Friday 25 February 2011

OUT OF THE FDA

The following is copied from news released yesterday and it could well be a stepping stone for our long awaited apology for the DES tragedy from the US FDA:
(www.scottbrown.senate.gov/public/index.cfm/2011/2/kerry-brown-fda-finally-recognizes-prescription-drug-tragedy)

Feb 24 2011
Kerry, Brown:FDA Finally Recognizes Prescription Drug Tragedy

BOSTON - Forty years after doctors at Massachusetts General Hospital first discovered a link between the drug Diethylstilbestrol (DES) and a rare form of cancer, the FDA has sent a letter to Senators John Kerry and Scott Brown acknowledging that the widespread prescription of DES was a tragedy with devastating health consequences. The letter also outlines FDA's new initiatives to prevent similar drug disasters in the future. This letter comes in response to a letter the Senators sent to the FDA Commisioner Margaret Ann Hamburg last October on behalf of constituents affected by DES.

"The FDA is the first of defense for patients nationwide who need to know the medicines they use are safe, and it's important that today they've recognized the heartbreaking consequences that DES had for millions of people over the thirty years it was deemed safe."

"The FDA's acknowledgement of the devastating impact DES has had on patients across the country is long overdue, and I am pleased to hear of their admission, "said Sen. Brown.

Diethylstilbestrol (DES) was a synthetic estrogen that was developed to supplement a woman's natural estrogen production. Originally prescribed by physicians in 1938 for women who experienced miscarriages or premature deliveries, DES was considered safe and effective for both mother and developing baby until the New England Journal of Medicine published a report in 1971 suggesting a link between DES use by pregnant women and a rare vaginal cancer in female offspring.

The Food and Drug Administration (FDA) subsequently issued a Drug Bulletin to physicians advising them to discontinue prescribing DES in pregnant women. According to the Centers for Disease control (CDC), approximately 5-10 million persons were exposed to DES between 1938-1971, including pregnant women and the children born from those pregnancies.

More news: The Boston Globe in a following article, mentions the request for an apology with "DES and birth defects; FDA acknowledges 'tragedy'from 40 years ago". Find this at http://www.boston.com/lifestyle/health/blog/dailydose/2011/02/des_and_birth_d.html

Feel free to register to make comments on this Boston Globe article!

Out of Boston - a 40th Anniversary

On February 18, 2011, WCVB-TV Boston's newsmagazine Chronicle interviewed longtime DES activist/DES historian Andrea Goldstein, DES Daughter and Wonder Drug screenwriter Caitlin McCarthy, and DES researcher Dr. Julie Palmer for its segment on DES (diethylstilbestrol). DES is a toxic and carcinogenic synthetic estrogen that was prescribed to millions of pregnant women for decades because drug companies claimed it prevented miscarriages and problem pregnancies, even though no controlled studies were ever conducted to determine the effectiveness or safety of DES for use in pregnancy. As early as 1938, studies showed that DES promoted cancer in lab animals, and as early as 1953, research revealed DES did not work - that DES actually brought about higher rates of premature birth and infant mortality - yet DES continued to be prescribed to pregnant women for decades because the drug was a top moneymaker for drug companies. Doctors at Boston's Massachusetts General Hospital discovered the DES cancer link and published their findings in the April 1971 issue of New England Journal of Medicine . However, the FDA did not issue a *warning* about DES until November 1971; the FDA *did not ban* DES for human use. DES was contraindicated for pregnancy by the FDA in 1972. 2011 marks the 40th anniversary of the DES cancer link being made.

See the WCVB-TV Boston segment about DES:

www.thebostonchannel.com/r-video/26938692/detail.html

Wednesday 9 February 2011

Forced Adoption Victims and DES

DES Action Australia-NSW has made submissions to the Australian Senate Inquiry "Commonwealth contribution to former forced adoption policies and practices".

These can be found on Google Search "Australian Senate Inquiries", click on "Current Inquiries", click on "Commonwealth contribution to former forced adoption policies and practices", click on "Submissions received".
Click on No:21, followed by Supplementary Submission.

DES Action Australia-NSW has received numerous phone calls from women who were forced adoption victims and given DES as lactation suppressant (to stop breast milk). They report DES being given without informed consent and sometimes as excessive doses. There is an anecdotal report of extraordinarily high (80%) incidence of breast, cervical and ovarian cancers in a survey of forced adoption victims by the group, Origins NSW. Another survey by Care Leavers Australia Network (CLAN), a support organisation for former State Wards, shows 41% incidence of teenage pregnancy.

