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Don’t omit extragenital gonorrhea, chlamydia testing
ESTES PARK, COLO. – Close to 80% of men who have sex with men who had gonorrhea or chlamydia in a recent study were infected only at extragenital sites – and therein lies a tale for primary care physicians.
“Five or six years ago my infectious diseases colleagues were pushing extragenital testing in MSM, and I thought then it was a little over the top and excessive. But I now think this is something we should be doing. Two studies from last year highlight this. I think we’re probably missing a lot of infections if we’re only doing genitourinary testing,” John Koeppe, MD, said at a conference on internal medicine sponsored by the University of Colorado.
“It takes labs quite a while to get certified for extragenital testing. Many of my colleagues were sending samples to noncertified labs as urethral samples even though they were actually from the rectum or pharynx. The results were probably reliable. I’ll let you decide if that’s ok,” said Dr. Koeppe, an internist and infectious diseases specialist at the university.
He highlighted one recent potentially practice-changing study in which University of Pittsburgh investigators tested 224 MSM and 175 women with a history of receptive anal intercourse for genitourinary, rectal, and oral gonorrhea and chlamydia. A total of 22.8% of men and 3.4% of women had gonorrhea, while 21.9% of men and 12.6% of women had chlamydia. The major finding: 79.6% of the chlamydia infections and 76.5% of the gonorrhea infections in men were detected by NAAT only in the pharynx or rectum. So were 18.2% of chlamydia and 16.7% of gonorrhea infections in women (Sex Transm Dis. 2016 Feb;43[2]:105-9).
“So in gay men we’d be potentially missing more than three-quarters of infections by only doing genitourinary testing. And in women, it would be more than 16%,” Dr. Koeppe observed.
Moreover, in a national cross-sectional study of 1,071 MSM and bisexual men known as the One Thousand Strong Panel, the prevalence of gonorrhea and chlamydia in urine testing was 0.5% and 1.4%, respectively, whereas in rectal samples the rates were more than threefold higher at 1.8% for gonorrhea and 4.4% for chlamydia.
“Our finding that insertive CAS [condomless anal sex acts] was associated with rectal GC/CT highlights that providers should screen patients for GC/CT [gonococcus/Chlamydia trachomatis] via a full range of transmission routes, lest GC/CT go undiagnosed” the investigators concluded (Sex Transm Dis. 2016 Mar;43[3]:165-71).
Dr. Koeppe noted that major guidelines are in discord regarding chlamydia and gonorrhea screening in men. The U.S. Preventive Services Task Force and American Academy of Family Physicians don’t recommend the practice, while the Centers for Disease Control and Prevention and the Canadian STD guidelines do. The Canadian guidelines even include a series of specific questions to ask men to determine if they are at increased risk. If any of the answers raise a concern, then the guidelines urge testing, since chlamydia and gonorrhea are often asymptomatic.
Dr. Koeppe believes the CDC and the Canadians got it right.
“I think it makes sense to screen men. The CDC’s STD surveillance data indicate the incidence of chlamydia infection in U.S. women is twice as high as in men. That probably has a lot to do with the fact that all of the guidelines recommend screening sexually active women under age 25. I don’t think women are getting most of their chlamydia from other women, they’re probably getting it from men who we’re not screening,” said Dr. Koeppe.
He reported having no financial conflicts regarding his presentation.
ESTES PARK, COLO. – Close to 80% of men who have sex with men who had gonorrhea or chlamydia in a recent study were infected only at extragenital sites – and therein lies a tale for primary care physicians.
“Five or six years ago my infectious diseases colleagues were pushing extragenital testing in MSM, and I thought then it was a little over the top and excessive. But I now think this is something we should be doing. Two studies from last year highlight this. I think we’re probably missing a lot of infections if we’re only doing genitourinary testing,” John Koeppe, MD, said at a conference on internal medicine sponsored by the University of Colorado.
“It takes labs quite a while to get certified for extragenital testing. Many of my colleagues were sending samples to noncertified labs as urethral samples even though they were actually from the rectum or pharynx. The results were probably reliable. I’ll let you decide if that’s ok,” said Dr. Koeppe, an internist and infectious diseases specialist at the university.
He highlighted one recent potentially practice-changing study in which University of Pittsburgh investigators tested 224 MSM and 175 women with a history of receptive anal intercourse for genitourinary, rectal, and oral gonorrhea and chlamydia. A total of 22.8% of men and 3.4% of women had gonorrhea, while 21.9% of men and 12.6% of women had chlamydia. The major finding: 79.6% of the chlamydia infections and 76.5% of the gonorrhea infections in men were detected by NAAT only in the pharynx or rectum. So were 18.2% of chlamydia and 16.7% of gonorrhea infections in women (Sex Transm Dis. 2016 Feb;43[2]:105-9).
“So in gay men we’d be potentially missing more than three-quarters of infections by only doing genitourinary testing. And in women, it would be more than 16%,” Dr. Koeppe observed.
Moreover, in a national cross-sectional study of 1,071 MSM and bisexual men known as the One Thousand Strong Panel, the prevalence of gonorrhea and chlamydia in urine testing was 0.5% and 1.4%, respectively, whereas in rectal samples the rates were more than threefold higher at 1.8% for gonorrhea and 4.4% for chlamydia.
“Our finding that insertive CAS [condomless anal sex acts] was associated with rectal GC/CT highlights that providers should screen patients for GC/CT [gonococcus/Chlamydia trachomatis] via a full range of transmission routes, lest GC/CT go undiagnosed” the investigators concluded (Sex Transm Dis. 2016 Mar;43[3]:165-71).
Dr. Koeppe noted that major guidelines are in discord regarding chlamydia and gonorrhea screening in men. The U.S. Preventive Services Task Force and American Academy of Family Physicians don’t recommend the practice, while the Centers for Disease Control and Prevention and the Canadian STD guidelines do. The Canadian guidelines even include a series of specific questions to ask men to determine if they are at increased risk. If any of the answers raise a concern, then the guidelines urge testing, since chlamydia and gonorrhea are often asymptomatic.
Dr. Koeppe believes the CDC and the Canadians got it right.
“I think it makes sense to screen men. The CDC’s STD surveillance data indicate the incidence of chlamydia infection in U.S. women is twice as high as in men. That probably has a lot to do with the fact that all of the guidelines recommend screening sexually active women under age 25. I don’t think women are getting most of their chlamydia from other women, they’re probably getting it from men who we’re not screening,” said Dr. Koeppe.
He reported having no financial conflicts regarding his presentation.
ESTES PARK, COLO. – Close to 80% of men who have sex with men who had gonorrhea or chlamydia in a recent study were infected only at extragenital sites – and therein lies a tale for primary care physicians.
“Five or six years ago my infectious diseases colleagues were pushing extragenital testing in MSM, and I thought then it was a little over the top and excessive. But I now think this is something we should be doing. Two studies from last year highlight this. I think we’re probably missing a lot of infections if we’re only doing genitourinary testing,” John Koeppe, MD, said at a conference on internal medicine sponsored by the University of Colorado.
“It takes labs quite a while to get certified for extragenital testing. Many of my colleagues were sending samples to noncertified labs as urethral samples even though they were actually from the rectum or pharynx. The results were probably reliable. I’ll let you decide if that’s ok,” said Dr. Koeppe, an internist and infectious diseases specialist at the university.
He highlighted one recent potentially practice-changing study in which University of Pittsburgh investigators tested 224 MSM and 175 women with a history of receptive anal intercourse for genitourinary, rectal, and oral gonorrhea and chlamydia. A total of 22.8% of men and 3.4% of women had gonorrhea, while 21.9% of men and 12.6% of women had chlamydia. The major finding: 79.6% of the chlamydia infections and 76.5% of the gonorrhea infections in men were detected by NAAT only in the pharynx or rectum. So were 18.2% of chlamydia and 16.7% of gonorrhea infections in women (Sex Transm Dis. 2016 Feb;43[2]:105-9).
“So in gay men we’d be potentially missing more than three-quarters of infections by only doing genitourinary testing. And in women, it would be more than 16%,” Dr. Koeppe observed.
Moreover, in a national cross-sectional study of 1,071 MSM and bisexual men known as the One Thousand Strong Panel, the prevalence of gonorrhea and chlamydia in urine testing was 0.5% and 1.4%, respectively, whereas in rectal samples the rates were more than threefold higher at 1.8% for gonorrhea and 4.4% for chlamydia.
“Our finding that insertive CAS [condomless anal sex acts] was associated with rectal GC/CT highlights that providers should screen patients for GC/CT [gonococcus/Chlamydia trachomatis] via a full range of transmission routes, lest GC/CT go undiagnosed” the investigators concluded (Sex Transm Dis. 2016 Mar;43[3]:165-71).
Dr. Koeppe noted that major guidelines are in discord regarding chlamydia and gonorrhea screening in men. The U.S. Preventive Services Task Force and American Academy of Family Physicians don’t recommend the practice, while the Centers for Disease Control and Prevention and the Canadian STD guidelines do. The Canadian guidelines even include a series of specific questions to ask men to determine if they are at increased risk. If any of the answers raise a concern, then the guidelines urge testing, since chlamydia and gonorrhea are often asymptomatic.
Dr. Koeppe believes the CDC and the Canadians got it right.
“I think it makes sense to screen men. The CDC’s STD surveillance data indicate the incidence of chlamydia infection in U.S. women is twice as high as in men. That probably has a lot to do with the fact that all of the guidelines recommend screening sexually active women under age 25. I don’t think women are getting most of their chlamydia from other women, they’re probably getting it from men who we’re not screening,” said Dr. Koeppe.
He reported having no financial conflicts regarding his presentation.
EXPERT ANALYSIS FROM THE ANNUAL INTERNAL MEDICINE PROGRAM
VIDEO: Prescription-strength ibuprofen worsens blood pressure more than other NSAIDs
BARCELONA – Prescription-strength ibuprofen has a bigger adverse effect on blood pressure than celecoxib or naproxen, a finding that suggests a likely mechanism for the worse cardiovascular event rate documented in ibuprofen-treated arthritis patients in the PRECISION trial, Frank Ruschitzka, MD, said at the annual congress of the European Society of Cardiology.
“Prescription-strength ibuprofen is under pressure – it has a high incidence of new-onset hypertension, particularly when compared to the more selective COX-2 inhibitor celecoxib. Before we did this study, many would have said it’s the other way around,” observed Dr. Ruschitzka, professor of cardiology at the University of Zurich.
He presented the results of PRECISION-ABPM (Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen Ambulatory Blood Pressure Measurement).
“These results will have impact on your daily practice when you go home,” the cardiologist promised.
PRECISION-ABPM was a prespecified double-blind, randomized, 60-center substudy of the published PRECISION trial, which included 24,081 U.S. patients who needed daily NSAIDs for arthritis and were also at increased cardiovascular risk. They were randomized to the COX-2 inhibitor celecoxib at 100-200 mg b.i.d. or the nonselective NSAIDs ibuprofen at 600-800 mg three times a day or naproxen at 375-500 mg twice daily. Participants also received a proton pump inhibitor to protect against NSAID-related GI bleeding. In the on-treatment analysis, the ibuprofen group was significantly more likely to experience cardiovascular and all-cause mortality and renal events than were those on celecoxib (N Engl J Med. 2016 Dec 29;375[26]:2519-29).
The PRECISION-ABPM substudy included 444 arthritis patients, 92% of whom had osteoarthritis. During the 4-month study, investigators amassed roughly 60,000 automated blood pressure measurements across the three study arms.
The primary outcome was change from baseline in mean 24-hour systolic blood pressure (SBP). It increased by 3.7 mm Hg in the ibuprofen group and declined by 0.3 mm Hg in the celecoxib group, while the naproxen group occupied the middle ground with a 1.6-mm Hg increase.
The nearly 4-mm Hg increase in mean 24-hour SBP at 4 months in the ibuprofen group is of sufficient magnitude to be clinically important, Dr. Ruschitzka noted. He noted that fully 23.2% of ibuprofen-treated patients who had normal baseline blood pressure developed hypertension as defined by a mean 24-hour SBP of at least 130 and/or a diastolic blood pressure of at least 80 mm Hg. In contrast, incident hypertension occurred in only 10.3% of the celecoxib group and 19% of naproxen-treated patients. Thus, the likelihood of developing hypertension was 61% less with celecoxib than ibuprofen and 51% less with celecoxib than naproxen.
Not treating chronic arthritic pain to avoid the cardiovascular risk of NSAIDs is not a legitimate option.
“Pain is a cardiovascular risk factor,” Dr. Ruschitzka emphasized. “It’s unethical not to treat it. If you don’t treat pain, the patient’s blood pressure goes up, heart rate goes up, and you’re driving patients into inactivity.”
Although he’s convinced there’s no such thing as a safe NSAID from a cardiovascular risk standpoint, the PRECISION and PRECISION-ABPM data show celecoxib is less unsafe than ibuprofen. And as for the oft-heard statement that naproxen is the safest NSAID for the heart, Dr. Ruschitzka snorted, “What an urban legend.”
