Medtronic Helped Write, Edit Positive 'Infuse' Spine Studies

By John Fauber, Reporter, Milwaukee Journal Sentinel/MedPage Today

Published: October 25, 2012

 

Highly positive studies published in peer-reviewed medical journals depicted Medtronic's spine fusion product as a major breakthrough in back surgery, but those studies drafted and edited with direct input from company employees, while the doctors listed as authors were paid millions, according to a U.S. Senate investigation.

The company's heavy, undisclosed manipulation of information about its bone morphogenetic protein-2 product called Infuse included removing and downplaying concerns about serious complications linked to the product and overstating its benefits.

The Money Trail
Over the course of 15 years, Medtronic paid $210 million to a group of 13 doctors who co-authored the series of now-repudiated papers about the product. The payments also included two corporate entities associated with some of the doctors.

The investigation by Senate Committee on Finance was prompted in part by Journal Sentinel/MedPage Today investigations that showed how the practice of medicine has been corrupted by conflicts of interest involving doctors, drug and device companies and medical journals.

The Senate report, to be released Thursday, details how Medtronic employees, including some working in the company's marketing department, covertly collaborated with the academic physician authors in producing 11 different papers between 2002 and 2009.

Such "ghostwriting," though not illegal, has been condemned as a breach of integrity and transparency because doctors and patients rely on information in those articles to make medical decisions, not knowing that the papers may contain biased, inaccurate or potentially harmful information.

The Senate's findings highlight problems that should have been reported as at least a decade ago, said Ray Baker, MD, a Kirkland, Wash., pain specialist who served on an advisory panel to Medicare and Medicaid on Infuse.

"I am just sad this happened," he said. "At every level when we thought, 'that wouldn't happen,' it happened. The integrity of our scientific literature is our foundation. It's what predicates our treatments."

Medtronic Denies
Medtronic disputed many of the findings in the Senate's report.

"Medtronic vigorously disagrees with any suggestion that the company improperly influenced or authored any of the peer-reviewed published manuscripts discussed in the report, or that Medtronic intended to under-report adverse events," a statement emailed by the company said.

The company said it reported the adverse events to the Food and Drug Administration and those risks also are listed the product label for Infuse. Medtronic also called the report's characterization of the payments to the doctors misleading and unfair.

"The vast majority of such payments were royalty payments made to compensate physicians for their intellectual property rights and contributions, not consulting payments," the company said.

In 2011, after the Spine Journal devoted an entire issue to repudiating Infuse research, the company, under its new CEO, Omar Ishrak, hired Yale University to oversee an independent review of the safety and effectiveness of Infuse.

"This sounds eerily familiar to many of the transgressions we've read about from the pharmaceutical industry," said Harlan Krumholz, MD, a professor of medicine at Yale University, when told of the Senate report. "It paints a picture of a company very heavily involved in the science; marketing contaminating the science; and the medical profession and researchers being complicit.

The Public Trust
"It's no wonder the public has lost confidence in the drug and device industries." Krumholz is overseeing Yale's review of Infuse. Those results are expected in January.

Medtronic's behavior also drew sharp criticism from two key senators on the committee.
"Medtronic's actions violate the trust patients have in their medical care," Sen. Max Baucus, (D-Mont.), chairman of the committee, said in a statement. "Patients everywhere will be better served by a more open, honest system without this kind of collusion."

Senior member Chuck Grassley (R-Iowa) said the findings support the Physician Payments Sunshine Act that he and Sen. Herb Kohl (D-Wis.) authored. That legislation will require drug and device companies to disclose such payments beginning next year.

"The findings also should prompt medical journals to take a very proactive approach...," Grassley said in a statement. "...The public will benefit from more transparency and accountability on their part."
In response to the Senate investigation, Medtronic turned over more than 5,000 documents, including emails involving the doctors and Medtronic employees as well as 14 years of payments from Medtronic to the doctors.

The Infuse Story
In January 2002, Hal Mathews, MD, spoke glowingly about Infuse to a FDA advisory panel that was considering whether to recommend approval of the product.

Mathews, then a Richmond, Va. spine surgeon who had taken part in the pivotal Infuse clinical trial, told the panel he had no direct financial interest in the product and that he was not being paid to appear at the meeting.

However, a 2001 email shows that Medtronic worked with the New York-based public relations firm, Ketchum, to prepare Mathews' speech to the panel, which went on to recommend approval of the product.

In addition, though Medtronic told the committee that Mathews was not paid for any activity undertaken in January 2002, Mathews was paid under consulting arrangements with the company in 2001.

In 2007, Mathews was hired by Medtronic as its vice president of medical and clinical affairs.

From the Pen of Medtronic
An email indicated that a Medtronic marketing employee, Julie Bearcroft, was involved in editing a 2005 Journal of Bone and Joint Surgery article and recommended against publishing a complete list complications related to the structural integrity of the fused area.

Those complications -- known as implant migration, subsidence and end-plate fracture -- had been observed in a clinical trial and had been formatted in a detailed table, according to an internal Medtronic email. But, following the advice of Bearcroft, that table was not included in the published paper.
"I personally think it is appropriate to simply report the adverse events were equivalent in the two groups without the detail," Bearcroft wrote in a note on a draft of the article.

