Use the labels in the right column to find what you want. Or you can go thru them one by one, there are only 34,148 posts. Searching is done in the search box in upper left corner. I blog on anything to do with stroke. DO NOT DO ANYTHING SUGGESTED HERE AS I AM NOT MEDICALLY TRAINED, YOUR DOCTOR IS, LISTEN TO THEM. BUT I BET THEY DON'T KNOW HOW TO GET YOU 100% RECOVERED. I DON'T EITHER BUT HAVE PLENTY OF QUESTIONS FOR YOUR DOCTOR TO ANSWER.
Changing stroke rehab and research worldwide now.Time is Brain!trillions and trillions of neuronsthatDIEeach day because there areNOeffective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.
What this blog is for:
My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.
Study found low-dose rivaroxaban to be unsafe and ineffective compared to standard of care.The National Institutes of Health (NIH) has stopped an investigational treatment arm of the Comparison of Anti-coagulation and Anti-platelet Therapies for Intracranial Vascular Atherostenosis (CAPTIVA) study following a regular review by the Data Safety and Monitoring Board (DSMB). The DSMB is an independent group of experts that regularly check if the study is safe. NIH’s National Institute of Neurological Disorders and Stroke, the trial’s funder, accepted the DSMB recommendation that CAPTIVA discontinue the low-dose rivaroxaban arm of the trial due to an increase in safety events and evidence of futility, a pre-specified stopping point to enable the study to end if early results showed the treatment is unlikely to help people. Rivaroxaban is a U.S. Food and Drug Administration-approved anticoagulant medication used to treat or prevent blood clots. All study sites that have active participants randomized to the discontinued arm have received instructions for drug discontinuation. Study participants who have completed their evaluation of the discontinued arm will be contacted by the site where they received treatment. Participant safety remains NIH’s top priority.The CAPTIVA study is a large, two-stage, double-blind randomized trial in participants age 30 and older with a stroke attributed to 70-99% narrowing, or stenosis, of a major intracranial artery. The study is testing whether either of two new treatments works better than the current treatment to prevent another stroke. The study, part of NIH’s StrokeNet is in the midst of enrolling and evaluating up to 1,683 volunteers at over 100 study sites over a four-year period. Participants were randomized 1:1:1 to one year of treatment with:
Ticagrelor (180 mg loading dose, then 90 mg twice daily) plus aspirin (81 mg daily)
Clopidogrel (600 mg loading dose, then 75 mg daily) plus aspirin (81 mg daily)
In addition, participants will receive intensive risk factor management and lifestyle coaching. They will be evaluated at one month, four months, eight months, and one year after randomization into one of the study arms. At these intervals, participants will have their blood pressure checked, risk factors optimized and will be assessed for study outcomes.
CAPTIVA will not determine which new treatment is best. It will only show if either new treatment is better than what doctors currently use. Comparing the two new treatments directly would require many more patients. Nevertheless, CAPTIVA will provide important safety and efficacy data on both novel therapies.
The CAPTIVA Study and NIH’s StrokeNet are funded by NIH’s NINDS.
About the National Institute of Neurological Disorders and Stroke (NINDS): NINDS is the nation’s leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. https://www.ninds.nih.gov
First of all, it is not muscle fatigue, so they have the wrong starting point. The NIH is totally incompetent for not stating the problem correctly. It is post stroke fatigue that needs to be solved! My God, the absolute stupidity of it all!
Marquette and the Medical College of Wisconsin have received an R01
grant from the National Institutes of Health to study muscle fatigue in
stroke survivors and solutions to increase their muscle performance. The
grant has an expected value of $3.2 million over five years and was
awarded by the Eunice Kennedy Shriver National Institute of Child Health
and Human Development.
Dr. Allison Hyngstrom, chair and professor of physical therapy in Marquette’s College of Health Sciences, and Dr. Matt Durand, associate professor of physical medicine and rehabilitation at MCW, are the principal investigators on the award.
“Increased
fatigability, which is the acute, exercise-induced reduction in force,
is an understudied consequence of stroke,” Hyngstrom said. “This is a
clinically meaningful area of study because increased neuromuscular
fatigability can negatively affect endurance for activities like
walking. Also, successful post-stroke rehabilitation strategies require
repeated levels of muscle activation and overload to cause functional
gains in motor performance.”
Hyngstrom and Durand’s team will
examine how blood flow is regulated to the exercising leg muscle of
individuals post-stroke as muscles become fatigued if there is not
enough blood flow to the area. They will use a safe and simple
non-invasive intervention called ischemic conditioning, which has known
effects to improve blood flow in exercising muscle, to determine its
effects on muscle fatigue.
“Our central hypothesis is that people
who have suffered a stroke face impaired functional sympatholysis—the
mechanism by which the body maintains blood flow to exercising muscles
to meet the energy demands of the task—and this results in dysregulated
blood flow during exercise,” Durand added. “This exacerbates
neuromuscular fatigability and limits motor function. Our goal is,
ultimately, to determine if we can improve muscle performance through
ischemic conditioning and understand if the improvements are associated
with increased blood flow to the muscle and reduced paretic muscle
fatigability.”
“This grant award validates the viability of the
present hypothesis on muscle fatigability,” said Dr. William Cullinan,
dean of Marquette’s College of Health Sciences. “Muscle fatigue can
hinder post-stroke rehabilitation efforts and lead to adverse outcomes
not only physically, but mentally and financially. Their research has
the opportunity to be a positive development for stroke survivors as
they work towards pre-stroke mobility.”
The research team also includes Dr. Chris Sundberg, assistant professor of physical therapy; Dr. Sandra Hunter, professor of exercise science; and Dr. Brian Schmit, Hammes Family Professor in the Marquette and MCW Joint Department of Biomedical Engineering.
