EasyDiagnosis Second Opinions

CBS Evening News (6/28, story 10, 0:30, Smith) reported FDA experts meet in two weeks to decide whether or not to pull Avandia (GlaxoSmithKline) off the market, while Brian Williams of NBC News  also reported yesterday (June 28,3010) , however, that the drug’s maker, GlaxoSmithKline, “said today the drug is effective and safe.” The drug (Rosiglitazone) is still used for millions of patients with type II diabetes, although several other drugs are available for treatment of the condition.

The drug was linked to 304 deaths in the third quarter of last year. Yet, three years ago in May 2007, and followed by many other reports, Avandia was linked to a 43 percent greater risk of heart attack and death in a study published by the New England Journal. See this link.

The FDA is still in a bind despite a recommendation last February that the drug be taken off the market. (Supposedly) when a drug maker refuses to pull a potentially fatal medication off the market, the FDA, believe it or not, does not necessarily have the authority to force a recall. “In the interests of free commerce” (see link above), though The FDA has authority to force a black box warning be placed on the drug, the Agency does not have explicit power to force a company to remove the drug from the market. According to the above link  “As long as the risks and benefits of a drug are fully disclosed to a patient and the patient voluntarily consents to its use, the FDA has no power to interfere in that patient’s treatment.”

Stay tuned.

According to the AMA Morning Rounds, World Health Organization (WHO) official still insist that the swine flu, H1N1 continues to be a “pandemic,” even though the period of most intense activity appears to have passed. The June 3 announcement came two days after a virtual meeting of international flu experts who advise Director-General Margaret Chan “on setting the global body’s pandemic alert level.”

This was surprising to many observers, because they “had expected the 15-member committee of experts, whose members are anonymous, to declare that the pandemic was in its ‘post-peak’ phase, or even in its ‘post-pandemic’ phase, which would mean that the pandemic was over.” But, Dr. Chan quickly pointed out that while “‘the period of most intense pandemic appears likely to have passed for many parts of the world,’ activity is continuing in some areas (Cuba, Central America) and many people remain vulnerable.”See my blog of Jan.26  and comments by Dr. Wolfgang Wodarg, chairman of the Parliamentary Assembly of the Council of Europe (PACE) Health Committee, cited previously, whom I quoted, “The WHO’s “false pandemic” flu campaign is “one of the greatest medicine scandals of the century.” Dr. Wodarg introduced the parliamentary motion to hold an emergency debate and inquiry into the “influence” exerted by the pharmaceutical industry on the World Health Organization’s (WHO) global H1N1 flu campaign.  “The definition of an alarming pandemic must not be under the influence of drug-sellers,” he added.

Orlistat (Xenical), used as a weight loss drug, is notorious for its gastrointestinal side effects- described as “treatment effects”, which can include steatorrhea  (oily, loose stools), since it inhibits the digestion of fat. The drug, which appeared to be safe for long-term use-don’t all drugs?-is available without prescription in the United States, the European Union, and Australia. Over-the-counter approval was controversial in the United States with consumer advocacy group, Public Citizen repeatedly opposing it on safety and efficacy grounds.

The AMA in its “Morning Rounds” reports the FDA is now requiring a liver-injury warning label, after receiving reports of liver damage by patients on this wildly popular diet drug.  (ABC World News 5/26, story 8, 0:20, Diane Sawyer.) The drug has been taken by nearly 40 million people.

The FDA has decided to put the new warning on Xenical (orlistat), developed by Roche’s Genentech, and its over-the-counter version,”Alli,” which is manufactured by GlaxoSmithKline (GSK).  To date, the agency has identified 32 cases of severe liver damage hepatocellular necrosis or acute hepatic failure, 2 of them outside the US.

Now, the revised label for orlistat (Xenical) will include new safety information about rare cases of severe liver injury. The agency stated, however, that “it has not yet established a causal relationship between orlistat use and severe liver injury.” For instance, some of the patients in question were taking other drugs while using the diet medications, others may have had conditions that exacerbated their liver disease.

