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Postuar nga NS-6 datë 03 Tetor 2007 - 14:49:

A Link Between Eosinophilic Esophagitis and Celiac Disease?

Cod. B03102007

Eosinophilic esophagitis (EoE) is an inflammatory disorder that is characterized by severe, isolated eosinophilic infiltration of the esophagus; it is associated with a variety of clinical findings, including dysphagia, food impaction, vomiting, chest pain, and weight loss. Although its causes are unknown, EoE has been linked to food hypersensitivity, particularly among children. In fact, the primary approach for treating pediatric EoE is elimination diets, which typically exclude cow’s milk, soy, wheat, eggs, peanuts, and seafood. Now, investigators describe a possible association between EoE and celiac disease.

During a 21-month period at a single center in Italy, 17 children (age, <10 years) met the established clinical and histologic criteria for EoE diagnosis. All had presenting complaints of dysphagia, epigastric pain, or regurgitation or vomiting; none had presenting complaints of diarrhea, failure to thrive, anemia, or anorexia. During evaluation, celiac disease — established by serologic testing (anti–tissue transglutaminase and antiendomysial antibodies) with histologic confirmation by duodenal biopsies — was diagnosed in six of the patients. These patients all switched to gluten-free diets, whereas the remaining 11 patients switched to restricted diets based on allergy-testing results.

During an average follow-up of 6 months, all six patients with celiac disease had complete resolution of their presenting EoE complaints, and repeat endoscopy demonstrated complete resolution of esophageal eosinophilia in the three who underwent the procedure. In contrast, only 7 of the 11 patients without celiac disease had moderate improvement in their presenting complaints; repeat endoscopy in 7 patients showed improvement, but not resolution, of esophageal eosinophilia.

Comment: Food antigens have been implicated in both EoE and celiac disease, but this report is the first to demonstrate a potential association between the two conditions. The clinical and histologic improvements in EoE seen among patients with celiac disease in this study were impressive. Whether this finding reflects a real association or a selection bias clearly warrants further evaluation in both pediatric and adult patients with EoE.

— David A. Johnson, MD

Published in Journal Watch Gastroenterology September 21, 2007

the origin of the article:
Quaglietta L et al. Eosinophilic oesophagitis and coeliac disease: Is there an association? (Aliment Pharmacol Ther 2007 Aug 1; 26:487).

per celiakine me shume mund te shihni:
-celiakia (Cod. A 22092007)
- pronjoza e celiakise (Cod. B 22092007)


Postuar nga MARSMED datë 08 Tetor 2007 - 23:49:

Hip Size of Mothers Linked to Breast Cancer in Daughters

Cod. A09102007

Hip Size of Mothers Linked to Breast Cancer in Daughters



Postuar nga NS-6 datë 16 Tetor 2007 - 00:06:

FDA Approves Raltegravir Tablets, First-in-Class Oral HIV-1 Integrase Inhibitor

Cod. B16102007

FDA Approves ISENTRESS™ (raltegravir) Tablets, First-in-Class Oral HIV-1 Integrase Inhibitor

WHITEHOUSE STATION, N.J., Oct. 12, 2007 - Merck & Co., Inc., announced today that the U.S. Food and Drug Administration (FDA) granted ISENTRESS™ (raltegravir) tablets accelerated approval for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced adult patients who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents.

This indication is based on analyses of plasma HIV-1 RNA levels up through 24 weeks in two controlled studies of ISENTRESS [pronounced i-sen-tris]. These studies were conducted in clinically advanced, three-class antiretroviral [nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs)] treatment-experienced adults. The use of other active agents with ISENTRESS is associated with a greater likelihood of treatment response. The safety and efficacy of ISENTRESS have not been established in treatment-naïve adult patients or pediatric patients. There are no study results demonstrating the effect of ISENTRESS on clinical progression of HIV-1 infection. Longer term data will be required before the FDA can consider traditional approval for ISENTRESS.

ISENTRESS is the first medicine to be approved in a new class of antiretroviral drugs called integrase inhibitors. ISENTRESS works by inhibiting the insertion of HIV DNA into human DNA by the integrase enzyme. Inhibiting integrase from performing this essential function limits the ability of the virus to replicate and infect new cells. There are drugs in use that inhibit two other enzymes critical to the HIV replication process - protease and reverse transcriptase - but ISENTRESS is the only drug approved that inhibits the integrase enzyme.