The
NIH’s Research Project Grant (R01) is the original and historically
oldest grant mechanism used by the NIH. The R01 provides support for
health-related research and development based on the mission of the NIH.
R01s can be investigator-initiated or can be solicited.
The
Eunice Kennedy Shriver National Institute of Child Health and Human
Development was founded in 1962 to investigate human development
throughout the entire life process, with a focus on understanding
disabilities and important events that occur during pregnancy. Since
then, research conducted and funded by NICHD has helped save lives,
improve wellbeing, and reduce societal costs associated with illness and
disability. NICHD’s mission is to lead research and training to
understand human development, improve reproductive health, enhance the
lives of children and adolescents, and optimize abilities for all.
Researchers at Northwestern University and John Hopkins University plan to study if an Apple Watch app can help prevent strokes.
The
National Heart, Lung, and Blood Institute, a National Institutes of
Health division, awarded a $37 million grant for researchers to test
whether Apple Watches can be used as part of a strategy to cut down the
use of expensive blood thinners used to prevent strokes from atrial
fibrillation.
The NIH has to tell you this as their only hope since they know full well that stroke recovery is a complete fucking failure and they're doing nothing to solve it. So the distraction is to emphasize prevention
As we get older, unfortunately our chances of having a stroke rise.
While there’s obviously no way to turn back the clock on our age,
fortunately there are ways to lower our risk of a stroke and that
includes staying physically active. Take walks, ride a bike, play a
favorite sport. According to our current exercise guidelines for
American adults, the goal is to get in at least two and a half hours
each week of moderate-intensity physical activity as well as two days of
muscle-strengthening activity [1].
But a new study, published in the journal JAMA Network Open,
shows that reducing the chances of a stroke as we get older doesn’t
necessarily require heavy aerobic exercise or a sweat suit [2]. For
those who are less mobile or less interested in getting out to exercise,
the researchers discovered that just spending time doing
light-intensity physical activity—such as tending to household
chores—“significantly” protects against stroke.
The study also found you don’t have to dedicate whole afternoons to
tidying up around the house to protect your health. It helps to just get
up out of your chair for five or 10 minutes at a time throughout the
day to straighten up a room, sweep the floor, fold the laundry, step
outside to water the garden, or just take a leisurely stroll.
That may sound simple, but consider that the average American adult
now spends on average six and a half hours per day just sitting [3].
That comes to nearly two days per week on average, much to the
detriment of our health and wellbeing. Indeed, the study found that
middle-aged and older people who were sedentary for 13 hours or more
hours per day had a 44 percent increased risk of stroke.
These latest findings come from Steven Hooker, San Diego State
University, CA, and his colleagues on the NIH-supported Reasons for
Geographic and Racial Differences in Stroke (REGARDS) study. Launched in
2003, REGARDS continues to follow over time more than 30,000 Black and
white participants aged 45 and older.
Hooker and colleagues wanted to know more about the amount and
intensity of exercise required to prevent a stroke. Interestingly, the
existing data were relatively weak, in part because prior studies
looking at the associations between physical activity and stroke risk
relied on self-reported data, which don’t allow for precise measures.
What’s more, the relationship between time spent sitting and stroke risk
also remained unknown.
To get answers, Hooker and team focused on 7,607 adults enrolled in
the REGARDS study. Rather than relying on self-reported physical
activity data, team members asked participants to wear a hip-mounted
accelerometer—a device that records how fast people move—during waking
hours for seven days between May 2009 and January 2013.
The average age of participants was 63. Men and women were
represented about equally in the study, while about 70 percent of
participants were white and 30 percent were Black.
Over the more than seven years of the study, 286 participants
suffered a stroke. The researchers then analyzed all the accelerometer
data, including the amount and intensity of their physical activity over
the course of a normal week. They then related those data to their risk
of having a stroke over the course of the study.
The researchers found, as anticipated, that adults who spent the most
time doing moderate-to-vigorous intensity physical activity were less
likely to have a stroke than those who spent the least time physically
active. But those who spent the most time sitting also were at greater
stroke risk, whether they got their weekly exercise in or not.
Those who regularly sat still for longer periods—17 minutes or more
at a time—had a 54 percent increase in stroke risk compared to those who
more often sat still for less than eight minutes. After adjusting for
the time participants spent sitting, those who more often had shorter
periods of moderate-to-vigorous activity—less than 10 minutes at a
time—still had significantly lower stroke risk. But, once the amount of
time spent sitting was taken into account, longer periods of more
vigorous activity didn’t make a difference.
While high blood pressure, diabetes, and myriad other factors also
contribute to a person’s cumulative risk of stroke, the highlighted
paper does bring some good actionable news. For each hour spent doing
light-intensity physical activity instead of sitting, a person can
reduce his or her stroke risk.
The bad news, of course, is that each extra hour spent sitting per
day comes with an increased risk for stroke. This bad news shouldn’t be
taken lightly. In the U.S., almost 800,000 people have a stroke each
year. That’s one person every 40 seconds with, on average, one death
every four minutes. Globally, stroke is the second most common cause of
death and third most common cause of disability in people, killing more
than 6.5 million each year.
If you’re already meeting the current exercise guidelines for adults,
keep up the good work. If not, this paper shows you can still do
something to lower your stroke risk. Make a habit throughout the day of
getting up out of your chair for a mere five or 10 minutes to straighten
up a room, sweep the floor, fold the laundry, step outside to water the
garden, or take a leisurely stroll. It could make a big difference to
your health as you age.
