Friday, July 31, 2015

PANDAS presenting as a conversion disorder

In November, 2012, I wrote:  An 11 1/2 yo boy presented with complaints of dizziness, meaning light-headedness and occipital discomfort, associated with marked dysequilibrium. His presentation to several pediatric neurologists, including myself, is that of astasia-abasia. Psychiatry consultation finds him to have features consistent with conversion disorder. The imaging and laboratory studies that one might consider reasonable have been done with negative findings. He did, however have an ASO titer of 431 (0-240) and a streptococcal antibody titer of 798 (less than 376). Throat streptococcal culture was negative.
So, is this PANDAS or PANS or whatever the nom du jour might be?  If streptococcus or mycoplasma or whatever can cause OCD, why not conversion disorder?  Maybe a unifying hypothesis for the girls of Leroy would be that they had an autoimmune disorder which, in turn, caused conversion disorder?
A colleague replied:   Regarding the case of boy with conversion disorders and elevated ASO and some other streptococcal titer (was that anti-DNAase B?). Those titers imply NOTHING about etiology. All they mean is that the boy has likely had a strep infection in the past several weeks or months. Ed Kaplan did a study years ago showing that the average 3rd grader has 3 strep infection per year - most asymptomatic. Thus, the elevated titers are not surprising given his age. While I can't say it's impossible that immune / inflammatory mechanisms are involved in conversion disorder, I think it is unlikely. The Leroy girls had a "mass psychogenic illness" and have mostly recovered. In that situation, it is incredibly unlikely that 15 girls from the same high school all developed an autoimmune disorder within weeks of each other with identical symptoms.
Colleague 2 came to my aid:  I assume that Galen's comments were "tongue in cheek" and not serious since an elevated ASO is common in the pediatric population.

Colleague 3 wrote:   Why not, indeed? Like a lot of other people, I wrestle with the whole PANDAS business. But functional imaging studies can demonstrate transient abnormalities even with typical conversion. Ultimately, all normal and abnormal neurological function is brain-mediated, including conversion.

I replied to Colleague 3:  Indeed, I would suggest that the link between streptococcal titers and cultures and conversion disorder may be no less or more than that thus far established for tics and OCD. If I could come to believe the latter, then the former might be plausible, as well. It would seem a little oxymoronic, would it not, to have an identified "organic" cause for a conversion disorder? 

I replied to Colleague 1:  Where is your sense of humor?  Yes, it was anti-DNAase B.  As an antiPANDAS person, my point was that if you want to blame the standard tics and OCD on streptococcal cultures and serology, which I do not, then why not by the same criteria assert that streptococcal infection is in some way causing conversion disorder.
Colleague 1 replied to me:  My sense of humor about "PANDAS" is seriously lacking. I see at least one patient a month referred from someone who has diagnosed "PANDAS" based on a single elevated ASO titer, treated the child with 21 days of some antibiotic (usually an expensive alternative to Pen VK) and doesn't know what more to do.  3 or 4 times a year the diagnosis has been made by a child neurologist.
I replied to Colleague 1, in turn:  I was attempting a reductio ad absurdum using the type of reasoning you describe.
My comment to Colleague 2:  As you indicate, the 11/23 submission, "PANDAS manifesting as conversion disorder", was made with my tongue firmly inserted into my cheek. 
A further comment:  I would want to emphasize, though, that this is a real patient with real laboratory data where there was a request for consultation "to rule out PANDAS".

See: Maybe one day I'll see one June 10, 2015

Shaken baby syndrome 2

Laura Elizabeth Cowley, Charlotte Bethan Morris, Sabine Ann Maguire, Daniel Mark Farewell, Alison Mary Kemp.    Validation of a Prediction Tool for Abusive Head Trauma.  Pediatrics.  Published online July 27, 2015.


BACKGROUND AND OBJECTIVES: Abusive head trauma (AHT) may be missed in the clinical setting. Clinical prediction tools are used to reduce variability in practice and inform decision-making. From a systematic review and individual patient data analysis we derived the Predicting Abusive Head Trauma (PredAHT) tool, using multilevel logistic regression to predict likelihood of AHT. This study aims to externally validate the PredAHT tool.

METHODS: Consecutive children aged <36 months admitted with an intracranial injury, confirmed as abusive or nonabusive, to 2 sites used in the original model were ascertained. Details of 6 influential features were recorded (retinal hemorrhage, rib and long -bone fractures, apnea, seizures, and head or neck bruising). We estimated the likelihood of an unrecorded feature being present with multiple imputation; analysis included sensitivity, specificity, and area under the curve, with 95% confidence intervals (CIs).

RESULTS: Data included 133 non-AHT cases and 65 AHT cases, 97% of children were <24 months old. Consistent with original predictions, when ≥3 features were present in a child <36 months old with intracranial injury, the estimated probability of AHT was >81.5% (95% CI, 63.3–91.8). The sensitivity of the tool was 72.3% (95% CI, 60.4–81.7), the specificity was 85.7% (95% CI, 78.8–90.7), area under the curve 0.88 (95% CI, 0.823–0.926).

CONCLUSIONS: When tested on novel data, the PredAHT tool performed well. This tool has the potential to contribute to decision-making in these challenging cases. An implementation study is needed to explore its performance and utility within the child protection process.

See:   Shaken baby syndrome 3/30/15


Thursday, July 30, 2015

Sports traumatic brain injury and CT

Todd Glass, Richard M. Ruddy, Elizabeth R. Alpern, Marc Gorelick, James Callahan, Lois Lee, Mike Gerardi,  Kraig Melville MD, Michelle Miskin, James F. Holmes, Nathan Kuppermann.  Traumatic Brain Injuries and Computed Tomography Use in Pediatric Sports Participants.  American Journal of Emergency Medicine.  Published online 6 July 2015.
Childhood sports-related head trauma is common, frequently leading to emergency department (ED) visits. We describe the spectrum of these injuries and trends in computed tomography (CT) use in the Pediatric Emergency Care Applied Research Network (PECARN).
This was a secondary analysis of a large prospective cohort of children with head trauma in 25 PECARN EDs between 2004–6. We described and compared children 5–18 years by CT rate, TBI on CT and clinically-important TBI (ciTBI). We used multivariable logistic regression to compare CT rates, adjusting for clinical severity. Outcomes included frequency of CT, TBIs on CT, and ciTBIs (defined by a) death, b) neurosurgery, c) intubation >24 hours, or d) hospitalization for ≥2 nights).
3,289 / 23,082 (14%) children had sports-related head trauma. 2% had Glasgow Coma Scale scores <14. 53% received ED CTs, 4% had TBIs on CT, and 1% had ciTBIs. Equestrians had increased adjusted odds [1.8 (95% CI 1.0, 3.0)] of CTs; the rate of TBI on CT was 4% (95% CI 3, 5%). Compared to team sports, snow [AOR 4.1 (95% CI 1.5, 11.4)] and non-motorized wheeled [AOR 12.8 (95% CI 5.5, 32.4)] sports had increased adjusted odds of ciTBIs.
Children with sports-related head trauma commonly undergo CT. Only 4% of those imaged had TBIs on CT. ciTBIs occurred in 1%, with significant variation by sport. There is an opportunity for injury prevention efforts in high-risk sports and opportunities to reduce CT use in general by use of evidence-based prediction rules.
What is known about this subject – Pediatric sports-related head injuries are a common and increasingly frequent emergency department (ED) presentation, as is the use of computed tomography (CT) in their evaluation. Little is known about traumatic brain injuries (TBIs) resulting from different types of sports activities in children.
What this study adds to existing knowledge – This study broadens the understanding of the epidemiology of pediatric TBIs resulting from different sports activities through a prospective assessment of frequency and severity of clinically-important TBIs, and ED CT use in a large cohort of head-injured children in a network of pediatric EDs.