The FDA's decision was based on a 24-week analysis of clinical trials in which ISENTRESS in combination with optimized background therapy (OBT) in treatment-experienced patients, provided significant reductions in HIV RNA viral load and increases in CD4 cell counts.

"The development of ISENTRESS is a significant milestone in the history of HIV/AIDS therapy because we now have a drug that's potent against another key enzyme essential for viral replication," said Joseph J. Eron Jr., M.D., professor of medicine, Division of Infectious Diseases, UNC Chapel Hill School of Medicine. "It's important for physicians to know that ISENTRESS should always be used in combination with other active agents."

Data from two ongoing Phase III multi-center, double-blind, randomized, placebo-controlled studies (BENCHMRK-1 and BENCHMRK-2) in 699 treatment-experienced adult patients with documented resistance to at least one drug in each of three classes (NRTIs, NNRTIs and PIs) of antiretroviral therapies showed that ISENTRESS 400 mg dosed twice daily in combination with OBT was significantly more effective at both reducing levels of HIV viral RNA and increasing CD4 cell counts in these patients living with HIV, when compared to a regimen of placebo plus OBT.

Pooled analyses from the two Phase III studies showed that after 24 weeks of therapy, 75.5 percent of patients (216 out of 286) receiving ISENTRESS in combination with OBT achieved HIV viral RNA load reduction to below 400 copies/mL compared to 39.3 percent of patients (59 out of 150) receiving placebo plus OBT. In addition, after 24 weeks of therapy, 62.6 percent of patients (179 out of 286) receiving ISENTRESS plus OBT achieved viral load reduction to below 50 copies/mL compared to 33.3 percent of patients (50 out of 150) receiving placebo plus OBT. After 24 weeks of therapy, increases in CD4 cell counts from baseline were 89 and 35 cells/mm3 for patients receiving ISENTRESS plus OBT and for those receiving placebo plus OBT, respectively.

Important safety information about ISENTRESS
ISENTRESS does not cure HIV or AIDS and does not prevent passing HIV to others. Healthcare providers should know that immune reconstitution syndrome has been reported in patients treated with antiretroviral therapy, which may necessitate further evaluation and treatment.

The most commonly reported adverse experiences of any severity (mild, moderate or severe) regardless of drug relationship were diarrhea (16.6 percent vs. 19.5 percent), nausea (9.9 percent vs. 14.2 percent), headache (9.7 percent vs. 11.7 percent) and fever (4.9 percent vs. 10.3 percent) for ISENTRESS plus OBT and placebo plus OBT, respectively.

Creatine kinase elevations were observed in subjects who received ISENTRESS. Myopathy and rhabdomyolysis have been reported; however, the relationship of ISENTRESS to these events is not known. ISENTRESS should be used with caution in patients at increased risk of myopathy or rhabdomyolysis, such as patients receiving concomitant medication known to cause these conditions.

Safety and tolerability profile of ISENTRESS
Results from pooled safety analyses from three separate studies in treatment-experienced patients taking 400 mg of ISENTRESS dosed twice daily plus OBT or placebo plus OBT showed that after 24 weeks of therapy the rates of discontinuation of therapy due to adverse experiences were 2.0 percent in patients receiving ISENTRESS plus OBT and 1.4 percent in patients receiving placebo plus OBT. In addition, drug-related clinical adverse events of moderate to severe intensity occurring in greater than or equal to 2.0 percent of patients were diarrhea (3.7 percent vs. 4.6 percent), nausea (2.2 percent vs. 3.2 percent) and headache (2.4 percent vs. 1.4 percent) for ISENTRESS plus OBT and placebo plus OBT, respectively.

Drug interactions
Based on the results of drug interaction studies and the clinical trials data, no dose adjustment of ISENTRESS is required when coadministered with other antiretroviral agents. Also, preclinical studies show that ISENTRESS is not metabolized by cytochrome P450 enzymes. Caution should be used when coadministering ISENTRESS with strong inducers of uridine diphosphate glucuronosyltransferase (UGT) 1A1 (e.g., rifampin) due to reduced plasma concentrations of ISENTRESS.

About ISENTRESS
ISENTRESS is a single 400 mg tablet taken twice daily without regard to food. ISENTRESS does not require boosting with ritonavir.

Merck has worked closely with the HIV community regarding the price of ISENTRESS. The wholesale acquisition cost (WAC) of ISENTRESS will be $27 per day, comparable to the price of several available ritonavir-boosted protease inhibitors.

