MaryO
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Endocrine Society Urges NIH to Delay Public Access Plan
CHEVY CHASE, Md., Nov. 12 /PRNewswire/ -- The Endocrine Society today asked the National Institutes of Health (NIH) to delay implementation of its plan to enhance public access to scientific research. While The Endocrine Society supports the concept of open access, it cannot support the NIH's proposal, as it raises several concerns and questions that must be addressed before any new policy can be applied.
In a letter sent to NIH Director Elias A. Zerhouni, M.D., The Endocrine Society shared several concerns regarding the NIH plan.
"We not only support free access to literature," writes Endocrine Society President Anthony Means, Ph.D., "we have invested our financial resources in developing and implementing definitive Web technology to accomplish this."
The Society currently makes all accepted manuscripts from its four peer- reviewed journals immediately available, without charge, to the public through its Web site. All of the Society's final published content also becomes available, free-of-charge, after 12 months.
The Endocrine Society's letter notes that the NIH plan duplicates existing resources; uses an untested publishing model; and leaves several unanswered questions regarding costs and measurements. The Society also conveys disappointment that in developing its plan for public access, the NIH failed to consult with established members of the scholarly publishing community, many of whom have advocated for NIH funding increases in recent years.
"The Endocrine Society is gravely concerned about the effect this wholesale shift in policy will have on the publishing models of the scholarly publishing community," notes the letter.
While the NIH calls for publicly funded scientific research to be freely available after six months, it has not shared the methodology and data used to establish this timeframe. A majority of journal publishers have determined that a 12-month free access policy is more sustainable than a six-month policy. The Endocrine Society also points out the NIH's failure to provide information about how it will assess the effectiveness of its policy and monitor its impact on stakeholders.
"We urge the NIH not to implement this proposal until sufficient data are collected to gauge the impact -- economic and otherwise -- of such a policy," said Dr. Means who offered to work with the NIH to revise their plan.
"We suggest there are other models that the NIH can use to promote open availability of scientific information and manage its research portfolio, and we would be happy to be part of a process to develop such models."
Founded in 1916, The Endocrine Society is the world's oldest, largest, and most active organization devoted to research on hormones, and the clinical practice of endocrinology. Today, The Endocrine Society's membership consists of over 11,000 scientists, physicians, educators, nurses and students in more than 80 countries. Together, these members represent all basic, applied, and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Maryland. To learn more about the Society, and the field of endocrinology, visit our web site at http://www.endo-society.org
SOURCE The Endocrine Society
CO: Endocrine Society; NIH; National Institutes of Health
ST: Maryland
SU: EXE
Web site: http://www.endo-society.org
11/12/2004 10:22 EST
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LOS ANGELES (AP) - World champion figure skater Scott Hamilton was diagnosed Thursday with a benign brain tumor, his publicist said.
Hamilton, 46, underwent a biopsy at The Cleveland Clinic in Ohio, and doctors expected to release him from the hospital by Friday.
Hamilton has a slow-growing, non-cancerous tumor in the region of the pituitary gland, said Dr. Gene Barnett, chairman of the clinic's brain tumor institute. Hamilton's publicist, Michael Sterling, said the skater has had vision problems in recent weeks.
``We will be working with him on a treatment plan moving forward,'' Barnett said.
Hamilton was diagnosed with testicular cancer in 1997 and treated with surgery and chemotherapy.
Hamilton, who lives in Los Angeles, is a four-time U.S. national champion, a four-time world champion and the 1984 Olympic gold medalist. He is now a skating show producer.
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http://story.news.yahoo.com/news?tmpl=stor...e/flu_shots_ark
Arkansas Receives More Flu Vaccine
By AVA THOMAS BENSON, Associated Press Writer
LITTLE ROCK - Arkansans especially at risk from the flu — but who haven't been able to get a flu shot this year because of a vaccine shortage — may get the protection they need from 80,000 more doses of the flu vaccine being sent to the state.
The additional doses will be ready for distribution by next week, state Health Department officials said Monday.
Arkansas originally received only 114,850 doses of the vaccine. Health department officials sent 48,640 to nursing homes and the remaining 66,000 to each of Arkansas 75 counties for distribution to the state's at-risk population, estimated at more than 420,000. Clinics around the state began administering the shots Wednesday, and officials said fewer than 4,000 of the original shots are left.
The state had asked the federal government for more doses of the vaccine, but did not know if it would receive the doses.
"We just couldn't believe it," health department spokeswoman Ann Wright said. "We thought we might get more vaccine, but 80,000 doses is just wonderful, great news. We're just thrilled to death."
Wright said the additional vaccines would be sent to health clinics throughout the state for distribution and that details of how the shots are administered would likely be left to individual clinics. The department still plans to restrict the shots to those in at-risk categories, she said.
"(The extra doses) are for people in the high-risk groups so they've got protection. They can really go into complications from the flu and (Arkansas receiving the extra shots) is such great news for them."
People in high risk categories include anyone 65 years of age or older, children younger than 2 years old, pregnant women and people with certain medical conditions.
It takes about two weeks for immunity to develop after a person receives the shot and the shot's effectiveness lasts for about three months.
The supply of flu vaccines was cut nearly in half this year when British regulators stopped production at one of the two companies that provide the U.S. with its vaccines. Officials said the flu vaccines produced at the Liverpool-based Chiron Corp. had become contaminated.
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http://story.news.yahoo.com/news?tmpl=stor...lu_vaccine_mass
Massachusetts Getting More Flu Vaccine
BOSTON - Massachusetts is getting more than 262,000 additional doses of flu vaccine, which state Public Health Commissioner Christine C. Ferguson said should be enough to vaccinate people most at risk of death or serious complications from the flu.
However she said healthy children older than 2 and healthy adults younger than 75 will not yet be able to be vaccinated.
"What we don't know at this point is how many additional doses might be available in the state over the course of the next month, month and a half, over and above the 1.2 million that we are currently counting on," Ferguson said at a news conference Monday.
Contamination concerns at a British plant wiped out nearly half the U.S. supply.
The state Department of Public Health said it will receive the additional 262,630 from Aventis Pasteur, the lone remaining maker of vaccine for the U.S. market. That brings the state agency's total to 660,000, and roughly 600,000 flu shots have been shipped directly to doctors' offices and hospitals by Aventis.
The new doses will be sent to local boards of health, doctors' offices and hospitals.
Local boards of health placed their orders based on last year's demand, which is estimated at less than half of those who were at high risk, health authorities said.
"We're trying to meet a heightened demand, because a lot of people weren't coming forward in previous years," Ferguson said.
Flu season typically peaks in January or February, and only one case in the Greater Boston area so far has been reported.
Each year, about 800 Massachusetts residents die of complications from the flu.
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1) Novartis is conducting a 10-12 week clinical research study to find out if the combination of two FDA approved study drugs will be safe and effective in treating patients for both high blood pressure and cholesterol.. This study is being conducted in:
- Cadillac, MI online at http://www.centerwatch.com/patient/studies/stu65763.html
- Canton, OH online at http://www.centerwatch.com/patient/studies/stu65815.html
- Kettering, OH online at http://www.centerwatch.com/patient/studies/stu65785.html
- Norfolk, VA online at http://www.centerwatch.com/patient/studies/stu65777.html
- Port Orchard, WA online at http://www.centerwatch.com/patient/studies/stu65759.html
- Portland, OR online at http://www.centerwatch.com/patient/studies/stu65791.html
- Portland, OR online at http://www.centerwatch.com/patient/studies/stu65805.html
- San Diego, CA online at http://www.centerwatch.com/patient/studies/stu65817.html
- Stamford, CT online at http://www.centerwatch.com/patient/studies/stu65765.html
- Tustin, CA online at http://www.centerwatch.com/patient/studies/stu65783.html
- Vista, CA online at http://www.centerwatch.com/patient/studies/stu65775.html
- Warminster, PA online at http://www.centerwatch.com/patient/studies/stu65813.html
- White Plains, NY online at http://www.centerwatch.com/patient/studies/stu65797.html
2 Pregnancy in Polycystic Ovary Syndrome online at PPCOS. This study is being conducted in:
- Charlottesville, VA online at http://www.centerwatch.com/patient/studies/stu65607.html
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Merck Should Have Pulled Vioxx in 2000-Study
2 hours, 17 minutes ago Health - Reuters
By Tom Armitage
BERNE (Reuters) - U.S. drugs giant Merck & Co Inc. should have pulled its Vioxx painkiller from the market four years ago because data showing it raised the risk of heart attacks has existed since 2000, Swiss scientists said on Friday.
In a report for British medical journal The Lancet, researchers at the University of Berne said there was substantial evidence of the dangerous side effects of the drug by the end of 2000, but the mounting data was not analyzed properly.
"Our findings indicate that rofecoxib (Vioxx) should have been withdrawn several years earlier," the scientists said.
Merck did not recall Vioxx, a COX-2 inhibitor taken by about 20 million Americans, from the worldwide market until five weeks ago.
Merck said in a statement it "was vigilant in monitoring and disclosing the cardiovascular safety of Vioxx and we absolutely disagree with any implication to the contrary." The company said it also disagrees with the conclusion that the drug should have been withdrawn several years ago.
"The company could and should have made the statement several years back, when the data we analyzed were readily available," Matthias Egger, a professor at the university's department for Social and Preventative Medicine, told a news conference.
Merck said the data contained in the Swiss analysis are not new and are essentially consistent with combined analyzes of clinical trials that the company had previously published.
The Swiss research follows newspaper reports earlier this week that Merck had tried to fight mounting concerns about the drug's safety in order to protect sales.
The U.S. Food and Drug Administration recently published a study estimating that Vioxx could have caused about 28,000 heart attacks or deaths since it was approved in 1999.
Merck's shares have slumped around 40 percent since the recall, and analysts estimate that it could face a bill of between $10 billion and $15 billion in litigation.
INDEPENDENT EVALUATION
The Swiss scientists performed a meta-analysis on the data, taking in results from past studies, some of which were available on the FDA Web site. They found that patients who took Vioxx were at greater risk even after a few months, regardless of how much of the drug was taken.
Using 18 randomized controlled trials and 11 observational studies, researchers saw that heart-attack risk more than doubled when Vioxx was taken.
By the end of 2000, 52 heart attacks had occurred in 20,742 patients, the researchers said. Of these, 41 were patients using Vioxx. The increased heart-attack risks became apparent in studies that were evaluated by external watchdogs.
"It could be that without independent evaluation of the data, the assessment of adverse effects is biased so that the risks of a drug appear smaller," Egger said.
"We therefore recommend that all studies be carried out with independent external data evaluation."
Drug licensing authorities should review their procedures, the study concluded, to ensure that data released after the drug launch is analyzed for signs of side effects.
The authors also said an independent panel of experts should investigate why manufacturers and licensing authorities did not evaluate the data available on Vioxx sooner.
In an editorial in the journal, editor Richard Horton criticized both Merck and the FDA, saying they acted out of "ruthless, short-sighted, and irresponsible self interest."
