The Blind Can See - Proto Magazine

Our third and last article (for now) is on advances in vision care.

 

IN 1991 ROBERT GREENBERG was an M.D./Ph.D. student observing his first operation. On the table lay a blind man under local anesthesia. As Greenberg watched, an ophthalmic surgeon guided a tiny electrode into the man’s eye and brought it as close as possible to the surface of his retina.

“An assistant turned on the current, and the patient saw a spot of light,” Greenberg remembers. “Then he put in a second electrode, and the patient saw two spots of light.” The experiment was the first investigation into how a blind person’s retina would respond to electricity inside the eye and whether it might trigger something like sight.

What if you kept adding electrodes, Greenberg wondered. If he could find a way to deliver many precise bursts of electricity to targeted positions on the retina, it might produce a kind of synthetic vision. The idea combined two of his passions: medicine and electronics. That evening he told his girlfriend, “I think I know what I’m going to do with my career.”

Greenberg saw his task—bringing sight to the blind—as a relatively simple engineering problem. He would build a tiny implantable device with many electrodes, each producing a spot of light in the darkness, to restore the whole visual field. “I wanted to build it for my Ph.D. project,” says Greenberg.

Greenberg co-founded a company called Second Sight in 1998 to develop a retinal prosthetic, but it took until 2011 for the company’s Argus II device to be approved for market use in Europe; U.S. clinical approval came two years after that. And the device was not as effective in restoring vision as he had hoped. Activating its electrodes in careful patterns enables patients to see flickering arrangements of light and dark—just enough to make out a crosswalk or to tell whether someone’s face is turned their way.

Those limitations don’t obscure the extraordinary fact that this and other treatments for blindness are rapidly becoming a reality. And while the Argus II is the first artificial vision therapy to make it to the clinic, several other treatments are on their way, says Paul Sieving, director of the National Eye Institute.

“The retinal prosthesis is a tremendous advance that takes patients from nothing to something,” Sieving says. Other approaches to ending blindness use technology in similarly ingenious ways, he notes. In 2013, Sieving launched the NEI’s Audacious Goals Initiative to fund research on restoring vision by regenerating damaged cells in the retina. “We’ve made remarkable progress in understanding the biology of the eye,” Sieving says. “It seems time to harness this biology and do something big.”

Some therapies may eventually be adapted for treating people who are at the beginning stages of vision loss, making them more blindness prevention than cure. But Joan Miller, a retina specialist and chief of ophthalmology at Mass. Eye and Ear and Massachusetts General Hospital, says cures will probably always be needed. “People fall through cracks,” she says, “so the notion of having regenerative or hardware solutions is very appealing.”

sp17_thumb_curing-blindness_3_630x420

Many of the most promising approaches fall into four categories: the retinal prosthetic, gene therapy, stem cell treatments, and a technique that uses optogenetics, a way to engineer nerves to fire in response to bursts of light. Each approach has shown potential in restoring at least partial vision, says Stephen Rose, chief research officer of the Foundation Fighting Blindness. His group funds research on all of them.

No single therapy is likely to restore natural vision in the near future, Rose cautions. Progress is rapid but the problem is complex, and the treatments being developed may not work for everyone. But he wants patients to know that a cure is on the way. “Too many people still get a diagnosis from their doctor and are told there’s nothing that can be done; they’d better learn to use a cane or a guide dog,” Rose says. “Instead, patients should be told that great advances are being made. There is true hope.”

MILLIONS ARE WAITING IN the darkness for that hope. The World Health Organization estimates that 39 million people worldwide are blind from a host of causes, including infectious diseases and uncorrected cataracts. In well-off countries such as the United States, where 1.3 million people are legally blind, the most common causes involve the breakdown of cells in the retina.

The retina is a thin piece of tissue about the size of a postage stamp at the back of the eye; it’s so delicate that it’s often likened to wet, one-ply toilet paper. Light travels through the eyeball to reach the retina, then passes through several transparent layers of cells to strike the rod- and cone-shaped photoreceptor cells. The photoreceptors convert light into an electrical signal that travels along a complex network as a pattern of “firing” cells. It goes to a layer of bipolar cells for processing, and they convey the information to a layer of ganglion cells, which do more processing before sending the refined signal up the long sections (axons) of nerve cells that form the optic nerve, which brings the signal to the brain. There, the pattern of electrical pulses resolves into something recognizable—a landscape, printed words, a face.