So I guess your doctors are still flailing in the dark since these are guidelines NOT PROTOCOLS. They seem to be after you get to the hospital, not treatments that will prevent you from having to go to the hospital.
I see nothing on heparin, colchicine or aspirin.
But I'm not medically trained so don't listen to me. Don't tough this out at home.
Why I'm getting heparin. Heparin
binds to cells at a site adjacent to ACE2, the portal for SARS-CoV-2
infection, and "potently" blocks the virus, which could open up therapy
options.
"On
the other hand, in most patients with COVID-19 associated ischaemic
stroke, very early anti-coagulation is probably not warranted as a
strategy to prevent inpatient stroke recurrence, as this outcome is too
uncommon to justify the increased risk of secondary haemorrhage,"
according to the group.(So you wait until the clots are severe before you do anti-coagulation. OK, not for me.)
Researchers found that hospitalized COVID patients
who took a daily low dose of aspirin had a significantly lower risk of
complications and death from the virus. Aspirin users were 43 percent
less likely to be put in the intensive care unit (ICU) and 44 percent
less likely to be placed on a ventilator. They also had a 47 percent
decrease in the risk of dying from their coronavirus infection compared to hospitalized patients who were not taking daily aspirin doses.
But I'm sure your doctor will be more worried about bleeding risks from aspirin. I'm doing 325(low dose is 81) and have been for 15 years.
January 4, 2021
-- A study conducted by a team of researchers from the U.S. National
Institutes of Health (NIH) found brain damage in patients who died of
COVID-19 but no signs of SARS-CoV-2 in tissue samples. The research was
published December 30 in the New England Journal of Medicine.
The
study results suggest that the brain damage "was not caused by a direct
viral attack," senior author Dr. Avindra Nath said in a statement
released by the NIH.
"We found that the brains of patients who contract infection from
SARS-CoV-2 may be susceptible to microvascular blood vessel damage,"
Nath said. "Our results suggest that this may be caused by the body's
inflammatory response to the virus."
Although COVID-19 primarily manifests in the respiratory system, patients also experience neurological complications. The reas...
To read this and get access to all of the exclusive content on AuntMinnie.com create a free account or sign-in now.
I include only one paragraph from here; hopefully our stroke medical professionals take it to heart and stop using the irritatingly stupid quote' All strokes are different, all stroke recoveries are different'. I did see nothing in here that suggested that patients were involved as part of that interdisciplinary team.
“We cannot conduct large, adequately powered trials of rehabilitation interventions.”
After working as a mental health clinician and researcher in the
Department of Veterans Affairs, where psychotherapeutic interventions
were randomized, tested, implemented, revised, and evaluated [9],
there is no question that rehabilitation could mirror this approach.
What interferes with progress in this area are two commonly accompanying
statements: “Each patient is different, you can’t have a standard approach,” and “There is no way to blind or control for exposure to the treatment.”Work currently ongoing in the field rebuts these contentions [10].
There is a glaring need for standardization of approaches to support
the rigor and reproducibility of the science. Standardization does not
ignore the individual, it allows for broader application of techniques
supported by evidence. New approaches to clinical trials, such as
adaptive trials, pragmatic trials, and other methodologic approaches,
may allow for more flexibility in clinical trial design and can be used
to evaluate whether an intervention or approach is effective in the real
world.
Molecules released into the blood following mild traumatic brain
injury (TBI) may be indicators of neuronal damage associated with
conditions such as post-traumatic stress disorder (PTSD) and depression,
researchers from the National Institute of Nursing Research (NINR),
part of the National Institutes of Health, have found. This study
included military veterans and servicemembers who were enrolled in the Chronic Effects of Neurotrauma Consortium (CENC)(link is external) multicenter observational study of the long-term effects of mild TBI and is published in Neurology.
“This study brings us closer to identifying biomarkers to predict
risk for PTSD, depression, and similar conditions in military personnel
and others who have experienced a traumatic brain injury,” said Jessica
Gill, Ph.D., R.N., F.A.A.N., deputy scientific director, and acting
deputy director, NINR, and chief of NINR’s Tissue Injury Branch, who
conducted the study with colleagues.
The researchers analyzed blood samples from former military personnel
who had experienced one to two TBIs, more than two TBIs, or no TBIs.
They screened for molecules released directly into the blood by cells of
damaged tissue or inside vesicles called exosomes—bubble-like
structures that contain a representative sample of cellular molecules.
There was a significant correlation between multiple mild TBIs across
the lifespan and higher levels of neurofilament light (NfL), a
structural protein found inside neurons, and molecules involved in
inflammation, such as tumor necrosis factor-alpha (TNF-alpha) and
interleukin 6 (IL-6).
Further analysis revealed associations between increases in plasma
and exosome levels of NfL, length of time since the last TBI, multiple
TBIs, and increased severity of neurological and behavioral symptoms.
These findings provide insights into potential mechanisms of
TBI-associated neuroinflammatory and neurodegenerative processes
correlated with persistent molecular effects of neuronal damage. About the National Institute of Nursing Research (NINR): NINR
supports research and training to advance symptom science, promote
wellness, support self-management of chronic conditions, enhance
palliative and end-of-life care, and develop the next generation of
nurse scientists. For more information about NINR, visit https://www.ninr.nih.gov.
I completely and totally disagree with the NIH only recommending testing for clinical trials. If we don't know how many have this gene and will likely get Alzheimers we will NEVER do the research necessary to find out how to prevent it. This head in the sand approach has to stop. If you have this gene you need to kick your Alzheimers prevention protocol into high gear. Oh, your doctor doesn't have one, well then too fucking bad, that head in the sand approach worked for them but not you.