"The licensing of Vioxx and its continued use in the face of unambiguous evidence of harm have been public-health catastrophes," said Horton.
"This controversy will not end with the drug's withdrawal."
Shares of Merck closed down 3 percent at $27.02 on the New York Stock Exchange on Thursday.
The study was part of a wider investigation into anti-inflammatory drugs and their side effects conducted by the University of Berne on behalf of the Swiss National Science Foundation. Full results are due mid-2006. (Additional reporting by Deena Beasley in Los Angeles)
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A New Indication for Norditropin® (somatropin rDNA injection)
.c The Associated Press
Novo Nordisk's Human Growth Hormone Now Approved for Use in Adults
PRINCETON, NJ (Market Wire) - (http://www.novonordisk-us.com) http://media.marketwire.com/attachments/20...4324-Novonordis logoSmall.jpg
Novo Nordisk (NYSE: NVO) today announced that the Food and Drug Administration (FDA) has approved the use of Norditropin@ (somatropin rDNA injection) in adults with severe growth hormone deficiency. Norditropin was approved by the FDA in 1997 for use in children.
Today's action by the FDA makes it possible for children being treated with Norditropin for growth hormone deficiency to continue their treatment into adulthood, and also allows for the treatment of adults with conditions that result in a deficiency of growth hormone. Earlier this year the FDA approved Novo Nordisk's Norditropin NordiFlex@, the first prefilled, multidose, disposable growth hormone pen in the United States.
``We are dedicated to meeting the needs of individuals who require growth hormone therapy treatment,'' said Michael Shalmi, M.D., vice president of biopharmaceuticals, Novo Nordisk Pharmaceuticals, Inc. ``This approval by the FDA is yet another step in Novo Nordisk's proud history of innovation in the field of growth hormone therapy.''
Growth Hormone Deficiency in Adults
GH deficiency in adults is a clinical syndrome that usually results from a pituitary or peri-pituitary tumor or as a direct result of the surgery or radiation used to treat the tumor. GH deficiency also occurs from other pituitary-related disease or from a deficiency in childhood(1). The prevalence rate of adults with GH is approximately two in 10,000 of the adult population, with adult-onset GH accounting for approximately one in 10,000(2).
About Norditropin
Norditropin from Novo Nordisk is human growth hormone that has been biosynthetically produced to resemble growth hormone the body makes naturally. It is essentially identical to natural growth hormone in composition.
Novo Nordisk first produced biosynthetic growth hormone in 1985. In 1999, the company introduced a liquid growth hormone formulation that did not require a reconstitution or mixing procedure before injection. This was a major advance in simplifying growth hormone therapy for patients.
Norditropin is indicated for the long-term treatment of children with growth failure due to inadequate secretion of endogenous growth hormone and for replacement of endogenous growth hormone in adults with growth hormone deficiency (GHD) who meet either of the following two criteria: 1. Adult Onset (AO): Patients who have GHD, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy, or trauma; or 2. Childhood Onset (CO): Patients who were growth hormone deficient during childhood should have GHD confirmed as an adult before replacement therapy with Norditropin is started. GHD should be confirmed by an appropriate GH stimulation test.
Norditropin should not be used in patients with known hypersensitivity to somatropin or any of its excipients, in patients with proliferative or preproliferative diabetic retinopathy. Growth hormone (GH) should not be used in patients with active neoplasia and should be discontinued if evidence of neoplasia develops. Growth hormone (GH) should not be used in pediatric patients with closed epiphyses.
Increased mortality may occur in patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma or acute respiratory failure.
Deaths have been reported in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment. Male patients with one or more of these factors may be at greater risk than females. Unless patients with Prader-Willi syndrome also have a diagnosis of GHD, Norditropin is not indicated for the long-term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome.
Funduscopic examination of patients is recommended at the initiation and periodically during the course of growth hormone therapy.
Monitor patients with GHD secondary to an intracranial lesion for progression or recurrence of the underlying disease process. Monitor patients with glucose intolerance closely; insulin dosage may need to be adjusted. Monitor carefully if GH is administered in combination with other drugs metabolized by the CP450 pathway. Patients with coexisting ACTH deficiency should have their glucocorticoid replacement dose carefully adjusted to avoid an inhibitory effect on growth. Periodically monitor bone age in pediatric patients, especially in patients who are pubertal and/or receiving concomitant thyroid hormone replacement therapy.
Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea and/or vomiting has been reported in a small number of patients treated with growth hormone products.
As with all protein drugs, a small percentage of patients may develop antibodies to the protein. Since antibodies to somatropin have the potential to inhibit further linear growth, only patients failing to respond to treatment should be tested for antibodies.
The following adverse events have been reported during clinical studies in growth hormone deficient children: headache, local reactions at the injection site, localized muscle pain, rash, weakness, mild hyperglycemia, glucosuria and arthralgia. Fluid retention and peripheral edema may occur.
In clinical studies with Norditropin in GHD adults the majority of side effects were symptoms of fluid retention including peripheral edema, arthralgia, myalgia, infection (non-viral) and parasthesia. In general, these side effects were mild and transient in nature.
Full prescribing information for Norditropin@ and Norditropin NordiFlex@ is available by contacting Novo Nordisk Pharmaceuticals, Inc. or visiting (http://www.norditropin.com) www.norditropin.com.
Norditropin and Norditropin NordiFlex are registered trademarks of Novo Nordisk A/S.
Novo Nordisk is a healthcare company and a world leader in diabetes care. The company has the broadest diabetes product portfolio in the industry, including the most advanced products within the area of insulin delivery systems. In addition, Novo Nordisk has a leading position within areas such as hemostasis management, growth hormone therapy and hormone therapy for women. Novo Nordisk manufactures and markets pharmaceutical products and services that make a significant difference to patients, the medical profession and society. With headquarters in Denmark, Novo Nordisk employs approximately 20,000 full-time employees in 69 countries, and markets its products in 179 countries. Novo Nordisk's B shares are listed on the stock exchanges in Copenhagen and London. Its ADRs are listed on the New York Stock Exchange under the symbol 'NVO.' For more information, visit novonordisk.com, or in the US, (http://www.novonordisk-us.com) www.novonordisk-us.com.
(1) American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children 2003 update. Endocrine Practice. Vol 9 No. 1 January/February 2003.
(2) Bryan J, Loveman E, Chase D, Mihaylova B, Cave C, Gerard K, Milne R. Clinical effectiveness and cost-effectiveness of growth hormone in adults in relation to impact on quality of life: a systematic review and economic evaluation. Health Technology Assessment NHS R&D HTA Programme. 2002; Vol. 6:No.19
For further information please contact: Media: Susan Jackson 609-919-7776 Investors: Christian Kanstrup 609-919-7937
Copyright © 2004 Market Wire
Distributed by the Associated Press
11/04/04 13:10 EST
Copyright 2004 The Associated Press. The information contained in the AP news report may not be published, broadcast, rewritten or otherwise distributed without the prior written authority of The Associated Press. All active hyperlinks have been inserted by AOL.
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This article is for those of you who have inquired about Miscarriages and Pit Tumors:
http://news.newkerala.com/india-news/?acti...llnews&id=40422
Miscarriages can be prevented by measuring hormones: Study:
[Health India]: London, Nov 2 : Doctors would now be able to predict the risk of a miscarriage in a woman by measuring their hormones, researchers at the University College of London claim.
According to the BBC, researchers have found that women who have lower blood level hormones produced by the placenta face a greater risk of having a miscarriage.
Professor Eric Jauniaux and his team, investigated whether this hormone and others produced by the placenta might be useful markers of early pregnancy loss and are now hpeful that by correcting the cause of these imbalances miscarriages may be prevented.
"If we are able to identify these clear hormone variations early enough, we believe there is a real window of hope for the development of preventative terapies for these patients,"Professor Jauniaux was quoted as saying.
Researchers are also oping that correcting these harmonical imbalances may lead to the development of treatments to prevent recurrent miscarriage as well.(ANI)
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Meri (drmeriftr) sent me this great info. Thanks so much, Meri!
http://www.fitcommerce.com/News/NewsView.asp?newsId=2157
October 30, 2004 Newcastle upon Tyne -- Green tea, long lauded as favored substitute for coffee among the health conscience especially for its anti-oxidant capabilities, has risen a couple of notches in promoting better mental health as well. Coffee is believed to elevate cortisol to unhealthy levels which causes premature aging.
The latest study out of England's University of Newcastle herald the merits of green tea in delaying the onset of Alzheimer's disease. The study has found that both green and black teas may inhibit certain brain enzymes linked to Alzheimer's disease.
Black and green tea hail from the same plant. The difference between the two teas is that green tea is not fermented thus keeping its natural green color. Black tea, on the other hand, has been fermented, resulting in a change in taste and a dark appearance. Coffee, by contrast, did not show any significant effects upon Alzheimer's.
The researchers discovered that both green and black tea inhibited the activity of the enzyme acetylcholinesterase (AChE), which breaks down the neurotransmitter, acetylcholine. Alzheimer's disease is characterized by a drop in acetylcholine.
The teas also stopped the activity of other chemicals known to be key in making plaques and tangles in the brains of Alzheimer's patients. The second chemical is called butyrylcholinesterase (BuChE).
Green Tea Best
The study found that only green tea also obstructed the activity of beta-secretase, which plays a role in the production of protein deposits in the brain that are associated with Alzheimer's disease. The positive effects of green tea lasted for an entire week, while the enzyme-inhibiting properties of black tea only lasted for one day.
As Professor Clive Ballard, of Newcastle General Hospital and director of research at the Alzheimer’s Society, stated: "This interesting research builds on previous evidence that suggests that green tea may be beneficial due to anti-oxidant properties."
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Date: October 28, 2004
For Release: Immediately
Contact: HHS Press Office
(202) 690-6343
HHS IDENTIFIES MORE INFLUENZA VACCINE
Department Takes Steps To Acquire Foreign Vaccine, Redirect Government Doses
HHS Secretary Tommy G. Thompson announced today significant progress toward expanding the nation's supply of vaccines for flu season: the Food and Drug Administration (FDA) has identified about 5 million doses of influenza vaccine from foreign manufacturers; HHS has been able to recoup an additional 300,000 doses of the injectable vaccine originally bought for federal employees and the military; and a major pneumonia vaccine manufacturer plans to triple its production.
Secretary Thompson said these medicines would add to the nation's growing supply of vaccines and medicines to protect Americans during the coming flu season. These new doses would add to the 61 million doses of vaccine already available, including 58 million doses of vaccine from Aventis and 3 million of FluMist nasal spray from MedImmune. Additionally, the nation has a supply of antiviral medicines, potentially enough for more than 40 million people that can be used to prevent or treat the flu.
With the news of additional supply, the Secretary stressed again that millions of influenza vaccine doses are still to be distributed to states this flu season. Specifically, about 17 million of the Aventis vaccine is still to come (about 3 million doses a week are being distributed), as well as 2 million doses of FluMist.