In view of the above information, the submissions by DES Action Australia-NSW urge that there be research on possible effects of DES usage as lactation suppressant.

News update:On 29/4/11 DES Action Australia-NSW made representation as witness before the Senate Committee for this Inquiry. The Committee conveyed intention of investigating the matter of researching this usage as lactation suppressant and commented that they had "homework"to do on this. A suggestion was flagged about the merits of bringing all involved groups together to gather information about possible long-term effects of DES as lactation suppressant.
The witness transcript is available for viewing by clicking the link for Sydney Location (29/4/11) at:
Some media response:
UPDATE 15/3/12
In February the Senate Committee released the Inquiry's Report, recommending that Australian Governments must apologise to the mothers and children who suffered because of forced adoption practices. Whilst this is pleasing, the Report has ignored the issue of excessive DES dosages given (reported by doctor witness in NSW Inquiry "Releasing the Past", 2000). Similar to "Releasing the Past", this report has failed to mention that to date there has been no research conducted on possible health effects of DES usage as a lactation suppressant. There is no mention of any of the concerns raised in the Submission by DES Action Australia-NSW.
UPDATE 11/4/12
The following concerns about the Inquiry Report have been forwarded to the office of Senator Sue Boyce (Inquiry committee member):
  • its failure to mention instances where DES was administered sometimes in excessive doses (as was acknowledged by a witness doctor in the NSW Inquiry "Releasng the Past", 2000)
  • its failure to mention the health concerns by forced adoption victims in relation to DES usage and their observation of frequent reports of cancer incidence
  • its failure to mention that there is no existent research in relation to possible effects with the usage of DES as lactation suppressant
  • its failure to mention that babies of forced adoption victims would have ingested DES in breast milk when breastfed by other women patients with abundant breast milk who were receiving DES as lactation suppressant
  • its failure to give indication of further consultation with forced adoption groups or any further investigation on the matter of this DES usage.
UPDATE 22/8/12
Senator Boyce's office suggested that representation of these matters be made on the National Apology Reference Committee.
The following was relayed to us by Senator Boyce's office yesterday:
DES Action Australia-NSW is NOT included in the National Forced Adoption Apology Reference Group and this has been the decision of Attorney General Nicola Roxon.

UPDATE 21/2/13
A few years ago DES Action Australia-NSW requested copy of Origins group health survey that was submitted to the NSW Inquiry "Releasing the Past", 2000. The reason for this request was cited that a copy was not made by Origins when submitting this document.  The request was unsuccessful because NSW Parliament deemed this document as "not for public". The Origins group recently requested copy of this submission and were informed that this document has been lost.

Our Right to be Informed about DES

DES Action Australia-NSW is constantly asked by people: Why haven't we been told about DES?
The suffering and anxiety as a result of not being told about DES is clear to us.

So we now ask: What about the right of Australians to be informed of the possibility of having been DES exposed?

DES Action Australia-NSW has recently sent the following correspondence to the Australian Human Rights Commissioner (attachments not included here):

Dear Commissioner Branson

I am coordinator of the organisation, DES Action Australia-NSW, a support group for Australians who have been exposed to the harmful carcinogenic, anti-miscarriage drug, DES (diethylstilboestrol), which was prescribed to pregnant women from 1938-1971 (and sometimes beyond). I am writing to you due to our organisation's concern for the right of Australians to be directly informed of the possibility of having been exposed to DES. From Australian data, our organisation is able to estimate there are up to 740,000 Australians exposed to DES (DES mothers, daughters and sons).

