Eye Exam Detects Signs of Alzheimer's Disease

The new research is a "small step forward," said Dr. Richard Isaacson, director of the Alzheimer's Prevention Clinic at NewYork-Presbyterian/Weill Cornell Medicine.

"But future studies need to focus on earlier stages of the disease," Isaacson said in an email. "We already have more definitive ways to diagnose dementia due to Alzheimer's, but we need to see if OTCA can be a useful cost-effective screening test for pre-symptomatic Alzheimer's."

 Using an ultrasensitive scanning technique, researchers can detect signs of Alzheimer's disease in the tiny blood vessels at the back of the eye, according to a new report.

Duke University researchers found that these small retinal blood vessels were altered in patients with Alzheimer's disease, but in not in those with mild cognitive impairment (MCI) or those with no signs of mental decline.

"Among the folks who had Alzheimer's there was a significant reduction in the density of the blood vessels in the superficial layer of the retina compared to controls and those with mild cognitive impairment," said Dr. Dilraj Grewal, an associate professor of ophthalmology at the Duke Eye Center. "We also found a reduction in the thickness of (of a specific layer of the retina) in Alzheimer's patients compared to controls and those with mild cognitive impairment."

The findings were reported March 11 online in Ophthalmology Retina, a publication of the American Academy of Ophthalmology.

"The retina is an extension of the brain," Grewal said. "And it's thought that changes that occur in the brain are mirrored in the retina. With any neurodegenerative disease, you lose nerve tissue. Along with a measurable loss of brain volume, there's a loss of the vasculature that supplies the brain. And because the retina is part of the central nervous system, the same changes occur there."

Practical Essentials

The current diagnosis of Alzheimer disease is made by clinical, neuropsychological, and neuroimaging assessments. Routine structural neuroimaging evaluation has long been based on nonspecific features such as atrophy, which is a late feature in the progression of the disease. More recently, a variety of imaging modalities, including structural and functional magnetic resonance imaging (MRI) and positron emission tomography (PET) studies of cerebral metabolism, have shown characteristic changes in the brains of patients with Alzheimer disease in prodromal and even presymptomatic states. ^[1, 2, 3]

Alzheimer disease was first described in 1907 by Alois Alzheimer. From its original status as a rare disease, Alzheimer disease has become one of the most common diseases in the aging population, ranking as the fourth most common cause of death. Alzheimer disease is a progressive neurodegenerative disorder characterized by the gradual onset of dementia. The pathologic hallmarks of the disease are beta-amyloid (Aβ) plaques, neurofibrillary tangles (NFTs), and reactive gliosis. ^[4, 5, 6] (See the images below.)

fMRI revealing changes from Alzheimers Disease

Left Healthy Brain Right Alzheimer Brain  

                          

Coronal, T1-weighted magnetic resonance imaging (MRI) scan in a patient with moderate Alzheimer disease. Brain image reveals hippocampal atrophy, especially on the right side.

Eye Exam Detects Signs of Alzheimer's Disease: Using an ultrasensitive scanning technique, researchers can detect signs of Alzheimer's disease in the tiny blood vessels at the back of the eye, according to a new report.

Retinal fundus photography

Retina Fundus Camera

Using a high-definition eye scan developed especially for the study, researchers detected the crucial warning signs of Alzheimer's disease: amyloid-beta deposits, a buildup of toxic proteins. The findings represent a major advancement toward identifying people at high risk for the debilitating condition years sooner.

In addition to retinal imaging, there may be other ocular findings associated with Alzheimer's disease.

Low levels of amyloid-β and tau proteins, biomarkers of Alzheimer's disease (AD), in eye fluid were significantly associated with low cognitive scores, according to a new study published in the Journal of Alzheimer's Disease. Led by researchers at Boston Medical Center, the study is the first to connect these known AD protein biomarkers in the eye to mental status. These findings indicate that proteins in the eye may be a potential source for an accessible, cost-effective test to predict future Alzheimer's disease.

https://www.hindawi.com/journals/joph/2018/8538573/

https://www.ncbi.nlm.nih.gov/pubmed/25095818

https://www.sciencedirect.com/science/article/abs/pii/S0304394007002492

Drug Pricing |

For years, American patients have suffered under a drug-pricing system that provides generous incentives for innovation, while too often failing to deliver important medications at an affordable cost. We have access to the greatest medicines in the world, but access is meaningless without affordability.