After the editing change was made, the lead author of the paper, Ken Burkus, MD, a Columbus, Ga. surgeon, sent a draft of the paper to his co-authors with the note, "this manuscript documents the superiority in clinical and radiographic outcomes with (Infuse)..."  Burkus, who got $6.4 million from Medtronic between 1998 through 2010, did not respond to an email seeking his comment.

Medtronic officials inserted into papers language that attempted to portray Infuse as a better, less painful alternative to the standard technique of using a small amount of a patient's own hip bone for fusing vertebrae, a claim that has been questioned by independent spine surgeons.

Giving Infuse the Edge
In 2001 and 2002, after viewing early drafts of a 2002 Infuse paper, Neil Beals, a Medtronic marketing official recommended that the physician authors make "a bigger deal" out of the supposed pain reduction with Infuse.

Subsequently, a sentence was inserted in the paper stating that Infuse spared patients from being exposed to problems associated using their own bone for the fusion.
 
In its review of Infuse last year, doctors writing in the Spine Journal said the often-cited donor site pain was less frequent and serious than Infuse proponents suggested.

In addition, in a draft of a 2003 paper the authors said that any pain at the site of the hipbone graft site had been resolved in the study subjects within a year of the surgery. But Beals questioned that and inserted language saying residual effects of the donor site should be noted.

The final article appears to have adopted his suggestions, noting that even 24 months after the surgeries "some patients continued to experience residual pain at the donor site and rated the appearance of the site as only fair."

Downplaying Safety Concerns
The company also tried, unsuccessfully, to adopt weaker patient safety rules for a clinical trial testing the effectiveness of Infuse in the cervical spine, a use that remains unapproved and which has been linked to life threatening swelling in neck.

In 2008, the FDA warned doctors against using Infuse in cervical spine fusions, citing 38 cases of swelling in the neck and throat leading to compression of the airway. Some of those cases required emergency tracheotomies.

The weaker safety rules sought by Medtronic would have allowed the company to continue the clinical trial even if patients experienced severe swelling in neck.

Infuse is a powerful biological agent that stimulates the growth of new bone, but excess bone growth can be a serious problem when the product is used in certain off-label surgeries. It was approved in 2002 for lumbar spine fusions in which the surgical approach is from the front.

The unapproved use has caused serious problems for Patricia Caplinger and hundreds of other spine surgery patients like her, according to a lawsuit filed earlier this year against Medtronic in federal court in Oklahoma.

The complication experienced by Caplinger was the subject of a 2004 paper written by doctors who have received millions of dollars from Medtronic. That paper involved a clinical trial of Infuse that had to be halted five years earlier because of excess bone growth in the spinal canals of 70% of the patients.

That clinical trial used Infuse in a surgery similar to what Caplinger underwent in 2010. The surgeons who wrote the article said that patients weren't harmed by the excess bone growth. But that claim that was refuted by an Oklahoma surgeon who took part in the trial and told the Journal Sentinel/MedPage Today last year that he had two patients who developed painful, excess bone growth that required additional surgeries. Caplinger who lives in Missouri was not one of those patients.

A helping hand in the OR
Caplinger says that her doctor and others surgeons were persuaded by Medtronic and its "paid physician promoters" to use Infuse in dangerous, off-label surgeries, according to her lawsuit.
In Caplinger's case, a Medtronic representative actually was present during her surgery and "was actively involved," providing information about use of Infuse in Caplinger's procedure, according to the lawsuit.

Because of the excess bone growth, Caplinger suffers continuous pain in her back and legs and developed a condition known as foot drop, which, in turn, led to a ligament tear in her right knee. She also has required revision surgery on her back and will need another revision surgery because the bone growth is continuing.

In an email, Caplinger, a nurse, said she is worried that the pain eventually will prevent her from doing what she loves the most, working in the emergency department. "I live with pain every minute of every day," she said. "I have forgotten what not being in pain feels like."  A Medtronic spokesperson said the complaint lacks and the company has the court to dismiss the case.

Medtronic had answers
The Senate report and accompanying documents also show Medtronic employees -- in addition to editing drafts of a paper -- at times covertly drafted responses to questions raised by other doctors who were examining the work as part of medical journal peer review.

Case in point: A 2004 paper was published in the Spine Journal where co-author Charles Branch Jr., MD, also served as deputy editor. Branch, chairman of neurosurgery at Wake Forest University, received $3.1 million from Medtronic from 1998 to 2010. His royalty payments have been split with the university.

That article also was subject of a 2011 Journal Sentinel/MedPage Today investigation.
The Senate documents include a 2003 email, as the article was being drafted, in which Bill Martin, the company's vice president of spinal marketing, wrote: "We may want to steer clear of calling it a flawed technique. There are still quite a few surgeons utilizing this technique..."

About a week later, Rick Treharne, another Medtronic executive, wrote to one of the paper's authors: "In looking over the data, I was impressed with how well the BMP (Infuse) patients actually did. So much so that I added a few paragraphs at the end that you may not agree with."

As peer reviewers for the journal looked over the paper, they raised concerns that it was a slanted, advertising piece. "This manuscript is full of biased statements that are a reflection of the data evaluators -- the company that markets the product," wrote one reviewer.  "Unless the authors can discuss the results in this study in an unbiased manner, which they have been unable to do in its present form, this data should not be published," wrote another.