To assist you, here is some background information about DES:
Diethylstilboestrol (DES or commonly known as "stilboestrol") is a synthetic oestrogen that was developed to supplement a woman's natural oestrogen production. It was first prescribed in 1938 for women experiencing miscarriages or premature deliveries and originally considered effective and safe. DES was available in the form of tablets, injections, vaginal suppositories (also called pessaries) and sometimes as an ingredient in pregnancy vitamins. In 1971 physicians were advised to stop prescribing DES to pregnant women because it was linked to a rare vaginal/cervical cancer in female offspring. Since 1971 research has shown:
-women prescribed DES while pregnant, known as DES mothers, are at 30% increased risk for breast cancer and require annual mammography and clinical breast examinations.
-Women exposed to DES before birth (in the womb), known as DES daughters, are at increased risk for clear cell adenocarcinoma (CCA) of the vagina and cervix, have almost two times increased risk of breast cancer after age 40, reproductive tract structural differences, pregnancy complications and infertility. The risk for developing CCA is about 1:1,000 DES daughters. Although DES daughters appear to be at highest risk for clear cell cancer in their teens and early 20s, cases have been reported in the 30-50 age groups [http://obgyn.bsd.uchicago.edu/registry.html#accessions]. This cancer is aggressive; it can be symptomless and is not always detected by the usual Pap smear. It should be detected early. DES daughters require life-long special annual "DES examinations", along with annual mammography and clinical breast examination. DES daughters also require high-risk care during pregnancy.
-Men exposed to DES before birth (in the womb), known as DES sons, are at risk for non-cancerous epididymal cysts (cysts behind the testicles).

Researchers are still following the health of the DES exposed population to determine whether other health problems occur with age and whether subsequent generations are affected. There is recent research showing menstruation irregularity in DES granddaughters, which hints the possibility of increased risk of infertility. There may be many people who do not know whether they were exposed to DES and some women may not remember taking DES. DES information is important because people who were exposed must be vigilant about their own health care - to detect cancers early, demand high obstetric care when pregnant and factor in their exposure when making decisions about HRT use. It is as much part of a person's medical history as a family history toward heart disease or diabetes.

The Adverse Drug Unit of the Therapeutic Goods Administration (TGA) has data of 18 case reports of DES associated cancer. The failure to report cases has been acknowledged, thus rendering the TGA's database unreliable. There has also been refusal by the TGA to complete regular reciprocal cross-checks of Australian cases that have been reported to the International DES Registry, held in Chicago, USA.

Prior to the DES problem, the cancer type linked to DES was rare and typically occurred in post-menopausal women. Using data held by the Australian Institute of Health and Welfare (AIHW) and State Cancer registries before 1982, our organisation has been able to estimate that up to 2010 there are up to 740,000 DES exposed mothers, daughters and sons in Australia. From AIHW data, our organisation estimates there have been 8 deaths due to DES exposure. There is no upper age limit for the development of DES-type cancer, with cases now occurring in DES daughters in the 40s and 50s age group.

In 2004 the TGA issued a media release about DES, gaining nation-wide media attention. However, this media release contained information mistakenly stating that the increased cancer risks for DES daughters had now passed and that DES daughters no longer require their special annual "DES examination" for their life-saving cancer prevention. In lobbying government, the organisation DES Action Australia-NSW eventually required legal assistance to ensure that a media release with correct information was issued by the TGA. In 2008 the TGA issued a further media release with information that DES daughters require life-long follow-up with annual DES examinations. Unfortunately, this 2008 media release did not receive nation-wide media attention.

Due to the time lapse, doctors are unable to track down Australians exposed to DES. It cannot be presumed that doctors have already alerted affected patients about their DES exposure. There has been no public health education campaign by any Australian government to help alert the many DES exposed Australians who are still oblivious to the fact of their exposure, unaware of the harmful effects of DES, and unaware of the special health care they require, including their special vital cancer preventive health care. The public's response to DES Action Australia-NSW following intermittent media attention to DES exposure over the years shows that the health of DES exposed victims has been neglected due to the absence of prominent public information about DES - information which would have prompted earlier access to their rightful health care. Since the 1990s the Australian government has continued to advise DES Action Australia-NSW that raising public awareness of DES could create unnecessary anxieties for women who may not know if they have been exposed to DES. The Therapeutic Goods Administration has no capacity to monitor medicines that are no longer available for supply in Australia. This includes DES, even though it has been proven a dangerous drug with serious ongoing adverse effects. It is stated that in Australia, no single body has the responsibility for providing advice about the risks of medicines after their withdrawal from supply.