Courtesy of:

Intranasal midazolam

Lara Kay, Philipp S. Reif,  Marcus Belke, Sebastian Bauer, Detlef Fründ, Susanne Knake, Felix Rosenow, Adam Strzelczyk.  Intranasal midazolam during presurgical epilepsy monitoring is well tolerated, delays seizure recurrence, and protects from generalized tonic–clonic seizures.  Epilepsia.  published online: 27 JUL 2015.
To evaluate the tolerability and efficacy of the ictal and immediate postictal application of intranasal midazolam (in-MDZ) in adolescents and adults during video–electroencephalography (EEG) monitoring.
Medical records of all patients treated with in-MDZ between 2008 and 2014 were reviewed retrospectively. For each single patient, the time span until recurrence of seizures was analyzed after an index seizure with and without in-MDZ application. To prevent potential bias, we defined the first seizure with application of in-MDZ as the in-MDZ index seizure. The control index seizure was the preceding, alternatively the next successive seizure without application of in-MDZ.
In total, 75 epilepsy patients (mean age 34 ± 14.7 years; 42 male, 33 female) were treated with in-MDZ (mean dose 5.1 mg). Adverse events were observed in four patients (5.3%), and no serious adverse events occurred. The median time after EEG seizure onset before administration of in-MDZ was 2.17 min (interquartile range [IQR] 03.82; range 0.13–15.0 min). Over the next 12 h after in-MDZ, the number of seizures was significantly lower (p = 0.031). The median seizure-free interval was significantly longer following treatment with in-MDZ (5.83 h; IQR 6.83, range 0.4–23.87) than it was for those with no in-MDZ treatment (2.37 h; IQR 4.87, range 0.03–21.87; p = 0.015). Conversely, the likelihood of the patient developing a subsequent seizure was four times higher (odds ratio [OR] 4.33, 95% confidence interval [CI] 1.30–14.47) in the first hour and decreased gradually after 12 h (OR 1.5, 95% CI 1.06–2.12). The occurrence of generalized tonic–clonic seizures was lower in the in-MDZ group in the 24-h observation period (OR 4.67, 95% CI 1.41–15.45; p = 0.009).
Ictal and immediate postictal administration of in-MDZ was well tolerated and not associated with serious adverse events. We demonstrated a significant reduction of subsequent seizures (all seizure types) for a 12 h period and of generalized tonic–clonic seizures for 24 h following in-MDZ.

Courtesy of:


When men could lift boulders no six men can lift now

During an expedition to the Antarctic, Russian surgeon Leonid Rogozov became seriously ill. He needed an operation - and as the only doctor on the team, he realised he would have to do it himself...

The Novolazarevskaya Station was up and running by the middle of February 1961, and with their mission complete the group settled down to see out the hostile winter months...

But by the end of April, Rogozov's life was in danger and he had no hope of outside help. The journey from Russia to the Antarctic had taken 36 days by sea, and the ship wouldn't be back for another year. Flying was impossible because of the snow and blizzards.

"He was confronted with a very difficult situation of life and death," says Vladislav. "He could wait for no help, or make an attempt to operate on himself."

"He had to open his own abdomen to take his intestines out," says Vladislav. "He didn't know if that was humanly possible."...

The commander in charge of the Novolazarevskaya base had to get Moscow's blessing for the operation to go ahead. "If my father was to fail and die it would definitely put a hard hat of negative publicity on the Soviet Antarctic programme," says Vladislav...

"Still no obvious symptoms that perforation is imminent, but an oppressive feeling of foreboding hangs over me… This is it… I have to think through the only possible way out - to operate on myself… It's almost impossible… but I can't just fold my arms and give up."...

Rogozov worked out a detailed plan for how the operation would unfold and assigned his colleagues specific roles and tasks.

He nominated two main assistants to hand him instruments, position the lamp, and hold a mirror - he planned to use the reflection to see what he was doing. The station director was also in the room, in case one of the others became faint.

"He was so systematic he even instructed them what to do if he was losing consciousness - how to inject him with adrenalin and perform artificial ventilation," says Vladislav. "I don't think his preparation could have been better."

A general anaesthetic was out of the question. He was able to administer a local anaesthetic to his abdominal wall but once he had cut through, removing the appendix would have to be done without further pain relief, in order to keep his head as clear as possible.

"My poor assistants! At the last minute I looked over at them. They stood there in their surgical whites, whiter than white themselves," Rogozov wrote later. "I was scared too. But when I picked up the needle with the novocaine and gave myself the first injection, somehow I automatically switched into operating mode, and from that point on I didn't notice anything else."

Rogozov had intended to use a mirror to help him operate but he found its inverted view too much of a hindrance so he ended up working by touch, without gloves.

As he reached the final and hardest part of the operation, he almost lost consciousness. He began to fear he would fail at the final hurdle.

"The bleeding is quite heavy, but I take my time... Opening the peritoneum, I injured the blind gut and had to sew it up," Rogozov wrote. "I grow weaker and weaker, my head starts to spin. Every four to five minutes I rest for 20 - 25 seconds.

"Finally here it is, the cursed appendage! With horror I notice the dark stain at its base. That means just a day longer and it would have burst… My heart seized up and noticeably slowed, my hands felt like rubber. Well, I thought, it's going to end badly and all that was left was removing the appendix."

But he didn't fail. After nearly two hours he had completed the operation, down to the final stitch.

