chemo is a terrible cure -- the equivalent of a nuclear bomb. You win the war, but you're left with a lot of fallout.

New one-time injection therapies are proving promising, but many of these are even quite toxic as well.

It looks like the next-generation cures are still a few years off, unfortunately.

If it makes you feel any better my two friends in Brooklyn who have cars forget where they're parked all the time.

More seriously: you make an excellent point about people simply not knowing in what instances their doctors are able to help them. The insurance industry, through high deductibles and copays encourages people to assume that they shouldn't make an appointment, even when they should. Overworked but well meaning HMO employees probably make people think that they're not going to get a great answer if they go, so they don't bother.

This is a consequence of making the consumer decide about things that a consumer really doesn't have enough information about.

An entire industry is pushing people away from what makes sense: when it doubt, go ask the person with the MD degree. I gotta admit, I don't follow that advice nearly enough. You've made me think it's time for a physical.

thosethingswesay.blogspot.com

Comes with age

That's a hell of a thing to say to a nice lady. Even I'm not so old that I've forgotten manners. :-)

Drugs do affect the mind. I read a veterinarian worrying about what the ubiquitous drug prednisone might do to the dogs he treats. It does real bad things to people however much good it does for them.

I spent hours looking for the car I parked in San Francisco once. I organized searches. I felt the panic rising. I began to worry that it had been towed away. Then as the sun was setting I got a hit that was better than the trout that once used to bite just as the sun went off the water.

That was when I was young.

Maybe I shouldn't be driving at all these days but I don't lose my car and I don't tell a woman she is getting old. :-)

Best, Terry

I agree with you, ninepatch. Nor do I wish to belittle the discomfort that this chemo side-effect produces in younger women. The Times article does mention that the 'brain fog' side-effect of chemo can be caused by an abrupt onset of menopause. Nine years after a normal menopause my memory problems are outrageous! But my husband appears to have equally bad problems. Luckily, between the two of us, we can usually manage to fill in each other's blanks on names, dates, words, spelling, etc., etc. Although we often treat it with humor, it's really not funny at all.

Totally agree with what you said. But since most breast cancer victims are postmenopausal, the before/after therapy evaluations could have to do with a decreasing memory function due to elapsed time between therapy and evaluation, i.e., a matter of years, and hence be less confirmatory as to cause. Certainly, the conclusions of evaluations of pre-menopausal women before and after chemotherapy, would most certainly point to chemotherapy alone as cause.

The issue under discussion is not that there may be a deterioration in memory etc with age, but whether a therapy tends to accelerate memory decreases... This phenomenon is not the "natural" decrease in memory associated with aging.

Police in New Jersey stopped a suspicious man who had been wandering around a neighborhood for some time in the early morning hours.

"What is your name?" the police asked.

"Albert Einstein," was the answer.

"Yeah and I'm Winston Churchill."

The cop wasn't Winston Churchill but the man was Albert Einstein, then a professor at Princeton. Einstein had lived in the neighborhood for years but couldn't find his house.

Another physics professor at Princeton wrote a book denying many of the stories about Einstein's memory but Einstein's own writings talk of his wonderment at his inability to remember, most notably his early childhood. Einstein's Epitaph has a wonderful line about his guilt at cheating in order to secure his academic degrees but a burden he gladly bore for the free time it allowed him for pleasurable pursuits. It was not so much willful as a necessity.

The brain remains a most mysterious region and never moreso than in a case like Einstein's.

Temple Grandin, an autistic professor in Colorado, writes of the advantage that Einstein and other notables had with "visual learning" over normal people. Her inclusion of DaVinci seems to me to cast doubt on some of her thesis - Einstein was the polar opposite of such a renaissance man as DaVinci - but I think few any longer doubt that Einstein was a fellow autistic.

The mild brain dysfunction following heart surgery has only been described in recent years and seems to have much in common with mild traumatic brain injury.

I note that you correctly put quotes around the "natural" decrease in memory associated with aging, rmrd. It would be ludicrous to deny that aging and memory loss are associated but there is nothing automatic about disease of any kind.

I had the great good fortune to talk to my elementary school teacher about a year before she died in her 90's. She had been blind for many years and had lived a shut-in life in a tiny village where she had taught four grades in one room. It was her failing eyesight that had ended her teaching decades before but her mind seemed as crisp and clear as it had ever been. She could remember the names of everyone of my small class though I could not. I would guess she could have recalled the name of every student she ever taught and much more. "Sammy always looked at your paper," said the old teacher. "But he was very bright. I guess he was just checking." Never missed a trick.

Others of us just wander through life in a perpetual fog.