The Trump Administration Blueprint to Lower Drug Prices and Reduce Out-of-Pocket Costs 

• Fact Sheet: 100 Days of Results: President Trump’s American Patients First Blueprint - PDF
• Report on 100 Days of Action on the American Patient First Blueprint - PDF

The Trump blueprint has already made significant gains in controlling and perhaps reversing costs of pharmaceutical benefits.

In an address to the American Medical Association, Alex Azar, head of the Dept of Health and Human Services, had this opening remark,

"The first principle of our vision for value-based healthcare is about empowering patients—but we are fully aware this cannot be done without empowering physicians, too. So I want you all to imagine a system where patients are finally in the driver’s seat, free to work with physicians who have been empowered as navigators of the best options for their patient, rather than navigators of a sea of paperwork."

The mission of HHS is to enhance and protect the health and well-being of every American—and I know that is the mission and vocation of every member of the AMA as well.

That includes the four priorities I’ve chosen as Secretary:  1. combating the opioid crisis, 2. reforming the individual insurance market,  3. lowering the price of prescription drugs, and 4.  transforming our healthcare system into one that pays for value.

HHS has identified four challenges in the American drug market: • High list prices for drugs • Seniors and government programs overpaying for drugs due to lack of the latest negotiation tools • High and rising out-of-pocket costs for consumers • Foreign governments free-riding of American investment in innovation goal of the blueprint was very clear: bringing down prescription drug prices and patient out-of-pocket costs. We laid out dozens of possible actions in the blueprint, many of which will entail some disruption to existing industry players.

That’s why we laid out the blueprint in a deliberative way. We want to disrupt how drugs are priced in America because that system is so deeply broken. But we have to accomplish this goal in a way that minimizes any disruption for patients and providers.

HHS has identified four challenges in the American drug market: • High list prices for drugs • Seniors and government programs overpaying for drugs due to lack of the latest negotiation tools • High and rising out-of-pocket costs for consumers • Foreign governments free-riding of of American investment in innovation Under President Trump, HHS has proposed a comprehensive blueprint for addressing these challenges, identifying four key strategies for reform: • Improved competition • Better negotiation • Incentives for lower list prices • Lowering out-of-pocket costs HHS’s blueprint encompasses two phases: 1) actions the President may direct HHS to take immediately and 2) actions HHS is actively considering, on which feedback is being solicited.Last fall, the President put forth a model for overhauling how Medicare pays for physician-administered drugs, in Medicare Part B fee-for-service.

Today’s Part B status quo is totally unacceptable: America pays almost twice as much, and sometimes five or six times as much, as other wealthy countries pay for the most costly physician-administered drugs. Meanwhile, physicians are put in the position of having to acquire and hold these drugs, which are often extremely expensive, risky acquisitions.

Our new International Price Index model, or IPI, is primarily aimed at delivering for American patients a share of the discounts that drug manufacturers currently give to other wealthy countries. Through the advance notice of proposed rulemaking (ANPRM), CMS is seeking feedback on the potential parameters of the IPI Model. The ANPRM can be downloaded from the CMS Newsroom.

Background

Medicare Part B drug expenditures have increased significantly over time. From 2011 to 2016, Medicare FFS drug spending increased from $17.6 billion to $28 billion under Medicare Part B, representing a compound annual growth rate (CAGR) of 9.8 percent, with per capita spending increasing 54 percent, from $532 to $818. Medicare beneficiaries and the Medicare program are also paying more for Part B drugs than international comparators. Based on a HHS analysis comparing Medicare spending for separately payable Part B physician-administered drugs to the prices of those drugs in sixteen other developed economies – Austria, Belgium, Canada, Czech Republic, Finland, France, Germany, Greece, Ireland, Italy, Japan, Portugal, Slovakia, Spain, Sweden, and United Kingdom – spending in the U.S. was 1.8 times higher. As a result, Medicare beneficiaries and the Medicare program are bearing unnecessary, potentially avoidable costs for Part B drugs.