Discussant Scott Solomon, MD, opined that, while PRECISION-ABPM doesn’t support the notion that conventional NSAIDs such as naproxen or ibuprofen are any safer than celecoxib, it would be wrong to conclude from the study that celecoxib doesn’t affect blood pressure and is safer than the others from a cardiovascular standpoint. That’s because the three study drugs weren’t compared in an equipotent way. Because of safety concerns, the Food and Drug Administration required that the daily dose of celecoxib be capped at the low end of the therapeutic range, while no such constraints were placed on the two nonselective NSAIDS.
“Compared to placebo, all NSAIDs likely raise blood pressure, especially in patients prone to hypertension, those with chronic kidney disease, the elderly – and this is exactly the type of patients who require NSAIDs for arthritis. Whichever NSAID is chosen, clinicians should be aware of this effect and treat hypertension according to guidelines,” said Dr. Solomon, director of noninvasive cardiology at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School.
Dr. Solomon has been a key figure in the COX-2 inhibitor controversy of the last decade. He was lead author of a 2005 review of data from clinical trials of COX-2 inhibitors for colorectal adenoma prevention, which concluded that the drugs had a cardiovascular safety issue in that setting (N Engl J Med. 2005 Mar 17;352[11]:1071-80).
“Our analysis of celecoxib concluded that a dose-dependent increase in cardiovascular events was there, was real, but notably occurred at doses which were substantially higher than what we typically use for patients with arthritis,” he said.
That report triggered a fevered reaction.
“Amid an enormous amount of hype, hyperbole, and hysteria, the safety of these agents was thrown into question, leading to the withdrawal of all but one of them from the market and a black-box warning around the one remaining agent, celecoxib,” he recalled.
Dr. Ruschitzka discussed his findings in a video interview.
PRECISION-ABPM was sponsored by Pfizer. Dr. Ruschitzka and Dr. Solomon reported having no financial conflicts of interest regarding their presentations.
BARCELONA – Prescription-strength ibuprofen has a bigger adverse effect on blood pressure than celecoxib or naproxen, a finding that suggests a likely mechanism for the worse cardiovascular event rate documented in ibuprofen-treated arthritis patients in the PRECISION trial, Frank Ruschitzka, MD, said at the annual congress of the European Society of Cardiology.
“Prescription-strength ibuprofen is under pressure – it has a high incidence of new-onset hypertension, particularly when compared to the more selective COX-2 inhibitor celecoxib. Before we did this study, many would have said it’s the other way around,” observed Dr. Ruschitzka, professor of cardiology at the University of Zurich.
He presented the results of PRECISION-ABPM (Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen Ambulatory Blood Pressure Measurement).
“These results will have impact on your daily practice when you go home,” the cardiologist promised.
PRECISION-ABPM was a prespecified double-blind, randomized, 60-center substudy of the published PRECISION trial, which included 24,081 U.S. patients who needed daily NSAIDs for arthritis and were also at increased cardiovascular risk. They were randomized to the COX-2 inhibitor celecoxib at 100-200 mg b.i.d. or the nonselective NSAIDs ibuprofen at 600-800 mg three times a day or naproxen at 375-500 mg twice daily. Participants also received a proton pump inhibitor to protect against NSAID-related GI bleeding. In the on-treatment analysis, the ibuprofen group was significantly more likely to experience cardiovascular and all-cause mortality and renal events than were those on celecoxib (N Engl J Med. 2016 Dec 29;375[26]:2519-29).
The PRECISION-ABPM substudy included 444 arthritis patients, 92% of whom had osteoarthritis. During the 4-month study, investigators amassed roughly 60,000 automated blood pressure measurements across the three study arms.
The primary outcome was change from baseline in mean 24-hour systolic blood pressure (SBP). It increased by 3.7 mm Hg in the ibuprofen group and declined by 0.3 mm Hg in the celecoxib group, while the naproxen group occupied the middle ground with a 1.6-mm Hg increase.
The nearly 4-mm Hg increase in mean 24-hour SBP at 4 months in the ibuprofen group is of sufficient magnitude to be clinically important, Dr. Ruschitzka noted. He noted that fully 23.2% of ibuprofen-treated patients who had normal baseline blood pressure developed hypertension as defined by a mean 24-hour SBP of at least 130 and/or a diastolic blood pressure of at least 80 mm Hg. In contrast, incident hypertension occurred in only 10.3% of the celecoxib group and 19% of naproxen-treated patients. Thus, the likelihood of developing hypertension was 61% less with celecoxib than ibuprofen and 51% less with celecoxib than naproxen.
Not treating chronic arthritic pain to avoid the cardiovascular risk of NSAIDs is not a legitimate option.
“Pain is a cardiovascular risk factor,” Dr. Ruschitzka emphasized. “It’s unethical not to treat it. If you don’t treat pain, the patient’s blood pressure goes up, heart rate goes up, and you’re driving patients into inactivity.”
Although he’s convinced there’s no such thing as a safe NSAID from a cardiovascular risk standpoint, the PRECISION and PRECISION-ABPM data show celecoxib is less unsafe than ibuprofen. And as for the oft-heard statement that naproxen is the safest NSAID for the heart, Dr. Ruschitzka snorted, “What an urban legend.”
Discussant Scott Solomon, MD, opined that, while PRECISION-ABPM doesn’t support the notion that conventional NSAIDs such as naproxen or ibuprofen are any safer than celecoxib, it would be wrong to conclude from the study that celecoxib doesn’t affect blood pressure and is safer than the others from a cardiovascular standpoint. That’s because the three study drugs weren’t compared in an equipotent way. Because of safety concerns, the Food and Drug Administration required that the daily dose of celecoxib be capped at the low end of the therapeutic range, while no such constraints were placed on the two nonselective NSAIDS.
“Compared to placebo, all NSAIDs likely raise blood pressure, especially in patients prone to hypertension, those with chronic kidney disease, the elderly – and this is exactly the type of patients who require NSAIDs for arthritis. Whichever NSAID is chosen, clinicians should be aware of this effect and treat hypertension according to guidelines,” said Dr. Solomon, director of noninvasive cardiology at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School.
Dr. Solomon has been a key figure in the COX-2 inhibitor controversy of the last decade. He was lead author of a 2005 review of data from clinical trials of COX-2 inhibitors for colorectal adenoma prevention, which concluded that the drugs had a cardiovascular safety issue in that setting (N Engl J Med. 2005 Mar 17;352[11]:1071-80).
“Our analysis of celecoxib concluded that a dose-dependent increase in cardiovascular events was there, was real, but notably occurred at doses which were substantially higher than what we typically use for patients with arthritis,” he said.
That report triggered a fevered reaction.
“Amid an enormous amount of hype, hyperbole, and hysteria, the safety of these agents was thrown into question, leading to the withdrawal of all but one of them from the market and a black-box warning around the one remaining agent, celecoxib,” he recalled.
Dr. Ruschitzka discussed his findings in a video interview.
PRECISION-ABPM was sponsored by Pfizer. Dr. Ruschitzka and Dr. Solomon reported having no financial conflicts of interest regarding their presentations.
BARCELONA – Prescription-strength ibuprofen has a bigger adverse effect on blood pressure than celecoxib or naproxen, a finding that suggests a likely mechanism for the worse cardiovascular event rate documented in ibuprofen-treated arthritis patients in the PRECISION trial, Frank Ruschitzka, MD, said at the annual congress of the European Society of Cardiology.
“Prescription-strength ibuprofen is under pressure – it has a high incidence of new-onset hypertension, particularly when compared to the more selective COX-2 inhibitor celecoxib. Before we did this study, many would have said it’s the other way around,” observed Dr. Ruschitzka, professor of cardiology at the University of Zurich.
He presented the results of PRECISION-ABPM (Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen Ambulatory Blood Pressure Measurement).
“These results will have impact on your daily practice when you go home,” the cardiologist promised.
PRECISION-ABPM was a prespecified double-blind, randomized, 60-center substudy of the published PRECISION trial, which included 24,081 U.S. patients who needed daily NSAIDs for arthritis and were also at increased cardiovascular risk. They were randomized to the COX-2 inhibitor celecoxib at 100-200 mg b.i.d. or the nonselective NSAIDs ibuprofen at 600-800 mg three times a day or naproxen at 375-500 mg twice daily. Participants also received a proton pump inhibitor to protect against NSAID-related GI bleeding. In the on-treatment analysis, the ibuprofen group was significantly more likely to experience cardiovascular and all-cause mortality and renal events than were those on celecoxib (N Engl J Med. 2016 Dec 29;375[26]:2519-29).
The PRECISION-ABPM substudy included 444 arthritis patients, 92% of whom had osteoarthritis. During the 4-month study, investigators amassed roughly 60,000 automated blood pressure measurements across the three study arms.
The primary outcome was change from baseline in mean 24-hour systolic blood pressure (SBP). It increased by 3.7 mm Hg in the ibuprofen group and declined by 0.3 mm Hg in the celecoxib group, while the naproxen group occupied the middle ground with a 1.6-mm Hg increase.
The nearly 4-mm Hg increase in mean 24-hour SBP at 4 months in the ibuprofen group is of sufficient magnitude to be clinically important, Dr. Ruschitzka noted. He noted that fully 23.2% of ibuprofen-treated patients who had normal baseline blood pressure developed hypertension as defined by a mean 24-hour SBP of at least 130 and/or a diastolic blood pressure of at least 80 mm Hg. In contrast, incident hypertension occurred in only 10.3% of the celecoxib group and 19% of naproxen-treated patients. Thus, the likelihood of developing hypertension was 61% less with celecoxib than ibuprofen and 51% less with celecoxib than naproxen.
Not treating chronic arthritic pain to avoid the cardiovascular risk of NSAIDs is not a legitimate option.
“Pain is a cardiovascular risk factor,” Dr. Ruschitzka emphasized. “It’s unethical not to treat it. If you don’t treat pain, the patient’s blood pressure goes up, heart rate goes up, and you’re driving patients into inactivity.”
Although he’s convinced there’s no such thing as a safe NSAID from a cardiovascular risk standpoint, the PRECISION and PRECISION-ABPM data show celecoxib is less unsafe than ibuprofen. And as for the oft-heard statement that naproxen is the safest NSAID for the heart, Dr. Ruschitzka snorted, “What an urban legend.”
Discussant Scott Solomon, MD, opined that, while PRECISION-ABPM doesn’t support the notion that conventional NSAIDs such as naproxen or ibuprofen are any safer than celecoxib, it would be wrong to conclude from the study that celecoxib doesn’t affect blood pressure and is safer than the others from a cardiovascular standpoint. That’s because the three study drugs weren’t compared in an equipotent way. Because of safety concerns, the Food and Drug Administration required that the daily dose of celecoxib be capped at the low end of the therapeutic range, while no such constraints were placed on the two nonselective NSAIDS.
“Compared to placebo, all NSAIDs likely raise blood pressure, especially in patients prone to hypertension, those with chronic kidney disease, the elderly – and this is exactly the type of patients who require NSAIDs for arthritis. Whichever NSAID is chosen, clinicians should be aware of this effect and treat hypertension according to guidelines,” said Dr. Solomon, director of noninvasive cardiology at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School.
Dr. Solomon has been a key figure in the COX-2 inhibitor controversy of the last decade. He was lead author of a 2005 review of data from clinical trials of COX-2 inhibitors for colorectal adenoma prevention, which concluded that the drugs had a cardiovascular safety issue in that setting (N Engl J Med. 2005 Mar 17;352[11]:1071-80).
“Our analysis of celecoxib concluded that a dose-dependent increase in cardiovascular events was there, was real, but notably occurred at doses which were substantially higher than what we typically use for patients with arthritis,” he said.
That report triggered a fevered reaction.
“Amid an enormous amount of hype, hyperbole, and hysteria, the safety of these agents was thrown into question, leading to the withdrawal of all but one of them from the market and a black-box warning around the one remaining agent, celecoxib,” he recalled.
Dr. Ruschitzka discussed his findings in a video interview.
PRECISION-ABPM was sponsored by Pfizer. Dr. Ruschitzka and Dr. Solomon reported having no financial conflicts of interest regarding their presentations.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: Incident hypertension occurred within 4 months in 23.2% of arthritis patients on ibuprofen, compared with 10.3% taking celecoxib and 19% on naproxen.
Data source: This was a randomized, double-blind, multicenter, prospective trial including 444 arthritis patients at increased cardiovascular risk who underwent 4 months of ambulatory blood pressure monitoring after being assigned to prescription-strength ibuprofen, naproxen, or celecoxib.
Disclosures: The PRECISION-ABPM trial was sponsored by Pfizer. The presenter reported having no financial conflicts of interest.
CANTOS sings of novel strategy for cardiovascular, cancer prevention
BARCELONA – Inhibiting the interleukin-1 beta innate immunity pathway with canakinumab reduced recurrent cardiovascular events and lung cancer in the groundbreaking phase III CANTOS trial, Paul M. Ridker, MD, reported at the annual congress of the European Society of Cardiology.
“These data provide the first proof that inflammation inhibition in the absence of lipid lowering can improve atherogenic outcomes and potentially alter progression of some fatal cancers,” declared Dr. Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School.
“Just like we’ve learned that lower LDL is better, I think we’re now learning that lower inflammation is better,” he said.
CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) was a randomized, double-blind, placebo-controlled trial involving 10,061 patients in 39 countries, all of whom had a previous MI and a chronically high level of systemic inflammation as reflected in a median baseline high-sensitivity C-reactive protein (CRP) level of 4.1 mg/L. Ninety-one percent of participants were on statin therapy, with a median LDL cholesterol of 82 mg/dL when randomized to subcutaneous canakinumab at 50, 150, or 300 mg or to placebo once every 3 months.
Canakinumab is a fully human monoclonal antibody targeting IL-1B, a key player in systemic inflammation. The cytokine is activated by the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, a part of the innate immune system. Canakinumab is approved as Ilaris for treatment of several uncommon rheumatologic diseases, including cryopryin-associated periodic syndrome and systemic juvenile idiopathic arthritis.
At a median follow-up of 3.7 years, the incidence of the primary composite efficacy endpoint of nonfatal MI, nonfatal stroke, or cardiovascular death was 4.5 events per 100 person-years in the control group, significantly higher than the 3.86 and 3.9 events per 100 person-years in patients on canakinumab at 150 and 300 mg, respectively.
Since event rates were virtually identical in the 150- and 300-mg study arms, Dr. Ridker combined those two patient groups in his analysis. They showed a 15% reduction in the risk of the primary efficacy endpoint, compared with placebo-treated controls, along with a 39% reduction from baseline in CRP. They also were 30% less likely to undergo percutaneous coronary intervention or coronary artery bypass graft during follow-up.
“That’s quite important, because that’s a progression-of-atherosclerosis endpoint and also obviously a cost and financial endpoint,” he observed.
A key finding in CANTOS was that patients with a reduction in CRP at or exceeding the median decrease just 3 months into the study – that is, after a single injection – had a 27% reduction in major vascular events during follow-up. Patients with a lesser reduction in CRP at that point did not experience a significant reduction in the primary endpoint, compared with placebo.
“The clinician in me would say we probably ought to give a single dose of the drug, see what happens, and if you get a large inflammation reduction we could perhaps consider treating that patient, but if you did not get a large reduction perhaps this is not a therapy for that patient. Why not avoid the toxicity in people who aren’t going to respond?” Dr. Ridker said.
Side effects related to canakinumab consisted of mild leukopenia and a small but statistically significant increase in fatal infections, which he called “not surprising.”
“It’s in the same range as one gets in treating rheumatoid arthritis with a biologic drug, which rheumatologists are very comfortable doing. You would imagine that if this does become a treatment, physicians will get much better at bringing patients in early when they have signs and symptoms of infection,” the cardiologist continued.
Patients on canakinumab showed significant reductions in incident rheumatoid arthritis, gout, and osteoarthritis. The drug had no kidney or liver adverse events.
Cancer was a prespecified secondary outcome in CANTOS. The investigators saw the trial as an opportunity to test a longstanding hypothesis that inhibiting IL-1B would have a positive impact on lung cancer in particular.
“Smoking, exposure to diesel fuel, inhalation of asbestos or other silicates – these cause inflammation which activates the NLRP3 inflammasome, but in the pulmonary system rather than the arteries,” Dr. Ridker explained.
An entry requirement in CANTOS was that patients needed to be free of known cancer. During study follow-up, 129 patients were diagnosed with lung cancer. The risk was reduced in dose-dependent fashion with canakinumab: by 39% relative to placebo in the 150-mg group and by 67% in the 300-mg group. Lung cancer mortality was reduced by 77% in the canakinumab 300-mg group.
“I don’t think this is about oncogenesis per se. I think the tumors are already there, but they don’t progress because we’ve altered the tumor’s inflammatory microenvironment,” he continued.
Since CANTOS was first and foremost a study of atherosclerotic disease prevention, the cancer results need to be replicated on a high-priority basis. Dr. Ridker predicted that Novartis, which sponsored CANTOS, will quickly mount a clinical trial examining canakinumab’s potential as an adjunctive treatment to either chemotherapy or radiation following resection of lung cancer.
He stressed that CANTOS is only the beginning stanza in what will be an entirely new approach to preventive cardiology. Numerous other inflammatory pathways also might serve as targets.
“I think this is going to open up all kinds of approaches using a variety of agents that have really been in the rheumatology and immunology world,” the cardiologist predicted.
For example, he is principal investigator in the ongoing National Heart, Lung, and Blood Institute–sponsored Cardiovascular Inflammation Reduction Trial (CIRT), a randomized, double-blind, placebo-controlled study of low-dose methotrexate for prevention of cardiovascular events in a planned 7,000 patients with type 2 diabetes or metabolic syndrome who’ve had an MI or have multivessel CAD. Results are probably 4-6 years off.
“Right now, we know canakinumab works. If methotrexate were to work, then we’d have a generic, inexpensive approach as well,” Dr. Ridker noted.
Novartis officials indicated that, on the basis of the positive CANTOS results, the company plans to file for an expanded indication for canakinumab for cardiovascular prevention. The company also is gearing up for studies of the drug in oncology.
Simultaneous with Dr. Ridker’s presentation in Barcelona, both the atherosclerotic disease findings (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914) and the cancer findings (Lancet. 2017 Aug 27. doi: 10.1016/S0140-6736(17)32247-X) were published.
He reported serving as a consultant to Novartis.
BARCELONA – Inhibiting the interleukin-1 beta innate immunity pathway with canakinumab reduced recurrent cardiovascular events and lung cancer in the groundbreaking phase III CANTOS trial, Paul M. Ridker, MD, reported at the annual congress of the European Society of Cardiology.
“These data provide the first proof that inflammation inhibition in the absence of lipid lowering can improve atherogenic outcomes and potentially alter progression of some fatal cancers,” declared Dr. Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School.
“Just like we’ve learned that lower LDL is better, I think we’re now learning that lower inflammation is better,” he said.
CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) was a randomized, double-blind, placebo-controlled trial involving 10,061 patients in 39 countries, all of whom had a previous MI and a chronically high level of systemic inflammation as reflected in a median baseline high-sensitivity C-reactive protein (CRP) level of 4.1 mg/L. Ninety-one percent of participants were on statin therapy, with a median LDL cholesterol of 82 mg/dL when randomized to subcutaneous canakinumab at 50, 150, or 300 mg or to placebo once every 3 months.
Canakinumab is a fully human monoclonal antibody targeting IL-1B, a key player in systemic inflammation. The cytokine is activated by the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, a part of the innate immune system. Canakinumab is approved as Ilaris for treatment of several uncommon rheumatologic diseases, including cryopryin-associated periodic syndrome and systemic juvenile idiopathic arthritis.
At a median follow-up of 3.7 years, the incidence of the primary composite efficacy endpoint of nonfatal MI, nonfatal stroke, or cardiovascular death was 4.5 events per 100 person-years in the control group, significantly higher than the 3.86 and 3.9 events per 100 person-years in patients on canakinumab at 150 and 300 mg, respectively.
Since event rates were virtually identical in the 150- and 300-mg study arms, Dr. Ridker combined those two patient groups in his analysis. They showed a 15% reduction in the risk of the primary efficacy endpoint, compared with placebo-treated controls, along with a 39% reduction from baseline in CRP. They also were 30% less likely to undergo percutaneous coronary intervention or coronary artery bypass graft during follow-up.
“That’s quite important, because that’s a progression-of-atherosclerosis endpoint and also obviously a cost and financial endpoint,” he observed.
A key finding in CANTOS was that patients with a reduction in CRP at or exceeding the median decrease just 3 months into the study – that is, after a single injection – had a 27% reduction in major vascular events during follow-up. Patients with a lesser reduction in CRP at that point did not experience a significant reduction in the primary endpoint, compared with placebo.
“The clinician in me would say we probably ought to give a single dose of the drug, see what happens, and if you get a large inflammation reduction we could perhaps consider treating that patient, but if you did not get a large reduction perhaps this is not a therapy for that patient. Why not avoid the toxicity in people who aren’t going to respond?” Dr. Ridker said.
Side effects related to canakinumab consisted of mild leukopenia and a small but statistically significant increase in fatal infections, which he called “not surprising.”
“It’s in the same range as one gets in treating rheumatoid arthritis with a biologic drug, which rheumatologists are very comfortable doing. You would imagine that if this does become a treatment, physicians will get much better at bringing patients in early when they have signs and symptoms of infection,” the cardiologist continued.
Patients on canakinumab showed significant reductions in incident rheumatoid arthritis, gout, and osteoarthritis. The drug had no kidney or liver adverse events.
Cancer was a prespecified secondary outcome in CANTOS. The investigators saw the trial as an opportunity to test a longstanding hypothesis that inhibiting IL-1B would have a positive impact on lung cancer in particular.
“Smoking, exposure to diesel fuel, inhalation of asbestos or other silicates – these cause inflammation which activates the NLRP3 inflammasome, but in the pulmonary system rather than the arteries,” Dr. Ridker explained.
An entry requirement in CANTOS was that patients needed to be free of known cancer. During study follow-up, 129 patients were diagnosed with lung cancer. The risk was reduced in dose-dependent fashion with canakinumab: by 39% relative to placebo in the 150-mg group and by 67% in the 300-mg group. Lung cancer mortality was reduced by 77% in the canakinumab 300-mg group.
“I don’t think this is about oncogenesis per se. I think the tumors are already there, but they don’t progress because we’ve altered the tumor’s inflammatory microenvironment,” he continued.
Since CANTOS was first and foremost a study of atherosclerotic disease prevention, the cancer results need to be replicated on a high-priority basis. Dr. Ridker predicted that Novartis, which sponsored CANTOS, will quickly mount a clinical trial examining canakinumab’s potential as an adjunctive treatment to either chemotherapy or radiation following resection of lung cancer.
He stressed that CANTOS is only the beginning stanza in what will be an entirely new approach to preventive cardiology. Numerous other inflammatory pathways also might serve as targets.
“I think this is going to open up all kinds of approaches using a variety of agents that have really been in the rheumatology and immunology world,” the cardiologist predicted.
For example, he is principal investigator in the ongoing National Heart, Lung, and Blood Institute–sponsored Cardiovascular Inflammation Reduction Trial (CIRT), a randomized, double-blind, placebo-controlled study of low-dose methotrexate for prevention of cardiovascular events in a planned 7,000 patients with type 2 diabetes or metabolic syndrome who’ve had an MI or have multivessel CAD. Results are probably 4-6 years off.
“Right now, we know canakinumab works. If methotrexate were to work, then we’d have a generic, inexpensive approach as well,” Dr. Ridker noted.
Novartis officials indicated that, on the basis of the positive CANTOS results, the company plans to file for an expanded indication for canakinumab for cardiovascular prevention. The company also is gearing up for studies of the drug in oncology.
Simultaneous with Dr. Ridker’s presentation in Barcelona, both the atherosclerotic disease findings (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914) and the cancer findings (Lancet. 2017 Aug 27. doi: 10.1016/S0140-6736(17)32247-X) were published.
He reported serving as a consultant to Novartis.
BARCELONA – Inhibiting the interleukin-1 beta innate immunity pathway with canakinumab reduced recurrent cardiovascular events and lung cancer in the groundbreaking phase III CANTOS trial, Paul M. Ridker, MD, reported at the annual congress of the European Society of Cardiology.
“These data provide the first proof that inflammation inhibition in the absence of lipid lowering can improve atherogenic outcomes and potentially alter progression of some fatal cancers,” declared Dr. Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital, Boston, and professor of medicine at Harvard Medical School.
“Just like we’ve learned that lower LDL is better, I think we’re now learning that lower inflammation is better,” he said.
CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) was a randomized, double-blind, placebo-controlled trial involving 10,061 patients in 39 countries, all of whom had a previous MI and a chronically high level of systemic inflammation as reflected in a median baseline high-sensitivity C-reactive protein (CRP) level of 4.1 mg/L. Ninety-one percent of participants were on statin therapy, with a median LDL cholesterol of 82 mg/dL when randomized to subcutaneous canakinumab at 50, 150, or 300 mg or to placebo once every 3 months.
Canakinumab is a fully human monoclonal antibody targeting IL-1B, a key player in systemic inflammation. The cytokine is activated by the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, a part of the innate immune system. Canakinumab is approved as Ilaris for treatment of several uncommon rheumatologic diseases, including cryopryin-associated periodic syndrome and systemic juvenile idiopathic arthritis.
At a median follow-up of 3.7 years, the incidence of the primary composite efficacy endpoint of nonfatal MI, nonfatal stroke, or cardiovascular death was 4.5 events per 100 person-years in the control group, significantly higher than the 3.86 and 3.9 events per 100 person-years in patients on canakinumab at 150 and 300 mg, respectively.
Since event rates were virtually identical in the 150- and 300-mg study arms, Dr. Ridker combined those two patient groups in his analysis. They showed a 15% reduction in the risk of the primary efficacy endpoint, compared with placebo-treated controls, along with a 39% reduction from baseline in CRP. They also were 30% less likely to undergo percutaneous coronary intervention or coronary artery bypass graft during follow-up.
“That’s quite important, because that’s a progression-of-atherosclerosis endpoint and also obviously a cost and financial endpoint,” he observed.
A key finding in CANTOS was that patients with a reduction in CRP at or exceeding the median decrease just 3 months into the study – that is, after a single injection – had a 27% reduction in major vascular events during follow-up. Patients with a lesser reduction in CRP at that point did not experience a significant reduction in the primary endpoint, compared with placebo.