In 2001 the USA Centers for Disease Control (CDC) launched the first national public education campaign to educate the US public and physicians about DES (www.cdc.gov/des). It is estimated that in USA there are 5-10 million DES exposed people. The US campaign launch included an extensive media campaign across USA. Australian government information about DES is buried in websites, significantly decreasing the chance that the population would become aware in the first instance that there is any health problem associated with DES. It is the opinion of DES Action Australia-NSW that it is the right of Australians to be informed of the possibility of having been exposed to this dangerous drug. Accordingly, lobbying efforts over the past 5 years have been directed to the Australian government towards ensuring the promotion of information about DES exposure directly to the public in health programs. The situation remains that many people are suffering the effects of DES exposure, without knowing why and what they can do about it.
In view of the harmful effects experienced (including cancer) by many unknowing victims of DES exposure, it seems to our members, that there has been a breach of human rights by successive governments since the early 1970s, through their failure to appropriately inform the Australian public about DES exposure, when it is reasonable and facilities exist to do so. The nature of this matter would be hypothetically akin to successive governments failing to keep the Australian public alert and informed about the dangers of asbestos. When our organisation has made enquiries to Australian legal authorities on this matter, we are advised that DES exposed victims have no standing legally with the government on this matter. As a suggestion, Australian legal authorities advise that the only recourse is to approach Australian media. Our experience is that this advice is mostly ineffective, since the Australian media is not always interested in the DES subject.

Upon perusal of the International Covenant on Civil and Political Rights (ICCPR), I have found Article 19, pertaining to the right of freedom to receive information. However, I also note that this article carries special duties and responsibilities and may have restrictions by law. In USA, legislation has been necessary to ensure that the needs of the US DES exposed population are addressed. In 1978 there was legislature in New York State for a public education campaign and the identification of clinics to provide "DES examinations" for DES daughters unable to pay. (http://www.nejm.org/doi/full/10.1056/NEJM198101013040111) In 1979 a bill was passed in California State, which mandated the Department of Health Services to train doctors and nurses, designate DES screening centres and produce a public education campaign. (See attachments: Bill1, bill2, bill3 pdf) In 1985 the US President Ronald Reagan issued proclamation of National DES Awareness Week. (See attachment: USProclamation pdf) In 1992 US Federal Congress passed a DES Education and Research bill which allowed the aforementioned national public eduction campaign by the CDC. This bill specified that prior consultation with non-profit private entities representing individuals who have been exposed to DES should take place. The following is a testimonial statement for this bill by two DES Action board members:

The history of our exposure to DES is a story of enormous suffering and needless death caused by a harmful chemical approved by the FDA and promoted as a wonder drug. It is a story of unsuspecting pregnant women and inadequately informed doctors; a story of unquestioned faith in a poorly tested product. Most importantly it is a story of millions of people - mothers, daughters and sons - whose lives have been tragically and permanently affected by DES.

DES Action/USA, a non-profit organization established in 1979, is the only national entity to which DES-exposed Americans can turn for support, information and education. Together with the DES Cancer Network, we are engaged in the only outreach effort to identify this high-risk population and to inform them of their special health needs. We work on a national scale with a minimal budget.

Despite our efforts on the past thirteen years, it is our belief that the majority of DES-exposed Americans are not aware of their exposure to this toxic and dangerous drug....

The known adverse physical effects of DES exposure, coupled with unknown future risks, often lead to lasting psychological injuries. We invite you to imagine the guilt for having taken a drug that irrevocably harmed your child. Or imagine at age 19 that you have vaginal cancer and that the standard treatment is removal of your reproductive organs. Imagine having to face the reality of infertility, confronting the anxiety of bearing an unhealthy child, or coping with the burden of caring for a seriously disabled child. Then imagine dealing with the...marital and familial stress that each of these problems creates...

The bill also authorizes funding for DES education for health professionals and the general public for fiscal years 1993 through 1996. At present, a critical lack of knowledge about the drug and its effects leads to tragedies that can be prevented: cancer not caught at an early stage because a simple, yet specialized exam was not performed; the loss of a Fallopian tube because of an unanticipated, life-threatening ectopic pregnancy; or a baby lost late in pregnancy because the mother was not treated as a high-risk patient. Funds spent wisely now wil not only prevent the senseless loss of lives, but will also help curb the need for expensive, crisis-oriented medical treatment for the DES-exposed.

In view of the above legislation that was considered necessary in USA for DES exposed victims, will you consider action towards ensuring legislation in Australia (Australian law) which will allow the many unknowing victims of DES exposure in Australia to become directly informed of their DES exposure and which will respect the rights of all Australians to be directly informed of the possibility of having been exposed to DES?