Then, before allowing himself to rest, he instructed his assistants how to wash the surgical instruments and only when the room was clean and tidy did Rogozov take some antibiotics and sleeping tablets.
Courtesy of a colleague

Wednesday, July 29, 2015

Face blindness

Imagine going to school to pick up your child and not being certain which kid is yours. Imagine brushing your teeth every morning and not wholly recognizing the face in the mirror. All of this is unimaginable for most of us, but a basic fact of life for people with the mysterious neurological condition called "face blindness" -- or prosopagnosia - which can make it almost impossible to recognize faces, even of one's nearest and dearest. Dr. Oliver Sacks knows something about the condition, and not only because he's a neurologist, but also because Dr. Sacks himself is face blind. Lesley Stahl reports.

Most of us take for granted that we can instantly recognize people we know by looking at their faces. It's so automatic, it almost sounds silly to even say it. Friends can put on a hat, cut their hair, and still we know them by their face. We can do this for thousands upon thousands of faces without ever giving it a moment's thought. But imagine for a second what life would be like if you couldn't, if your wife or husband looked like a stranger; you couldn't tell your kids apart; couldn't recognize yourself in a mirror. Well that's what life is like for people who suffer from a mysterious condition called face blindness, or prosopagnosia, that can make it nearly impossible to recognize or identify faces.
If you've never heard of face blindness, you're not alone -- chances are your doctor hasn't either. It's been unknown to most of the medical world until very recently. Hearing about it can feel a little like entering the twilight zone. But for people who are face blind, the condition is very real...

So they have to rely on other strategies to identify people: hair, body shape, the way people walk, their voice, even style of dress. But Jacob told us it can all fall apart when someone changes their hair, like a colleague named Sylvia who he couldn't find one day until she started putting her hair into her usual ponytail.

Jacob Hodes: And she like put it into the ponytail. And once it was in place that was Sylvia. It clicked. Then she took her hair back out of that ponytail.

Lesley Stahl: Right then and there?

Jacob Hodes: Yep. She just put it in and then took it out and--

Lesley Stahl: So she went from Sylvia, not Sylvia, Sylvia, not Sylvia?

Jacob Hodes: She disappeared.

Lesley Stahl: Come on.

Jacob Hodes: Yeah....

We were baffled that a condition so extreme it could keep people from recognizing their own children could have been almost completely unknown until very recently. We asked Dr. Oliver Sacks, the famous chronicler of fascinating and bizarre neurological conditions, who wrote about face blindness in his latest book, "The Mind's Eye."...

Jo only learned there was such a thing as face blindness when she stumbled across this article, and came in to be tested in Duchaine's lab. A few hours after her second visit, in a bizarre coincidence, she and Duchaine ended up attending the same event.

Brad Duchaine: I kept placing my face in a position where she could see it.

Jo Livingston: I realized that one of the group was staring at me in a way that people don't normally.

Brad Duchaine: And so finally at one point I said, "Do you know who I am?"

Jo Livingston: "Ah."

Brad Duchaine: And she put it all together.

Duchaine had seen face blindness in action; Jo had seen the missed connections of her life.

Jo Livingston: If that had been anybody else, they would have been presumably furious, would not have spoken to me and would have probably never have spoken to me again. But I would never have known they were there.

I feel your pain

You've heard the expression, "I feel your pain," but some people actually do, including a doctor in Boston who is able to connect with his patients in a way most can't.

As CBS Boston's Dr. Mallika Marshall reports, Dr. Joel Salinas, a neurologist at Massachusetts General Hospital, has a rare condition called mirror-touch synesthesia.

"When I see people, I have the sensation of whatever touches their body on my own body as well and it's kind of reflected as a mirror," Salinas explained.

Salinas, like many with the condition, says he's been able to physically feel the pain of others since was a child, when he thought it was normal.

"When I was a kid, having these experiences where if I would see someone hug I would feel the hug on myself or if I would see someone get hit, I felt the sensation on me as well," he said.

The ability to experience several senses together creating a unique, compounded experience is referred to as synesthesia. It's believed to affect about one to two percent of the population. People with mirror-touch synesthesia may have a heightened sense of touch that overlaps with sight and/or hearing, triggering pronounced feelings of empathy.

Even without the condition, people who see others in pain may activate the same body response that would be used if they were in pain themselves. "Mirror neurons" help people mimic and identify with what they see.

Recent studies say that the mirroring reaction can be greatly heightened for those with mirror-touch synesthesia. Though researchers don't know exactly why, they have two main theories: people with mirror-touch synesthesia may have hyperactive mirror neurons that exaggerate the mimicking response, or they could possibly have difficulty distinguishing themselves from other people. For some who have the condition, the intense sense of empathy and physical adoption of pain can result in an overwhelming flood of emotions.

"They're kind of crushed by those sensations because it's too much and it's overwhelming," Salinas said. "They develop issues with anxiety and depression and essentially become shut-ins at times." Salinas says he sees his mirror-touch synesthesia as an asset and he's learned to focus his thoughts and use the feelings in his practice.

"I think it's empowered me to really connect with my patients. There's a wall that's torn down when you feel a lot of the sensations that your patients feel as well. It's like being aggressively put in somebody else's shoes."
Courtesy of a friend

Neural efficiency hypothesis

The brains of more intelligent people are capable of solving tasks more efficiently, which is why these people have superior cognitive faculties, or as Elsbeth Stern, Professor for Research on Learning and Instruction at ETH Zurich, puts it: “when a more and a less intelligent person are given the same task, the more intelligent person requires less cortical activation to solve the task.” Scientists refer to this as the neural efficiency hypothesis, although it ceased being a hypothesis quite some time ago and is now accepted by experts as an undisputed fact, with ample evidence to support it.
While working on her doctoral thesis in Stern's work group, Daniela Nussbaumer also found evidence of this effect for the first time in a group of people possessing above-average intelligence for tasks involving what is referred to as working memory. “We measured the electrical activity in the brains of university students, enabling us to identify differences in brain activity between people with slightly above-average and considerably above-average IQs,” explained Nussbaumer. Past studies conducted to identify the effect of neural efficiency have generally used groups of people that exhibit extreme variations in intelligence...

In order to test these abilities, the ETH researchers asked 80 student volunteers to solve tasks of varying complexity on a computer.

One task, for example, was to determine whether individual letters or faces were part of a selection of letters or faces that had been shown to the subjects immediately beforehand. An especially difficult task involved identifying letters and faces shown to the subjects during past runs of the test within a time limit. While the students were completing the tests, the researchers used electroencephalography (EEG) to measure their brain activity. For the results analysis, the researchers had the subjects take a conventional IQ test and then split them into two groups: one with slightly above-average IQs and another with well above-average IQs.

The researchers found no differences in brain activity in either group of subjects when they performed very easy or very difficult tasks. They did, however, see clear differences in the case of moderately difficult tasks. Stern attributes this to the fact that none of the subjects had any trouble whatsoever with the simple tasks and that the difficult tasks were cognitively demanding even for the highly intelligent subjects. In contrast, all subjects succeeded in solving the moderately difficult tasks, but the highly intelligent subjects required fewer resources to do so.

