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THE SEARCHLIGHT MESSENGER
Clinical Update
Reviewed by C. M. Counce: Posted on Monday, May 14, 2018 10:20 AM
The CGRP Receptor and Migraines.
A video review from Eli Lilly. Venture 17 has no economic relationship with Eli Lilly. This video is for educational purposes only.
Click this image to view the video.
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Will Boggs, MD: Posted on Friday, August 19, 2016 3:31 PM

Venetoclax monotherapy appears to improve outcomes in some patients with acute
myelogenous leukemia (AML), according to a phase 2, single-arm study.
"This study included patients that
were in categories that are difficult to treat - relapsed, refractory, and/or
elderly and deemed medically unfit to receive induction therapy," Dr.
Anthony Letai from Dana-Farber Cancer Institute in Boston told Reuters Health
by email.
"The fact that some of these
patients had leukemias that were relapsed or refractory to very tough regimens,
including regimens that require multi-week inpatient hospital stays, but
nonetheless responded to an oral outpatient therapy taken once a day was a very
interesting result," he said.
Venetoclax, a highly selective, oral
small-molecule B-cell leukemia/lymphoma-2 (BCL2) inhibitor, received FDA
approval for chronic lymphocytic leukemia (CLL) earlier this year.
 Dr. Letai and colleagues
investigated the efficacy and biological correlates of response in the first
clinical study of venetoclax monotherapy in 32 patients with
relapsed/refractory AML or untreated AML unfit for intensive therapy.
The objective response rate was 19%
(six of 32), with two patients achieving a complete response and four achieving
a complete response with incomplete blood count recovery. All objective
responses were achieved by the week-4 assessment.
An additional 19% had antileukemic
activity demonstrated by partial bone marrow response and incomplete
hematologic recovery.
The six-month leukemia-free survival
rate was 10% (median leukemia-free survival, 2.3 months), and the six-month
overall survival estimate was 36% (median overall survival, 4.7 months), the
researchers report in Cancer Discovery, online August 12. At the time of this report, all
patients had discontinued venetoclax: 29 due to progressive disease, one due to
adverse event, one withdrew consent, and one proceeded to allogeneic
hematopoietic stem cell transplant after achieving stable disease.
 "Our data provide evidence that
AML with IDH1/2 mutations exhibits BCL2 dependence and validates preclinical
data that suggest suppression of cytochrome c oxidase activity in IDH1/2 mutant
AML lowers the mitochondrial threshold to trigger apoptosis upon BCL2
inhibition," the researchers note. "However, activity observed in
patients with wild-type IDH1/2 suggests targeting BCL2 with venetoclax should
not be restricted to patients with mutations in IDH1/2."
Venetoclax monotherapy was generally
well tolerated, although treatment-emergent adverse events were reported for
all patients. Nausea, diarrhea, hypokalemia, vomiting, and headache were the
most commonly reported adverse events. "This study was the first
report of venetoclax in AML, and as such was a single-agent study," Dr.
Letai said. "However, I do not think single-agent use will be common in
AML for this drug. I think that venetoclax will be incorporated into
combinations with many other agents active in AML."
"Right now, in the elderly setting,
it is being combined with either hypomethylating agents (vidaza or decitabine)
or low-dose cytarabine, both commonly used in the elderly in AML," he
said. "The response rates have been fantastic, around 70%, as reported in
abstracts at ASH and ASCO. There will likely be clinical testing of
combinations including venetoclax at all stages of AML therapy, including
induction, consolidation, salvage. Indeed, some of these trials are already
starting. Who knows, perhaps even maintenance? It is well tolerated, so lends
itself to combination."
"Genomics and genetics are
often equated with personalized medicine, the job of which is to match the
right patient with the right drugs," Dr. Letai added. "Venetoclax has
so far demonstrated activity in CLL, mantle cell lymphoma, AML. There are no
genetic abnormalities
related to BCL-2 that would indicate activity in these cancers. If we relied on
genetics alone, these would have missed."
"Instead, we and others took a
functional approach to identifying BCL-2 dependence in cancers, and thus
identifying good targets for venetoclax," he said. "I think that
these functional precision-medicine approaches are going to be vital to taking
advantage of all the new drugs that are appearing in cancer. If we rely on genomics
alone, we will probably miss most of our therapeutic opportunities."
Dr. Fernando Ramos from the
University of Leon in Spain, who recently reviewed AML in older adults, told
Reuters Health by email, "Venetoclax may be an interesting option for
rescue therapy in this patient subset." "Precision medicine has come a
long way," added Dr. Ramos, who was not involved in the study.
"Venetoclax may be an interesting partner to azanucleosides in unfit AML
patients."
Currently, venetoclax is in phase 2
testing for AML, diffuse large B-cell lymphoma, and non-Hodgkin lymphoma and in
phase 3 testing for multiple myeloma.