Treharne then sent one of the co-authors a draft of a letter to be sent to the editor of the journal addressing the concern. Another Medtronic executive also helped formulate a response to the editor.
The letter that ultimately was sent to the journal's editor sought to reassure him, claiming that three of the co-authors were independent, the Senate investigation found.

But between 1997 and 2003, two of the "independent" authors had received $8.5 million from Medtronic. "We were falsely reassured that there were independent people looking at the data," said Eugene Carragee, MD, who took over as editor of the Spine Journal in 2009. "It's a violation of the fundamental trust of peer review."

When published, the paper described the results of halted clinical trial as "encouraging."

This story was reported as a joint project of the Journal Sentinel and MedPage Today.

Appeals Court hears case on medical value of marijuana

Appeals Court hears case on medical value of marijuana

October 16th, 2012
Posted by Jonathan Bair This morning, the federal Appeals Court for the DC Circuit heard an appeal in the case called Americans for Safe Access v Drug Enforcement Administration. The case is an appeal of the DEA’s rejection of a petition filed in 2002 seeking to change the placement of marijuana as a Schedule I drug per the Controlled Substances Act. Based on the scientific evidence, ASA and our fellow plaintiffs feel that it is simply untrue that cannabis is a drug with a “high potential for abuse” and “without accepted medical use in treatment in the United States.” The hearing today offered a glimpse at the Court’s approach to this topic.
In front of a packed courtroom in Washington, the three-judge panel questioned ASA’s Chief Counsel Joe Elford and a federal lawyer about the merits of the scientific case, and the crucial legal issue of “standing.” Standing is a legal concept that restricts the right to sue to injured parties – people who are directly hurt by what they are fighting, and can get relief from a legal judgement. The issue of standing has been the reason why two prior appeals of the DEA’s classification of marijuana were rejected. In the past, patients have not been part of lawsuits against the Controlled Substances Act. The three judges were Merrick Garland, Karen Henderson, and Harry Edwards.
ASA’s Chief Counsel Joe Elford opened his appeal by arguing that the federal “Department of Health and Human Services plays a game of gotcha” by tightly controlling research access to cannabis and then claiming that there is not enough compelling research to justify reconsidering it as Schedule I. The Drug Enforcement Administration erred by determing that cannabis has a high potential for abuse when its findings determine its abuse and harm potential is less than other substances in less-controlled schedules, such as cocaine.
Elford opened his arguments with the issue of standing. He pointed to the affidavit of plaintiff Michael Krawitz, a veteran denied access to Veterans Administration services because of his medically necessary use of marijuana. The Veterans Administrastion’s harmful policy is based on marijuana’s status as a Schedule I substance. He also spoke of the many members of Americans for Safe Access, who are fearful of the consequences of cultivating their own cannabis for their medical needs, and that a medical necessity defense in court could be allowed if marijuana were not in Schedule I.
Elford then turned to the issue of the merits of the DEA’s position on marijuana’s medical value, to prove their position was “arbitrary and capricious” and therefore impermissible. The contention that there is not a complete consensus was argued to be an unreasonable interpretation of the regulatory standard, and that many of HHS’s standards are inapplicable to an organic substance. Significantly, the lack of access to marijuana for medical research is a consequence of the scheduling, yet the lack of suitable research is cited by the DEA as a reason for maintaining the schedule. Despite this lack of research access, ASA cited a growing body of high-quality scientific and medical research into the benefits of marijuana.
Judge Garland asked Elford if he was arguing that marijuana in fact meets HHS’s standard for studies. ASA’s counsel cited over 200 studies and argued that a circular standard is impossible to meet. He also said that, given that the schedule is relative, the DEA is ignoring even its own studies showing that marijuana has merely a “mild” potential for abuse.
Joe Elford concluded by arguing that Schedule I was an inappropriate classification of marijuana and it caused harm to patients and prevented meaningful medical research. Rescheduling marijuana would allow for a reasonable policy solution for suffering patients and uphold the intent of the Controlled Substances Act.
Judge Edwards asked about the standing of Mr. Krawitz, and his access to medical marijuana. The judges asked about access in medical states and noted that marijuana would not be legal just because it were rescheduled.
Federal counsel Lena Watkins then presented her position against appealing the DEA’s decision to continue cannabis in Schedule I. She noted that state legislatures or popular votes do not determine accepted medical use. She said that research is inadequate and has not progressed, and argued that the government does provide access for research.  Turning to the abuse potential, Watkins said, “marijuana is the most widely abused drug in America,” and dependency is a factor in making that assessment.
The judges questioned the level of access provided for research, and Watkins said that fifteen studies of a specific federal “quality” metric have been allowed. Pressed to explain why these studies haven’t persuaded the DEA that marijuana has medical benefits, she said, “we don’t have the final results yet.” To many in the audience, the circular nature of the government’s position on the science of marijuana was clear. The judges then invited Elford to give a rebuttal.
Focusing on rebutting the government’s claims about research, Elford argued that there has been adequate study and even more since this case was filed in 2002, and noted that he would like to admit additional evidence to the case. Summarizing by turning the government’s “no substantial evidence” argument on its head, Elford said that both sides agree more research needs to be done and that research can only happen if marijuana is released from Schedule I. Requiring the DEA to make scientific determinations on a new schedule would lead to better policy and more relief for suffering patients.
The patients spoke out at a well-attended press conference after the hearing, and Americans for Safe Access is proud to have given patients a day in court. Many observers felt the judges were willing to consider the argument of Michael Krawitz’s direct harm from the Controlled Substances Act, and this issue of “standing” has been the Achilles heel of past lawsuits against Schedule I. However, Judge Garland asked at one point, “Don’t we have to defer to the agency? We’re not scientists. They are.”
We’ll find out whether the judges felt the DEA’s science is adequate, or if patients can sue for a medical necessity defense against harsh marijuana laws, when the judges rule. We don’t expect it for a few months. This opportunity is thanks to the brave plaintiffs who took on the federal government on behalf of many others.
Jonathan Bair is ASA’s Social Media Director. Recordings of any kind were not allowed in the courtroom.

