Tuesday, October 4, 2016

Sovaldi cured my Hep C but killed me by reactivating Hep B

FDA Adds Boxed Warning to Hepatitis C Drugs, Warns of Hepatitis B Reactivation Risk 

Posted 04 October 2016By Zachary Brennan
The US Food and Drug Administration (FDA) on Tuesday warned of serious risks for some patients who have been infected with the hepatitis B virus (HBV) and are being treated with certain direct-acting antiviral (DAA) medicines for hepatitis C virus (HCV).
FDA identified 24 cases of HBV reactivation reported to FDA and from the published literature in HCV/HBV co-infected patients treated with DAAs between 22 November 2013 and 18 July 2016. 
Of the cases reported, two patients died and one required a liver transplant, though FDA cautions that this number includes only cases submitted to FDA, so there are likely additional cases.
- See more at: http://www.raps.org/Regulatory-Focus/News/2016/10/04/25946/FDA-Adds-Boxed-Warning-to-Hepatitis-C-Drugs-Warns-of-Hepatitis-B-Reactivation-Risk/#sthash.BVELqNYl.dpuf

Friday, September 30, 2016

Healthcare deductible costs rose at 16x the rate of inflation since 2006/ NYT

A NYT editorial discussed healthcare costs last week using two simple graphs. In case you still have good insurance, take a look at what has happened to the rest of us.  Over seventeen years, the cost of insurance premiums has risen at 6 times the rate of inflation.  Over ten years, deductibles rose at 16 times the rate of inflation. Someone called this "strip mining the middle class." The NYT says,
"The reaction to opening a medical bill these days is often shock and confusion — for the insured and the uninsured. Prices and deductibles keep rising, policies are drowning in fine print, and doctors are jumping on and off networks...  With incomes for most Americans stagnant, individuals and families insured under the Affordable Care Act or through employers are bearing more of the cost of medical treatment..."

Workers’ contribution
to premiums

Thursday, September 29, 2016

CDC urges Americans to get a flu shot as soon as possible/ NPR

NPR tells us influenza vaccine comes in twelve flavors this year.  You can pick 3 antigens or 4.  With or without a squalene adjuvant? (Fluad is the first US vaccine to use the MF59 squalene adjuvant, though its manufacturer worked to get it into the US market for almost 2 decades.)  High dose or regular strength? Made in armyworm cellsdog kidney cells, or just the usual egg-based vaccine?

Sorry--the nasal spray flu vaccine (FluMist by AstraZeneca) is not recommended this year, since it didn't work the last three years.

CDC is concerned that fewer elders got flu shots last year.  Maybe that is because they, or their doctors, finally learned that there is no reliable evidence flu shots work in those over 65. Also see this.  (They do work to a degree in younger adults and older children.)

I averaged the efficacy results for the last 12 years, from CDC's website and an MMWR report for the 2008-9 seasonal flu vaccine, since CDC had omitted that (negative efficacy) year from its list. Using CDC's own data, the average efficacy of flu shots (how well they work in controlled clinical trials, which may be better than their real life efficacy) was a whopping 37%.

So if 5% of the population gets flu each year without being vaccinated, only 3 or 4% will get the flu when everyone is vaccinated.

As the Cochrane Collaboration noted in a 2014 review of this subject (one of many they have done) you would need to vaccinate 71 people to prevent one case of flu.

Got it?  Now go get your shot.

P.S.  There are 80 million American children.  Last year, there were 85 influenza-associated deaths in children, or one in a million.  We have no idea how many children suffered serious side effects from influenza vaccines.  We have no idea how many suffered side effects from FluMist, which gave them no protection.  Fifteen million doses of Flumist were delivered to the US market last year, at a cost of about $23 each, or $350 million total.  Nice work if you can get it.

