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Trapper John
07-11-2013, 05:40
From the Wall Street Journal: http://online.wsj.com/article/SB10001424127887324694904578597444105321914.html?m od=e2tw

While many chronic disabling conditions play only a limited role in premature death, they are major drivers of health-care costs, Dr. Murray said. "We are not very good at preventing them or curing them and only mildly good at treating them."

The US healthy life expectancy has declined from 13th (1990) among OECD nations to 26th (2010). The biggest contributing factor is the morbidity of chronic diseases. All of the treatments are palliative not curative - allowing patients to live longer with disease. This may be good for PhRMA markets and the bottom line, but not so good for patients. Moreover, chronic disease management is the major driver of escalating health care costs in the US. And as we all know, health care costs are a major contributor to our national debt. This situation is economically unsustainable!

IMO, there are two major problems that need to be corrected: (1) Innovation in pharmaceutical drug discovery/development and (2) the business model for drug development to market.

PhRMA would have us believe that the problem lies in the long regulatory approval process (FDA) and that is why it costs $0.8 B - $1.2 B to bring a new drug to market. Not true! Most of the cost is the infrastructure and overhead cost of PhRMA that stems in a large part from the failure rate of new drug candidates. Only 1:1,000 new molecular entities makes it market! Moreover, the ones that do are not curative of the diseases target and only allow the patient to live with the disease. What PhRMA company wants to erode its market by curing the disease? As long as this is the focus then the trend of living longer less healthy lives will continue and the cost of health care will continue to spiral upwards.

So as to Innovation, well don't look to PhRMA on that one for reasons I just mentioned. What about Universities? Traditionally, university research laboratories were the caldron of innovation. Not so much today. The problem is funding research. In order to survive an university investigator must get grants (primarily NIH for medical research). In order to get a grant the application must be scored favorably for funding. In order to get scored favorably the researcher must propose something that his peers can readily comprehend and believe that can be accomplished. In other words the NIH is in the business of picking winners and losers. The smart researcher will therefore propose something that is simple, comprehensible extension of that which is already known. I liken this to proposing to extend the known value of Pi by one decimal place. Not exactly transformative research. Unfortunately that is exactly what is needed in medical research. A good read of the trials and tribulations of pioneers in cancer research is Catching Cancer by Claudia Cornwall.

But even if the researcher overcomes the research funding hurdle the worst is yet to come - the discovery must now cross the "Valley of Death". Aptly named because no one wants to take the risk of developing a discovery through the maze of transforming the discovery into a drug candidate. Yep, even if the discovery negotiates the Valley of Death it still is only a drug candidate and has yet to go through human testing in clinical trials (Phases I, IIa/IIb, and III) and await final FDA approval.

The whole process kinda reminds me of SF selection. Fortunately some of us are willing to follow this path. Not for personal glory, but because the mission is just that damned important! :lifter

Doczilla
07-13-2013, 13:29
I'll respectfully disagree about drug development being a key issue here, though I completely agree with you that health care costs are a huge driver of national debt, that chronic conditions drive those costs, and that it is economically unsustainable. These chronic health conditions are directly a result of inactivity and obesity. Looking at the national map, there is a direct correlation between shorter average life span and the above issues. We know this to be true medically, and patients who successfully make lifestyle changes like losing weight, increasing exercise, and quitting smoking, see significant improvements in their health issues such as hypertension, type 2 diabetes, and cardiovascular disease.

50% of personal bankruptcies in this country are due to health care costs. Fixing health care costs, to the consumer and the society, is VITAL to the economic survival of our nation.

The great advances in life span in this country were never about advances in medical treatment. They came about because of clean water, clean food, wider availability of good food for good nutrition, and decreased infant mortality.

100 years ago, the average life expectancy for males and females were 50 and 55, respectively. That's not a terribly fair comparison because of the infant mortality rate. With vaccines, the infant mortality plummeted. A better way of looking at it is what the life expectancy was/is of a child that reaches age 5. This has also been increasing, as evidenced by the fact that a 5 year old in 1850 could expect to live to about 55, whereas today he can expect to live to nearly 70. Taking out those who died in childhood and before age 40, between 1850 and 2000 the average male gained about 10 years in life expectancy, and women even more.

I don't mean to downplay the many benefits of medications which decrease mortality and lengthen life and improve quality of that life. However, the number needed to treat to bring about 1 improved outcome with these medications for hypertension, hyperlipidemia, CAD, DM, etc. is usually in the hundreds (meaning you need to treat hundreds of patients before you prevent 1 bad outcome). Ultimately, these drugs are trying to slow an avalanche that started years before. They may delay it some, but the chance to really intervene is before these problems develop.