"We're continuing to build our arsenal of vaccines and medicines to confront the coming flu season," Secretary Thompson said. "We are encouraged about the potential for some 5 million doses of vaccine from foreign manufacturers and we're sending our inspectors to those facilities. We're redirecting vaccine originally purchased by the government for federal employees and the military to priority populations throughout the country.
"We're growing stronger each week in our supply of vaccines and medicines, which makes us optimistic about our ability to protect the American public as we go into flu season," he added.
Secretary Thompson said FDA inspectors would be traveling to two foreign manufacturing facilities -- GlaxoSmithKline's facility in Germany and IDBiomedical's facility in Canada -- to inspect their manufacturing plants and products. The inspection teams will confirm the availability of the 5 million doses, assure that the vaccine can be used safely, and then make arrangements to acquire them. The department is still exploring the potential of additional doses of vaccine from other foreign sources as well.
The vaccine from foreign manufacturers would be distributed according to greatest need at the time of acquisition this flu season. These doses would most likely have to be distributed as an investigational new drug (IND), requiring recipients to sign a consent form and follow-up with a health care worker.
Additionally, the department has recouped about 300,000 doses of influenza vaccine that had been purchased by the federal government for federal employees and the military this flu season.
This includes 200,000 doses of vaccine purchased originally for the military, which will now use FluMist thus freeing up the injectable vaccine for the priority populations who cannot take FluMist. This shift will not affect the timing or supply of vaccine for members of the military who are eligible to receive the flu vaccine. Additionally, HHS has recouped nearly 100,000 doses from the Federal Occupational Health service. All of these doses will now be redirected to states based on need for their priority populations.
Secretary Thompson also announced that Merck & Co. is tripling its production of pneumococcal vaccine used to prevent one of the major complications of the flu, pneumonia. The company, which typically sells 6 million to 7 million doses of Pneumovax 23, will increase its production to between 17 and 18 million for this flu season. The vaccine is for adults and children ages 2 years and older who are at increased risk for pneumonia.
Pneumovax is not a substitute for the influenza vaccine, but can help shield people against flu complications. A single dose can protect against 23 different types of Streptococcus pneumoniae bacteria that are responsible for causing more than 90 percent of pneumonia cases. Many people who fall into the priority groups for the influenza vaccine should also get the pneumonia vaccine, including seniors.
Secretary Thompson said the Centers for Disease Control and Prevention (CDC) is making flu vaccine data available for state health commissioners on a secure Web site to help them track supplies coming to their states. He noted that the data is proprietary information that Aventis asked be protected through the secure Web site. The Web site is the result of efforts by the CDC and Aventis to redirect undistributed vaccine to places of greatest need.
The CDC also has asked states to submit their high-risk needs that are not being met as soon as possible, so that this information can be used to distribute remaining doses to where they are most needed.
Furthermore, the Secretary wants states to be clear that vaccines and medicines will be covered through Medicaid and Medicare for the populations those programs serve. This includes children in Medicaid and seniors in Medicare. In fact, Medicare will reimburse seniors who received their vaccine from a provider who is not enrolled in Medicare, and it will cover the costs of antiviral medicines that can prevent or treat the flu.
Secretary Thompson thanked the American public for its cooperation in making sure the flu vaccine goes to those in priority groups. He reminded the public that the priority groups for influenza vaccination are all children aged 6 months to 23 months; adults aged 65 and older; persons aged 2 to 64 with underlying chronic conditions; all women who will be pregnant during influenza season; residents of nursing homes and long-term care facilities; children aged 6 months-18 years on chronic aspirin therapy.
"On behalf of the President, I want to extend the administration's appreciation to citizens across America, who in accordance with CDC guidelines, are forgoing the flu shot so that someone in a priority category can get one," Secretary Thompson said. "Working together, we can make sure that the vaccine doses go to those who are most vulnerable."
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Leroy, there's some info and discussion about flu shots and such on the News Items board because they've been so, well, newsworthy this year.
Since Cushing's I've always gotten a flu shot. I think it's a good idea, if you acn. Our bodies just can't handle any more assault than we already have.
I haven't been able to find any place that thas any available, though
The best I've gotten so far is "maybe in January".Best of luck to you!
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http://story.news.yahoo.com/news?tmpl=stor...ulin_inhaled_dc
Inhaled Insulin as Effective as Injection
Fri Oct 22, 3:24 PM ET Health - Reuters
By Megan Rauscher
NEW YORK (Reuters Health) - For people with type 2 diabetes, taking an inhaled form of insulin before meals and a single daily injection of long-acting insulin provides blood sugar control comparable to that of a conventional all-injection insulin regimen, researchers report.
Dr. Priscilla A. Hollander told Reuters Health that this shows that "inhaled insulin does offer a means of insulin therapy without injections. This approach could be very attractive to patients."
The study involved 299 diabetic patients who previously had to make at least two daily insulin injections to keep blood sugar under control. Half the participants switched to inhaled dry-powder insulin (Exubera) before each meal and a single injection of ultralente insulin at bedtime for 6 months. The others continued to receive all of their required insulin by injection.
Results showed that blood sugar levels improved to a similar degree in the inhaled and subcutaneous insulin groups. However, more patients in the inhaled insulin group (47 percent) than in the subcutaneous insulin group (32 percent) achieved target glucose levels.
Episodes of excessively low glucose occurred slightly less often in the inhaled insulin group, and there were no differences in severe adverse events, the investigators report in the journal Diabetes Care. There have been concerns that inhaled insulin affects the lungs, but there were "no major differences in the comprehensive pulmonary testing done during the study" Hollander said. "Safety concerns are a paramount concern when giving a drug like insulin in a totally new way," she added.
Nevertheless, cough of mild-to-moderate severity was reported more frequently in the inhaled insulin group, but it occurred less often as the study progressed.
"Patients liked the inhaled insulin better," Hollander noted. "There were significant differences in the quality of life testing between the two groups."
In addition, "patients treated with inhaled insulin gained significantly less weight than the patients treated with injected insulin."
Further long-term studies of inhaled insulin are currently underway.
SOURCE: Diabetes Care, October 2004.
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http://story.news.yahoo.com/news?tmpl=stor...lth_steroids_dc
Bush Signs Law Banning Certain Steroid-Like Drugs
Fri Oct 22, 8:32 PM ET Health - Reuters
WASHINGTON (Reuters) - President Bush signed a law on Friday banning certain steroid-like drugs, used by some athletes as performance enhancers.
The new law adds 18 substances to the list of banned anabolic steroids, including androstenedione, also known as "andro," which was made famous by baseball slugger Mark McGwire in the 1990s.
When injected, these substances metabolize into testosterone or other illicit steroids, and federal regulators have been seeking to crack down on the makers of these drugs.
"Steroid use by young people is a serious health issue," said Sen. Joseph Biden, who crafted the measure.
"This new law sends a strong message about andro and other steroid precursors. We are calling them what they really are: drugs, performance enhancing drugs," the Democrat from Delaware said.
The newly signed "Anabolic Steroid Control Act of 2004," also requires a review of federal sentencing guidelines for offenses involving anabolic steroids. It calls for criminal penalties for those caught making, selling or possessing the substances.
The new law also provides $15 million for education programs to teach children about the dangers of steroids.
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Ferring Introduces Bravelle® With First Needle-Free Reconstitution Device
Q-Cap Previewed at Annual ASRM Meeting
PHILADELPHIA, Oct. 18 /PRNewswire/ -- Ferring Pharmaceuticals introduced today the Q-Cap, the first device enabling needle-free reconstitution (process of dissolving medication in diluent) of fertility treatments. It is for exclusive use with the Company's human-derived fertility treatments and will be packaged with Bravelle® (urofollitropin for injection, purified). The device allows user-friendly reconstitution of medication(s) in a single vial, in single or mixed protocols, simplifying preparation for injection, and eliminating product waste and accidental needle sticks. The Q-Cap was previewed at the 60th Annual Meeting of the American Society for Reproductive Medicine (ASRM) in Philadelphia, October 16-20, 2004.
"In a recent survey by the International Council on Infertility Information Dissemination (INCIID), 77% of the 537 in vitro fertilization (IVF) polled patients reported reconstitution as the most stressful part of IVF therapy," said William Garbarini, director of marketing, Ferring Pharmaceuticals. "Part of that stress was specifically attributed to the use of needles. Since the Q-Cap is needle-free, it eliminates patients' anxiety associated with needle use during this process and increases comfort levels, making patients more confident in their self-treatment while ensuring that the full prescribed medication dose is administered from the vial."
The Q-Cap provides fast and easy reconstitution that is consistent with the traditional needle and syringe injection method that patients have become accustomed to and may need to use with other medications prescribed during their treatment cycle. It allows patients to easily withdraw the full contents of each vial needle-free. It does not interfere with the patient's ability to withdrawal her full dose without wasting product.
The device can also be used with Ferring's Repronex® (menotropins for injection, USP) fertility treatment.
How Q-Cap Works
For reconstitution, the patient twists the Q-Cap onto the syringe, pushes the tip through the diluent vial's rubber stopper, and pulls back on the plunger to remove the diluent. Next, the patient places the Q-Cap on the vial containing the Bravelle® or Repronex® powder, pushes the tip into the rubber stopper, then slowly injects the diluent into the vial and swirls the diluent and medication until the medication is dissolved. The solution can be used to dissolve up to six vials in one syringe.
The Q-Cap can be used to reconstitute medication(s) in one syringe regardless of protocol and allows the patient to administer only one injection per day. If more than one medication is required, the patient simply repeats the process with the additional vial(s) of medication(s) before attaching the injection needle to the vial. This improved reconstitution process reduces time required to educate patients since it mirrors the reconstitution process with the standard needle and syringe technique, eliminates accidental needle sticks and eliminates product waste.
"The Q-Cap is a new feature designed to make self-treatment with Bravelle® easier and less stressful for patients," said Dr. Richard T. Scott, Jr., Director and Managing Partner of Reproductive Medicine Associates of New Jersey. "Another benefit of the Q-Cap is that it requires only one injection in mixed protocols, whereas other devices require at least two. By using the Q-Cap, different ratios of Bravelle® and Repronex® can be delivered in one syringe to meet individual patient needs."
The Q-Cap will be commercially available in late 2004. For more information, complete instructions for use and a video demonstrating the reconstitution process with Q-Cap, please visit http://www.ferringfertility.com.
About Bravelle® and Repronex®
Bravelle®, a highly purified human-derived follicle-stimulating hormone (hFSH) for infertility treatment, contains 75 IU of FSH and up to two percent LH activity. Bravelle®, administered SC or IM in conjunction with hCG, is indicated for ovulation induction following pituitary suppression. Bravelle®, administered SC in conjunction with hCG, is also indicated for multiple follicular development during ART cycles in patients who have previously received pituitary suppression.
Repronex® is the only human menopausal gonadotropin (hMG) on the market and is approved for both subcutaneous and intramuscular administration. Bravelle® and Repronex®, like all gonadotropins, are potent substances capable of causing mild to severe adverse reactions, including OHSS (incidence of 6.0% and 3.5%, respectively), with or without pulmonary or vascular complications, in women undergoing therapy for infertility.