Stern uses the analogy of a more and less efficient car: “When both cars are travelling slowly, neither car consumes very much fuel. If the efficient car travels at maximum speed, it also consumes a lot of fuel. At moderate speeds, however, the differences in fuel consumption become significant.”...

The ETH researchers' intelligence study also suggests that it is impossible to “exercise” working memory. This has been a controversial issue among scientists in recent years because of contradictory findings in different studies. If subjects practise a certain task for a prolonged period, they improve with time. As Stern and her peers have now shown in their study, people who have practised certain tasks do not have any advantage over their unpractised counterparts when confronted with new, yet similar tasks.

Nussbaumer D, Grabner RH, Stern E: Neural efficiency in working memory tasks: The impact of task demand. Intelligence 2015. 50: 196-208
Courtesy of:

Tuesday, July 28, 2015

Ketogenic diet in infancy

Anastasia Dressler, Petra Trimmel-Schwahofer, Eva Reithofer, Gudrun Gröppel, Angelika Mühlebner, Sharon Samueli, Viktoria Grabner, Klaus Abraham, Franz Benninger, Martha Feucht.  The ketogenic diet in infants – Advantages of early use. Epilepsy Research, online 07/28/2015
To evaluate the efficacy and safety of the ketogenic diet (KD) in infants (<1.5 years of age) compared with older children.
Patients with complete follow-up data of ≥3 months after initiation of the KD were analyzed retrospectively. Infants <1.5 years at initiation of the KD (Group A) were compared with children >1.5 years (Group B).
127 children were screened, 115 (Group A: 58/Group B: 57) were included. There were no significant differences between groups with respect to responder rates (63.8% vs. 57.9% at 3 months), but more infants became seizure free (34.5% vs. 19% at 3 months; 32.7% vs. 17.5% at 6 and 12 months). This result remained stable also after termination of the KD (30.6% vs. 3.9% at last follow-up) (p = 0.000). Looking at infants <9 months of age separately (n = 42), this result was even stronger with significantly more infants being seizure free at 6 and at 12 months (p = 0.005, p = 0.014, respectively). In addition, a significantly higher number of infants remained seizure free in the long-term (p = 0.001).
No group differences between infants and children with respect to safety were observed. Overall 52/115 patients (45.21%) reported side effects, but withdrawal of the KD was only necessary in one infant. Acceptance of the KD was better in infants compared with children at 3 months (0 vs. 14, p = 0.000), but became difficult when solid food was introduced (16 vs. 14; n.s.).
According to our results, the KD is highly effective and well tolerated in infants with epilepsy. Seizure freedom is more often achieved and maintained in infants. Acceptance of the diet is better before the introduction of solid food. Therefore, we recommend the early use of the KD during the course of epilepsy.
The authors aim to evaluate the efficacy and safety of the ketogenic diet (KD) in infants (<1.5 years of age) compared with older children. According to the results, the KD is highly effective and well tolerated in infants with epilepsy. Seizure freedom is more often achieved and maintained in infants. Acceptance of the diet is better before the introduction of solid food. Therefore, they recommend the early use of the KD during the course of epilepsy.


  • Patients with complete follow-up data of ≥3 months after initiation of the KD were analyzed retrospectively.
  • Infants <1.5 years at initiation of the KD (Group A) were compared with children >1.5 years (Group B).


  • 127 children were screened, 115 (Group A: 58/Group B: 57) were included.
  • There were no significant differences between groups with respect to responder rates (63.8% vs. 57.9% at 3 months), but more infants became seizure free (34.5% vs. 19% at 3 months; 32.7% vs. 17.5% at 6 and 12 months).
  • This result remained stable also after termination of the KD (30.6% vs. 3.9% at last follow-up) (p = 0.000).
  • Looking at infants <9 months of age separately (n = 42), this result was even stronger with significantly more infants being seizure free at 6 and at 12 months (p = 0.005, p = 0.014, respectively).
  • In addition, a significantly higher number of infants remained seizure free in the long-term (p = 0.001).
  • No group differences between infants and children with respect to safety were observed.
  • Overall 52/115 patients (45.21%) reported side effects, but withdrawal of the KD was only necessary in one infant.
  • Acceptance of the KD was better in infants compared with children at 3 months (0 vs. 14, p = 0.000), but became difficult when solid food was introduced (16 vs. 14; n.s.).

Fetal tissue procurement

Scientists at major universities and government labs have quietly been using fetal tissue for decades. They say it is an invaluable tool for certain types of research, including the study of eye diseases, diabetes and muscular dystrophy. Nevertheless, some agree to talk about it only if their names and their universities’ names are withheld, because they have received threats of violence from abortion opponents. Companies that obtain the tissue from clinics and sell it to laboratories exist in a gray zone, legally. Federal law says they cannot profit from the tissue itself, but the law does not specify how much they can charge for processing and shipping...

“Think of fetal tissue as a kind of instruction booklet,” said Sheldon Miller, the scientific director of the intramural research program at the National Eye Institute.
Eye tissue from fetuses has played a crucial role in studies aimed at finding treatments for degenerative diseases of the retina that are a major cause of vision loss in people as they age, according to Dr. Miller.
“We couldn’t get this information any other way,” Dr. Miller said. He said the eye institute bought fetal tissue from a company, created specialized cultures of retinal tissue from it and sent them to other researchers...
Many buy the tissue from companies that act as middlemen. Those companies pay small fees, usually $100 or less a specimen, to abortion providers like Planned Parenthood, who say they charge only what they need to cover their expenses. The companies then process the tissue and sell it to researchers for higher prices that reflect the processing.
The fees, which can run to thousands of dollars for a tiny vial of cells, do not break the law, according to Arthur Caplan, the director of the division of medical ethics at NYU Langone Medical Center.
“It appears to be legal, no matter how much you charge,” Dr. Caplan said, adding that there appears to be little or no oversight of the processing fees. “It’s a very gray and musty area as to what you can charge.”...
But critics note several references in the flyer to financial benefits for clinics. By teaming with StemExpress, “you will also be contributing to the fiscal growth of your own clinic,” it says, a statement that some contend suggests clinics may be illegally profiting from providing fetal tissue.
George J. Annas, a law professor and bioethicist at Boston University, said, “What’s going on now is probably legal, but Congress won’t like it.”
Regarding the companies, Mr. Annas said: “They won’t be real happy that this is all out in the public. This threatens their business. Even if what they’re doing is legal, the law can easily be changed.”
Courtesy of:

Monday, July 27, 2015

Gadolinium brain deposits

The US Food and Drug Administration (FDA) is looking into the risk for brain deposits with repeated use of gadolinium-based contrast agents (GBCAs) for MRI, the agency said today in a drug safety communication.