The problems that need to be fixed are cultural. There is no pill or surgery that will correct the root cause of these medical issues. People have to want not to be overweight, they must want to be fit, they must want to live healthy, if any shift is going to take place. As long as they keep packing on the pounds without caring enough to limit their portions, they will still get fat, hypertensive, diabetic, and miserable. Looking at the map of the US, there are regional variations in life expectancy, hypertension, and obesity, which further strengthens the belief that these are cultural and ingrained, as there are regional variations in our culture. If not, there would be no "hush puppy belt", and these problems would be scattered more randomly over the map. The encouraging thing is that in a relatively short time span (1 generation), we've slid down this slope, so it is one that may be reversed in such a short span as well.

'zilla

Gypsy
07-13-2013, 20:02
I People have to want not to be overweight, they must want to be fit, they must want to live healthy, if any shift is going to take place. As long as they keep packing on the pounds without caring enough to limit their portions, they will still get fat, hypertensive, diabetic, and miserable.

'zilla

It's also about what people are consuming, not just portions. Fast foods, canned foods, prepackaged foods...none of it is healthy for anyone if that is the constant intake. Hell, non-fat items generally have other "flavor enhancing" crap in them and can be worse than eating the full fat item.

I spent most of the day reading one report after another about all the additives, antibiotics, GMOs and basic trash that is in our food and it is disgusting.

If I cannot pronounce it, I don't eat it. I've been trying to stick with local growers, producers and/or organic whenever possible.

JHD
07-14-2013, 05:55
It's also about what people are consuming, not just portions. Fast foods, canned foods, prepackaged foods...none of it is healthy for anyone if that is the constant intake. Hell, non-fat items generally have other "flavor enhancing" crap in them and can be worse than eating the full fat item.

I spent most of the day reading one report after another about all the additives, antibiotics, GMOs and basic trash that is in our food and it is disgusting.

If I cannot pronounce it, I don't eat it. I've been trying to stick with local growers, producers and/or organic whenever possible.

Ditto. And even though I can pronounce high fructose corn syrup and hydrogenated, those foods should be avoided as well.

Also, the highest cost diseases to cure and treat include those not just caused by obesity, but smoking as well (cancer, heart disease, emphysema, etc.) I am not attempting to step on anyone's rights here, but when does my obligation as a taxpayer to pay for healthcare costs to all those who choose to live less than a healthy lifestyle get a little relief?

The_Mentalist
07-14-2013, 06:22
It's also about what people are consuming, not just portions. Fast foods, canned foods, prepackaged foods...none of it is healthy for anyone if that is the constant intake. Hell, non-fat items generally have other "flavor enhancing" crap in them and can be worse than eating the full fat item.

I spent most of the day reading one report after another about all the additives, antibiotics, GMOs and basic trash that is in our food and it is disgusting.

If I cannot pronounce it, I don't eat it. I've been trying to stick with local growers, producers and/or organic whenever possible.
Pre packaged is not necessarily a bad thing. Flash frozen vegetables for example have no additives. Canned foods, on the other hand tend to have them. Processed foods like microwave meals, packaged meals etc are not a good thing. Burger joints are a major contributor to obesity. I remember when a Big Mac or Whopper really were large sandwiches. Today, they are on the smaller side. Most of the time when I do (on rare occasion) get a fast food burger, I rarely eat the entire burger. I tend toward the "99 cent" burger because of size.

Another issue is our own FDA tampering with foods. For years they told us to use margarine instead of butter. Now it is stay away from hydrogenated oils and polyunsaturated fats. Well, what are Driscoll and margarine? Our bodies are attuned to natural fats and process those well. Artificial fats are not processed and are stored. Also, "low fat" items like milk cause the body to believe it is being shorted on fats. A certain amount of fat is required by the body. So, it will hoard what natural fats it gets. Whole milk is healthier than low fat milk. If we return to natural fats and unprocessed foods, we will make giant strides to improving our health.

Example. Obesity is rampant among the Native American tribes and Central American immigrants. They have switched their diets from natural foods to "American" processed foods and are showing the side effects of that to a greater extent because their bodies have not had multiple generations working toward our dietary habits. Our bodies may learn to eventually adjust to the new diets, but I see a lot more damage happening long before I see an improvement.

PRB
07-14-2013, 09:15
Nice pics of early WW2 Stateside....focus on the civvy crowds and what do you notice

http://warbirdinformationexchange.org/phpBB3/viewtopic.php?f=3&t=49758ee

Trapper John
07-14-2013, 09:38
Doczilla,
Thanks for your post. You are absolutely correct wrt the effect of environmental and cultural factors on the epidemic of chronic diseases related to obesity in particular. No question that this trend needs to be reversed. But this is not simply a matter of personal choices - availability of and affordable access to healthy food is a major problem. High fructose corn syrup, high sodium content, and low levels of antibiotics in processed foods are a major contributing factor. But the diseases (with the exception of atherosclerosis) were not what I had in mind. I should have made that clear.