Still, HealthDay (5/26, Gardner) reported, the agency is “‘telling consumers and healthcare providers to be vigilant should patients develop symptoms suggestive of liver impairment,” said FDA spokeswoman Elaine Gansz Bobo. She added, “We are not advising routine monitoring of liver enzymes as that will not help predict who may develop hepatic impairment on the drug.” People taking Orlistat — the active ingredient in both drugs — were warned to be on the lookout for itching, yellow eyes or skin, dark urine and loss of appetite, all of which are symptoms of liver problems.

If history is any guide, many more cases of serious liver problems will emerge in future.  The true extent of most drug reactions, serious, and not-so-serious-take years to come to the attention of the authorities and the public before proper warnings are issued or the offending drug is taken off the market.

Proton pump inhibitors (PPIs) are among the most popular drugs used to treat acid reflux and ulcers. They are sold under brand names like Nexium (the famous “purple pill”), Prilosec and Prevacid, and generate “$13.5 billion in sales. In 2009, approximately 119 million PPI prescriptions were written in the US, making the medicines part of the third-largest selling class of drugs. The six available PPI medicines are roughly equal in effectiveness and safety but differ markedly in cost. Two—omeprazole (Prilosec, Prilosec OTC) and lansoprazole (Prevacid,)—are available as both a prescription and a nonprescription drug. Taking effectiveness, safety, cost, and other factors into account, if you need a PPI,  consider following Consumer Reports Best Buy Drugs:

■ Prilosec OTC
■ Generic omeprazole OTC

Both of these drugs are available without a prescription. You could save about $200 a month or more by choosing one of these drugs over a more expensive medication listed above. See this informative report.

Unfortunately, like all drugs, PPI’s have problems. The Wall Street Journal reviews several recent reports from the medical literature about complications, and CNN  reported on its website that medical experts claim the risks of taking PPIs may outweigh the benefits for people with less serious conditions. PPI’s can have rare but serious side effects, including an increased risk of GI bacterial infection and bone fracture, according to several new studies in the Archives of Internal Medicine.  Over prescribing these drugs for simple heartburn or dyspepsia has become almost reflexive.

The Boston Globe (5/10, Cooney) “WhiteCoat Notes” blog reported that patients on PPI’s had a 47 percent increased risk of spine fractures, a 26 percent increased risk of forearm or wrist fractures, and a 25 percent increased risk of other fractures.”

Doctors at the Beth Israel Deaconess Medical Center in Boston, analyzed data on more than 100,000 patients discharged from the hospital over a five-year period, HealthDay (5/10, Goodwin). They found that taking a proton pump inhibitor each day increased the chances of a serious diarrheal disease, C. difficile infection by 74 percent,” and “patients who took proton pump inhibitors longer than that had more than double the chance.”

Five years ago, I wrote that “the oldest and still the most widely used first line drugs for heartburn and dyspeptic symptoms are the antacids, such as Tums, Maalox, Mylanta, Rolaids, etc. These have the advantage of rapid relief in most patients, and low price. …With GERD and ulcer, the H2-receptor antagonists, Zantac (ranitidine), Pepcid (famotidine), and Tagamet (cimetidine), etc. are in most cases as effective as the PPI’s.

“Proton pump inhibitors are often over prescribed in long-term care, disregarding published guidelines for their use..”  It is interesting to note that PPI’s are not approved for treatment of simple dyspepsia or uncomplicated heartburn.

NBC Nightly News (4/29, story 3, 2:00, Williams) reported that “the FDA has approved” Provenge (sipuleucel-T), “a vaccine for prostate cancer. It doesn’t prevent the disease, so vaccine is a bit of a misnomer, ..it could be a game-changer.”  The the media hype goes on: “It could help as many as 100,000 men with advanced prostate cancer,” the CBS Evening News (4/29, story 7, 2:00, Katie Couric) reported.  It offers “a new way to attack the disease which could be deployed against other kinds of cancer,” ABC World News (4/29, story 7, 1:55, Diane Sawyer) reported. But this is typical media hype, unsupported pure speculation.