AbbVie and Genentech funded the
study, employed 13 of the 22 authors, and had various relationships with four
other authors, including Dr. Letai.
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From the Rare Disease Report; Edited with Introduction by Dr. C. M. Counce: Posted on Wednesday, August 12, 2015 9:02 AM
 Von Willebrand disease (VWD) is an inherited, genetically and
clinically heterogeneous hemorrhagic disorder caused by a deficiency or
dysfunction of the protein called Von Willebrand factor (VWF). This protein is a necessary step in the coagulation cascade, but also involved in the initiation of platelet aggregation for proper blood clotting.
Consequently, defective VWF interaction between platelets and the vessel
wall impairs primary hemostasis. Von Willibrand factor circulates in blood
plasma at concentrations of approximately 10 mg/mL. In response to
numerous stimuli, VWF is released from storage granules in platelets and
vascular bed endothelial cells.
VWF performs two major roles in hemostasis, wether intrinsic or extrinsic. First, it
mediates the adhesion of platelets to sites of vascular injury. Second,
it binds and stabilizes the procoagulant protein factor VIII (FVIII).
The disease is divided into three major categories: Partial Quantitative Deficiency (type I), Qualitative Deficiency (type II), and Total Deficiency (type III). VWD type II is further divided into
four variant conditions (IIA, IIB, IIN, IIM), based on characteristics of
dysfunctional VWF.
According
to data pre-published online August 3rd, 2015, in Blood, successful management
of bleeding episodes were observed in 100% of subjects treated with BAX 111 for
von Willebrand disease (VWD) during a recently completed Phase 3 clinical
trial.
Bleeding-episode-management success was the primary endpoint
of the clinical trial. BAX 111 is a highly purified recombinant von
Willebrand factor (VWF) analog manufactured by Baxalta, Inc.
VWD is a rare, inherited, incurable, gene-based bleeding disorder in which a
missing or defective clotting protein (VWF) fails to bind with platelets in
blood vessel walls.
Normally, a blood-vessel tear initiates
bleeding and VWF assists in the repair. When VWF is absent or under-represented, the formation of platelet plugs are
inhibited during the clotting process, resulting in excessive bleeding and easy
bruising.
In more severe forms of VWD, the bleeding can be
life-threatening and require emergency treatment.
Efficacy and Safety of BAX 111
Gill et al derived their findings
from a Phase 3, multicenter, international, open-label study which evaluated
the safety, efficacy and pharmacokinetics of BAX 111 in 37 patients with severe
VWD.
Study participants evidenced a mean efficacy rating of < 2.5 on a 4-point
scale wherein lower numbers correlated with a higher degree of bleed control
(see sidebar below). Bleed control for all treated bleeding events (N=192
bleeds in 22 subjects) was rated as good or excellent (96.9% excellent; 119/122
minor, 59/61 moderate, and 6/7 major bleeds). In 81.8% of bleeds, 1 infusion
was sufficient to attain control. For major bleeds, the infusion median was
Sidebar: Hemostatic Efficiency Rating Scale
1 (Excellent)
• Minor and Moderate Bleeding Events o
Actual number of infusion less than or equal to estimated number of infusion
required to treat that bleeding episode. No additional
VWF-containing/coagulation factor containing product required. • Major
Bleeding Events o
Actual number of infusion less than or equal to estimated number of infusion
required to treat that bleeding episode. No additional
VWF-containing/coagulation factor containing product required.
2 (Good)
• Minor and Moderate Bleeding Events
o 1 to
2 infusions greater than estimated required to control that bleeding episode.
No additional VWF-containing/coagulation factor containing product required. • Major
Bleeding Events o Less
than 1.5x greater than estimated required to control that bleeding episode.
No additional VWF-containing/coagulation factor containing product required.
3 (Moderate)
• Minor and Moderate Bleeding Events
o 3 or
more infusions greater than estimated used to control that bleeding event. No
additional VWF-containing/coagulation factor containing product required. • Major
Bleeding Events o
Greater than or equal to 1.5x greater than estimated used to control that
bleeding event. No additional VWF-containing/coagulation factor containing
product required.
4 (None)
• Minor and Moderate Bleeding Events
o
Severe uncontrolled bleeding or intensity of bleeding not changed. Additional
VWF-containing/coagulation factor containing product required. • Major
Bleeding Events o
Severe uncontrolled bleeding or intensity of bleeding not changed. Additional
VWF-containing/coagulation factor containing product required.References:
Safety and tolerability outcomes - evaluated via clinical assessments of
adverse events, hematology panels, coagulation panels, serum chemistry,
urinalysis, viral serology and immunological assessments - were also
encouraging. With the exception of 1 patient, adverse events were minor or
unrelated to treatment. No thrombotic events or severe allergic reactions
occurred, and none of the participants developed anti-VWF binding or
neutralizing antibodies to VWF.