Both treatments are marketed by Ferring Pharmaceuticals Inc., a world leader in naturally occurring protein hormones. Only physicians thoroughly familiar with infertility treatment, including the risk of multiple births and adverse reactions, should prescribe these medications. Like other products for ovarian stimulation, treatment with Repronex® and/or Bravelle® may result in multiple gestations.
About Ferring Pharmaceuticals
Ferring Pharmaceuticals, part of the Ferring Group, a privately owned, international pharmaceutical company, markets Bravelle®, Repronex® and Novarel in the U.S. to infertility specialists and their patients. The Ferring Group specializes in the research, development and commercialization of compounds in general and pediatric endocrinology, urology, gastroenterology, obstetrics/gynecology and infertility. For more information, call 888-337-7464 or visit http://www.ferringusa.com or http://www.ferringfertility.com.
SOURCE Ferring Pharmaceuticals
CO: Ferring Pharmaceuticals
ST: Pennsylvania, Denmark
SU: PDT
Web site: http://www.ferringfertility.com
10/18/2004 08:30 EDT
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Survey Suggests Women with Prevalent Incurable Hormonal Disorder Understand the Importance of and Seek Self-Help Lifestyle Modification Services
Lack of Insurance for Self-Help Services Could Prove Obstacle for the Millions of Women with Polycystic Ovary Syndrome Seeking to Prevent Diabetes and Heart Disease
PHILADELPHIA, and SYLVA, N.C., Oct. 18 /PRNewswire/ -- Women with Polycystic Ovary Syndrome (PCOS), an incurable hormonal disorder which affects 10% of all reproductive age women, understand the importance of and seek self- help lifestyle modification support services, according to the results of a survey conducted by PCOStrategies, Inc. and the Reproductive Associates of Delaware. PCOS, which previous research has shown is best treated through lifestyle intervention, is a leading cause of infertility and if left untreated long term risks include the development of chronic diseases such as diabetes, heart disease and endometrial cancer. These results are being presented Wednesday, October 20, 2004 at 2:15 p.m. EDT at the American Society of Reproductive Medicine's Annual Meeting in Philadelphia, which is currently in progress.
Lesa Childers, MSW, President & CEO, PCOStrategies and board members Ronald Feinberg, M.D., Ph.D. and Barbara McGuirk, M.D., of Reproductive Associates of Delaware sought to determine the attitude, motivation, level of importance and cost thresholds of self-help life management options considered beneficial to women with PCOS. The issues of relevance to women with PCOS were incorporated into an Internet-based Likert questionnaire, which assessed respondents' level of interest in seeking professional services to improve their metabolic and emotional well-being. In addition, the survey sought information about respondents' willingness to utilize doctor-referred programs for improving nutrition and positive attitude.
The survey found that women with PCOS understand the importance of professional services that focus on their health, fertility and emotional well-being. They recognize the value and would even embrace referrals by their physicians to group and/or individualized life management programs with 78 percent expressing an interest in life management programs, 49 percent preferring weekly group sessions while 44 percent desired individualized counseling. They would prefer more frequent visits to their physicians while working to heal their underlying metabolic syndrome with 57 percent desiring weekly visits. However, access to insurance reimbursements for these activities may prove to be a hindrance for many women as only 15 percent of women expressed a willingness to participate with 25 percent or less insurance coverage.
The most common endocrine disorder in women, PCOS is a complex hormonal disorder effecting approximately 10 percent of reproductive-age women worldwide. Previous research has pinpointed its cause to the body's failure to respond to insulin correctly resulting in an excess of insulin, which further creates an imbalance with other bodily hormones. PCOS symptoms include lack of, infrequent or irregular menstrual cycles, infertility, hirsutism or excessive body or facial hair growth, weight gain, obesity, baldness and thinning hair, adult acne, depression, skin tags or teardrop- shaped pieces of skin and acanthosis nigricans or patches of rough brown to black skin.
"The willingness of those with PCOS to embrace lifestyle changes has long been a question of ours," said Ronald Feinberg, M.D., Ph.D., Chairman of the Professional Advisory Board for PCOStrategies and author of the new book "Healing Syndrome O". "This survey confirms that the majority of women with PCOS are not only willing but are seeking lifestyle modification services to improve their health and are looking for their treating medical professionals to provide more guidance."
PCOStrategies is a national non-profit organization dedicated to educating, motivating and stimulating women with PCOS and Syndrome O. Their mission is to assist women with PCOS in the development of a healthy lifestyle through their Syndrome O Coaching Services and Survival Strategies Programs, O Rounds Magazine and online support services to enhance fertility and overall well-being. Comprised of leaders in their respective fields, PCOStrategies has successfully helped many women with PCOS to realize better health and well-being and to conceive.
For more information visit http://www.asrm.org or http://www.pcostrategies.org.
About PCOStrategies, Inc.
Founded in 2003 and headquartered in Sylva, NC, PCOStrategies, Inc. is a national non-profit organization dedicated to educating, motivating and stimulating women with PCOS and Syndrome O. Their mission is to assist women with PCOS in the development of a healthy lifestyle through their Syndrome O Coaching Services and Survival Strategies Programs, O Rounds Magazine and online support services to enhance fertility and overall well-being. Comprised of leaders in their respective fields, PCOStrategies has successfully helped many women with PCOS to realize better health and well- being and to conceive.
SOURCE PCOStrategies, Inc.
CO: PCOStrategies, Inc.
ST: Pennsylvania, North Carolina
SU: SVY WOM NPT
Web site: http://www.asrm.org
10/18/2004 08:56 EDT
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I'm not sure that any of this would help protect us from the flu, but here
s some more, from thirdage.com:
How to Ward Off the Flu This Winter
The wisdom mothers have been dispensing for ages -- wash your hands, eat your vegetables, go to bed earlier -- turns out to be great advice for avoiding the flu.
Doctors and nutritionists say careful hygiene, a balanced diet and plenty of rest and fluids can go a long way toward keeping people healthy during the influenza season, especially considering this year's vaccine shortage.
"Taking care of yourself from a health standpoint is probably the best thing you can do," said Dr. R. Michael Gallagher, a family physician and dean of the University of Medicine and Dentistry of New Jersey's School of Osteopathic Medicine.
"People who are run down, they're overworked, not getting proper rest or proper nutrition, these people increase their risk" of illness, he said.
Besides getting enough sleep -- at least seven hours a night for adults and more for youngsters -- managing stress is important, Gallagher said, because too much can weaken one's immune system.
Frequent hand-washing, using soap and hot water and rubbing vigorously for about half a minute, also is crucial.
"What you want to do it is try to interrupt transmission of disease with the kinds of things our mothers taught us," said Dr. Mitchell Cohen of the federal Centers for Disease Control and Prevention.
Avoid touching your eyes, nose or mouth, because germs on your hand could infect you, he said. And, if you do get the flu, stay home from work or school so you don't infect others.
The United States will get only half its expected supply of flu vaccine this year because British health authorities suspended the license of vaccine producer Chiron Corp. at the company's Liverpool, England, factory because of contamination.
Cohen said the CDC is planning two public education campaigns, first to explain the shortage and who should or shouldn't get vaccinated, and second to teach people how to protect themselves through hygiene and "cough etiquette."
The old advice was to cough or sneeze into your hands, then wash them, but children and many adults don't wash up immediately. That means they can spread the flu virus or other germs via a handshake or touching a doorknob, computer keyboard or other surface, where those germs can live for hours. Now doctors are urging that, if a tissue isn't at hand, people -- especially children -- should sneeze into their sleeve.
"Doctors have been emphasizing this in the last several years," said Dr. Ron Davis, an American Medical Association trustee and preventive medicine specialist.
Davis said hand sanitizers are a good option when soap and water aren't available, but anti-bacterial soaps offer little benefit.
Another new piece of advice is to stop refilling the bottles of water so many of us carry.
The bottles accumulate germs and shouldn't be reused or shared, said American Dietetic Association spokeswoman Gail Frank, a professor of nutrition at California State University-Long Beach. But don't skip the water, because eight glasses of fluid a day is essential to health, aiding in almost every process in the body.
People, especially the elderly and those in poor health, also should avoid crowds and people who are coughing or sneezing, said Dr. Michele Bachhuber, an internal medicine specialist at Marshfield Clinic in Marshfield, Wis.
"Regular exercise helps boost our immune system, so that's important, too," she said.
Then there's the role of diet. Frank said it's crucial to eat a healthy and substantial breakfast, about one-fourth of the day's calories.
Variety in the diet is important, but people should emphasize plant foods, including whole grains and at least five servings of fruits and vegetables a day, said Elisa Zied, another American Dietetic Association spokeswoman and a registered dietitian in New York.
She said people can help keep their immune system strong by eating foods rich in vitamins A, C and E: milk, eggs and fish oil; citrus fruits, melons and red peppers; and nuts, spinach, peanut butter and corn oil.
Moms, doctors and health officials have been dispensing most of this advice for decades, but many people clearly forget or ignore it.
"We always worry about the healthy behavior fading over time as the crisis subsides, so we have to keep reminding people about the benefits of good hygiene and vaccination and taking care of themselves," said Davis, of the AMA. "I expect that people will listen more carefully ... because many people are going to have a hard time getting their flu shot."
Source: Associated Press. Powered by YellowBrix, Inc.
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http://www.medscape.com/viewarticle/490845?src=mp
Polycystic Ovary Syndrome May Lead to Diabetes, Cardiovascular Disease
Andrew Bowser
Oct. 7, 2004 (New York) — Treating metabolic and cardiovascular risk factors associated with polycystic ovary syndrome (PCOS) could reduce the incidence of serious medical consequences, according to a position statement from the American Association of Clinical Endocrinologists (AACE).
"Physicians should no longer regard PCOS as a cluster of annoying cosmetic complaints, or a condition primarily associated with infertility," but as a condition linked to metabolic disorders "that may be associated with type 2 diabetes mellitus and cardiovascular events," the position paper states.
No large, prospective longitudinal studies definitively link PCOS to diabetes or cardiovascular disease. However, many expert endocrinologists now believe the evidence is finally compelling enough to merit a formal warning.
"Data has been building up for the last 15 years," said Rhoda H. Cobin, MD, chair of the AACE task force on PCOS. "This is the first time anybody has put everything together and come forward to say, 'we need a call to action.' "
Women with PCOS often receive treatment for infertility and non–life-theatening symptoms such as acne and hirsutism. However, many also have an underlying metabolic disorder, characterized by insulin resistance, which often goes untreated, according to experts who drafted the position paper.
Call to Action
The AACE is the first professional society to come out with a statement strongly endorsing the need to recognize underlying medical risks in PCOS, a condition "that heretofore has not been seen as a significant risk factor for illness and death," Dr. Cobin told Medscape.
Today, many PCOS patients receive treatment only for infertility or cosmetic issues, and later in life they develop overt diabetes or coronary disease, she added.