I look forward to hearing from you on this very important matter.
Thanking you in anticipation
Yours sincerely

Carol Devine
Coordinator, DES Action Australia -NSW
Ph (02) 98754820
c_devine@bigpond.net.au
Blogsite: www.desnsw.blogspot.com
(DES Action Australia-NSW operates independently of the Melbourne-based group DES Action Australia)

# # #
News Update: On 1/3/11 DES Action Australia-NSW received notification that the Australian Human Rights Commission has raised the above issue with the Department of Health and Ageing and will be informed when a response is received from the Department.

July 2011 Update:
The response by the Department of Health and Ageing was not satisfactory. In June DES Action Australia-NSW received notification from the Australian Human Rights Commission that the Commission is not in a position to assist in our matter and that it has limited resources. The Commission explained it must make difficult choices when identifying its priorities and fixing its work program. Nonetheless, the Commission has asked to be kept informed of DES issue developments.

On 22nd June DES Action Australia-NSW sent the following to the Commission:

Dear Ms Aggarwal

Our members consider it extremely unfortunate that the matter of DES exposure has been given low priority. It is important for your Commission to be informed that the DES health problem is not going to disappear. It is very likely that the estimate figure of 740,000 affected Australians will increase as more cases of clear cell adenocarcinoma of the vagina and cervix are reported. This cancer is occurring in women exposed to DES in utero in older age groups. Usage of DES during pregnancy in Australia is known to have extended beyond 1971. It is therefore likely that reports will continue for many years to come. When the numbers reported per year so far are averaged, this means a likely estimate increase of 20,000 affected Australians per year. Without legislation to ensure promotion of DES information in public health programs, it is highly probable the great majority of those affected will die in ignorance, with many having suffered unnecessarily due to their lack of knowledge of their DES exposure. There is the added possibility that their children, the next generation, may be affected and will likewise, be unaware of DES exposure risks. The repercussions of inaction by your Commission in consideration of human rights in this matter are great, and for the Australian government, there is the greater cost through health care subsidies that would otherwise have been averted.

We hope that the above information is helpful in your prioritisation decision in relation to the DES exposure issue.

Yours sincerely

# # # # # # # #

On 13th July DES Action Australia-NSW sent the following to the Commission:

Dear Ms Aggarwal

Our organisation wishes to inform you of a few more developments.

Recently the French government has seen fit to publish a very important paper about DES, which emphasises possible multi-generational effects and recommends that patients exposed to DES hand down the "record" of their exposure to the next generations to allow monitoring and care. Please find English translation attached. The original French version can be found at the Reseau DES France website
http://www.des-france.org/professionnels-sante/note-info.php#mideaupoint2011
I have forwarded this information to the Therapeutic Goods Administration and to the Minister for Health and Ageing. This issue of multi-generational effects is one more factor about DES which should be conveyed to the Australian population in the event of promoting DES information in public health promotion programs.

Problems are likely to continue as a result of inaction in properly informing the Australian population about DES. Only a few weeks ago our organisation was alerted to two cases of DES associated cancer in DES daughters who were diagnosed in their 20s, (1991 and 2004), one of whom died of complications and the other currently suffering complications. Both women were totally unaware of the special cancer preventive care they required, which placed them at risk of their aggressive cancers not being detected early. It is extremely harrowing and difficult task explaining the government's stance on DES public education to the DES daughter involved, and in particular, to the grieving mother involved, when such publicity may well have saved her daughter's life. Also, as per usual, our effort for DES Awareness Week June 1-7 has gained response from people who up to now, have been oblivious to their vital preventive care for their DES exposure and suffering the effects of DES without knowing why. It is very traumatic to these people to also learn about the government's stance on DES public education, which has contributed to their unnecessary suffering due to lack of appropriate care for their DES health effects.

As requested, we shall continue to alert you of developments that come to hand about the DES exposure issue. I wish to inform you that our members are extremely irate to learn that in Australia, a so-called developed nation, its own Human Rights Commission is under-resourced to be able to assist in our matter. Can you please keep us informed of any developments by the Commission towards finding the resources to address our matter?

