients and 73% of RTACC patients) arrived with a blood pressure of 0, reported Dr. Teeter.
Importantly, patients in the RTACC group who had penetrating chest injury were excluded for this analysis, Dr. Teeter noted, adding that there was a slightly higher incidence of blunt trauma within the REBOA group likely due to “a change in practice at the trauma center during this time.”
All resuscitations were captured with real-time videography. Continuous vitals were also collected and analyzed.
While more RTACC patients survived to the operating room (53% vs. 68%), among the REBOA group there were more patients who experienced return of spontaneous circulation (53% vs. 37%). However, neither of these results was statistically significant.
Following occlusion of the aorta, the blood pressure measures, taken from continuous vital signs and averaged over a 15-minute period, were 80 mmHg for the REBOA group and 46 mmHg for the RTACC group. Again, this result was statistically insignificant but trended toward favoring REBOA.
Overall, patient survival was dismal. Only one patient who received REBOA survived.
Following Dr. Teeter’s presentation, the study’s assigned discussant, Nicole A. Stassen, MD, of the University of Rochester Medical Center, N.Y., noted that while post-occlusion blood pressure was higher for the REBOA group it seemed not to matter as the majority of patients did not survive. Dr. Stassen also asked if these preliminary results were sufficient to inform or change clinical practice.
In response, Dr. Teeter explained that the pilot study was conducted at a time when the literature was unclear about how patients would respond to open versus endovascular occlusion, and this data helped guide further research and resuscitation efforts.
“At our center there has been a marked change in practice regarding which patients receive resuscitative thoracotomy and which get REBOA,” he added and concluded that “these and previous data suggest that the time performing thoracotomy for resuscitation purposes may be better spent performing CPR with REBOA.”
At the very least, this pilot study demonstrated that “REBOA may be an acceptable alternative to RTACC.” Further analysis of larger study populations will be published soon and will show that REBOA may be preferred over RTACC, according to Dr. Teeter.
A major hindrance to wider-spread REBOA use in the United States is the lack of endovascular training for surgeons during residency which has resulted in a limited number of surgeons who can perform the REBOA technique and a limited number of surgeons who can teach the procedure to others, said Dr. Hampton.
In lieu of experience, formalized 1- or 2-day endovascular simulation courses, such as BEST, were created to prepare surgeons to use techniques such as REBOA. Prior validation studies, including those conducted by researchers at the University of Maryland, demonstrated that surgeons who participated in these courses improved surgical technique and increased their surgical knowledge base, Dr. Hampton reported.
To further elucidate the benefits of these training courses on the successful use of REBOA in the acute care setting, Dr. Hampton and his associates selected nine acute care surgeons with varying endovascular surgical experience to complete the 1-day BEST course and then compared surgeons’ performances of the REBOA technique after successful course completion.
During the study, a total of 28 REBOA procedures were performed, 17 by the surgeons with no endovascular experience, and the remaining 11 by surgeons with endovascular surgical experience.
Overall, there was no difference in wire placements, sheath insertion, position or localization of balloons, or balloon inflation. In addition, there was no difference in mortality among patients, and there were no known REBOA complications during this study.
In conclusion, endovascular experience during residency is not a prerequisite for safe REBOA placement, Dr. Hampton commented.
Taken together, these two research studies are really helping to break ground on REBOA use in the acute care setting, commented an audience member.
The Department of Defense funded Dr. Teeter’s study. Dr. Teeter and Dr. Hampton both reported having no disclosures.
[email protected]
On Twitter @jessnicolecraig
WASHINGTON – Resuscitative endovascular balloon occlusion of the aorta (REBOA) could be an acceptable alternative to thoracotomy in traumatic arrest patients who are hemorrhaging below the diaphragm, according to the results of a small pilot study which were presented by William Teeter, MD, at the annual clinical congress of the American College of Surgeons.
Furthermore, virtual simulation training sufficiently prepares surgeons to safely use the REBOA technique in the acute care setting, a separate study found. Importantly, this training has the potential to allow REBOA to become a widespread tool for surgeons regardless of their endovascular surgical experience.
Dr. Teeter presented the preliminary results of a pilot study involving 19 patients who received RTACC between 2008 and 2013 and 17 patients who received REBOA between 2013 and 2015. All study participants were trauma patients who arrived at the R Adams Cowley Shock Trauma Center in arrest or arrested shortly after arrival.