The organization is calling for "widespread case finding" of PCOS, along with screening and treatment for the "hidden risks" of the condition, including myocardial infarction, stroke, and the complications of uncontrolled diabetes, such as retinopathy, kidney failure, and amputation.
Treatment may reduce risk of early death and debilitating complications. The experts recommend lifestyle modification, emphasizing exercise, controlled eating, and tobacco avoidance. Medication to treat diabetes, hypertension, and lipid abnormalities may be considered, depending on the patient.
The antihyperglycemic drug metformin (Glucophage) should be considered in "most women with PCOS as initial therapy" because it can improve metabolic abnormalities and may improve potential for pregnancy. Although metformin is not approved for use in PCOS, "abundant literature" supports its efficacy in this setting, experts said.
Common Condition
Simply identifying PCOS remains a major challenge. Most women see several physicians before receiving a definitive diagnosis. "This is the whole tragedy," said Walter Futterweit, MD, a PCOS expert who wrote the first textbook on the condition in 1984.
"It's getting a little better, as more lectures and literature are coming out, but even some endocrinologists...are still not aware of the intricacies," said Dr. Futterweit, a clinical professor of medicine at Mount Sinai School of Medicine in New York City.
Approximately 10% of reproductive-age women have PCOS, making it the most common metabolic abnormality in young women, according to AACE.
Most experts base the diagnosis of PCOS on a history of irregular menstrual cycles and anovulation, along with the presence of hyperandrogenism, ruling out similar hormonal disorders such as hyperprolactinemia or Cushing's syndrome. At least half of women with PCOS meet obesity criteria.
Insulin resistance with compensatory hyperinsulinemia is a common clinical feature of PCOS, occurring in at least 75% of these patients, recent reports show. Consequently, experts said in the position paper, women with PCOS should be evaluated for components of the insulin resistance syndrome (IRS), a cluster of clinical syndromes and abnormalities such as low levels of high-density lipoprotein cholesterol, increased triglycerides levels, hypertension, and insulin resistance with increased tendency toward type 2 diabetes mellitus.
Since 2001, AACE has recommended that women with PCOS be screened for diabetes by the age of 30 years because multiple investigations have suggested diabetes and its complications may develop at a relatively young age.
Evidence of Harm
In the Nurses' Health Study, which included more than 116,000 women aged 25 to 42 years who were followed for eight years, incidence of type 2 diabetes mellitus was increased by 2.0- to 2.5-fold in women with a history of abnormal or infrequent menstrual cycles. That finding is "highly suggestive" of PCOS as a risk factor for diabetes, because about 80% of women with irregular menstrual cycles have underlying PCOS, according to the authors of the AACE position paper.
Women with PCOS also appear to be prone to hypertension and atherosclerosis, and separate investigations have found these patients may have increased levels of coronary artery calcification and carotid intima media thickness, two "major" surrogate markers for cardiovascular risk factors, the authors stated.
There are no prospective, longitudinal studies assessing cardiovascular outcomes in PCOS patients. A number of retrospective epidemiologic studies have been completed. Most, but not all, of those studies confirmed increased risk of cardiovascular events. Notably, the Nurses' Health Study results suggest a twofold increased risk for nonfatal myocardial infarction in women with irregular menstrual cycles.
"It is likely that a large proportion of these women had PCOS, yielding indirect confirmation of increased adverse cardiovascular outcomes," according to the position paper.
Reviewed by Gary D. Vogin, MD
Andrew Bowser is a freelance writer for Medscape.
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Same here, Sue
No one seems to be able to get any. I was thinking, maybe if I volunteered as an aide at the hospital that they'd have to give me a shot. Then I could quit! Whatcha think? 
Seriously, this is very scary.
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Date: October 5, 2004
For Release: Immediately
Contact: HHS Press Office
(202) 690-6343
STATEMENT FROM THE DEPARTMENT OF HEALTH AND HUMAN SERVICES
Regarding Chiron Flu Vaccine
Clearly, the loss of the Chiron flu vaccine poses a serious challenge to our
vaccine supply for the upcoming flu season. Chiron was to produce between
46-48 million doses of influenza vaccine for the United States. The
Department has begun pursuing contingencies for this loss of supply.
We currently anticipate having approximately 54 million doses of influenza
vaccine from Aventis and about another 1-2 million doses of FluMist nasal
spray. HHS had planned for a vaccine supply of about 100 million doses this
season, after a demand of about 87 million doses last flu season.
Our immediate focus will be on making sure that the supply we do have
reaches those who are most vulnerable. The Centers for Disease Control and
Prevention is convening its Advisory Committee on Immunization Practices to
prioritize its recommendations on who should get the flu vaccine for this
season based on the new vaccine supply information.
We will need the help of the public, the public health community and the
medical community to make sure that the vaccine goes to those who truly need
it most.
We are in the process of learning more detailed information about why the UK
regulatory authority suspended Chiron's license for three months and whether
anything can be done to address the issues involved. The Department of
Health and Human Services, including its Food and Drug Administration,
Centers for Disease Control and Prevention, and National Institutes for
Health, are working with their counterparts in the British government as
well as Chiron regarding this matter.
The Department also has begun exploring whether more flu vaccine can be
manufactured for this flu season. This includes working with Aventis on its
ability to provide more vaccine. At this point, however, it is not known
whether it's possible to get more vaccine.
HHS and its agencies will make more information available regarding the
influenza vaccine supply as it becomes available.
###
Note: All HHS press releases, fact sheets and other press materials are
available at http://www.hhs.gov/news.
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For many states, voter registration closes soon. Be sure to register to vote, if you're not already. -
http://story.news.yahoo.com/news?tmpl=stor...health_merck_dc
Merck Pulls Arthritis Drug from Market
By Ransdell Pierson
NEW YORK (Reuters) - Merck & Co Inc. on Thursday pulled its arthritis drug Vioxx off the market because it increases the risk of heart attack and stroke, a move that sent the company's shares plunging, erasing $25 billion of its market value.
Vioxx, used by two million people around the world, accounts for 10 percent of Merck's annual sales.
The withdrawal of the drug casts a cloud over an entire class of widely used arthritis and pain drugs known as COX-2 inhibitors. "This has implications for all members of this class," said Dr. Garret FitzGerald, chairman of the Department of Pharmacology at the University of Pennsylvania.
Merck said that in a colon cancer trial, patients who took Vioxx for three years faced twice the risk of cardiovascular events, such as heart attack and stroke, as patients taking a placebo.
"Patients who are currently taking Vioxx should contact their health care providers to discuss discontinuing use of Vioxx and possible alternative treatments," it said.
Concerns over the drug's side effects have been building in recent years after several studies showed risks attached to it. Other drugs in the same class, including Pfizer Inc.'s Celebrex and Bextra and Novartis AG's Prexige, have so far not shown the same dangers.
However, the U.S. Food and Drug Administration (news - web sites) said it would closely watch other such drugs.
Worldwide sales of Vioxx totaled $2.55 billion last year. Since its introduction in 1999, 84 million people have used the medication. In the United States alone, 91 million Vioxx prescriptions have been written. The drug is sold in some countries under the name Ceoxx.
"This is a very significant negative for Merck. Not only is this a nearly $3 billion drug, but it calls into question the future of one the key drugs in its pipeline, Arcoxia," said Scott Henry, an analyst at Oppenheimer & Co.
Arcoxia, which is similar to Vioxx, is sold outside the United States but has not yet been approved by the FDA (news - web sites) because of concerns about heart and stroke risk. Some analysts had expected the agency to rule on Arcoxia by late October.
Merck is already struggling with slowing earnings growth and faces the loss of patent protection for its biggest-selling drug, cholesterol fighter Zocor, in 2006.
Despite the setback, Merck Chairman and Chief Executive Raymond Gilmartin said he had no intention of resigning.
Merck is already gearing up for lawsuits over Vioxx. "We have substantial defenses in these cases and will defend them vigorously," said Kenneth Frazier, Merck's general counsel.
Merck shares fell 25 percent on the New York Stock Exchange (news - web sites). Shares of Pfizer, which sells two rival arthritis drugs, edged higher.
Vioxx sales have been flat in recent years amid safety concerns. Clinical trial data have shown the drug increased the incidence of blood clots tied to strokes and heart attacks.
A recent study by the U.S. Food and Drug Administration suggested patients taking Vioxx faced a 50 percent greater risk of heart attack and sudden cardiac death than those taking Celebrex.
Sales of the Pfizer drugs Celebrex and Bextra have steadily grown as doctors have turned to those medications, which have not been linked to heart attack and stroke.
The colon cancer trial was designed to evaluate the effectiveness of the standard 25-milligram Vioxx dose in preventing recurrence of colon polyps. Such polyps sometimes become cancerous.
Vioxx was used in the trial because some researchers theorize that inflammation, present in arthritis, may be linked to colon cancer.
Merck said the heart attacks and strokes were not spotted during the first 18 months of the trial but became apparent later.
"Given the availability of alternative therapies, and the questions raised by the data, we concluded that a voluntary withdrawal (of Vioxx) is the responsible course to take," Merck chief Gilmartin said.
Merck said it expects the cost associated with the recall to reduce earnings by 50 cents to 60 cents per share in the second half of the year, and will give more financial details on Oct. 21.
Merck said it planned to cut costs and said it remains comfortable with its earnings forecast for full-year 2004 of $3.11 to $3.17 per share.
Vioxx and the two Pfizer arthritis drugs are designed to block inflammation and pain as effectively as standard nonsteroidal anti-inflammatory drugs such as aspirin and ibuprofen, while causing far fewer ulcers and gastrointestinal problems than the older treatments.
The newer medicines block a protein called COX-2 that has been linked to inflammation.
Merck said it would continue to market Arcoxia, which is sold in 47 countries. (Additional reporting by Toni Clarke and Edward Tobin)
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I just called my doctor to be notified when they come in here. Like Lorrie, I always get one of those. It's pretty painless and good protection for a Cushie, I think.
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STATEMENT BY TOMMY G. THOMPSON
Secretary of Health and Human Services
Urging Americans To Get Influenza Vaccine
A flu vaccination will protect the health of millions of Americans this flu season. That's why we have worked with manufacturers to ensure that there is more vaccine available in the United States this year than ever before.
We are urging people to visit a health professional and get vaccinated to protect themselves and their loved ones from the flu. Among those we recommend get vaccinated are people 50 years and older, women who will be pregnant during the flu season, and all children six to 23 months of age.
