The CDC discusses Gardasil HPV vaccine safety

Produced and interviewed by Steven E. Greer, MD

Dr. Barbara Slade of the CDC discusses her recent JAMA article on the safety and adverse event reports for Merck’s HPV cervical cancer vaccine Gardasil. Back in 1976, a swine flu vaccine caused Guillain-Barrė syndrome and this has led to subsequent vaccines being under scrutiny for any neurologic adverse events.

New therapies for Multiple Sclerosis

Interviewed by Steven E. Greer, MD

Best viewed in full screen, 1080i HD

Barbara Giesser, MD, neurologist and Medical Director of the Multiple Sclerosis Center at UCLA, discusses the soon-to-be-approved new therapy for MS called BG-12 (fumarate), made by Biogen Idec. Biogen also makes Tysabri, which is known to cause the very serious adverse event of PML caused by the JC virus.

Dr. Giesser discusses whether BG-12 will be rapidly adopted as a new first-line therapy, and also replace existing options for failed first line therapy, such as Gilenya and Tysabri. She then reviews the recent NEJM publications on BG-12.

The FDA’s new Breakthrough designation for new drug approvals

Courtesy of The Healthcare Channel, Dr. Janet Woodcock, the Director of the FDA’s drug division, CDER, discusses the newly created “Breakthrough” pathway for new drug applications. Distinct from Fast-track, a drug will receive a “Breakthrough” designation if, during early clinical trials, the drug shows significant efficacy for serious and life-threatening diseases. The new pathway could be a paradigm change for drugs in development to treat Alzheimer’s, ALS, and many other diseases.

The false epidemic of autism

Update March 20 , 2013

The annual CDC autism report is out again, misleading the public about a non-epidemic.

Update March 29, 2012

The high prevalence of “autism” was in the news again with a CDC report claiming that the rates were even higher than reports last year.

May 9, 2011 Steven Greer, MD

The national TV news and papers jumped on a press-release-promoted paper in The American Journal of Psychiatry that summarized a trial led by Yale researchers evaluating the prevalence of autism on South Korea. The press misinterpreted the goals and conclusions of the paper and led with sensational headlines indicating that American children might have a 100% higher prevalence of autism than previously estimated. Previous estimates suggested a 1/100 or lower prevalence, and the new paper suggested a 1/38 (2.64%) prevalence.

The authors of the paper, Kim et al, never intended the study to answer any hypothesis about autism in North America. Studies were heretofore lacking in Asia. They wrote, “Research suggests that ASD onset, core symptoms, and prevalence are similar across European and North American populations. Nevertheless, with the exception of Japan and Australia, the data are insufficient to characterize ASD prevalence in other cultures. This is the first population-based autism prevalence study in Korea.”

The authors of the paper made no conclusions about autism in North America. They wrote, ” Conclusions: Two-thirds of ASD cases in the overall sample were in the mainstream (Korean) school population, undiagnosed and untreated. These findings suggest that rigorous screening and comprehensive population coverage are necessary to produce more accurate ASD prevalence estimates and underscore the need for better detection,  assessment, and services.”

It is becoming increasingly known that non-North American data, such as these from the Yale Korean study, are not adequately relevant to the North American population to allow for clinical changes or approval of new drugs. These Korean data were from a homogenous population that represent a small portion of the North American population.

One also needs to be aware of political factors that have caused the increase in “autism” being diagnosed. In the year 2000, President Clinton signed into law the Children’s Health Act of 2000. The law specifically addressed autism and created new research branches within the CDC, NIH, and several medical centers. Congress has allocated close to a billion dollars to these programs in total, with a significant portion going toward the autism efforts.

It is a rule of political science that all bureaucracies have a tendency to grow and claim more of the federal budget. Lowering the bar and expanding the diagnostic criteria for “autism” is consistent with increased funding. The authors of the paper acknowledge this and wrote, “The increased prevalence appears to be attributable to greater public awareness, broadening ASD diagnostic criteria, lower age at diagnosis, and diagnostic substitution. Additionally, study design and execution have affected prevalence estimates, limiting the comparability of more recent estimates.”

