USPSTF Breast Cancer Epidemiology Nonsense, Part 3

Yesterday Health and Human Services Director, Kathleen Sebelius, tried to do some damage control in regard to the the public response to the new United States Preventive Services Task Force guidelines regarding screening mammography. She said to women "keep doing what you've been doing for years" and indicated that the task force " does not set federal policy and they don't determine what services are covered by the federal government".

One of the task force members, Dr. Timothy Wilt, indicated that he stuck by the new recommendations.

I don't have anything new to say about this. I am just providing updates for those who are following this issue.

Thought for the day

Keep it simple.

USPSTF Breast Cancer Epidemiology Nonsense Part 2

Yesterday I briefly discussed the new breast cancer screening guidelines published by the United States Preventive Services Task Force (USPSTF). The USPSTF is not a government agency but is funded by the federal government and operates under a congressional mandate. The highlights and controversial aspects of the recommendations are:

Against self breast examination

Uncertainty about whether a doctor's clinical breast exam does more harm than good

and the main one- recommendations against routine mammography screening for women age 39-49

Both the American Cancer Society and the American College of Obstetrics and Gynecology have written responses challenging these new guidelines. Why the challenge? The USPSTF report indicates that screening mammography for women in their forties does more harm than good. The report indicates that 1339 women in their 50's need to be screened to save one life and that 1904 women in their 40's need to be screened to save one life. With 22,327,592 women age 40-49 in the United States as of July 1, 2008 the difference between 1339 and 1904 seems pretty small to me. 17% of all breast cancer deaths each year are in women diagnosed in their 40's. Over 45,000 deaths from breast cancer occur in women age 40-49 over a 10 year time span.

The USPSTF report acknowledges that the benefits of screening mammography for women in their forties are the same as for those in their 50's with a mortality risk of 0.85 from 39-49 and 0.86 for women in their 50's. But because of the total smaller number of diagnoses in the 40-49 age range and more false positives the USPSTF believes that due to "anxiety, distress and other psychosocial effects" the risks outweigh the benefits. I believe that the anxiety and distress caused by learning of a breast cancer that could have been diagnosed earlier far outweighs the anxiety of a false positive mammogram. The only psychosocial benefit in not screening women in their 40's is cost reduction.

I would welcome any thoughts or comments on this issue.

Thought for the day

One day at a time.

USPSTF Breast Cancer Epidemiology Nonsense

The United States Preventive Services Task Force (UPSTF) has published new breast cancer screening guidelines in the Annals of Internal Medicine. The USPSTF is not a government agency. It is an independent body financially supported by the Agency for Healthcare Research and Quality which is a federal agency. The new guidelines are a bit surprising and I am sure will generate a lot of controversy.

The new guideline recommendations are:

Against teaching breast self examination.

Against routine mammography screening for women age 40-49.

Women age 50-75 years old should have biannual rather than annual screening mammography.

Insufficient evidence to determine the benefits and harms for clinical breast exams

Insufficient evidence to determine the benefits and harms of screening mammography after age 75.

Insufficient evidence to determine the benefits and harms of digital mammography or MRI vs film mammography screening

How did they come up with this? This was determined after a meta analysis of all studies that were identified through the Cochrane Register of Controlled Trials, the Cochrane Database of Systematic Reviews, a MEDLINE search from January 2001 to December 2008, Web of Science searches, and the Breast Cancer Surveillance Consortium for screening mammography. The problem with such meta analysis studies is that they often miss the trees for the forests. They compile statistical data but do not take into account the great individual and even group differences that can be widely different and need different recommendations. The guidelines are made for everyone and that is how we end up with what I call epidemiological nonsense.

Women -don't do self breast examinations? Doctors - don't do clinical breast exams? It may do more harm than good? Don't do mammography screening for women ages 39-49 even though this analysis even shows that mammography screening in this age range results in a 15 % decrease in breast cancer mortality rates? This is nonsense . Our faith in and dependence upon large scale meta analyses has led to absurdities such as these USPSTF guidelines. These guidelines are not just absurd, they are dangerous. Women will be confused about what they should do and because of this confusion women will die who would not otherwise. These guidelines will encourage insurance companies to deny payment for mammograms until age 50. At least women can appeal these denials. Under a government run health care system there would be no recourse.

I am interested to see what other health organizations including the American Cancer Society will have to say.

Thought for the day

" Cast your anxieties upon the Lord as He cares for you"

St. Peter

.