“The clinician in me would say we probably ought to give a single dose of the drug, see what happens, and if you get a large inflammation reduction we could perhaps consider treating that patient, but if you did not get a large reduction perhaps this is not a therapy for that patient. Why not avoid the toxicity in people who aren’t going to respond?” Dr. Ridker said.
Side effects related to canakinumab consisted of mild leukopenia and a small but statistically significant increase in fatal infections, which he called “not surprising.”
“It’s in the same range as one gets in treating rheumatoid arthritis with a biologic drug, which rheumatologists are very comfortable doing. You would imagine that if this does become a treatment, physicians will get much better at bringing patients in early when they have signs and symptoms of infection,” the cardiologist continued.
Patients on canakinumab showed significant reductions in incident rheumatoid arthritis, gout, and osteoarthritis. The drug had no kidney or liver adverse events.
Cancer was a prespecified secondary outcome in CANTOS. The investigators saw the trial as an opportunity to test a longstanding hypothesis that inhibiting IL-1B would have a positive impact on lung cancer in particular.
“Smoking, exposure to diesel fuel, inhalation of asbestos or other silicates – these cause inflammation which activates the NLRP3 inflammasome, but in the pulmonary system rather than the arteries,” Dr. Ridker explained.
An entry requirement in CANTOS was that patients needed to be free of known cancer. During study follow-up, 129 patients were diagnosed with lung cancer. The risk was reduced in dose-dependent fashion with canakinumab: by 39% relative to placebo in the 150-mg group and by 67% in the 300-mg group. Lung cancer mortality was reduced by 77% in the canakinumab 300-mg group.
“I don’t think this is about oncogenesis per se. I think the tumors are already there, but they don’t progress because we’ve altered the tumor’s inflammatory microenvironment,” he continued.
Since CANTOS was first and foremost a study of atherosclerotic disease prevention, the cancer results need to be replicated on a high-priority basis. Dr. Ridker predicted that Novartis, which sponsored CANTOS, will quickly mount a clinical trial examining canakinumab’s potential as an adjunctive treatment to either chemotherapy or radiation following resection of lung cancer.
He stressed that CANTOS is only the beginning stanza in what will be an entirely new approach to preventive cardiology. Numerous other inflammatory pathways also might serve as targets.
“I think this is going to open up all kinds of approaches using a variety of agents that have really been in the rheumatology and immunology world,” the cardiologist predicted.
For example, he is principal investigator in the ongoing National Heart, Lung, and Blood Institute–sponsored Cardiovascular Inflammation Reduction Trial (CIRT), a randomized, double-blind, placebo-controlled study of low-dose methotrexate for prevention of cardiovascular events in a planned 7,000 patients with type 2 diabetes or metabolic syndrome who’ve had an MI or have multivessel CAD. Results are probably 4-6 years off.
“Right now, we know canakinumab works. If methotrexate were to work, then we’d have a generic, inexpensive approach as well,” Dr. Ridker noted.
Novartis officials indicated that, on the basis of the positive CANTOS results, the company plans to file for an expanded indication for canakinumab for cardiovascular prevention. The company also is gearing up for studies of the drug in oncology.
Simultaneous with Dr. Ridker’s presentation in Barcelona, both the atherosclerotic disease findings (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914) and the cancer findings (Lancet. 2017 Aug 27. doi: 10.1016/S0140-6736(17)32247-X) were published.
He reported serving as a consultant to Novartis.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: Canakinumab reduced the risk of recurrent cardiovascular events in a very-high-risk population by 15%, compared with placebo, while cutting incident lung cancer by 67% in a major clinical trial.
Data source: CANTOS was a phase III, randomized, double-blind, placebo-controlled trial involving 10,061 patients in 39 countries, all with a previous MI and chronically high systemic inflammation.
Disclosures: The study was sponsored by Novartis. The presenter reported serving as a consultant to the company.
VIDEO: Inflammation’s role in atherosclerosis confirmed in CANTOS
BARCELONA – The results of the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) mark the validation of many years of research on inflammation for Peter Libby, MD, Mallinckrodt Professor of Medicine, Harvard Medical School, Boston.
The CANTOS investigator said that, although some trials, most notably JUPITER, have linked reduced markers of inflammation with reduced cardiovascular events, none have been able to separate the effects of lowering LDL cholesterol from those of lowering the inflammatory marker interleukin-1B.
But using the monoclonal antibody canakinumab to target only interleukin-1B in CANTOS reduced the composite endpoint of nonfatal MI, nonfatal stroke, or cardiovascular death by 15% at the highest dosage tested, compared with placebo, while lowering high-sensitivity C-reactive protein by 39 percentage points.
Dr. Libby has been studying interleukin-1B since the 1980s. “Now, today, for the first time, in a rigorous trial, we can show that an anti-inflammatory agent that is neutral for lipids (that doesn’t lower LDL) can provide a benefit for our patients, and that’s a real step forward,” Dr. Libby said in a video interview at the annual congress of the European Society of Cardiology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Importantly, a dividend of the investigation was that “we found a decrease in fatal cancers, particularly lung cancer. So this again opens the door toward a whole new therapeutic window in patients not just in the cardiovascular space, but also in oncology. So it’s a doubly exciting day for us.”
CANTOS was presented at the meeting by Paul Ridker, MD, also of Harvard Medical School; the results were also published online (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914).
BARCELONA – The results of the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) mark the validation of many years of research on inflammation for Peter Libby, MD, Mallinckrodt Professor of Medicine, Harvard Medical School, Boston.
The CANTOS investigator said that, although some trials, most notably JUPITER, have linked reduced markers of inflammation with reduced cardiovascular events, none have been able to separate the effects of lowering LDL cholesterol from those of lowering the inflammatory marker interleukin-1B.
But using the monoclonal antibody canakinumab to target only interleukin-1B in CANTOS reduced the composite endpoint of nonfatal MI, nonfatal stroke, or cardiovascular death by 15% at the highest dosage tested, compared with placebo, while lowering high-sensitivity C-reactive protein by 39 percentage points.
Dr. Libby has been studying interleukin-1B since the 1980s. “Now, today, for the first time, in a rigorous trial, we can show that an anti-inflammatory agent that is neutral for lipids (that doesn’t lower LDL) can provide a benefit for our patients, and that’s a real step forward,” Dr. Libby said in a video interview at the annual congress of the European Society of Cardiology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Importantly, a dividend of the investigation was that “we found a decrease in fatal cancers, particularly lung cancer. So this again opens the door toward a whole new therapeutic window in patients not just in the cardiovascular space, but also in oncology. So it’s a doubly exciting day for us.”
CANTOS was presented at the meeting by Paul Ridker, MD, also of Harvard Medical School; the results were also published online (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914).
BARCELONA – The results of the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) mark the validation of many years of research on inflammation for Peter Libby, MD, Mallinckrodt Professor of Medicine, Harvard Medical School, Boston.
The CANTOS investigator said that, although some trials, most notably JUPITER, have linked reduced markers of inflammation with reduced cardiovascular events, none have been able to separate the effects of lowering LDL cholesterol from those of lowering the inflammatory marker interleukin-1B.
But using the monoclonal antibody canakinumab to target only interleukin-1B in CANTOS reduced the composite endpoint of nonfatal MI, nonfatal stroke, or cardiovascular death by 15% at the highest dosage tested, compared with placebo, while lowering high-sensitivity C-reactive protein by 39 percentage points.
Dr. Libby has been studying interleukin-1B since the 1980s. “Now, today, for the first time, in a rigorous trial, we can show that an anti-inflammatory agent that is neutral for lipids (that doesn’t lower LDL) can provide a benefit for our patients, and that’s a real step forward,” Dr. Libby said in a video interview at the annual congress of the European Society of Cardiology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Importantly, a dividend of the investigation was that “we found a decrease in fatal cancers, particularly lung cancer. So this again opens the door toward a whole new therapeutic window in patients not just in the cardiovascular space, but also in oncology. So it’s a doubly exciting day for us.”
CANTOS was presented at the meeting by Paul Ridker, MD, also of Harvard Medical School; the results were also published online (N Engl J Med. 2017 Aug 27. doi: 10.1056/NEJMoa1707914).
AT THE ESC CONGRESS 2017
Big risk of serious falls after first episode of syncope
BARCELONA – Patients have an exorbitant 80% increased risk of hospitalization for falls resulting in fracture or head injury in the first year after discharge following a first-ever episode of syncope, according to a Danish national cohort study. One in five patients who sustained a fall resulting in hospitalization experienced a hip fracture, according to Anna-Karin Nume, MD, of the University of Copenhagen.
In this interview at the annual congress of the European Society of Cardiology, Dr. Nume highlights findings from her study, which included 125,763 Danish adults with first-time syncope.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BARCELONA – Patients have an exorbitant 80% increased risk of hospitalization for falls resulting in fracture or head injury in the first year after discharge following a first-ever episode of syncope, according to a Danish national cohort study. One in five patients who sustained a fall resulting in hospitalization experienced a hip fracture, according to Anna-Karin Nume, MD, of the University of Copenhagen.
In this interview at the annual congress of the European Society of Cardiology, Dr. Nume highlights findings from her study, which included 125,763 Danish adults with first-time syncope.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BARCELONA – Patients have an exorbitant 80% increased risk of hospitalization for falls resulting in fracture or head injury in the first year after discharge following a first-ever episode of syncope, according to a Danish national cohort study. One in five patients who sustained a fall resulting in hospitalization experienced a hip fracture, according to Anna-Karin Nume, MD, of the University of Copenhagen.
In this interview at the annual congress of the European Society of Cardiology, Dr. Nume highlights findings from her study, which included 125,763 Danish adults with first-time syncope.
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 ESC CONGRESS 2017
Lessons on using cannabinoids for pediatric epilepsy
DENVER – holds useful lessons for physicians in states where legal marijuana is a far more recent development, Amy R. Brooks-Kayal, MD, said at the annual meeting of the Teratology Society.
Medical marijuana has been legal in Colorado for nearly 20 years. But the drug’s potential role in treating intractable pediatric epilepsy started getting a lot more attention in 2013 when a CNN report by Sanjay Gupta, MD, chronicled a child’s remarkable turnaround in response to medical marijuana. The story triggered a migration to the state by what has been termed “marijuana refugees”: desperate families with children who had the most severe, complex, treatment-refractory seizure disorders, said Dr. Brooks-Kayal, professor of pediatrics and neurology and chief of pediatric neurology at the University of Colorado at Denver, Aurora.
The situation, fortunately, has improved. There is now phase 3 randomized, double-blind, placebo-controlled clinical trial evidence of efficacy for an investigational proprietary cannabidiol oral solution known as Epidiolex for children and young adults with Dravet syndrome and drug-resistant seizures, as well as documentation of multiple adverse effects (N Engl J Med. 2017 May 25;376[21]:2011-20).
Dr. Brooks-Kayal, a past president of the American Epilepsy Society, said she believes this medication is potentially approvable by the Food and Drug Administration.
“In the world of new seizure medications, what is usually required by the FDA is a 50% reduction in seizures, which this agent gets close to reaching. But it does have a higher adverse event rate than many of our medications. However, this is a tough crowd. These are very, very difficult-to-treat children. So I think any addition to our armamentarium for these kids is going to be beneficial,” she said. “Unfortunately, though, it’s not going to be the panacea that I think some of our families are looking for.”
Based upon the Colorado experience, Dr. Brooks-Kayal offered the following suggestions for colleagues around the country as they begin fielding questions from families about medical marijuana for pediatric epilepsy:
- Provide families with the current data, discuss what’s known and still unknown, and encourage families to disclose the use of cannabinoids so the child can be monitored.
- Have the family keep a seizure diary. Get a baseline EEG and another at about 12 weeks. Do routine laboratory monitoring every 4 weeks, including liver function tests. “We think CBDs [cannabinoids] have the potential to worsen liver function,” she said.
- Stress the importance of leaving other seizure medications unchanged. “When this first started, the medical marijuana providers were recommending patients stop their other medications. The providers don’t do that anymore, fortunately,” Dr. Brooks-Kayal said. “Every week we were putting a child in a medically induced coma because they had status epilepticus, and it was the only way to stop their seizures. They started using marijuana products, they were sure it was going to be the cure, they stopped all their other medications, and they developed status epilepticus.”
- Establish policies with the hospital administration and pharmacy about how to handle marijuana products when a child is in the hospital. The Children’s Hospital Colorado pharmacy cannot store or dispense marijuana products because of federal regulations. And again, it’s unsafe to stop seizure medications abruptly, including marijuana products. Informed consent procedures need to be developed for when patients on cannabinoids are hospitalized.
- Encourage families to participate in one of the six Food and Drug Administration–approved double-blind, placebo-controlled trials of Epidiolex for Dravet syndrome, Lennox-Gastaut syndrome, tuberous sclerosis complex, and infantile spasms sponsored by GW Pharmaceuticals.
Breaking down the evidence
Here’s what’s known and what is still unknown about the safety and efficacy of cannabinoids for the treatment of refractory pediatric epilepsy, according to Dr. Brooks-Kayal.