Alzheimer's disease stopped in its tracks!

The results of this study are so amazing, I am posting it on both my blogs.  Just keep in mind

• This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• Note that this very small study reports long term stabilization of Alzheimer's disease symptoms with IVIG treatment over a period of 36 months.

http://www.medpagetoday.com/MeetingCoverage/AAIC/33780

Chemical Intolerance in Primary Care Settings: Prevalence, Comorbidity, and Outcomes

I just received an article on the results of the above-named study from a friend with multiple health challenges.  I thank my friend for sharing this article with me.  I know how difficult it can be to sit at the computer and type for people living with these types of challenges.

The study indicated that Chemical Intolerance was noted at a much higher rate than previously thought, 20.3% of the participants in the study.  The researchers found that socioeconomic status had a positive and significant relationship with Chemical Intolerance.  The study also showed a greater rate of Chemical Intolerance among Hispanics.

The researchers hypothesize that the increased prevalence of chemical intolerance among patients in the low-SES group may be related to their occupations, which may increase their exposure to "solvents, cleaning agents, pesticides, and other substances now clearly linked with the development of chemical intolerance and associated neuropsychiatric symptoms, via a process referred to as toxicant-induced loss of tolerance. (emphasis mine)

The study indicated that Chemical Intolerance was linked to loss of function and social activities, "chemical intolerance is associated with poor quality of life and functional impairments leading to loss of employment and socioeconomic hardships."  The link to the entire article is below and can be found on Medscape.com.  There is also a link to the full text of the original article in Annals of Family Medicine.  Thanks again to my friend for sharing this important article.

Medscape.com article HERE.               Ann Fam Med. 2012;10:357-365. Full text HERE

Pharmaceutical companies must provide pain drug education to docs

http://www.pmlive.com/pharma_news/fda_education_programmes_opioid_pain_drugs_411623

PMLIVE:  Pharmaceutical companies in the US will have to provide doctors with an education programme for any extended-release (ER) and long-acting (LA) opioid medications they market in an effort to prevent drug abuse and misuse in patients.
The requirement is part of wider measures from the US Food and Drug Administration (FDA) to reduce risks and improve safe use of the pain drugs that include Pfizer’s Avinza, Actavis’ Kadian, Janssen’s Nucynta ER and Duragesic and several products from Purdue Pharma, all of which can cause serious harm and even death if used improperly.

The extra training will be based on an FDA design and will inform healthcare professionals about the safe prescribing of ER/LA opioid medications so they can have a greater knowledge and awareness when having a conversation with a patient about the risks and appropriate use of a prescribed medicine.

Companies are expected to achieve goals established by the FDA for the percentage of prescribers of ER/ LA opioids who complete the training, and prescriber understanding will be audited and assessed. Courses will either be free or charged at a small fee. Despite pharma firms being made to provide such training, prescribers are not required to take it under current US law.

Instead, the FDA said it “continues to support this approach, but absent the needed legislation, intends to exercise its authority to require mandatory elements for companies and voluntary elements for prescribers”.
In addition, the full risk evaluation and mitigation strategy (REMS) also includes an updated medication guide for each drug, provided to patients via pharmacists that explains how to safely use ER/LA opioid medicines.
“Misprescribing, misuse, and abuse of extended-release and long-acting opioids are a critical and growing public health challenge,” said FDA commissioner Dr Margaret Hamburg.

“The FDA’s goal with this REMS approval is to ensure that healthcare professionals are educated on how to safely prescribe opioids and that patients know how to safely use these drugs.” The FDA is also encouraging the safe storage of such medicines to prevent them being taken by someone other than the person they are prescribed for.  "Just because it's safe for the patient, doesn't mean it's safe for someone else," said Dr Sharon Hertz, deputy director of the FDA's division of anaesthesia, analgaesia and addiction products.

According to IMS Health, it is estimated that 22.9m prescriptions of the painkillers were dispensed in 2011. There were 15,597 deaths involving these medications in 2009, said the US Centers for Disease Control and Prevention.