Age, gender, Glasgow Coma Scale, and injury severity score were the same or similar between the two groups, Dr. Teeter reported. Mean systolic blood pressure at admission was 14 mmHg for the REBOA group and 28 mmHg for the RTACC group; however, the majority of patients (82% of REBOA patients and 73% of RTACC patients) arrived with a blood pressure of 0, reported Dr. Teeter.
Importantly, patients in the RTACC group who had penetrating chest injury were excluded for this analysis, Dr. Teeter noted, adding that there was a slightly higher incidence of blunt trauma within the REBOA group likely due to “a change in practice at the trauma center during this time.”
All resuscitations were captured with real-time videography. Continuous vitals were also collected and analyzed.
While more RTACC patients survived to the operating room (53% vs. 68%), among the REBOA group there were more patients who experienced return of spontaneous circulation (53% vs. 37%). However, neither of these results was statistically significant.
Following occlusion of the aorta, the blood pressure measures, taken from continuous vital signs and averaged over a 15-minute period, were 80 mmHg for the REBOA group and 46 mmHg for the RTACC group. Again, this result was statistically insignificant but trended toward favoring REBOA.
Overall, patient survival was dismal. Only one patient who received REBOA survived.
Following Dr. Teeter’s presentation, the study’s assigned discussant, Nicole A. Stassen, MD, of the University of Rochester Medical Center, N.Y., noted that while post-occlusion blood pressure was higher for the REBOA group it seemed not to matter as the majority of patients did not survive. Dr. Stassen also asked if these preliminary results were sufficient to inform or change clinical practice.
In response, Dr. Teeter explained that the pilot study was conducted at a time when the literature was unclear about how patients would respond to open versus endovascular occlusion, and this data helped guide further research and resuscitation efforts.
“At our center there has been a marked change in practice regarding which patients receive resuscitative thoracotomy and which get REBOA,” he added and concluded that “these and previous data suggest that the time performing thoracotomy for resuscitation purposes may be better spent performing CPR with REBOA.”
At the very least, this pilot study demonstrated that “REBOA may be an acceptable alternative to RTACC.” Further analysis of larger study populations will be published soon and will show that REBOA may be preferred over RTACC, according to Dr. Teeter.
A major hindrance to wider-spread REBOA use in the United States is the lack of endovascular training for surgeons during residency which has resulted in a limited number of surgeons who can perform the REBOA technique and a limited number of surgeons who can teach the procedure to others, said Dr. Hampton.
In lieu of experience, formalized 1- or 2-day endovascular simulation courses, such as BEST, were created to prepare surgeons to use techniques such as REBOA. Prior validation studies, including those conducted by researchers at the University of Maryland, demonstrated that surgeons who participated in these courses improved surgical technique and increased their surgical knowledge base, Dr. Hampton reported.
To further elucidate the benefits of these training courses on the successful use of REBOA in the acute care setting, Dr. Hampton and his associates selected nine acute care surgeons with varying endovascular surgical experience to complete the 1-day BEST course and then compared surgeons’ performances of the REBOA technique after successful course completion.
During the study, a total of 28 REBOA procedures were performed, 17 by the surgeons with no endovascular experience, and the remaining 11 by surgeons with endovascular surgical experience.
Overall, there was no difference in wire placements, sheath insertion, position or localization of balloons, or balloon inflation. In addition, there was no difference in mortality among patients, and there were no known REBOA complications during this study.
In conclusion, endovascular experience during residency is not a prerequisite for safe REBOA placement, Dr. Hampton commented.
Taken together, these two research studies are really helping to break ground on REBOA use in the acute care setting, commented an audience member.
The Department of Defense funded Dr. Teeter’s study. Dr. Teeter and Dr. Hampton both reported having no disclosures.
[email protected]
On Twitter @jessnicolecraig
WASHINGTON – Resuscitative endovascular balloon occlusion of the aorta (REBOA) could be an acceptable alternative to thoracotomy in traumatic arrest patients who are hemorrhaging below the diaphragm, according to the results of a small pilot study which were presented by William Teeter, MD, at the annual clinical congress of the American College of Surgeons.
Furthermore, virtual simulation training sufficiently prepares surgeons to safely use the REBOA technique in the acute care setting, a separate study found. Importantly, this training has the potential to allow REBOA to become a widespread tool for surgeons regardless of their endovascular surgical experience.
Dr. Teeter presented the preliminary results of a pilot study involving 19 patients who received RTACC between 2008 and 2013 and 17 patients who received REBOA between 2013 and 2015. All study participants were trauma patients who arrived at the R Adams Cowley Shock Trauma Center in arrest or arrested shortly after arrival.