Best, Terry

Now, I give the disclaimer that I'm just back from a rather annoyingly administered sleep study, so I am especially irritable toward the hospital functionaries on the night shift. "Well meaning" would be a step forward from this crew, whose answer to any request they didn't initiate was "No, I [the functionary] might get into trouble." There was never even a "hello."

Among other things, I design hospital workflow, decision support, and related systems. We never build in a task such that there is not always a human being responsible for it. As far as I am concerned, the answer I was given is never acceptable. A minimum answer would be "I don't have the authority to give you that information, but Mr. Jones, the night supervisor, or your doctor do." Realistically, no matter how well I know my HIPAA rights, there was no way to exercise them at 5 AM.

So, even when I am a "consumer" with thorough knowledge for my decisions, I may have to wait weeks to get the data. When data gets to my own physician, or, now that he's told his staff that they may do so, I immediately get copies. When I next see him, we are, if you will, playing from the same sheet of music. If need be, I've done the appropriate research, sometimes coming up with hard data that my physician hasn't yet read. He laughs about needing a minute or two for shifting mental gears, from the patient who finally brings in the brown paper bag with all their meds so he can figure out what they are actively taking, to discussing, in a meaningful way, the synergy between two drugs affecting different peroxisome proliferator-activated receptor types.

I have to agree that much of the industry deals with keeping things from the physician, or indeed getting the physician out of the loop if the issue is one of reimbursement.
--
Howard

*equal opportunity offense to both extremes*

"Those who cannot remember the past are condemned to repeat it" [George Santayana]

The study had controls. The controls were age-matched people with the same disease, but who received radiation or surgery but not chemotherapy. Thus the suggestion hat chemotherapy playeda role in the mental changes. Age was controlled.
There are acute mental effects noted after some procedures in some patients. The classic example is the person who was able to do the Sunday NYT Crossword puzzle in 30 minutes prior to coronary artery bypass grafting but now requires an hour to perform the same task.
Some patients have acute effects, others chronic changes. The study quoted above is just one looking into the effects of chemotherapy on mental function.

Second, the coloring agents are not always truly inert.

Last I heard sugar was not inert. :-)

I doubt any excipient is inert but what distinguishes them is that they have no therapeutic value.

Of interest is that one long ago approved cancer vaccine may be re-introduced with a new excipient.

BCG is not much like the modern cancer vaccines under development but has been used as an adjuvant in experimental cancer vaccines and was approved for treating superficial bladder cancer. It was withdrawn from the market because of problems with the excipient.

Best, Terry

Assuming there are no contraindications such as uncontrolled hypertension, there is literature, although not FDA approval, for cautious use of amphetamines and other sympathetic amines for memory improvement, especially in an aging population.

A friend resigned a government position because White House orders came down not to publish the results of contract/government research on the effects of drugs on cognitive impairment in roughly 60-plus year olds. Apparently, the political rationale was that it might offend the AARP and cost votes. The study actually had some reasonable results, certainly not banning people from driving. It did, however, suggest that some potentially sedating drugs, such as first-generation antihistamines, needed a slower rate of dosage increase and possibly avoiding driving for a matter of under a week, until the effects on reaction were clear.

I would note that some of the personal organization techniques mentioned are generally useful, not only for memory problems. My friends tell me my brain must be neat, since I certainly don't appear to be a Virgo in the organization of my desk. While I have a very sharp visual memory for where I put things, I am finding myself hunting for things a bit more.

--
Howard

*equal opportunity offense to both extremes*

"Those who cannot remember the past are condemned to repeat it" [George Santayana]

I'm sure you didn't mean it this way, but your dismissive attitude towards this problem is really indicative of the attitude taken by health care givers in oncology.

Chemotherapy is different for each person and so are the side effects and most people are reluctant to discuss the side effects just because people can have such a dismissive attitude towards them. Yes, aging can result in memory loss, but the side effects of inability to concentrate, brain fog, inability to organize and prioritize are very real for chemo patients. Other side effects of chemo and chemo therapy agents (such as tamoxofin) are glaucoma, cataracts, loss of hearing, fatigue, mouth sores, skin rashes, hair loss, sudden fevers, nausea, vomiting, sensitivity to noise, metallic taste in the mouth, sleep deprivation, hair loss, a compromised immune system and bone pain just to name a few.

Some doctors who enlist patients in chemotherapy drug studies, (for which they are reimbursed) are dismissive of side effects because adding drugs outside the test protocols is additional paperwork and aggravation for them and the research study. It's easier to tell the patient it's all in his/her mind than to add to the paper work load with additional tests and drugs.