The knowns
Cannabinoids show activity against seizures in animal models. Moreover, initial clinical data suggest they may decrease seizures in some children with refractory epilepsy. This evidence includes a retrospective study from Children’s Hospital Colorado reliant upon parental reports of improvement (Epilepsy Behav. 2015 Apr;45:49-52), an Israeli retrospective study (Seizure. 2016 Feb;35:41-4), a positive open-label trial of an investigational oral oil-based solution of a pharmaceutical-grade cannabidiol known as Epidiolex (Lancet Neurol. 2016 Mar;15[3]:270-8), and evidence from a Food and Drug Administration–authorized phase 3, randomized clinical trial of Epidiolex (N Engl J Med. 2017 May 25;376[21]:2011-20).
The incidence of short-term adverse events associated with cannabinoids is substantial. The rate seems to be higher with Epidiolex than with many other medical marijuana products, although the potency is greater, too. These include somnolence, fatigue, and convulsions.
In addition, gastrointestinal side effects are common with Epidiolex. “Some are probably due to the oil base; some [are] probably due to the cannabidiol itself,” said Dr. Brooks-Kayal.
The unknowns
What types of seizures does it work for? This is under study in a series of FDA-authorized phase 3 randomized trials.
What is the placebo-subtracted response rate to cannabidiol? In the randomized trial published in the New England Journal of Medicine, the median monthly frequency of seizures decreased from 12.4 to 5.9 with cannabidiol, compared with a reduction from 14.9 to 14.1 with placebo. This needs confirmation in additional trials.
What’s the optimal dose? The randomized trial tested just one dose – 20 mg/kg per day.
What are the drug interactions and their possible impact on cannabidiol efficacy? Outcomes appear to be better in patients on concomitant clobazam (Onfi), perhaps because of the significantly higher blood levels of clobazam’s major metabolite in children on cannabidiol.
Long-term effects
The jury is still out on the long-term adverse effects. “These medical marijuana products are being given by families to 2- and 3-month-olds. It will be years before we know about potential long-term cognitive and behavioral effects,” Dr. Brooks-Kayal said.
Dr. Brooks-Kayal reported having no financial conflicts of interest regarding her presentation.
DENVER – holds useful lessons for physicians in states where legal marijuana is a far more recent development, Amy R. Brooks-Kayal, MD, said at the annual meeting of the Teratology Society.
Medical marijuana has been legal in Colorado for nearly 20 years. But the drug’s potential role in treating intractable pediatric epilepsy started getting a lot more attention in 2013 when a CNN report by Sanjay Gupta, MD, chronicled a child’s remarkable turnaround in response to medical marijuana. The story triggered a migration to the state by what has been termed “marijuana refugees”: desperate families with children who had the most severe, complex, treatment-refractory seizure disorders, said Dr. Brooks-Kayal, professor of pediatrics and neurology and chief of pediatric neurology at the University of Colorado at Denver, Aurora.
The situation, fortunately, has improved. There is now phase 3 randomized, double-blind, placebo-controlled clinical trial evidence of efficacy for an investigational proprietary cannabidiol oral solution known as Epidiolex for children and young adults with Dravet syndrome and drug-resistant seizures, as well as documentation of multiple adverse effects (N Engl J Med. 2017 May 25;376[21]:2011-20).
Dr. Brooks-Kayal, a past president of the American Epilepsy Society, said she believes this medication is potentially approvable by the Food and Drug Administration.
“In the world of new seizure medications, what is usually required by the FDA is a 50% reduction in seizures, which this agent gets close to reaching. But it does have a higher adverse event rate than many of our medications. However, this is a tough crowd. These are very, very difficult-to-treat children. So I think any addition to our armamentarium for these kids is going to be beneficial,” she said. “Unfortunately, though, it’s not going to be the panacea that I think some of our families are looking for.”
Based upon the Colorado experience, Dr. Brooks-Kayal offered the following suggestions for colleagues around the country as they begin fielding questions from families about medical marijuana for pediatric epilepsy:
- Provide families with the current data, discuss what’s known and still unknown, and encourage families to disclose the use of cannabinoids so the child can be monitored.
- Have the family keep a seizure diary. Get a baseline EEG and another at about 12 weeks. Do routine laboratory monitoring every 4 weeks, including liver function tests. “We think CBDs [cannabinoids] have the potential to worsen liver function,” she said.
- Stress the importance of leaving other seizure medications unchanged. “When this first started, the medical marijuana providers were recommending patients stop their other medications. The providers don’t do that anymore, fortunately,” Dr. Brooks-Kayal said. “Every week we were putting a child in a medically induced coma because they had status epilepticus, and it was the only way to stop their seizures. They started using marijuana products, they were sure it was going to be the cure, they stopped all their other medications, and they developed status epilepticus.”
- Establish policies with the hospital administration and pharmacy about how to handle marijuana products when a child is in the hospital. The Children’s Hospital Colorado pharmacy cannot store or dispense marijuana products because of federal regulations. And again, it’s unsafe to stop seizure medications abruptly, including marijuana products. Informed consent procedures need to be developed for when patients on cannabinoids are hospitalized.
- Encourage families to participate in one of the six Food and Drug Administration–approved double-blind, placebo-controlled trials of Epidiolex for Dravet syndrome, Lennox-Gastaut syndrome, tuberous sclerosis complex, and infantile spasms sponsored by GW Pharmaceuticals.
Breaking down the evidence
Here’s what’s known and what is still unknown about the safety and efficacy of cannabinoids for the treatment of refractory pediatric epilepsy, according to Dr. Brooks-Kayal.
The knowns
Cannabinoids show activity against seizures in animal models. Moreover, initial clinical data suggest they may decrease seizures in some children with refractory epilepsy. This evidence includes a retrospective study from Children’s Hospital Colorado reliant upon parental reports of improvement (Epilepsy Behav. 2015 Apr;45:49-52), an Israeli retrospective study (Seizure. 2016 Feb;35:41-4), a positive open-label trial of an investigational oral oil-based solution of a pharmaceutical-grade cannabidiol known as Epidiolex (Lancet Neurol. 2016 Mar;15[3]:270-8), and evidence from a Food and Drug Administration–authorized phase 3, randomized clinical trial of Epidiolex (N Engl J Med. 2017 May 25;376[21]:2011-20).
The incidence of short-term adverse events associated with cannabinoids is substantial. The rate seems to be higher with Epidiolex than with many other medical marijuana products, although the potency is greater, too. These include somnolence, fatigue, and convulsions.
In addition, gastrointestinal side effects are common with Epidiolex. “Some are probably due to the oil base; some [are] probably due to the cannabidiol itself,” said Dr. Brooks-Kayal.
The unknowns
What types of seizures does it work for? This is under study in a series of FDA-authorized phase 3 randomized trials.
What is the placebo-subtracted response rate to cannabidiol? In the randomized trial published in the New England Journal of Medicine, the median monthly frequency of seizures decreased from 12.4 to 5.9 with cannabidiol, compared with a reduction from 14.9 to 14.1 with placebo. This needs confirmation in additional trials.
What’s the optimal dose? The randomized trial tested just one dose – 20 mg/kg per day.
What are the drug interactions and their possible impact on cannabidiol efficacy? Outcomes appear to be better in patients on concomitant clobazam (Onfi), perhaps because of the significantly higher blood levels of clobazam’s major metabolite in children on cannabidiol.
Long-term effects
The jury is still out on the long-term adverse effects. “These medical marijuana products are being given by families to 2- and 3-month-olds. It will be years before we know about potential long-term cognitive and behavioral effects,” Dr. Brooks-Kayal said.
Dr. Brooks-Kayal reported having no financial conflicts of interest regarding her presentation.
DENVER – holds useful lessons for physicians in states where legal marijuana is a far more recent development, Amy R. Brooks-Kayal, MD, said at the annual meeting of the Teratology Society.
Medical marijuana has been legal in Colorado for nearly 20 years. But the drug’s potential role in treating intractable pediatric epilepsy started getting a lot more attention in 2013 when a CNN report by Sanjay Gupta, MD, chronicled a child’s remarkable turnaround in response to medical marijuana. The story triggered a migration to the state by what has been termed “marijuana refugees”: desperate families with children who had the most severe, complex, treatment-refractory seizure disorders, said Dr. Brooks-Kayal, professor of pediatrics and neurology and chief of pediatric neurology at the University of Colorado at Denver, Aurora.
The situation, fortunately, has improved. There is now phase 3 randomized, double-blind, placebo-controlled clinical trial evidence of efficacy for an investigational proprietary cannabidiol oral solution known as Epidiolex for children and young adults with Dravet syndrome and drug-resistant seizures, as well as documentation of multiple adverse effects (N Engl J Med. 2017 May 25;376[21]:2011-20).
Dr. Brooks-Kayal, a past president of the American Epilepsy Society, said she believes this medication is potentially approvable by the Food and Drug Administration.
“In the world of new seizure medications, what is usually required by the FDA is a 50% reduction in seizures, which this agent gets close to reaching. But it does have a higher adverse event rate than many of our medications. However, this is a tough crowd. These are very, very difficult-to-treat children. So I think any addition to our armamentarium for these kids is going to be beneficial,” she said. “Unfortunately, though, it’s not going to be the panacea that I think some of our families are looking for.”
Based upon the Colorado experience, Dr. Brooks-Kayal offered the following suggestions for colleagues around the country as they begin fielding questions from families about medical marijuana for pediatric epilepsy:
- Provide families with the current data, discuss what’s known and still unknown, and encourage families to disclose the use of cannabinoids so the child can be monitored.
- Have the family keep a seizure diary. Get a baseline EEG and another at about 12 weeks. Do routine laboratory monitoring every 4 weeks, including liver function tests. “We think CBDs [cannabinoids] have the potential to worsen liver function,” she said.
- Stress the importance of leaving other seizure medications unchanged. “When this first started, the medical marijuana providers were recommending patients stop their other medications. The providers don’t do that anymore, fortunately,” Dr. Brooks-Kayal said. “Every week we were putting a child in a medically induced coma because they had status epilepticus, and it was the only way to stop their seizures. They started using marijuana products, they were sure it was going to be the cure, they stopped all their other medications, and they developed status epilepticus.”
- Establish policies with the hospital administration and pharmacy about how to handle marijuana products when a child is in the hospital. The Children’s Hospital Colorado pharmacy cannot store or dispense marijuana products because of federal regulations. And again, it’s unsafe to stop seizure medications abruptly, including marijuana products. Informed consent procedures need to be developed for when patients on cannabinoids are hospitalized.
- Encourage families to participate in one of the six Food and Drug Administration–approved double-blind, placebo-controlled trials of Epidiolex for Dravet syndrome, Lennox-Gastaut syndrome, tuberous sclerosis complex, and infantile spasms sponsored by GW Pharmaceuticals.
Breaking down the evidence
Here’s what’s known and what is still unknown about the safety and efficacy of cannabinoids for the treatment of refractory pediatric epilepsy, according to Dr. Brooks-Kayal.
The knowns
Cannabinoids show activity against seizures in animal models. Moreover, initial clinical data suggest they may decrease seizures in some children with refractory epilepsy. This evidence includes a retrospective study from Children’s Hospital Colorado reliant upon parental reports of improvement (Epilepsy Behav. 2015 Apr;45:49-52), an Israeli retrospective study (Seizure. 2016 Feb;35:41-4), a positive open-label trial of an investigational oral oil-based solution of a pharmaceutical-grade cannabidiol known as Epidiolex (Lancet Neurol. 2016 Mar;15[3]:270-8), and evidence from a Food and Drug Administration–authorized phase 3, randomized clinical trial of Epidiolex (N Engl J Med. 2017 May 25;376[21]:2011-20).
The incidence of short-term adverse events associated with cannabinoids is substantial. The rate seems to be higher with Epidiolex than with many other medical marijuana products, although the potency is greater, too. These include somnolence, fatigue, and convulsions.
In addition, gastrointestinal side effects are common with Epidiolex. “Some are probably due to the oil base; some [are] probably due to the cannabidiol itself,” said Dr. Brooks-Kayal.
The unknowns
What types of seizures does it work for? This is under study in a series of FDA-authorized phase 3 randomized trials.
What is the placebo-subtracted response rate to cannabidiol? In the randomized trial published in the New England Journal of Medicine, the median monthly frequency of seizures decreased from 12.4 to 5.9 with cannabidiol, compared with a reduction from 14.9 to 14.1 with placebo. This needs confirmation in additional trials.
What’s the optimal dose? The randomized trial tested just one dose – 20 mg/kg per day.
What are the drug interactions and their possible impact on cannabidiol efficacy? Outcomes appear to be better in patients on concomitant clobazam (Onfi), perhaps because of the significantly higher blood levels of clobazam’s major metabolite in children on cannabidiol.
Long-term effects
The jury is still out on the long-term adverse effects. “These medical marijuana products are being given by families to 2- and 3-month-olds. It will be years before we know about potential long-term cognitive and behavioral effects,” Dr. Brooks-Kayal said.
Dr. Brooks-Kayal reported having no financial conflicts of interest regarding her presentation.
EXPERT ANALYSIS FROM TERATOLOGY SOCIETY 2017
Acute lobar nephronia often has misleading presentation
MADRID – Acute lobar nephronia needs to be considered in children with high fever, abdominal pain, and markedly elevated acute-phase reactants, even if their urinalysis and ultrasound results are negative, Paula Sanchez-Marcos, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
She presented a retrospective study of 18 episodes of acute lobar nephronia (ALN) in 16 children seen at the hospital, a tertiary referral center. Six of the children had vesicoureteral reflux or another underlying uropathy. Mean age at diagnosis was 79 months, with a range of 5 to 180 months.