Currently, Medicare payment for separately payable outpatient drugs in physician offices, hospital outpatient departments, and certain other settings is based on drug manufacturers’ average sales prices in the United States plus a six percent add-on payment (+6 percent), and is subject to the sequestration, which effectively reduces the add-on to +4.3 percent. The dollar amount of the add-on is larger as drug prices increase, which may encourage physicians to prescribe higher-cost drugs and raise beneficiary and program spending.

Stakeholders have stated that the high cost of Part B drugs for treating cancer, rheumatoid arthritis, multiple sclerosis, other immune disorders, and other conditions, may pose a barrier to providers furnishing these therapies and beneficiaries receiving treatment. CMS has heard from many physicians, specialty groups and patient advocates that the high cost of drugs is a growing financial risk for beneficiaries and providers.

The ongoing struggle against rising drug costs continues. These provisions apply only to CMS and Medicare Beneficiaries.  This segment is a considerable portion of users and ignores private payers. That is another story and also needs to be addressed. 

A Letter from American Health Insurance Plans (Matthew Eyles, President and CEO) explores the ramification and cost shifting that could come about by the International Price Index Model .




Drug Pricing | HHS.gov: Blueprint for bringing down the high price of drugs and reducing out-of-pocket costs for the American consumer.

Cystic Fibrosis drug could be made available as early as NEXT MONTH | UK | News | Express.co.uk

BREXIT has invaded the cystic fibrosis space, threatening the health of CF patients in the U.K.

A WONDER drug (ORKAMBI)  could dramatically improve the lives of thousands of Cystic Fibrosis patients may be available to use next month if a funding deadlock is broken, it emerged yesterday.

ORKAMBI has been unavailable for three years since the FDA approved its use in the United States of America. VERTEX developed and distributes Orkambi thanks to a generous donation and a partnership with the Cystic Fibrosis Foundation (USA)

Vertex has been a major player in CF treatment. They also developed the following CF therapeutics

Kalydeco generic name: ivacaftor  class: CFTR potentiators		10
Orkambi generic name: ivacaftor/lumacaftor  class: CFTR combinations	N/A
Symdeko generic name: ivacaftor/tezacaftor  class: CFTR combinations

All of these drugs have a specific indication for the F508 chromosomal deletion affecting the CFTR protein on cell membranes which is a gatway for chloride transfer.

A description of Cystic Fibrosis was noted in the middle ages.

“Woe is the child who tastes salty from a kiss on the brow, for he is cursed and soon must die”.

Cystic Fibrosis drug could be made available as early as NEXT MONTH | UK | News | Express.co.uk:

Heart Disease Morbidity and Mortality Improve drastically

Apple News

In the US in the 1990s, having a heart attack was basically a death sentence for some 20% of the people who suffered one.

The country’s medical community has spent the last three decades or so working on this problem, and experts widely believe the efforts have paid off. Until now, however, researchers with Yale University say there hasn’t been clear evidence to show that the heart-attack death rate has actually fallen.

Eager to fix that, they set out to analyze data from more than 4.3 million Americans aged 65 or older who had suffered heart attacks. All of them were Medicare fee-for-service patients. The data spans from January 1995 to January 2015 and was pulled from 5,680 US hospitals. The results were published on March 15 in the Journal of the American Medical Association Open Network.

Researchers find heart attacks aren't as frequent or deadly for Americans

The numbers are pretty striking. Back in 1995, 20% of the patients whose cases were included in the study died from their heart attacks. By 2014, that number fell to just 12%. Over the same period, the rate of hospitalization for a first-time heart attack dropped by 38%—from 914 to 566 per 100,000 Medicare beneficiary-years. Because the number of people admitted to the hospital after a heart attack dropped, the healthcare costs attributed to heart attacks has decreased, even though hospital costs overall have increased (pdf) in the US over time.