The national media coverage of the paper in question also failed to explain that the researchers counted all forms of mild “autism” in the study. These were not the profoundly autistic patients that one thinks of when they hear the word “autism”. Many people with mild forms of autism are highly functional professionals that seem just a bit “odd”. These broad inclusion criteria can be found here. The new DSM-V expands the criteria ever further.

Proponents of diagnosing more children with “autism” claim that early treatment improves lifelong outcomes. Critics are worried that labeling a child for life carries with it tremendous stigma and harm to self esteem. They assert that it also places the child at risk of receiving harmful unnecessary medications as seen in the inappropriate prescribing of powerful antipsychotics to toddlers with “bipolar disorder”.

Moreover, as the incidence and prevalence of “autism” rise, human nature will erroneously attribute other medical therapies as the cause. Currently, the world medical societies are actively trying to undue the myth that vaccinations cause autism.

Every news outlet with a large viewership must begin to make an attempt to hire qualified producers who can properly screen press release medical news and filter out the junk science. Unlike other news, bad reporting on healthcare affects lives.

Hemorrhagic Complications Associated With Aspirin

Best viewed in full screen mode

July 23, 2012 By Steven Greer, MD

An article in the June, 2012, JAMA reported the findings of a large meta-analysis of the use of daily aspirin for primary prevention of myocardial infarctions and ischemic stroke. The authors concluded, “Despite important reductions in nonfatal MI, aspirin prophylaxis in people without prior CVD does not lead to reductions in either cardiovascular death or cancer mortality. Because the benefits are further offset by clinically important bleeding events, routine use of aspirin for primary prevention is not warranted and treatment decisions need to be considered on a case-by-case basis.”

We interviewed the author of the companion editorial, Dr. Jolanta Siller-Matula. She explains why the European cardiology guidelines now no longer recommend aspirin for primary prevention even though the American guidelines still do. She explains the “Number Needed to Treat” concept and why the risk-benefit ratio is not favorable for aspirin.

Daily aspirin for prevention of death from MI unwarranted in most people

Interviewed by Steven Greer, MD

For decades, doctors have recommended daily aspiring to prevent death from myocardial infarction to patients with certain risk factors other than previous MI (i.e. primary prevention). However, numerous randomized trials have been adding to the mounting evidence that the serious bleeding risks from aspirin outweigh the benefits. Dr. Kausik Ray from St. George’s University of London was an author of the latest meta-analysis of these trials, and discusses the findings.

(In full screen 1080i HD)

Thomas Brott, MD: Review of the CREST trial of carotid stenting

The CREST trial, published earlier this year, was the latest large-scale, randomized, controlled trial to test the safety and efficacy of carotid artery stenting versus standard open CEA surgery. Divisions of the HHS and medical societies might next make changes to reimbursement and clinical guidelines based on the trial. The PI and lead author, Thomas Brott of the Mayo Clinic in Florida, discussed the paper. Topics discussed include:

• The results which met the primary endpoint: a composite of death, stroke, or MI
• Were the periprocedural minor strokes caused by the stents releasing debris
• Were the greater number of myocardial infractions seen in the CEA surgery group significant Q-wave MI’s or just enzyme bumps?
• The other carotid stenting trial from the ICSS group that showed in a subset of patients MRI evidence of stroke more often with the stent group than CEA

 

After 18 months of real world experience, why the new blood thinners are not displacing warfarin.

April 26, 2012 By Steven Greer, MD

Millions of patients have atrial fibrillation that can lead to blood pooling and clot formation, which then can migrate to the brain and cause ischemic strokes. For many decades, warfarin has been the only option available to anticoagulate these patients at risk of stroke. However, warfarin (also used as a rat poison) is infamous for being tricky to properly dose and requires frequent blood draws and testing to prevent hemorrhagic stroke or ischemic stroke.

To address this unmet clinical need, and large potential market, the pharmaceutical industry, cardiology community, and certain academic research organizations, such as Harvard’s TIMI and Duke’s DCRI, have helped introduce to the market new oral drugs that promise to replace warfarin.

