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Vol. 90 May 15, 2013 Medical Marijuana and Other Designer Drugs

In current events, drugs, evidence-based medicine, Pediatrics on May 15, 2013 at 5:01 PM

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The implied expectation of the term “medical marijuana” is that a physician can write a prescription like any other prescription; one with a drug name, a precise dosage, a frequency, a mode of administration, and a quantity for a stated duration. For example, “Penicillin, 250 mg. tablets, take three times a day for 10 days”. Fat chance when it comes to a prescription for marijuana. There are over a hundred different types and strengths of marijuana (cannabis) and each marijuana product itself contains at least 460 active chemicals. The breeding efforts and expertise that has gone into producing “a better marijuana” is impressive. Anyone that protests “genetically engineered” tomatoes or oranges should not be smoking marijuana. Prescribing cannabinoids, a single active chemical often referred to as “synthetic marijuana”, in tablet or capsule form has been used as medical marijuana by oncology  and pain management centers for years.  ”It just ain’t the same” according to marijuana advocates, and some research suggests that with 460 active chemicals in marijuana they may be right.
medicalmarijuana

The Massachusetts Department of Health has just issued 52 pages of regulations for dispensing medical marijuana. They will require a prescription to have a maximum amount that is expected to be sufficient for 60 days, defined as 10 oz. Ten ounces is about 284 grams and a “blunt” is about 1 gram, so that would be about 4 “blunts” a day for 60 days. Prescriptions can be written for patients over 18 yrs. with a “debilitating medical condition” (7 are specifically named plus “others”) or a “life-limiting illnesses” (expected death in 2 years). Patients under 18 yr. may get a prescription for the same reasons as agreed to by two physicians, one of whom is a pediatrician. Independent labs will be responsible for testing the product for contamination, usually a variety of heavy metals. The strength of the dispensed product and the degree of its effects will be variable.

So, what is so bad about marijuana? Use of marijuana (MJ) can acutely slow reflex time, impair motor coordination, and alter perceptions, similar to alcohol. Of course, these functions are all important for safe driving. There are more permanent and potentially more significant effects of heavy use of marijuana in adolescents.

According to recent research MJ is really not so bad for you if you are over 20 years old. Using the new techniques of functional MRI (fMRI) by which brain function as well as structure can be measured, it has been shown that contrary to previous thought, the frontal lobe is still undergoing maturation up to the age of 20.  Maturation of the brain as measured by the increase of white matter, the “tissue of connections” between all the components of the brain, is retarded by heavy (daily) use of MJ, especially in “early users” (start at age 13). The old TV spot of “This is your brain, and this is your brain on drugs” using the frying egg image may be correct for MJ use by those under 20. Adolescents in general tend to be impulsive and have some difficulty in judging the long-term consequences of present actions, and these are functions of the frontal lobe.

Unlike tobacco use that can be measured easily  in terms of number of cigarettes smoked per day and alcohol use that can be measured in ounces drunk per day or per hour, the variety of MJ product’s strength is so diverse that “daily use” is the only reliable marker for heavy users of MJ. Unlike tobacco and alcohol, heavy use of marijuana can NOT kill you. Lester Grinspoon, MD years ago called marijuana “the safest drug in the world”  since it is impossible to commit suicide with it. It is rare to hear about an accidental “marijuana overdose”.

MJ-morphine cartoon

The three drugs of adolescent choice today, tobacco, alcohol, and marijuana, do share a common denominator in that those who use one of the three drugs by age 13, will use one or more of the others before 18 yr. There is no evidence that one is the “gateway” to another. In fact, one research remarked that the concept of a gateway is more of a myth than a reality. He called development of addiction to one or the other substance as a “shared vulnerability”.

By their senior year in high school 36% in one survey had tried MJ. There is no way of predicting which of those could eventually become heavy (daily) users in danger of suppressing their higher neuro-cognitive functions. It is not a question of access to MJ. Student users in a treatment program and researchers presenting at a recent conference made it clear that access to MJ in middle and high school was currently wide open.  In fact, remember that Dr. Grinspoon’s wife got marijuana for their son undergoing chemotherapy for cancer in his schoolyard in 1967! Medical marijuana dispensaries are NOT going to increase access to MJ for adolescents.