Published: 11/07/2012

"Highless" cannabis developed for medicinal use in Israel

I just got an email from a friend of mine who has relatives in Israel with some impressive news regarding medical cannabis research there.  It seems that a new strain has been developed with negligible THC, but very large percentages of CBD.  What this does, is let those individuals who are sensitive to the "high" of cannabis utilize it for its potent anti-inflammatory properties.

We all know that cannabis has a number of medicinal properties, but everyone using it for medical reasons is always accused of  "just wanting to get high."  This should put an end to that argument.  However, THC has potent medicinal properties of its own, so not everyone will be happy with a strain without it.  But for those who cannot tolerate the effects of THC, this strain could be a blessing.  Thanks to the researchers in Israel for all the work they have done on it.

Below is an excerpt from the original article which you can find at:
http://www.medscape.com/viewarticle/766803?src=mpnews&spon=12
Note:  This site requires a free registration to read the article.

Dr. Ruth Gallily of the Hebrew University, who works for the company and has been studying CBD for more than 12 years, said she has found that the substance has impressive anti-inflammatory qualities. She has been testing the effects of Tikun Olam's CBD-enhanced cannabis on mice and expects clinical trials to begin in a few months.

Avidekel is a new strain of a plant that is already permitted for medical use so there is nothing stopping patients who are already being treated with marijuana from trying Avidekel. About 10 patients began using it in the past six months, Klein said.

"The cannabis plant, enriched with CBD, can be used for treating diseases like rheumatoid arthritis, colitis, liver inflammation, heart disease and diabetes," she said, adding there are no side effects.

"It's a huge advantage," said one 35-year-old patient who asked not to be identified, "I can smoke during the day, function with a lot less pain and still be focused, work and drive. It is a great gift."

Comment on ME/CFS Mitochondrial Dysfunction Paper

You can find another related article HERE.

By Norman E. Booth, Sarah Myhill, John McLaren-Howard • ProHealth.com • July 4, 2012

Source: Press Release, July 4, 2012

Dr. Norman E. Booth, Dr. Sarah Myhill and Dr. John McLaren Howard are pleased to announce the publication of a second paper concerning the link between mitochondrial dysfunction and ME/CFS. [“Mitochondrial Dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)", published June 30, 2012]

COMMENT

In 2009 we published our first paper looking at mitochondrial function in ME/CFS patients. What we found is that those patients with the worst mitochondrial function had the worst levels of fatigue and vice versa. There was a very clear relationship between the two. The importance of this paper was that it gave backing to certain treatment interventions and also that it clearly established ME/CFS as a physical condition with physical causes. The mitochondrial function can be used as an objective assessment of fatigue and of course this has obvious practical implications.

Hitherto any assessment of the level of disability had to be subjective and this created great difficulties for patients in cases where their physicians disbelieved the serious nature of their symptoms. For a detailed explanation of the clinical issues please see http://www.drmyhill.co.uk/wiki/CFS_-_The_Central_Cause:_Mitochondrial_Failure.

This second paper further explores the above ideas. In this second paper the size of the patient group is much larger with 138 ME/CFS patients involved. Their mitochondrial function tests were compared with 53 normal healthy controls.

The findings of the first paper were repeated and confirmed, but the analysis of this second paper was carried out slightly differently.

It was found on careful inspection of the biochemistry that there were various sub-groups of ME/CFS patients with their own characteristic biochemical pattern. In particular, one of the five parameters measured, namely translocator protein function IN, can  be  higher  as  well  as  lower  for patients as compared with controls.

This second paper also attempts to explain what is happening at the biochemical level to result in such an abnormality.

To this end, Dr. Booth provides an alternative method of assessing mitochondrial function. He noticed that the percentage inhibition of ATP closely correlates with TL-in factor – this is probably because the biochemistry of these two measured quantities is so closely associated.

So instead of using TL-in to calculate the mitochondrial energy score, he used percentage ATP inhibited – this provided a solution to the problem of translocator protein IN being higher in some patients than in controls, a factor which in itself is abnormal.

Dr. Booth then went on to plot the relationship between mitochondrial energy score and the number of factors within the normal region to achieve an extremely close correlation.

Importantly this test identifies a clean separation between the ME/CFS cases and the healthy controls.

So this first part of the paper very much confirms the work of the first paper published in 2009 which is that those patients with the worst ME/CFS had the worst mitochondrial function and vice versa.

It must be remembered that patients attending a clinic for ME/CFS are usually the most severely fatigued – no mildly ill patients were tested. Within these limitations the ATP profile is an exclusive and sensitive test for ME/CFS. However, we cannot claim that it is specific to ME/CFS because there are many other neurological illnesses and metabolic syndrome also associated with mitochondrial dysfunction. 

Dr. Booth went on to analyze sub-groups within the main group.

When mitochondria are stressed, i.e., energy demand exceeds energy delivery, in the short term they can switch into an alternative means of making ATP, of which there are 2 possibilities identified. Dr. Booth called these patients cohort 1 and cohort 2.

• In cohort 1, the mitochondria switch into anaerobic metabolism with increased glycolosis in order to produce ATP.