So what led to these significant declines in costs and fatality rates for heart-attack patients? Much of it has to do with a concerted effort on the parts of three national organizations—the Centers for Medicare & Medicaid Services, the American College of Cardiology, and the American Heart Association—to spearhead changes in treatment.

In the 1990s, the health care community established that aspirin and a class of drugs called beta-blockers (used to reduce blood pressure) were some of the best ways to improve chances of survival after a heart attack. Also over the last 30 years, coronary angioplasty has become more widely available. Physicians use this non-surgical procedure to open arteries that are clogged with a buildup of plaque, thus helping blood flow from the heart. It’s a highly effective way to decrease the risk of mortality, far more so than any medication alone.

The researchers also credit lifestyle changes, such as more healthful dieting, for contributing to the decreases in heart-attack hospitalization and mortality rates.

Not everyone in the US has seen these benefits, however. After analyzing data from thousands of hospitals spread across the US, the researchers uncovered issues of disparity. In places where unemployment is high, the risk of death after suffering a heart attack is higher than in areas with a healthy employment rate. The study didn’t have a clear answer for why that’s the case.

This could be due to more uninsured patients, poor access to hospitals with cardiac excellence centers, and lack of timely emergency transportation, and lack of preventive care. The study did not analyze location parameters.

“This is no time to be complacent,” one of the researchers, Harlan Krumholz, told Consumer Affairs. “We document extraordinary gains—but the effort is far from finished. The goal is to one day relegate heart attacks to the history of medicine.”

WOMEN'S PAIN IS DIFFERENT FROM MEN'S—THE DRUGS COULD BE TOO 

MEN AND WOMEN can’t feel each other’s pain. Literally. We have different biological pathways for chronic pain, which means pain-relieving drugs that work for one sex might fail in the other half of the population.

So why don’t we have pain medicines designed just for men or women? The reason is simple: Because no one has looked for them. Drug development begins with studies on rats and mice, and until three years ago, almost all that research used only male animals. As a result, women in particular may be left with unnecessary pain—but men might be too.

Now a study in the journal Brain reveals differences in the sensory nerves that enter the spinal cords of men and women with neuropathic pain, which is persistent shooting or burning pain. The first such study in humans, it provides the most compelling evidence yet that we need different drugs for men and women.  There’s a huge amount of suffering that’s happening that we could solve," says Ted Price, professor of neuroscience at the University of Texas, Dallas, and an author of the Brainarticle. “As a field, it would be awesome to start having some success stories.”

Modern-day pain control is notoriously dismal. Our go-to medicines—opioids and anti-inflammatories—are just new versions of opium and willow bark, substances we’ve used for thousands of years. Although they are remarkably effective in relieving the sudden pain of a broken bone or pulled tooth, they don’t work as well for people with persistent pain that lasts three months or longer. The failure to include sex differences in the search for better pain relief stems in part from flawed but deep-seated beliefs. “[Medical researchers] made the assumption that men and women were absolutely identical in every respect, except their reproductive biology,” says Marianne Legato, a cardiologist who began sounding an alarm in the 1980s about differences in heart attack symptoms among women. She went on to pioneer a new field of gender-specific medicine.

The physiology of pain is just one of many ways that men and women differ, she says. But she isn’t surprised that no sex-specific medicines have emerged. The medical community—including pharmaceutical companies—didn’t appreciate the variation between men and women, including in their metabolisms, immune systems, and gene expression. "If there were differences in how their drugs worked between men and women, they didn’t want to hear about it," she says. New studies must have separate cohorts for pain studies, rather than aggregating it into one data set. 

What is the legacy of gender-blind research? Mogil once emailed a researcher, asking whether a pain drug worked better in men than women. The researcher didn’t know, and couldn’t pursue the question because the data was controlled by the pharmaceutical company. Mogil was left wondering if drugs that looked promising in male-only animal studies might have failed in clinical trials when the results were blended with those in women, depriving men of a viable treatment.

Medicines that could work best for women wouldn’t make it into the pipeline at all when basic science excluded female animals. Price wonders if unresolved pain among women might have led to their higher levels of chronic pain.  