Tuesday, September 27, 2016

Five Recent Medical News Stories That Invite Cynicism/ John Mandrola, MD

From Dr. Mandrola at Medscape, a compilation of recent events in medical "science" that make one wonder whether the practice of medicine is going to last much longer, given the amount of corruption now woven into it:  
Cynic: A person who believes that people are motivated purely by self-interest rather than acting for honorable or unselfish reasons
I don't want to be this person. Cynicism is ugly.
But when it comes to the making and translating of medical evidence, five recent events are ugly.
Event Number 1. The Journal of the American College of Cardiology (JACC)recently retracted a paper[1] published earlier this year. This is notable because JACC is cardiology's biggest journal and because retraction is the highest form of scientific punishment.
The retracted paper reported the results of the OASIS trial—a test of whether ablation of atrial fibrillation (AF) using the controversial Topera Physiologic Rotor Mapping Solution was better than conventional techniques.
The OASIS trial results dealt a crushing rebuke for rotor ablation. The proprietary mapping system failed to deliver. The authors of OASIS, led by Dr Andrea Natale, are widely published and influential in the field. Their paper was presented as a late-breaking session of this year's Heart Rhythm Society meeting.
JACC retracted the paper because of irregularities in the randomization process (basically, the editors said OASIS was presented as a randomized trial, but it wasn't) and because patients were recruited before the trial was registered.
Dr Natale countered publicly, saying that industry influenced the decision to retract the paper. In an email toheartwire from Medscape journalist Patrice Wendling, discussing the decision by JACC's editors, Dr Natale said the information contained in letters to JACC were known only to the investigators and industry; "thus, it [was] obvious that these individuals were acting on behalf and in the best interest of the company."
I wrote a column outlining three possible explanations for this event, all of which, in my opinion, are depressing: a seriously flawed trial made it through the editorial and peer-review process of a major journal, or an influential research group were guilty of scientific misconduct, or industry influenced an editorial decision of a scientific journal.
Event Number 2. Another cynicism-inducing paper[2] out this month detailed the finding that the "sugar industry paid for and was closely involved in development of an influential literature review,"[3,4] published by the New England Journal of Medicine in 1967. This review downplayed dietary sugar's links to coronary heart disease while pointing the finger at fat and cholesterol intake."
Authors from University of California, San Francisco analyzed internal documents from the Sugar Research Foundation, the precursor to the Sugar Association, to probe the history of how dietary guidelines were developed. They looked at more than 1500 pages of documents from a range of publicly available sources, including damning correspondence between sugar-industry representatives and Harvard researchers.
Speaking to heartwire , Dr Cristin E Kearns, the lead author of the report, said that if the evidence had been fairly presented, the recommendations would have been to reduce both fat and sugar, not just saturated fat.
Think of the people that may have been harmed by substitution of sugar for fat.
My friends—this is a big story. Think of the people that may have been harmed by substitution of sugar for fat. Look around at the populace of Western countries.George Santayana's famous, often misquoted, quote fits: "Those who cannot remember the past are condemned to repeat it."[5]
Event Number 3. The third article[6] that gets me down deals with the problem of medical overuse.
In a structured review of English-language articles on PubMed published in 2015, Daniel Morgan and colleagues identified 821 articles which addressed medical overuse. Their paper, published in JAMA Internal Medicine and available in full text online, identified the 10 most influential of these papers, detailing important types of overuse.
I see overuse too often; it's harmful to patients because it exposes them to more harm than benefit, and it is harmful to society because it wastes resources. At the core of the overuse detailed in this review was poor translation of evidence into practice. Does overuse persist because people are motivated out of self-interest?