To help patients in the United States who cannot afford treatment with ISENTRESS, the SUPPORT™ program is available. The SUPPORT program is a patient assistance program to help patients who have been prescribed ISENTRESS by providing personalized support and patient advocacy regarding individual reimbursement issues. In addition, Merck also participates in the Partnership for Prescription Assistance program, a single point of access to more than 475 public and private patient assistance programs. ISENTRESS will be available in pharmacies in approximately two weeks. For more information on ISENTRESS, visit www.isentress.com.

Expanded access program
ISENTRESS is currently available worldwide to qualified patients through an expanded access clinical research program, EARMRK. This global program provides early access to ISENTRESS for patients failing current therapy whose HIV is resistant to drugs in three existing classes (NRTIs, NNRTIs, PIs) of antiretroviral medications. Information about the program can be found at www.benchmrk.com.

Merck HIV research
Merck is committed to developing innovative therapies that offer advances in the treatment of infectious diseases - including HIV. Merck's efforts to develop investigational treatments for HIV/AIDS have been under way for more than 20 years and continue today. Merck began its HIV integrase inhibitor research in 1993 and was the first to demonstrate inhibition of HIV integrase in vitro and in vivo.

Prevalence of HIV/AIDS
In 2006, over one million Americans were living with HIV/AIDS and it is estimated that approximately 40,000 new cases of HIV/AIDS are diagnosed each year in the United States. Worldwide, an estimated 40 million people are infected with HIV/AIDS, and more than four million new infections occurred in 2006.

"As the AIDS crisis continues, new drugs like ISENTRESS are needed, which target the virus in unique ways," said Ben Cheng, deputy director, Forum for Collaborative HIV Research. "The HIV Advocacy Community is really excited and encouraged by this new treatment."

About Merck
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.

Forward-looking statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2006, and in its periodic reports on Form 10-Q and Form 8-K, which the company incorporates by reference.

ISENTRESS™ is a trademark of Merck & Co., Inc.
SUPPORT™ is a trademark of Merck & Co., Inc.


Postuar nga NS-6 datë 20 Dhjetor 2007 - 00:07:

Anastrozole VS Tamoxifen

Cod. A20122007

Source : The Lancet Oncology
Date of Publication : 15 dicember 2007

Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial

Background

Little data exist on whether efficacy benefits or side-effects persist after 5 years of adjuvant treatment with an aromatase inhibitor. We aimed to study long-term outcomes in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial that compares anastrozole with tamoxifen after a median follow-up of 100 months.

Methods

We analysed postmenopausal women with localised invasive breast cancer. The primary endpoint disease-free survival (DFS), and the secondary endpoints time to recurrence (TTR), incidence of new contralateral breast cancer (CLBC), time to distant recurrence (TTDR), overall survival (OS), and death after recurrence were assessed in the total population (intention to treat; ITT: anastrozole, n=3125; tamoxifen, n=3116; total 6241) and the hormone-receptor-positive subpopulation, the clinically important subgroup for which endocrine treatment is now known to be effective (84% of ITT: anastrozole, n=2618; tamoxifen, n=2598; total 5216). After treatment completion, fractures and serious adverse events continued to be collected blindly (safety population: anastrozole, n=3092; tamoxifen, n=3094; total 6186). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN18233230.

Findings

At a median follow-up of 100 months (range 0–126), DFS, TTR, TTDR, and CLBC were improved significantly in the ITT and hormone-receptor-positive populations. For hormone-receptor-positive patients: DFS hazard ratio (HR) 0·85 (95% CI 0·76–0·94), p=0·003; TTR HR 0·76 (0·67–0·87), p=0·0001; TTDR HR 0·84 (0·72–0·97), p=0·022; and CLBC HR 0·60 (0·42–0·85), p=0·004. Absolute differences in time to recurrence increased over time (TTR 2·8% [anastrozole 9·7% vs tamoxifen 12·5%] at 5 years and 4·8% [anastrozole 17·0% vs tamoxifen 21·8%] at 9 years) and recurrence rates remained significantly lower on anastrozole compared with tamoxifen after treatment completion (HR 0·75 [0·61–0·94], p=0·01). The fewer deaths after recurrence (anastrozole 245 vs tamoxifen 269) was not significant (HR 0·90 [0·75–1·07], p=0·2), and no effect was noted for OS (anastrozole 472 vs tamoxifen 477) HR 0·97 [0·86–1·11], p=0·7). Fracture rates were higher in patients receiving anastrozole than in those receiving tamoxifen during active treatment (number [annual rate]: 375 [2·93%] vs 234 [1·90%]; incidence rate ratio [IRR] 1·55 [1·31–1·83], p<0·0001), but were not different after treatment was completed (off treatment: 146 [1·56%] vs 143 [1·51%]; IRR 1·03 [0·81–1·31], p=0·79). We did not note any significant difference in risk of cardiovascular morbidity or mortality between anastrozole and tamoxifen treatment groups.

