How We Do Harm (41 page)

CHAPTER 9

There is a significant academic literature on the practice of medicine in the ER and especially decision-making by residents.
Many patients use the ER as a place for social interaction.
For the doctor, the hardest decision is when to admit.
See J.
M.
Pines, B.
R.
Asplin, A.
H.
Kaji, R.
A.
Lowe, D.
J.
Magid, M.
Raven, E.
J.
Weber, and D.
M.
Yealy, “Frequent users of emergency department services: Gaps in knowledge and a proposed research agenda,”
Academic Emergency Medicine
18, no.
6 (June 2011): e64–69, doi:10.1111/j.1553-2712.2011.01086.x; L.
B.
Mellick, D.
van Staen, and R.
Perkin, “The role of emergency medicine in a teaching hospital: Decision making in an uncontrolled environment,”
American Journal of Emergency Medicine
11 (1993): 187; and M.
C.
Raven, J.
C.
Billings, L.
R.
Goldfrank, E.
D.
Manheimer, and M.
N.
Gourevitch, “Medicaid patients at high risk for frequent hospital admission: Real-time identification and remediable risks,”
Journal of Urban Health
86, no.
2 (March 2009): 230–41 (epub, December 12, 2008).

CHAPTERS 10 AND 11

For an overview of the Bakke case and the issue of affirmative action, see Howard Ball,
The Bakke Case: Race, Education, and Affirmative Action
(Lawrence: University Press of Kansas, 2000).

The acceptance of the end of life is difficult for the family and the patient: “The practice of universal presumed consent to CPR is often questioned but still in place,”
American Journal of Bioethics
10, no.
1 (January 2010): 61–67; J.
P.
Bishop, K.
B.
Brothers, J.
E.
Perry, and A.
Ahmad, “Reviving the conversation around CPR/DNR.
End of life care,”
Journal of the American Medical Association
286, no.
11 (September 19, 2001): 1349–55; and N.
G.
Levinsky, W.
Yu, A.
Ash, M.
Moskowitz, G.
Gazelle, O.
Saynina, and E.
J.
Emanuel, “Influence of age on Medicare expenditures and medical care in the last year of life,”
Journal of the American Medical Association
286, no.
11 (2001): 1349–55; and A.
E.
Barnato, C.
C.
Chang, M.
H.
Farrell, J.
R.
Lave, M.
S.
Roberts, and D.
C.
Angus, “Is survival better at hospitals with higher ‘end-of-life’ treatment intensity?”.
Medical Care
48, no.
2 (February 2010): 125–32.

The data suggest that many doctors do not understand the limits of our abilities, and intensity of and cost of care at the end of life can vary significantly: L.
R.
Shugarman, S.
L.
Decker, and A.
Bercovitz, “Demographic and social characteristics and spending at the end of life,”
Journal of Pain and Symptom Management
38, no.
1 (July 2009): 15–26.

Doctors are affected by what happens to their patients and what they do to patients.
Most doctors do not discuss this.
James S.
Kennedy, MD, did discuss this issue in his article “Physicians’ feelings about themselves and their patients,”
Journal of the American Medical Association
287 (2002): 1113–14.

CHAPTER 13

The profession of medical oncology and the National Cancer Institute were shaped by the National Cancer Act of 1971 (P.L.
92-218) signed by President Richard M.
Nixon on December 23, 1971.
It created many of the powers and authorities of the present-day National Cancer Institute.

CHAPTERS 14 TO 16

Informed consent
was a term from the late 1950s: C.
K.
Daugherty, D.
M.
Banik, L.
Janish, amd M.
J.
Ratain, “Quantitative analysis of ethical issues in phase I trials: A survey interview of 144 advanced cancer patients,”
IRB
22, no.
3 (May–June 2000): 6–14; and C.
K.
Daugherty, “Informed consent, the cancer patient, and phase I clinical trials,”
Cancer Treatment and Research
102 (2000): 77–89.

It is well established that doctors and patients put too much hope in clinical trials: K.
P.
Weinfurt, D.
M.
Seils, J.
P.
Tzeng, K.
L.
Compton, D.
P.
Sulmasy, A.
B.
Astrow, N.
A.
Solarino, K.
A.
Schulman, and N.
J.
Meropol, “Expectations of benefit in early-phase clinical trials: Implications for assessing the adequacy of informed consent,”
Medical Decision Making
28, no.
4 (July–August 2008): 575–81 (epub, March 31, 2008); and D.
P.
Sulmasy, A.
B.
Astrow, M.
K.
He, D.
M.
Seils, N.
J.
Meropol, E.
Micco, and K.
P.
Weinfurt, “The culture of faith and hope: Patients’ justifications for their high estimations of expected therapeutic benefit when enrolling in early phase oncology trials,”
Cancer Journal
116, no.
15 (August 1, 2010): 3702–11.