You can't use mine, I'm not medically trained, your doctors' better be EXACT.
Genes are one of many risk factors for dementia. While a quarter of
Alzheimer's patients have a strong family history of the disease, only
1% directly inherit a gene mutation that causes early-onset Alzheimer's,
also known as familial Alzheimer's disease (FAD) [1]. But another gene called APOE can influence your risk for the more common late-onset type of Alzheimer's.
There are three types of the APOE gene, called alleles: APOE2, E3 and
E4. Everyone has two copies of the gene and the combination determines
your APOE "genotype"—E2/E2, E2/E3, E2/E4, E3/E3, E3/E4, or E4/E4. The E2
allele is the rarest form of APOE and carrying even one copy appears to
reduce the risk of developing Alzheimer's by up to 40%. APOE3 is the
most common allele and doesn't seem to influence risk. The APOE4 allele,
present in approximately 10-15% of people, increases the risk for
Alzheimer's and lowers the age of onset. Having one copy of E4 (E3/E4)
can increase your risk by 2 to 3 times while two copies (E4/E4) can
increase the risk by 12 times [2].
Despite this association, the National Institutes of Healthonly recommends genetic testing for APOE status to advance drug
research in clinical trials.(Because if people know it they will clamour for prevention protocols and you can't have the general public directing research initiatives. Best to keep people in the dark.)APOE4 is just one of many risk factors for
dementia and its influence can vary across age, gender, race, and
nationality [3][4].
For example, having one copy of the E4 allele may pose more risk to
women while having two copies seems to affect men and women similarly [5].
To learn more about the genetics of Alzheimer's disease and the contribution of the APOE genes, check out the National Institute on Aging's Alzheimer's Disease Genetics Fact Sheet.
THE BIOLOGY OF APOE
The APOE protein plays many important roles, including the transport
of cholesterol across different tissues and cells. The proteins made by
varying APOE alleles handle this transport function differently.
Outside the brain, APOE4 can increase the risk of atherosclerosis (i.e., hardening of the arteries) and stroke [4], which may explain why APOE4 is a risk factor for vascular causes of cognitive impairment and dementia [6][7].
Inside the brain, APOE helps to clear beta-amyloid, a component of
plaques. APOE2 appears to perform this function more effectively than
APOE4, with APOE3 in the middle. This difference in beta-amyloid
transport represents what scientists call "loss-of-function" toxicity.
However, researchers suspect that APOE4 proteins may also have toxic
"gain-of-function" activities, such as increased response to stress or
injury [4]. APOE4 may increase the risk of dementia
through toxic gain of function and through the loss of normal healthy
function. Figure adapted from [4]
APOE4 AND ALZHEIMER'S DRUG DISCOVERY
Some drugs in development (called "structure correctors") may change
the physical structure of the APOE4 protein so that it behaves more like
the APOE2 protein [8]. Another approach is gene therapy, which attempts to insert APOE2 genes into the brains of people with APOE4 genes [9].
To learn more about these programs and other APOE-related drug
discovery programs supported by the Alzheimer's Drug Discovery
Foundation, review our research portfolio with a filter for "APOE4."
DOES APOE AFFECT HOW THERAPIES WORK?
Researchers are exploring whether the APOE genotype influences the
effects of drugs and other therapies in development for Alzheimer's
disease and general cognitive health. Highlights of the scientific
research in which a differential effect is possible follows, with links
to reports. Estrogen:
Several studies suggest that the side effects of estrogen-containing
hormone replacement therapy may be worse in people who carry the APOE4
allele, at least in terms of brain aging and dementia risk. However, the
evidence is inconsistent. Hypertension Management:
Effective management of mid-life hypertension is likely to reduce the
risk of dementia and cognitive decline in most people. Observational
studies suggest that APOE4 carriers might be particularly likely to reap
the benefits of effective hypertension management. However, the complex
relationships between cardiovascular health, APOE status, and cognition
are not well understood. DHA:
Although DHA may be part of a healthy diet for APOE4 carriers, evidence
from observational studies, clinical trials, and some preclinical
research suggests that it is less likely to protect against dementia or
cognitive decline in APOE4 carriers. Some researchers are testing the
idea that APOE4 carriers simply need higher doses of DHA because it does
not reach their brains as effectively [10]. Statins:
Evidence is mixed on whether statins have different effects on brain
health in people who carry at least one APOE4 allele. Several
observational studies found that APOE4 allele status had no effect while
another suggested different effects on cognition in patients with at
least one APOE4 allele. Nicotine:
Although there is no evidence suggesting different Alzheimer's disease
benefits from nicotine between APOE4 carriers and non-carriers, some
evidence suggests nicotine may be a stronger acute cognitive enhancer in
APOE4 carriers than non-carriers. Cerebrolysin:
One clinical trial comparing the Exelon™ patch with cerebrolysin found
no difference in response rates in patients with at least one APOE4
allele but a 3-fold higher response rate in patients without an APOE4
allele.
As research on Alzheimer’s disease (AD) advances, a desperate need
remains for an easy blood test to help diagnose the condition as early
as possible. Ideally, such a test could also distinguish AD from other
forms of dementia that produce similar symptoms. As published recently
in Nature Medicine, an NIH-funded research team has designed a simple blood test that is on course to meet these criteria [1].
The latest work builds on a large body of work showing that one
secret to predicting a person’s cognitive decline and treatment response
in AD lies in a protein called tau.
Using the powerful, but expensive, approach of PET scan imaging, we
know that tau builds up in the brain as Alzheimer’s disease progresses.
We also know that some tau spills from the brain into the bloodstream.