Researchers concluded that the data offer evidence that BAX 111 is “safe and
hemostatically effective in severe VWD patients in a variety of clinical
bleeding presentations.”
Addressing a Pressing Therapeutic
Need
“Von
Willebrand disease is the most common hereditary bleeding disorder, yet few
treatment options exist,” noted John Orloff, MD, Head of Research &
Development and Chief Scientific Officer, Baxalta. BAX 111, Dr. Orloff
asserted, “has the potential to transform the standard of care for patients
with severe von Willebrand disease by offering an effective, individualized
treatment option.”
Both the FDA and the European Medicines Agency granted orphan drug designation
to BAX 111 back in November 2010.2 Currently, BAX 111 remains under FDA review,
a pending Biologics License Application having been filed in December 2014.5
While no official Prescription Drug User Fee Act (PDUFA) date has been set,
December 22, 2015, has been cited by industry insiders as a speculative
estimation.
The PDUFA date is an FDA approval deadline for new
drugs. If approved, BAX 111 would become the first recombinant
replacement treatment indicated for the management of VWD-related bleeding
episodes.
References - Gill JC, Castaman G, Windyga
J, et al. Hemostatic efficacy, safety and pharmacokinetics of a
recombinant von Willebrand factor in severe von Willebrand disease. Blood
2015. DOI 10.1182/blood-2015-02-629873. http://www.bloodjournal.org/content/bloodjournal/early/2015/08/03/blood-2015-02-629873.full.pdf?sso-checked=true Advance copy pre-published
online August 3, 2015. Accessed online August 4, 2015.
- Blood Publishes Phase III
Data on Baxalta’s Investigational Treatment for Von Willebrand Disease,
the Most Common Type of Inherited Bleeding Disorder [press release].
Deerfield, Illinois. Baxalta Incorporated August 3, 2015. http://www.businesswire.com/news/home/20150803005068/en/Blood-Publishes-Phase-III-Data-Baxalta%E2%80%99s-Investigational#.VcCXYfmUf4Z
- National Hemophilia
Foundation website. von Willebrand Disease. https://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders/Von-Willebrand-Disease Accessed August 4, 2015.
- National Heart, Lung and
Blood Institute. What is von Willebrand Disease?
http://www.nhlbi.nih.gov/health/health-topics/topics/vwd Updated June 1,
2011. Accessed August 4, 2015.
- Burden A. Large cap PDUFA
dates have been added to BioPharmCatalyst. http://www.biopharmcatalyst.com/2015/01/large-cap-pdufa-dates-have-been-now-added-to-biopharmcatalyst-20-in-total-today/ BioPharmCatalyst.
Published January 26, 2015. Accessed August 4, 2015.

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By Jeffery Bendix: Posted on Saturday, May 16, 2015 1:36 PM
Doctors Strike Back
Underlying
much of the controversy surrounding Maintenance of Certification (MOC), is the question of how much, or even
whether, the process as currently structured actually improves physician
performance and/or patient outcomes.
On February 3, 2015, many physicians
received a surprising email from Richard Baron, MD, MACP, president and chief
executive officer of the American Board of Internal Medicine (ABIM). Referring to the board’s controversial maintenance
of certification (MOC) program, Baron wrote, “ABIM clearly got it wrong. We
launched programs that weren’t ready and we didn’t deliver a MOC program that
physicians found meaningful…We got it wrong and sincerely apologize. We are
sorry. ”
Baron’s email— which went to the
approximately 200,000 internists and practitioners of 20 sub-specialties who
have obtained their board certifications from the ABIM—followed by a few weeks
(and many believe was at least partially in response to) the announcement a new
organization, the National Board of Physicians and Surgeons (NBPAS), with the announced goal of giving doctors “an
alternative route for continued board certification.” It is led by Paul
Teirstein, MD, chief of cardiology at the Scripps Clinic in La Jolla, California, and an outspoken MOC critic.
While the controversy surrounding MOC
remains far from settled, it seems clear that critics of the process and of
ABIM have scored some significant gains, by forcing ABIM to review or scrap
some elements of MOC, and by possibly opening new paths to maintaining
certification.
Evolution of MOC requirements
The creation of NBPAS and the ABIM’s
apology are but the latest developments in a long-simmering dispute over how
doctors should best keep their skills and knowledge up-to-date—and prove that
they are doing so. The controversy dates to the 1990s, when the ABIM instituted
a policy whereby, beginning in 2000, physicians who certified after 1990 would
have to recertify every 10 years. (Until then certification had been
life-long.) The change was subsequently adopted by the other 24 boards
comprising the American Board of Medical Specialties (ABMS).
The 10-year maintenance requirement
produced some grumbling among doctors, but no organized resistance. That
changed at the start of 2014 when ABIM announced that doctors would need to
earn accreditation points on a continual basis over the 10 years between taking
the recertifying examination. Moreover, doctors who had board certified before
1990 would be listed as “certified, not meeting MOC requirements” on the ABIM’s
web site.