Age, gender, Glasgow Coma Scale, and injury severity score were the same or similar between the two groups, Dr. Teeter reported. Mean systolic blood pressure at admission was 14 mmHg for the REBOA group and 28 mmHg for the RTACC group; however, the majority of patients (82% of REBOA patients and 73% of RTACC patients) arrived with a blood pressure of 0, reported Dr. Teeter.
Importantly, patients in the RTACC group who had penetrating chest injury were excluded for this analysis, Dr. Teeter noted, adding that there was a slightly higher incidence of blunt trauma within the REBOA group likely due to “a change in practice at the trauma center during this time.”
All resuscitations were captured with real-time videography. Continuous vitals were also collected and analyzed.
While more RTACC patients survived to the operating room (53% vs. 68%), among the REBOA group there were more patients who experienced return of spontaneous circulation (53% vs. 37%). However, neither of these results was statistically significant.
Following occlusion of the aorta, the blood pressure measures, taken from continuous vital signs and averaged over a 15-minute period, were 80 mmHg for the REBOA group and 46 mmHg for the RTACC group. Again, this result was statistically insignificant but trended toward favoring REBOA.
Overall, patient survival was dismal. Only one patient who received REBOA survived.
Following Dr. Teeter’s presentation, the study’s assigned discussant, Nicole A. Stassen, MD, of the University of Rochester Medical Center, N.Y., noted that while post-occlusion blood pressure was higher for the REBOA group it seemed not to matter as the majority of patients did not survive. Dr. Stassen also asked if these preliminary results were sufficient to inform or change clinical practice.
In response, Dr. Teeter explained that the pilot study was conducted at a time when the literature was unclear about how patients would respond to open versus endovascular occlusion, and this data helped guide further research and resuscitation efforts.
“At our center there has been a marked change in practice regarding which patients receive resuscitative thoracotomy and which get REBOA,” he added and concluded that “these and previous data suggest that the time performing thoracotomy for resuscitation purposes may be better spent performing CPR with REBOA.”
At the very least, this pilot study demonstrated that “REBOA may be an acceptable alternative to RTACC.” Further analysis of larger study populations will be published soon and will show that REBOA may be preferred over RTACC, according to Dr. Teeter.
A major hindrance to wider-spread REBOA use in the United States is the lack of endovascular training for surgeons during residency which has resulted in a limited number of surgeons who can perform the REBOA technique and a limited number of surgeons who can teach the procedure to others, said Dr. Hampton.
In lieu of experience, formalized 1- or 2-day endovascular simulation courses, such as BEST, were created to prepare surgeons to use techniques such as REBOA. Prior validation studies, including those conducted by researchers at the University of Maryland, demonstrated that surgeons who participated in these courses improved surgical technique and increased their surgical knowledge base, Dr. Hampton reported.
To further elucidate the benefits of these training courses on the successful use of REBOA in the acute care setting, Dr. Hampton and his associates selected nine acute care surgeons with varying endovascular surgical experience to complete the 1-day BEST course and then compared surgeons’ performances of the REBOA technique after successful course completion.
During the study, a total of 28 REBOA procedures were performed, 17 by the surgeons with no endovascular experience, and the remaining 11 by surgeons with endovascular surgical experience.
Overall, there was no difference in wire placements, sheath insertion, position or localization of balloons, or balloon inflation. In addition, there was no difference in mortality among patients, and there were no known REBOA complications during this study.
In conclusion, endovascular experience during residency is not a prerequisite for safe REBOA placement, Dr. Hampton commented.
Taken together, these two research studies are really helping to break ground on REBOA use in the acute care setting, commented an audience member.
The Department of Defense funded Dr. Teeter’s study. Dr. Teeter and Dr. Hampton both reported having no disclosures.
[email protected]
On Twitter @jessnicolecraig
AT THE ACS CLINICAL CONGRESS
Key clinical point:
Major finding: More RTACC patients survived to the operating room (53% vs. 68%), but more REBOA patients experienced return of spontaneous circulation (53% vs. 37%).
Data source: Pilot study involving 36 trauma patients who received either RTACC or REBOA.
Disclosures: The Department of Defense funded Dr. Teeter’s study. Dr. Teeter and Dr. Hampton both reported having no disclosures.
