Much ado about nothing: Too many research, not many results!

Introduction:

That is sad to learn that the world, specially the strongest economies and the most powerful countries on the face of earth, care and spend more on killing their own kinds and each others than caring and spending on their well-being! The U.S. outpaces all other nations in military expenditures. The world military spending totaled more than $1.6 trillion in 2015. The U.S. as we see in the diagram below, accounted for 37% of the total. U.S. military expenditures are roughly the size of the next seven largest military budgets around the world, combined. Interestingly, a third world country, Saudi Arabia, that basically survives on oil resources, and now seems not to have an immediate enemy, such as Iraq in the past, is the third leading country in the world on military spending, even more than England, France, Japan and many other countries! (1)

 The military spending of the united states swallows more than half (54%) of this country’s total budget, as we see in the diagram below, while science takes only 3%, education and health only 6% each! (2)

While, the health and science portions of the US budget are trivial, the medical research in discovery of new treatments and the well-being of people comprises only a small portion of this skim budget. The NIH (National Institute of Health) of US invests nearly $32.3 billion annually in medical research, more than 80% of this funding goes to the universities and medical schools than the community health centers, the first gates of entry of people into medical arena, seeking help and treatment. As we see in the graph below, more than three times of NIH budget, i.e. $98.3 billions are only spent by the top 10 pharmaceutical companies in US, not on improvement of the people’s health or even drugs research, but on marketing. The amounts spent on sales and marketing are shown in orange, while the amounts spent on research and development are in blue. (3)

Now lets see, how this meager amount of money spent on the health research that is the main focus of this article. Spending less money and efforts by the governments on the health research could be at the first glance, the reason of humans’ failure to overcome common and simple disabling and killing diseases. But probing deeper into the issue, reveals that even the meager health research budget are not spent wisely, and while there are many researches, there are very few discoveries and solutions.

 A search in the archives of NIH (4), where one can find most published health research papers, on “cancer” in general yields to more than 3 million articles, with more than 300,000 on breast cancer, more than 270,000 on lung cancer, and more than 137,000 on prostate cancer, more than 117,000 on Alzheimer’s disease, close to 70,000 on MS (Multiple Sclerosis), more than 220,000 on heart attack, more than 250,000 on stroke, more than 425,000 on hypertension, more than 552,000 on diabetes, more than 350,000 on depression, more than 122,000 on anxiety disorders, more than 121,000 on schizophrenia. Of all the research papers, more than 9 millions are on treatments, and very limited number on prevention of human diseases.

 Too many assumptions and risk factors, a few causes:

Throughout the articles on this website, I have shown that our medical knowledge about the etiology of human diseases are very limited. Other than making assumptions about risk factors related to each disease, we know less about the real causes and pathophysiology of diseases so to do the right treatment, and beyond to do the preventions. For example, there are more than 48,000 study reports on the link between cigarette smoking and different diseases. While I have argued on the article on lung cancer that smoking is not a cause and only a risk factor in susceptible persons with past history of lung infections (5), rarely any studies explains how smoking is a risk factor in lung cancer. The same scenario is true for other risk factors and other diseases that they mention and report about the risk factors, but there are rarely any plausible explanations of the pathophysiology of the link between a risk factor and a disease! So we do not know how exactly for example smoking can get to ovaries and cause ovarian cancer, or how can be a risk factor in autoimmune disorders such as Lupus! (6)

 Since all these studies and reports could not be critiqued here as there are too many, I will focus on a few examples in the following to make the point of argument:         

Screening for identification of a killer cancer:

In 2008 US Preventive Services Task Force (USPSTF) published a screening recommendation for colorectal cancer. (7) This document recommended screening with colonoscopy every 10 years, annual fecal immunochemical test (FIT) , annual high-sensitivity fecal occult blood test (FOBT) , or flexible sigmoidoscopy every 5 years combined with high-sensitivity FOBT every 3 years. Most recently in 2016, the same organization has published its updated recommendations, have found no priority of one screening test over another and has come up with unequivocal manifesto. This time and after 8 years, USPSTF instead of emphasizing specific screening approaches, it has instead chosen to highlight only the importance of screening of colorectal cancer that reduces deaths from the disease among adults aged 50 to 75 years and that not enough adults in the United States are using this effective preventive intervention. The USPSTF mentions the reasons for this gap between evidence and practice are multifaceted and will require sustained effort among clinicians, policy makers, advocates, and patients to overcome. (8)