• In cohort 2 there was an alternative process to supply additional ATP. This alternative process involves the adenylate kinase reaction in which two molecules of ADP combine to make one of ATP and one of AMP. The problem with this reaction is that for every molecule of ATP generated, so is one of AMP. This is not recycled, but mainly lost in the urine. So there may be short term metabolic benefits here, but in the longer term metabolic disaster ensues as the energy molecules literally leak away. It takes time to replace these leaked molecules of ADP (leaked in the form of a ‘lost’ AMP molecule) and so this may explain one of the clinical features of ME/CFS, namely delayed fatigue.

A vital feature of ATP studies is that they identify the mechanisms by which mitochondria ‘go slow’. Essentially they can ‘go slow’ for one of three common reasons:

• Either there is substrate deficiency, i.e. lack of essential co-factors for mitochondria to work such as Co-enzyme Q10, magnesium, vitamin B3, or acetyl-L-carnitine,

• Or secondly, because mitochondria are blocked by toxins. Typically the blockage can be of oxidative phosphorylation and/or translocator protein function. Dr. John McLaren Howard has developed several further tests to look at the nature of these blockages. These tests include microrespirometry studies, translocator protein function studies, intracellular calcium studies and so on.

• The third possible mechanism for mitochondria malfunctioning has to do with membrane function. The membranes of mitochondria need to be of just the right consistency in order to hold the bundle of enzymes in the correct 3D configuration to allow efficient movement of substrate from one enzyme complex to another. To this end, again Dr. John McLaren Howard has developed cardiolipin studies which look in more detail at mitochondrial membrane structure and function.

Many of the above tests have been available in research laboratories, some John has developed through his own brilliance and initiative. What is so wonderful is how he has given these cutting edge research tests a clinical application.

This is extremely helpful for patients and clinicians because we can see exactly why mitochondria are ‘going slow’ and thereby correct deficiencies using both nutritional supplements, correct gut function, as well as being able to tailor detoxification regimes to individual patients.

This second paper also goes on to look at cell free DNA in ME/CFS patients.

Cell free DNA is a measure of DNA in the bloodstream that is not bound up within cell membranes. It can only, therefore, come from damaged cells and therefore is a measure of cell damage within the body.

What we found is a strong negative correlation with mitochondrial energy scores, ATP levels and the rate of oxidative phosphorylation. What this means is that those patients with mitochondria that perform extremely poorly have the highest level of cell damage and vice versa. This makes perfect biochemical sense – if mitochondria ‘go slow’ one can expect there to be the production of free radicals which have the potential to damage tissues.

Therefore addressing these issues of poor antioxidant status is an essential part of the package of treatment for ME/CFS patients.

These abnormal results clearly show that the effect on mitochondria is a systemic effect, not just confined to the neutrophils that are being tested. Very often we see levels of cell free DNA of a similar magnitude to those in patients who are experiencing a serious illness such as cancer, stroke, autoimmunity, or severe viral infection. Again this underpins the fact that ME/CFS is a physical condition with clear indications of marked cell damage.

This puts ME/CFS firmly in the realm of major organic pathology.

IMPLICATIONS FOR THE TREATMENT OF ME/CFS

These bio-medical tests have been extremely helpful in the diagnosis and management of ME/CFS patients. This is because they clearly identify the biochemical lesions that underpin the cause of this illness. Furthermore, identification of these lesions has clear implications for management using the standard methods of nutritional and environmental medicine.

We are currently preparing a third paper which looks at the efficacy of these interventions in patients by measuring mitochondrial function tests before and after such interventions and correlating these with the clinical picture.

For further information as to what these interventions are please see http://www.drmyhill.co.uk/wiki/CFS_-_CFS_Book_published_by_Dr_Sarah_Myhill, which is available on line without charge.

It bears repeating that this paper would not have been remotely possible without the brilliance of Dr. John McLaren Howard at Acumen Laboratory, who has developed these wonderful tests for looking at mitochondrial function, together with the analytical mind of Dr. Norman Booth, who has analyzed the data in detail to identify the biochemical metabolic pathways involved.

- July 4, 2012

Ramblings about wanting to work

I have been feeling better than usual for the past few weeks.  That's great right?  Well, it is great, at least compared to how I've felt for the past year.  So I've been spending quite a bit of time looking through the want ads, thinking about how great it would be to find a part-time job.  Then I start thinking about what that would really entail.

I'd have to be able to respond to a set schedule--like getting up at a certain time every day.  Sounds easy enough doesn't it?  I've been doing it for the last couple of weeks, waking up early and sleeping well at night.  If only I could count on that experience.  But in my heart, I know I can't.  I am experiencing this profound improvement in my well-being, because I can sit down and rest whenever I need to.

I have the option of sleeping late if I wake up one morning feeling like I've been hit by a bus, and it WILL happen.  I just don't know when.  How many times can I go through the process of job-search, interviews, and hiring only to work a few months and have to give it all up because of my disabilities?  I want to work.  I want to work so terribly at times that I can hardly stand it, but I am unable to succeed at what the Social Security Administration calls gainful employment. 

This only adds to my symptoms of depression.  So even when I'm feeling relatively good, like I have been lately, I still have to contend with the fact that I will never be able to contribute gainfully to the finances of our household.  I have to fight off the feeling that I am a freeloader in my own home.