Following administration, GBCAs are mostly eliminated from the body through the kidneys. However, recent reports suggest that GBCAs can linger in the brains of patients who undergo four or more contrast MRI scans as part of management of multiple sclerosis, cancer, or other illnesses, even in those with normal kidney function, the FDA says.

It's not known whether these deposits are harmful or can lead to adverse health effects. "To date, no signs or symptoms of adverse health effects and no pathological changes have been associated with these gadolinium deposits in the brain," the FDA notes.

However, they do err on the side of caution in their recommendation. "To reduce the potential for gadolinium accumulation, health care professionals should consider limiting GBCA use to clinical circumstances in which the additional information provided by the contrast is necessary. Health care professionals are also urged to reassess the necessity of repetitive GBCA MRIs in established treatment protocols," the FDA advises.

Cognitive rest

On April 5, 2011, I wrote:  Regarding postconcussive patients: "Cognitive rest is an aspect of postconcussion treatment that involves avoidance of excessive neurometabolic processes associated with cognitive activities...Cognitive rest requires the patient to refrain from all activities that involve mental exertion, such as working on a computer, watching television, using a cell phone, reading, playing video games, text messaging and listening to loud music. Any of these activities may exacerbate symptoms and could delay recovery."
Do my colleagues believe this? If so, on what is their belief based?
One response: Thank you for writing in your question about cognitive rest. When I've read that and similar quotes in the pediatric and neurology literature, and of course in the media, its struck me as bizarre. The person is supposed to lie on a bed, eyes closed, ears blocked and told to make sure not to think either? It reminds me of the article I had hanging over my desk during my fellowship. It was from The Weekly World News (an awesome tabloid filled with stories of alien invasions, Jesus citings in grilled cheese sandwiches and the like) about the death of a brilliant chess player who was thinking so hard that the electricity in his brain got out of whack and his brain exploded "like popcorn".
Another colleague wrote:  Actually, (he said a bit sheepishly) I do. I approach the concussed brain the way I would a badly sprained ankle and recommend, metaphorically speaking: 'Ace, Ice and Elevate'. Just as walking and running on a sprained ankle will prolong the pain and delay recovery, I accept the idea that cognitive activity is the equivalent of 'exercising' the brain, which should be 'rested' after an injury. I recommend gradual re-introduction of cognitive activity just as I do physical activity, even to the point of starting patients on junk novels before text books, with the recommendation that they back off if they become symptomatic with an activity. My, admittedly anecdotal, experience leads me to believe this is helpful; I've had kids with prolonged post concussive symptoms feel better after doing this (acknowledging that time, rather than 'cognitive rest' may have made the difference) and have seen kids have recurrence of symptoms with specific activities, such as math, when reading was not a problem, suggesting to me that the math was more of a 'sprint' for their brain, which wasn't ready for it.
I replied:  I would suggest, on the contrary, that I have seen invalids and chronic complainers created by traumatic brain injury interventionists who convey a message that the patient is so-so injured by their often rather trivial head bonk, with subsequent prolonged absence from school and chronic intractable headaches. I would like to know whether patients who are not seen in a traumatic brain injury program do not demonstrate prompter and better recovery than those who are.
A third colleague wrote:  worry about not being employed making money, doing schoolwork, keeping up with peers, who is dating who must not count as cognitive work!
A fourth colleague wrote:  Times, perceptions, concerns and medical practices have certainly changed. I had a little cycling accident in Princeton NJ 20 years ago, wearing a helmet properly fitted and buckled on, of course. I ran the Yellow light at a T- intersection, but as I did a pedestrian started to cross directly in my path. Next thing I knew the rescue squad was hovering over me. Over my remonstrations and objections I and my bicycle were lifted into the ambulance and taken to the hospital ER. I was x-rayed for my shoulder complaint, told I had a minor separation, and went on my way (in my wife's car), promising to see an orthopedist. I was clearly unconscious for the time it took for someone to call the squad and for them to get there, a distance of a busy town mile. Maybe 15-20 minutes. I was perfectly lucid thereafter and i don't recall a skull x-ray. Last week a saw a five year old boy (for his developmental issues) who had been knocked over by another five year-onl while standing next to the bleachers at a high-school basketball game two weeks earlier. He sustained a 3 cm gash in his scalp, right fronto-parietal area, presumably from hitting the metal frame or the edge of the bench. He was up on his feet in seconds, crying for mom, told her the whole story of who, what and where, was never drowsy, confused, disoriented, and did not vomit at any time. He was taken to the ER, where the wound was closed with metal clips after he had a skull film and a CT scan. The scan showed a "minute defect in the outer table" but nothing, nothing, nothing anywhere in his head. The child was then referred to a pediatric neurosurgeon twenty-five miles away and a difficult trip for a car-less family. This physician made a diagnosis of concussion, skull fracture and referred the child for an MRI. I (probably un-tactfully) suggested that the MRI and accompanying half-day hospitalization and sedation could be safely dispensed with. I dare say I have sown up 500 such scalp lacerations under these clinical conditions and this negative history without benefit of CT scans and never missed a neurological consequence. I think the whole medical world has gone mad but thee and me, but sometimes I fear…
Oops! I forgot    possibly as a result of my own concussion twenty years ago or my 83 years           the end of the story about the five year old with a scalp laceration. The diagnosis of skull fracture and concussion was followed by a mandate that the child stay home from school for one week and out of gym and recreation for one month and return to the neurosurgeon for followup. The office notes "report" are boiler-plate computer generated. To reiterate: The child had no clinical symptoms or signs of concussion. He was knocked over by another same size child. His head traveled forward approximately three feet before striking the bleacher. The minute defect in the outer table of the skull was not attended by any "crack" of the inner table and the CT was otherwise entirely negative. Is this not madness compounded?
A fifth colleague wrote:  There are at least two hypotheses supporting the recommendation for rest until cognitive recovery is achieved. Scientific experimentation may provide answers as to the first of these, bearing in mind that there have been some serious missteps in such work such as the well-known violations of protocol and baboon mistreatment at the U Penn head injury laboratory in the early 1980s. There is the second reason, an hypothesis for which there is already human data. Concussion may produce errors or at least slowing in execution of motor activities and to the extent that decision making, response time, memory, and alteration of performance in accordance with the timely appreciation of unexpected circumstances of play evolution are affected, second head injuries in the wake of an initial concussive event are very likely to be worse than those typical for the player. At competitive levels of play, excellent athletic performance may require an expected degree of split second sequences of activity upon which a player may rely because the speed and sequence of activities and necessary adaptation to unexpected circumstances is deeply ingrained and is not retarded in execution by very conscious reflection. That slowing is exemplified by the manner in which an average pianist (not an accomplished one) may execute a piece of music at a certain intended speed until the sequence is disrupted by an error--thinking one's way out of it slows the music down: perhaps too much cortical consciousness outweighing the cerebellorubroextrapyramidopyramidal shortcuts. An example in sports was the "tweener" passing shot from baseline to the far opponent court corner that Federer must have executed by such practice without the interference of reasoning, vision, or conscious thought--the practice effect is exemplified by the fact that he achieved this unbelievable shot in two successive US Opens--against Djikovic (2009) and Dabul (2010)(apologies if I have misspelt their names) Head injuries are not frequently encountered in tennis, but a quarterback (o for the Rugby playing world the tight-head or hooker)may greatly increase their chances of injury (neck rather than head for the Rugby front-liners) by executing actions with anticipated speed and effect at a given practiced pace, not anticipating the dangers that lurk when that speed and momentary adaptations are impaired.
The fifth colleague also wrote:  Cognitive rest cannot help but bring to everyone's mind the "rest cure" ideas of Weir Mitchell. Of course it is best known now in the setting of the chronic headaches of Philadelphia’s wealthy society matrons. He prescribed prolonged inactive bed rest, closed curtains in a darkened room, with no distractions/visitors/activities, for a set interval of time (a month in some cases I think). He said to Osler and others that he had considerable success in finding these individuals relived of headache when released from their rest. There was one temporary exception--a grand dame who when he came to release her was told him that she had no intention of leaving her comfortable bed. Mitchell's response was "If you intend to remain in bed then I have no choice but to join you." As she showed no tendency to relent he proceeded to start to unbutton his vest. The result, he related on a number of occasions, was that the old lady made haste to demonstrate her intention of getting up. Mitchell also applied this method as a last resource in erythromelalgia of Weir Mitchell and in the neuralgia of locomotor ataxia.
A sixth colleague wrote: Given that more than 90% of cerebral energy metabolism is spent in the brain's so-called default mode of maintaining brain structure and connections (listen to Marcus Raichle's musings @ http://www.youtubexomiwatch?v=ualOUAtwUA8 ), behaviorally imposed cognitive rest (an imaginary concept) in reality has trivial to no potential for actually "resting" the brain in terms of curtailing cerebral energy utilization - unless there is pharmacologically mediated suppression of trans-synaptic communications.
Bad enough for us to fool or mislead others, but far worse to fool ourselves. Cognitive rest? Humbug.
PS: Sorry for the Faulknerian run-on sentence.
A seventh colleague wrote:  A good example of colleague six’s warning about "cognitive rest" is the way the retina works. In the absence of light, there is an energy-consuming "dark current": stimulating the eye with light reduces energy expenditure. So less stimulation can mean more energy use.   