The AP  reports that “three years ago…the FDA delayed a decision on the treatment, “despite an expert panel’s recommendation for approval.” According to the Los Angeles Times  “agency officials were concerned that, even though the vaccine extended lifespan in men with metastatic cancer who did not respond to hormone-deprivation therapy…it did not slow tumor growth.” The FDA also said that too few men given Provenge had been studied and asked Dendreon to perform a larger trial in more than 500 men.

Those results were presented last year, see TheWashington Post. During the trial, which involved “512 patients with advanced prostate cancer, Provenge increased overall survival by about four months, boosting median survival from 21.7 months to 25.8 months.”

The New York Times (4/30, A13, Pollack) reports that “a full treatment (with Provenge) will cost $93,000. Dendreon officials defended that price, saying it was in line with those of other cancer drugs in terms of cost per extra month of life provided by the drug.”

Bloomberg News said that the treatment “will initially be available at about 50 sites used for clinical trials, and more widely distributed after four plants are cleared for use by mid-2011, Seattle-based Dendreon said in a statement.”

But why did the FDA approve the drug without further testing?  It’s increasingly clear that  public pressure for life-extending new drugs for cancer is irresistible.  Would you like to take a chance on 4 miserable months for $23,000 a month, on the basis of this single study? Tough question. Is it time to load up on Dendreon stock?

The new Health Care Reform Act recently signed into law by President Obama has been attacked  by opposition to the legislation, now more virulently than before the bill was passed by the Senate. Yet here are some of the benefits we can expect from this, the first Federal health legislation passed in over forty years. See this site for some valuable information, including but not limited to the following:

“It makes insurance more affordable by providing the largest middle class tax cut for health care in history, reducing premium costs for tens of millions of families and small business owners who are priced out of coverage today.  This helps 32 million Americans afford health care who do not get it today – and makes coverage more affordable for many more.  Under the plan, 95% of Americans will be insured.

“It sets up a new competitive health insurance market giving millions of Americans the same choices of insurance that members of Congress will have.

“It brings greater accountability to health care by laying out commonsense rules of the road to keep premiums down and prevent insurance industry abuses and denial of care.

“It will end discrimination against Americans with pre-existing conditions. …
The Children’s Health Insurance Reauthorization Act on February 4, 2009, provides quality health care to 11 million kids – 4 million who were previously uninsured.

“The President’s American Recovery and Reinvestment Act protects health coverage for 7 million Americans who lose their jobs through a 65 percent COBRA subsidy to make coverage affordable.

“The Recovery Act also invests $19 billion in computerized medical records that will help to reduce costs and improve quality while ensuring patients’ privacy.

The Recovery Act also provides: $1 billion for prevention and wellness to improve America’s health and help to reduce health care costs;$1.1 billion for research to give doctors tools to make the best treatment decisions for their patients by providing objective information on the relative benefits of treatments; and$500 million for health workforce to help train the next generation of doctors and nurses.”

Another summary in The New York Times Science Section, Mar. 30, is a “must read.”

SO, WHAT’S NOT TO LIKE? The continued opposition to this landmark legislation boggles the mind. Yet I am convinced that once the vast majority of Americans begin to experience the changes and improvements in their access to health care and innovations in providing that care health care the outrageous opposition to this bill will melt away.

According to Dr. Richard J. Ablin, Research Professor of Immunobiology at the University of Arizona College of Medicine in a New York Times Op-Ed article March 10, “Prostate screening is inaccurate and a waste of money.”   Each year 30 million American men undergo testing for  prostate-specific antigen (P.S.A.), a prostate enzyme believed, when elevated, to be a reliable marker for the presence of prostate cancer.  While 16% of men have a lifetime chance of receiving a diagnosis of prostate cancer, they have only 3% chance of dying from the disease. Curious, isn’t it.  The fact is, that infections, over-the-counter drugs like ibuprofen and simple prostatic enlargement occurring in the majority of older men, can all falsely elevate PSA. Moreover, the test detects only a small percentage of cases, and cannot distinguish between the cancers that kill and the vast majority which grow so slowly that 97% of men will die of something else.