Damage to any of these retinal cells can impair vision, and such damage is a major cause of blindness. It’s the root problem in macular degeneration, diabetic retinopathy, glaucoma and a handful of genetic diseases. Second Sight’s retinal prosthesis is currently approved only for patients with inherited retinal disorders (IRD), formerly known as retinitis pigmentosa, a group of genetic diseases characterized by a loss of photoreceptors.

A patient using the Argus II wears sunglasses with a tiny built-in video camera. A small processor that the person carries converts the camera’s stream of video data into simple patterns of light and dark on a grid of 60 pixels. The processor then sends that pattern wirelessly to a chip implanted above the retina, where 60 electrodes stimulate undamaged cells, creating signals that travel up the optic nerve. Two devices being developed by other companies, Retina Implant in Germany and Pixium Vision in France, operate on similar principles.

The Argus II’s 60 electrodes are trying to do the job of the eye’s roughly 125 million photoreceptor cells, so it’s not surprising that they produce extremely crude images. But Second Sight’s engineers are working on new software that will allow the video processors to increase resolution, an update that the more than 200 current users of Argus II will be able to download to their devices.

Second Sight’s other major initiative, dubbed Orion, has many similarities to the Argus II. It also uses sunglasses, a processor and an implant with electrodes to stimulate nerves. But the Orion implant is surgically installed on the brain’s surface, bypassing the retina and the optic nerve, sending data to electrodes pressed against the surface of the visual cortex. That connection may benefit those who have lost vision because of damage in the structures between the eye and the brain—the loss of an eye through trauma, for instance, or damage to the optic nerve. Greenberg expects clinical trials to begin this year.

The Blind Can See - Proto Magazine

Blind Spots - Proto Magazine

This is our second article on advances in vision care

WHEN SHINOBOU ISHIHARA JOINED THE JAPANESE IMPERIAL ARMY IN 1907, it was badly in need of eye specialists. Ishihara’s superiors sent him to study with the country’s first professor of ophthalmology in Tokyo. There, Ishihara had the chance to document Japan’s first case of a patient who was completely color blind. 

Blind Spots - Proto Magazine

Hope in Sight - Proto Magazine

Today begins a series on advances in vision care.  

H

HOW MANY ELECTRODES CAN FIT ON THE BACK OF AN EYE? For the scientists who have spent the past 20 years competing to create a sight-restoring artificial retina, the question is hardly metaphysical. Taking inspiration from the cochlear implant, a device that stimulates the auditory nerve to produce sound the deaf can make sense of, the inventors of visual prostheses think they can prompt healthy cells in the retina to send visual information to the brain. One design uses a tiny camera mounted in eyeglasses to capture images, which are then sent to a video processor worn at the waist that converts them to light and dark pixels—like those that create images on electronic scoreboards. The signals are transmitted to electrodes implanted in the retina and thence along the optic nerve to the brain.

The 50 or so people who have received artificial retinal implants say they can now differentiate walls from windows, detect whether a computer monitor is on, point to the location of a person standing silently in a room and sort dark socks from white ones. Such achievements would represent a major advance in accomplishing what long has seemed beyond hope: restoring sight to the sightless. But some of these cases involve people who had some vision before the implant, making it difficult to know if the devices improved their vision, says neurologist and ophthalmologist Joseph Rizzo, director of neuro-ophthalmology at the Massachusetts Eye and Ear Infirmary and director of the Center for Innovative Visual Rehabilitation at the VA Boston Health Care System.

“It is utterly clear that people who have been blind for decades can see something when you stimulate the retina,” says Rizzo, who in the late 1980s was the first scientist to receive funding for work on an artificial retina. “But there is no evidence that the vision we’re able to create at this point provides enough detail to really make a difference in someone’s life.”