For Teirstein and many of the
physicians boarded by the ABIM, these latest changes were the final straw. They
were further incensed by what they regarded as the excessive growth of the
nonprofit ABIM—whose budget exceeded $59 million—and the nearly $29 million
spent on salaries, benefits and “other expenses” during the ABIM’s 2014 fiscal
year. A few months later Teirstein launched an online petition opposing the MOC
requirements that to-date has garnered more than 23,000 signatures, he says. In addition, he says, “I began getting
comments like, ‘it’s great we have all these signatures, but what do we have to
show for it? Have they [the ABIM] actually changed anything?’ And they had
not.”
The NBPAS alternative
Teirstein’s response was to found the NBPAS, a nonprofit organization
with what he describes as “a much less expensive, much simpler approach to
life-long learning.” In the news release announcing its formation, the
organization says it is “committed to providing certification that ensures
physician compliance with national standards and promotes lifelong learning.”
Among the requirements for continued certification are that a candidate be
previously certified by an ABMS-member board and have completed 50 hours of CME
in the past two years. Teirstein describes NBPAS as a “grass- roots organization,” one
that is funded entirely by its members. Membership fees are $85 per year or
$169 for two years, and cover all specialties and sub-specialties covered by
the ABMS. “Right now we’ve got about a thousand members and we’re making ends
meet doing that,” he says. Teirstein is taking no salary.
As of mid-April none of the nation’s hospitals were accepting
NBPAS certification as a basis for admitting privileges, but Teirstein notes
that the process usually involves approval from numerous boards and committees
and thus will take some time. “I’m of the firm belief that the as long as the
medical community is willing to stand up and say this is what they want we’ll
figure out a way to make it happen, but it won’t be overnight,” he says.
Teirstein and other NBPAS board members say they support the
notion of physicians keeping their knowledge and skills up to date, but think
CME offers the best method for accomplishing that. Teirstein notes that CME
courses must be accredited by the American Council for Continuing Medical
Education (ACCME) to count towards license renewal. “We’ve decided the best
compromise is where you can have lifelong learning which doctors don’t consider
onerous,” he says. “The doctors can choose which offerings to attend. They’re
not going to pay and take time to go to something that’s not relevant.”
‘It’s not good learning’
Harry Sarles, MD, FACG, an NBPAS board member and past president
of the American College of
Gastroenterology objects to what he calls the “esoterica” on the
certification examinations. “It’s not good learning. It’s learning for the
test,” he says.
“ABIM should not be allowed to set the bar, make the rules, and
then provide all the CME that can only be accepted to meet their rules,” he
adds. “I’m answering to my hospital, my state, my patients, the health plans,
in terms of my quality being measured and monitored. And now ABIM steps in and
says you should be doing something for us too. I felt like I was in the middle
of a shakedown.”
“When I took my certification I felt proud and driven to
continuously improve myself,,” he says. “But everything ABIM has instituted
since then, to my way of thinking, has really been about themselves and not
what’s best for physicians.”
Sarles endorses the idea of physicians demonstrating quality and
a commitment to ongoing education, but wants to see “multiple pathways” for
doing so. “I’m all for competition, because it will make us all better,” he
says. “If we only had one kind of car to buy it would probably be a crappy car.
Whatever your criteria are, competition is very healthy and I believe in it.”
The ABIM response
ABIM’s February 3 statement, while not
directly acknowledging NBPAS, did appear to address some of its complaints and
those of others who have been critical of the MOC process. It said that the
board will:
- Suspend the practice assessment,
patient voice and patient safety requirements of the MOC program for at
least two years,
- By August, 2015 change the
language used to report a diplomate’s MOC status on the ABIM’s website
from “meeting MOC requirements” to “participating in “MOC,”
- Update the internal medicine exam
so that it better reflects what practicing physicians are doing,
- Keep MOC enrollment fees at or
below 2014 levels through at least 2017, and
- Allow internists to use most forms
of ACCME-approved CME to demonstrate self-assessment of medical knowledge
by the end of 2015.
In addition, according to the
statement, “ABIM will work with medical societies and directly with diplomates
to seek input regarding the MOC program” via meetings, webinars, forums, and
other venues. “We are embarked on a whole new way of doing business and much
more engagement with our community,” Baron said in a phone interview with Medical
Economics.
As evidence, he cites implementation of
“a sub-specialty board structure that involves depth in each of the disciplines
in internal medicine,” and that includes physicians in community practice as
well as patients and other public stakeholders.
“Those groups have been reaching out to
colleagues and members of their societies,” Baron says. “And what we’re hearing
is that lots of the activities we had either as board products or expectations
maybe are being done by other people in the [healthcare] delivery system better
than we’re doing them. And in that case we want to learn more about those and
figure out how to give people credit for the work that they’re doing during
their day jobs and avoid redundancy and wasting members’ time.”