Unlike USPSTF, many other US medical organizations, have more clear and certain screening recommendations for colorectal cancer as follow:

In 2008, the American Cancer Society, American College of Radiology, and the US Multi-Society Task Force (including the American Gastroenterological Association, American College of Gastroenterology, and American Society for Gastrointestinal Endoscopy) jointly issued recommendations. They prioritized flexible sigmoidoscopy every 5 years, colonoscopy every 10 years, double-contrast barium enema every 5 years, and CT colonography every 5 years as preferred tests “designed to both prevent and detect cancer” if resources are available but also recommended annual high-sensitivity FOBT or FIT-DNA testing (interval uncertain). Shortly thereafter, the American College of Gastroenterology released an independent guideline recommending colonoscopy every 10 years as the single preferred screening strategy. It stated that if colonoscopy is not available or is unacceptable to a patient, recommended alternative strategies include flexible sigmoidoscopy every 5 to 10 years or CT colonography every 5 years (preferred) or annual FIT, annual Hemoccult II SENSA, or FIT-DNA testing every 3 years (acceptable). (9)

 In 2012, the National Comprehensive Cancer Network recommended colonoscopy every 10 years as the preferred screening strategy if available; otherwise, it recommended annual FOBT or FIT, with or without flexible sigmoidoscopy, every 5 years or flexible sigmoidoscopy alone every 5 years as secondary approaches to screening. (10) In 2015, the American College of Physicians recommended that average-risk adults aged 50 to 75 years should be screened for colorectal cancer by 1 of 4 strategies: (1) annual high-sensitivity FOBT or FIT, (2) flexible sigmoidoscopy every 5 years, (3) high-sensitivity FOBT or FIT every 3 years plus flexible sigmoidoscopy every 5 years, or (4) colonoscopy every 10 years. It advised that average-risk adults younger than 50 years, older than 75 years, or with an estimated life expectancy of less than 10 years should not be screened. (11) The American Academy of Family Physicians is in the process of updating its guidelines. In 2016, the Canadian Task Force on Preventive Health Care recommended that adults aged 50 to 59 years (weak recommendation) and 60 to 74 years (strong recommendation) be screened for colorectal cancer with FOBT or FIT every 2 years or flexible sigmoidoscopy every 10 years. It recommended against screening in adults 75 years and older (weak recommendation) and using colonoscopy as a primary screening test (weak recommendation). (12)

 As it has been suggested in a related article on this site (13), after acquiring sufficient knowledge about the pathophysiology of this killer cancer, preventive measures should be the priority on the agenda, and more time, efforts and money spent on the prevention, that often is simply life style and eating habit changes. While most medical agencies and advocates are not certain what screening tool(s) is (are) the best, the management or treatment of the discovered such cancer hold the following potential scenarios:

1.Surgical Resection: of the polyp or tumor in stage 1 & 2, that has not extended or metastasized beyond the regional spot and the wall of large bowel.

2. Chemotherapy: in adjunct with surgical removal of the cancer in stage 3 & 4 where the tumor has metastasized and has involved the lymph nodes or other organs such as liver and lungs.

The identification of cases at the early stages of 1 & 2 obviously carries on high survival rates of up to %90 in 5 years, but the chance of survival is reduced in later stages of advanced cancer. (14) Therefore while general screenings are still of great benefits, more targeted screenings are demanded in order to improve the patients’ adherence and self-referral for screening (as this is still under-utilized by the public even in developed countries such as US), and also increase the positive rate of detection.

The targeted screening other than older age that is followed by the current different screening recommendations, needs to specifically cover all cases of inflammatory bowel diseases such as Crohn’s and ulcerative colitis, and cases with history of severe large bowel infections, as they have the highest risk of developing colon cancer. As discussed elsewhere in a related article on this site (13), “chronic constipation” is a very simple but dangerous symptom, that often is simply treated with laxatives or else, but could be a very high risk factor of colorectal cancer, specially in old age. Long-term constipation, that causes repeated pressure and trauma to the colorectal lumina could damage the colorectal epithelium and colonocytes, cause inflammation and increase the vulnerability to opportunistic infections, hence initiating an oncogenic process. Constipation and laxative use in large sample studies have been shown to increase the risk of colorectal cancer up to 2-3 times, more so in the distal parts of colon and even in younger age groups. (15-16) Therefore more stringent screening in older age group with history of chronic constipation may yield to higher rate of early colorectal cancer detection and improve the overall survival rate, beyond 5 years.