And so, more electrodes. The first generation of artificial retinas, created in the past decade, had as few as 16, while the most advanced current devices have 64. Each electrical contact stimulates cells in the eye—so additional electrodes mean more stimulation and, perhaps, better vision. Typically, the electrodes are embedded in a substrate that is many times thinner than human hair. This tiny electronic component can be tacked to the front of the retina or slid behind it. Now Rizzo and others are developing prototypes that pack as many as 200 electrodes onto the device. “With 200, people may be able to find the sidewalk and see cars, so they can safely navigate in an unfamiliar environment without a cane or a guide dog,” says Rizzo, who predicts the device will be ready for clinical trials as early as 2011. “Being able to do those things would be a stunningly large accomplishment.”

But there’s another, more direct approach to treating gene-related diseases: replacing a malfunctioning gene with a healthy one. While most attempts at gene therapy have turned out to be ineffective, there are several reasons injecting genes into the eye could succeed, says Katherine A. High, director of the Center for Cellular and Molecular Therapeutics at Children’s Hospital of Philadelphia.

The primary risk in gene therapy is that the immune system will reject either the donated genetic material or the viral vector—a virus that has had its own DNA replaced by the new gene—used to carry the gene into a cell. The body might also mount an autoimmune response that could threaten healthy cells. But since the eye is an “immunoprivileged” site, secluded from the direct blood supply, a harmful immune response is less likely. “Also, several molecules that inhibit the immune response are found in high prevalence in the eye, and it’s geographically segregated from other tissues,” says Jean Bennett, a researcher at the University of Pennsylvania School of Medicinein Philadelphia. “It’s a self-sustaining organ surrounded by pretty tough barriers.” What’s more, the retina, and particularly the tiny macula, are comparatively small, making it easier to deliver a high concentration of viral vectors relative to the number of cells to be treated—a result much more difficult to achieve when replacing genes in large organs.

The eye has yet one more advantage. Because people are born with a full complement of retinal cells, which don’t divide after birth, the healthy gene can be injected directly into the diseased tissue and expected to stay there, continuing to produce the protein that is lacking because of the faulty host gene.

All those factors convinced High, Bennett and others that the eye might indeed be uniquely suitable for gene therapy, and their work on Leber’s congenital amaurosis 2 has produced remarkable breakthroughs. In LCA2, which affects just 80 people in the United States, photoreceptor cells stop functioning and eventually die. The disease is caused by a defect in a single gene, RPE65, that normally produces a protein responsible for processing vitamin A; the retina’s photoreceptors use it to create the visual pigment rhodopsin, which absorbs light entering the eye. Without the RPE65 protein, there’s profound vision loss at birth and total blindness by age 30 or 40.

With just one gene involved and with a window of several decades during which retinal cells are injured but not defunct, LCA2 seemed an ideal testing ground for gene therapy. Bennett and her husband, Albert Maguire, a retina surgeon at Children’s Hospital of Philadelphia, made it work in animals, restoring sight to nearly 60 briards, a sheepdog with a gene that causes severe retinal degeneration similar to that of LCA2. Yet because the human disease is so rare, biotechnology companies had little interest in supporting a trial. So High convinced Children’s Hospital to produce the vectors and test the safety of the gene-transfer therapy.

Twelve people with LCA2, whose ages ranged from 8 to 44, participated in the trial. Before being treated, they all had trouble navigating a dimly lit obstacle course, and several could read nothing on an eye chart and were dependent on others to lead them everywhere. Afterward their vision was partially restored, and within two months a father who hadn’t been able to see his baby’s face was taking the child on neighborhood walks. Road signs and the numbers on cell phones and digital clocks suddenly came into view. The day vision of most subjects improved significantly, and in all subjects, night vision improved as much as 40,000-fold as their retinas became more sensitive to light.

But the most dramatic improvements occurred in four children, ages 8 to 11, who had less damage to their retinas from the progressive disease than did the adults. An eight-year-old who could read only large print on an electronic screen now needs no special visual devices and plays baseball. Another child, who since birth had been able to see only light and shadow, now plays soccer. And all the children navigated the obstacle course more quickly and with fewer errors than before gene therapy. (Not all of the adults improved their performance on the test course.)