All patients had a fever greater than 38.5° C when they presented with a mean 6-day history of illness. Of the 16 children, 14 had abdominal pain. The mean C-reactive protein level was 197 mg/L, with a WBC count of 21,962 cells/mcL and a neutrophil count of 17,372 cells/mcL.
Urine dipstick was negative in five episodes. However, urine culture was eventually productive in 10 episodes, with Escherichia coli the most commonly isolated microorganism, found in five of these cases.
All patients underwent ultrasound imaging a mean of 1.7 days into their hospital admission, although it established the diagnosis of ALN in only two episodes. Additional imaging with CT had a 91% sensitivity, showing positive results in 10 of 11 cases, while MRI had 100% sensitivity.
Patients received IV antibiotics for a median of 14 days before switching to sequential oral antibiotics for a median of 8.7 days.
Three patients developed renal abscesses, with percutaneous drainage required in two instances. Unilateral renal scarring occurred in 7 of 16 patients.
Dr. Sanchez-Marcos recommended technetium-99m dimercaptosuccinic acid renal scintigraphy as a tool to confirm improvement in response to antimicrobial therapy.
She reported having no financial conflicts regarding her presentation.
MADRID – Acute lobar nephronia needs to be considered in children with high fever, abdominal pain, and markedly elevated acute-phase reactants, even if their urinalysis and ultrasound results are negative, Paula Sanchez-Marcos, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
She presented a retrospective study of 18 episodes of acute lobar nephronia (ALN) in 16 children seen at the hospital, a tertiary referral center. Six of the children had vesicoureteral reflux or another underlying uropathy. Mean age at diagnosis was 79 months, with a range of 5 to 180 months.
All patients had a fever greater than 38.5° C when they presented with a mean 6-day history of illness. Of the 16 children, 14 had abdominal pain. The mean C-reactive protein level was 197 mg/L, with a WBC count of 21,962 cells/mcL and a neutrophil count of 17,372 cells/mcL.
Urine dipstick was negative in five episodes. However, urine culture was eventually productive in 10 episodes, with Escherichia coli the most commonly isolated microorganism, found in five of these cases.
All patients underwent ultrasound imaging a mean of 1.7 days into their hospital admission, although it established the diagnosis of ALN in only two episodes. Additional imaging with CT had a 91% sensitivity, showing positive results in 10 of 11 cases, while MRI had 100% sensitivity.
Patients received IV antibiotics for a median of 14 days before switching to sequential oral antibiotics for a median of 8.7 days.
Three patients developed renal abscesses, with percutaneous drainage required in two instances. Unilateral renal scarring occurred in 7 of 16 patients.
Dr. Sanchez-Marcos recommended technetium-99m dimercaptosuccinic acid renal scintigraphy as a tool to confirm improvement in response to antimicrobial therapy.
She reported having no financial conflicts regarding her presentation.
MADRID – Acute lobar nephronia needs to be considered in children with high fever, abdominal pain, and markedly elevated acute-phase reactants, even if their urinalysis and ultrasound results are negative, Paula Sanchez-Marcos, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
She presented a retrospective study of 18 episodes of acute lobar nephronia (ALN) in 16 children seen at the hospital, a tertiary referral center. Six of the children had vesicoureteral reflux or another underlying uropathy. Mean age at diagnosis was 79 months, with a range of 5 to 180 months.
All patients had a fever greater than 38.5° C when they presented with a mean 6-day history of illness. Of the 16 children, 14 had abdominal pain. The mean C-reactive protein level was 197 mg/L, with a WBC count of 21,962 cells/mcL and a neutrophil count of 17,372 cells/mcL.
Urine dipstick was negative in five episodes. However, urine culture was eventually productive in 10 episodes, with Escherichia coli the most commonly isolated microorganism, found in five of these cases.
All patients underwent ultrasound imaging a mean of 1.7 days into their hospital admission, although it established the diagnosis of ALN in only two episodes. Additional imaging with CT had a 91% sensitivity, showing positive results in 10 of 11 cases, while MRI had 100% sensitivity.
Patients received IV antibiotics for a median of 14 days before switching to sequential oral antibiotics for a median of 8.7 days.
Three patients developed renal abscesses, with percutaneous drainage required in two instances. Unilateral renal scarring occurred in 7 of 16 patients.
Dr. Sanchez-Marcos recommended technetium-99m dimercaptosuccinic acid renal scintigraphy as a tool to confirm improvement in response to antimicrobial therapy.
She reported having no financial conflicts regarding her presentation.
AT ESPID 2017
Key clinical point:
Major finding: Urine dipstick results were negative in 5 instances, and ultrasound was negative in 16 cases.
Data source: This was a single-center, retrospective, descriptive study of 18 episodes of acute lobar nephronia in 16 children.
Disclosures: Dr. Sanchez-Marcos reported having no financial conflicts of interest.
Cancer screening in elderly: When to just say no
ESTES PARK, COLO. – A simple walking speed measurement over a 20-foot distance is an invaluable guide to physiologic age as part of individualized decision making about when to stop cancer screening in elderly patients, according to Jeff Wallace, MD, professor of geriatric medicine at the University of Colorado at Denver.
“If you have one measurement to assess ‘am I aging well?’ it’s your gait speed. A lot of us in geriatrics are advocating evaluation of gait speed in all patients as a fifth vital sign. It’s probably more useful than blood pressure in some of the older adults coming into our clinics,” he said at a conference on internal medicine sponsored by the University of Colorado.
Dr. Wallace also gave a shout-out to the ePrognosis cancer-screening decision tool, available free at www.eprognosis.org, as an aid in shared decision-making conversations regarding when to stop cancer screening. This tool, developed by researchers at the University of California, San Francisco, allows physicians to plug key individual patient characteristics into its model, including comorbid conditions, functional status, and body mass index, and then spits out data-driven estimated benefits and harms a patient can expect from advanced-age screening for colon or breast cancer.
Of course, guidelines as to when to stop screening for various cancers are available from the U.S. Preventive Services Task Force, the American Cancer Society, and specialty societies. However, it’s important that nongeriatricians understand the serious limitations of those guidelines.
“We’re not guidelines followers in the geriatrics world because the guidelines don’t apply to most of our patients,” he explained. “We hate guidelines in geriatrics because few studies – and no lung cancer or breast cancer trials – enroll patients over age 75 with comorbid conditions. Also, most of these guidelines do not incorporate patient preferences, which probably should be a primary goal. So we’re left extrapolating.“
Regrettably, though, “it turns out most Americans are drinking the Kool-Aid when it comes to patient preferences. It’s amazing how much cancer screening is going on in this country. We’re doing a lot more than we should,” said Dr. Wallace.
All of that is clearly overscreening. Experts unanimously agree that if someone is not going to live for 10 years, that person is not likely to benefit from cancer screening. The one exception is lung cancer screening of high-risk patients, where there are data to show that annual low-dose CT screening is beneficial in those with even a 5-year life expectancy.
As part of the Choosing Wisely program, the American Geriatric Society has advocated that physicians “don’t recommend screening for breast, colorectal, prostate, or lung cancer without considering life expectancy and the risks of testing, overdiagnosis, and overtreatment.”
That’s where gait speed and ePrognosis come in handy in discussions with patients regarding what they can realistically expect from cancer screening at an advanced age.
The importance of gait speed was highlighted in a pooled analysis of nine cohort studies totaling more than 34,000 community-dwelling adults aged 65 years and older with 6-21 years of follow-up. Investigators at the University of Pittsburgh identified a strong relationship between gait speed and survival. Every 0.1-m/sec made a significant difference (JAMA. 2011 Jan 5;305[1]:50-8).
A gait speed evaluation is simple: The patient is asked to walk 20 feet at a normal speed, not racing. For men age 75, the Pittsburgh investigators found, gait speed predicted 10-year survival across a range of 19%-87%. The median speed was 0.8 m/sec, or about 1.8 mph, so a middle-of-the-pack walker ought to stop all cancer screening by age 75. A fast-walking older man won’t reach a 10-year remaining life expectancy until he’s in his early to mid-80s; a slow walker reaches that life expectancy as early as his late 60s, depending upon just how slow he walks. A woman at age 80 with an average gait speed has roughly 10 years of remaining life, factoring in plus or minus 5 years from that landmark depending upon whether she is a faster- or slower-than-average walker, Dr. Wallace explained.
The U.S. Preventive Services Task Force currently recommends colon cancer screening routinely for 50- to 75-year-olds, declaring in accord with other groups that this strategy has a high certainty of substantial net benefit. But the USPSTF also recommends selective screening for those aged 76-85, with a weaker C recommendation (JAMA. 2016 Jun 21;315[23]:2564-75).
What are the practical implications of that recommendation for selective screening after age 75?
Investigators at Harvard Medical School and the University of Oslo recently took a closer look. Their population-based, prospective, observational study included 1,355,692 Medicare beneficiaries aged 70-79 years at average risk for colorectal cancer who had not had a colonoscopy within the previous 5 years.
The investigators demonstrated that the benefit of screening colonoscopy decreased with age. For patients aged 70-74, the 8-year risk of colorectal cancer was 2.19% in those who were screened, compared with 2.62% in those who weren’t, for an absolute 0.43% difference. The number needed to be screened to detect one additional case of colorectal cancer was 283. Among those aged 75-79, the number needed to be screened climbed to 714 (Ann Intern Med. 2017 Jan 3;166[1]18-26).
Moreover, the risk of colonoscopy-related adverse events also climbed with age. These included perforations, falls while racing to the bathroom during the preprocedural bowel prep, and the humiliation of fecal incontinence. The excess 30-day risk for any adverse event in the colonoscopy group was 5.6 events per 1,000 patients aged 70-74 and 10.3 per 1,000 in 75- to 79-year-olds.
In a similar vein, Mara A. Schonberg, MD, of Harvard Medical School, Boston, has shed light on the risks and benefits of biannual mammographic screening for breast cancer in 70- to 79-year-olds, a practice recommended in American Cancer Society guidelines for women who are in overall good health and have at least a 10-year life expectancy.
She estimated that 2 women per 1,000 screened would avoid death due to breast cancer, for a number needed to screen of 500. But roughly 200 of those 1,000 women would experience a false-positive mammogram, and 20-40 of those false-positive imaging studies would result in a breast biopsy. Also, roughly 30% of the screen-detected cancers would not otherwise become apparent in an older woman’s lifetime, yet nearly all of the malignancies would undergo breast cancer therapy (J Am Geriatr Soc. 2016 Dec;64[12]:2413-8).
Dr. Schonberg’s research speaks to Dr. Wallace.
“It’s breast cancer therapy: It’s procedures; it’s medicalizing the patient’s whole life and creating a high degree of angst when she’s 75 or 80,” he said.
As to when to ‘just say no’ to cancer screening, Dr. Wallace said his answer is after age 65 for cervical cancer screening in women with at least two normal screens in the past 10 years or a prior total hysterectomy for a benign indication. All of the guidelines agree on that, although the American Congress of Obstetricians and Gynecologists recommends in addition that women with cervical intraepithelial neoplasia 2 be screened for the next 20 years.
For prostate cancer, Dr. Wallace recommends his colleagues just say no to screening at age 70 and above because harm is more likely than benefit to ensue.
“I don’t know about you, but I have a ton of patients over age 70 asking me for PSAs. That’s one place I won’t do any screening. I tell them I know you’re in great shape for 76 and you think it’s a good idea, but I think it’s bad medicine and I won’t do it. Even the American Urological Association says don’t do it after age 70,” he said.
For prostate cancer screening at age 55-69, however, patient preference rules the day, he added.
He draws the line at any cancer screening in patients aged 90 or over. Mean survival at age 90 is another 4-5 years. Only 11% of 90-year-old women will reach 100.
“Everybody has to die eventually,” he mused.
Dr. Wallace reported having no financial conflicts regarding his presentation.
ESTES PARK, COLO. – A simple walking speed measurement over a 20-foot distance is an invaluable guide to physiologic age as part of individualized decision making about when to stop cancer screening in elderly patients, according to Jeff Wallace, MD, professor of geriatric medicine at the University of Colorado at Denver.
“If you have one measurement to assess ‘am I aging well?’ it’s your gait speed. A lot of us in geriatrics are advocating evaluation of gait speed in all patients as a fifth vital sign. It’s probably more useful than blood pressure in some of the older adults coming into our clinics,” he said at a conference on internal medicine sponsored by the University of Colorado.
Dr. Wallace also gave a shout-out to the ePrognosis cancer-screening decision tool, available free at www.eprognosis.org, as an aid in shared decision-making conversations regarding when to stop cancer screening. This tool, developed by researchers at the University of California, San Francisco, allows physicians to plug key individual patient characteristics into its model, including comorbid conditions, functional status, and body mass index, and then spits out data-driven estimated benefits and harms a patient can expect from advanced-age screening for colon or breast cancer.
Of course, guidelines as to when to stop screening for various cancers are available from the U.S. Preventive Services Task Force, the American Cancer Society, and specialty societies. However, it’s important that nongeriatricians understand the serious limitations of those guidelines.