As Dr. Ablin points out, the FDA in approving the procedure relied “heavily” on a study showing that testing could detect 3.8% of prostate cancers.  Not a very large figure.  The result over the past several years has been the subjection of hundreds of thousands of men to radical prostate cancer surgery or radiation, resulting in a tragically high percentage of permanent impotence,  incontinence of urine, or both.

Last year the New England Journal of Medicine published the two largest studies of the screening procedure, one in Europe which showed that 48 men would have to be treated to save one life “That’s 47 men who, in all likelihood, can no longer function sexually or stay out of the bathroom for long.”  The American study showed that over a period of 7 to 10 years, screening did not reduce the death rate in men 55 and over.

Dr. Ablin asks why PSA screening is still used, and answers his own question.”Because drug companies continue peddling the tests and advocacy groups push “prostate cancer awareness” by encouraging men to get screened. Increasing numbers of early screening proponents, like Thomas Stamey, a well-know Stanford urologist came out against routine testing, and the American Cancer Society urged more caution in using the test. Certain subsets of patients, e.g. those with a family history of prostate cancer, those patients after treatment with rising levels should be tested, of course.  But this is quite different from subjecting a normal population to widespread screening, something I have discussed in a previous blog, and re-published in my newsletter, Second Opinions, an interview with Dr. Otis Brawley by Maryann Napoli in 2004!

By the way, the good Dr.  Albin who wrote the Op-Ed article from which this blog borrowed freely, invented the PSA test 40 years ago.

Stay tuned.

When researchers, reporters, and others use data to compare two or more different groups, they may present their results in two very different and often confusing ways to emphasize a point of view. These relations may be expressed as either absolute or relative differences. An absolute difference is a subtraction; a relative difference is a ratio.To emphasize how easily people and even most physicians can be fooled, consider the following: Which drug would you rather take, one that reduces your risk of cancer by 50 percent, or another drug that only reduces your risk of cancer from two to one out of 100? Most people would choose the drug that reduces their risk of cancer by 50 percent, but in fact both these numbers refer to the same outcome. They’re just two different ways of looking at the same numbers. Without any qualification, both statements “reduced the risk by 50%” and “reduced the risk by 1 in a hundred” (1%) could be construed as representing either an absolute or relative difference. But note the difference in “feel” between 50% and 1%. Which figure sticks in your mind?

The headlines read, “Tamoxifen Cuts Breast Cancer Risk by 33% in Healthy Women!,” yet it turns out, among all the women in a study who took Tamoxifen, less than 2% got breast cancer, and among those that took the placebo, less than 3% got breast cancer. The real difference was 1%. {”How to Lie With Statistics,” Real Health Breakthroughs, Dr. William Campbell Douglass, 2004}

One of the main studies being cited in support of a drug for advanced breast cancer, Herceptin©, saw 34 deaths in the control group (2.0% of the participants) and 23 deaths (1.4%) in the group treated with Herceptin. According to the authors, this translates into a 46% Relative Reduction in cancer deaths, (wrong calculation; should have been 2.0-1.4 divided by 2.0 or 30%) But the true absolute reduction in deaths is only 0.6% (2.0%-1.4%), almost certainly not statistically significant in this series. Is this a miracle drug? The number, of course, is pure marketing and statistical spin. As reported some time ago in the New Scientist magazine, one of the main cheerleaders for Herceptin is none other than Hortobagyi, a paid consultant of Genentech, who received somewhere between $10,000 and $100,000 from the drug company. He’s one of the proponents who calls Herceptin a “cure.”

Keep in mind that headlines promoting a drug will almost always refer to relative risk, “A breathtaking 40% reduction in risk!” -and this numerical shell game will be copied in the mainstream media, press, medical journals, even the FDA... Pharmaceutical companies, marketing reps, even some physicians anxious to publish and usually supported by commercial drug interests are constantly pushing and exaggerating the supposed benefits of their drugs while minimizing their risks.