A full list of people who should get vaccinated is available at http://www.cdc.gov/flu/
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NIH OPENS NEW CLINICAL RESEARCH HOSPITAL
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
NIH Office of the Director (OD) http://www.nih.gov/icd/od/
FOR IMMEDIATE RELEASE
Thursday, September 16, 2004
CONTACT:
Don Ralbovsky
Bonnie Kinney
301-496-5787
NIH OPENS NEW CLINICAL RESEARCH HOSPITAL
WHAT:
The National Institutes of Health will open a new hospital totally dedicated to clinical research on Wednesday, September 22. The Mark O. Hatfield Clinical Research Center will provide a unique opportunity for clinicians, scientists, and patients to study and conquer both chronic and acute disease in the 21st century. This new 870,000-square-foot facility will connect to the existing NIH Clinical Center, which opened its doors to patients in 1953. In the 50 years since its opening, NIH has worked in partnership with more than 350,000 participants in clinical studies from every state in the U.S. and from around the world. Some advances include:
-- First cure of a solid tumor with chemotherapy
-- First chemotherapy for childhood leukemia and Hodgkin's disease
-- Discovery of evidence of a genetic component in schizophrenia
-- First use of nitroglycerin for acute myocardial infarction
-- First use of hydroxyurea to treat sickle cell anemia
-- First gene therapy
-- First successful replacement of a mitral valve
-- First use of AZT to treat AIDS
-- Development of screening tests for AIDS and hepatitis, which reduced the transmission rate of transfusion- transmitted hepatitis from 30 percent to near zero
-- MaryO and some great Cushing's Patients
More than 1,000 clinical studies will be conducted in the Mark O. Hatfield Clinical Research Center. The promise of prospective cures energizes scientists, clinicians, and patients today no less than in previous decades. This new hospital will continue to set the pace for developing the most promising medical advances, providing a synthesis of medical knowledge to radically improve human health. The proximity of labs, equipment, and patient care units in the new hospital will help to rapidly move biomedical laboratory findings into the mainstream of medical practice -- carrying on the "bench-to-bedside" tradition of the original NIH Clinical Center.
WHEN:
Wednesday, September 22, 2004, 10:30 a.m.
WHERE:
National Institutes of Health, Bethesda, Maryland
WHO:
Senior officials, researchers, and patients will be available to discuss the importance of this new hospital and the impact it will have, and to relay personal stories of triumph.
-- Tommy G. Thompson - Secretary, Department of Health and Human Services
-- Elias A. Zerhouni, M.D. - Director, National Institutes of Health
-- John I. Gallin, M.D. - Director, NIH Clinical Center
-- U.S. Rep. C.W. Bill Young - Chairman, Committee on Appropriations, U.S. House of Representatives
NOTE TO EDITORS:
Press credentials are mandatory. Press should enter at the Press Only Entrance, located at the front of the Clinical Research Center. Public affairs staff will register TV crews and reporters and distribute press kits, B-roll, and other materials. B-roll is available in English and Spanish. Highlights include NIH leaders, patient stories, aerial shots, and architectural footage. A press room will be available on Monday, September 20 at http://clinicalcenter.nih.gov>.
This NIH News Release is available online at: http://www.nih.gov/news/pr/sep2004/od-16.htm
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Growth Hormone Outgrows Growth
Posted 07/26/2004
S. M. Shalet
Abstract and IntroductionAbstract
Growth hormone (GH) replacement has been offered to GH-deficient (GHD) children for approximately 40 years whereas it has only been a licensed indication for the treatment of GHD adults since 1996. Nonetheless, the advent of GH replacement for adult GHD patients (Jorgensen et al., 1989; Salomon et al., 1989) has proved informative about the overall management of the GHD child and teenager; equally, the longstanding experience of the paediatric endocrinologist with GH replacement has provided some guidance about potential pitfalls in the diagnosis and management of the adult GHD patient. It is the knowledge exchange at this professional interface that forms the focus of this article.
IntroductionThe type of underlying pathophysiology differs in childhood-onset (CO) compared with adult-onset (AO) GHD. In childhood the commonest aetiology is isolated idiopathic GHD (August et al., 1990; Vanderschueren-Lodeweyckx, 1994), a blanket term that includes some children with distinctive pathophysiology that may be demonstrated radiologically, and others in whom the pathological insult is unknown and the explanation for the GHD ill-understood. By contrast, AOGHD is most frequently due to a pituitary adenoma and/or treatment with surgery or radiotherapy (Rosen & Bengtsson, 1990; Toogood et al., 1994). In GHD children poor growth dominates the clinical imperative to offer GH replacement whereas in adult life there is no single symptom or sign that is pathognomonic of GHD; nonetheless, GHD in adult life is associated with increased fat mass, particularly distributed in the truncal region (Salomon et al., 1989; DeBoer et al., 1992), reduced lean mass (Salomon et al., 1989; DeBoer et al., 1992), osteopenia (Johansson et al., 1992; Kaufman et al., 1992; Holmes et al., 1994), an adverse cardiovascular risk factor profile (Amato et al., 1993; Beshyah et al., 1994; Johansson et al., 1994, 1995), reduced exercise capacity (Cuneo et al., 1991; Nass et al., 1995) and reduced quality of life (Rosen et al., 1994). In addition, the standardized mortality rate is increased in hypopituitary adult patients on full replacement therapy with glucocorticoids, thyroxine and sex steroids but in whom GHD remains untreated; thus the increased mortality has been attributed to the GHD to a varying degree dependent on the interpretation of the literature by different endocrinologists (Murray and Shalet, 2000).
Dose requirements and the biochemical severity of the hormone deficiency also vary between GHD children and adults; children with all grades of GHD from mild to severe, but only adults with severe GHD, are considered for GH replacement and the replacement dose of GH is significantly greater in children than in adults, the variation in dose requirement reflecting the evolution of change in endogenous GH secretion with age in normal individuals.
Diagnosis
GH secretion is a continuum between normality and abnormality; therefore, with rare exception the diagnosis of GHD must be made on arbitrary grounds. The more severe the GHD, the less arbitrary the diagnosis, whereas the lesser degrees of GHD (GH insufficiency) merge into normality. In recent years more normative data about the GH response to the entire range of provocative stimuli in childhood have become available (Zadik et al., 1990; Marin et al., 1994; Ghigo et al., 1996); however, over the years the threshold level used to characterize a normal GH response has been defined arbitrarily. Initially it was set at 5 ng/ml (considered equivalent to 10 mU/l at the time) based on the results of studies such as those performed by Kaplan et al. (1965, 1968), in which 80 of 91 (88%) children who were not GHD showed a peak GH response to an insulin tolerance test (ITT) of > 5 ng/ml whereas all 53 GHD children had a peak GH response below 5 ng/ml to the same stimulus. The GH response setpoint was gradually moved to 7 ng/ml (Frasier, 1974) as GH testing became more common, and finally reached 10 ng/ml (20 mU/l) with the increased availability of biosynthetic GH. Not only is normality defined arbitrarily, but the same threshold GH level is used inappropriately to define normality irrespective of the pharmacological stimulus applied.
The gradual 'slippage' in the definition of GHD in childhood from 5 ng/ml to 10 ng/ml brought with it certain consequences; given the fact that GH secretion is a continuum between normality and abnormality, the higher the threshold for diagnosing GHD is raised, the more likely there will be overlap between normality and abnormality. Thus the relaxing of the biochemical definition of childhood GHD causes diagnostic problems and, at the same time, introduces therapeutic dilemmas because of the increasing mildness of the degree of GHD of some of the children now being considered for GH replacement; the milder the deficiency the less the expected impact of GH replacement on biological endpoints such as growth. In other words, how much difference does it make to offer standard GH replacement to a child with a peak GH response of 9 ng/ml rather than another child with a peak GH response to provocation of 11 ng/ml?
Perceived wisdom, at the time adult GH replacement was introduced, suggested that establishing a diagnosis of GHD in the adult might provide even greater diagnostic dilemmas than in the child, given that auxology was of no use in the adult. In practice this has not proved to be the case for the majority of adults considered for GH replacement. This is for two reasons; first, only adults with biochemically severe GHD are even considered for GH replacement; and second, there is a natural history of evolution of hypopituitarism in patients with a mass lesion of the hypothalamic-pituitary region or in those who have undergone surgery and/or radiotherapy to this region. GH is usually the first of the anterior pituitary hormones to be affected by these various pathological insults, which means that in a patient with multiple pituitary hormone deficits the probability of severe GHD being present is extremely high (Klibanski, 1987; Littley et al., 1989). Thus Toogood et al. (1994) showed that the median peak GH response to an ITT in four age-matched groups of adult patients with isolated GHD and GHD plus one, two and three additional pituitary hormone deficits was 3·8, 1·5, 0·8 and 0·7 ng/ml (1 ng/ml = 2·6 mU/l), respectively (Fig. 1). Of patients with two or three additional pituitary hormone deficits, 91% had a peak GH response less than 1·9 ng/ml. Similar conclusions regarding the relationships between GHD and additional pituitary hormone deficits have been drawn irrespective of whether GH status has been assessed by ITT (Weissberger et al., 1994), urinary GH (Bates et al., 1995) or 24-h spontaneous profile (Toogood et al., 1997b).
Figure 1. (click image to zoom) The distribution of the peak serum GH levels in response to an ITT in 190 patients divided into groups according to the degree of hypopituitarism present, that is the number of anterior pituitary hormone deficiencies, in each patient. Horizontal bars represent medians; 1 ng/ml = 2·6 mU/l. (a) GHD0; ( 
GHD1; © GHD2; (d) GHD3. Reproduced from Toogood et al. (1994).The pattern of evolution of hypopituitarism in children with hypothalamic-pituitary disease is similar to that seen in adults; the observation is, however, less useful in the child in whom the commonest cause of GHD is 'isolated idiopathic'. Thus in the investigation of GH status in a child, a strategy consisting of two tests of GH status evolved; the rationale being based on the observation that any normal child might 'fail' any single GH provocative test. Additionally, in recent years with the advent of IGF-I and IGFBP-3 databases derived from normal prepubertal and pubertal children, the use of IGF-I/IGFBP-3 estimations has been increasingly incorporated into the investigation of the short child, either to replace one of the two GH provocative tests or to be performed in addition to the GH provocative tests (Juul & Skakkebaek, 1997). In the meantime, however, the 'two GH test' approach has never been formerly validated. This left some uncertainty as to how best to investigate GH status in an adult with partial hypopituitarism, a problem subsequently studied by Lissett et al. (1999); the latter group reviewed the results of GH provocative tests in 103 adult patients with documented or potential hypothalamic-pituitary disease and 35 adult normal volunteers. All patients and normal volunteers underwent an ITT and an arginine stimulation test (AST). Severe GHD was defined in a stimulus-dependent manner. Patients were categorized into groups according to the number of anterior pituitary hormone deficits present other than GHD. The concordance between the AST and the ITT (percentage of patients in whom both tests confirmed or refuted the biochemical diagnosis of severe GHD) was 100%, 76·8%, 66·6%, 83·3% and 92·3% in the controls and in those GHD patients with 0, 1, 2 and 3 additional deficits, respectively. Thus 16/69 GHD0, 5/15 GHD1, 1/6 GHD2 and 1/13 GHD3 patients were misclassified by one or other test.