The trouble is that the circulating tau protein breaks down far too
quickly for a blood test to offer a reliable measure of what’s happening
in a person’s brain. A few years ago, researchers discovered a possible
solution: test for blood levels of a slightly different and more stable
version of the protein called pTau181 [2]. (The “p” in its name comes
from the addition of phosphorus in a particular part of the protein’s
structure.)
In the latest study, researchers in the lab of Adam Boxer, University
of California, San Francisco, followed up further on this compelling
lead. Boxer’s team measured pTau181 levels in blood samples from 362
people between the ages of 58 and 70. Those samples included 56 people
with an Alzheimer’s diagnosis, along with 47 people with mild cognitive
impairment and 69 healthy controls.
The researchers also included another 190 people diagnosed with frontotemporal lobar degeneration
(FTLD). It is a relatively rare form of dementia that leads to a
gradual decline in behavior, language, and movement, often in connection
with a buildup of tau in the brain.
The study found that levels of pTau181 were roughly 3.5-times higher
in the blood of people with AD compared to people without AD. Those with
mild cognitive impairment due to underlying AD also showed an
intermediate increase in blood levels of pTau181.
Importantly, people with FLTD had normal blood levels of pTau181. As a
result, the blood test could reliably distinguish between a person with
AD and a person with FLTD. That’s important because, while FLTD is a
relatively rare condition, its prevalence is similar to AD in people
under the age of 65. But both conditions have similar symptoms, making
it often challenging to distinguish them.
The findings add to evidence that the new blood test can help in
diagnosing AD and in distinguishing it from other neurodegenerative
conditions. In fact, it does so with an accuracy that often rivals more
expensive PET scans and more invasive cerebrospinal fluid tests, which
are now the only reliable ways to measure tau.
There’s still plenty of work to do before this blood test is ready
for a doctor’s office. But these initial findings are very promising in
helping to simplify the diagnosis of this devastating condition that now
affects an estimated 5.5 million Americans [3]. References:
[1] Diagnostic value of plasma phosphorylated tau181 in Alzheimer’s disease and frontotemporal lobar degeneration.
Thijssen EH, La Joie R, Wolf A, Strom A, Wang P, Iaccarino L, Bourakova
V, Cobigo Y, Heuer H, Spina S, VandeVrede L, Chai X, Proctor NK, Airey
DC, Shcherbinin S, Duggan Evans C, Sims JR, Zetterberg H, Blennow K,
Karydas AM, Teunissen CE, Kramer JH, Grinberg LT, Seeley WW, Rosen H,
Boeve BF, Miller BL, Rabinovici GD, Dage JL, Rojas JC, Boxer AL;
Advancing Research and Treatment for Frontotemporal Lobar Degeneration
(ARTFL) investigators. Nat Med. 2020 Mar 2.
[2] Plasma
phospho-tau181 increases with Alzheimer’s disease clinical severity and
is associated with tau- and amyloid-positron emission tomography.
Mielke MM, Hagen CE, Xu J, Chai X, Vemuri P, Lowe VJ, Airey DC, Knopman
DS, Roberts RO, Machulda MM, Jack CR Jr, Petersen RC, Dage JL.
Alzheimers Dement. 2018 Aug;14(8):989-997.
[3] Alzheimer’s Disease Fact Sheet. National Institute on Aging, May 22, 2019.
If we had a great stroke association with a fully functioning database of all stroke trials and their results we would know immediately when results should be available. Then the president of that great stroke association could do their job and get the results published. THIS IS WHY WE NEED SURVIVORS IN CHARGE. Existing stroke leadership is a complete fucking failure, see here for why I say that; 13 stroke problems with no cure
For 20 years, the U.S. government has urged companies, universities,
and other institutions that conduct clinical trials to record their
results in a federal database, so doctors and patients can see whether
new treatments are safe and effective. Few trial sponsors have
consistently done so, even after a 2007 law made posting mandatory for
many trials registered in the database. In 2017, the National Institutes
of Health (NIH) and the Food and Drug Administration (FDA) tried again,
enacting a long-awaited “final rule” to clarify the law’s expectations
and penalties for failing to disclose trial results. The rule took full
effect 2 years ago, on 18 January 2018, giving trial sponsors ample time
to comply. But a Science investigation shows that many still ignore the requirement, while federal officials do little or nothing to enforce the law.
Science examined more than 4700 trials whose results should
have been posted on the NIH website ClinicalTrials.gov under the 2017
rule. Reporting rates by most large pharmaceutical companies and some
universities have improved sharply, but performance by many other trial
sponsors—including, ironically, NIH itself—was lackluster. Those
sponsors, typically either the institution conducting a trial or its
funder, must deposit results and other data within 1 year of completing a
trial. But of 184 sponsor organizations with at least five trials due
as of 25 September 2019, 30 companies, universities, or medical centers never met a single deadline.
As of that date, those habitual violators had failed to report any
results for 67% of their trials and averaged 268 days late for those and
all trials that missed their deadlines. They included such eminent
institutions as the Harvard University–affiliated Boston Children’s
Hospital, the University of Minnesota, and Baylor College of
Medicine—all among the top 50 recipients of NIH grants in 2019.
The violations cover trials in virtually all fields of medicine, and
the missing or late results offer potentially vital information for the
most desperate patients. For example, in one long-overdue trial,
researchers compared the efficacy of different chemotherapy regimens in
200 patients with advanced lymphoma; another—nearly 2 years late—tests
immunotherapy against conventional chemotherapy in about 600 people with
late-stage lung cancer.