Spice is a vegetable product sprayed with synthetic marijuana, cannabinoids, that can be smoked or brewed as a tea. It is sold in convenience and incense stores with the label “not for human consumption” to avoid FDA regulations. The cannabinoids can have 50 to 100 more of an affinity for binding to marijuana sites in the brain than MJ itself. Its effects are similar to but can be much stronger than “smoking a joint”, and about 11% of high school seniors have tried “Spice”. Cannabinoids are easily manipulated synthetic chemicals so that simple chemical changes are made in manufacturing to skirt FDA regulations.

Bath Salts are completely useless for baths. It is a white crystal of chemicals (cathinones) that produce amphetamine effects when ingested, smoked, or snorted. Like Spice it carries the label “not for human consumption”. It was sold as an over the counter health supplement free of FDA regulations.  Both Spice and Bath Salts were first introduced in the U.K. and  Europe, and after much commercial success there they have come to the U.S. and Canada. Bath Salts were Federally banned in the U.S. in July 2012.

“Take home messages”:
1. Marijuana use before the age of 20 does have structural and functional effects on brain development, primarily but not limited to the frontal lobe. (“The frontal lobe, responsible for impulse control, is the last to develop and the first to go.”)

2. After the age of 20 there is little current evidence that MJ causes any permanent effect on brain function or structure.

3. There are  currently no predictors that will identify an occasional user of MJ as one who will become dependent or addicted to MJ (daily use), but the earlier one starts using marijuana (13 yo.) the more likely brain function will be effected.

4. Despite the “trustworthy karma” of medical marijuana, marijuana prescriptions will result in the dispensing of varied, complex, and inconsistent products.

5. Access to marijuana by middle and high school students in 2013 is now so easy according to both students and researchers  that medical marijuana dispensaries will provide little increased access to adolescents.

Resources:
1. The National Center on Addiction and Substance Abuse at Columbia University
2.ASAP, Adolescent Substance Abuse Program, Boston Children’s Hospital, Sharon Levy, MD MPH, Director

Vol. 89 May 1, 2013 Science, Personalities, and Politics of the Polio Vaccines

In evidence-based medicine, government, Infectious Disease, politics, vaccinations on May 2, 2013 at 10:35 PM

hub_2Dr. Hilary Koprowski, the creator of the live polio vaccine, died last month at age 96. What? I thought Dr. Albert Sabin developed that vaccine.

At a physicians’ educational meeting last month, Dr. Larry Pickering of the CDC and the University of Georgia recounted the headline-grabbing, fearsome, panic-causing polio epidemic of 1952-53 and gave us some insight into the sometimes dramatic duel between Dr. Sabin (with his oral live virus vaccine) and Dr. Salk (with his injectable killed vaccine) in everyone’s urgent efforts to stop the spread of the disease. I read Dr. Koprowski’s obituary the next week.

Dr. Koprowski was a Polish immigrant, earned his MD at the University of Warsaw, and helped develop a yellow fever vaccine with the Rockefeller Foundation. That success led him to the idea of using the same process to develop an attenuated live virus vaccine for polio. He was working for the Lederele pharmaceutical company in Pearl River, NJ at the time, and so was some times dismissed as a “commercial scientist”. He was described as a loner who was most comfortable in the lab, never sought public attention, but occasionally referred to himself as the “developer of the Sabin polio vaccine” .

Koprowski first tested the safety of the vaccine by having himself and his family sip a grey slurry of the seventh pass of the virus through the brains of Swiss albino mice in 1948 (1). When none of them got polio, he then tested its efficacy by administering it, at the facility’s request, to 20 retarded residents of Letchworth Village, NY  in 1950. All showed excellent development of antibodies against polio. Dr. Koprowski sent a sample of his vaccine to Dr. Albert Sabin.

Dr. Albert Sabin, also a Polish immigrant and a Rockefeller grantee, received his MD from New York University and developed his live virus vaccine from Dr. Koprowski’s sample using monkey kidney tissue at Cincinnati’s Children Hospital. After testing vaccine safety on himself and his family, he gave it to institutionalized children in a Ohio reformatory in 1954. All developed antibodies, and none got polio.

Meanwhile Dr. Jonas Salk, also a graduate of New York University School of Medicine, received a grant from the National Foundation for Infantile Paralysis to study the three types of polio virus at the University of Pittsburgh. The grant allowed Dr. Sabin to finally establish his own lab after several years of difficulty due to the traditional “academic jewish quotas” of the time. When he succeeded in developing a killed-virus vaccine, he successfully tested it in 1953 in 43 children at the D.T. Watson Home for retarded and feeble-minded children in Pittsburgh.