Today, more than two years after the first subjects received the gene therapy, their enhanced sight hasn’t waned, and some have even reported ongoing improvements. Although Bennett isn’t sure how long the treatment will be effective, she is already thinking about how gene therapy might be used to treat “a huge list of single-gene defects that destroy the retina’s photoreceptors.” And the breakthrough sets the stage for inserting genes to slow or prevent other eye diseases. “The gene therapy trial for LCA2 has advanced a big area of potential treatment involving 500 identified genes that cause people to lose vision,” says Sieving of the National Eye Institute.

IT’S NO ACCIDENT THAT GENE THERAPY IN THE LCA2 TRIAL WORKED best with the youngest participants. Their retinal cells hadn’t died off altogether and could be revived by the introduction of healthy genes. But that approach won’t help older people, already blind, whose retinal cells will never grow back. For them the best hope may be self-renewing stem cells, which, at least theoretically, can replicate and differentiate themselves into many types of specialized cells—including those in the eye. “By putting a cocktail of stem cells in the eye that will proliferate in the right quantity and have the right characteristics, we can replace missing retinal cells and make the entire retina work again,” says Sieving. “This technology is poised to explode.”

David Gamm, assistant professor of ophthalmology and visual sciences at the University of Wisconsin–Madison, is a leader in that effort. He’s building on a landmark 2007 discovery by other University of Wisconsin scientists, who inserted four genes into an adult skin cell and programmed it back to an embryolike state capable of differentiating into any of the body’s 220 cell types. Gamm has taken those undifferentiated cells—known as induced pluripotent stem cells, or iPS cells—and used a chemical bath of proteins and growth factors to coax them into becoming retinal cells.

This approach has enabled Gamm to observe the entire process of how undifferentiated cells turn into retinal cells, moving from a primitive form to a fully developed retina. Now researchers can study the genes produced by those cells to understand better what goes awry in degenerative retinal diseases.

But perhaps the most exciting possibility is that iPS cells could replace dead or damaged retinal cells. A clinical trial, scheduled to begin soon in the United Kingdom, will test the viability of using embryonic stem cells to replace degenerated retinal pigment epithelium, which nourishes retinal cells, in people with AMD. The stem cells will be placed on an artificial membrane that will be inserted in the back of the eye. If the results are positive, Gamm hopes to test whether iPS cells—which avoid the ethical issues of harvesting stem cells from human embryos—would also work. He has grown retinal cells from both embryonic and induced stem cells and says they appear identical. “Five years from now, there could be clinical trials to replace cells in people with retinal degenerative diseases such as AMD and retinitis pigmentosa,” says Gamm.

Hope in Sight - Proto Magazine

Study: Telehealth Doesn't Lead to Excessive Healthcare Use | HealthLeaders Media

Contrary to what Medicare and Private health payers said, telehealth does not lead to excessive healthcare use.

A popular criticism of telehealth is that people will be using it more than they should, leading to unnecessary healthcare appointments and expenses. But researchers at the University of Michigan say that's not true in the Medicare market.

An analysis of Medicare data through 2021 finds that while virtual visits have increased considerably as a result of the pandemic, with roughly one-third of traditional Medicare members taking part in at least one telehealth visit last year, those numbers aren't excessive. This means that the Medicare population, comprised primarily of older Americans, is using the platform to replace in-person care, rather than just because they can.

“As telehealth use hits its stride in the Medicare fee-for-service population, the fears that flexible telehealth rules might lead to an increase in the total volume of outpatient visits have not panned out,” Chad Ellimoottil, MD, MS, director of the Telehealth Research Incubator at UM's Institute for Healthcare Policy and Innovation and lead author of the study, said in a press release. “With all the evidence we have to date, it appears that telehealth has been used as a substitute for in-person care rather than an expansion of care.”

The distinction is important, especially as the nation moves away from the pandemic and the healthcare industry looks to adopt a long-term telehealth strategy when the public health emergency ends. Advocates say telehealth should be a standard practice of care, comparable to in-person care, and regulated along the same lines. Opponents argue the platform is ripe for misuse and abuse, and that it should be governed more strictly to prevent waste and abuse.