The problem doctor--unpleasant behavior does happen

Most people working in healthcare probably have encountered a "problem" or "disruptive" doctor. Physician antisocial behavior takes many forms, ranging from the petty and silly to the dangerous and criminal. Temper tantrums, demeaning attitudes toward staff and patients, and a refusal to abide by the practice's or hospital's policies are all too common.

"I've seen everything—doctors striking patients, destroying hospital property, stalking nurses, surfing the Web for porn while at the hospital, shouting profanities at staffers, you name it," says Will Latham, a practice management consultant in Charlotte, North Carolina.

The problem of "problem" doctors is more extensive than many realize and has a far-reaching impact on patient safety, staff retention, a group's or hospital's malpractice liability risk, and the organization's financial bottom line.

More than 70% of physicians say that disruptive physician behavior occurs at least once a month at their organizations, and more than 10% say that such incidents occur every day, according to a 2011 study of more than 840 physicians and physician leaders from QuantiaMD and the American College of Physician Executives.  One half of the respondents reported that they know patients have left their practices because of disruptive physician behavior.

"You can put up with only so much abusive behavior before it crushes your spirit," says Ken Hekman, a practice management consultant in Holland, Michigan. "Some employees and patients will start voting with their feet and just quit. Patients are more likely to find another doctor rather than report the problem to the practice administrator."

In 2008, the Joint Commission for Accreditation of Healthcare Organizations started requiring hospitals to confront disruptive medical staff members, implement a code of conduct, and provide education to address the behavior. That new requirement has made hospitals far less tolerant of doctors who act out by throwing instruments or abusing staff...

"A really good surgeon who was well liked was persistently late in doing his charts," says MGMA's Dr Fischer-Wright. "The group even hired a consultant to work with him, because the practice was losing more than $20,000 a month owing to his incomplete charting. Finally, there was a seminal event. The surgeon knew that a patient had an allergy to a medicine but never charted it. So a colleague who was on call prescribed that medication. The patient ended up on a ventilator for 3 days in the intensive care unit owing to an allergic reaction. Then the group finally insisted that the surgeon complete his charting or be dismissed."

Other practices deal with late charting and similar issues by hitting doctors where it hurts—in their pocketbook. "Some practices have 'good citizenship' pools where each doctor deposits several thousand dollars per quarter," says Judy Aburmishan. "The rules may say that charts have to be turned in within 5 days. At the end of the year, the group splits the pool based on how doctors comply with various rules. Late charters are penalized financially."...

Many times, a disagreeable doctor is suffering from burnout and it shows in his work, says Dr Fischer-Wright. "These doctors are slightly disengaged, sometimes belligerent. They don't take good histories or encourage patient questions. Group leaders need to approach the doctor in a collegial way, saying such things as, 'We're a little concerned because you seem unhappy. Do you need some help? Do you need time off?' This gives the doctor some options, and he doesn't feel like he's being attacked."

If the problem remains unresolved, the next step might be a more formally documented conversation, in the presence of the practice administrator and senior partners. The group's leaders can outline an improvement plan, perhaps recommending or requiring anger management classes. "If that doesn't work," Hekman says, "the group has to be more serious, telling the doctor that he may need to take some time off to think about the issue and that he may ultimately be terminated if the behavior doesn't improve."...

Many times, someone who's distracted or disruptive may only be acting that way because he or she is having personal problems that you may be in a unique position to see and help address. So don't be quick to dismiss or otherwise penalize someone who's talented and an asset to the practice. Find out what's really going on. But if the bad behavior is unrelated to a particular situation that could be solved, or a disruptive physician doesn't shape up, patient safety and the integrity of the practice are more important than one physician's hurt feelings.

Friday, July 24, 2015

You’re not dead until you’re warm and dead

A 22-month-old toddler was revived after falling into a frigid creek near his home and undergoing 101 minutes of CPR -- a recovery that one doctor said may have been made possible by a type of "suspended animation."

Gardell Martin was pulled from a nearly frozen creek March 11 after going missing for approximately 20 minutes, said his mother, Rose Martin. The toddler had been playing outdoors with his older brother near their home in Mifflinburg, Pennsylvania, when he fell into the fast-moving water.
By the time a neighbor found Gardell, the boy was face-up in the water and was not responsive, his mother said.