Yours sincerely

# # # # #
Note: Attachment not provided here. However, English translation of French paper is available on request.

November 2011 Update:

A member of DES Action Australia-NSW received letter (21/10/11) from the Human Rights Policy Branch of the Attorney General's Department which states their Department shares our concern that people may not be aware they have been exposed to DES. Unfortunately their Department is unable to intervene on the decision taken by the Australian Human Rights Commission. However, their letter suggests raising our concerns with the Federal Health Minister who has portfolio responsibility for these issues.
On the 18/10/11 DES Action Australia-NSW sent a letter to the Commission requesting a time frame for action regarding the DES issue. So far there has been no response from the Commission.

September 2012 Update:

The Attorney General's Department has engaged non-government organisations to have input in the National Human Rights Action Plan. A submission making clear that the DES exposure health issue in Australia is a human rights matter has been sent to the Attorney General's Department. It is hoped that the issue regarding people not being aware of their DES exposure will be included in the Australian Human Rights Plan.

Monday 7 February 2011

Women's Health Policy shuns DES

Last year, the Australian government developed a new National Women's Health Policy, intent on focusing on prevention, health inequalities and the social determinants of those inequalities.


DES Action Australia-NSW, in representing up to an estimated 555,000 DES exposed women in Australia, made submission for this policy, highlighting:
-prevention needs by way of direct public promotion of DES information
-inequality where Australian DES exposed women have not benefited from the overall improvements in health experienced by most woman as a result of their being deprived of appropriately delivered information.
-the social determinant of the inequality as being political, ie, the government's belief that the promotion of DES information is likely to create anxiety.

DES exposure has not rated any mention anywhere in the newly released Women's Health Policy. Without DES exposure being specifically stated and addressed within the Women's Health Policy document, this signifies a gross injustice, continued abuse of the rights of every Australian woman to be informed of the possibility of having been DES exposed and the perpetuation of inequality for women and inequity between women.

Sunday 6 February 2011

Makena -The Jaw Dropper

www.businessweek.com/print/lifestyle/content/healthday/649631.html

Over the past few years there have been articles stating that doctors have been prescribing progesterone to pregnant women, based only on anecdotal reports of its effectiveness in preventing miscarriage. The US Food & Drug Administration (FDA) has now approved Makena (hydroxyprogesterone caproate) to prevent premature births.

For its approval, the FDA only reviewed a trial of 463 pregnant women and reviewed the development their babies only between 2.5 to 5 years of age. This drug is a reissue of an earlier drug and received accelerated approval. Makena's ingredient, hydroxyprogesterone caproate, has had previous safety concerns, including possible association with second trimester miscarriages. For more information about this see http://en.wikipedia.org/wki/17-Hydroxyprogesterone_caproate

TV Press article (www.presstv/ir/detail/163935.html) states: Further studies, however, are needed to show whether the infants whose births were delayed by the use of this drug will suffer fewer health and developmental problems or not.

For all those familiar with the DES story, this approval by the US FDA rings alarm bells.

Tuesday 1 February 2011

Cancer Council has DES exposure silenced and zipped

Last week the Irish Medical Times published an article to mark Cervical Cancer Prevention Week in Ireland. This article commendably included the statement: Exposure to diethystilboestrol (DES) also increases cervical cancer risk. (www.imt.ie/clinical/2011/01/early-detection-is-key-to-prevention.html)

Sadly in Australia, there is no such nationally held Prevention Week which could help raise awareness of the risks of prenatal DES exposure. In South Australia, there are only some small funding grants provided by the SA Cancer Council to community applicants to promote a Pap Smear Awareness Week in SA.

So far, Cancer Council Australia and the Cancer Councils of Qld, WA, Vic and ACT have responded to the requests of DES Action Australia-NSW to include prenatal DES exposure as a risk in their respective cervical cancer publications. However, our organisation's experience shows that merely including DES information in publications does not go far enough in raising awareness of DES exposure to the Australian public. Even more frustrating, is the low priority status of the NSW Cancer Council's information fact sheet, DES and Cancer Position Statement - tragically positioned well away from direct public attention and dormant with its glaring statement: Many people remain unaware of their exposure and the potential adverse effects of DES.

This week, the Australian Cancer Council and all State and Territory Cancer Councils have been asked by DES Action Australia-NSW : Why isn't there a national Cervical Cancer Prevention Week which could help raise awareness of the risk of prenatal DES exposure?