Other leading NIH grantees did only slightly better in Science’s analysis based on data collected from the TrialsTracker website
of the University of Oxford, which automatically mines information from
ClinicalTrials.gov. The University of Texas MD Anderson Cancer Center
and the Mayo Clinic both failed to report results on time, or at all, in
about two-thirds of their trials. Yale University failed to do so in
84% of its trials. NIH’s own institutes also had a bad record. They are
directly responsible for reporting results when they sponsor studies
done by agency staff or some grantees, and the top four NIH institute
sponsors, taken together, reported results late or not at all in more
than six of every 10 trials Science looked at.
Contacted for comment, none of the institutions disputed the findings of this investigation. In all 4768 trials Science
checked, sponsors violated the reporting law more than 55% of the time.
And in hundreds of cases where the sponsors got credit for reporting
trial results, they have yet to be publicly posted because of quality
lapses flagged by ClinicalTrials.gov staff (see sidebar).
Although the 2017 rule, and officials’ statements at the time,
promised aggressive enforcement and stiff penalties, neither NIH nor FDA
has cracked down. FDA now says it won’t brandish its big
stick—penalties of up to $12,103 a day for failing to report a trial’s
results—until after the agency issues further “guidance” on how it will
exercise that power. It has not set a date. NIH said at a 2016 briefing
on the final rule that it would cut off grants to those who ignore the
trial reporting requirements, as authorized in the 2007 law, but so far
has not done so.
Missed deadlines
Among more than 4700 clinical trials examined by Science, less than 45% had their results reported early or on time to ClinicalTrials.gov.
150631.6%
Not reported
113223.7%
(GRAPHIC) N. DESAI/SCIENCE; (DATA) CLINICALTRIALS.GOV, VIA TRIALSTRACKER
Many scientists who conduct clinical trials, and their sponsors
or funders, have downplayed concerns about late or missing results in
ClinicalTrials.gov. Researchers, doctors, and patients can instead learn
about trial outcomes from peer-reviewed publications, they say. But
thousands of trials are never published, particularly when they find
treatments ineffective, history has shown. ClinicalTrials.gov also uses a
common format, allowing relatively easy comparisons of results across
trials that journal articles rarely make possible. Doctors, researchers,
and potential trial participants rely on the site, to judge from its
215 million monthly page views.
Deborah Zarin, a physician at Brigham and Women’s Hospital and
Harvard who headed ClinicalTrials.gov between 2005 and 2018, says the Science findings
show failures of the research culture, FDA, and NIH. “If this was a
priority for the leadership of NIH, then they could ensure that
high-quality, timely reporting happened all of the time,” says Zarin, an
NIH-paid research consultant for the database. “You can set up
processes so trial reporting is an expectation. You can’t pass ‘go’ and
collect $200 until this is done.”
Zarin, who works in a program to advance clinical research, adds that
the problem persists because “reporting to ClinicalTrials.gov is
frequently seen by sponsors, funders, and trialists as an annoying
administrative and perhaps legal burden, not a scientific imperative.
Human nature being what it is, people follow the requirements when
forced to do so.”
NIH and FDA officials do not seem inclined to apply that pressure.
Lyric Jorgenson, NIH deputy director for science policy, says her agency
has been “trying to change the culture of how clinical trial results
are reported and disseminated; not so much on the ‘aha, we caught you,’
as much as getting people to understand the value, and making it as easy
as possible to share and disseminate results.” To that end, she says,
ClinicalTrials.gov staff have educated researchers about the website and
improved its usability.
As for FDA, Patrick McNeilly, an official at the agency who handles
trial enforcement matters, recently told an industry conference session
on ClinicalTrials.gov that “FDA has limited resources, and we encourage
voluntary compliance.” He said the agency also reviews reporting of
information on ClinicalTrials.gov as part of inspections of trial sites,
or when it receives complaints.
McNeilly declined an interview request, but at the conference he
discounted violations of ClinicalTrials.gov reporting requirements found
by journalists and watchdog groups. “We’re not going to blanketly
accept an entire list of trials that people say are noncompliant,” he
said. Such determinations require “nonpublic information” submitted to
the agency by trial sponsors. In response to Science’s
findings, a spokesperson said an absence of posted results on
ClinicalTrials.gov did not mean a trial sponsor has broken the 2007 law.
Yet that law and the 2017 final rule detail only a few exemptions
that would allow trial sponsors to withhold results on the basis of
nonpublic information. The very few registered trials that qualify for
those exemptions are not flagged as violators by TrialsTracker or in Science’s analysis. Congress approved the creation of ClinicalTrials.gov
in 1997, after allegations that patients were harmed because companies
withheld evidence showing their medicines were ineffective or hazardous.
A widely cited case involved the GlaxoSmithKline antidepressant Paxil
(paroxetine). According to legal filings and a report in The BMJ,
the firm held secret data showing that in clinical trials the drug was
ineffective and caused suicidal thoughts in teenagers, yet encouraged
doctors to prescribe it for young people.
Registration was only required initially for trials of
treatments for serious or life-threatening diseases. But the 2007 law,
the Food and Drug Administration Amendments Act, required sponsors to
register a much broader range of trials within 21 days of enrolling the
first patient, and to post summary results, adverse events, and other
data to ClinicalTrials.gov within 1 year of collecting the last patient
data. Although many trials, such as industry-sponsored early-stage
evaluations of drug safety, are exempt from reporting, about 326,000
have been registered, and results have been posted for more than 40,000.
Yet until 2015, even the most active investigators at clinical
research institutions treated the law more as a suggestion—not
surprising given that the government enforced no penalties and did not
publicly identify violators. A report on the news website STAT by
this author and Talia Bronshtein first drew significant attention to
specific trial sponsors—companies, government agencies, universities,
and individuals—that routinely ignored reporting requirements. It
sparked immediate improvement, according to NIH. (Those same authors
documented some of that improvement in a 2018 STATarticle.)