The Alliance for Human Research Protection (AHRP) reported last week that the New York State Senate Senate is about to vote on legislation permitting a school nurse of doctor the power to vaccinate children under 18 with the controversial vaccine, Gardasil (and hepatitis B) without parental “consent or knowledge.”Gardasil, a human papilloma virus vaccine, promoted by Merck as an immunization against cervical cancer, is riddled with controversy, and covered extensively in the media, and in my previous blogs.

Dr. Diane Harper, an acknowledged researcher who conducted pre-marketing clinical trials for both Gardasil and GlaxoSmithKline’s Cevarix vaccines, blasted marketing strategies for HPV vaccine, offered the New York State Committee her expert opinion on the vaccines. As Dr. Harper and others have already written, its period of effectiveness is unknown, and evidence shows it poses serious risks for some children and young women such that its risk/benefits are highly debatable.

AHRP has stated the bill, S4779B, violates parental rights to make medical decisions on behalf of their children. If a child is harmed by a vaccine given without consent, and, according to this law, beyond the bounds of school authority, who will bear medical, financial, and Legal authority? In a landmark decision last March, the U.S. Supreme Court ruled that in case of severe injuries or death, federal law does not prevent consumers from suing drug companies in State Court.

But who, if anyone would be entitled to sue the drug company or the State of New York-or both- in cases of misadventure following mandated vaccination of the HPV vaccine?To be noted is Merck’s record of aggressive, illegal marketing of drugs including the Gardasil vaccine.According to the AHRP Newsletter, Merck is on record of having bribed state legislators to support similar bills in Texas. Merck indeed made campaign contributions to the Governor of  Texas to mandate Gardasil. Other states are considering mandating HPV vaccinations. In my opinion, the HPV controversy should be investigated by the FTC, and the FDA if not the Congress.For further information, contact: Vera Hassner Sharav at veracare@ahrp.org

Most patients with susceptible cancers are thankful for chemotherapy and radiation, and are willing to suffer crippling and dangerous side effects, even death, if treatment can help them or prolong their lives. But would you take a drug to treat a bad smoking habit with more warnings than a travel advisory to a war zone, and 90,000 URL’s under its combined search term for “adverse reactions”?

I guess it depends on what you read about Chantix, (Champix in Europe), the trade name for Varenicline, marketed in the U.S. by Pfizer to treat smoking addiction. For starters, the ad for doctor, running for weeks in the JAMA, has almost two pages out of four of “important safety information”- warnings and adverse reactions. Included in the ad are neuropsychiatric symptoms ranging from suicidal and violent behavior, worsening of psychiatric illness, as well as  nausea, sleep disturbance, constipation, vomiting, to which you might add Steven Johnson Sydrome, Erythma Multiforme, and angioedema, etc.

The drug portal, druglib.com  reported an index of adverse events during 2007 alone of 2319 serious events related to ingestion of Chantix from patients and non-professionals Cases resulting in death, 42, life-threatening events, 52, hospitalizations, 306. Because of the findings of a medical watchdog group, the Institute for Safe Medication Practices (ISMP), the drug has been grounded by the FAA for pilots and air traffic controllers. Fearing for the safety of passengers. 150 pilots and 30 ground controllers were ordered to stop taking the drug. The ISMP findings indicate from May 2006 until December 2007 there were 227 reports of suicide attempts, 28 actual suicides, 397 cases of possible psychosis and 52 reports of hostility or aggression. The latter, according to the news report, is what led to the death of popular Dallas musician Carter Albrecht, “…after he flipped out, assaulted his girlfriend and attempted to break into a neighbor’s home before being shot dead.”

A “Black Box Warning(a notice on the packaging of a prescription drug which warns patients and prescribers that the drug has potentially dangerous side effects) was not issued by the FDA until July 2009, 14 months after the FAA issued their edict for pilots and air traffic controllers! I seriously wonder how a drug for smoking addiction can survive the press it’s been receiving for almost three years and why doctors and patients continue to use a drug with this reputation. Will Chantix finally be taken off the market, or will the FDA, as is too often the case, cave in to pressure from Big Pharma, just as the medical profession and the public continue to succumb to drug advertising blitzes?