Prenatal Tobacco Exposure Neurodevelopmental

We have known for some time that tobacco use during pregnancy is not a good idea. One of the consistent findings has been the association with tobacco use and low birth weights. Low birth weights are a nonspecific factor that correlates with fetal growth retardation which can occur from a variety of different factors. Tobacco use is one of those. Three studies recently presented at the 56th annual meeting of the American Academy of Child and Adolescent Psychiatry suggest longer term neurodevelopmental problems.

These three studies are all prospective studies. These were not chart reviews looking for correlating factors but involved looking directly at children and their behavior. The first study enrolled 304 women before their fourth month of pregnancy. Self reports were used to assess smoking during pregnancy. The investigators examined the newborn children 1-3 days after birth and at weeks 2 and 4 looking at reflex assessments, orientation to audio and visual stimuli and response to stressors. The infants of mother's who smoked were less attentive and exhibited consistently more irritability. This is consistent with previous findings that suggest some tobacco withdrawal symptoms do occur.

The second study involved 207 infants from the first study evaluated at 6 months of age. The infants exposed to tobacco prenatally showed lower attention spans than non exposed infants.

A third study evaluated self regulation and executive control in a different population of 237 otherwise normally developing three year olds. Those exposed to tobacco prenatally showed poorer ability to wait for a reward and to regulate motor behavior. While Attention Deficit Hyperactivity Disorder (ADHD) is not diagnosed in preschoolers these findings are similar to the problems that do show up in children with ADHD. The study is ongoing and will follow these children on an ongoing basis.

These three studies suggest that smoking during pregnancy is related to attention and self regulatory problems at multiple points of development. Given that about 20% of expectant mothers smoke a large number of children are affected. Tobacco cessation is difficult but perhaps these findings may increase the motivation to quit in women who smoke during pregnancy.

Thought for the day

Tobacco use during pregnancy is simply not a good idea.

Pregnancy Anxiety Depression SSRI's

There has been a great deal of uncertainty in the last several years about the risks of the selective serotonin reuptake inhibitors (SSRI's) in pregnancy. These medications which include Prozac, Zoloft, Paxil, Celexa, Luvox, and Lexapro are used to treat both depression and anxiety disorders. All of them are considered Category C medications which mean there are not adequate well controlled studies in women to answer the question of safety to the developing child, that caution is advised, and that the benefits of the medication may outweigh the potential risks of not using the medication. As you can see this guideline is extremely vague and doesn't really help the clinician in knowing what to do with a pregnant woman with depression or an anxiety disorder.

There are several areas of concerns for a pregnant woman. First, does the medication cause any congenital malformations? Secondly does the medication increase the risks of low birth weight or preterm delivery? Are there ill effects on the newborn such as lower Apgar scores, withdrawal symptoms, or increased need for Neonatal Intensive Care (NICU) services and finally what is the effect on the developing brain of the fetus when medications are used during pregnancy and how might that affect the cognitive and emotional development of the child? These are a lot of questions and we don't have clear answers. I will leave aide the issue of nursing for now.

What is known at this time is that SSRI's put infants at risk of low preterm birth, lower 5 minute Apgar scores and increased risk of admission to the NICU. Paxil has been associated with a slightly higher risk of congenital abnormalities than in the general population. A number of infants will develop some withdrawal symptoms of increased irritability and poor muscle tone, seizures and respiratory problems. On the other hand untreated depression is linked to preterm birth, lower birth weights, and lower Apgar scores indicating that untreated depression has an adverse effect on the developing fetus as well. Pregnant women with untreated depression ate also at significantly higher risk of alcohol use and abuse (which clearly causes fetal problems) and failure to receive adequate prenatal care. In all the studies it has also been unclear whether the adverse effects are due to the SSRI's themselves or that the SSRI use is not simply linked to women who experience significant depression who develop more problems.

A recent study published in the November issue of Paeditaric and Perinatal Epidemiology does give us some new information about untreated anxiety in pregnancy. 763 women were assessed and followed during the course of pregnancy which indicated that mild or moderate anxiety is not associated with any adverse fetal effects but that high levels of anxiety were associated with smaller birth weights and risk of preterm delivery. This does not necessarily help us with the medication issue though. It does tell us that anxiety needs to be assessed and addressed in pregnancy but there are non medication means of reducing anxiety.

So, little by little we are gaining more knowledge but for now the clinician and soon to be mother have to decide in each individual case whether it is better to continue ore use antidepressant medication during pregnancy.

Thought for the day

There are not always easy answers in medicine.