In addition, the magnitude of the difference between the GH responses to the ITT and AST increased with the underlying mean GH value (mean of the peak responses to the two tests) (Fig. 2). Thus it is a constant ratio that links the GH response to an ITT and AST in an individual rather than a constant difference and the difference between the GH responses to two provocative stimuli is greater in those patients with milder degrees of GHD. There are implications from this study for investigation of GH status in both children and adults. In children it lends support to the idea that the two-test approach is increasingly worthwhile the higher the threshold definition of GHD is set, and in adults, while a single GH provocative test can be used with confidence in patients with two or three additional pituitary hormone deficits, in patients with suspected isolated GHD or with only one additional pituitary hormone deficit, two tests of GH status are required.
Figure 2. (click image to zoom) Magnitude of the difference between each individual's GH response to the ITT and AST is plotted against mean GH value: black square, normal individuals; black circle, patients. Spearman's rank correlation, r = 0·88; P Thus far, the discussion about the number of tests that are required to establish GH status assumes that the information gained from each of the tests is the same and independent of the nature of the pathophysiological changes affecting the hypothalamic-pituitary region. The latter belief has been challenged by the data arising from recent studies; Darzy et al. (2003) investigated GH status in 49 adult patients, all of whom had received cranial irradiation for nonpituitary brain tumours or leukaemia, and 33 sex- and age-matched controls. A combined GH releasing hormone (GHRH) plus AST and an ITT were performed in all patients and controls on separate occasions. GH responses to either test were significantly lower in the patients than in the controls; in patients and controls the median peak GH response to the GHRH + AST was significantly greater than the response to the ITT. However, the ratio of the peak GH response to the GHRH + AST over that achieved with the ITT (discordancy ratio) was significantly higher in the patients compared with normals, consistent with dominant hypothalamic damage and relatively preserved somatotroph responsiveness.
The peak GH response to the ITT fell significantly within 5 years of irradiation with little further change over the subsequent 10 years. By contrast, the peak GH response to the GHRH + AST barely changed within 5 years of irradiation but subsequently declined significantly over the next 10 years (Fig. 3). Thus the evolution of change in GH responsiveness to the two different stimuli over time was markedly different, resulting in a significantly raised discordancy ratio of 6 within the first 5 years postradiotherapy, which then normalized (3-4) over the next 10 years (Darzy et al., 2003).
Figure 3. (click image to zoom) Box and whisker plots representing the peak GH responses to the ITT (a), the GHRH + AST ( and the discordancy ratio © in normals and patients according to the time interval since irradiation. The lower boundary of the box indicates the 25th percentile, a line within the box marks the median, and the upper boundary of the box indicates the 75th centile. Error bars above and below the box indicate the 90th and 10th percentiles, respectively. P-values are derived from comparison of each patient group with the normal control group. Note the BED (biological effective dose of irradiation reaching the hypothalamic-pituitary region) was not different among the groups. Reproduced from Darzy et al. (2003).At a practical clinical level the discordancy between the GH test results is important; 50% of patients classified as severely GHD by the ITT were judged normal or only GH insufficient by the GHRH + AST. The bigger question arising from the observation that for the first 5 years after cranial irradiation the definition of GH status utilizing pharmacological tests is stimulus dependent must centre around the broader application of this principle; in other words are there other hypothalamic pathologies, such as infiltrative disorders, in which discordant GH responses may be seen to different pharmacological stimuli?Therapy The biological endpoint that has dominated GH replacement for GHD children is auxology. Growth is easily quantified in terms of current height, and height velocity over 12 months; it is an endpoint that is defined in the context of the normal population as well as the target height for the individual child, providing the heights of both parents are known. The rationale underpinning GH treatment for short children, however, has been less well substantiated -'whilst individual short children may show psychological stress, as groups (statistically) they do not appear to have clinically significant behavioural or emotional problems and it needs to be established whether being made taller produces measurable benefit in terms of academic or material success or psychological contentment. Currently there is no strong evidence that GH therapy improves psychological adaptation in short stature children' (Kelnar, 2003). Exactly the same comments might have been written about the GH-insufficient child treated with GH replacement.
A major question that arises from our inability to substantiate the rationale for childhood GH treatment is do we need to optimize final height in GHD children receiving GH replacement? In previous times, prior to the introduction of recombinant GH preparations, the supply of pituitary-derived GH was limited; therefore it was often considered adequate for the GH-replaced child to attain a final height within the normal population (3rd to 97th centile) range but not necessarily within the target height range. With the unlimited availability of recombinant GH preparations a much greater possibility exists for the child to achieve his or her target height range, but how much does such an achievement matter?
A recent study by Attanasio et al. (2002) has shed light on this question by determining body composition parameters in 92 COGHD patients, mean age 20·9 years, who had been treated to final height with GH for just under 9 years and had stopped treatment a mean of 1·57 years previously, but who remained severely GHD with an IGF-I level below the first centile of the age-matched normal range; these were compared with 35 age-matched GH-naïve hypopituitary patients with AOGHD. Lean body mass (LBM), fat mass (FM) and total bone mineral content (BMC) were assessed by dual-energy X-ray absorptiometry (DEXA) and corrected for actual height. Within genders, COGHD patients had about 20% less total body mass, LBM, FM and BMC than AOGHD patients. In addition, statistically significant correlations were present between final height SD score minus target height SD score and LBM and BMC in both genders (Attanasio et al., 2002). The implications from these observations are important; they indicate that the achievement of target height in the GH-replaced child does matter and that failure to reach target height has detrimental consequences in terms of skeletal health and body composition. Height is not necessarily meaningful per se, but as a surrogate for normalization of body composition it is crucial!
Influence of Timing of Onset of GHD in Adult Life
While the clinical and biochemical picture of the GHD adult is essentially the same in broad terms irrespective of whether the onset of GHD occurred in childhood or adult life, there are important differences that are of practical as well as biological interest.
Dyslipidaemia (Murray et al., 2002) and significant impairment of quality of life (QOL) (Murray et al., 1999) are less frequently seen in adults with COGHD compared with AOGHD patients; nonetheless the QOL response to GH replacement is not significantly influenced by the timing of onset of GHD (Murray et al., 1999); in other words for those with severe impairment of QOL, the response to GH replacement is similar in both groups of patients. Interestingly, however, in the early days of adult GH replacement when supraphysiological GH dosage dominated the clinical studies, the side-effects related to fluid retention occurred predominantly in AOGHD patients and rarely in COGHD patients (Holmes & Shalet, 1995); the latter observation sits easily with the rarity of such complications during childhood GH replacement.
The IGF-I status of the GHD adult is significantly affected by the timing of onset of GHD (Lissett et al., 2003); thus if all other relevant variables are controlled then the IGF-I SD score is 1·4 SDS lower in age-matched patients with COGHD compared with those with AOGHD (Fig. 4). There are practical implications from this observation in that the dominant variable influencing the adult GH replacement dosage required to normalize the IGF-I level in GHD adults is the pretreatment IGF-I level (Murray et al., 2000); therefore, the replacement dose utilized in adults with COGHD is significantly greater than in those with AOGHD. The scientific explanation for the lower IGF-I status of COGHD adults is also of interest; does it reflect inappropriate programming of IGF-I production in childhood? If this is the case does it simply imply suboptimal GH dosage during childhood or could it be influenced by the nonphysiological nature of the once-daily GH subcutaneous injection?
Figure 4. (click image to zoom) A box and whisker plot of IGF-I SDS, subdivided by age at onset of pituitary disease and timing of onset of pituitary disease. Subjects with onset of pituitary disease at age 16-20 years occurred in both groups but had significantly different IGF-I SDS, P GH is intricately involved in bone growth and turnover; this is supported by the finding of reduced serum and urinary markers of bone turnover in GHD adults (Toogood et al., 1997a; Colao et al., 1999a), and the increase in these markers following GH replacement therapy (Binnerts et al., 1992; Bengtsson et al., 1993; Vandeweghe et al., 1993; Johannsson et al., 1996). Bone turnover is a coupled process that occurs continuously throughout life, bone resorption being followed in time by bone formation. With ageing it has been proposed that at the level of the remodelling unit, this process becomes increasingly inefficient. Thus in the elderly at the end of each remodelling cycle, small deficits in bone mass are accrued (Marcus, 1997, 1998), which lead to the observed age-related loss of bone mass. Predictably, therefore, the effect of GHD on the skeleton is heavily influenced by the patient's age; GHD during adolescence and young adult life before attainment of peak bone mass, when bone mass is being accrued, slows this acquisition and results in osteopenia. However, in the elderly in whom bone turnover is inefficient, a reduction in bone turnover, as a consequence of GHD, may reduce the rate of bone mineral loss, resulting in a normal bone mineral density (BMD).
Observational studies (Murray et al., 2004b) support the latter conclusions; osteopenia is seen in young adult GHD patients, with approximately 20-30% of those under 30 years of age having BMD z-scores below – 2 at the lumbar spine, hip and radius. By contrast, those adult GHD patients over the age of 60 years are no more frequently osteopenic than the normal age-matched population.
Thus the skeletal indication for GH replacement is primarily a consideration for young adult patients who acquired GHD either during childhood or early after completion of linear growth. The clinical occasion when this becomes an extremely important concern is during the transfer of management of the severely GHD teenager from paediatric to adult endocrine care.
Transitional Care of the GHD Teenager
It is the GHD teenager that has done more to bring the adult and paediatric endocrine communities together than any other category of patients, with several practical questions facing these communities. Which diagnostic criteria should be used to confirm severe GHD at completion of linear growth? In all those confirmed to be severely GHD, should GH replacement be continued throughout teenage years and the rest of adult life or would there be disadvantages if GH replacement was stopped for a few years and only reintroduced later on an individual basis? Furthermore, if GH replacement is continued seamlessly, what is the optimal dose – that used in adult or paediatric practice?
Currently the criteria used for the diagnosis of severe GHD in a teenager are identical to those adopted for severe GHD in adult life. GH secretion, however, is far greater in the normal teenager than in the middle-aged healthy adult; therefore, the threshold adopted for the diagnosis of severe GHD in the teenager may be inappropriately set too low. This raises further important questions about how to manage and follow those teenagers who retest GH insufficient using such criteria. Relatively little information is available to answer these questions, and in a practical world in which a health-economic battle to provide GH replacement for all adults with severe GHD prevails, these are questions for the future.
Recent discontinuation studies and placebo-controlled randomized therapeutic trials, however, are beginning to provide guidance about the need for continuation of GH replacement for GHD throughout the transition phase (Johannsson et al., 1999; Norrelund et al., 2000a,
, and the choice of GH dose. More recently, we have completed a large multinational controlled 2-year study in patients who had terminated paediatric GH at final height (Shalet et al., 2003). Patients were randomized to GH at 25 µg/kg/day (paediatric dose, n = 58) or 12·5 µg/kg/day (adult dose, n = 59) or no GH treatment (control, n = 32); all patients had severe GHD with an IGF-I value less than the first centile of age-related normative values. Bone mineral content (BMC) and BMD were measured by DEXA and evaluated centrally. After 2 years significant increases were seen with both GH treatments compared with control in bone-specific alkaline phosphatase (BAP) and type 1 collagen C-terminal telopeptide : creatinine (ICTP/creatinine) ratio, but there were no significant dose effects.Total BMC increased by 9·5 ± 8·4% in the adult group, 8·1 ± 7·6% in the paediatric dose group and 5·6 ± 8·4% in controls (anova, P = 0·008), with no significant GH dose effect. BMC increased predominantly at the lumbar spine rather than at the femoral neck or hip. There were no gender-related differences in BMC changes with either dose whereas the IGF-I increase was significantly higher with the paediatric than with the adult dose in females but not males.