Report Provides Update on Alzheimer’s Disease Drug Pipeline
WASHINGTON, DC—Fifty-seven new drugs for Alzheimer’s disease currently are in phase II studies, according to an analysis conducted by Researchers Against Alzheimer’s (RA2). Nearly twice as many mechanisms of action are being tested in phase II than in phase III clinical trials, the group said. This diverse pipeline could provide physicians, persons with Alzheimer’s disease, and their loved ones with new ways to combat the disease in the future.
Advancements in Alzheimer’s Disease Drug Development
As the development of these compounds progresses, and the science of Alzheimer’s disease drug development advances, policy makers, clinical researchers, drug developers, and other Alzheimer’s disease drug partners need to create new clinical trial infrastructure and designs that allow for rapid recruitment and testing, consistent high-quality data, and prompt data disclosure, said RA2.
“These potentially game-changing drugs on the horizon may make Alzheimer’s [disease] a manageable disease,” said George Vradenburg, Cofounder and Chair of USAgainstAlzheimer’s, a group that advocates for a cure for Alzheimer’s disease. “To assure our best shot at success, we must ensure that the necessary investments are being made to build a 21st-century infrastructure to test their effectiveness and an innovation-friendly path to market [for] those in need,” he said. 
The first RA2 pipeline analysis released in March found 17 Alzheimer’s disease drugs in phase III clinical trials planned to launch in the next five years. However, since the initial phase III pipeline report was issued, several Alzheimer’s disease drug candidates have moved from phase II to phase III clinical trials. According to the most recent analysis, 23 Alzheimer’s disease drugs are in phase III clinical trials. In all, 19 drugs could reach the market in the next five years, according to RA2.
Researchers and pharmaceutical companies are increasingly focusing on disease-modifying prevention drugs, such as those that can be administered to people at risk for Alzheimer’s disease before symptoms appear. These drugs could prevent or delay the development of dementia symptoms.
A similar approach is used to prevent people who are HIV-positive from developing AIDS symptoms. These drugs represent a different approach from symptomatic drugs, which are intended to treat Alzheimer’s disease symptoms such as agitation, cognitive loss, hallucinations, or depression.
Several changes are required to maintain a diverse pipeline of preventive and symptomatic drugs, according to the analysis, which was reviewed by academic research experts and select RA2 members. These changes include a standing, high-performance clinical trial infrastructure that allows for rapid testing and fast failure or success.
In addition, the field needs robust biomarkers that help to indicate disease severity or progression and help to assess the effectiveness of drugs in populations without any symptoms, potentially preventing the development of symptoms altogether, according to the analysis. A greater understanding of biomarker research will assist researchers and clinicians to prescribe medicines to the appropriate populations.
New end points for trials are another necessary change, said the group. Many of the current scales used in Alzheimer’s disease trials will not be effective in people in early stages of the disease, since symptoms like cognitive decline may occur late in the disease.
Clinicians and researchers also should develop mechanisms for actively sharing information about which treatments work best with certain patient populations, according to the analysis.
Finally, the field requires innovative clinical trial designs to increase flexibility for drug developers. Such designs include adaptive trials that are modified based on patient outcomes, as well as trials of combinations of novel treatments. The latter trials could include drugs with demonstrated target engagement, but without efficacy as monotherapy.
Phase II/III and Phase III Drug Trials
Trials of several phase II/III drugs and one phase III drug will be completed in 2017. The phase II/III treatments include AC-1204, an oral drug intended for patients with mild to moderate Alzheimer’s disease that improves mitochondrial metabolism through chronic ketosis. A combination of albumin and immunoglobulin is being studied for patients with mild to moderate Alzheimer’s disease. It is an IV immunosuppressant with possible antiamyloid antibodies and albumin-binding capacity. Finally, a phase III trial of suvorexant, an oral orexin receptor antagonist under investigation for patients with Alzheimer’s disease and insomnia, will conclude in 2017.
“I am encouraged to see such a range of approaches to treating Alzheimer’s [disease] in phase II development,” said David Morgan, PhD, CEO of the Byrd Alzheimer Institute at the University of South Florida in Tampa. “There is much work that still needs to be done, but the drugs in phase II clinical trials offer a great deal of hope for the future,” he added.
—Erica Tricarico
Suggested Reading
Jacobson LH, Callander GE, Hoyer D. Suvorexant for the treatment of insomnia. Expert Rev Clin Pharmacol. 2014; 7(6):711-730.
Cummings J, Aisen PS, DuBois B, et al. Drug development in Alzheimer’s disease: the path to 2025. Alzheimers Res Ther. 2016;8:39.