Health Care Reform HR 3962

The views expressed in this blog are my own personal opinions and do not represent the views of Cottonwood nor it's administration.

As everyone knows by now HR 3962, the health care reform bill, passed in the House of Representatives by a vote of 220-215. Our own representative in Congress, Gabrielle Giffords, voted in favor of the bill. I have previously outlined my concerns about this version of health care reform, indicating that it goes beyond health care reform and is essentially a government takeover of the entire health care system. I don't have anything new to say except that while the initial version HR 3200 was 1300 pages long HR 3962 is 1900. I will next comment on this issue after the final version is complete after coordination and merger with the Senate version which we have yet to see.

There is a lot that will be said by many on this bill that is based upon rumor.. I won't comment on it until I have read the final version in it's entirety just as I did HR 3200 so it will be awhile. I read the previous version while my wife was out of town and I had plenty of time on my hands!

Thought for the day

Give thanks to the Lord for He is good. His mercy endures forever.

Human Genome Project NIH Watson

I left out this post by mistake and it should have come before today's,

The Human Genome Project is the most important scientific advancement that we have made in this century. It was a huge undertaking sponsored by the US Department of Energy, the National Institute of Health(NIH) with involvement of a number of other countries as well Incredibly by 2003 all the genes in human DNA were identified as well as the sequence of the 3 billion chemical base pairs that make up human DNA.This has enormous implications in a wide variety of areas but in medicine it has allowed examination of specific genes that may be involved in a number of diseases, including psychiatric disorders. One of the goals of the project was to address the ethical, legal, and social issues that arise from this project. It didn't tale long for controversy to emerge


J.Venter, a biologist at NIH, began the process of requesting patents. He had not sequenced whole genes but rather fragments of DNA referred to as EST (Expressed Sequence Tags). I have tried to understand what exactly is an EST but it is way over my head. By the early 90's he had requested over 7,000 patents for different EST's. In effect he was trying with NIH to basically patent the human gene which would be a disaster for science. James Watson opposed this policy and had to resign as Director of the project as NIH was planning on continuing the patenting process. The controversy eventually was resolved when the US Patent Office rejected all the applications.


So as much as there is present controversy regarding James Watson he did lose the chance to complete The Human Genome Project by standing up for scientific principles over profit.



Thought for the day

Sometimes it is hard to do the right thing.

James Watson Eugenics Cold Spring Harbor Lab

This is the last of a series of postings in regard to James Watson who along with Francis Crick and Maurice Wilkins won a Nobel prize in 1962 for their work in 1953 in determining the chemical structure of DNA. Watson has been a controversial figure because of statements he has made over the years that seem to indicate his continuing interest in eugenics. Eugenics is the attempt to improve mankind and enhance human development by weeding out problematic genes and enhancing those that are associated with better physical and mental health. Eugenics is nothing new but the ethical dilemmas are much increased now that the entire human genome has been sequenced.

Eugenics was the movement in the early 1900's that increased in influence until 1940 when it essentially went underground. The idea of a "master race" did not originate with Adolf Hitler. He used already prevalent eugenics ideas to justify his extermination of the Jews. The heart of the eugenics movement was not Nazi Germany however. It was the United States and it's intellectual center was Cold Spring Harbor Laboratory in New York. It was there that eugenics "research " was begun and it was there where there was a eugenics register kept. The ideas of those believing in eugenics were widely adopted here in the 1930's and resulted in the mass involuntary sterilization of thousands of the mentally ill and developmentally disabled.

Although the Cold Spring Harbor Laboratory changed it's major focus to cancer research, for years it was headed by James Watson who was the Director, later the President, and then the Chancellor of the research center.. Watson has made no secret about his eugenics ideas and leanings and the fact that he directed Cold Spring Harbor Laboratory for many years is disturbing. He was only forced into retirement in 2007 when a statement he made to the effect that Africans were not as intelligent as whites became widely publicized.

Watson is not alone among genetic researchers in thinking that the new genetic knowledge we have can be put to use to improve the human race. While hopefully there will be many positive benefits to us all from the new genetics I want to say that the eugenics movement is not dead and we must all keep vigilance to make sure that the ideas of weeding out the weak or ethnic groups is not repeated.

Thought for the day

One mark of a society is how it treats it's weakest members.

The Double Helix Watson DNA Part 3

Since I have already recommended The Double Helix by James Watson I will not discuss anymore the bock except for a few brief points. I then want to move into two different scientific controversies in which Watson has subsequently been involved.