No matter how well I feel now, I know it's only a matter of time before I'm hit with another blow from my traitorous body and mind.  That feeling of knowing the other shoe is bound to drop nags at me constantly even when I'm at my best, which used to be great but is now a low mediocre.  It is as if my successful ability to function has gone from a symphony to a barely perceptible hum.

So to all those of you out there who suffer with chronic pain, disability, depression, or all of the above, enjoy the good times, no matter how limited they are.  It isn't going to kill me to fantasize a little about working again, as long as I understand that fantasy is all it is.  I've had my heart broken enough by trying to do something I am no longer capable of doing.  Who knows, maybe someday a miracle cure will come my way.

What's the real story on the new fibromyalgia and cannabis studies?

There are stories all over the web this week about a new study by Dr. Mary-Ann Fitzcharles that confirms at least 13% of folks with fibromyalgia are using marijuana for pain control.  Now, that is quite interesting to me, because it has been determined by previous studies that about 19.8 percent of U.S. adults -- 43.4 million people -- were smokers in 2007. That was a percentage point below the 2006 figure.  

It seems strange to me that a lower percentage of people with fibromyalgia (who are in chronic, excruciating pain) would use a medication that has been proven to significantly reduce their suffering than the general population uses.  In other words, something just doesn't sound right here.

So, I've included links to a few articles on this new study.  You can check them out and determine for yourself if you think the new study is valid.  I don't know, but I think the results beg for more research.

Marijuana Use for Fibromyalgia Pain

About - News & Issues - ‎45 minutes ago‎

By Adrienne Dellwo, About.com GuideJune 29, 2012 A new study examining the use of marijuana for fibromyalgia pain revealed that 13% of people at one Canadian pain center were using some form of cannabis (the plant that produces marijuana.) ...

Fibromyalgia Pot Stats Are Crap

Cannabis Culture - ‎11 hours ago‎

CANNABIS CULTURE - Dr Mary-Ann Fitzcharles of McGill University Health Centre released a fibromyalgia medical marijuana study that's beyond bogus. People with fibromyalgia actually use cannabis less than the national average, but that's not in their ...

Illegal Marijuana Used by 10 Per Cent of Fibromyalgia Patients: Study

Cannabis Culture - ‎Jun 25, 2012‎

By QMI Agency - Monday, June 25 2012 People who suffer from a medical disorder that causes chronic pain are buying marijuana on the street for relief, a new study has revealed. The study, led by Dr. Mary-Ann Fitzcharles, a rheumatologist at the McGill ...

Clinical Trials for chronic pain patients

There are hundreds of clinical trials being held throughout the U.S. and the world for individuals struggling with chronic pain.  I am going to list some places on the web where you may find information on specific clinical trials such as whether they are recruiting, where they are located, and requirements for test subjects.  You may reach these sites by following the links below.  These links will give you the information on over a thousand clinical trials.


National Institutes of Health Clinical Trials

National Institute of Neurological Disorders and Stroke Trials

U.S. and Worldwide Clinical Trials

Depression - it's not just feeling down

Blue Randomness: Depression - it's not just feeling down:

Don't get me wrong, I do not mean I've been in a depressive episode my entire life—I've had periods, sometimes years long, that have been quite pleasant and productive. I've held very good jobs, been creative, lively, and happy. But those periods when I am depressed can be hellish. They have also been torturous to those that love me. I am not the only one who worries that “this time” might be the time when I don't come back from a major depressive episode.

 I have been struggling with depression for much of my adult life. I am technically diagnosed as bipolar, but I have not been subjected to...

A very good reason for non-lethal alternatives to opioids

Chronic Abuse of Painkillers on the Rise

from  MyHealthNewsDaily

Along with the rise in overdose deaths from prescription pain medication, there has been a rise in the percentage of people who regularly abuse the drugs, ...follow link above.

HCAN comments on Supreme Court ruling regarding healthcare

This is an email I just received from Health Care for America Now (HCAN).  You can make up your own mind about it, but I thought it needed to be shared.  HCAN is an advocacy group created to support the idea that all Americans deserve and need to have adequate health insurance coverage.

What’s at the heart of health care reform?

At every rally, in each blog post, in every comment we’ve made to the press or email we’ve sent you, HCAN has talked about how Obamacare expands coverage to more than 30 million people and eliminates the worst insurance company abuses.

We don’t talk about the so-called “mandate” because it’s a means to an end – it’s one of the ways everyone gets health care and it’s how we stop the big insurance companies from discriminating against people who are sick.

But the mandate isn't what Obamacare is all about, even if that’s what the right-wing says to stir up anger against the Affordable Care Act.

Please take a moment to read our latest blog post in the Huffington Post about what’s at stake with the Supreme Court’s ruling. Help us spread the truth.

Please share it on Facebook and Tweet about it.

Thanks,

Will O'Neill
Health Care for America Now

Medicare and Medicaid Services put kibosh on TENS for back pain

By Emily P. Walker, Washington Correspondent, MedPage Today

Published: June 11, 2012

WASHINGTON -- Medicare will no longer cover most uses of transcutaneous electrical nerve stimulation (TENS) for chronic low back pain, according to a memo issued by the Centers for Medicare and Medicaid Services (CMS).