At a 2016 press briefing, NIH and FDA rolled out the final rule,
aimed at boosting even greater compliance with the 2007 law. It took
effect in January 2017, with first deadlines for results, and ostensibly
enforcement, 1 year later. Then–FDA Commissioner Robert Califf said it
would thereafter “be pretty hard to hide that you are doing a clinical
trial or hide the result.” FDA, he vowed, was finally prepared, if
necessary, to enforce the daily $10,000 penalty for noncompliance
allowed under the law. (Adjusted for inflation, that figure recently
rose above $12,000.)
“I don’t think anybody wants to be on the wall of shame,” NIH
Director Francis Collins said at the press event, promising that NIH
would publicly flag reporting violations on ClinicalTrials.gov itself.
“We are serious about this,” Collins said, threatening for the first
time to enforce provisions of the 2007 law that allow NIH to rescind
funding to grantees who violate the statute. “It’s hard to herd cats,
but you can … take their food away,” he said. “This is about maintaining
the trust that we have with participants in clinical trials. … If we
fail to live up to that expectation, then that is an ethical failure.”
Three years later, TrialsTracker conservatively estimates that FDA
could have collected more than $6 billion in ClinicalTrials.gov
penalties so far. The agency has yet to demand a single dollar. And
despite more than 2600 trials for which results are overdue or were
filed late, NIH has yet to withhold a single grant as a result or post a
single violation notice on ClinicalTrials.gov. No “wall of shame”
exists.
“Public-facing websites run by the government should be accurate.
That’s not asking much,” Senator Chuck Grassley (R–IA), who advocated
for the 2007 law, wrote in an email after reviewing a summary of the Science findings.
“It’s a question of basic management and agency competence. The
government has a duty to police its work product, especially because the
public trusts .gov websites will be accurate and reliable.”
To physician Ben Goldacre, who directs the Oxford program behind TrialsTracker, “The lack of urgency is really troubling.”
Reporting problems
Science analyzed
ClinicalTrials.gov records of all clinical trials with results legally
required to be reported between 18 January 2018 and 25 September 2019.
The chart, covering trial sponsors with 15 or more results due in that
window or reported early, shows that some results deposited were not
posted due to quality lapses. It also highlights that pharma’s record
has been markedly better than that of academia and the federal
government.Academic/nonprofit
Federal government
Industry
Avg.days late
Totaltrials
Reported on time or early
Reported late
Not reported
Quality problems
Massachusetts General Hospital
Mayo Clinic
Memorial Sloan Kettering Cancer Center
University of North Carolina, Chapel Hill
University of California, San Francisco
Duke University
University of Pennsylvania
Emory University
UT Health Science Center, Houston
Wash. Univ. School of Medicine in St. Louis
University of Chicago
Stanford University
Johns Hopkins University
University of Washington
Wake Forest University Health Sciences
University of Virginia
Sidney Kimmel Comp. Cancer Center
University of Michigan
New York State Psychiatric Institute
Columbia University
Yale University
Dana-Farber Cancer Institute
Icahn School of Medicine at Mount Sinai
Indiana University
University of Colorado, Denver
Medical University of South Carolina
Montefiore Medical Center
Northwestern University
University of Alabama, Birmingham
University of Wisconsin, Madison
National Cancer Institute
Natl. Inst. of Allergy and Infectious Diseases
VA Office of Research and Development
Natl. Heart, Lung, and Blood Institute
Novartis Pharmaceuticals
Gilead Sciences
Pfizer
GlaxoSmithKline
Hoffmann-La Roche
AstraZeneca
Eli Lilly and Company
Allergan
Amgen
Bristol-Myers Squibb
Merck & Co.
Sanofi
Alcon
AbbVie
Celgene
Novo Nordisk
Boehringer Ingelheim
Johnson & Johnson Vision Care
Bayer
Janssen Research & Development
Teva Pharmaceutical Industries
MD Anderson Cancer Center
(GRAPHIC) N. DESAI/SCIENCE; (DATA) CLINICALTRIALS.GOV, VIA TRIALSTRACKER
In a recent article in The BMJ, Goldacre
and colleagues highlighted a long-running MD Anderson trial as an
example of what’s at stake when clinical research results go AWOL.
Started in 1999, the trial tested a specialized hormone therapy in
patients who had surgery for prostate cancer and faced a high risk of
recurrence. The treatment might reduce that risk significantly, but
other trials suggested it had serious side effects, including reduced
bone density, sexual dysfunction, and greater risk of diabetes and
cardiovascular events. When Science collected the
ClinicalTrials.gov data, the MD Anderson trial’s results were overdue by
1 year and 8 months without explanation, and no journal appears to have
published them. Doctors and prostate cancer patients weighing the most
appropriate treatment have been left in the dark.
Stephen Hahn, who served as chief medical officer at MD Anderson
until last month, when he became the new FDA commissioner, was
unavailable for comment. An MD Anderson spokesperson said the center
“believes in transparency,” and is making “every effort to comply” with
trial reporting rules, but did not respond to a question on the missing
cancer trial data.
Mayo, Yale, the University of Minnesota, Baylor, and Boston
Children’s, which have similarly poor reporting records, all said via
email that they, too, were committed to fulfilling ClinicalTrials.gov
requirements. Mayo said it deployed dedicated staff to assist
researchers. Yale noted it had registered hundreds of trials exempt from
reporting requirements and added a layer of review to help ensure
compliance. The University of Minnesota recently created a monitoring
system and has made rapid progress on reporting, according to a
spokesperson. Baylor said it planned to centralize trial monitoring, as
“a top priority.” Boston Children’s said it was “committed to achieving
100% compliance.” It submitted data for one long-overdue study after
being contacted by Science, but four others remain in apparent violation as of the end of 2019.