Interpretation

These data show long-term safety findings and establish clearly the long-term efficacy of anastrozole compared with tamoxifen as initial adjuvant treatment for postmenopausal women with hormone-sensitive, early breast cancer, and provide statistically significant evidence of a larger carryover effect after 5 years of adjuvant treatment with anastrozole compared with tamoxifen.


Postuar nga NS-6 datë 02 Janar 2008 - 19:37:

Revised AHA Guidelines for Prevention of Infective Endocarditis

Cod. A02012008

The 2007 guidelines reflect questions about the effectiveness of antimicrobial prophylaxis for IE associated with dental, GI, or GU tract procedures.

[Sponsoring Organizations: American Heart Association, American Dental Association, Infectious Diseases Society of America, Pediatric Infectious Diseases Society]

Background and Purpose: Morbidity and mortality associated with infective endocarditis (IE) remain high despite great advances in medicine and surgery. Prevention of IE has therefore been a priority for the American Heart Association for more than 50 years. The 2007 document updates the AHA’s guidelines, last revised in 1997. The key rationale for the current revision is to address the persistent question of whether antimicrobial prophylaxis effectively prevents IE associated with dental, gastrointestinal, or genitourinary (GU) tract procedures.

Key Points:
1. Prophylactic antibiotics based on a patient’s lifetime risk for acquiring IE are no longer recommended for dental, GI, or GU tract procedures. This recommendation follows from the observation that most cases of IE result from bacteremia caused by routine activities such as chewing food, brushing teeth, and flossing. Moreover, no published data clearly indicate that prophylaxis prevents IE from invasive procedures.

2. Dental disease may increase IE risk, but emphasis should shift from antibiotic prophylaxis for dental procedures to improved dental care and oral health in patients with conditions that carry the highest risk for IE.

3. IE prophylaxis is reasonable (Class IIb, level of evidence C) for dental procedures that involve gingival tissues or the periapical region of a tooth and for procedures that perforate the oral mucosa, in patients with cardiac conditions associated with the highest risk for adverse outcomes from IE:

* prosthetic cardiac valve
* previous IE
* unrepaired congenital heart disease (including palliative shunts and conduits)
* completely repaired congenital heart defect with prosthetic material or device, during the first 6 months after the procedure
* repaired congenital heart disease with residual defects at the site or adjacent to the site of a prosthetic patch or device
* cardiac transplantation recipients who develop cardiac valvulopathy

4. IE prophylaxis is no longer recommended for patients with mitral valve prolapse.

5. If administered, antibiotics should be given in a single dose before the procedure. The preferred antibiotic is amoxicillin (2 g in adults and 50 mg/kg in children).

6. IE prophylaxis is not strongly recommended for respiratory tract procedures and not recommended at all for bronchoscopy, unless incision of the respiratory tract mucosa is necessary.

7. IE prophylaxis is not recommended for GU or GI procedures.

Comment: These guidelines represent a marked change in approach to IE prevention, limiting the situations in which antimicrobial prophylaxis is considered reasonable and eschewing strong endorsement of prophylaxis in any setting (the guidelines contain no Class I recommendations). The shift is away from antibiotics and toward dental health. The authors also called for further studies so that future recommendations may be built on a stronger evidence base.

— Harlan M. Krumholz, MD, SM

Published in Journal Watch Cardiology May 30, 2007


Postuar nga NS-6 datë 24 Shkurt 2008 - 22:32:

Insurance Fears Lead Many to Shun DNA Tests

Cod. A24022008

Source : New York Times
Published : 24/02/2008
Author : Amy Harmon

Victoria Grove wanted to find out if she was destined to develop the form of emphysema that ran in her family, but she did not want to ask her doctor for the DNA test that would tell her.