WASHINGTON, DC—Fifty-seven new drugs for Alzheimer’s disease currently are in phase II studies, according to an analysis conducted by Researchers Against Alzheimer’s (RA2). Nearly twice as many mechanisms of action are being tested in phase II than in phase III clinical trials, the group said. This diverse pipeline could provide physicians, persons with Alzheimer’s disease, and their loved ones with new ways to combat the disease in the future.
Advancements in Alzheimer’s Disease Drug Development
As the development of these compounds progresses, and the science of Alzheimer’s disease drug development advances, policy makers, clinical researchers, drug developers, and other Alzheimer’s disease drug partners need to create new clinical trial infrastructure and designs that allow for rapid recruitment and testing, consistent high-quality data, and prompt data disclosure, said RA2.
“These potentially game-changing drugs on the horizon may make Alzheimer’s [disease] a manageable disease,” said George Vradenburg, Cofounder and Chair of USAgainstAlzheimer’s, a group that advocates for a cure for Alzheimer’s disease. “To assure our best shot at success, we must ensure that the necessary investments are being made to build a 21st-century infrastructure to test their effectiveness and an innovation-friendly path to market [for] those in need,” he said.
The first RA2 pipeline analysis released in March found 17 Alzheimer’s disease drugs in phase III clinical trials planned to launch in the next five years. However, since the initial phase III pipeline report was issued, several Alzheimer’s disease drug candidates have moved from phase II to phase III clinical trials. According to the most recent analysis, 23 Alzheimer’s disease drugs are in phase III clinical trials. In all, 19 drugs could reach the market in the next five years, according to RA2.
Researchers and pharmaceutical companies are increasingly focusing on disease-modifying prevention drugs, such as those that can be administered to people at risk for Alzheimer’s disease before symptoms appear. These drugs could prevent or delay the development of dementia symptoms.
A similar approach is used to prevent people who are HIV-positive from developing AIDS symptoms. These drugs represent a different approach from symptomatic drugs, which are intended to treat Alzheimer’s disease symptoms such as agitation, cognitive loss, hallucinations, or depression.
Several changes are required to maintain a diverse pipeline of preventive and symptomatic drugs, according to the analysis, which was reviewed by academic research experts and select RA2 members. These changes include a standing, high-performance clinical trial infrastructure that allows for rapid testing and fast failure or success.
In addition, the field needs robust biomarkers that help to indicate disease severity or progression and help to assess the effectiveness of drugs in populations without any symptoms, potentially preventing the development of symptoms altogether, according to the analysis. A greater understanding of biomarker research will assist researchers and clinicians to prescribe medicines to the appropriate populations.
New end points for trials are another necessary change, said the group. Many of the current scales used in Alzheimer’s disease trials will not be effective in people in early stages of the disease, since symptoms like cognitive decline may occur late in the disease.
Clinicians and researchers also should develop mechanisms for actively sharing information about which treatments work best with certain patient populations, according to the analysis.
Finally, the field requires innovative clinical trial designs to increase flexibility for drug developers. Such designs include adaptive trials that are modified based on patient outcomes, as well as trials of combinations of novel treatments. The latter trials could include drugs with demonstrated target engagement, but without efficacy as monotherapy.
Phase II/III and Phase III Drug Trials
Trials of several phase II/III drugs and one phase III drug will be completed in 2017. The phase II/III treatments include AC-1204, an oral drug intended for patients with mild to moderate Alzheimer’s disease that improves mitochondrial metabolism through chronic ketosis. A combination of albumin and immunoglobulin is being studied for patients with mild to moderate Alzheimer’s disease. It is an IV immunosuppressant with possible antiamyloid antibodies and albumin-binding capacity. Finally, a phase III trial of suvorexant, an oral orexin receptor antagonist under investigation for patients with Alzheimer’s disease and insomnia, will conclude in 2017.
“I am encouraged to see such a range of approaches to treating Alzheimer’s [disease] in phase II development,” said David Morgan, PhD, CEO of the Byrd Alzheimer Institute at the University of South Florida in Tampa. “There is much work that still needs to be done, but the drugs in phase II clinical trials offer a great deal of hope for the future,” he added.
—Erica Tricarico
Suggested Reading
Jacobson LH, Callander GE, Hoyer D. Suvorexant for the treatment of insomnia. Expert Rev Clin Pharmacol. 2014; 7(6):711-730.
Cummings J, Aisen PS, DuBois B, et al. Drug development in Alzheimer’s disease: the path to 2025. Alzheimers Res Ther. 2016;8:39.