 Amid the promise of "personalized" medicine, with drugs tailored to patients based on genetic sequencing, developing pain medicines for half the population seems like a no-brainer. "Now there’s a whole new frontier opening up in front of our eyes," Price says. 

Pain physiology is poorly understood. We have difficulty  ranking pain from individual to individual,  let alone along gender classification. The proportionality of pain due to purely neuron transmission to the brain (somatic) vs the second brain (gut) and the role of humoral intermediaries. And lastly the patient's perception of pain is not well measured objectively. Indirectly it can be estimated by changes in vital signs (pulse, blood pressure, respiration, pupillary responses, or involuntary somatic muscle responses.

Basic neurophysiological mechanisms of pain and pain control

Women's Pain Is Different From Men's—the Drugs Could Be Too | WIRED: A new study shows clear differences in the biology of how men and women feel pain, a reminder that sex-specific pain medications might benefit us all.

Dr. Weinstein. A surgeon's struggle with mental health.

Doctors are the healers and the helpers. But what happens when it’s the doctors 
who need the healing and the help?

An estimated 300 to 400 doctors die by suicide each year, a rate of 28 to 40 
per 100,000; more than double that of general population (according to a review 
of 10 years of literature on the subject presented at the American Psychiatry 
Association annual meeting in May 2018).

Doctors who die by suicide often have untreated or undertreated depression or 
other mental illnesses, a fact that underscores the need for early diagnosis 
and treatment.

However, the stigma of a mental illness may be too overwhelming for some 
in the medical community to deal with, and they often mask their pain, rather 
than seek help.  That’s why Dr. Michael Weinstein, a surgeon at Thomas 
Jefferson University Hospital, is so very brave.

When his piece was published, Dr. Weinstein couldn’t anticipate the 

response, but said he received an overwhelming number of affirming

 messages from people from all different walks of life. However, 

perhaps most importantly inthis case, he heard from many colleagues in the 

medical field from across the countryand across the world who saw themselves 

in Dr. Weinstein’s story, and no longer felt alone in their own journeys.

“I realize that, from the outside looking in at me, I’m in potentially a position 

of power, of 

influence.  I’m in a world that could be stereotyped as a world that should be strong 

and courageous and infallible,” he said. “Telling a story from that perspective might

both be able to help folks in similar situations.”

Today, Dr. Weinstein is on a new path of healing. He has embraced Buddhist

 philosophy, and has found the practice of mindfulness meditation to be an 

important part of his recovery. 

Listen to him read excerpts from his inspiring essay “Out of the Straight Jacket” 

and listen to his reflections on his journey to date in this very moving 

OC87 Recovery Diaries video. 

EDITOR IN CHIEF: Gabriel Nathan | EDITOR: Glenn Holsten | 

DESIGN: Leah Alexandra Goldstein | PUBLISHER: Bud Clayman

 

AHRQ launches app to help patients preplan questions for doctors | MobiHealthNews

AHRQ launches app to help patients preplan questions for doctors | MobiHealthNews: The new app, called Question Builder, lets consumers input their health information and then brings up potential questions for them to ask their doctors.

7 Enabling Capabilities To Improve Poor Results From Massive AI

 A survey of over 1,200 executives has just revealed that despite massive and increasing investments in digital transformation and technologies such as artificial intelligence and big data, companies are struggling to turn those investments into real business results.

A survey unveiled today by Deloitte has found that the number of companies investing heavily in digital transformation has almost doubled in the past year.

The accounting and services giant questioned 1,200 executives at organizations of at least 500 people with above $250 million in revenue, finding that 19% planned to invest $20 million or more during 2019. When asked the same question at the start of 2018, 10% gave that answer.

Despite Massive Investments In AI And Digital Transformation, Survey Finds Poor Results And 7 Enabling Capabilities

The term “digital transformation” has come to mean steps that move an organization towards adopting data-driven business models, typically involving artificial intelligence (AI), big data and predictive analytics technology.

The survey also found that budgets dedicated to this transformation at medium to large-sized companies increased from an average of $11 million to $13.5 million this year.

However, it also highlighted the finding that most organizations still report a gap between their investment in this technology and the impact it is having on key performance indicators such as profits, revenues and customer satisfaction.