She worried that she might not be able to get health insurance, or even a job, if a genetic predisposition showed up in her medical records, especially since treatment for the condition, alpha-1 antitrypsin deficiency, could cost over $100,000 a year. Instead, Ms. Grove sought out a service that sent a test kit to her home and returned the results directly to her.

Nor did she tell her doctor when the test revealed that she was virtually certain to get it. Knowing that she could sustain permanent lung damage without immediate treatment for her bouts of pneumonia, she made sure to visit her clinic at the first sign of infection.

But then came the day when the nurse who listened to her lungs decided she just had a cold. Ms. Grove begged for a chest X-ray. The nurse did not think it was necessary.

“It was just an ongoing battle with myself,” recalled Ms. Grove, of Woodbury, Minn. “Should I tell them now or wait till I’m sicker?”

The first, much-anticipated benefits of personalized medicine are being lost or diluted for many Americans who are too afraid that genetic information may be used against them to take advantage of its growing availability.

In some cases, doctors say, patients who could make more informed health care decisions if they learned whether they had inherited an elevated risk of diseases like breast and colon cancer refuse to do so because of the potentially dire economic consequences.

Others enter a kind of genetic underground, spending hundreds or thousands of dollars of their own money for DNA tests that an insurer would otherwise cover, so as to avoid scrutiny. Those who do find out they are likely or certain to develop a particular genetic condition often beg doctors not to mention it in their records.

Some, like Ms. Grove, try to manage their own care without confiding in medical professionals. And even doctors who recommend DNA testing to their patients warn them that they could face genetic discrimination from employers or insurers.

Such discrimination appears to be rare; even proponents of federal legislation that would outlaw it can cite few examples of it. But thousands of people accustomed to a health insurance system in which known risks carry financial penalties are drawing their own conclusions about how a genetic predisposition to disease is likely to be regarded.

As a result, the ability to more effectively prevent and treat genetic disease is faltering even as the means to identify risks people are born with are improving.

“It’s pretty clear that the public is afraid of taking advantage of genetic testing,” said Dr. Francis S. Collins, director of the National Human Genome Research Institute at the National Institutes of Health. “If that continues, the future of medicine that we would all like to see happen stands the chance of being dead on arrival.”

Caught in a Bind

For Ms. Grove, 59, keeping her genetic condition secret finally became impossible. When her symptoms worsened she was told to come back to the clinic before antibiotics would be prescribed. But there had been a snowstorm that day, and she could not summon the strength to drive.

“I have alpha-1,” she remembers sobbing into the phone. “I need this antibiotic!”

The clinic called in the prescription.

Ms. Grove, who does freelance accounting from home and has health insurance through her husband’s employer, allowed herself to be identified here because she said she felt an obligation to others — including some in her own family — to draw attention to the bind she sees herself in.

“Something needs to be done so that you cannot be discriminated against when you know about these things,” she said. “Otherwise you are sicker, your life is shorter and you’re not doing what you need to protect yourself.”

Employers say discrimination is already prohibited in the workplace by the Americans with Disabilities Act and existing laws governing privacy of medical records. But employee rights advocates say nothing in those laws explicitly prevents employers hard-pressed to pay for mounting health care costs from trying to screen out employees they know are more likely to get sick.

Courts have yet to rule on the subject. When the Equal Employment Opportunities Commission sued the Burlington Northern Santa Fe Railway for secretly testing the blood of employees who had filed compensation claims for carpal-tunnel syndrome in an effort to discover a genetic cause for the symptoms, the case was settled out of court in 2002.

And in 2005 when Eddy Curry, then the center for the Chicago Bulls, refused a genetic test to learn if he was predisposed to a heart ailment, the team traded him to the New York Knicks.

Insurers say they do not ask prospective customers about genetic test results, or require testing. “It’s an anecdotal fear,” said Mohit M. Ghose, a spokesman for America’s Health Insurance Plans, whose members provide benefits for 200 million Americans. “Our industry is not interested in any way, shape or form in discriminating based on a genetic marker.”

Still, a recent study by the Georgetown University Health Policy Institute found otherwise. In 7 of 92 underwriting decisions, insurance providers evaluating hypothetical applicants said they would deny coverage, charge more for premiums or exclude certain conditions from coverage based on genetic test results.

The Medical Cost

Regardless of whether discrimination actually occurs, many health care professionals say the pervasive anxiety over it demands legislative action. Geneticists complain that discrimination fears prevent them from recruiting research participants, delaying cures and treatments for disease. At Memorial Sloan-Kettering Cancer Center in New York, the same concern is a leading reason people cancel appointments for tests that detect cancer risk.