Event Number 4. Recent decisions at the US Food and Drug Administration (FDA) suggest the bar for approval of new devices and drugs is too low.
Last year, the FDA approved the Watchman (Boston Scientific) left atrial appendage closure device, which is a plug placed in the left atrial appendage to prevent stroke. Only it doesn't.
In a clinical trial called PREVAIL, the device was tested against warfarin—the standard of care. The trialists set the lowest possible bar for the device; all it had to do was prove noninferiority. It failed. In counting up events, the device proved inferior to warfarin.
That an agency charged with judging clinical science considers the opinion of Hollywood actors demeans the process.
How did Watchman get approved, then? Advocates for the device used multiple tactics. They combined previous trial data, they "meta-analyzed" multiple studies; they criticized the PREVAIL trial for providing management of warfarin patients that was too good; and they harnessed the power of patient advocacy. The well-known actor Wilford Brimley spoke at the FDA session on behalf of the device. That an agency charged with judging clinical science considers the opinion of Hollywood actors demeans the process.
Event Number 5. And finally, a far worse crisis at FDA came to light on September 19, 2016, when the agency gave accelerated approval to eteplirsen (Exondys 51, Sarepta Therapeutics), the first drug for a rare form of Duchenne muscular dystrophy, specifically patients with a confirmed mutation of the dystrophin gene amenable to exon 51 skipping.
During the first pass at the FDA, an advisory committee evaluated the data and rejected it by a 7 to 3 margin with three abstentions. The scientific advisors rejected the drug because the trial included only 12 boys and had deeply flawed methodology.
Despite the negative vote, patient-advocacy groups and others pressured the FDA into a second hearing. And now, the agency has gone against its advisors and granted approval. A clinical benefit of eteplirsen, including improved motor function, has not yet been established, and in its approval, the FDA did require that the manufacturer complete a clinical trial to confirm the drug's benefit. The company estimates the cost of the unproven drug will be $300,000 annually.[7]
Compassion for patients with rare diseases does not mean we can or should suspend scientific principles.
Compassion for patients with rare diseases does not mean we can or should suspend scientific principles. Luciana Borio, MD, the acting chief scientist at the Agency Scientific Dispute Process Review Board, the board that resolves internal disputes at the FDA, wrote that she "does not believe the available data and information support accelerated approval of" the drug."[8]
Ellis Unger, MD, the director of FDA's Office of Drug Evaluation within the Center for Drug Evaluation and Research and the chair of the advisory committee, in an appeal of this eteplirsen decision, exuded both empathy and common sense: "Many of us would wish to approve this drug if we could. DMD is a horrible disease and there are no approved treatments. FDA takes seriously the patient perspective and our mandate to be flexible."[8]
But in this case, Unger explains, "FDA is charged with the responsibility of ensuring that drugs are shown to be effective prior to marketing, based on substantial evidence. If we were to approve eteplirsen without substantial evidence of effectiveness, or on the basis of a surrogate end point with a trivial treatment effect, we would quickly find ourselves in the position of having to approve a myriad of ineffective treatments for groups of desperate patients—in essence, allowing marketing based on desperation, patient lobbying, and the desire and need of hope."[8]
The Sarepta story is terrible because it shows the darkest side of healthcare—one that I see too often: the hijacking of fear and hope in susceptible people in order to foster profits and self-interest of others.
Editor's note: The FDA has made a Summary Review of this decision, including documents from FDA's scientists, available in full online.]
Patients and doctors want to approach new developments in science and medical evidence with the belief that it is honest and born from the desire to foster the greater good. We want our default bias to be rooted in a place of benevolence.
Taken together, these five events give me great concern about the profession that is my life's work. I will continue to fight back cynical thoughts, but it's getting harder.

Tuesday, September 20, 2016

We don't know if it works or is safe--but don't let that stop you, Doctor. Push Gardasil

WebMD Professional
Developed under the direction and sponsorship of Merck.
Helpful information when talking to parents about HPV vaccination

Prescribing Information     Patient Information
When talking to parents about the HPV vaccine…
Focus clearly on cancer prevention
The CDC suggests:
Consider telling parents that HPV vaccination is about cancer prevention: cervical, vaginal, vulvar, and anal1
"HPV can cause certain cancers, and the vaccine helps prevent HPV-related cancers and diseases caused by 9 types. I want to help protect your child from these cancers."
CDC=Centers for Disease Control and Prevention.
GARDASIL 9 is a vaccine indicated in females 9 through 26 years of age for the prevention of cervical, vulvar, vaginal, and anal cancers caused by human papillomavirus (HPV) Types 16, 18, 31, 33, 45, 52, and 58; precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.

GARDASIL 9 is indicated in males 9 through 26 years of age for the prevention of anal cancer caused by HPV Types 16, 18, 31, 33, 45, 52, and 58; precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by HPV Types 6 and 11.
(Indication continued below)

Select Safety Information
GARDASIL®9 (Human Papillomavirus 9-valent Vaccine, Recombinant) is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of GARDASIL 9 or GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant].
(Select Safety Information continued below)
Learn more about how to clearly recommend
HPV vaccination in your office ▶

Saturday, July 30, 2016

The case of the vanishing pandemic: Deadly bird flu flies the coop in the US/ Ars Technica

Remember when we kept on hearing that the next big disaster was going to be avian (bird) flu?  Well, bird flu petered out and instead of jumping to humans jumped into a black hole.  The lack of flu vaccinations for farmed chickens and ducks in North America may be key.  The following excerpts come from Ars Technica :
  • The case of the vanishing pandemic: Deadly bird flu flies the coop in the US
  • Scientists puzzled by disappearance, but think lack of vaccination may be key. 
In November of 2014, a highly pathogenic strain of bird flu derived from Eurasia called H5N2 popped up in North America—in a Canadian turkey farm east of Vancouver, to be exact. From there, the virus quickly spread and mutated into new varieties, including H5N1, fanning fears it would vault to humans and cause a deadly pandemic. By March of 2015, it and its kin had swooped into 15 US states, causing 248 outbreaks in domestic birds and $5 billion worth of damages to poultry operations.Then, it vanished. 
…In a controversial twist, it may mean that bird vaccines, which aren't used in the US, are boosting potential pandemic flu viruses in other places of the world.

Webster and his team didn’t find any of the high-pathogenic H5N2 viruses in the wild US birds, nor any of the virus’ hybrid offspring… wild water fowl in the US had not tested positive for a highly pathogenic H5N-something virus once in the 43 years prior to the outbreak.

Webster hypothesizes that the garden-variety flu viruses essentially elbow out the highly pathogenic ones. So, when those nasty varieties move into wild bird populations, they don’t stay long. 
But, if Webster is right, it raises more questions about why and how some places, particularly in Asia, continually see the spread and maintenance of those highly pathogenic flu viruses in wild birds. And this is where vaccines come in to Webster’s hypothesis. 
Flu vaccines for domestic birds don’t always completely block the virus. In a small number of vaccinated birds, highly pathogenic flu viruses can still get a foot in the door and cause an infection. But those infections are mild, more like seasonal flus—unnoticeable to poultry farmers and perhaps even the bird. However, those domestic birds will still poop and shed massive amounts of highly pathogenic viruses. And those viruses can then continually be picked up by wild birds. 
In many places in Asia, poultry farmers clamor for vaccinations. But, in the US and Europe, which don’t see the same levels of highly pathogenic viruses, vaccines aren’t regularly used.

Instead, the US Department of Agriculture adopted a system of monitoring, quarantining, and culling.  It’s expensive, Webster noted, but it may be the best way to squash a potential pandemic.

