references and links to further reading

Links to References

from Chapter 1

1. Exodus, chapters 19-31 from the Bible.

2. Although the principle likely pre-dated the man to whom we ascribe it, the history of Occam's (also spelled Ockham's) razor and its namesake are discussed at length in the Encyclopædia Britannica and Wikipedia.

3. Two studies by the same group of investigators reviewed the prevalence of abnormal findings in MRIs of the spine in the neck and the lower back of adults without any related complaints.

The first study identified disc abnormalities in 25 percent of the necks of individuals under forty who were scanned and in 60 percent of individuals over forty. Major abnormalities were found in 19 percent.

The second study showed there was degeneration or bulging of a disc at one lumbar level in 35 per cent of the subjects between twenty and thirty-nine years old and in all but one of the sixty to eighty-year-old subjects.

4. The Health Insurance Plan (HIP) of New York trial was the first major study of mammography. It began in 1963 and offered annual mammography to women between 40 year and 64 years old. It showed a reduction in death from breast cancer by 23-24 percent for all ages screened, but only detected breast cancer by mammography in 6 study patients under 50. Some analyses have found this statistically significant. Others have not. Here is one analysis that found a benefit.

The Malmö trial invited 21 thousand women over age 45 to screening and followed another 21 thousand in a control group. As a whole, it showed no difference between groups. Five screenings over a decade were performed. The under-55 age group saw a 29 percent increase in death from breast cancer. The over-55 age group saw a 20 percent decrease in death from breast cancer.

The Two County trial enrolled 133 thousand women from two adjacent counties in Sweden. Multiple reports have come from these parallel cohort studies, with later results at long-term follow-up maintaining the benefit seen early on at a reduction of about 31 percent in deaths from breast cancer. 1985, 1989, 2011.

The Edinburgh trial enrolled 44 thousand women and found a not statistically significant reduction of breast cancer mortality of 17 percent overall, but a significant reduction of 20 percent in patients over 50.

The Stockholm trial also found a non-significant reduction of 26 percent in breast cancer mortality overall, but 38 percent significant reduction for women over 50. Women 40 to 49 years old had a non-significant increase in breast cancer mortality of 8 percent.

The Gothenburg trial, a later trial, showed decreased mortality in a young population.

The Canadian trial, which is considered the most rigorously designed trial, including a control group of patients that undergoes regular clinical examinations, just not mammography, found no added benefit of mammography itself. It was reported in two papers, for two different age groups: women in their forties and fifties.

The medical literature has numerous opinion papers written on this subject. In one of the most often cited, the investigators have rigorously evaluated the quality of the trial designs for each of the above studies, ultimately finding only the Malmö and the Canadian trials as have adequate randomization and control groups, as well as optimal detection and follow-up of cases. They actually conclude that mammography of any kind isn't justified, let alone that for the younger age populations.

from Chapter 2

1. A number of studies have investigated the sensitivity (ability to detect as positive truly positive cases) and specificity (ability to detect as negative truly negative cases) of the rapid strep test.
This study found the rapid strep test 81 percent sensitive and 97 percent specific, compared to throat culture as a gold standard.

2. This article offers a review of the diagnostic criteria for Marfan syndrome that began with completely clinical findings.

Medical genetics specialists refer to the criteria for diagnosis of Marfan syndrome in this paper as the "Berlin nosology," because they were discussed and agreed upon at an international conference focused on diagnostic criteria for a inherited diseases, which took place in Berlin.

The next round of internationally agreed upon diagnostic criteria for Marfan syndrome followed a meeting in Ghent, Belgium. These criteria are referred to as the "Ghent nosology." Importantly, these criteria added dural ectasia, a specific finding in the spine to the prior criteria.

This paper documents the impact of the two different sets of diagnostic criteria on a population of patients under treatment for Marfan syndrome. Almost a quarter of the patients wouldn't have been diagnosed using the Berlin criteria, but were from the Ghent criteria, because of the addition of the spine findings.

Another version of the Ghent criteria has recently been published.

3. Dr. James Ewing described the tumor that would eventually bear his name in 1921.

Another study marked the beginning of the shift toward defining Ewing sarcoma by its staining with CD99 immunohistochemistry.

This paper first identified the chromosomal translocation in Ewing tumors from patients.

Then, it was found that most Ewing sarcomas had the specific chromosomal translocation.

A larger series of patients confirmed the translocation in 95% of Ewing sarcoma cases.

This review article discusses the shift in diagnostic strategies from the appearance of tumors under a microscope to the use of specific molecular tests.