“We are dealing with potential lifesaving interventions,” said Dr. Kenneth Offit, chief of the center’s clinical genetics service. “It’s a tragedy that people are being scared off by this.”

The Genetic Information Nondiscrimination Act, which passed the House of Representatives by a wide margin last year, would prohibit insurers from using genetic information to deny benefits or raise premiums for both group and individual policies. (It is already illegal to exclude individuals from a group plan because of their genetic profile.) The bill would also bar employers from collecting genetic information or using it to make decisions about hiring, firing or compensation. But it has yet to reach the Senate floor.

Meanwhile, a $300 genetic test for prostate cancer risk announced last month immediately drew callers to a public radio station in Washington that was discussing the test, voicing fears of insurance discrimination. Dr. Karim Kader, who made the test possible with his discovery that men who carry certain DNA variants are four to five times likelier to develop prostate cancer, assured one caller that the test would be “very private.”

For some, that is not good enough.

Linda Vahdat, director of the breast cancer research program at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, estimates that 20 percent of her patients choose to pay for the DNA test for inherited breast cancer risk with cash, to avoid submitting insurance claims.

And last year, hundreds of customers paid the start-up company DNA Direct for tests that range in cost from $175 to $3,456 to ensure that no third party, not even a doctor, had access to their results. Mary, a freelance camera assistant in Brooklyn, for instance, sent a swab of her cheek cells to DNA Direct to find out if her extreme fatigue was caused by hemochromatosis, a genetic condition in which the body retains too much iron.

“I would rather not lay out the $200 myself,” said Mary, who requested that her last name be withheld for the same reason she paid for her own test. “But it seemed safer.”

Treatment for hemochromatosis typically involves removing a unit of blood twice-weekly by phlebotomy. But that would mean disclosing the condition to a doctor, so Mary is planning on becoming a frequent blood donor.

Kathy, a financial analyst in Houston who would like to know if she, like her two sisters, has a genetic predisposition to breast cancer, said she was not going to take even an anonymous test. “Then,” she said, “I’m just in a position of having to lie.”

The culture of secrecy around genetic information is stronger in the United States, some experts say, than in countries where people are guaranteed health care. Among Americans at risk for Huntington’s disease, an incurable brain disorder, only 5 percent take the DNA test to determine if they will develop it, compared with 20 percent of Canadians in the same position, according to Michael R. Hayden, a professor of human genetics at the University of British Columbia in Vancouver.

Here, doctors often feel obligated to inform patients of the potential financial downside.

“I always warn them,” said Dr. Stephen Moll, director of the Thrombophilia Program at the University of North Carolina, who uses a genetic test to determine the best treatment for patients with blood clots. “Especially if they are self-employed, I don’t want it to be a surprise if their health insurance premium goes up.”

Unknown Risks

After receiving a similar warning from her doctor, Katherine Anderson’s parents did not allow her to be tested for Factor V Leiden, a genetic condition she might have inherited from her father that increases the risk of blood clots.

But last year, with nothing in Ms. Anderson’s record to indicate reason for concern, a gynecologist prescribed a birth control pill to regulate her uneven periods. Six weeks later, Ms. Anderson, then 16, developed a clot that stretched from her knee to her abdomen. The pill, combined with the gene she had indeed inherited, had increased her clotting risk by 30-fold.

Now largely recovered, her primary concern is whether she will be viewed as a health insurance liability for the future.

“I don’t want to have to work for a big business just to get insurance,” she said. “This could be determining what I can do for my whole life.”

For Judith Berman Carlisle, the price of privacy was forgoing the DNA test that would have convinced her not to have surgery. Ms. Carlisle, 48, who was setting up her own therapy practice, was afraid testing positive for the high-risk breast and ovarian cancer gene that runs in her family would prevent her from buying health insurance.

But her sister had developed ovarian cancer the year before, an aunt had died of it, and Ms. Carlisle was desperate not to get it herself. Her doctor agreed to remove her ovaries based on her family history — the way such decisions were commonly made before a genetic test was available.

Ms. Carlisle was convinced the surgery would be less damning than proof that she carried a defective BRCA1 gene, which also confers a very high chance of developing breast cancer.