There is also this prevalent view that the patient must always maintain an upbeat, positive and chipper attitude and "pro-active" in their treatment, and of course in reality, no one, much less cancer patients can always be upbeat and cheerful and positive. No matter how "pro-active" a patient thinks he/she is, never is a person's life more in the control and at the mercy of other people than undergoing cancer treatment.

The least recognized psychological disorder that cancer survivors suffer from is post traumatic stress disorder. A cancer patient is hit with the news that they have cancer, they undergo many times surgery and quite toxic and virulent chemical treatment which is afterall, poison, and then told that those patients who are always "positive" are most likely to survive - that often leaves especially women who have undergone mastectomies without a way to grieve their amputation (which is exactly what it is) and recognize the significant loss and overwhelming life changes that occur to cancer patients.

Many oncologists really do believe that you should just be grateful that you survived or are still alive, and they fail to recognize that for human beings, life is more than surviving - it is about trust, self-recognition, control of one's destiny, the quality of the life a person chooses to lead and a real and traumatic confrontation of mortality.

Since you've never had chemotherapy, you really can't understand that it's more than "forgetfulness" or "preoccupation with other thoughts" - there are real and lasting side effects from this experience that until you go through it yourself, you can't begin to understand, so telling survivors who are really and truly suffering from these side effects that they "should pursue some research" isn't very helpful. The best thing to do is to validate and recognize their experience which is what most people want anyway.

Just some thoughts from someone who has been there...

The least recognized psychological disorder that cancer survivors suffer from is post traumatic stress disorder.

--
Howard

*equal opportunity offense to both extremes*

"Those who cannot remember the past are condemned to repeat it" [George Santayana]

I agree, controlled trials of new therapy is the best current solution.
I am well aware of the trails and tribulations of Dr David Graham at the FDA dealing with the adverse effects of COX-II inhibitors. I am also aware of the Ketek debacle. Those are internal/political problems that will have to be addressed by a competent and ethical administration, not a condemnation of clinical trials.
My understanding of citicoline is that the results have been variable. Pooled data showed some benefit, while most isolated trials did not. There is a multi-center study being conducted at 56 centers in Spain and Portugal to address the issue. As of February, 39 patients had been enrolled.

http://www.strokecenter.org/Trials/TrialDetail.aspx?tid=679

I admit that it is best to be skeptical of the interests of the drug companies, the paid investigators, and the management of the FDA when reviewing trial data. This is skepticism is heightened given a politization of multiple government organizations by a GOP that puts party above the country and the fact that drug manufacturers are a major funding source for the FDA. The dug companies pay for the reviews of their drug studies. This could result in a tendency for the FDA to approve drugs rather than spent money to verify the validity of some clinical trial findings with longer term follow-up. My bias would be that rather than rejecting an ineffective drug, the current FDA would be more prone to allow a drug of questionable value. The "Orrin Hatch" FDA model.

What would you recommend as an approval technique not involving statistical significance?

Though anyone literate in math, let alone statistics, will tell you statistical significance is a line drawn in the sand rather than a rigorous definition, I don't recall ever saying one should discard statistical significance.

In fact I insist one should be very careful to eliminate chance occurrence as best one can. Anything else is nonsensical.

What is crucial, of course, is the determination of what the statistical significance refers to.

Don't you think one should use the most objective measures available in testing?

If you do, you disagree with the braindead zombies at the FDA who thought that there was no good evident in keeping brain cells of stroke victims alive.

Other countries around the world think it is best to keep brain cells alive.

Best, Terry

I don't think it's braindead to address, when national health dollars are limited, the general question of whether a drug improves both years of life saved and quality-adjusted years of life saved. There are indeed cases where even a modest advance is worth getting into practice and give more information, as with the first modestly effective drug for Alzheimer's syndrome, tacrine.

When looking at stroke, however, I believe the consensus, in emergency medicine, is getting stroke patients to a facility capable of assessing a progressing stroke, preferably within 3 hours and in no more than 6. With proper assessment, the majority of strokes may be helped by thrombolytic therapy. Of course, using a thrombolytic in the field, without the ability to differentiate between a cerebral occlusion and cerebral hemorrhage, is a fine way to kill the bleeding patients. Again, even with the bleeders, getting them to a facility that can patch the hole with angiographic techniques also can address the direct stroke mechanism.

While I recognize there is no national mechanism for balancing various therapies, I would hate to see dollars go to what might be a marginal drug rather than to fast transport to invasive neuroradiological facilities, if the drug has less potential benefit for dollar expended.

If you do, you disagree with the braindead zombies at the FDA who thought that there was no good evident in keeping brain cells of stroke victims alive.