The “flutamide withdrawal” phenomenon (Snuffy Myers really discovered it, but he did not realize he had discovered it.
He attributed the positive response to the administration of the experimental drug suramin) was first published in W.
K.
Kelly and H.
I.
Scher, “Prostate specific antigen decline after antiandrogen withdrawal: The flutamide withdrawal syndrome,”
Journal of Urology
149, no.
3 (March 1993): 607–9.

The study that showed suramin was not useful in the treatment of prostate cancer was E.
J.
Small, S.
Halabi, M.
J.
Ratain, et al., “Randomized study of three different doses of suramin administered with a fixed dosing schedule in patients with advanced prostate cancer: Results of intergroup 0159, cancer and leukemia group B 9480,”
Journal of Clinical Oncology
20, no.
16 (August 15, 2002): 3369–75.

A summary of the Food and Drug Administration Oncologic Drug Advisory Committee’s review of suramin for prostate cancer was reported in
Oncology News International
7, no.
10 (1998).

A wonderful discussion of the early NCI is in John Laszlo,
The Cure of Childhood Leukemia: Into the Age of Miracles
(Piscataway, NJ: Rutgers University Press, 1996).

CHAPTER 17

The quality of surgery is extremely important in the treatment of colon cancer: S.
R.
Steele, S.
L.
Chen, A.
Stojadinovic, A.
Nissan, K.
Zhu, G.
E.
Peoples, and A.
Bilchik, “The impact of age on quality measure adherence in colon cancer
,”
Journal of the American College of Surgeons
213, no.
1 (July 2011): 95–103; discussion, 104–5 (epub, May 20, 2011).

A good review of what is known, what is not known, and what is believed regarding chemotherapy after surgical removal of all known colon cancer is H.
C.
Moore and D.
G.
Haller, “Adjuvant therapy of colon cancer,”
Seminars in Oncology
26, no.
5 (1999): 545.

The trial looking specifically at Stage II disease (keep in mind that the patient had an even better prognosis Stage I): W.
Schippinger, H.
Samonigg, R.
Schaberl-Moser, et al., Austrian Breast and Colorectal Cancer Study Group, “A prospective randomised phase III trial of adjuvant chemotherapy with 5-fluorouracil and leucovorin in patients with stage II colon cancer,”
British Journal of Cancer
97, no.
8 (2007): 1021.

A review of leukemias and blood diseases caused by cancer chemotherapy is in L.
A.
Godley and R.
A.
Larson, “Therapy-related myeloid leukemia,”
Seminars in Oncology
35 (2008): 418.

Colon cancer chemotherapy poses significant neurological and other quality-of-life issues, as discussed in I.
Chau, A.
R.
Norman, D.
Cunningham, et al., “Longitudinal quality of life and quality adjusted survival in a randomised controlled trial comparing six months of bolus fluorouracil/leucovorin vs.
twelve weeks of protracted venous infusion fluorouracil as adjuvant chemotherapy for colorectal cancer,”
European Journal of Cancer
41, no.
11 (2005): 1551; and S.
R.
Land, J.
A.
Kopec, R.
S.
Cecchini, et al., “Neurotoxicity from oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: NSABP C-07,”
Journal of Clinical Oncology
25, no.
16 (2007): 2205.

CHAPTER 18

Gonadotropin-releasing hormone (GnRH) agonists such as leuprolide and Zoladex are used in the treatment of metastatic prostate cancer.
The American Society of Clinical Oncology has established guidelines to define their appropriate use: D.
A.
Loblaw, K.
S.
Virgo, R.
Nam, et al., “Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2006 update of an American Society of Clinical Oncology practice guideline,”
Journal of Clinical Oncology
25 (2007): 1596.

In a well-done study, the high reimbursement for androgen deprivation therapy seems to be correlated with overuse and misuse of the drugs.
Lowering physician reimbursement seemed to be correlated with less misuse of these drugs: V.
B.
Shahinian, Y.
F.
Kuo, and S.
M.
Gilbert, “Reimbursement policy and androgen-deprivation therapy for prostate cancer,”
New England Journal of Medicine
363, no.
19 (November 4, 2010): 1822–32.