Responding to the complaint that MOC
tests doctors on knowledge and skills they don’t encounter in their practice,
Baron says he took the exam a year ago and acknowledges that it included topics
he’d not seen in his general internist/geriatrics practice. On the other hand,
he says, “I think all of us in practice confront that there’s a difference
between what we use every day and what we might need to use some time.”
Baron recalls joining the ABIM’s
test-writing committee in the summer of 2001 and being surprised to find the
test included a question on anthrax. But several months later it was a
board-certified internist in Miami, Florida (Larry Bush, MD) who first
identified anthrax as the mysterious substance being sent through the mail that
was sickening—and in the case of Bush’s patient, killing—recipients was anthrax.
”That’s a doctor who had a piece of
knowledge that he didn’t use every day, but fact that he had it made a huge
difference for a patient,” Baron says. (Bush subsequently coauthored an article
about the incident in The New England Journal of Medicine.)
Regarding the fees associated with MOC,
Baron says, “Nobody likes to write checks, and when I was in practice there
were a lot of things I wished I didn’t have to pay for. But I want to
acknowledge that it’s really hard for doctors in practice now and every check
is a painful check. We are looking at ways to reduce the cost.” As evidence, he points to the February
3 announcement regarding enrollment fees. “We are taking time to listening to
physician feedback about all aspects of our program before announcing any
additional changes,” he says. “We know that doctors need to
experience more value in the program, and the areas we pulled back on were
those that doctors were in effect saying, ‘I’m not getting much out of this,’”
he says.
What do the data show?
Underlying much of the controversy surrounding MOC is the
question of how much—or even whether—the process as currently structured
actually improves physician performance and/or patient outcomes. A great many
internists clearly believe it does not, according to a study published in the
January 2015 issue of JAMA Internal Medicine.
The authors assembled a focus group consisting of 50
board-certified primary care and subspecialist internal medicine and family
medicine physicians in an academic medical center and community sites. They
found that “at present, MOC is perceived by physicians as an inefficient and
logistically difficult activity for learning or assessment, often irrelevant to
practice, and of little benefit to physicians, patients, or society.”
Data on the effectiveness of certification since the institution
of time limitations is sparse, consisting largely of a handful of studies
published over the past 15 years in Academic Medicine, the Journal of the American
College of Cardiology and JAMA, among others. And while MOC
supporters say the studies support MOC’s effectiveness, in a debate earlier
this year with Baron and Lois M. Nora, president and chief executive officer of
the ABMS, Teirstein maintained that the studies’ results are, at best,
ambiguous.
He cited, for example, the results of a 2014 investigation
published in JAMA comparing clinical outcomes among patients at four
Veterans Administration hospitals treated by internists with time-limited and
time-unlimited certifications (i.e. those who were grandfathered out of the
ABIM’s 10-year certification requirements and those who were not.) The authors
found “no significant differences” between the two groups on 10 primary care
performance measures.
“If you say we have data that supports our MOC process, you’d
better have the data,” Teirstein said in his interview with Medical
Economics. “And if you look at the papers they cite, they’re very
unconvincing.” Baron acknowledges that the evidence in support of MOC “could be
stronger,” but also notes “at least one of the studies he (Teirstein)
criticized met rigorous methodological standards.”
“I don’t think it’s unusual to have good faith people arguing
about whether the evidence shows ‘x’ or ‘y,” Baron says. “Every clinician
operates all the time in an environment where the patient didn’t walk out of an
article in a journal. You have to navigate between what you know you know and
how close the patient before you gets to that.” Teirstein says NBPAS has no plans to try and link ongoing
education and training to quality and patient outcomes. “I just don’t think you
can measure this adequately,” he says. “Would randomizing really work? A doctor
might be more inspired to do a good job because he wants to prove you don’t
have to do this [maintain certification.] It’s just not the kind of thing that
lends itself to scientific study.”
Looking ahead, Teirstein envisions the NBPAS playing a watchdog
role for the ABMS and its member boards, in addition to providing
certification. “We’ll be keeping an eye on things and making sure everyone
knows physicians are not just going to take whatever they’re given. We’re going
to react and try to make our voices heard.”
ABIM requirements
- Possess a valid and unrestricted
license to practice medicine and enroll in maintenance of certification
(MOC)
- Earn MOC points by completing some
MOC activity every two years and earn 100 points every five years (at
least 20 points in medical knowledge). Points earned every two years will
also count toward your five-year requirement, and also count toward the
milestones for the certifications you are maintaining. Points earned count
toward all certifications being maintained.
- If you are dual-boarded by one or
more of the other American Board of Medical Specialties (ABMS) member
Boards, your self-evaluation requirements will be waived.