--
Howard

*equal opportunity offense to both extremes*

"Those who cannot remember the past are condemned to repeat it" [George Santayana]

Well there may be a few psychologists, but I have yet to hear of any oncologists who recognize it.

No one is saying that the cause is chemotherapy alone. That's not even the issue. The issue is recognition of real side effects of chemotherapy that have not been recognized before this. It isn't just women recovering from breast cancer, men and children are also experiencing the same side effects. Children who have been treated with chemotherapy have a higher incidence of learning disabilities, memory impairment and organizational skills.

Keeping brain cells alive, in a general sense, is a good goal

That's progress.

Thank you. I will take what I can get.

if either this drug or neuroradiological intervention don't keep enough alive for demonstrable clinical benefit, neither is advisable other than as a research protocol.

The problem, of course, is the measure used.

There are numerous discussions of the appropriate way of measuring efficacy that is beyond the scope of this blog but I will rest my case on the fact that the drug has been approved in advanced countries around the world that found clinical benefit while the FDA insisted on a test that did not find a statistically significant benefit and presumably would not anywhere else.

The hilarity with the FDA's approval process is manifold.

One anaesthetic on the market for many years in Germany failed to gain approval because the sponsor had been unable to find any harm to lab rats despite vast quantities fed them. Without harm, there was no way of establishing a threshhold. Bon appetit, rats.

What sometimes happens is that valuable drugs are discarded in the process, costs soar and the drug behemoths are protected from competitors. One estimate by Frost & Sullivan gave $1.8B as the cost to get a new drug to market. I guess they arrived at that figure using all the failures but I don't really know. In the meantime patients die or lose their health - or their memory - needlessly. Sometimes good to forget I suppose.

Best, Terry

What would that more objective measure be?

--
Howard

*equal opportunity offense to both extremes*

"Those who cannot remember the past are condemned to repeat it" [George Santayana]

What would that more objective measure be?

A global neurological test at 6 months rather than the one that had been required.

After six months there is the usual rebound that masks the damage that was done. A more comprehensive test would have demonstrated efficacy more clearly according to some experts.

It is an old war that was lost - one of many. Americans pay the price with their lives and health as well as their taxes.

Best, Terry

Feed it to lawyers, and the regulators will accept there are experimental animals that can't be damaged.

A most valuable suggestion.

There have been suggestions that researchers use lawyers for medical experimenters because rats do less damage and are far more adorable.

I suspect we have bored people sufficiently.

Say a prayer for the dear departed and bow before the FDA that helped so to end their misery, pay tribute to Merck and Pfizer and all their kin and light a candle for Ralph Nader and the MSM who have done so much for the behemoths.

Best, Terry

I see I made my point. Even the FDA does not require that people be infected with ebola to approve a cure though it appears you would.

The point is that you have no point. I said I would consider participation in a vaccine trial. Key word vaccine. I would consider a vaccine trial if I lived in an endemic area.

Regarding the malaria study, are talking about the phase-three malaria drug trial that has just taken off in Kintampo. The purpose of this study is to investigate if a new drug called CDA (Lapdap-artesunate) is as safe and effective to artemether-lumifantrine in the treatment of uncomplicated P. falciparum malaria.
LAPDAP (chlorproguanil-dapsone) has been approved for the treatment of uncomplicated Plasmodium falciparum malaria across a number of sub-Saharan Africa. The combination of chlorproguanil-dapsone-artesunate (CDA) is being developed to supercede LAPDAP for the same indication, but the addition of an artemisinin derivative, artesunate, is expected to provide additional population benefits over LAPDAP alone.
Artemether-lumefantrine (Coartem) is the only available fixed-dose Artemisinin-based Combination Therapy actually available and is considered as the gold standard for the treatment of P.falciparum malaria. If successful, CDA is expected to come out as another fixed dose combination therapy for the treatment of P. falciparum.

http://www.ghana-khrc.org/aspfiles/cda_malaria.asp

The entry criteria is for 1395 patients between 1-14 who have uncomplicated malaria prior to entry into the trial. Is this the study that you are talking about? I know of others involving the 12 countries where malaria is endemic, but the ones I am aware of involve those already infected. New drugs are needed because of multi-drug resistance. Please provide a reference or a link for your trial if .

A somewhat similar trial can be found at
http://www.mmv.org/article.php3?id_article=343

Getting back to citocoline, what is your basis for certainty that the drug is of value? Are you involved in drug trials?

"each person was also evaluated for these problems" (of depression,etc.)

But they didn't bother to prescribe anti depressants to see if that would fix the problem.