Emergency crews started CPR, which continued as the boy was flown to Geisinger’s Janet Weis Children’s Hospital, where he was rushed to the critical care department, according to ABC News affiliate WNEP-TV in Scranton, Pennsylvania.
"A couple things were in his favor," Rose Martin told ABC News. "The cold water helped preserve his organs and his brain."

A hospital official confirmed that Gardell's body temperature was a frigid 77 degrees when he arrived for care. As CPR continued, doctors worked to warm the boy up and see if his heart could get started. After 101 minutes of continuous CPR, doctors found a tentative pulse.
“In my 23 years, I have not seen an hour-and-41-minutes comeback to this degree of neurological recovery,” said Dr. Frank Maffei, a pediatric critical care doctor at Geisinger Medical Center in Danville, Pennsylvania. "That doesn’t happen by accident. It happens because people are trained."
Dr. Alexandre Rotta, chief of pediatric critical care medicine at UH Rainbow Babies and Children's Hospital in Cleveland, said the case clearly demonstrates how, in rare cases, hypothermia can lead to a kind of "suspended animation" that can protect the body when the heart stops.
"Hypothermia has been known for years to slow down metabolism," said Rotta, who said at around 77 degrees a body needs only 30 percent of its normal oxygen intake, which can help preserve the organs...
"At 28 degrees Celsius [82 degrees Fahrenheit], [you] can safely arrest someone for 20 minutes," Rotta said. "There was a saying ... that you’re not dead until you’re warm and dead."...
However, Rotta said, these cases are extremely rare and he, himself, has seen only one case of a child coming back after being found in cold water in cardiac arrest.
"These cases are out there, but it requires tremendous [luck] your way," he said.
Gardell's mother told ABC News the family is just happy to have the toddler back at home and "pretty much back to normal" after his ordeal. She said his relatives feel his survival was "an act of God."
"I feel like we’re trying to get back to normal life and everyone is trying to get back to normal," said Martin. "He’s smothered with love. We can’t give him enough attention right now."

Dry and secondary drowning

When the weather gets hot kids and their parents flock to the water, beating the heat by splashing around in oceans, lakes and pools.

The last place parents want to be flocking to during the summer is the emergency room, yet every year dozens of children end up there for drowning. This particular drowning doesn't occur while swimming though. It happens hours after the child has left the water, CBS New York station WCBS reports.

Sports medicine specialist Dr. Lewis Maharam explains to WCBS it is a condition known as "dry drowning" and it is landing a lot of kids in the hospital hours after swimming in the pool. He said it takes just a few teaspoons of water to go down the wrong way and into the lungs that causes this condition.

"Dry drowning" happens when children playing around in the pool or lake accidentally inhale water. They may cough, but then they seem fine. But, sometimes, they are not fine.

"They had a normal day and then they go to bed and they're coughing or they're wheezing or their parents see bubbling from the mouth," Dr. Maharam explained.

Dr. Maharam said the lungs are irritated and start to secrete fluid -- and as a result children can actually drown in their body's own fluid.

WCBS spoke to parents at a Long Island pool and asked what they knew about the condition. One parent said she was shocked, and especially shocked it can occur nearly a day after leaving the water.

"This is why it's so important to get the word out," Dr. Maharam said.

The symptoms can include lethargy, irritability and trouble breathing.

Jim Hazen with the swim school Safe-T-Swim advises caregivers to go straight to the emergency room, not the pediatrician, after noticing a problem after their child has been in the water.
Hazen says most cases are treatable and preventable.

"The prevention is obviously adult supervision, number one, learn to swim, number two," Hazen said.
WCBS reports that research shows not all children are susceptible to "dry drowning." And while it can also happen in adults -- it's rare.

If you're like most parents, you probably figure once your child is done swimming or playing in the water, his risk of drowning is over. But "dry" and "secondary" drowning can happen hours after he's toweled off and moved on to other things. There are steps you can take to keep your child safe.
These types of drowning can happen when your child breathes water into his lungs. Sometimes that happens when he's struggling while swimming. But it can be a result of something as simple as getting water in his mouth or getting dunked.

It can happen to adults, but it's more common in kids because of their small size, says Raymond Pitetti, MD, associate medical director of the emergency department at Children's Hospital of Pittsburgh.
With dry drowning, water never reaches the lungs. Instead, breathing in water causes your child's vocal chords to spasm and close up after he's already left the pool, ocean, or lake. That shuts off his airways, making it hard to breathe.
Secondary drowning happens a little bit differently. Your child's airways open up, letting water into his lungs where it builds up, causing a condition called pulmonary edema. The end result is the same: trouble breathing.
Symptoms of dry drowning usually happen right after any incident in the water. Secondary drowning generally starts later, within 1-24 hours of the incident, Pitetti says.
Both events are very rare. They make up only 1%-2% of all drowning incidents, says James Orlowski, MD, chief of pediatrics at Florida Hospital Tampa.
Dry drowning and secondary drowning have the same symptoms. They include:
  • Coughing
  • Chest pain
  • Trouble breathing
  • Feeling extremely tired
Your child may also have changes in behavior such as such as irritability or a drop in energy levels, which could mean the brain isn't getting enough oxygen.
What to Do
If your child has any signs of dry drowning and secondary drowning, get medical help. Although in most cases the symptoms will go away on their own, it's important to get him checked out.
"The most likely course is that the symptoms are relatively mild and improve over time," says Mark Reiter, MD, president of the American Academy of Emergency Medicine.
Any problems that do develop are usually treatable if you get medical help right away. Your job is to keep a close eye on your child for the 24 hours after he or she has had any problems in the water.
If the symptoms don’t go away or get worse, take your child to the emergency room, not your pediatrician's office.
"Your child will need a chest X-ray, an IV, and be admitted for observation," Pitetti says. "That can't be done in an office."
Because there are no drugs for dry or secondary drowning, your child will probably get "supportive care" at the hospital. This means checking that his airways are clear and monitoring his oxygen level. If he's having severe trouble breathing, he may need to temporarily use a breathing tube.

Thursday, July 23, 2015

A new technique to indicate risk of SUDEP?

[S14.003] Transcutaneous pCO2 and Seizures in the Epilepsy Monitoring Unit: Associations with Markers of Seizure Severity

Derek J. Chong,1Palak S. Patel,1Alla Ahmed,1Nilofer M. Khan,2Bryan J. Still,3Evan Marzouk,4Daniel Friedman,1Orrin Devinsky1
1New York, NY, USA, 2Livingston, NJ, USA, 3Winston-Salem, NC, USA, 4Saratoga Springs, NY, USA.