- Pass the MOC exam in your
specialty(ies) every 10 years (first exam attempt in each certification
area you maintain earns 20 MOC points).
- Other requirements may apply
depending on your specialty and situation. For complete requirements,
visit: http://www.abim.org/maintenance-of-certification/requirements.aspx
Source: American
Board of Internal Medicine
NBPAS requirements
- Candidates must have been
previously certified by an American Board of Medical Specialties (ABMS)
member board.
- Candidates must have a valid,
unrestricted license to practice medicine in at least one US state.
Candidates who only hold a license outside of the U.S. must provide
evidence of an unrestricted license from a valid non-U.S. licensing body.
- Candidates must have completed a
minimum of 50 hours of continuing medical education (CME) within the past
24 months, provided by a recognized provider of the Accreditation Council
for Continuing Medical Education (ACCME). CME must be related to one or
more of the specialties in which the candidate is applying. Re-entry for
physicians with lapsed certification requires 100 hours of CME with the
past 24 months. Physicians in or within two years of training are exempt.
- Other requirements may apply
depending on your specialty and situation. For complete requirements,
visit: https://nbpas.org/why-nbpas/
Source: National
Board of Physicians and Surgeons
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News Author: Pauline Anderson CME Author: Charles P. Vega, MD; Edited by Dr. C. M. Counce: Posted on Monday, April 20, 2015 12:25 PM
 Headache is one of the most common pain
disorders seen in outpatient practice, and the authors of the current study
provide a brief overview of the epidemiology and larger consequences of
headache. Nearly everyone experiences headache at some point, and the
prevalence of recurrent, severe headaches approaches 25%.
The high prevalence of headache is
associated with substantial societal costs. There are approximately 12 million
clinician office visits for headache per year in the United States, and
headaches are estimated to cost the US economy $31 billion per year. The
evaluation of headache accounts for some of this financial cost, but it can also
have severe medical consequences. One study estimated that 4000 additional
cancers were promoted by the 18 million computed tomography (CT) scans of the
head performed in the United States in 2007. Another study found that the
majority of all CT imaging of the head and brain were inappropriate, based on
current recommendations. Most inappropriate CT imaging was ordered for
headache.
The inappropriate use of resources in
the management of headache has led to recommendations to reduce the use of
brain imaging and physician referral, as well as limited use of opioids and
barbiturates in the treatment of headache. But are clinicians following these
recommendations? The current study by Mafi and colleagues explores this issue.
Study
Synopsis and Perspective
Contrary to practice guidelines,
clinicians treating patients with headache are increasingly ordering costly
imaging tests and referring patients to other physicians, and they are doing
less counseling on lifestyle changes, authors of a new review suggest.
The researchers found an almost
doubling of the use of CT and magnetic resonance imaging (MRI) in a recent
10-year period.
Although given the nature of the study
they could not determine which referrals or imaging studies were not
appropriate, the trend toward a doubling of these tests is concerning, said
lead study author John N. Mafi, MD, fellow, general internal medicine, Beth
Israel Deaconess Medical Center, Boston, Massachusetts.
"We have no reason to suspect that
headache is a disease that epidemiologically or pathophysiologically has
changed over the past decade, so this, we think, is inappropriate changes in
physician practice patterns."
The study was published online January 8 in the Journal of General Internal Medicine.
Inappropriate
Changes?
Researchers used data from the National
Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory
Medical Care Survey (NHAMCS) from January 1, 1999, to December 31, 2010. Both
surveys obtain nationally representative samples of ambulatory patient visits
across the United States.
From these surveys, researchers
identified ambulatory visits (excluding emergency department visits) with a
chief complaint and/or a primary diagnosis of headache. They also included
those with secondary complaints and diagnoses of headache but unrelated primary
reasons for the visit (eg, hyperlipidemias).
In the group of patient visits with a
chief complaint of headache (80.8%), the surveys provide duration or context of
symptoms in 5 categories: new onset (<3 months), acute-on-chronic flare-up,
chronic routine, routine/preventive, and preoperative or postoperative visit.
Researchers studied 4 types of
measures: use of advanced imaging, including CT and MRI; referrals to other
physicians; counseling on diet, nutrition, exercise, mental health, and stress
management; and use of medications. The analysis included 9362 visits
related to headache, which represented approximately 144 million visits during
the study period. Almost 75% of the patients were women, and their mean age
remained the same during the study, at approximately 46 years.
The study showed that advanced imaging,
including CT or MRI, increased from 6.7% of visits in 1999-2000 to 13.9% in
2009-2010 (P < .001), as did referrals to other physicians, which
rose from 6.9% to 13.2% (P = .005).
Although rare, there are "real
concerns" about kidney injury due to use of contrast dye and radiation
during imaging tests, commented Dr Mafi.
The study showed that during the same
study period, counseling for headache prevention declined from 23.5% to 18.5% (P
= .041).