I think a study should be done to see if anti depressant medication helps. As we don't know if stealth cases of depression showed up on the radar.

The therapist that I know using it definitely works with mainstream oncologists. I'd have to check on the status at NIH Clinical Center, but I know they are working with a variety of therapies.

At the very least, I'd tend to look for the opinion of a psychiatrist working with an oncology service. I'd be very nervous about a psychiatrist trying to figure the cardiac toxicity of a course of Adriamycin, about as I would about a very good oncologist dealing with bleeding-edge therapies for stress reactions.
The gold standard for PTSD is cognitive-behavioral therapy, with the role of drugs tending to focus on psychiatric comorbidities. EMDR and EMI are relatively new, but seem to have potential in dealing with PTSD. With all of these therapies, we have functional brain imaging that shows some changes in the abnormalities often associated with PTSD, but I can't say we really understand the changes -- simply that something is happening in the brain.
--
Howard

*equal opportunity offense to both extremes*

"Those who cannot remember the past are condemned to repeat it" [George Santayana]

Talking about avoiding the issue, could you provide a reference for the infecting people with malaria to test a drug therapy?

I have avoided not one thing except personal attacks.

An excerpt from a press release by the folks exposing volunteers to infection:

Volunteer participants will be enrolled in a “challenge” study of malaria infection that will take place in a specialized clinical trial unit. The primary purpose of the study is to determine whether pafuramidine can prevent the initial infection of the liver and also prevent development of symptoms caused by malaria parasites infecting red blood cells. Each volunteer will be given either pafuramidine or a placebo (sugar pill), and then exposed to (“challenged with”) malaria parasites that are sensitive to treatment with chloroquine. All subjects will be carefully monitored for malaria and promptly treated if they should become infected.

http://www.immtechpharma.com/documents/news_120906.pdf

Pafuramidine essentially failed prior trials as a solitary general purpose treatment for malaria.

We will have to disagree that the available studies clearly support that citocoline prove that the drug is valuable.

So you did an indepth study of the trials and determined that citicoline is marketed only in "some European countries?" You might want to check your facts before posting.

Political science and math isn't the best way to judge drugs IMO but that is just my prejudice speaking.

Best, Terry

Me: We will have to disagree that the available studies clearly support that citocoline prove that the drug is valuable.

You: So you did an indepth study of the trials and determined that citicoline is marketed only in "some European countries?" You might want to check your facts before posting.

I said that I am not convinced that the data supported that citocoline was effective. I provided experience with a drug used for 8-10 years in Europe as being effective. When brought to the US, the dtug was found to have a variety of side effcets,, some life-threatening. There had not been sufficient follow-up of the drugi Europe. I did not think viewing European usage with skepticism was a personal attack. All drug companies are profit oriented, thus their claims must be verified.
Regarding ineptitude at the FDA, I think I pointed out with examples like Ketek that it does exist. I stated my belief that snce drug companies were funding drug research at the FDA, it was more likely that an ineffective drug would be released, because of economic pressure from the drug manufacturer who is now paying FDA salaries.
You seem to believe that he FDA is releasing drugs, later removed from the marketplace because of side effects. These adverse efects could have been detected with better FDA oversight. We agree on that point.
We disagree on the value of citocoline. I require statistical values, you do not.
Thanks for providing the malaria study data.
Pafuramidine has received orphan drug status for pneumocystis carinii pneumonia in HIV/AIDS and African Sleeping Sickness.
The drug is in phase IIb trials for patiets already infected with uncomplicated malaria.
The trial you provided is designed to expose people to chloroquine-sensitive parasites to determine if pafuramidine can prevent the initial infection. You were correct
Two points: One is that there is a treatment for the parasites to which they are being exposed and it is being used in one center in a specialty unit. It is not equivalent to exposure to ebola. Second, if the drug failed in previous trials and is still being used as a preventative agent, is it not possible that since drug manufacturers pays the FDA for analyzing the drug study, the FDA is under more pressure to greenlight the study?
Again I come away with the impression that the curent FDA is more likely to release a questionable medication than halt an effective one. Given experience with drugs used in Europe that had to be re-evaluated aftr coming to the US, the monetary gain ssociated with marketing a drug, and the political atomosphere at the FDA, I don't see a way around adherence to full disclosure of drug trial data and statistical analysis to protect the public.
This includes releasing data from drug trials that failed to show benefit of the drug. Physicians and patients would have a better understanding of the medication
Thanks for the malaria study information. I am sorry if you felt a personal attack.
The current political hacks will be in place until Bush leaves. Tere is no rapid solution to that problem.