What I was referring to do were the neurodegenerative diseases, the so called auto immune diseases (a misnomer IMO) like SLE, RA, etc., inflammatory bowel disease (Chron's), fibrotic diseases (COPD, Scleroderma, NASH), asthma, cancer. (I can go on but you get the point).

My thinking wrt to these diseases is that we are looking at them in the wrong way-we look at them as they manifest themselves in clinic, study them in that silo, and miss the bigger picture. When viewed at the molecular biology level a surprising observation comes to light - these diseases have a common protein that is dysregulated and that is the inflammasome. Inflammasomal dysregulation comes about as a result of a chronic injurious event (infection, hyperglycemia, hypoxia, environmental factor, etc.). Depending upon the tissue that is injured/infected disease manifests as you see it clinically. You see cancer and SLE as two different diseases, I see them as the same disease just different manifestations.

Let's take cancer as an example. I think that you would probably agree with the current thinking that each cancer is a unique disease to be managed - not cured. The treatment regimen is tailored to the particular patient, the particular cancer and will often involve surgical excision of the primary tumor followed by radiation treatment and chemotherapy both of which are designed to kill the cancerous tissue and hopefully provide a 5-year survival for the patient. The mantra is "once a cancer, always a cancer". I recall a similar mantra for ulcers and we both know that is no longer true thanks to Barry Marshall and Robin Warren.

We now know for certain that some cancers are caused by chronic infections (HPV-cervical cancer, HBV-liver cancer, H.pylori-gastric cancer, EBV-lymphoma). I know that the pro-oncogenic state is driven by inflammasome dysregulation. My hypothesis is that many, if not most, cancers have a chronic infectious etiology. If that is the case, then pharmaceutical intervention to override the pathogen dysregulation of the inflammasome will restore the innate cellular response to clear the pathogen and hence the cancer.

To test this hypothesis we treated three dogs in a pilot study with our experimental drug (an inflammasome regulator). This study was with 3 different cancers (osteosarcoma, rectal carcinoma, and lymphoma). After a 4-week course (2 treatments per week) the rectal carcinoma and the lymphoma became sterile suppurative abscesses, were treated with antibiotics (prophylactic) and surgically drained. No evidence of the cancer in either. As to the osteosarcoma, the drug had no effect. I think this was because we couldn't get drug into this poorly perfused tumor. The dogs leg was amputated and we gave a 2-week course of our drug to scavenge any metastatic cells. We are following this patient to see if there is recurrence elsewhere. We are now expanding this study to include 15 dogs with either hemangiosarcoma or lymphoma and cats with oral SCC. We are publishing the results of the pilot study and I will post it in a few weeks when its published.

As a side note, about 18 months ago I treated a 2cm fibroma on my Lab's right forepaw that she had for over a year. Same result - suppuration and gone. She has had no recurrence in 18 months. Also, the dogs in our pilot study had received aggressive chemotherapy with multiple agents for the disease with no effect. All dogs were off chemo for 1 month prior to our treatment.

Sorry for the length of this post, but I wanted to illustrate my point - we need to be thinking about diseases differently, not as they manifest themselves, but at the most basic level of molecular biology.

When we reach the stage of treating human diseases you can thank me and say you heard it here first. :D

Trapper John
07-14-2013, 09:42
Nice pics of early WW2 Stateside....focus on the civvy crowds and what do you notice

http://warbirdinformationexchange.org/phpBB3/viewtopic.php?f=3&t=49758ee

Yep, before the days of HFC and processed food.

But, which one was you in the Pic of the troops? :D

JHD
07-14-2013, 09:48
Yep, before the days of HFC and processed food.

But, which one was you in the Pic of the troops? :D

And before the loss of good manners and deportment.

MR2
07-14-2013, 09:59
Great word! One that has gone into disuse along with its meaning.


de·port·ment [dih-pawrt-muhnt, -pohrt-]
noun
1. demeanor; conduct; behavior.
2. the conduct or obedience of a child in school, as graded by a teacher.

Gypsy
07-14-2013, 12:33
Pre packaged is not necessarily a bad thing. Flash frozen vegetables for example have no additives. Canned foods, on the other hand tend to have them. Processed foods like microwave meals, packaged meals etc are not a good thing. .


Good catch, I actually meant to include the word "processed" in front of prepackaged foods...agree on the flash frozen veggies and fruits.