Ellimootil and his colleagues found that about 9% of all outpatient appointments made by people with traditional Medicare coverage were virtual in the latter half od 2021. That represents a decline in virtual visits compared to the time period between mid-2020 and mid-2021, but a large increase compared to prior to the pandemic in 2019.

The surge in telehealth use during the pandemic was helped by a series of federal and state waivers aimed at increasing access to and coverage of telehealth so that health systems could protect their staff and isolate those infected by the COVID-19 virus from others. Those waivers will end with the end of the PHE, and telehealth supporters want new or revised regulations in place to continue the momentum and allow health systems to continue their programs.

Whether this will occur remains to be seen.  My bet is that it will, because both physicians and patients need it.

Study: Telehealth Doesn't Lead to Excessive Healthcare Use | HealthLeaders Media

Telehealth Diagnoses Match In-Person Clinical Visit Diagnoses in 86.9% of Cases, Study Finds | HealthLeaders Media

The COVID-19 pandemic created a dependency on remote patient visits using telehealth.  Studies from several credible sources reveal how accurate a diagnosis is in a telehealth visit.

 In non-primary care specialties, a diagnostic agreement between telehealth visits and in-person visits ranged from 77.3% for otorhinolaryngology to 96.0% for psychiatry. Diagnostic agreement between telehealth visits and in-person visits was significantly higher for specialty care compared to primary care (88.4% versus 81.3%).

There is a significant level of agreement between telemedicine diagnoses and in-person outpatient visit diagnoses, a recent research article found.

In the early phase of the coronavirus pandemic, telehealth utilization increased exponentially—one published estimate pegged the increase in utilization in April 2020 at 20-fold. A concern associated with this increase in telehealth utilization is the accuracy of telemedicine diagnoses compared to in-person visits.

IMPORTANT TAKEAWAYS 

Among the 313 (13.1% of the total) cases where there was no agreement between the telehealth diagnosis and the in-person visit diagnosis, 166 cases had the potential for morbidity and 36 of those cases had actual morbidity.

 Among the 313 cases where there was not an agreement between the telehealth diagnosis and the in-person visit diagnosis, 30 had the potential for mortality, and 3 of those cases had actual mortality.  

Telehealth diagnoses often should be paired with in-person visit diagnoses, the study's co-authors wrote. "These findings suggest that video telemedicine visits to home may be good adjuncts to in-person care. Primary care video telemedicine programs designed to accommodate new patients or new presenting clinical problems may benefit from a lowered threshold for timely in-person direct follow-up in patients suspected to have diseases typically confirmed by physical examination, neurological testing, or pathology."

There are important caveats about using telehealth for diagnosis.

INTERPRETING THE DATA

Telehealth Diagnoses Match In-Person Clinical Visit Diagnoses in 86.9% of Cases, Study Finds | HealthLeaders Media

Weight-Loss Drug Semaglutide Making People Disgusted by Coffee, Fries

Staci Rice had been a daily coffee drinker since the seventh grade. A marketing professional and mom in Georgia, she likes the taste, the routine, and how it makes her feel: awake. 

But about six months ago, she walked into the kitchen to make a pot — and poured it out. "All of a sudden," she said, "I had no desire for it." 

Rice, 40, had recently gone on the popular weight-loss drug semaglutide, which has since helped her lose nearly 50 pounds. She's now wearing pants she shelved 16 years ago, and seeing results she could never sustain on diets like Weight Watchers and Optavia. 

But Rice still isn't able to stomach her morning coffee. "Every morning, I would try to make coffee, thinking that one day it would just taste good to me again." No such luck. "I miss having energy," she said. 

Rice has lost her taste for other food and drinks she once loved, and acquired a few new ones. Long a fan of Chick-fil-A's "Number 1" — a 440-calorie fried-chicken sandwich served on a white buttered bun — she now describes the chain's kale salad as "delicious." 

Ground beef is off the dinner rotation ("my husband and son are kind of upset," she said), and chocolate's lost its appeal, too. 