Leaks Show DNC Asked White House to Reward Donors With Slots on Boards and Commissions

Political Corruption comes in many forms.  Here is just one of them--Meryl
by Alec Goodwin, Center for Responsive Politics

Email exchanges involving top officials at the Democratic National Committee released along with private documents by WikiLeaks show that DNC officials hoped to reward top donors and insiders with appointments to federal boards and commissions in coordination with the White House.
The revelations give an inside look into how the Democratic Party attempted to leverage its access and influence with the White House to bring in cash.
In an April 20, 2016 email, DNC National Finance Director Jordan Kaplan canvassed what appears to be the committee's finance department -- its fundraising office -- for names of people (mainly donors) to reward with federal appointments on boards and commissions.
That email exchange yielded a list compiled by DNC Finance Chief of Staff Scott Comer and emailed to Kaplan on April 26 titled "Boards and Commissions Names_Final," which listed the names of twenty-three DNC donors and insiders.
Kaplan emailed the list to Amanda Moose, special assistant to the president for presidential personnel, later that day. In an email without a subject line, Kaplan wrote just one line: "For your review," seemingly referring to a previous conversation or exchange.
Then on April 28, Kaplan missed a call with Moose. He emailed Comer asking for Moose's number that afternoon, presumably to call her back. Comer sent Kaplan the number. It's unclear if Kaplan and Moose spoke.
But the two may have spoken several days later; a May 3 email from Comer to Kaplan shows that Moose wanted to set up a "20 minute conversation" with Kaplan.
None of the individuals on the list have been appointed to boards or commissions since the email exchanges took place almost three months ago. A few were named to slots in previous years.
The White House strongly denied any link between financial support for the party and appointments.
"Being a donor does not get you a role in this administration," said White House spokesman Eric Schultz in an email to OpenSecrets Blog, "nor does it preclude you from getting one. We've said this for many years now and there's nothing in the emails that have been released that contradicts that."
The people on the list weren't just hefty donors to the DNC; many also gave big money to Obama.
The practice of rewarding big donors with federal positions dates back to the times of the founding fathers.
Bob Biersack, who spent 30 years at the Federal Election Commission and is a senior fellow at the Center for Responsive Politics, said that "Big donors have always risen to the top of lists for appointment to plum ambassadorships and other boards and commissions around the federal landscape. This example shows that party fundraisers continue to see these appointments as an important tool in the donor maintenance process."
Most of the people on the list gave huge sums to the Democratic National Committee, as well as the party's primary fundraising arms for its congressional candidates: the Democratic Congressional Campaign Committee (DCCC) and the Democratic Senatorial Campaign Committee.
As the table shows, the people whose names were on the list for possible federal appointments are big donors to the DNC, hold important positions there, and/or are big donors to Obama.
Many on the list bundled for the Obama campaign and are bundlers for Democratic nominee Hillary Clinton. Notably, the individuals on the list gave significant sums to Clinton and none to Bernie Sanders.
Wade Randlett, also who formed the Democratic PAC, was appointed to the Advisory Committee on Trade Policy and Negotiations in 2014. Another on the list -- Shekar Narasimhan -- was appointed to Obama's Advisory Commission on Asian Americans and Pacific Islanders in 2014. David Shapira, CEO of supermarket company Giant Eagle, was nominated to be on the board of governors of USPS by Obama in 2014, but the nomination was blocked by Congress.
In the emails leaked by WikiLeaks, Kaplan wrote "this is the last call for boards and commissions; if you have someone, send to Comer -- full name, city, state, email and phone number."
"Send as many as you want, just don't know how many people will get to," Kaplan wrote in an email sent April 20 to what appears to be the DNC's finance department.
Comer clarified in a later email, "Any folks who you'd like to be considered to be on the board of (for example) USPS, NEA, NEH. Basically anyone who has a niche interest and might like to serve on the board of one of these orgs."
These emails appear to show that DNC finance staffers -- the DNC's fundraising staff, in other words -- could suggest people they felt should be rewarded with federal appointments.
Responding to another question, Comer wrote "I should say, though, that the likelihood of landing a spot on ones as prestigious as NEA/USPS is unlikely. It's much more likely they'll get something like 'President's Commission on the Celebration of Women in American History.' (no shade to women)." In that same email, sent on April 21, Comer also said "when you submit your names, we don't need specific designations."
Comer's statements imply that the DNC could neither guarantee any specific position nor ensure that a person suggested would receive an appointment at all from the Obama administration.
Reached at her office in the White House, Moose said she was not authorized to comment. OpenSecrets Blog did manage to contact Kaplan, but he hung up after realizing it was a reporter. Comer directed our request for comment to a political consultant, who forwarded it to the DNC, which did not respond by press time.
The list was first reported on by the Daily Caller, a conservative news organization. The Caller article implied that the documents and emails showed Clinton traded appointments for donations. But the publication did not note the direct coordination with the Obama administration shown in the emails. 