This is a classic paper on the use of diethylstilbestrol in prostate cancer: D.
P.
Byar and D.
K.
Corle, “Hormone therapy for prostate cancer: Results of the Veterans Administration Cooperative Urological Research Group studies,” NCI Monograph, 1988; and D.
P.
Byar, “Proceedings: The Veterans Administration Cooperative Urological Research Group’s studies of cancer of the prostate,”
Cancer Journal
32, no.
5 (1973): 1126.

Prilosec sales reached their peak globally in 2000, reaching $6.1 billion, accounting for 35 percent of all product sales in this drug class:
http://www.panopharma.com/world_pharma_sales_2000.htm
.
Sales remained constant in 2001:
http://www.panopharma.com/world_pharma_sales_2001.htm
.
By 2002, Prilosec sales dropped to $5.2 billion worldwide, as a result of competition and AstraZeneca’s promotion of its follow-up product, Nexium (esomeprazole):
http://www.panopharma.com/
world_pharma_sales_2002.htm.
By 2005, both Prilosec and omeprazole were among the top-one-hundred-selling drugs in the United States, with AstraZeneca’s follow-on isomeric replacement, Nexium, in the top thirty:
http://www.rxlist.com/script/main
/art.asp?articlekey=79509.
By 2007, Nexium was the second-largest-selling drug in the United States, with sales of $4.355 billion; prescription Prilosec still accounted for another $174 million in sales (the 171
^st
-largest-selling product):
http://www.drugs.com/top200.html
.
By 2007, generic omeprazole was the twenty-fourth-most-prescribed drug in the United States, and the tenth-largest-selling generic pharmaceutical product, with sales of more than $835 million, a 30 percent increase over 2006:
http://drugtopics.modernmedicine.com/drugtopics/data/articlestandard//drugtopics/072008/491181/article.pdf
; and
http://drugtopics.modernmedicine.com/drugtopics/data/articlestandard//drugtopics/102008/500218/article.pdf
.

The development of Nexium as a successor to Prilosec was reported on by Malcolm Gladwell, “High Prices: How to Think about Prescription Drugs,”
New Yorker,
October 25, 2004.
The trials that made us appreciate that most nonsteroidal anti-inflammatory drugs and especially rofecoxib (Vioxx) and celecoxib (Celebrex) increased risk of heart attack and stroke were J.
A.
Baron, R.
S.
Sandler, R.
S.
Bresalier, et al., APPROVe Trial Investigators, “A randomized trial of rofecoxib for the chemoprevention of colorectal adenomas,”
Gastroenterology
131, no.
6 (December 2006): 1674–82; and S.
D.
Solomon, J.
J.
V.
McMurray, M.
A.
Pfeffer, et al., for the Adenoma Prevention with Celecoxib (APC) Study Investigators, “Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention,”
New England Journal of Medicine
352 (2005): 1071–80.

Estimated risk of radiation-induced cancer due to medical radiation varies.
Some estimate that that 1 percent of all cancers in the United States are due to diagnostic radiation: J.
Hall and D.
J.
Brenner, “Cancer risks after radiation exposure in middle age,”
Journal of the National Cancer Institute
102, no.
21 (2010): 1628; and A.
J.
Einstein, M.
J.
Henzlova, and S.
Rajagopalan, “Estimating risk of cancer associated with radiation exposure from 64-slice computed tomography coronary angiography,” Journal of the American Medical Association 298, no.
3 (2007): 317.

Despite its popularity, robotic surgery has not been proven superior to conventional surgery in the surgeries for which it is most commonly used: A.
Mottrie, G.
De Naeyer, G.
Novara, and V.
Ficarra, “Robotic radical prostatectomy: A critical analysis of the impact on cancer control,”
Current Opinion in Urology
21, no.
3 (May 2011): 179–84; and M.
A.
Orvieto, G.
J.
Decastro, Q.
D.
Trinh, C.
Jeldres, M.
H.
Katz, V.
R.
Patel, and K.
C.
Zorn, “Oncological and functional outcomes after robot-assisted radical cystectomy: Critical review of current status,”
Urology,
September 2, 2011.

A discussion of the limited scientific data to support for the use of IMRT: M.
T.
Guerrero Urbano and C.
M.
Nutting, “Clinical use of intensity-modulated radiotherapy: Part II,”
British Journal of Radiology
77, no.
915 (2004): 177.