In 1938 Basil O’Conner, CEO of the National Foundation and a former law partner of Franklin D. Roosevelt (the most famous polio victim in the world), had started a fund-raising effort called the March of Dimes which in its first year literally inundated the White House with coins and letters. When Sabin’s vaccine proved efficacious in 1953 Basil O’Conner successfully urged the U.S. government to launch a field trial of his grantee’s vaccine. That “field trial” eventually distributed vaccine to 1.8 million children with the help of 20,000 physicians, 64,000 school personnel, and 220,000 other volunteers. (Now THAT’S a “field trial”.) The success of the trial was announced on April 12, 1955 in a Waldorf Astoria Hotel press conference and radio broadcast supported by a $250,000 grant from Eli Lilly and Company, and Salk became a superstar. Salk, himself, valued his privacy, abhorred the resulting publicity, and refused any effort to patent the vaccine.

Basil O’Connor was much more energetic in promoting the use of the Salk vaccine and a fearful public embraced it. An adversarial situation soon developed between Salk and Sabin as each pushed the government in Congressional committee hearings to use their vaccine. Sabin became “openly hostile to Salk” and would provide immediate “specific critiques of his presentations at scientific meetings”. Basil responded in the newspapers by saying in 1955, “Those who would prevent its [Salk vaccine] use must be prepared to be haunted for life by the crippled bodies of little children who could have been saved from paralysis had they been permitted to receive the Salk vaccine.”

The oral live virus vaccine was used to immunize over 100 million Russian children between 1955 and 1961, but it’s first U.S. trial was in 1961 on 180,000 school children in Cincinnati, Ohio. The live virus vaccine reproduces itself in the intestines of those vaccinated and spread of the attenuated virus from those vaccinated can protect others in the community. This was an advantage in endemic, poorly developed countries, but caused the U.S. to stop using the Sabin vaccine for fear of secondary spread.

The polio vaccine we give today is a 1988 refinement of an injectable killed-virus for all 3 types of polio and is 100% protective after three injections in the first year of life and a booster at 6 yrs.

All three physicians went on to develop or lead separate, stellar research organizations bearing their name and  continuing their superb work.

In 2007 Dr. Hilary Koprowski was awarded  the annual Albert B. Sabin Gold Medal given by the Sabin Vaccine Institute.

Relevance today?
1. Even in science, what you know is important, but WHO you know can be also.
2. Yesterdays “field trial” is today’s mass immunization campaign, and NOBODY tests drugs or vaccines, whether from mice brains or monkey kidneys, on themselves and their family members anymore!
3. The history of testing vaccines and drugs on impaired or incarcerated populations reminds us again of the necessity for “informed consent”.
4. As more academic institutions seek joint contracts with big pharma to replace reduced NIH support of research (MGH and Sanofi, AztraZenenca, etc.) accusations of being a “commercial scientist” seem moot.
5. Some immigrants can be very smart, focussed, and hard-working, and they can contribute immensely to our country’s health and wealth.
6. Science keeps gathering data and testing hypotheses, so we should not be surprised when its recommendations change.

References:  1. NY Times, April 21, 2013, pg.18

Vol. 88 April 15, 2013 How Do You Feed a Baby in a Patient-Centered World?

In computers and physicians, current events, evidence-based medicine, health care reform, medical jargon, patient-centered care, Pediatrics on April 14, 2013 at 7:50 PM

hub “Patient-centered medicine” is one of the new buzz words in health care reform. It is second only to “medical home”; the label for the multi-disciplinary team incentivized by governmental reimbursement to use electronic technology to provide the coordinated, individualized primary care that the family doctor used to provide by himself (yes, it was usually a “he” back then).

“Patient-centered medicine” champions joint decision-making between physician and patient. Most illustrative examples of patient-centered medicine given are high cost, high drama events like alternative cancer treatments, cardiac interventions, and even DNR or “keep plugging” choices. The central tenet is that the patient knows best his or her needs, desires, and feelings and medical decisions should consider those as paramount.

  • Pediatricians recommend breast feeding exclusively for at least 6 months, ideally for 12 months. (1)
  • Nearly half of mothers started solids at age 4 months to 6 months so the infant would sleep through the night and/or they would spend less on expensive formula. (2)

How might “patient-centered medicine” sound when it comes to “feeding baby”?
We pick up the conversation near the end of a routine well-baby visit:

PHYSICIAN SITS CLICKING ON A LAPTOP BACK TO BACK WITH THE PARENT WHO IS DIAPERING AND DRESSING HER INFANT ON THE EXAM TABLE.