Pradaxa (dabigatran, made by Boehringer-Ingelheim) and Xarelto (rivaroxaban, co-marketed by Johnson&Johnson, developed and manufactured by Bayer) are currently approved in The U.S. to prevent ischemic stroke and systemic embolism in non-valvular A-fib. Brilinta (ticagrelor, made by AstraZeneca) and Effient (Prasugrel, made by Daichi Sankyo and marketed by Eli Lilly) are on the U.S. market, but are not approved for A-fib stroke prevention. Eliquis (apixaban, being developed by Pfizer and Bristol-Meyers Squibb) is not approved for any indication and is currently under regulatory review.

After more than a year of real-world experience with Pradaxa (approved in October of 2010), and just a few months after the approval of Xarelto to prevent stroke in the A-fib setting, the drugs are not being widely adopted. Total Pradaxa prescriptions in January, 2012, were 76,000, or just 3% of the 2.6 Million warfarin prescriptions.

Why is warfarin still the dominant drug? The bad economy, high unemployment, and fewer people with health insurance, has made costly drugs an unacceptable option for many patients. Pradaxa costs more than $3,000 per year, compared to less than $100 per year for generic warfarin. But safety issues of excessive bleeding are equally concerning.

Patients often need to have their anticoagulation reversed if they are overdosed or need emergency procedures. Warfarin can be reversed with Vitamin K. However, neither Pradaxa nor Xarelto have convenient antidotes and hemodialysis might be required, especially in the setting of life-threatening bleeding.

How can doctors prescribe Pradaxa and Xarelto safely, and which patients should receive the new drugs with uncertain safety profiles? Most cardiologists agree that the patients with small body mass and/or extremes in ages pose too great a risk to try the new drugs. These drugs should be avoided in patients with poor renal function (creatinine clearance less than 15-30 ml/min). Patients taking aspirin and Plavix (clopidogrel) should also be cautioned about increased bleeding risk while also taking Pradaxa or Xarelto.

Regarding the GI bleeding adverse events, many doctors mistakenly believe that upper GI remedies of proton pump inhibitors or other antacids can reduce the risk. In fact, the risk of bleeding is primarily in the lower GI tract where PPIs, etc, have no effect.

Most patients with A-fib undergo attempts to electrically shock (cardiovert) them to normal rhythm. The data are lacking as to how best to use Pradaxa or Xarelto in these patients. Should they be switched to warfarin with the potential increased risk of hemorrhagic stroke that ensues?

With the higher cost, lack of superior efficacy, and increased safety concerns of the new drugs, what type of patient should be attempted therapy with Pradaxa or Xarelto? Patients who are poorly controlled on warfarin; some patients who develop rare but life-threatening side effect of skin necrosis on warfarin; others who are unable or unwilling to go through the blood tests and monitoring required for warfarin might be considered appropriate candidates.

Compounding the real adverse events is the Weber effect. New drugs have a higher reporting rate of adverse events than old familiar drugs, such as warfarin.

As a result of the headwinds against adoption of Pradaxa, Xarelto, and possibly Eliquis, many doctors who study the anticoagulation clinical data for a living are skeptical that the new drugs will make significant gains in market share over warfarin for the next five years.

Jon Resar, MD: The PARTNER B trial

Interviewed by Steven Greer, MD

Dr. Jon Resar, Cath Lab Director for Johns Hopkins, discusses the PARTNER B cohort trial data and what this means for the field of TAVI. He comments on:

• Is it ethical to continue to randomize patients in TAVI trials to balloon valvuloplasty?
• Will the stroke rate become a problem as it has with carotid stenting in the general population?
• How can the vascular complications and bleeding be reduced?
• Why does the Sapien valve have a lower rate of post-implant heart block?

 

William O’Neill, MD: Minimally invasive replacement of the aortic valve

William O’Neill, MD, interventional cardiologist and investigator for the PARTNER trial, just released online in the New England Journal of Medicine, discusses this landmark trial investigating vascular routes for replacing worn out aortic valves. Current methods require chest splitting open-heart surgery. As this trans-catheter aortic vascular implantation (TAVI) evolves and the devices get smaller and better, traditional surgery may become less necessary. However, significant safety hurdles must be overcome before that is a reality.