Reimbursement for TENS for low back pain will be available only when patients are participating in a randomized, controlled trial of the technology's clinical effectiveness, CMS officials wrote in the final decision, which was released Friday and is effective immediately.

"TENS is not reasonable and necessary for the treatment of [chronic low back pain]," they wrote.

Currently, Medicare pays for FDA-approved TENS equipment and supplies when prescribed by a physician for chronic intractable pain and reimburses physicians and physical therapists for evaluating patients' suitability for the treatment, which is typically used at home.

Depression crushes the will

I am posting this on my other blog, Blue Randomness, as well as here:

It has obviously been some time since I've written anything on this blog.  I have been struggling with a severe case of clinical depression over the past months, and I have just not had the energy, the will (if you will), to write.  I am feeling better the last couple of weeks, so I am going to try to write something on the blog at least once a week for the next month and see how it goes.

Have any of you ever struggled with a major depressive or bipolar disorder?  If so, please feel free to attach your comments to this article. I know I am not alone in this and would love to hear from those of you who have also experienced it.

The role of benign joint hypermobility in the pain experience in Juvenile Fibromyalgia: an observational study

 – Source: Pediatric Rheumatology Online Journal, Jun 15, 2012

Abstract:
Background: Juvenile Fibromyalgia (JFM) is characterized by chronic widespread musculoskeletal pain, and approximately 40% of children and adolescents with JFM also suffer from benign joint hypermobility (HM). It is not currently known if the presence of HM affects the pain experience of adolescents with JFM.

The objective of this study was to examine whether there were any differences in self-reported pain intensity and physiologic pain sensitivity between JFM patients with and without joint HM.

[Note: the full text of this article is available free here. Other research, in women with hypermobile joints (able to extend joints beyond what is considered 'normal'), found that 75% of them also suffer from migraines (“'Loose Joints’ Highly Associated with migraine.” Statistics also indicate that joint hypermobility often co-occurs with orthostatic intolerance and/or chronic fatigue syndrome.)]

Fibromyalgia drug news

The newest fibromyalgia (FMS) drug, Savella (milnacipran), won FDA approval 3 years ago this month. We have yet to see a single drug approved for chronic fatigue syndrome (ME/CFS). Will 2012 see a drug come on the market that's proven to be effective for both FMS & ME/CFS?
The drug Northera (droxidopa) is currently before the FDA, and Chelsea Therapeutics requested Priority Review, which means we should hear something from the FDA by March 28. The New Drug Application is for Northera as a treatment for orthostatic hypotension in Parkinson's disease and related conditions, but early studies have shown promise in FMS and ME/CFS.
Orthostatic hypotension causes dizziness upon standing, when the blood pressure drops instead of rising like it's supposed to. This symptom is common in FMS and ME/CFS in addition to Parkinson's. However, studies suggest Northera is also effective against several more symptoms of FMS and ME/CFS. Chelsea announced last month that Phase II trials in fibromyalgia showed success in several key areas, but those data are not yet publicly available.
Northera contains a synthetic form of an ingredient your body uses to make the neurotransmitter/hormone norepinephrine, which is often dysregulated in FMS and ME/CFS. Some of the drugs shown to be most effective at easing symptoms of these conditions alter the levels or function of norepinephrine.
If Northera is approved and comes on the market this year, it'll be available as an off-label treatment for FMS and ME/CFS.
Not much else is in the pipeline for this year. However, 2011 saw promising research for a cancer drug in ME/CFS that will likely spur further work. Also, scientists announced they'd found a way to remove the "high" from marijuana without eliminating the pain-relieving properties. With several studies showing marijuana is effective against FMS pain, I hope we'll see something develop in this area.
Looking ahead to 2013, there's some good financial news - patent protection will expire for the FMS drugs Lyrica (pregabalin) and Cymbalta (duloxetine), meaning inexpensive generic forms could come on the market. A company has already received FDA permission to begin producing and selling generic duloxetine once the protection ends.

Zohydro for chronic pain?

Do Chronic Pain Patients Need Zohydro?

By Carol Eustice, About.com Guide   January 3, 2012

Several drug companies are developing a more potent pain medication containing hydrocodone. The new drug would contain up to 10 times the amount of hydrocodone that is found in drugs currently available, such as Vicodin. One of the drug companies, Zogenix, plans to apply for FDA approval of its timed-released version, known as Zohydro, this year and have it on the market in 2013. The possible addition of Zohydro to painkilling options has brought forward proponents and opponents.

Proponents say Zohydro will present doctors with another option for treating chronic pain patients, since not all medications are equally effective for all patients. It also has been suggested that a pure hydrocodone medication eliminates problems associated with analgesics that have acetaminophen as part of their composition. Acetaminophen overdose has been linked to potentially fatal liver toxicity. Zohydro will be closely monitored and you will be required to visit your doctor each time you need more pills, unlike current hydrocodone-acetaminophen medications that permit 5 refills.

Opponents believe Zohydro will provide the same abuse potential as OxyContin did, when crushing the timed-release pills produced an intense high. The maker of OxyContin reformulated the medication to make it more tamper-proof. With Zohydro, are drugmakers just reinventing an old problem? Does any of this make sense to arthritis patients who are still angry at the FDA for taking Darvocet off the market in November 2010? Share your thoughts below.