But there were also somewhat
encouraging results. For example, use of opioids and barbiturates, which are
not recommended for headache, remained the same at approximately 18%.
"That's still quite a high number
for a discouraged medication, so there's lots of room for improvement,"
commented Dr. Mafi.
Also, preventive medication for
migraine, such as verapamil, amitriptyline, propranolol, and topiramate, nearly
doubled — from 8.5% to 15.9% (P = .001). Abortive therapies, such as
triptans and ergot alkaloids, rose from 9.8% to 15.4% (P = .022).
Use of nonsteroidal anti-inflammatory
drugs and acetaminophen remained stable at roughly 16%.
The trends remained after adjustment
for age, gender, race, geographic region, insurance status, symptom duration,
urban location, and whether the physician was identified as the primary care
practitioner. As well, there were similar trends between visits related to
migraine vs nonmigraine headache, although patients with migraine received
triptans/ergot alkaloids and preventive therapies more often, and their use of
opioid or barbiturates was higher.
Use of CT/MRI rose more rapidly for
those with nonmigraine headache, as did referrals to other physicians.
Acute vs Chronic
As for acute vs chronic headache, again
the trends were similar. Use of CT/MRI appeared to rise more rapidly among
patients with acute symptoms, although this difference did not achieve
significance.
In addition, patients with chronic
headache had lower adjusted odds of receiving referrals to other physicians
(odds ratio [OR], 0.59; 95% confidence interval [CI], 0.42 - 0.82) or
undergoing advanced imaging (OR, 0.47; 95% CI, 0.35 - 0.63) compared with other
presentations. However, there were no significant differences across time as
trends in referrals and imaging still nearly doubled for both groups.
Numerous factors are driving these
trends, including a growing number of assertive and demanding patients, the
authors suggest. "They come in and say 'I need an MRI for my headache' as
opposed to 'I have a headache'," said Dr Mafi, adding that MRI and CT are
more available now than ever before.
As well, physicians have an incentive to
make patients happy because they are increasingly being rated on satisfaction
surveys, said Dr Mafi.
There are also financial incentives for
physicians to do more testing and concerns about legal liability if tests are
not ordered.
Time constraints are another
contributing factor. "There is simply not enough time during the visit to
counsel" patients on making lifestyle modifications to help treat their
headache, said Dr Mafi.
Reversing the trends will require a
change in approach to reimbursement that relies less on the physical clinician
visit and more on new technologies, said Dr Mafi.
"Rather than lengthen the visit or
pay doctors more, I think we need to move away from that 20th-century mindset
and really think about reimbursing care across a continuum of time," he
said. "We need to think about reimbursing high-quality care at any time,
whether it's electronic or through a secure email message between the patient
and physician, or an electronic visit or telemedicine visit where patients can
contribute to their records online and have the doctor provide feedback."
Appropriateness
Unclear
For a comment, Medscape Medical News
reached out to Elizabeth Loder, MD, chief, Division of Headache and Pain,
Brigham and Women's Hospital, Boston, Massachusetts, and immediate past
president, American Headache Society (AHS), who headed the AHS "Choosing
Wisely" project that looked at opioid prescribing.
The new study was well done, has
"some fascinating findings," and is important in light of the fact
that headache treatment and management trends are a neglected medical problem,
said Dr Loder.
However, she raised several issues
about interpretation. For one thing, she pointed out that the NAMCS and NHAMCS
do not provide information that would help determine whether imaging studies
were appropriately or inappropriately ordered.
"In clinical practice, we see both
underuse and overuse of imaging studies. Patients with complex, refractory
chronic headache problems frequently have multiple — usually unnecessary —
imaging studies. In contrast, it remains common for us to see in a headache
clinic patients with worrisome presentations of headache who have not been
imaged."
The data suggest that much of the
increase in imaging may be due to an increase in acute as opposed to chronic
headache, said Dr Loder. "This is exactly the situation where imaging
is most likely to be appropriate."
As well, the results show that imaging
is more common in patients with nonmigraine headache rather than migraine
headache. "Again, this is a situation where imaging may well be
appropriate."
Dr Loder stressed that when the AHS
formulated its "Choosing Wisely" recommendations, the committee felt
that evidence to discourage imaging was strong only for patients with stable
headache who met criteria for migraine.
According to the recommendations,
imaging in patients without migraine is not necessarily inappropriate.
"The proportion of scan
abnormalities is higher in patients with nonmigraine headaches and we did not
feel evidence was sufficient to discourage imaging in those cases."
Dr Loder also noted that the increase
in imaging and referrals has occurred alongside an "enormous downward
pressure" on the time physicians can devote to patient concerns during an
office visit. Physicians have to spend more time on paperwork, electronic
medical record "meaningful use" requirements, and other things, she
said.
"Ordering tests and making
referrals are both relatively quick ways to demonstrate concern for a patient's
symptoms and maintain patient satisfaction."