When Rice tried a Kit-Kat, which she believes is the superior chocolate bar, for Halloween, she winced. "I can't even describe what kind of flavor it had," she said. "I just didn't want it." 

Rice before, left, and after six months on semaglutide. 

Staci Rice

Others on the drug have reported similar experiences. They anticipated that semaglutide would decrease their appetite, but in some cases, it seems to have hijacked their taste buds, turning french-fry fiends into kale enthusiasts and coffee snobs into smoothie kings. 

And while many people say the trade-off is worth it, the unexpected hit to their identity and social lives can be tough to swallow.

"Food is so much more than just fuel. Culturally, we have rituals around food that bring us joy and fond memories," Rachel Goldman, a New York City psychologist who specializes in weight management, said. "What do you do to fill the void?"  

Semaglutide is making people miss their favorite foods

Semaglutide, sold under the brand names Wegovy and Ozempic, is an injectable drug that boosts the production of insulin, a hormone that helps regulate blood sugar. While semaglutide was originally developed to help manage diabetes, Wegovy was approved as a weight-loss drug in June 2021. 

Some obesity-medicine experts have called the drug a "game changer." Research has found it can lead to a 15% to 20% reduction in body weight over 68 weeks when paired with a reduced-calorie diet and regular exercise. 

Weight-Loss Drug Semaglutide Making People Disgusted by Coffee, Fries

A patient’s ode to healers

MICHELE LUCKENBAUGH 

PATIENT

Pages of my life turn over
As the breezes of time flow over me.
Remembrances of your presence
As the world welcomed my firstborn so many years ago.

Your calming voice and words of wisdom reminded me that life
Would be different, but oh so much better.
My little baby girl would grow to be a healer just as you,
Offering hope and consolation to those who seek her out.

Expert hands stitching the brow of my rambunctious toddler,
Telling me that my son would be fine.
Now he is a man grown tall and strong,
Finding his own pathway in this world.

How time has raced on.
When my heart waged a skirmish against me
You were there standing at my side,
Talking me down from the mountain of fear.

Your words of wisdom and compassionate care
Were a salve for my wounded heart.
The encouragement is given to spur me on,
Telling me the “sky is the limit”

And so it was.

As chapters of my life are being written, you are there to guide me.
Share advice, but always maintain our partnership, the give and take.
In this sacred clearing, we are each co-creators of this story that is my life.
One telling the story, the other patiently listening.

Roles flip back and forth as life moves forward.
You are the cushion to soften the fall when life deals a harsh blow.
Always encouraging, always hopeful.

What will happen when your kind is absent,
Forced out by clutching hands, greed, and impatience
Making you feel unimportant and powerless?

Who will be there for comfort and support,
For the healing, we search for?

The unconcerned do not see the forest for the trees,
Trees forming a  wall blurring the truth.
But the truth must shine forth.

It has to.

Healers, do not lose hope!
To lose hope is to surrender.
To let them win.

Hold your head high, and cluster together.
Let your voices make a resounding clamor, far and wide.
We, who need your healing touch, will be your support
as you have done for us.

This story has not reached its end.
We both have lines to write
And words to be spoken.

Our partnership is worth fighting for.

This is dedicated to all physicians, to all healers, who have played a significant role in helping us move safely past the roadblocks in our lives. Most recently, our physicians and nurses have served tirelessly on the front lines combatting the coronavirus, a pandemic that has brought a huge loss of life to all parts of the world. Often, they have done this without adequate facilities, protective gear, and supplies at their disposal. To them, we owe our deepest gratitude. They have potentially sacrificed their own lives to attend to the sick and dying during this terrible time.

In the times we live in, the role of the physician has been severely impacted from all sides. The corporatization of medicine and all that it entails has led to the weakening of the once-valued doctor-patient relationship. Visits to our physicians have become little more than business transactions between “providers” and “consumers.” Clicks on a keyboard replace face-to-face discourse.

Doctors are disheartened, overworked, and feeling powerless. Their voices have been silenced for fear of retribution. Many are leaving the profession they have worked so hard to obtain and have sacrificed so much for. We ask that their story be told so that the truth of just how dire the situation is becomes known. We deserve and need to have the complete story.

Our brightest are seeking other careers outside the field of medicine. Residencies are being underfunded by Medicare thereby further diminishing the supply of fully qualified doctors. So the shortage of physicians continues to increase with no real solutions in sight. The time will come when we all will have to be content in seeing a “substitute dressed in a white coat”. Someone without the knowledge or experience that you, our physicians, possess. America, this is our wake-up call. Hopefully, our recent experience with COVID-19 has taught us valuable lessons. We are, indeed, all in this together. Now is the time to write a different “ending” to this story, before it is too late.

It looked like his HEAD EXPLODED! 😱

The Cure for the Morning Headache

Clinical Whole Genome Sequencing - by Eric Topol

I remember a day when genetic testing was very expensive and only used for rare diseases.

Times and our ability have changed diagnosis and treatment for many diseases previously thought to not be worth genetic analysis.

So much attention has been placed on the cost of whole genome sequencing (WGS) over the years, from about $300 million for the first one in 2000 (some estimates are as high as $3 billion), to now starting to approach $100. That’s a long-sought and remarkable reduction in cost.  

But what is equally impressive is that a team at the University of Washington, led by Danny Miller, set a world record in September 2022, reducing the time from the sample (at the birth of a baby) to interpretation to 3 hours! That diagnosis (of lacking the pathogenic gene variant of concern) in a newborn was facilitated by knowledge of familial risk. Nevertheless, that acceleration of sequencing and analysis comes in the wake of the Stanford team, led by Euan Ashley, performing WGS in 12 people ranging from 3 months to 57 years, in a critical care setting, in as little as 7 hours and 18 minutes.

This acceleration of gene technology almost allows genetic testing to be available at the bedside for a cost approaching a complete blood count.

At times the advances are announced first in lay publications such as the NY Times.

Time course from presentation to diagnosis

At Scripps Research, our SRTI team works closely with Rady Children’s Institute for Genomic Medicine, the group that has pioneered WGS in sick newborns who do not have a diagnosis, accomplishing this from sample to interpretation and management recommendations all within 13 hours, using multiple AI tools (labeled 1-3 below) to expedite the readout and care of the baby.

An automated 13.5 hour system for scalable diagnosis and acute management guidance for genetic diseases

The reduction in cost and time for whole genome sequencing is historic and one of the most important advances that has occurred in life science in recent years. With the increasing use of AI tools to make the variant calling and interpretation more accurate and rapid, along with contextualizing the medical literature for a molecular diagnosis and possible treatment, this could become someday an exemplar, beyond the prediction of protein folding from the amino acid sequence (AlphaFold), for AI’s contribution to biomedicine. Hopefully, someday we will harness its value to advance individualized medicine.

Clinical Whole Genome Sequencing - by Eric Topol

Why Some People Might Never Get COVID

8 prior authorization terms that drive every doctor crazy | American Medical Association

Prior authorization

This is a health plan cost-control process that restricts patient access to treatments, drugs, and services. This process requires physicians to obtain health plan approval before delivery of the prescribed treatment, test, or medical service in order to qualify for payment.

According to an AMA survey (PDF) of 1,004 practicing physicians, more than nine in 10 respondents said prior authorization had a significant or somewhat negative clinical impact, with 34% reporting that PA had led to a serious adverse event such as a death, hospitalization, disability or permanent bodily damage, or other life-threatening events for a patient in their care. 

The vast majority of physicians (88%) described the administrative burden associated with PA as “high or extremely high,” and physician practices complete an average of 41 prior authorizations per physician per week. 

Utilization management

Prior authorization is just one subset of the larger field of insurer practices called utilization management (UM), which the Institute of Medicine—now known as the National Academy of Medicine—defined way back in 1989 as “a set of techniques used by or on behalf of purchasers of health care benefits to manage health care costs by influencing patient care decision-making through case-by-case assessments of the appropriateness of care prior to its provision.” That has a familiar ring to it.

The AMA is fighting for the passage of a bill that would require Medicare Advantage plans to implement prior-authorization reforms, easing the burden on physicians and their practice staff.

Step therapy

Another utilization-management technique that can drive doctors crazy is step therapy, sometimes called the fail-first requirement. Under such a policy, payers will require that patients first try and fail lower-cost tests, drugs or other treatments before moving on to higher-cost options, sometimes in cases when the patient has already unsuccessfully tried the therapy under a previous insurance plan.

Find out what doctors wish patients knew about prior authorization.

Medical necessity

Everyone agrees that patients should not get a drug, test or surgery unless it is medically needed. The reason why this common utilization-management term drives doctors crazy is that it seems as though each payer has its own definition of medical necessity, which makes navigating the process highly frustrating for physicians who just want their patients to get the care they deserve.

The AMA believes that what constitutes medically appropriate treatment should be based on clinical guidelines developed by the appropriate national medical specialty society and be consistent regardless of a patient’s insurer. There should be a standard medical necessity definition so that all insurers in a state are playing by the same rules and everyone understands what those rules are.

Learn more about what the AMA’s research has uncovered about prior authorization and share your story to help guide advocacy efforts to fix prior auth.

Peer-to-peer review

This is a process in which an ordering physician discusses the need for a procedure or drug with another physician who works for the payer in order to obtain a prior-authorization approval or appeal a previously denied PA. If properly implemented, the process can be helpful, as it affords the physician the opportunity to speak with another clinician. What drives doctors crazy is that it usually comes after days or even weeks of bureaucratic wrangling, and the health plan's “peer” often is from a completely different specialty and knows nothing about the disease or treatment in question.

The AMA says peer-to-peer review should be available at any point following an adverse PA determination, and that the peer to whom the physician speaks should be a genuine peer—a doctor practicing the same specialty and subspecialty as the ordering physician.

Learn about a gastroenterologist so sick of the runaround from payers that he has taken his prior auth pains to Twitter.

Related Coverage

House voice vote sets U.S. on the path to fix prior authorization

Standard pharmacy electronic prior authorization

Also called ePA, this capability automates prior authorization by integrating it into the physician’s electronic prescribing workflow and can make the PA process faster, consistent across insurers, and more efficient. Unfortunately, physicians interested in using this technology are often stymied, as ePA is far from the norm.

Too often, physician practices and health care organizations are stuck navigating telephone trees, waiting on hold, or feeding forms into their fax machines. Even when health plans offer electronic prior-authorization options, they often involve proprietary portals that require workflow disruption to exit the EHR, log into the insurer’s unique website, and time-consuming reentry of the patient and clinical data—not the streamlined standard ePA process embedded within the EHR. Astoundingly, the Cleveland Clinic has racked up a $10 million annual tally just to push their PA requests through the process.

Learn more about how ePA technology that integrates with practices' current electronic prescribing workflows can improve the drug prior authorization process, just one of the AMA’s PA practice resources.

Gold carding

This is a process under which a payer exempts physicians who consistently order or prescribe treatments and drugs in accordance with evidence-based guidelines, or have high approval rates from PA requirements. So if you’re not an outlier physician—if your prior-authorization requests are approved like clockwork—at, let’s say, a 90% rate—then payers should be happy to grant you that proverbial gold card, allowing you to get your patients quick access to the care towards which they have been paying their premiums.

While Texas has enacted prior-authorization “gold card” legislation and a bill in Congress would advance the idea in Medicare Advantage, such programs are not prevalent in health care today, and it drives doctors crazy that such a commonsense concept—one that would reduce PA burdens for both practices and insurers—hasn’t yet taken hold.  

The essential idea was outlined in a set of principles put forth (PDF) by the AMA and 16 other physician, patient and health care organizations: “Health plans should restrict utilization management programs to ‘outlier’ providers whose prescribing or ordering patterns differ significantly from their peers after adjusting for patient mix and other relevant factors.”

Moreover, a consensus statement (PDF) released by the AMA and national associations representing both providers and insurers encourages just these sorts of programs to lower the overall volume of PAs by selectively applying these requirements.

In 2018, payers agreed to rein in prior auth. Learn why the clock is still ticking.

The not-so-hidden cost of prior authorizations from the Cleveland Clinic

8 prior authorization terms that drive every doctor crazy | American Medical Association