Transcutaneous pCO2 (TCpCO2) may be an indicator of risk for Sudden Unexpected Death in Epilepsy (SUDEP).
SUDEP is the single largest direct epilepsy-related cause of death, and theories include central or obstructive apneas leading to hypoxemia and hypercapnia and cerebral shutdown. Studies have shown oxygen desaturation <70%, and increases in End-tidal CO2. TCpCO2 is a different technology, is less cumbersome, and its use during seizures has not yet been reported.
The Tosca500 (Radiometer America, Inc) was used in the epilepsy monitoring unit to continuously measure SaO2, heart rate and TCpCO2 in patients at high risk for cardiopulmonary distress during seizures and those undergoing intracranial EEG monitoring. We retrospectively reviewed data from 12 patients who underwent TCpCO2 recording. Seizure type, electro-clinical seizure duration, and the presence of post-ictal generalized electrographic suppression (PGES) were also assessed. PGES was defined as post-ictal EEG suppression <10uV, ending when 15/30 seconds of cerebral activity reached ≥10uV.
Peri-ictal TCpCO2 data were reliable in 15 seizures: 7 GTCs, 3 complex partial, 2 hemiclonic, 2 subclinical and 1 tonic seizure. The average peak increase in TCpCO2 was 8±7.3mmHg, with 7 seizures associated with a ≥20% elevation. TCpCO2 typically peaked several minutes after electrographic offset. Hemiclonic and GTC seizures were also associated with oxygen desaturations and tachycardia, and were left temporal in onset. PGES occurred in 2 GTCs. Seizure duration (p=0.009), seizure type (p=0.029) and PGES (p=0.02) were significantly correlated with ΔTCpCO2 (Spearman correlation). In multivariate analysis using these three variables, only PGES was significantly associated with ΔTCpCO2 (p=0.004).
TCpCO2 elevation was associated with PGES and may denote greater severity and duration of seizure activity. Further study and direct comparison with ETCO2 is required to better understand the cause of hypercapnea, and the potential of this novel modality in identifying SUDEP risks.
Category - Epilepsy and Clinical Neurophysiology (EEG): Co-Morbidities

Session: S14: Platform Session: Epilepsy/Clinical Neurophysiology (EEG): Clinical Epilepsy (3:15 PM-5:00 PM)
Date/Time: Tuesday, April 21, 2015 - 3:45 pm
AAN Annual Meeting 2015  Washington

Courtesy of:

See Respiration and SUDEP 5/18/15

Tuberous sclerosis tale

When I had just started my first real job after fellowship at St. Christopher's Hospital for Children in Philadelphia in 1984, I made my first visit to an outreach clinic at a nearby hospital. There I met an agitated and angry mother. Her until then perfect young son had experienced a seizure or two. She wanted her son to be seen by the finest pediatric neurologist, the eminence grise, Dr. Warren Grover. Unbeknownst to her, upon my arrival on the scene, I was substituted for Dr. Grover and she was to see a wet behind the ears pediatric neurologist just out of training. I indicated that I understood her plight and indicated that she could reschedule with Dr. Grover. "Are you board certified?" "Board eligible," I explained. She said, "Well, I'm here and you're here. We might as well go ahead." It was a great start. Her son had focal abnormalities on his EEG and he was started on carbamazepine. When cerebral imaging was done, it was clear that he had tuberous sclerosis. So I then needed to explain to this rather volatile and distrusting mother that her child had a diagnosis with multiple implications which he had a 50% chance of passing to his offspring, that there was a possibility that she or the father also had this disorder and that, if one of them did, there was a 50% likelihood of his siblings being affected. She and her son stayed with me until I left Philadelphia.

Wednesday, July 22, 2015

Shades of Questcor

Recently, Vertex received approval for a new two-drug therapy called Orkambi, designed to treat 8,500 cystic fibrosis patients over the age of 12 who have the most common mutation for this disease. Vertex has priced this drug at $259,000 per patient annually and, not surprisingly, many are outraged. As reported by the Boston Globe’s Robert Weisman, a group of prominent cystic fibrosis physicians are battling Vertex over the price.

“It’s egregious” said Paul M. Quinton, a professor at the University of California at San Diego who himself has cystic fibrosis. “This is more than five times the salary of an average American family. How can they in good conscience charge that much?”

In justifying the price of Orkambi, Vertex’s chief commercial officer, Stuart Arbuckle, cited four reasons: the small patient population, the clinical benefit of a drug combination that treats the underlying cause of the disease, the time and cost of Vertex’s efforts to bring the medicine to market, and the need to invest in new research to develop therapies to treat the remaining thousands of cystic fibrosis patients with other forms of cystic fibrosis. It should be pointed out that Vertex has been in business for 26 years and only turned a profit once in its history. Clearly, with Orkambi, Vertex is trying to make up some serious financial deficits.

Orkambi is a major breakthrough. Furthermore, it doesn’t come close to being the highest priced new drug. New breakthrough cancer drugs and drugs to treat rare diseases can be priced at almost double the cost of Orkambi. But the enormous publicity generated by the high cost of new drugs is skewing the public’s view of the impact of new drugs on the nation’s overall healthcare bill. This perception is certainly being seized on by payers anxious to drive down their drug costs, even when the costs of these drugs can be readily justified by the overall SAVINGS that breakthrough drugs can deliver thanks to reduced downstream costs and better health for patients in need.

Payers will undoubtedly focus on the fact that these same drugs will be cheaper in Europe, where the price of new drugs is set by negotiations between the innovative company and government regulators. In these negotiations, the country will set the price based on the VALUE it believes that the drug provides. Historically, the European agencies will support a high price for such a breakthrough like Orkambi , but usually the price will be significantly lower than that of the U.S.

This isn’t news to anyone – these practices have gone on for years. However, with the negative reputation of the biopharmaceutical industry and with the increased desire to bring the rising cost of healthcare under control, the public – and then the politicians – will seek to do this by evolving to the European system. The first measure likely to occur will be Congressional passage of legislation that would enable the U.S. secretary of health and human services to negotiate drug pricing. Then, much as happens in Europe, companies will need to justify the price they are seeking based on the value that this new drug brings. Companies already do this when negotiating prices, not just in Europe but also with insurers in the U.S. particularly when insurers have other therapeutic choices. The hepatitis C cure, Gilead’s Sovaldi, was famously launched at $1,000/pill, or $84,000 per patient treated. However, some months later when AbbVie launched its competitor, Viekira Pak, payers now were in position to negotiate with both companies. The result? Suddenly the price of these hepatitis C drugs dropped to European levels. That works when there are options, but that isn’t always the case.

To date, Congress has favored letting market forces set the price of new drugs. This works when there is competition. But when true breakthroughs occur, it can be years before a competitive therapy emerges. Thus, we have the current situation of higher prices in the U.S. It is hard to envision this remaining the status quo over the next five years.