Watson and Crick received a Nobel prize in 1962 for their work on DNA. What I did not know was that another researcher, Maurice Wilkins, at a different laboratory shared the Nobel prize along with Watson and Crick as they used a lot of his data on X ray crystallography in their own work. The interesting thing to me was that Rosalind Franklin who worked with Wilkins and did much of the crystallography work herself and whose x ray picture of DNA was used (some say stolen) as the final piece of evidence that Watson and Crick needed to develop their model did not share the Nobel. Four researchers and three prizes. The woman was left out. I hope we have come along way since 1962. Watson did in his book credit her. She died before the Nobels were awarded so never knew she was excluded.

In 1988 Watson became Director of the National Institute of Health (NIH) project on the human genome, an ambitious project to sequence the entire human genome. NIH had several goals. They wanted to identify all the approimately 20,00-25,000 genes in DNA, determine the sequencing of the 3 billion base pairs that make up human DNA, store the information in data bases, improve tools for data analyses, transfer technologies to the private sector and address the ethical, legal, and social issues that could arise from such a project. Amazingly the identification of all the human genes and determination of all the base pairs crompising DNA was accoilplished in 2003. Watson resigned in 1992, howsever and was not there to see the project to completion. I will discuss that in another post.

Thought for the day

"Utter not a word by which anyone could be wounded"

Ancient Hindu saying

The Double Helix DNA Watson Part 2

Yesterday I recommended the book The Double Helix by James Watson, his own first person account of the events leading up to the determination of the chemical structure of DNA. It is a short fascinating and actually suspenseful read that I thin anyone interested in science would enjoy. As I mentioned before I am extremely awed by all the orchestrations that must take place at the biochemical and molecular levels to sustain life and for some reason more awed than by contemplating the stars.

I have never been proficient in biochemistry. I love to read about it and have learned a lot but never was very good at it. I failed to pass biochemistry in two different attempts as an undergraduate. I dropped the courses before the drop deadlines so my grades were not affected but I know I would not have done well if I continued. In medical school I had to take it again and it was the only course that I came near to failing. At that time we had a large class at the University of Tennessee and no one would be allowed to continue to progress if one did not get at least a C grade in the course. If I failed this time I would have had to wait to join the next year class of medical students and take biochemistry again. Needless to say I sweated this one out and barely received my C grade, the only one I had in school.

What is comforting for me to know and is well described in The Double Helix is that James Watson though having a Ph.D in biology never was able to pass organic chemistry. He was co-discoverer of what may be the most important organic chemical molecular structure undelrying all of life but he couldn't pass his course. The difference is that he was a genius and having initially no interest in chemistry taught himself by reading The Nature of the Chemical Bond by Linus Pauling. I don't think it spoils the book (since we know the outcome) but Linus Pauling was studying DNA at the same time as Watson and Crick!

The only negative thing about The Double Helix is the intial descriptions of another DNA reasercher Rosalind Franklin who died before this book was written.

Thought for the day

It is never too late to teach an old dog new tricks.

The Double Helix DNA Watson

I finished rereading The Double Helix by James Watson this weekend. Watson along with Francis Crick first determined the chemical structure of DNA which has revolutionized the field of biology. While many people are awed by looking at the stars and contemplating the size of the universe I seem to be awed more by contemplating the very small but extremely complicated molecular interactions that sustain life. To me this area is very fascinating and strengthens my belief in a creator the same way that many find in astronomy.

I had just read The Astonishing Hypotheses: The Scientific Search for the Soul by Francis Crick. Crick was a reductionist and saw ourselves as just molecular interactions and nothing more. The book is from the 90's and since that time there has been a great deal more work on trying to understand awareness and consciousness. The subtitle is rather misleading as most of the book demonstrates the extensive knowledge that Crick had developed regarding the visual system and computer neural network models but it is a good read nonetheless. From there I was wanting to know more about the work that he and Watson did regarding DNA so I googled and found a copy of their original paper that was published in the journal Nature in 1953. It is amazing that this paper is only one page long. I never would have imagined this. They did follow-up with the implications of their findings in the very next issue of Nature but again this was a very short article.

There have been other books written on the early work on DNA but The Double Helix is particularly interesting as it is a first person account. This of course leads to potential for significant bias about these events but it is well written and actually quite suspenseful. It is a short book and I highly recommend it. I will discuss this further tomorrow.

Thought for the day.

It just seems incredible to me that the most far reaching discovery in biology and biochemistry was initially described in just one page.