Highly significant negative correlations were found between the time since the last GH injection of paediatric treatment and the baseline values for BAP (r = 0·31) and for the ICTP/creatinine ratio (r = 0·31) (Fig. 5). Even more interesting, the pattern of response in total BMC to GH treatment was also related to the time since withdrawal of paediatric GH therapy (Shalet et al., 2003). In the control group there was a significant negative correlation (r = –0·44) between the 2-year change in BMC and time since last GH injection, and for both treatment groups similar correlations were also found with BMC changes in the first year of GH treatment (r = –0·35).
Figure 5. (click image to zoom) Correlation of serum BAP and urinary ICTP/creatinine ratio with time since stopping paediatric GH treatment in patients with childhood GHD. Reproduced from Shalet et al. (2003). The results of this study confirm that in patients with severe COGHD accrual of bone mass continues after GH cessation, and the increase in BMC observed in the control group during the 2-year study period is consistent with the 4·5% increase described by Fors et al. (2001) in a smaller group of COGHD patients after discontinuation of GH treatment. These findings support the concept that the GH effect on bone persists for 1-2 years after cessation of GH treatment, but eventually disappears.
Without GH treatment the net gain in total BMC was about 5% and with GH treatment about 10%, confirming the hypothesis that continued GH treatment after attainment of final height induces significant additional bone maturation in patients with severe GHD (Shalet et al., 2003). The study period was 2 years, but, given the prolonged effect of GH on bone, it is likely that further progression to peak bone mass would have been observed with a longer follow-up period.
The observation that the overall treatment effect was substantially the same with both GH dosages was unexpected. One possible explanation of this finding is that different dosages may have had different effects on bone turnover. In fact, although differences were statistically nonsignificant, the increase in ICTP/creatinine was greater with the higher dose and the opposite was the case for BAP. It has been shown that high GH doses in young GHD adults cause desynchronization of bone turnover with predominance of bone resorption over bone formation (Balducci et al., 1995); the trends seen in the present study suggest a similar mechanism and indicate that the paediatric dose was inappropriately high for adequate bone mass accumulation.
In summary, this study demonstrated that withdrawal of GH replacement at final height may limit progression to peak bone mass in patients with severe COGHD and that adequate GH replacement is required to continue this process. The effect on bone is obtained with a dose regimen that is in the high adult replacement range and is of clinical relevance for subsequent bone health in adult life. The data also indicate that for optimal progress to peak bone mass, GH treatment after attainment of final height should not be discontinued.
Diagnostic and Therapeutic Studies in Adults Inform About Paediatric GH Practice
- The significant differences in body composition and BMC between young adults treated in childhood for COGHD and young adults with untreated AOGHD imply that paediatric GH replacement has often been suboptimal.
- The observation that there is a significant relationship between the statural amount by which a GH-replaced teenager fails to achieve target height and the reduction in total BMC and LBM implies that auxology deserves its role as the dominant clinical endpoint followed in paediatric GH practice; not because achieving target height is of itself crucial, but as a surrogate for the acquisition of normal body composition, optimization of growth is a very worthy goal.
- Information obtained from the use of two GH diagnostic tests in adult patients with varying degrees of hypopituitarism has provided some validity for the strategy of testing utilized in the investigation of the child with the putative diagnosis of isolated idiopathic GHD.
- The numerous studies of body composition changes in GHD teenagers confirm that growth and development do not end at attainment of final height, and show that GH makes a crucial contribution to the end result; thus GH replacement for developmental purposes should continue until adult acquisition of LBM and PBM and not stop once final height is achieved.
Partial GHD
There is no doubt that partial GHD exists; this is hardly surprising given that partial deficiencies of gonadotrophin, ACTH, TSH and vasopressin exist. Up until now, however, there have been relatively few studies of the impact of partial GHD on biological endpoints in adults. Furthermore, the paediatric GH experience has emphasized that it is the continuum in GH secretion between normal children and children with varying degrees of GHD that underlies the major difficulty in diagnosing GHD in childhood.
Initial studies by Colao et al. (1999a,
, using the arginine plus GHRH test to categorize GH status, showed dyslipidaemia but normal BMD in a cohort of adults with partial GHD. More recently, increased FM (Murray et al., 2004a), reduced LBM (Murray et al., 2004a) and abnormal insulin secretion (Murray & Shalet, 2001) have been observed in adults with partial GHD, the degree of abnormality tending to lie between that seen in normals and those with severe GHD. This is not very surprising, particularly as the biochemical diagnosis of severe GHD is arbitrarily based.These observational studies raise the possibility of potentially treating adults with partial GHD with GH; to do so, however, will first require the
endocrine community to diagnose partial GHD in adults.
The hypothetical patient will have a putative lesion of the hypothalamic-pituitary axis and, given the early timing of GHD in the evolution of hypopituitarism, usually have no other pituitary hormone deficits. Truncal obesity will be present, and it is now established in clinically nonobese healthy adults that relative adiposity, in the abdominal region in particular, is a major negative determinant of stimulated GH secretion (Vahl et al., 1996); therefore GH status will be defined as partial GHD. In practice, an IGF-I estimation is unlikely to be helpful. A pathologically low IGF-I level would point towards a diagnosis of GHD but obesity is associated with a normal IGF-I level and the majority of patients with partial GHD are also likely to exhibit a normal IGF-I level. The fundamental dilemma requiring resolution is the following; is this a fat patient in whom visceral obesity is responsible for the biochemical findings of partial GHD? Or is this a patient afflicted by partial GHD, which is itself responsible for the truncal obesity?
Therefore, if we do move in this therapeutic direction the current problems that torment the paediatric endocrinologist, regarding diagnostic criteria for GHD and selection of patients likely to benefit from GH therapy, will move on to plague the adult endocrine community.
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Acknowledgements
This review reflects the contents of my Clinical Endocrinology Trust Lecture (2003); its substance owes much to the efforts of numerous research fellows over the past 25 years. I am also grateful to Colin Beardwell for letting me be myself and Andrea Attanasio for many stimulating discussions about physical development during the transition years.
Reprint Address
Correspondence: S. M. Shalet, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK. Fax: + 44 0161 446 3772; E-mail: stephen.m.shalet@man.ac.uk
- The significant differences in body composition and BMC between young adults treated in childhood for COGHD and young adults with untreated AOGHD imply that paediatric GH replacement has often been suboptimal.
The best I've gotten so far is "maybe in January".
No one seems to be able to get any. I was thinking, maybe if I volunteered as an aide at the hospital that they'd have to give me a shot. Then I could quit! Whatcha think? 
GHD1; © GHD2; (d) GHD3. Reproduced from Toogood et al. (1994).
Next-Generation Growth Hormone
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Serono and Nautilus Biotech Sign Worldwide Agreement to Develop and Commercialize a Next-Generation Growth Hormone
GENEVA, Switzerland and PARIS, France, November 15 /PRNewswire/ -- Serono (virt-x: SEO and NYSE: SRA) and protein evolution company Nautilus Biotech (Private) announced today that they have signed an agreement under which Serono and Nautilus will work together to develop the next-generation of human growth hormone, with improved biological, pharmacological and clinical profiles. This improved version of human growth hormone would allow less frequent injections of this therapeutic protein which is currently administered daily.
Under the terms of the agreement, Serono will receive an exclusive license to develop the next-generation human growth hormone and an exclusive option to license exclusive worldwide rights to develop, manufacture, and commercialize improved variants of the protein generated by Nautilus's rational evolution technology, a process mimicking natural evolution. In return, Nautilus will receive an initial fee and potential milestone payments related to development progress, regulatory submissions and approvals. If a new version of growth hormone is successfully developed and registered worldwide, and Serono exercises its option right, the aggregate amount of these payments could reach Euro 19 million. Nautilus will also receive undisclosed royalties on sales of the improved protein.
"Serono has a long-term commitment to people with endocrine and metabolic disorders requiring growth hormone treatment", said Tim Wells, Senior Executive VP Research of Serono. "We believe that the rational evolution technology of Nautilus represents a promising approach to generate growth hormone variants with great potential to deliver improved patient care."
"Serono has an impressive track record in the development and marketing of protein therapeutics," said Manuel Vega CEO of Nautilus Biotech. " We are confident that in Serono we have found a strong and committed partner to fully exploit the power of our protein improvement technology and to develop this new product as a competitive improvement to currently marketed alternatives. This agreement with Serono, a world leader in protein pharmaceuticals, validates our strategy and business model in the area of biopharmaceuticals".
Serono forward-looking statements
Some of the statements in this press release are forward looking. Such statements are inherently subject to known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements of Serono S.A. and affiliates to be materially different from those expected or anticipated in the forward-looking statements. Forward-looking statements are based on Serono's current expectations and assumptions, which may be affected by a number of factors, including those discussed in this press release and more fully described in Serono's Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission on March 25, 2004. These factors include any failure or delay in Serono's ability to develop new products, any failure to receive anticipated regulatory approvals, any problems in commercializing current products as a result of competition or other factors, our ability to obtain reimbursement coverage for our products, and government regulations limiting our ability to sell our products. Serono has no responsibility to update the forward-looking statements contained in this press release to reflect events or circumstances occurring after the date of this press release.
About Serono
Serono is a global biotechnology leader. The Company has eight biotechnology products, Rebif®, Gonal-F®, Luveris®, Ovidrel® /Ovitrelle®, Serostim®, Saizen®, Zorbtive and Raptiva®. In addition to being the world leader in reproductive health, Serono has strong market positions in neurology, metabolism and growth and has recently entered the psoriasis area. The Company's research programs are focused on growing these businesses and on establishing new therapeutic areas. Currently, there are approximately 30 ongoing development projects.
In 2003, Serono achieved worldwide revenues of US$2,018.6 million, and a net income of US$390.0 million, making it the third largest biotech company in the world. Its products are sold in over 90 countries. Bearer shares of Serono S.A., the holding company, are traded on the virt-x (SEO) and its American Depositary Shares are traded on the New York Stock Exchange (SRA).
About Nautilus Biotech
Nautilus is focused on improving and developing next generation protein pharmaceuticals. Using its proprietary and unique technologies, Nautilus has generated a pipeline of improved therapeutic protein molecules with single amino acid substitutions; and has IP claims on 20 improved cytokines. Long lasting interferon alpha and interferon beta, presently in preclinical development, are Nautilus' lead molecules. Nautilus Biotech is a privately owned, VC backed company, founded in late 1999. More about Nautilus: www.nautilusbiotech.com
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