The slow, apparently forgiving regulatory approach favored by NIH and
FDA will never force such organizations into full compliance, some
advocates of clinical trial transparency say. “In an era when every
restaurant is obliged to publish on its front door the hygiene rating in
their kitchen, we’re seriously not saying whether a trial that costs
millions of dollars has broken the law and its obligation to … patient
participants by failing to report its results?” Goldacre asks. “That
seems like extraordinary special treatment for clinical trialists.”
Select institutions have made serious efforts to comply. Twenty big
pharma companies met all reporting requirements under the 2017 rule and
some major academic centers improved sharply compared with data
collected in 2017 (as detailed in the second STAT investigation).
Memorial Sloan Kettering Cancer Center, Duke University, and Johns
Hopkins University—poor performers in 2017—complied with the law in
nearly all their registered trials covered by the new rule. Johns
Hopkins added staff to track and assist on reporting and to identify
“problem records.” And it enlisted university executives to crack down
on recalcitrant investigators, according to Anthony Keyes, a clinical
research manager there.
But such good performance shouldn’t be an exception, Harvard's Zarin
says. “Further public accountability of the trialists, but also our
government organizations, has to happen. One possibility is that FDA and
NIH will be shamed into enforcing the law. Another possibility is that
sponsors will be shamed into doing a better job. A third possibility is
that ClinicalTrials.gov will never fully achieve its vital aspirations.” This story was supported by the Science Fund for Investigative Reporting.
Researchers
will test promising drugs aimed at preventing Alzheimer’s and identify
and validate biological targets for novel therapies, with approximately
$45 million in new funding from the National Institutes of Health. The
initiative will support innovative new studies as part of an intensified
national effort to find effective interventions for this devastating
degenerative brain disease.
The studies are among the first to be developed with direction from the 2012 NIH Alzheimer’s Disease Research Summit: Path to Treatment and Prevention and reflect research goals in the National Plan to Address Alzheimer’s Disease.
Of the funding, $40 million is from an allocation from the Office of
the NIH Director, Dr. Francis Collins, with additional funding from the
National Institute on Aging (NIA), the lead Institute within NIH for
Alzheimer’s research.
“As many as 5 million Americans face the challenge of Alzheimer’s
disease, which robs them of their memories, their independence, and
ultimately, their lives,” Dr. Collins said. “We are determined, even in a
time of constrained fiscal resources, to capitalize on exciting
scientific opportunities to advance understanding of Alzheimer’s biology
and find effective therapies as quickly as possible.”
The clinical trials investigate possible ways to stop the progression
of the disease. The translational research study awards are focused on
identifying, characterizing and validating novel therapeutic targets.
“We know that Alzheimer’s-related brain changes take place years,
even decades, before symptoms appear. That really may be the optimal
window for drugs that delay progression or prevent the disease
altogether,” said NIA Director Dr. Richard Hodes. “The clinical trials
getting under way with these funds will test treatments in symptom-free
volunteers at risk for the disease, or those in the very earliest
stages—where we hope we can make the biggest difference.”
Basic and genetic studies of the disease—from the abnormal proteins
involved, to genetic influences, to inflammation and other
Alzheimer’s-related brain changes—have advanced our knowledge. This has
given us new insights into the biological underpinnings of this
extremely complex disorder, Dr. Hodes said.
Today’s awards support the following clinical trials. (Individual
investigators can be contacted about when these studies will recruit
participants.):
- See more at:
http://www.nia.nih.gov/newsroom/2013/09/nih-funding-boosts-new-alzheimers-research-prevention-novel-drug-targets#sthash.LdFTJjkC.dpuf
Quiz your doctor on how this BRAIN initiative will help get all stroke survivors 100% recovered. If they aren't thinking about that, they need to be fired because they are just dead wood sitting around waiting for rot to set in. The status quo in stroke is a complete failure.
Walter Koroshetz, Joshua Gordon, Amy Adams, Andrea Beckel-Mitchener, James Churchill, Gregory Farber, Michelle Freund, Jim Gnadt, Nina Hsu, Nicholas Langhals, Sarah Lisanby, Guoying Liu, Grace Peng, Khara Ramos, Michael Steinmetz, Edmund Talley and Samantha White
Journal of Neuroscience 19 June 2018, 3174-17; DOI: https://doi.org/10.1523/JNEUROSCI.3174-17.2018
The BRAIN Initiative® arose from a grand challenge to “accelerate the development and application of new technologies that will enable researchers to produce dynamic pictures of the brain that show how individual brain cells and complex neural circuits interact at the speed of thought.” The BRAIN Initiative is a public-private effort focused on the development and use of powerful tools for acquiring fundamental insights about how information processing occurs in the central nervous system. As the Initiative enters its fifth year, NIH has supported over 500 principal investigators, who have answered the Initiative's challenge via hundreds of publications describing novel tools, methods, and discoveries that address the Initiative's seven scientific priorities. We describe scientific advances produced by individual labs, multi-investigator teams, and entire consortia that, over the coming decades, will produce more comprehensive and dynamic maps of the brain, deepen our understanding of how circuit activity can produce a rich tapestry of behaviors, and lay the foundation for understanding how its circuitry is disrupted in brain disorders. Much more work remains to bring this vision to fruition, and NIH continues to look to the diverse scientific community, from mathematics, to physics, chemistry, engineering, neuroethics, and neuroscience, to ensure that the greatest scientific benefit arises from this unique research Initiative.