She pointed out that although some
guidelines or recommendations encourage physicians to counsel about diet,
nutrition, and lifestyle, these are based only on expert opinion. "The
evidence that this type of counseling actually improves patient outcomes is
thin to nonexistent."
She also noted that the "Choosing
Wisely" recommendations were developed on the basis of processes that are
less rigorous and detailed than those used to create actual guidelines (eg,
those developed by the American College of Physicians in 2000), and the two
probably should not be confused.
Low Value
"'Choosing Wisely' recommendations
are intended to identify practices that often — although not always — represent
low-value care and that patients and physicians should discuss and
question," said Dr Loder. "That is not the same thing as saying they
are always inappropriate."
According to these recommendations,
situations exist where the use of opioids and barbiturates may be appropriate,
although they should not be first-line treatments in most situations, said Dr
Loder. Similarly, the recommendations encourage the use of advanced imaging
with MRI rather than CT in nonemergent headache for which imaging was thought
to be appropriate.
"I think the authors are
overstating the case for limiting imaging studies when they say that there is
'broad agreement' on these issues and characterize these things as 'low-value
services.' They are not inherently low value — they are low value only in
specific contexts."
Dr Loder found it "very
interesting" that among those presenting with headache, women were
significantly less likely than men to have imaging studies.
Dr Mafi and Dr Loder
have disclosed no relevant financial relationships. Dr Loder is acting director
of research at the BMJ but noted that
although she is paid for that work, her comments do not necessarily reflect the
views of the BMJ, the AHS, or Brigham and Women's Hospital.
J Gen Intern Med. Published online January 8, 2015. Abstract
Study
Highlights
- Researchers used data from visits
recorded in the NAMCS and NHAMCS between 1999 and 2010 to evaluate the
treatment of patients with headache. These surveys recorded information
from 112 primary geographic sites around the United States.
- All visits in the current study
featured a primary diagnosis (80.8% of the sample) or secondary diagnosis
(19.2%) of headache. Researchers excluded visits that included warning
signs of a potential serious cause of headache, such as fever or
neurologic examination findings.
- Researchers evaluated the
application of 4 standards of quality of care:
- Minimizing the use of advanced
imaging, such as CT or MRI
- Minimizing referrals to other
physicians
- Offering clinician counseling on
lifestyle modifications to treat headaches
- Avoiding the use of opioids and
barbiturates in favor of preferred medical treatment
- The main study outcome was
adherence to these best practices across time. Researchers stratified
their results based on the diagnosis of migraine vs nonmigraine headache
and the duration of symptoms. They considered acute or new-onset headaches
as the reference standard for evaluating the application of best
practices.
- Study results were also adjusted
to account for age, gender, race/ethnicity, insurance status, whether the
treating physician was the patient's primary care provider, and urban vs
rural setting.
- The researchers focused on 9362
office visits for headache. The mean age of the patients was 46 years, and
three-quarters were women. More than 70% of patients were white.
- The majority of visits for
headache were for acute or new-onset pain.
- The application of advanced
imaging for headache increased during the study period, from 6.7% of
visits in 1999-2000 to 13.9% in 2009-2010. The respective rates of referrals
to other physicians were 6.9% and 13.2%.
- The percentage of visits featuring
counseling decreased from 23.5% in 1999-2000 to 18.5% in 2009-2010.
- Regarding treatment, approximately
16% of patients were treated with acetaminophen or nonsteroidal anti-inflammatory
drugs, with little change during the study period. Triptans and ergot
alkaloids were prescribed in 9.8% of patients in 1999-2000 and 15.4% in
2009-2010. Treatment with preventive medications also increased, from 8.5%
at the outset of the study to 15.9% in 2009-2010. Approximately 18% of
patients received an opioid or barbiturate, with little change during the
study period.
- Patients with migraine headache
were more likely to receive opioids or barbiturates compared with patients
with nonmigraine headache.
- However, nonmigraine headache was
associated with higher rates of advanced imaging compared with migraine
headache.
- Chronic headache was associated
with less imaging and fewer referrals compared with acute headache.
- Compared with other physicians, primary
care physicians were less likely to order advanced imaging and more likely
to provide counseling to patients with headache.
- Female gender was associated with
lower rates of referral for imaging, but health insurance status failed to
affect any of the study outcomes.
Clinical
Implications
- The prevalence of recurrent,
severe headaches approaches 25%. There are approximately 12 million
clinician office visits for headache per year in the United States. The
inappropriate application of head CT imaging for headache has been
implicated in promoting higher rates of cancer. The most common indication
for inappropriate CT imaging is headache.
- The current study by Mafi and
colleagues suggests that physicians are actually doing worse across time
in offering best practices to patients with headache, particularly
regarding patient referrals and counseling. Rates of preventive
medications for headache did increase across time in the current study.
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