PHYSICIAN: Leonard is 4 months old so he’s due for his second round of immunizations today. Before we give those, do you have any other questions?

PARENT: He’s not sleeping through the night. I want to start some solid food. Is there any food I should avoid?

PHYSICIAN: Are you still breast feeding?

PARENT: Well…sort of. I went back to work when he was 2 1/2 months old. He gets formula at daycare, and I breast feed him at bedtime.

PHYSICIAN SWIVELS AROUND ON STOOL TO FACE MOTHER.

PHYSICIAN: As I am sure you know, we recommend breast feeding for the first year.

PARENT: R-i-g-ht… well I had to go back to work. Doesn’t breast feeding make him plumper and more likely to be fat as he gets older?

PHYSICIAN: Breast feed babies sometimes look plumper than formula babies, but we think breast feeding actually protects them from adult obesity.

PARENT: Really? I heard on Fox News last month that breast feeding didn’t actually do that. (3)

PHYSICIAN: Yes, that was a recent single study done in Europe. The NY Times and Time magazine also carried it. (4)

PARENT: Emma certainly isn’t fat. I remember I breast fed her for close to a year because I wasn’t working at the time. You told me not to start her on solids until after 6 months.

PHYSICIAN: Just a second. Let me look up Emma’s record. …

PHYSICIAN SWIVELS AROUND ON STOOL TO TYPE ON THE LAPTOP.

PHYSICIAN: What’s her birthdate?…our new computerized medical record keeps records only as individual patients, not families. I can’t find Emma’s record.

PARENT She’s eleven now, from my first marriage, her last name is different.

PHYSICIAN: Ah, yes, here she is. …Looks like we were concerned about your family’s history of food allergies, so we cautioned you about not starting foods until she was over 6 months old.

PARENT: Emma is doing great without any allergies. I’d like to start solids on Leonard because he is so fussy at night and seems hungry when he wakes up.

PHYSICIAN: A new recommendation is to start potentially allergic foods earlier rather than later . Small portions of those foods started as early as 2 months of age may actually reduce future allergic reactions. (5)

BEEP…BEEP…BEEP

PARENT: What’s that?

PHYSICIAN SWIVELS AGAIN TO FACE PARENT.

PHYSICIAN: Oh, that’s just my laptop letting me know that this visit is reaching 95% of the usual duration of a well baby visit.

PARENT: So, I should breast feed Leonard for a whole year, but could have started solid foods two months ago? Most of my friends swear that giving food makes their babies sleep longer at night.

PHYSICIAN: Exclusive breast feeding for 6 months has lots of advantages for the infant. There is no evidence that giving solid foods makes the infant sleep longer at night, but there is probably no harm in starting him on cereal now.

PARENT: Any particular kind of cereal?

PHYSICIAN: A 1994 Swedish study showed that introducing wheat before 6 months of age caused a big spike in gluten allergies and celiac disease, but a recent one there showed that giving wheat to breast fed babies at 4 months actually decreased the later occurrence of celiac disease and gluten allergy.

PARENT: So, wheat cereal could be either good or bad at his age? This is very confusing.

PHYSICIAN: Science can be confusing. It often changes its mind as new data is gathered.

PARENT: When I switch to all formula is there any one that is best? Should I start with soy? When I switch to milk, should it be whole milk? … or 2%? … or 1%? What about peanuts?

BAHUGGA!…BAHUGGA!…BAHUGGA!

PARENT: What’s THAT?!

PHYSICIAN: That’s a notice for me that the average duration of a well baby visit has been exceeded by 20%. I really must go on to the next patient. Please go to our practice website where we answer those questions and provide several nutritional advice sites for further information.
Your baby is doing fine.  We’ll see you again in two months.

PHYSICIAN EXITS THE EXAM ROOM AND PARENT STICKS HER HEAD OUT INTO THE HALLWAY TO DIRECT ONE MORE QUESTION TO HER RETREATING BACK.

PARENT: Oh, doctor….do I need a password for the website?

References:
1. American Academy of Pediatrics, AAP.org
2. Journal of Pediatrics, March 30, 2013
3. Fox News March 13, 2013 reporting on JAMA article March 12, 2013
4. NY Times March 14, 2013
5. American Academy of Allergy, Asthma, & Immunology, January 2013