WASHINGTON, DC—Fifty-seven new drugs for Alzheimer’s disease currently are in phase II studies, according to an analysis conducted by Researchers Against Alzheimer’s (RA2). Nearly twice as many mechanisms of action are being tested in phase II than in phase III clinical trials, the group said. This diverse pipeline could provide physicians, persons with Alzheimer’s disease, and their loved ones with new ways to combat the disease in the future.
Advancements in Alzheimer’s Disease Drug Development
As the development of these compounds progresses, and the science of Alzheimer’s disease drug development advances, policy makers, clinical researchers, drug developers, and other Alzheimer’s disease drug partners need to create new clinical trial infrastructure and designs that allow for rapid recruitment and testing, consistent high-quality data, and prompt data disclosure, said RA2.
“These potentially game-changing drugs on the horizon may make Alzheimer’s [disease] a manageable disease,” said George Vradenburg, Cofounder and Chair of USAgainstAlzheimer’s, a group that advocates for a cure for Alzheimer’s disease. “To assure our best shot at success, we must ensure that the necessary investments are being made to build a 21st-century infrastructure to test their effectiveness and an innovation-friendly path to market [for] those in need,” he said.
The first RA2 pipeline analysis released in March found 17 Alzheimer’s disease drugs in phase III clinical trials planned to launch in the next five years. However, since the initial phase III pipeline report was issued, several Alzheimer’s disease drug candidates have moved from phase II to phase III clinical trials. According to the most recent analysis, 23 Alzheimer’s disease drugs are in phase III clinical trials. In all, 19 drugs could reach the market in the next five years, according to RA2.
Researchers and pharmaceutical companies are increasingly focusing on disease-modifying prevention drugs, such as those that can be administered to people at risk for Alzheimer’s disease before symptoms appear. These drugs could prevent or delay the development of dementia symptoms.
A similar approach is used to prevent people who are HIV-positive from developing AIDS symptoms. These drugs represent a different approach from symptomatic drugs, which are intended to treat Alzheimer’s disease symptoms such as agitation, cognitive loss, hallucinations, or depression.
Several changes are required to maintain a diverse pipeline of preventive and symptomatic drugs, according to the analysis, which was reviewed by academic research experts and select RA2 members. These changes include a standing, high-performance clinical trial infrastructure that allows for rapid testing and fast failure or success.
In addition, the field needs robust biomarkers that help to indicate disease severity or progression and help to assess the effectiveness of drugs in populations without any symptoms, potentially preventing the development of symptoms altogether, according to the analysis. A greater understanding of biomarker research will assist researchers and clinicians to prescribe medicines to the appropriate populations.
New end points for trials are another necessary change, said the group. Many of the current scales used in Alzheimer’s disease trials will not be effective in people in early stages of the disease, since symptoms like cognitive decline may occur late in the disease.
Clinicians and researchers also should develop mechanisms for actively sharing information about which treatments work best with certain patient populations, according to the analysis.
Finally, the field requires innovative clinical trial designs to increase flexibility for drug developers. Such designs include adaptive trials that are modified based on patient outcomes, as well as trials of combinations of novel treatments. The latter trials could include drugs with demonstrated target engagement, but without efficacy as monotherapy.
Phase II/III and Phase III Drug Trials
Trials of several phase II/III drugs and one phase III drug will be completed in 2017. The phase II/III treatments include AC-1204, an oral drug intended for patients with mild to moderate Alzheimer’s disease that improves mitochondrial metabolism through chronic ketosis. A combination of albumin and immunoglobulin is being studied for patients with mild to moderate Alzheimer’s disease. It is an IV immunosuppressant with possible antiamyloid antibodies and albumin-binding capacity. Finally, a phase III trial of suvorexant, an oral orexin receptor antagonist under investigation for patients with Alzheimer’s disease and insomnia, will conclude in 2017.
“I am encouraged to see such a range of approaches to treating Alzheimer’s [disease] in phase II development,” said David Morgan, PhD, CEO of the Byrd Alzheimer Institute at the University of South Florida in Tampa. “There is much work that still needs to be done, but the drugs in phase II clinical trials offer a great deal of hope for the future,” he added.
—Erica Tricarico
Suggested Reading
Jacobson LH, Callander GE, Hoyer D. Suvorexant for the treatment of insomnia. Expert Rev Clin Pharmacol. 2014; 7(6):711-730.
Cummings J, Aisen PS, DuBois B, et al. Drug development in Alzheimer’s disease: the path to 2025. Alzheimers Res Ther. 2016;8:39.