“There’s a big difference between someone saying, ‘I have a strong family history,’ ” Ms. Carlisle said, “and saying, ‘I only have a 13 percent chance of not getting breast cancer during the time you’re insuring me.’ ”

Last fall, after the surgery to remove her ovaries, she began to consider a double mastectomy to remove any chance of breast cancer, the disease her grandmother and another aunt had died of. Having secured health insurance, she took the test for the BRCA1 mutation. It came back negative.

“The first thing they said to me,” Ms. Carlisle said, “is that I have no higher risk than anyone on the street.”


Postuar nga NS-6 datë 03 Prill 2008 - 09:41:

Warfarin Dose Modification by Genotyping

Cod. A03042008

Prescribing a therapy is not always as easy as it seems! You have to keep in mind a lot of variables in order to prevent any possible complication and at the same time be ready to act when that complication becomes evident,in order to avoid major problems.
Yet, a lot of complications occur. Most probably this is due to a incomplete understanding of the mechanisms of a drug or its target and because it is given based on statistical data that show its efficacy . Up to now we are still far away from what medicine should be: an individual based medicine. However,as the knowledge on human body function grows, therapies change in order to get closer to that aim.
The following script analysis one of the new frontiers of prescribing drugs: Genetic based prescription! (NS-6)
------------------

Decisions about initial dosing of warfarin are influenced by patient age, concurrent medications, diet, and comorbid diseases. Despite dose modifications based on these considerations, many patients receive initial dosing that is too high or too low and can experience serious consequences, such as bleeding or new thrombi. During the past few years, researchers have reported that polymorphisms in the genes whose products interact with warfarin can have marked clinical effects. For example, vitamin K epoxide reductase C1 (VKORC1) is critical for the formation of functional clotting factors and is inhibited by warfarin, and cytochrome P-2C9 (CYP2C9) degrades warfarin.

To assess the effects of these genetic variations on warfarin management, investigators from Vanderbilt University School of Medicine genotyped 297 patients who were beginning warfarin therapy. Patients’ ages, sex, racial or ethnic backgrounds, indications for warfarin therapy, target international normalized ratio (INR) ranges, initial warfarin doses, and concomitant medications were noted at baseline. Subsequent INR values and warfarin doses, frequency of monitoring, and bleeding events were recorded for as long as 168 days (median, 43 days).

Target INRs for most patients were 2 to 3, and the average warfarin dose was 4.8±0.8 mg. About 12% of white patients and no black patients were homozygous for polymorphisms in VKORC1 (VKORC1-A). INRs rose into the therapeutic range 2.4x faster and became excessively high (>4) 2.5x times faster in VKORC1-A homozygotes than in non-A–haplotype patients (P=0.02 and P=0.003, respectively). INRs were above the therapeutic range for a greater percentage of time in VKORC1-A homozygotes (18.8% vs. 9.1%; P=0.02). VKORC1-A heterozygotes also had higher risk for having INRs >4 than did non-A–haplotype patients. Among all patients, 12% and 4.8% had polymorphisms for CYP2C9 type *2 and type *3, respectively. Whereas CYP2C9 genotype did not affect the time needed for INRs to rise into the therapeutic range, patients with *2 or *3 alleles did reach INRs >4 more rapidly than did those without CYP2C9 mutations (P=0.03); CYP2C9 mutations also were associated with more time above the therapeutic INR range, although this did not reach significance (P=0.09). Eight major and five minor bleeding events occurred, but these were not limited to patients with the genetic polymorphisms and were not significantly higher in any one group.

Comment: Recently, the FDA recommended that the labeling of warfarin include a statement about initial lower doses for patients with genetic variations in the CYP2C9 or the VKORC1 gene. The results of the present study confirm that people with these mutations are more sensitive to the effects of warfarin and that VKORC1 mutations have a greater effect than do mutations in CYP2C9. However, whether lowering warfarin doses will lower the incidence of bleeding is unknown and will be difficult to demonstrate, because even people whose INRs are within the therapeutic range occasionally bleed. The National Heart, Lung, and Blood Institute currently is supporting a large, multicenter, double-blind, randomized trial of genotype-guided warfarin therapy designed to determine whether this strategy improves patient outcomes.

David Green, MD, PhD
Published in Journal Watch Oncology and Hematology April 1, 2008

Citations:
Schwarz UI et al. Genetic determinants of response to warfarin during initial anticoagulation. N Engl J Med 2008 Mar 6; 358:999


Postuar nga NS-6 datë 11 Qershor 2008 - 14:54:

Why Is Warfarin Such a Dangerous Drug?

Many patients who receive warfarin would have been excluded from the trials in which the drug’s efficacy versus safety was assessed.

Despite having a propensity to cause bleeding, vitamin K antagonists (VKAs) such as warfarin have been used widely to prevent thrombosis in patients with atrial fibrillation, venous thromboembolism, or cardiovascular disease. This practice is supported by the results of many randomized, controlled trials showing that benefits of thrombus prevention trump risks for bleeding. However, many patients who receive VKAs experience major hemorrhages, an outcome that has led investigators to question whether the populations in these pivotal trials accurately represent patients usually seen in practice.

To determine whether the type of patient seen in ordinary practice was excluded from clinical trials of VKA because of comorbidities or concurrent therapies and whether patient-exclusion criteria might have inadvertently skewed the risk-benefit ratios to favor VKA usage, Dutch researchers performed a 4-year case-control study. Cases consisted of approximately 1000 patients (mean age, 67; 57% male) who were admitted to a university hospital with VKA-associated bleeding (mean duration of VKA therapy, 3.2 years). Bleeding was categorized as gastrointestinal (60%), intracranial (15%), urogenital (15%), and other (10%). Controls, matched by age, sex, and VKA-therapy duration, had no hemorrhages and were hospitalized for respiratory or urinary tract infections. Compared with the control group, the case group had a significantly higher mean international normalized ratio (INR; 4.1 vs. 2.9), a higher incidence of INRs >5 (30% vs. 4.5%), higher mean creatinine levels (5.9% vs. 2.7%), and a higher incidence of liver failure (2.4% vs. 1.0%).

A greater proportion of cases than controls (40% vs. 23%) met at least one exclusion criterion: Unsuitability for anticoagulation therapy and use of restricted medications (such as aspirin, nonsteroidal anti-inflammatory drugs, and clopidogrel) were most common, followed by cardiac comorbidity, previous stroke, cancer, and risk factors for thrombosis. As such, these patients likely would not have been eligible for the trials of the pertinent indication for VKA therapy. Moreover, compared with patients who met no exclusion criteria, those who met one exclusion criterion had 3-fold higher risk for bleeding, and those who met three or more criteria had 15-fold higher risk. The authors concluded that, for patients who deviated from those in the pivotal VKA trials, the balance between risks and benefits of VKA therapy was shifted toward a less-favorable safety profile.

Comment: Evidence-based medicine supports the use of VKAs for management of patients with a variety of disorders. However, as this report indicates, each patient must be evaluated carefully for risk factors related to bleeding, such as renal failure and concurrent antithrombotic medications. The danger of VKAs lies in their use in patients for whom risks for bleeding exceed benefits of thrombus prevention. Careful assessment of each patient is essential, and the risks involved should be discussed fully with patients before therapy is initiated.

— David Green, MD, PhD

Published in Journal Watch Oncology and Hematology June 10, 2008

Citation(s):

Levi M et al. Bleeding in patients receiving vitamin K antagonists who would have been excluded from trials on which the indication for anticoagulation was based. Blood 2008 May 1; 111:4471.


Postuar nga ESHI datë 11 Qershor 2008 - 23:23:

Re: Insurance Fears Lead Many to Shun DNA Tests

[QUOTE]Po citoj ato që tha NS-6
[B]Cod. A24022008

Still, a recent study by the Georgetown University Health Policy Institute found otherwise. In 7 of 92 underwriting decisions, insurance providers evaluating hypothetical applicants said they would deny coverage, charge more for premiums or exclude certain conditions from coverage based on genetic test results.


Kjo eshte mese e vertete.
Kjo eshte politika e sigurimeve shendetesore ketu ne USA.
NS6 nuk e di sa i informuar je ne lidhje me sigurimet ketu ne US, nqse ke info te mjaftueshme per te krijuar nje opinion mbi rrolin e sigurime shendetesore ketu , do kisha shume interres ti ndanim mendimet dhe opinionet per aq sa dime.

FLM dhe Pershendetje .


Postuar nga NS-6 datë 11 Qershor 2008 - 23:44:

me te thene te drejten per sigurimet shendetsore ne Amerike di pak dhe kryesisht jane gjera qe kam lexuar neper shkrime si ai qe kam paraqitur me siper si dhe ne ato qe kam pare ne televizion...sic mund te jete dokumentari i Michael Moore "Sicko"...gjithsesi,cdo info nga ana jote do ishte i mirpritur!


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