“We’re not guidelines followers in the geriatrics world because the guidelines don’t apply to most of our patients,” he explained. “We hate guidelines in geriatrics because few studies – and no lung cancer or breast cancer trials – enroll patients over age 75 with comorbid conditions. Also, most of these guidelines do not incorporate patient preferences, which probably should be a primary goal. So we’re left extrapolating.“
Regrettably, though, “it turns out most Americans are drinking the Kool-Aid when it comes to patient preferences. It’s amazing how much cancer screening is going on in this country. We’re doing a lot more than we should,” said Dr. Wallace.
All of that is clearly overscreening. Experts unanimously agree that if someone is not going to live for 10 years, that person is not likely to benefit from cancer screening. The one exception is lung cancer screening of high-risk patients, where there are data to show that annual low-dose CT screening is beneficial in those with even a 5-year life expectancy.
As part of the Choosing Wisely program, the American Geriatric Society has advocated that physicians “don’t recommend screening for breast, colorectal, prostate, or lung cancer without considering life expectancy and the risks of testing, overdiagnosis, and overtreatment.”
That’s where gait speed and ePrognosis come in handy in discussions with patients regarding what they can realistically expect from cancer screening at an advanced age.
The importance of gait speed was highlighted in a pooled analysis of nine cohort studies totaling more than 34,000 community-dwelling adults aged 65 years and older with 6-21 years of follow-up. Investigators at the University of Pittsburgh identified a strong relationship between gait speed and survival. Every 0.1-m/sec made a significant difference (JAMA. 2011 Jan 5;305[1]:50-8).
A gait speed evaluation is simple: The patient is asked to walk 20 feet at a normal speed, not racing. For men age 75, the Pittsburgh investigators found, gait speed predicted 10-year survival across a range of 19%-87%. The median speed was 0.8 m/sec, or about 1.8 mph, so a middle-of-the-pack walker ought to stop all cancer screening by age 75. A fast-walking older man won’t reach a 10-year remaining life expectancy until he’s in his early to mid-80s; a slow walker reaches that life expectancy as early as his late 60s, depending upon just how slow he walks. A woman at age 80 with an average gait speed has roughly 10 years of remaining life, factoring in plus or minus 5 years from that landmark depending upon whether she is a faster- or slower-than-average walker, Dr. Wallace explained.
The U.S. Preventive Services Task Force currently recommends colon cancer screening routinely for 50- to 75-year-olds, declaring in accord with other groups that this strategy has a high certainty of substantial net benefit. But the USPSTF also recommends selective screening for those aged 76-85, with a weaker C recommendation (JAMA. 2016 Jun 21;315[23]:2564-75).
What are the practical implications of that recommendation for selective screening after age 75?
Investigators at Harvard Medical School and the University of Oslo recently took a closer look. Their population-based, prospective, observational study included 1,355,692 Medicare beneficiaries aged 70-79 years at average risk for colorectal cancer who had not had a colonoscopy within the previous 5 years.
The investigators demonstrated that the benefit of screening colonoscopy decreased with age. For patients aged 70-74, the 8-year risk of colorectal cancer was 2.19% in those who were screened, compared with 2.62% in those who weren’t, for an absolute 0.43% difference. The number needed to be screened to detect one additional case of colorectal cancer was 283. Among those aged 75-79, the number needed to be screened climbed to 714 (Ann Intern Med. 2017 Jan 3;166[1]18-26).
Moreover, the risk of colonoscopy-related adverse events also climbed with age. These included perforations, falls while racing to the bathroom during the preprocedural bowel prep, and the humiliation of fecal incontinence. The excess 30-day risk for any adverse event in the colonoscopy group was 5.6 events per 1,000 patients aged 70-74 and 10.3 per 1,000 in 75- to 79-year-olds.
In a similar vein, Mara A. Schonberg, MD, of Harvard Medical School, Boston, has shed light on the risks and benefits of biannual mammographic screening for breast cancer in 70- to 79-year-olds, a practice recommended in American Cancer Society guidelines for women who are in overall good health and have at least a 10-year life expectancy.
She estimated that 2 women per 1,000 screened would avoid death due to breast cancer, for a number needed to screen of 500. But roughly 200 of those 1,000 women would experience a false-positive mammogram, and 20-40 of those false-positive imaging studies would result in a breast biopsy. Also, roughly 30% of the screen-detected cancers would not otherwise become apparent in an older woman’s lifetime, yet nearly all of the malignancies would undergo breast cancer therapy (J Am Geriatr Soc. 2016 Dec;64[12]:2413-8).
Dr. Schonberg’s research speaks to Dr. Wallace.
“It’s breast cancer therapy: It’s procedures; it’s medicalizing the patient’s whole life and creating a high degree of angst when she’s 75 or 80,” he said.
As to when to ‘just say no’ to cancer screening, Dr. Wallace said his answer is after age 65 for cervical cancer screening in women with at least two normal screens in the past 10 years or a prior total hysterectomy for a benign indication. All of the guidelines agree on that, although the American Congress of Obstetricians and Gynecologists recommends in addition that women with cervical intraepithelial neoplasia 2 be screened for the next 20 years.
For prostate cancer, Dr. Wallace recommends his colleagues just say no to screening at age 70 and above because harm is more likely than benefit to ensue.
“I don’t know about you, but I have a ton of patients over age 70 asking me for PSAs. That’s one place I won’t do any screening. I tell them I know you’re in great shape for 76 and you think it’s a good idea, but I think it’s bad medicine and I won’t do it. Even the American Urological Association says don’t do it after age 70,” he said.
For prostate cancer screening at age 55-69, however, patient preference rules the day, he added.
He draws the line at any cancer screening in patients aged 90 or over. Mean survival at age 90 is another 4-5 years. Only 11% of 90-year-old women will reach 100.
“Everybody has to die eventually,” he mused.
Dr. Wallace reported having no financial conflicts regarding his presentation.
ESTES PARK, COLO. – A simple walking speed measurement over a 20-foot distance is an invaluable guide to physiologic age as part of individualized decision making about when to stop cancer screening in elderly patients, according to Jeff Wallace, MD, professor of geriatric medicine at the University of Colorado at Denver.
“If you have one measurement to assess ‘am I aging well?’ it’s your gait speed. A lot of us in geriatrics are advocating evaluation of gait speed in all patients as a fifth vital sign. It’s probably more useful than blood pressure in some of the older adults coming into our clinics,” he said at a conference on internal medicine sponsored by the University of Colorado.
Dr. Wallace also gave a shout-out to the ePrognosis cancer-screening decision tool, available free at www.eprognosis.org, as an aid in shared decision-making conversations regarding when to stop cancer screening. This tool, developed by researchers at the University of California, San Francisco, allows physicians to plug key individual patient characteristics into its model, including comorbid conditions, functional status, and body mass index, and then spits out data-driven estimated benefits and harms a patient can expect from advanced-age screening for colon or breast cancer.
Of course, guidelines as to when to stop screening for various cancers are available from the U.S. Preventive Services Task Force, the American Cancer Society, and specialty societies. However, it’s important that nongeriatricians understand the serious limitations of those guidelines.
“We’re not guidelines followers in the geriatrics world because the guidelines don’t apply to most of our patients,” he explained. “We hate guidelines in geriatrics because few studies – and no lung cancer or breast cancer trials – enroll patients over age 75 with comorbid conditions. Also, most of these guidelines do not incorporate patient preferences, which probably should be a primary goal. So we’re left extrapolating.“
Regrettably, though, “it turns out most Americans are drinking the Kool-Aid when it comes to patient preferences. It’s amazing how much cancer screening is going on in this country. We’re doing a lot more than we should,” said Dr. Wallace.
All of that is clearly overscreening. Experts unanimously agree that if someone is not going to live for 10 years, that person is not likely to benefit from cancer screening. The one exception is lung cancer screening of high-risk patients, where there are data to show that annual low-dose CT screening is beneficial in those with even a 5-year life expectancy.
As part of the Choosing Wisely program, the American Geriatric Society has advocated that physicians “don’t recommend screening for breast, colorectal, prostate, or lung cancer without considering life expectancy and the risks of testing, overdiagnosis, and overtreatment.”
That’s where gait speed and ePrognosis come in handy in discussions with patients regarding what they can realistically expect from cancer screening at an advanced age.
The importance of gait speed was highlighted in a pooled analysis of nine cohort studies totaling more than 34,000 community-dwelling adults aged 65 years and older with 6-21 years of follow-up. Investigators at the University of Pittsburgh identified a strong relationship between gait speed and survival. Every 0.1-m/sec made a significant difference (JAMA. 2011 Jan 5;305[1]:50-8).
A gait speed evaluation is simple: The patient is asked to walk 20 feet at a normal speed, not racing. For men age 75, the Pittsburgh investigators found, gait speed predicted 10-year survival across a range of 19%-87%. The median speed was 0.8 m/sec, or about 1.8 mph, so a middle-of-the-pack walker ought to stop all cancer screening by age 75. A fast-walking older man won’t reach a 10-year remaining life expectancy until he’s in his early to mid-80s; a slow walker reaches that life expectancy as early as his late 60s, depending upon just how slow he walks. A woman at age 80 with an average gait speed has roughly 10 years of remaining life, factoring in plus or minus 5 years from that landmark depending upon whether she is a faster- or slower-than-average walker, Dr. Wallace explained.
The U.S. Preventive Services Task Force currently recommends colon cancer screening routinely for 50- to 75-year-olds, declaring in accord with other groups that this strategy has a high certainty of substantial net benefit. But the USPSTF also recommends selective screening for those aged 76-85, with a weaker C recommendation (JAMA. 2016 Jun 21;315[23]:2564-75).
What are the practical implications of that recommendation for selective screening after age 75?
Investigators at Harvard Medical School and the University of Oslo recently took a closer look. Their population-based, prospective, observational study included 1,355,692 Medicare beneficiaries aged 70-79 years at average risk for colorectal cancer who had not had a colonoscopy within the previous 5 years.
The investigators demonstrated that the benefit of screening colonoscopy decreased with age. For patients aged 70-74, the 8-year risk of colorectal cancer was 2.19% in those who were screened, compared with 2.62% in those who weren’t, for an absolute 0.43% difference. The number needed to be screened to detect one additional case of colorectal cancer was 283. Among those aged 75-79, the number needed to be screened climbed to 714 (Ann Intern Med. 2017 Jan 3;166[1]18-26).
Moreover, the risk of colonoscopy-related adverse events also climbed with age. These included perforations, falls while racing to the bathroom during the preprocedural bowel prep, and the humiliation of fecal incontinence. The excess 30-day risk for any adverse event in the colonoscopy group was 5.6 events per 1,000 patients aged 70-74 and 10.3 per 1,000 in 75- to 79-year-olds.
In a similar vein, Mara A. Schonberg, MD, of Harvard Medical School, Boston, has shed light on the risks and benefits of biannual mammographic screening for breast cancer in 70- to 79-year-olds, a practice recommended in American Cancer Society guidelines for women who are in overall good health and have at least a 10-year life expectancy.
She estimated that 2 women per 1,000 screened would avoid death due to breast cancer, for a number needed to screen of 500. But roughly 200 of those 1,000 women would experience a false-positive mammogram, and 20-40 of those false-positive imaging studies would result in a breast biopsy. Also, roughly 30% of the screen-detected cancers would not otherwise become apparent in an older woman’s lifetime, yet nearly all of the malignancies would undergo breast cancer therapy (J Am Geriatr Soc. 2016 Dec;64[12]:2413-8).
Dr. Schonberg’s research speaks to Dr. Wallace.
“It’s breast cancer therapy: It’s procedures; it’s medicalizing the patient’s whole life and creating a high degree of angst when she’s 75 or 80,” he said.
As to when to ‘just say no’ to cancer screening, Dr. Wallace said his answer is after age 65 for cervical cancer screening in women with at least two normal screens in the past 10 years or a prior total hysterectomy for a benign indication. All of the guidelines agree on that, although the American Congress of Obstetricians and Gynecologists recommends in addition that women with cervical intraepithelial neoplasia 2 be screened for the next 20 years.
For prostate cancer, Dr. Wallace recommends his colleagues just say no to screening at age 70 and above because harm is more likely than benefit to ensue.
“I don’t know about you, but I have a ton of patients over age 70 asking me for PSAs. That’s one place I won’t do any screening. I tell them I know you’re in great shape for 76 and you think it’s a good idea, but I think it’s bad medicine and I won’t do it. Even the American Urological Association says don’t do it after age 70,” he said.
For prostate cancer screening at age 55-69, however, patient preference rules the day, he added.
He draws the line at any cancer screening in patients aged 90 or over. Mean survival at age 90 is another 4-5 years. Only 11% of 90-year-old women will reach 100.
“Everybody has to die eventually,” he mused.
Dr. Wallace reported having no financial conflicts regarding his presentation.