Friday, July 29, 2016

The Bizarre US Pharmaceutical Market

I wrote an Op-Ed for the Portland, Maine Sunday Telegram about my bizarre journey trying to get a prescription filled.  It was published August 7, 2016. Here it is.


ELLSWORTH — Pricing of and access to medication are handled in an insane manner in the United States. It has been said that between 20 and 30 percent of prescriptions are never filled, presumably because of cost or access issues.

Comparing plans is nearly impossible, because drug tiers, co-pays, deductibles and coinsurance vary from plan to plan and drug to drug. Those with high drug costs on Medicare are likely to fall into the dreaded “doughnut hole,” in which all pharmacy benefits go away, until you have reached an out-of-pocket limit of thousands of dollars.

The complexity almost seems designed to trap the unwary into paying more. Why must things be so complicated, and seemingly, so arbitrary?

My own recent experience is instructive.

I went to Walgreens to refill a prescription for zolpidem. The prescription was valid, but my insurer, Humana, refused to pay for it. I was informed by Walgreens that I could alternatively pay about $200 cash to fill the prescription. Instead, I purchased seven tablets for $17 cash, buying me a week to sort out the problem.


After 90 minutes on the phone with six Humana staff (who provided me several incorrect explanations for their refusal to pay for the prescription), I was finally able to learn that my private Humana Medicare part D policy limits me to only 90 tablets a year of zolpidem. However, they might allow more with a prior approval. No guarantees.

It was suggested that I ask my doctor to fill in their form and wait to see if it was approved. Since my doctor was away, and it was not apparent whether the process would be successful anyway, I asked Humana to send me the form but kept searching for another solution. (P.S.  Two weeks later, I am still waiting for the form to arrive.)

I was aware of several startup companies that are taking advantage of the huge profits to be made in pharmaceutical sales. Their business model relies on negotiating low prices with pharmacy chains because the startups can provide patient volume. Even though the prices paid are very low, both the pharmacy chain and the startup make a profit.

So I went to Blink Health online to see what they offer. For the grand total of $8 I could fill the prescription that Humana refused to fill and that Walgreens was going to charge me $200 to fill (in the absence of a Humana approval).

Blink charged my credit card $8 and allowed me to print a page (or bring a picture of the page on my phone) to Walgreens, or any one of 19 other pharmacy chains, to collect my prescription.

Wow! I could hardly believe this would work, but I was excited to try it. I gave Walgreens the $8 piece of paper and easily collected my three-month prescription without paying a penny more.

This cost me less than the Humana co-pay would have been.

In my view, it is unacceptable that Humana has given itself the right (with government approval) to decide that some physician prescriptions for its insured patients should be covered for only three months each year. Clearly, this sets up patients to be price gouged, because in my case, anyway, the prescription would still need to be filled for the other nine months.


It is also unacceptable that a medication on which Walgreens and Blink presumably make a profit at $8 is nonchalantly sold for $200 cash to those patients not savvy in the ways of the system.

Why do we Americans accept this treatment? Why has our government created systems that encourage it? I am a Medicare patient, and all of the above has been Medicare-approved.

No wonder health care costs over $10,000 per patient per year in the United States.
If I weren’t a doctor, used to searching the internet, and had not kept looking for ways around this conundrum, most likely I would be without my medication this week. How many of my patients are without theirs?