This report documents some Ewing sarcomas that don't fit the original diagnostic criteria, but would be treated as Ewing sarcoma today due to molecular test results.

4. The original publication of the SLICED study.

A second study, on the same topic but with different patient samples and a different group of diagnosticians, these from Europe, was published a couple of years later, reporting similar findings.

5. Although John Cameron's emphasis of physician responsibility is admirable, many have investigated the value of CT scans in the setting of possible acute appendicitis since then. Although still controversial, the consensus seems to fall toward favoring CT scans as a means of lowering (definitely not eliminating) the rate of surgical removal of what turn out to be normal appendices. This article reviews the data from a number of studies in a systematic fashion:

6. Three articles report on studies that measured the impact of multi-disciplinary tumor boards on patient care decisions and outcomes.
Gynecologic Cancers
Head and Neck Cancers
and Breast Cancers

7. Two very large studies have been reported, each arguing against the value of PSA screening for men. One is 2008, the other in 2009.

This third study estimates actual rates of overdiagnosis and the specific numerical value of lead-time bias from PSA screening in men.

from Chapter 3

1. In their working paper number 12436 from the National Bureau of Economic Research in 2006, David Autor and Mark Duggan reported that the percentage of the United States population currently supported by Social Security Disability Insurance rose from 2.2 percent in 1985 to 4.1 percent in 2005. The Social Security Administration paid out 85 billion dollars in 2005 to recipients of disability benefits. This comprised 17 percent of its overall spending. This cost ignores the cost of life-long Medicare supported healthcare for those on disability, beginning two years after the designated date of disability.

Worker's compensation is administered through state and private programs rather than federally/publicly run programs like Social Security Disability. The National Academy of Social Insurance in Washington, DC published a report on 26 August 2008 by Ishita Sengupta, Virginia Reno, and john F. Burton, Jr. that calculated 87.6 billion dollars in total cost of United States employers in 2006, with 26.5 billion of that going toward paying health care costs for injured workers and 28.2 billion going toward wage replacement benefits. That adds up to $1.58 out of every $100 spent on workers total.

2. The Waddell signs of incongruity define a psychological component to back pain.

Dr. Waddell published this later paper reviewing some of the psychology behind these "nonorganic" signs of psychological distress.

from Chapter 4

1. Lipitor was the single most prescribed drug in the United States in 2005, with sales upwards of 16 billion that year according to data from IMS Health, Annual Report on prescription drug trends (Feb 20, 2006).

2. A search on PubMed for the term "placebo effect," will render more than 400 hits.
Specific articles of interest include this one from 1955 and this from 2001.

In addition, more than 4000 books on the subject surface from an search. Certainly, many of these hits are different editions of the same books, but even 50 books on the topic would be more than enough for us to take notice, one would think.

3. The original publication of what has later been termed the "VA arthroscopy study."

4. Summary analysis of 36 different trials comparing these different devices for the fixation of what are called extra-capsular hip fractures or intertrochanteric hip fractures.

5. The 1999 report "To Err is Human" from the United States Institute of Medicine.

6. Sickle-cell anemia was first noted in a patient in 1910.

Although the first account described the sickle-shaped red blood cells, the name "sickle cell anemia" came in 1922.

Sickle-cell anemia later became the very first molecular disease in 1949, when Linus Pauling traced the abnormality to a genetic defect in the hemoglobin gene. To put this in perspective, the structure of DNA wasn't even known until 1953, four years later:

7. The two initial publications of the Women's Health Initiative that completely changed the thinking regarding hormone replacement therapy are the following: 2002 report and 2004 report.

8. This review article details the history of the rise of bisphosphonates, initially for use with osteoporosis and then for use in managing cancer metastasis to the bone.

This article reviews the emerging data about the unusual femur shaft fractures following long-term dosing of bisphosphonates.

9. One of the many articles voicing serious questions about the validity of the use of steroids for acute spinal cord injury.

This practice was promulgated by the National Acute Spinal Cord Injury Studies (NASCISs).

10. The following four trials with their spiffy names provided the boom and ultimately the bust for wide-spread use of COX2 selective inhibitors and then company's retraction of rofecoxib (Vioxx).

11. First article reporting measurement of the pump head phenomenon.

Two subsequent articles (first, second) argued that non-operative control groups were just as bad, suggesting that pumphead may be the natural history of patients with heart disease.

Three articles measured the pumphead phenomenon in patients undergoing open heart surgery on or off the bypass pump. The first found that off-pump surgery protected cognition. The second found an improvement only in short-term cognition, which disappeared by a year. The third showed no difference at all.