EXPERT ANALYSIS FROM THE ANNUAL INTERNAL MEDICINE PROGRAM
New acellular pertussis vaccine may solve waning immunogenicity problem
MADRID – A novel, monovalent, acellular pertussis vaccine containing a recombinant, genetically inactivated pertussis toxin displayed markedly greater sustained immunogenicity than the widely used Sanofi Pasteur Tdap, known as Adacel, which is used as a booster vaccination of adolescents and young adults, in a pivotal phase 3, randomized trial, Simonetta Viviani, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
“Our interpretation of these results is that they open up a new way to approach pertussis vaccination,” declared Dr. Viviani, director of clinical development at BioNet-Asia, a Bangkok-based biotech vaccine company.
The impetus for developing new acellular pertussis vaccines is the documented resurgence of pertussis.
“One suggested approach has been to replace chemically inactivated PT with a genetically inactivated PT. The rationale for that is the epitopes of the PT are conserved in the genetically modified PT toxin, as opposed to being destroyed in the chemical inactivation process,” Dr. Viviani explained.
The significant phase 3 trial included 450 Thai 12- to 17-year-olds who were randomized to a single 0.5-mL dose of Pertagen, Boostagen, or Adacel. Both Pertagen and Boostagen contain 5 mcg of the genetically inactivated PT and 5 mcg of filamentous hemagglutinin.
The seroconversion rate, defined as the proportion of subjects who reached at least a fourfold increase in titers of PT and filamentous-hemagglutinin antibodies over baseline, was far superior at both 28 days and 1 year in subjects who got Pertagen or Boostagen, compared with those who received Adacel.
Session chair Ulrich Heininger, MD, declared, “This is really, really exciting.”
It now will be very important that the monovalent Pertagen vaccine be formally studied in pregnant women, he observed.
“Since we’d like to immunize women in every pregnancy and they don’t necessarily need the Td component of Tdap every time, a monovalent vaccine might open a new path for acceptance,” commented Dr. Heininger, professor of pediatric infectious diseases at University Children’s Hospital in Basel, Switz.
Dr. Viviani said that a study in pregnant women is now in the early planning stages.
The study was sponsored by BioNet-Asia and Mahidol University. Dr. Viviani is a BioNet employee.
MADRID – A novel, monovalent, acellular pertussis vaccine containing a recombinant, genetically inactivated pertussis toxin displayed markedly greater sustained immunogenicity than the widely used Sanofi Pasteur Tdap, known as Adacel, which is used as a booster vaccination of adolescents and young adults, in a pivotal phase 3, randomized trial, Simonetta Viviani, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
“Our interpretation of these results is that they open up a new way to approach pertussis vaccination,” declared Dr. Viviani, director of clinical development at BioNet-Asia, a Bangkok-based biotech vaccine company.
The impetus for developing new acellular pertussis vaccines is the documented resurgence of pertussis.
“One suggested approach has been to replace chemically inactivated PT with a genetically inactivated PT. The rationale for that is the epitopes of the PT are conserved in the genetically modified PT toxin, as opposed to being destroyed in the chemical inactivation process,” Dr. Viviani explained.
The significant phase 3 trial included 450 Thai 12- to 17-year-olds who were randomized to a single 0.5-mL dose of Pertagen, Boostagen, or Adacel. Both Pertagen and Boostagen contain 5 mcg of the genetically inactivated PT and 5 mcg of filamentous hemagglutinin.
The seroconversion rate, defined as the proportion of subjects who reached at least a fourfold increase in titers of PT and filamentous-hemagglutinin antibodies over baseline, was far superior at both 28 days and 1 year in subjects who got Pertagen or Boostagen, compared with those who received Adacel.
Session chair Ulrich Heininger, MD, declared, “This is really, really exciting.”
It now will be very important that the monovalent Pertagen vaccine be formally studied in pregnant women, he observed.
“Since we’d like to immunize women in every pregnancy and they don’t necessarily need the Td component of Tdap every time, a monovalent vaccine might open a new path for acceptance,” commented Dr. Heininger, professor of pediatric infectious diseases at University Children’s Hospital in Basel, Switz.
Dr. Viviani said that a study in pregnant women is now in the early planning stages.
The study was sponsored by BioNet-Asia and Mahidol University. Dr. Viviani is a BioNet employee.
MADRID – A novel, monovalent, acellular pertussis vaccine containing a recombinant, genetically inactivated pertussis toxin displayed markedly greater sustained immunogenicity than the widely used Sanofi Pasteur Tdap, known as Adacel, which is used as a booster vaccination of adolescents and young adults, in a pivotal phase 3, randomized trial, Simonetta Viviani, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
“Our interpretation of these results is that they open up a new way to approach pertussis vaccination,” declared Dr. Viviani, director of clinical development at BioNet-Asia, a Bangkok-based biotech vaccine company.
The impetus for developing new acellular pertussis vaccines is the documented resurgence of pertussis.
“One suggested approach has been to replace chemically inactivated PT with a genetically inactivated PT. The rationale for that is the epitopes of the PT are conserved in the genetically modified PT toxin, as opposed to being destroyed in the chemical inactivation process,” Dr. Viviani explained.
The significant phase 3 trial included 450 Thai 12- to 17-year-olds who were randomized to a single 0.5-mL dose of Pertagen, Boostagen, or Adacel. Both Pertagen and Boostagen contain 5 mcg of the genetically inactivated PT and 5 mcg of filamentous hemagglutinin.
The seroconversion rate, defined as the proportion of subjects who reached at least a fourfold increase in titers of PT and filamentous-hemagglutinin antibodies over baseline, was far superior at both 28 days and 1 year in subjects who got Pertagen or Boostagen, compared with those who received Adacel.
Session chair Ulrich Heininger, MD, declared, “This is really, really exciting.”
It now will be very important that the monovalent Pertagen vaccine be formally studied in pregnant women, he observed.
“Since we’d like to immunize women in every pregnancy and they don’t necessarily need the Td component of Tdap every time, a monovalent vaccine might open a new path for acceptance,” commented Dr. Heininger, professor of pediatric infectious diseases at University Children’s Hospital in Basel, Switz.
Dr. Viviani said that a study in pregnant women is now in the early planning stages.
The study was sponsored by BioNet-Asia and Mahidol University. Dr. Viviani is a BioNet employee.
AT ESPID 2017
Key clinical point:
Major finding: One year after teens received a single dose of a novel acellular pertussis vaccine, they had a geometric mean titer of PT neutralizing antibody of 77 IU/mL, compared with just 12 IU/mL in adolescents who received a conventional Tdap vaccine.
Data source: This randomized, triple-arm, pivotal phase 3 clinical trial included 450 Thai 12- to 17-year-olds followed for 1 year after receiving a single dose of a novel monovalent pertussis vaccine or a novel Tdap vaccine, both of which contain genetically inactivated pertussis toxin, or, instead of those, a widely utilized conventional Tdap vaccine.
Disclosures: The study was sponsored by BioNet-Asia and Mahidol University. Dr. Viviani is a BioNet employee.
Helpful schedules ease task of tapering opioids
ESTES PARK, COLO. – Now that the opioid epidemic has formally been declared a national emergency, physicians can expect to encounter growing pressure to taper opioids in their chronic pain patients, Sunny Linnebur, PharmD, predicted at a conference on internal medicine sponsored by the University of Colorado.
As an example of what physicians around the country might expect, she added, Colorado state health officials recently announced that coverage of opioid therapy for Medicaid patients will be reduced. State health officials recommended that physicians taper down their patients’ opioids.
Fortunately, helpful tools for doing so are just a few mouse clicks away, according to Dr. Linnebur, professor of clinical pharmacy at the University of Colorado, Aurora.
Indications for opioid tapering as described in a guide provided by the Centers for Disease Control and Prevention include lack of a sustained or clinically meaningful improvement in pain and functioning as defined, for example, by at least a 30% improvement on the three-item PEG scale; use of opioids at a daily dosage of 50 morphine equivalent doses or more without evidence of benefit; signs of a substance use disorder other than tobacco dependence; warning signs of harms, such as drowsiness, slurred speech, or difficulty controlling use of the medication; patient request; and any situation where the physician deems that the benefits no longer outweigh the risks (www.cdc.gov/drugoverdose/pdf/clinical_pocket_guide_tapering-a.pdf).
General principles of tapering opioids as outlined by the CDC include reducing the dosage by about 10% a week at a time – although if a patient has been on opioids for years, then at a slower rate, perhaps 10% per month, may be more appropriate. If a patient has been using a 12.5 mcg/hour fentanyl patch, a switch to an oral opioid is recommended to complete the taper. When the smallest dosage has been reached, the interval between doses can be stretched; and once the medication is being taken less than once per day, it can be stopped.
She highlighted an opioid tapering schedule form developed by experts at the Washington State Health Care Authority as being particularly useful.
“If you type in a patient’s opioid medication and dose, it will give you a week-to-week calendar schedule for tapering,” she explained. “We know that getting patients on the safest dose of opioid is important, but it’s also difficult. This is an objective taper schedule that will prevent the patient from withdrawing from their opioid and hopefully will help in tolerating the reduction.”
Dr. Linnebur reported having no financial conflicts of interest regarding her presentation.
ESTES PARK, COLO. – Now that the opioid epidemic has formally been declared a national emergency, physicians can expect to encounter growing pressure to taper opioids in their chronic pain patients, Sunny Linnebur, PharmD, predicted at a conference on internal medicine sponsored by the University of Colorado.
As an example of what physicians around the country might expect, she added, Colorado state health officials recently announced that coverage of opioid therapy for Medicaid patients will be reduced. State health officials recommended that physicians taper down their patients’ opioids.
Fortunately, helpful tools for doing so are just a few mouse clicks away, according to Dr. Linnebur, professor of clinical pharmacy at the University of Colorado, Aurora.
Indications for opioid tapering as described in a guide provided by the Centers for Disease Control and Prevention include lack of a sustained or clinically meaningful improvement in pain and functioning as defined, for example, by at least a 30% improvement on the three-item PEG scale; use of opioids at a daily dosage of 50 morphine equivalent doses or more without evidence of benefit; signs of a substance use disorder other than tobacco dependence; warning signs of harms, such as drowsiness, slurred speech, or difficulty controlling use of the medication; patient request; and any situation where the physician deems that the benefits no longer outweigh the risks (www.cdc.gov/drugoverdose/pdf/clinical_pocket_guide_tapering-a.pdf).
General principles of tapering opioids as outlined by the CDC include reducing the dosage by about 10% a week at a time – although if a patient has been on opioids for years, then at a slower rate, perhaps 10% per month, may be more appropriate. If a patient has been using a 12.5 mcg/hour fentanyl patch, a switch to an oral opioid is recommended to complete the taper. When the smallest dosage has been reached, the interval between doses can be stretched; and once the medication is being taken less than once per day, it can be stopped.
She highlighted an opioid tapering schedule form developed by experts at the Washington State Health Care Authority as being particularly useful.
“If you type in a patient’s opioid medication and dose, it will give you a week-to-week calendar schedule for tapering,” she explained. “We know that getting patients on the safest dose of opioid is important, but it’s also difficult. This is an objective taper schedule that will prevent the patient from withdrawing from their opioid and hopefully will help in tolerating the reduction.”
Dr. Linnebur reported having no financial conflicts of interest regarding her presentation.
ESTES PARK, COLO. – Now that the opioid epidemic has formally been declared a national emergency, physicians can expect to encounter growing pressure to taper opioids in their chronic pain patients, Sunny Linnebur, PharmD, predicted at a conference on internal medicine sponsored by the University of Colorado.
As an example of what physicians around the country might expect, she added, Colorado state health officials recently announced that coverage of opioid therapy for Medicaid patients will be reduced. State health officials recommended that physicians taper down their patients’ opioids.
Fortunately, helpful tools for doing so are just a few mouse clicks away, according to Dr. Linnebur, professor of clinical pharmacy at the University of Colorado, Aurora.
Indications for opioid tapering as described in a guide provided by the Centers for Disease Control and Prevention include lack of a sustained or clinically meaningful improvement in pain and functioning as defined, for example, by at least a 30% improvement on the three-item PEG scale; use of opioids at a daily dosage of 50 morphine equivalent doses or more without evidence of benefit; signs of a substance use disorder other than tobacco dependence; warning signs of harms, such as drowsiness, slurred speech, or difficulty controlling use of the medication; patient request; and any situation where the physician deems that the benefits no longer outweigh the risks (www.cdc.gov/drugoverdose/pdf/clinical_pocket_guide_tapering-a.pdf).
General principles of tapering opioids as outlined by the CDC include reducing the dosage by about 10% a week at a time – although if a patient has been on opioids for years, then at a slower rate, perhaps 10% per month, may be more appropriate. If a patient has been using a 12.5 mcg/hour fentanyl patch, a switch to an oral opioid is recommended to complete the taper. When the smallest dosage has been reached, the interval between doses can be stretched; and once the medication is being taken less than once per day, it can be stopped.
She highlighted an opioid tapering schedule form developed by experts at the Washington State Health Care Authority as being particularly useful.
“If you type in a patient’s opioid medication and dose, it will give you a week-to-week calendar schedule for tapering,” she explained. “We know that getting patients on the safest dose of opioid is important, but it’s also difficult. This is an objective taper schedule that will prevent the patient from withdrawing from their opioid and hopefully will help in tolerating the reduction.”
Dr. Linnebur reported having no financial conflicts of interest regarding her presentation.
EXPERT ANALYSIS FROM THE ANNUAL INTERNAL MEDICINE PROGRAM