 Risk factors in psychiatric disorders:

Assumptions and link of risk factors to diseases in psychiatry are more, as the etiology and pathophysiology of these disorders are more uncertain. In the past and until the acceptance of many such disorders as dysfunctions of the brain, there were many man-made theories and psychological assumptions trying to explain the causes of these maladies. A common and popular of such assumptions and theories was made by Leo Kanner, who coined the term “autism” in late 40’s that stayed somewhat acceptable and popular even by experts, was the hypothesis of “refrigerating parents” in causation link to autism and schizophrenia. (17) Similar assumptions still exist to this day of biological psychiatry, for example a most recent report in the May issue of American Journal of Psychiatry (18), linking cigarette smoking during pregnancy to causation of schizophrenia. Although smoking can cause inflammation in the different organs of the body or in general beyond the lungs, and during pregnancy in the fetus and its development, such explanation is a rarity and most study reports suffice to stay at the surface of a link, not causal.

On the other side some risk factor link reports are so obvious that one wonders why to bother to waste so much money and time to report the obvious. For example in the May issue of this year, 2016 in the Canadian Journal of Psychiatry (19) , there is a report that healthy individual- and relationship-level factors are associated with better mental health and poverty or lack of such factors are related with poor mental health and the increase incidence of child abuse by parents. Among these factors have been reported, “good coping skills to handle problems and daily demands, and supportive relationships that foster attachment, guidance, reliable alliance, social integration, and reassurance of worth.” that are more among families with “higher education and income and with more physical activities”, that seems to be a common sense, specially among well off families, with no common problems such as poverty, substance abuse, guns and violence.

While after decades and millions of research studies in psychiatry, the causes of many disorders in this arena are not known and the psychiatric diagnostic manual (DSM 5) is still conveniently non-etiological and psychiatric illnesses are diagnosed solely by symptoms counting, the use of psychiatric medications, specially anti-depressants are the second most prescribed and sold of all medications. Treatment with psychiatric medications, while have some scientific basis, to the admission of the top experts, are not sufficient and still in many cases cannot beat placebos. (20) At the same time and with lack of certainty, clarity and explanations, such medications even anti-psychotics are easily prescribed to children even without any history of psychoses, e.g. in ADHD/ADD and the rate is climbing with pride! (21) Hypocritically anti-depressants are used not just in the treatment of depressive disorders, but in psychotic disorders, such as schizophrenia, anxiety disorders or panics, obsessive compulsive disorders (OCD) and more!

 Conclusion:

At this time and era that the governments do not care much about their citizens’ well being and health, if not the people of the world’s, and spend more on deaths than life, at least the scientists and medical experts need to spend the health research budgets more wisely and properly. The bottom line is that we need healthier lives and less diseases, so the first priority needs to be on prevention. Then when the diseases hit us before knowing it, that happens often, we need to identify it as soon as possible and nip it in the bud. To do these two important and vital steps, we need to know the pathophysiology of diseases, so we need to spend more time, effort and thoughts on such discoveries. We need to stop, for example, treating pains with pain killers, that are often narcotic analgesics and not only treat the cause of the pain, but adds addiction and rebound of the pain on withdrawal and so many other complications! We need to throw out almost the whole psychiatric nosology and diagnostic system and labeling out of the window and re-write the mental illnesses, like medical illnesses, by including the etiology or cause within the diagnoses. As we cannot label someone with lung infection as having a generic term of “pneumonia”, but include the cause even within the terminology, e.g. “viral pneumonia”, “streptococcal pneumonia”, etc. we need to stop labeling people with simple label of “depression”, or “anxiety”! The patients have the right to know what type of depression, they suffer from, so to have the right treatment. The term and label of “major depression” is only descriptive and not causal and does not say to the patient anything more than what he or she already knew. Medical research could not be an enterprise and source of profit, or even for the sake of a student to graduate. The result of any medical research needs to be fruitful and gives us something that we did not know and open the path towards better understanding of the pathophysiology of a disease and ultimately its early treatment and prevention. We have a long way to go and on this path, we need to act smart!        

 Dr.Mostafa Showraki, MD, FRCPC                                                                  Lecturer, School of Medicine, University of Toronto,Author: “ADHD:Revisited” Book/ “adhdrevisited.com”/”medicinerevisited.com” 

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