In an effort to understand this, it identifies 7 “pivots” - capabilities that, when developed, contribute towards a business successfully bringing about positive growth through a technology initiative.

It found that "higher maturity" organizations – those who had progressed their digital transformation to the point where they are driving positive growth - deploy an average of 40 initiatives targeting these pivots capabilities, suggesting they are indeed a contributing factor.

Data mastery is about aggregating, activating and monetizing data that is still often siloed and underutilized in order to generate better products, services and business operations that will drive business success.

“Those are the enabling pivots that allow us to begin thinking about transformation.”

Data mastery involves generating value from data to increase the efficiency and effectiveness of business processes.

“I would say that 90% of the corporate world is not going to capture value through naked monetization of their data assets the way Google or Amazon does. For the most part, they will capture data to increase the efficiency and effectiveness of their company.”

That could mean finding better ways of targeting customers and understanding their behavior and optimizing marketing and retail channels based on the data they collect. In other words, the majority of companies approaching levels of digital maturity where their data becomes a valuable asset is doing so by creating growth for existing, core products and services, rather than creating new ones from their "data exhaust."

The next key pivot – talent – revolves around the way data is used to understand and nurture a business’s most vital asset – it’s employees.

“This is actually the hardest thing to do,” explains Gurumurthy. “One can figure out cloud migration strategies, one can figure out how to collect and store data, and how to run analytics on it, but its harder to manage change around talent.

“If you ask people what their biggest challenges are in digital transformation they will say it is the talent deficit – there's often resistance to cultural change and a deficiency in the kind of talent that's needed.”

This is challenging because of the different mindset which becomes necessary when transitioning to data-driven business models, particularly when human staff are being asked to put their faith in technology like artificial intelligence and advanced analytics which may result in insights and observations which seem counter-intuitive to many of us.

"It's often about retraining the talent – another phrase we use is the ‘digital mindset,'" explains Gurumurthy.

So, what is holding businesses back from unlocking the full potential of digital transformation? Well, aside from the talent deficiency already mentioned (cited by 36% as a barrier), challenges posed by existing, legacy operating models, and a lack of a strategy for clearly prioritizing adoption of transformative technology were cited by 49% and 45% of respondents, respectively.

This makes it clear that whatever industry you’re in, the rewards of driving growth through digital transformation are there for the taking.

Suggested Reading,  

Artificial Intelligence in Practice: How 50 Successful Companies Used Artificial Intelligence to Solve Problems 1st Edition

by Bernard Marr  (Author)

7 Enabling Capabilities To Improve Poor Results From Massive AI:

VA Secretary Robert Wilkie announces precision medicine testing initiative with Sanford Health | FierceHealthcare

PRECISION MEDICINE FOR THE VA

Veterans will access the test at their local VA facility, and Sanford Health will process the tests at its South Dakota-based Imagenetics facility—which is overseen by former VA Secretary David Shulkin. (

Up to 250,000 veterans could receive access to no-cost pharmacogenomic testing by 2022 under a new partnership with Sanford Health. The announcement comes just months after the former secretary of the U.S. Department of Veterans Affairs took on the role of chief innovation officer at the Sioux Falls, South Dakota-based health system.



The program will launch at a pilot site in Durham, North Carolina, and will initially enroll cancer survivors, officials said. It will expand to up to 250,000 U.S. veterans at 125 sites by 2022.

PHASeR, or the Pharmacogenomics Action for Cancer Survivorship, is funded by a $25 million gift from philanthropist Denny Sanford and matching fundraising from Sanford Health.

Veterans will access the test at their local VA facility, and Sanford Health will process the tests at its South Dakota-based Imagenetics facility, officials said.

The test results will help physicians with clinical decision-making for a variety of drugs, including those for mental health, cardiovascular disease and pain management. The National Institutes of Health estimates that inappropriate treatments and adverse drug reactions cost up to $30 billion a year.

What is Precision Medicine ?

VA Secretary Robert Wilkie announces precision medicine testing initiative with Sanford Health | FierceHealthcare: