Thursday, March 31, 2016

ACTH is more effective than other standard therapies for infantile spasms

Knupp KG, Coryell J, Nickels KC, Ryan N, Leister E, Loddenkemper T, Grinspan
Z, Hartman AL, Kossoff EH, Gaillard WD, Mytinger JR, Joshi S, Shellhaas RA,
Sullivan J, Dlugos D, Hamikawa L, Berg AT, Millichap J, Nordli DR Jr, Wirrell E;
Pediatric Epilepsy Research Consortium. Response to treatment in a prospective
national infantile spasms cohort. Ann Neurol. 2016 Mar;79(3):475-84.

Infantile spasms are seizures associated with a severe epileptic encephalopathy presenting in the first 2 years of life, and optimal treatment continues to be debated. This study evaluates early and sustained response to initial treatments and addresses both clinical remission and electrographic resolution of hypsarrhythmia. Secondarily, it assesses whether response to treatment differs by etiology or developmental status.
The National Infantile Spasms Consortium established a multicenter, prospective database enrolling infants with new diagnosis of infantile spasms. Children were considered responders if there was clinical remission and resolution of hypsarrhythmia that was sustained at 3 months after first treatment initiation. Standard treatments of adrenocorticotropic hormone (ACTH), oral corticosteroids, and vigabatrin were considered individually, and all other nonstandard therapies were analyzed collectively. Developmental status and etiology were assessed. We compared response rates by treatment group using chi-square tests and multivariate logistic regression models.
Two hundred thirty infants were enrolled from 22 centers. Overall, 46% of children receiving standard therapy responded, compared to only 9% who responded to nonstandard therapy (p < 0.001). Fifty-five percent of infants receiving ACTH as initial treatment responded, compared to 39% for oral corticosteroids, 36% for vigabatrin, and 9% for other (p < 0.001). Neither etiology nor development significantly modified the response pattern by treatment group.
Response rate varies by treatment choice. Standard therapies should be considered as initial treatment for infantile spasms, including those with impaired development or known structural or genetic/metabolic etiology. ACTH appeared to be more effective than other standard therapies.

 It's a happy day at Questcor!
Courtesy of a colleague.

Have pain? Are you crazy?

Since writing about Justina and Rose, I’ve spoken with “Sick Chick,” a teen with chronic pain that was also misdiagnosed for some time. At age 11, Chick developed severe, incapacitating knee pain abruptly, without a prior injury, which is a common precipitant. Then she developed patchy loss of sensation. Her foot turned blue and cold. She saw multiple doctors trying to find out what was wrong, including a pediatrician who said “it didn’t make sense so it must be in her head.” When asked how she could make her feet different temperatures and colors, he replied “There are Swamis in India who can do that.” After being diagnosed by multiple doctors with Complex Regional Pain Syndrome (CRPS), she saw a neurologist, who immediately said she didn’t have CRPS and, in only a 30 minute appointment, diagnosed her with a conversion disorder (where symptoms are thought to have a psychological, rather than physical or medical cause). Chick says, “It made me very scared that it could be” this, “but I knew this was real and I wasn’t imagining the pain…Now I’m really angry [about that].”

Since then, Chick has traveled cross-country for care. She went to one inpatient rehabilitation unit where she says the therapist initially took her crutches, threw them across the room, and told her to go get them. Surprisingly, she seems less angry with them than I might have expected, as the intensive physical therapy did result in her regaining her ability to walk. The following year, the RSD spread to her other knee, and she was hospitalized again at a different rehab center. By this point, she had also developed symptoms of postural orthostatic dizziness and tachycardia (POTS, or Postural Orthostatic Tachycardia Syndrome) and dysautonomia (a malfunction of the autonomic nervous system that can cause unstable pulse and blood pressure, leading to fainting spells and GI symptoms, among other). ). These symptoms were explained away as anxiety and the possibility of conversion disorder was again raised, rather than their looking for a medical explanation…

Instead, Chick finally kissed the right frog, and found her prince—a caring, observant physician, who made the correct diagnoses, finding that she has Ehlers-Danlos syndrome (EDS), historically viewed as a connective tissue disease causing extremely hypermobile joints, but now known to be far more complex. She is now getting appropriate therapy for her CRPS, EDS, and other associated syndromes…

Hearing these and other similar stories, I studied these syndromes further. I first turned, as I frequently do, to UpToDate, an on-line subscription resource. The chapter on pediatric CRPS is written by Dr. David Sherry, a professor of pediatrics at University of Pennsylvania. Dr. Sherry has recategorized Complex regional pain syndrome (CRPS) as an “amplified musculoskeletal pain syndrome (AMPS).” He states that CRPS “is characterized by extreme pain in a limb out of proportion to the history and physical findings⁠, accompanied by one or more signs of autonomic dysfunction.” He adds that conversion symptoms are “not uncommon.” Yet CRPS is characterized by severe pain, induced by normally non-noxious stimuli (allodynia), edema, cyanosis (bluish purple discoloration typically seen with poor circulation), and excessive sweating. Skin and nail changes are common. In adults, CRPS frequently follows injuries such as fractures (1-2%), especially in women; precipitating injuries are less common in kids. CRPS is one of the few pain conditions that can be diagnosed with objective signs (temperature asymmetry, color asymmetry, abnormal hair and nail changes).

Sherry recommends intensive physical therapy for hours daily without offering these children any pain relief. “The treatment starts at the first visit with confirming the diagnosis, discontinuing further medical evaluations⁠, stopping medications for pain (these 2 steps are sometimes much harder on the doctor than the child)…It is important that the team is confident in its ability to cure these children, tolerate the child's pain, be genuinely interested in these children, and understand each other's roles and positions because both the child and parents are prone to try to split the team by playing one member off another.” When asked about not providing pain meds, Sherry responded, "There is no good data that medications work. The most recent Cochrane analysis do not support the use of medications...Most children do not do well with medications, have a lot of side effects and they are expensive."…

Sherry lists conversion symptoms his clinic commonly sees⁠, including in them involuntary muscle spasms and “Fainting and lightheadedness, often called postural orthostatic tachycardia syndrome (POTS) or dysautonomia.” He says “Up to 40 percent of children with AMPS will have at least one conversion symptom.”   Sherry adds, “The vast majority of these symptoms need to be ignored since calling attention to them tends to make them worse.” Of note, POTS and dysautonomia are well recognized medical conditions that can be objectively tested (e.g., Tilt Table Test, orthostatic vital signs). These conditions are often treated by cardiologists and neurologists.

Not all physicians believe in the psychiatric explanation for CRPS or pediatric pain commonly being due to conversion disorder. There is a non-profit organization I have become familiar with called The Coalition Against Pediatric Pain (TCAAP). They have a number of videos on their site (and YouTube) from an interdisciplinary conference last year focusing on Ehlers-Danlos syndrome. While this used to be viewed primarily as a problem of loose joints, EDS now has many overlaps with CRPS, as well as associated with neuropathies, POTS, and migraine. Dr. Pradeep Chopra, a Harvard trained pain specialist and Assistant Professor at Brown University's Medical School, and head of TCAPP’s medical advisory board, told me that there is a “huge component” of autoimmune diseases and that the “joint problem is the least of the issues” in EDS. Many of the children he sees with Ehlers-Danlos present with CRPS. Most notably, he observed, “I’ve never seen a child with conversion disorder.”

Similarly, Dr. Richard Barnum, a child and adolescent forensic psychiatrist formerly with U. Mass and Harvard Medical Schools, spoke at the TCAAP Think Tank. He, too, believes that conversion disorder, if it does exist, is very uncommon. He noted there that patients experience a “diagnosis” of conversion disorder as an accusation of dishonesty, and that it leaves the real problem untreated. Further, such labeling doesn’t ever lead to effective treatment and is very destructive, driving kids away from seeking further medical or psychiatric care.

I am troubled by other aspects of Dr. Sherry’s “boot camp” approach to treating children, particularly in not allowing children to receive any pain meds despite hours of intensive physical therapy. As a parent and occasional patient, myself, I find such an approach unconscionable…

As a physician, I understand the frustration of dealing with patients with chronic, unexplained symptoms. They are often angry and unpleasant, not without some justification. I know we don’t have answers for many symptoms. I have no problem admitting my lack of knowledge to patients, looking things up, or referring them elsewhere. Sometimes you know that a diagnosis will likely become clearer over time, like multiple sclerosis or many autoimmune illnesses, and you can explain that. Other times, making a diagnosis is very much like the story of the Elephant and the Blind Men. You see things or look for things with which you are the most familiar or feel are most probable. We have a limited fund of knowledge, and often too little time or opportunity to discuss difficult-to-diagnose symptoms with our colleagues. Often, we have no one to consult with.

And as a person who herself gets weird illnesses and the parent of a child who does the same, I share the frustrations my patients. Sometimes you have to persist in seeking other opinions—a search that is expensive and exhausting, financially and emotionally. It is discouraging. But, as I remind myself and my patients, some times you have to kiss a lot of frogs until you find the prince. Just like Sick Chick did.

Sam Berns a"h

Sam Berns was scheduled to serve as an honorary captain at Saturday night’s New England Patriots playoff game. Instead, the team planned to hold a moment of silence before the game in his honor. 

The Foxborough high school student, whose battle with progeria inspired a monumental effort to treat the rare and little-understood “accelerated aging” disease, died at home Friday night from complications of the disorder, his parents by his side, according to a family friend. He was 17. 

When Berns was diagnosed with progeria as a toddler, doctors told his family he might not live past 13. His parents, Leslie Gordon and Scott Berns, both doctors, worked to further understanding of the disease. Gordon began a research campaign that brought children with progeria to Boston from all over the world. 

In 2003, she and her team isolated the gene that causes the condition, and they have since identified drug treatment that has helped prolong lives of children such as her son. 

Their work on behalf of progeria patients is the subject of the feature film “Life According to Sam,” which was recently shortlisted for a nomination in the Academy Awards’ documentary category. The exposure has brought widespread recognition and a fund-raising windfall to the Progeria Research Foundation, a nonprofit based in Peabody, established and directed by Sam’s aunt, Audrey Gordon. 

Patriots owner Robert Kraft, after being introduced to Sam Berns and attending the HBO premiere of the documentary in New York in October, made a $500,000 matching pledge to the foundation. Sam Berns, an avid sports fan who played the snare drum in the Foxborough High School marching band, was invited to a Patriots practice that month, where he gave the players an impromptu motivational speech. 

At the practice, Berns was asked to name his favorite player. He did not have one, he replied — it takes a team to succeed.  

“I loved Sam Berns and am richer for having known him,” said Kraft in a statement Saturday. The film, he said, “was so beautifully done. It made you laugh. It also made you cry. Today, it’s the latter for all who knew Sam or learned of his story through that documentary.”  

Berns’s willingness to become the public face of progeria,  which causes musculoskeletal degeneration, cardiovascular problems, and other symptoms consistent with human aging, brought him a kind of celebrity status that his family worked hard to defuse. As much as possible, they wanted him to live the life of an average high school student. He loved comic books and the show “Game of Thrones,” and he recently became an Eagle Scout. 

Yet he also became friendly with the members of his favorite band, the Dave Matthews Band, and was a frequent VIP guest of the Boston Bruins.

Last month, the TED conference posted the talk Berns recently delivered called “My Philosophy for a Happy Life,” which earned the young man many more admirers through social media. 

“Even though there are many obstacles in my life,” he told his audience in Washington D.C., “I don’t want people to feel bad for me. I don’t think about these obstacles all the time, and I’m able to overcome most of them anyway.” 

The Progeria Research Foundation was initially established to find a cure for Berns, said Kim Paratore, a board member and a longtime family friend. “But it became this drive for all of them, this resolve to help all of the children. 

“Sam put himself in uncomfortable situations sometimes and took huge risks socially — this was a teenager, after all — to help other kids. It was such a selfless act for all of them.” “Even though there are many obstacles in my life,” he told his audience in Washington D.C., “I don’t want people to feel bad for me. I don’t think about these obstacles all the time, and I’m able to overcome most of them anyway.” 

He agreed to become the subject of the documentary after meeting with the award-winning codirectors, Sean Fine and Andrea Nix Fine, at a local Chili’s. 

“There had been some previous media happenings in my life, but I’d been generally out of the spotlight for a while,” he told the Globe in December. “I wanted to know more about what this process was going to be like. I was definitely hesitant at first, but these circumstances were the best I thought we could have to make an amazing film that could reach out to everyone out there and help other kids with progeria.” 

Though the family knew that Berns’s life expectancy was not long, they held out hope that each day would be the one that would lead to a cure. 

“I don’t think they were prepared for this,” said Paratore. “They were preparing for him to apply to college.”

Wednesday, March 30, 2016


Justina’s case caught my attention because I have helped care for a young patient with mitochondrial disease, who I will call “Rose,” since she is such a lovely person. I am sharing some of “Rose’s” story with her permission.

Rose has had a variety of vague symptoms “as long as she can remember,” including heat intolerance and dizziness. By the time she became a teen, she experience severe orthostatic hypotension (POTS) and fainting (syncopal) episodes. She then developed stroke-like episodes, with prolonged weakness and difficult recoveries, and severe migraines. Yet the diagnosis of POTS wasn’t made until she was 18, and mitochondrial disease was not the leading diagnostic consideration until she was 19. In the meantime she, like Justina, was “accused” of having a psychiatric rather than physical problem.

A surgeon, consulted to place a feeding tube, decided in that single visit that she had bulimia. For Rose, this isn't surprising; doctors diagnosing her after a single visit, or even sight unseen, happens all the time. (In her own case, Rose had been given several incorrect diagnoses of psychiatric disorders before doctors correctly diagnosed her with a mitochondrial disease—after a delay of many months). Rose goes on to note that not only is a delay in treatment harmful, "but it causes mental anguish, worry, and distrust. Every other mito, POTS, or chronic illness person I meet has had this happen. Every single one. And they all have some level of fear meeting a new doctor, opening up about their symptoms, and constantly worry it is going to happen again.

Complications worsened, with inability to swallow and with bowel dysmotility, requiring multiple surgeries and, ultimately, years of intravenous feeding (hyperalimentation). Through this, Rose has remained as active as possible, enjoying family, friends, and school.

Rose states, “Insurance is a constant battle. We've payed thousands out of pocket each year in past years. I've been denied medications that could improve my motility and aid me in staying off of TPN, which in turn would help prevent [my life-threatening] central line infections/sepsis. It has gratefully improved but only by stressful and constant fighting...”

“I've been refused inpatient physical and occupational therapy multiple times, including kicked out of the program twice. Once I was unable to walk on my own, making it a very dangerous situation in my multilevel home that was not set up for me. I didn't even have a proper wheelchair, and had to drag my feet and was constantly running them over. …I was also denied further studies for mito diagnostics.” This was because a diagnosis would not likely change the progressive decline in her condition.

Frankly, in caring for Rose, I have at times wondered if her insurance carrier hoped to hasten her death in order to save money.

Rose has had to travel far from home for her care, but now has a team she trusts. “Things since have been very good. All my doctors are wonderful, caring, understanding, and fight for me every day. My disease has progressed to the point of total TPN dependence, chronic respiratory failure, and general progression of other organ systems either becoming involved or worsening. However, I'm very much at peace and so grateful for my life.”

Last year, after well over a decade of progressive illness, Rose was finally able to have genetic testing done, and wrote “Validation: a diagnosis,”[see below in comment] expressing her relief at finally having a diagnosis for her horrible disease. She is hopeful that one day, the gene will have a treatment and a cure, though she knows she will not live to see that.

NBC should be ashamed. Last week, in a post about two remarkable young women with rare genetic diseases, I mentioned my outrage at NBC’s Chicago Med for the disservice they did to the mitochondrial disease community. The very next day, my young patient, “Rose,” died.

Especially given this young woman’s tragic death, I want to further explain why what NBC did is so wrong and destructive.
Chicago Med is a 2015 television series created by Dick Wolf and Matt Olmstead. It focuses on a group of fictional emergency room doctors. A number of the episodes have a significant psychological theme. Some also are thinly veiled fictionalized adaptations of news stories. The episodes receive a surprising (to me) 9-12 million viewers, which is why it is so important that their portrayals of disease be fair to patients and, ideally, be educational.

In an episode in February, called “Reunion,” a young girl with mitochondrial disease was “diagnosed” by the ER physicians as instead suffering from psychiatric disease and medical child abuse. There was considerable outrage from the mito community on NBC’s Facebook page. I wrote NBC, asking when they were going to apologize or make amends by accurately portraying the disease to their viewers, rather than looking to profit off a show obviously meant to capitalize on the Justina Pelletier case. Their response? “We don’t comment on our fictional storylines for our series programs.”


Sunday, March 27, 2016


Facing a storm of criticism over its plan to show a documentary about the widely debunked link between vaccines and autism, the Tribeca Film Festival on Saturday pulled the film from its schedule next month.
In a statement, Robert De Niro, a founder of the festival, wrote: “My intent in screening this film was to provide an opportunity for conversation around an issue that is deeply personal to me and my family. But after reviewing it over the past few days with the Tribeca Film Festival team and others from the scientific community, we do not believe it contributes to or furthers the discussion I had hoped for.”
The film, “Vaxxed: From Cover-Up to Catastrophe,” was directed and co-written by Andrew Wakefield, the author of a study that was published in the British medical journal The Lancet and then retracted in 2010. Mr. Wakefield’s medical license was also revoked over his failure to disclose financial conflicts of interest and ethics violations.
Information about the film no longer appears on the festival’s website, but on Friday, the site,, did not mention Mr. Wakefield’s revoked license or the 2010 retraction, saying instead that the study “would catapult Wakefield into becoming one of the most controversial figures in the history of medicine.” And on Twitter, Mr. Wakefield described the film as a “whistle-blower documentary.”
A festival spokeswoman said on Saturday that she had no further comment about what specifically in the film raised concerns for Mr. De Niro after he initially added it to the festival. The film was to have been shown just once, on April 24, and was to be followed by a discussion with the director and subjects of the film.
Dr. William Schaffner, a professor of preventive medicine at the Vanderbilt University School of Medicine, said on Saturday that he believed “the entire board as well as Mr. De Niro have learned a lot in the last several days.”
“My hat is off to them for listening, thinking about it, discussing it and responding,” he said.

Saturday, March 26, 2016

Difficult choices 2

At the beginning of my fourth year of medical school, I had an abortion, an experience about which I have written previously in detail. At the time, we had a 2-year-old daughter, and we found out during our routine anatomy scan around 19 weeks that the baby boy I was carrying had a severe disease. His kidneys were irreversibly damaged, and as a result, his lungs could not develop properly. No one could predict whether he would die during the pregnancy, shortly after birth, or perhaps survive into childhood if he received neonatal dialysis and qualified for a kidney transplant in the future. For us, the risk of prolonged suffering, pain and grave disability – a kidney transplant at best has a lifespan of 20 years – outweighed the possibility of what we considered to be meaningful quality of life, and we chose to terminate the pregnancy. Preventing our baby’s suffering is a motivation that most can relate to even if they disagree with our ultimate choice. But the aspect of our decision that is harder to talk about – because as mothers, specifically, we are still widely expected to sacrifice everything in the interest of our children – is the fact that we also took into account what it might mean for our careers, for our growing family, and for the trajectory of our lives, if we chose to carry the pregnancy to term...

As a pediatrician-in-training and now the mother of three healthy daughters, I think frequently about our son, and the decision we made. One of the first patients I took care of as a resident was a toddler whose prenatal diagnosis was eerily parallel to our son’s. Every morning when I walked into his room to examine him and see how his night had been, I would see his tiny body curled up in the hospital crib, his G-tube hooked up to continuous feeds. I would see his mother sleeping on the fold-out chair underneath a scratchy hospital sheet, and I would wonder what it would be like if it were my son in that crib, if it were me sleeping on the makeshift bed. I can’t pretend to know anything about that mother’s beliefs or the decisions she made while pregnant, about the dreams and plans she had for her boy’s future, or about how her life may have changed when she took on her role as his mother and protector, always by his side. What was obvious, though, was that she loved her son dearly, just as I would have loved our son had he been born. When I think about our son, I wonder what color his soft, sweet hair would have been, and I check the perpetually running calendar in my mind to see how old he would be today. I wonder if, had we continued the pregnancy, I would be here in this hospital room as a resident or as a mother; if I would have quit my medical training entirely, a path that was already challenging enough with a young daughter and a husband with a busy career...

Critics of abortion frequently leverage the accusation that abortion is tantamount to “playing God.” Many perceive a fundamental difference between withdrawing or withholding life-sustaining care, on the one hand, and abortion, an active procedure intended to cause fetal death. One needn’t spend long in an academic tertiary care hospital to understand, however, that the provision of intensive perinatal care is far from passive, and that the lengths we go to preserve life could just as fairly be considered “playing God.” The potential pain and suffering associated with life-prolonging medical interventions, and the downstream consequences for families, society and the economy – these are not automatically ethical or noble just because they are undertaken in the pursuit of life and survival. And as one of my mentors, a kind and accomplished physician who was born and trained in Europe, told me after my termination, “death is not always the worst outcome.”

Part of the trouble comes from a na├»ve understanding – widespread even among many medical professionals – of the murky complexities of medical prognostication and interventions. Standards of care for many fetal conditions – the majority of which are not diagnosed until the routine anatomy ultrasound that is recommended at 18 to 20 weeks gestation – are shockingly dependent on differences in institutional culture and resources, and on personal differences among doctors. For our son, if he had survived past birth, would the nephrologist who was on call in the neonatal intensive care unit have been one who believes that starting dialysis in a newborn is ethically obligatory, or one who feels that it is morally permissible to decline? For babies born with hypoplastic left heart syndrome, a condition that is uniformly fatal without surgical repair, some pediatric cardiologists believe that palliative care is not an ethical option to offer anymore; others, likely thinking of children like the 5-year-old I took care of who had been in the hospital since his third birthday, contending with heart failure, then a heart transplant, and then post-transplant cancer, feel strongly that it remains a morally acceptable and personal choice...

For some families, the phenomenal advances that have been made in neonatal intensive care and in medicine more broadly have opened up wonderful, meaningful choices. Opting for certain life-prolonging interventions may allow a family to gain more information by seeing how their child responds to a “trial” of therapy; to prevent complicated grief about “giving up without trying”; or to extend and shape the quantity and quality of time they have with their child. A recent study of families of children with trisomy 13 and 18 – conditions historically considered lethal, though such infants can sometimes survive well into childhood – concluded that many families find deep meaning and satisfaction in pursuing life-prolonging measures, which is an important challenge to the long-established paternalistic assumptions throughout the medical community that babies with trisomy 13 and 18 have lives that are uniformly not worth living...

The meaning and consequences of caring for a child with a severe, chronic medical condition may be vastly different for a young single mother with limited financial resources and secular beliefs than for a stay-at-home mother in a religious, financially comfortable, two-parent household. Continuing a pregnancy complicated by severe anomalies can have significant physical, psychological and socioeconomic effects on mothers and families. There are non-trivial concerns about the risks associated with pregnancy and delivery, the emotional impact of continuing a pregnancy with a gravely ill fetus, the psychological impact on siblings and family dynamics, and the logistical and financial details of how to access and afford the intensive medical care their child may need. Different families will prioritize these considerations differently, but the bottom line is that these perinatal decisions simply do not occur in a moral vacuum...

 As a senior medical student facing our baby’s diagnosis, I had already gotten glimpses not just of heartwarming medical triumphs, but also of cases in which outcomes were poor, and families were left to navigate through the aftermath and the potential for strained finances, strained relationships, and hard decisions about life-prolonging treatments and quality of life, in a society and a medical system that is poorly equipped to provide the needed help and support. I had learned the resistance profile of antibiotics and the indications for starting dialysis, but I had also learned that a great deal of medicine remains as much an art as a science, and that among the statistics and quoted prognoses, no one could tell us what the right thing was for our family given the particular constellation of risks, challenges and possibilities. So, we made the gut-wrenching decision for our son to live and die knowing only the warmth and safety of my body. For us, it was the most right and just decision in a situation that was, by all measures, impossibly wrong.

Wednesday, March 23, 2016

Eye tracking device and concussion management

A neuro-technology company has received Food and Drug Administration (FDA) clearance for a medical device that could detect concussions in less than 60 seconds on the sidelines of playing fields across the nation. EYE-SYNC, a product of SyncThink, is an integrated ad-mounted eye-tracking device that analyzes eye movement impairment through the use of virtual reheality.

Dr. Jamshid Ghajar, neurosurgeon at Stanford University, president of the Brain Trauma Foundation, and SyncThink founder, told the product is distinct mainly because it does not claim to diagnose a concussion but rather detects disruption in visual information.

“All of the other technologies out there say that they’re ‘diagnosing concussion,’ but there’s no accepted definition, so how are you diagnosing it?” he said…

While some of the current technologies available to players and coaches focus on measuring the impact of a hit, or gauging the level of symptoms, Ghajar was careful to say that a definitive diagnosis will not come from just one tool.

“We don’t know what a ‘concussion’ is; there is no accepted diagnosis,” Ghajar said.
Ghajar is working with the FDA to come up with a diagnostic endpoint so other technologies can be rated.

“Ninety percent of what the brain does is through visual information, and the main thing with a concussion is that it gets disrupted,” he said. “Your brain has to predict what’s about to happen and when the information is going to come in so that you can process it.”…

With the EYE-SYNC device, users see a dot traveling around a circle while a camera tracks how well their eye follows the dot and measures attention for about 30 seconds. In the case of injury to the brain, the eye may jump to where it believes the dot is going before the dot gets there rather than following the path the dot is taking. Returning to the tennis analogy, Ghajar said it would be like a player swinging before the ball has reached the racket.

Once results are determined, trainers can decide whether to sit the player out to avoid another injury or putting them in harm’s way. Stanford University’s football team uses EYE-SYNC on the sidelines as well as SCAT 3 concussion assessment, which includes evaluating symptoms, cognition, balance and coordination.

“If [the player’s] eye tracking was normal, they sent them back into play,” Ghajar said. “If they could focus, then the headache they had was from something else.”…

Once a patient’s eye tracking is determined to be affected, Ghajar has him or her work with a physical therapist to address vestibular balance issues, and a neuropsychologist to address anxiety or depression caused by the injury. Ghajar also recommends that all patients return to a low-level of cardiovascular exercise to help recovery. He referenced a recent study involving mice that determined rest between concussions was necessary for the brain to return to normal function. However, he pointed out that the study only went so far as to say that rest was classified as non-contact function.

“Rest doesn’t mean don’t exercise— it means don’t get hit again,” he said. “We’re not advocating banging on your head again. We’re advocating getting on a treadmill or a bike and getting cardio exercise.”

Citing a study published in the journal Pediatrics on the benefits of strict rest after a concussion, Ghajar said he believes the current practice of keeping a patient isolated during recovery can hinder the process. He said children who miss school may see their academics and friendships suffer, further leading to psychological stress. Ghajar called for more research in this area.

As far as diagnosing concussions goes, Ghajar said he thought the design of future tools would lay in eye tracking, whether it be the EYE-SYNC or another technology.

“Everybody is looking for some kind of an objective measure,” he said, “and I think the EYE-SYNC is a really good objective measure.”

Tuesday, March 22, 2016

Genetic counseling

Little Kate Summersgill certainly didn’t look like a child with Down syndrome — no upward slanting eyes or telltale flat facial features.

Devon and Mike Summersgill had believed baby Kate was all but certain to be born with the intellect-stunting disorder because of a blood test Devon’s doctor recommended during her 2014 pregnancy. Even after the birth, when their baby looked fine, their genetic counselor, Laura Limone, insisted that the result of the test was not a mistake, Devon says.

Only after the New Jersey couple agonized over Kate’s future and spent almost $2,000 more on another test were they satisfied that Limone was wrong — their baby was fine. And when they learned that Limone had a financial relationship with the company that makes the test, called MaterniT21 PLUS, they wondered whether money had influenced the counselor’s advice.

“My first reaction was just utter confusion followed by anger,” said Devon Summersgill, 33, a special education teacher.

Parents are starting to question the independence of the fast-growing field of genetic counseling as more and more counselors are paid by the companies that make the tests. About 14 percent of the nation’s 4,000 genetic counselors worked directly for testing labs in 2014, up from 9 percent just two years earlier, according to the latest count by their professional society. The balance tend to work for hospitals or doctors’ practices.

“It’s a mass exodus to labs,” where pay tends to be higher and the perks are better, said Cori Feist, a genetic counselor with Oregon Health & Science University...

But the insurance industry and some state regulators are beginning to crack down on the ties between genetic counselors and the testing companies. As of this year, some health plans offered by insurer UnitedHealthcare no longer cover certain genetic tests ordered by counselors that work for labs. Cigna Corp. already has a similar policy.

Concerns are also growing that counselors working in close proximity to patients in doctors’ offices may be over-promoting tests. Pennsylvania and Florida have prohibited lab personnel, including genetic counselors, from working at health-care providers’ sites.

George J. Annas, a bioethicist at Boston University’s School of Public Health, said counselors have an incentive to favor companies that pay them, and that may color what they tell patients, including what to say about a test’s limitations. Whenever a “highly competitive commercial business” gets involved in medical choices, “you’ve got problems,” he said...

All prenatal screening tests have limitations, but counselors don’t always explain them clearly, something Jessica Daviso of Andover, Massachusetts, learned in an alarming way. Daviso said her lab-employed counselor never told her “that my test result was probably wrong.”

Daviso, 33, received a prenatal test result from California-based Counsyl Inc., a lab company, in October that indicated a high likelihood her fetus had Turner syndrome, a condition marked by short stature and infertility in girls, according to emails between her and a Counsyl genetic counselor, Kristen Rauch.

Rauch told Daviso that a recent study showed the “false positive” rate for Turner and similar syndromes was about 1 percent, the emails show, and recommended a second test that would confirm the condition.

Daviso and her husband Eugenio then sought out experts at Tufts Medical Center, where a genetic counselor looked at the test and other factors, including her age and other personal data, and estimated there was only about a 14 percent chance that her fetus had Turner’s – not the near certainty that Daviso said she was led to believe.

That’s because the false positive rate is only one factor in measuring a test’s accuracy. In pregnancy, it represents the percentage of times that women carrying healthy fetuses are given false alarms.

But a pregnant woman who receives a positive result needs to know something more: among the much smaller group of women who test positive, how often is the test right? Many prenatal genetic-test companies do not prominently advertise this rate, known as the positive predictive value, the New England Center for Investigative Reporting has found.

After the Tufts input and ultrasounds that have not indicated a problem, Daviso declined to have the more-definitive test, which carries a risk of miscarriage. She is due in April and says she and her husband believe there’s little chance the baby will have Turner.

“The accuracy of these tests comes directly from the labs that analyze the results and seek to profit most from [their] administration,” said Daviso. “The companies are promoting an inaccurate test.”...

Several studies have found that non-invasive test results indicating a fetus is at high risk for some genetic problems can be wrong more than 50 percent of the time.

Some women appear to have terminated pregnancies based on the screening test alone, according to scientists and an industry-funded study. Officials at Stanford University in California said in 2014 that there have been at least three cases of women aborting healthy fetuses relying on results of a genetic screening test.

“Women are not getting complete information,” said Dr. John Williams III, director of Reproductive Genetics at Cedars-Sinai hospital in Los Angeles. “We have seen several cases in which the NIPT test results were false positives.”...

Devon Summersgill said it was her obstetrician, Dr. Neil Russo, who suggested she give a blood sample for Sequenom’s MaterniT21.

After the positive test result, Summersgill said Russo told her the screening test was 99 percent accurate and referred the couple to New Jersey Perinatal Associates, a high-risk pregnancy practice where Limone works. Limone said she is not paid by Sequenom for New Jersey Perinatal test orders.

Summersgill said Limone told her the test was almost certainly accurate. Limone said that the false positive rate for the test was tiny — 0.2 percent, according to medical records the Summersgills shared with NECIR. The Summersgills say Limone told them an amniocentesis would have to be done to confirm the finding.

Dr. Leon G. Smith, Jr., of New Jersey Perinatal, wrote to Summersgill’s obstetrician, saying she was “counseled” about “the definitive nature of NIPT studies” and said that there was a “very high likelihood that this baby has fetal Down syndrome.”

As a teacher, Summersgill had dealt with children with Down syndrome, and she and her husband had already decided abortion wasn’t an option because “we felt she could live a happy and fulfilling life.” They chose not to risk a confirmatory amniocentesis. The test result, and Limone’s comments felt “pretty definitive,” Summersgill said.

They began telling family and friends, that their daughter was almost certainly going to have the condition.

After Kate’s 2014 birth, another genetic test the couple sought from a hospital seemed to rule out Down, and they began to breathe easier. Then came a follow-up call from the obstetrician, Russo, who ordered the original test. The doctor insisted that he had never heard of a MaterniT21 test being wrong, according to Summersgill, and suggested another call to Limone...

Dr. Wayne LaMorte, who teaches medical-test interpretation in a course at Boston University, calculated that a positive Down screen from Sequenom was correct for someone of Summersgill’s age only about half the time.

The Summersgills said Limone never told them the test could be wrong so often for someone of her age group and did not disclose her association with Sequenom when she counseled them on the test results. They say the experience has left them concerned that women may terminate pregnancies based on test results that are shakier than portrayed.

“We squeezed a life time of worry into six months of pregnancy,” Mike Summersgill said.
Courtesy of a colleague

Monday, March 21, 2016

Sometimes that extra boost has saved their lives

There's a belief gaining popularity that when patients seem to be nearing death's door, doctors should back off from aggressive medical care and let them die in peace.

Providing "heroic" care has become a negative, and many doctors are stepping back from it. According to a 2011 study,  42% of primary care physicians believed they were overtreating patients. 

And yet some patients—even when debilitated by metastatic cancer, brain injury, or old age—still want to keep on fighting. They don't want the doctor to give up on them, and there are many documented cases when that extra boost has saved their lives.

These patients may be a minority, but they are a significant minority, and their numbers appear to be growing.  A study released in fall 2015 found that nearly one third of people who fill out advance healthcare directives requested medical interventions. And while polls conducted by the Pew Research Center show that 15% of the American public in 1990 agreed that that everything possible should be done to save a patient's life, that figure rose to 31% by 2013….

When patients—or, very often, their families, who are supposed to be representing their interests—insist on continuing care even though death seems near, their pleas can often be just wishful thinking, based purely on emotion. In a 2009 study of family members of intensive care unit (ICU) patients, 32% would choose continued treatment for their family member despite being told that there was less than a 1% chance of survival.

But in a surprising number of cases, the family is right: The right amount of "heroic" care could turn things around and provide many extra years of life. This was the case for the elderly mother of Kathleen Finlay, founder of the Center for Patient Protection, which advocates for patient rights in the United States and Canada. 

In a 2013 article on the center's website, Finlay recalled doctors' premature efforts to let her mother die. In 2008, when her mother was in her 80s, she was admitted to a Canadian hospital with a serious infection. The doctor asked the family to sign a "do not resuscitate" (DNR) order, which involves withholding cardiopulmonary resuscitation (CPR) in the event of cardiac or respiratory arrest.

The family refused to grant a DNR, citing their mother's wishes. But the doctor didn't take no for an answer, Finlay wrote. He went directly to Finlay's mother and sought her consent for a DNR. Even though she was delirious with a fever, the doctor decided that he had gotten consent from her and ordered the DNR…

But the family also had good reasons to fear a DNR. Having a DNR in your chart can set you up for poorer care. Although DNRs are supposed to be limited to withholding CPR, they can be misinterpreted to mean withholding other interventions, according to a 2002 study.  That still seems to be the case today. A study published in 2015 showed that even when DNRs were given to cardiac patients with the best prognosis, these patients experienced lower survival rates and less resource use than similar patients without DNRs.

Back to Finlay's mother: Against the doctor's expectations, she recovered and went home. A few years later, at age 89, she was again hospitalized, this time for cardiac arrest, and the physician in charge again wanted to place a DNR order. This time it was a resident who told Finlay that for patients her mother's age, the chances of surviving another cardiac arrest were almost zero, but the family refused to authorize a DNR, and this time the decision stuck. Lo and behold, Finlay's mother had another cardiac arrest, but she received CPR and recovered.

Three years later, when Finlay wrote her article, her mother was still alive. "She remains curious about the world around her, engages in conversations, and enjoys her music and her garden," the daughter wrote. "How would we feel today if we had deprived her, and ourselves, of that by acceding to the hospital's urgings?"…

But, in fact, US doctors in some hospitals have very high DNR rates. In a US study[12] in 2014, doctors' use of DNR orders for stroke cases varied from 23.2% in the highest quintile of hospitals to 2.2% in the lowest quintile.

One reason for the wide variation in the use of DNRs is that doctors may not agree on what could happen to patients, according to Constantine A. Manthous, MD, an intensivist at Lawrence and Memorial Hospital in New London, Connecticut. Even in some of the finest ICUs in the country, "experienced medical professionals have not been able to reliably predict patient outcomes," he says. 

US doctors frequently overrule patients' wishes on DNRs, just like the Canadian doctor did for Finlay's mother. In a survey of the end-of-life care for patients aged 80 years and older, 9% of those who died without getting CPR did not have a DNR order in their chart, and almost 40% of those who died without CPR or those who had a written DNR order had a previously expressed desire for CPR….

Sometimes, when doctors order DNRs without telling patients, they think the patient would get very upset over the mere mention of a DNR, Dr Manthous says. For this reason, he says, New York law waives any requirement to get the patient's consent for a DNR if the doctor believes it would "harm" the patient. But Dr Manthous says that doctors' concerns here are overblown. In a 2006 study he coauthored, 90% of patients said that they wanted to know about DNRs…

Thus, each doctor is expected to come up with his or her own working definition of futility. In doing so, part of what doctors look at is the odds of survival for the patient, based on studies on overall patient outcomes, and the quality of life if the patient were to survive.

Perceptions of the quality of life, however, can be quite different for doctors as opposed to patients, according to Stephen Drake, a research analyst from Not Dead Yet, a group that defends patients who are at risk of not getting care. Physicians, he says, tend to prefer outcomes that preserve the patient's intellect. "The intellect is central to physicians' identity, and the idea of losing your intellect is abhorrent," he says. "That means that physicians might place a lower value on a person with a brain injury than the family would."

Moreover, Drake thinks that doctors often overestimate the amount of disability the patient would have. Indeed, he's witnessed this first hand, with his own care. When Drake was born in 1955, he developed a severe hematoma as a result of a breech birth. The doctor bluntly told his parents that the baby would probably be "a vegetable," adding: "If I were you, I wouldn't even pray that he lives." But his parents insisted that everything should be done. Drake says that he's had to deal with neuromotor issues and learning disabilities, but he is very thankful that his parents didn't follow the doctor's advice. "I would have been the victim of a form of passive euthanasia," he says…

"A small physiological improvement might seem sufficiently beneficial to a patient but not to a doctor (or vice versa)," they wrote. When the values of doctors and patients clash, they concluded, the patient's values should come first. "It is the patient's life to lead and death to die," they argued. "A concern with professional integrity cannot trump that, when there is some possibility, however small, of survival, and the patient wants to take it."