12. Ernest Amory Codman's story is recorded in a number of venues. A brief biography is available on the New England Shoulder and Elbow Surgeons society page.

from Chapter 5

1. A brief history of Richard C. Johnston's professional life is recorded here.

2. The entire book might have focused on the problem of preventing clot formation in post-operative patients and all the research problems it introduces. This report contains the most recent "evidence-based" guidelines from the American College of Chest Physicians, mandating what surgeons should do to prevent clots.

This article reports a response of surgeons to the character of the data as entirely dependent on surrogates.

3. The large randomized controlled trial that finally confirmed the mortality benefit of aspirin use following a heart attack was called ISIS-2.

Earlier trials had shown no statistically significant difference. 1979, 1977, 1976.

4. Stephen Katz presented at the annual meeting of the American Orthopaedic Association in June 13-16 2007 in Asheville, North Carolina. This article arose from this same symposium, but left out the details of his question to the audience about whether there is any evidence that the orthopaedic community has changed practice from NIH-supported research results.

5. Decision Analysis has been used in many fields of medicine in the last decade. This is the article specifically discussed.

This second decision analysis followed the first article by a couple of years, but generated the exactly opposite conclusion.

Announcement of the 2010 DAS Practice Award by the Decision Analysis Society to the Chevron corporation.

from Chapter 6

1. A number of articles chronicle the history of chemotherapeutic treatments for osteosarcoma. This particular citation is an article published by one of the first practitioners using chemotherapy in this setting.

2. James N. Weinstein organized the 11-center clinical trial called the Spine Patient Outcomes Research Trial (SPORT). Results from this trial have been published in the New England Journal of Medicine and the Journal of the American Medical Association. Its initial design is described here.

Dr. Weinstein has published additional studies on the process of educating patients and enrolling them in randomized clinical trials, and has spoken broadly about the topic, based on his experiences in this trial of operative versus non-operative treatment.

3. Samuel de Sorbiere's book is quoted in translation in the this book about the history of informed consent by Jay Katz.

4. Details of the California 1972 court case Canterbury v. Spence are recorded, along with extracts from the judicial briefs, in this book about the history of informed consent.

5. This particular passage from Whitejacket is in chapter 63.

from Chapter 7

1. The specific study quoted to have reported three of 21 patients surviving to discharge is one of very few articles on the topic of terminal extubation that provides any data beyond opinion, even if it is only observational data.

The only larger study noted 6 patients surviving to hospital discharge after 166 terminal extubations in 15 ICUs in Canada.

The Karen Ann Quinlan story can be read in many textbooks and websites dedicated to the "Right to Die" movement, but is recorded in greatest detail by her parents' book.

2. This report details the case of man who awoke fully and returned home after being declared dead at the end of a session of CPR.

These articles review cases previously reported in the literature of Lazarus syndrome.
First, Second

3. The legend of Aesculapius is recorded in many venues. Some direct references to a mortal physician by this name can be found in Homer's Iliad itself. A few versions of the legend can be found on Wikipedia.

4. The natural history study of scoliosis.

5. None approaches 50-year results, but these papers (first, second, third) report the longest-term outcomes of scoliosis fusion surgery. All are from Sweden.

from Chapter 8

1. This website is dedicated to the biography and writings of John Graunt. It is curated by a historian focused on the Graunt heritage. The website includes images from Graunt's report on the Bills of Mortality.

2. Weiss Ratings 2004 report noted that the Life Insurance industry averages 8.2 percent profit margins.

3. This study from Dartmouth makes clear the massive effects on death by many causes for a population that smokes. So drastic is the impact that the epidemiologists at Dartmouth had to make two separate tables for causes of death among smokers and non-smokers.

4. Health care expenditures in the United States of America as estimated by the Office of the Actuary, The Centers for Medicare and Medicaid services.

5. Although people throw the consideration around liberally in conversation, the actual expenditures during the last two weeks of life have not been the focus of much detailed study to the best of my knowledge. Medicare estimates that nearly a third of its annual costs go toward expenditures during the last year of life, according to an article on 19 October 2006 by Julie Appleby in the USA Today newspaper.

Actual expenditures during the last week of life (much smaller numbers than are actually thrown around routinely in political conversation) have been found to change dependent on conversations have had with their families and physicians about end-of-life issues.

from Chapter 9

1. The Terri Schiavo case has been recorded by many authors and journalists. Most every record has some axe to grind. There are more than 370 books on Amazon that come up from a search of her name alone. The events are also skeletoned on Wikipedia. Most of the dates and details are also available in the public records of the state of Florida.