MEDICINES THAT BACKFIRE

Investigating Disease Patterns Through Epidemiology

Introduction

• Unfortunately, physicians sometimes induce disease in their efforts to cure it. Some drugs, diagnostic tests, and therapies can inadvertently cause disease and health problems. Diseases of these origins are referred to as “iatrogenic.” The word iatrogenic comes from the Greek words “iatros,” meaning healer or physician and “gennan,” meaning as a product of – hence, physician-induced disease. The principles of epidemiology have been applied to investigate these unfortunate relationships and provide insight into iatrogenic illnesses. Patterns of iatrogenic disease usually reveal not error but ignorance. Doctors were simply unaware of the potential side effects or consequences of seemingly helpful procedures and therapies.

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Early Example of Iatrogenic Disease

• Mid-19th century – Physician Ignaz Semmelweis noted instance of puerperal fever (fever associated with childbirth) was lower in poor patients than rich.

• Rich women received more supervised care.– Doctors spreading the infection from patient to patient

• Handwashing diminished death rates from infection in obstetrical cases.

• Semmelweis’ work anticipated Pasteur’s germ theory and Lister’s work on antisepsis.

Areas for Investigation

• Radiation

• Medications

• Over-the-Counter Drugs

Radiation and Leukemia

• X-ray imaging introduced to medicine in early 20th century

• Dangers of ionizing radiation were not recognized

• Radiologists placed hands and body in path of radiation

Connections between Radiation and Leukemia

• Long-term cohort study conducted at Johns Hopkins School of Public Health revealed: – Radiologists had higher rates of leukemia than

their counterparts in specialties where they were exposure to radiation was minimal

• Experimental studies with animals went on to demonstrate that ionizing radiation can initiate leukemia.

• Long-term cohort study conducted at Johns Hopkins School of Public Health revealed: – Radiologists had higher rates of leukemia than

their counterparts in specialties where they were exposure to radiation was minimal

• Experimental studies with animals went on to demonstrate that ionizing radiation can initiate leukemia.

Implications

• X-RAYS ARE NOW DEPLOYED IN THE LOWEST DOSES POSSIBLE

• SHIELDING PRECAUTIONS ARE THOROUGH

• CURRENT RESEARCH CONTINUES TO INVESTIGATE THE LONG-TERM RISK OF SCREENING TESTS SUCH AS THE MAMMOGRAM.

Some Important Epidemics Caused by Drug Therapies

Medications and Disease• Disease Linked to Adverse Drug

Reactions– Nebulizers containing isoproternol

• Linked to death in asthmatics

– Supplements of DES (diethylstilbestrol) for pregnant women with threatened miscarriage• Linked to vaginal cancer in adolescent girls

– Unopposed estrogen used for hormone replacement• Linked to uterine cancer in women

DES and Ovarian Cancer

• In the 1950s, diethylstilbestrol (DES) was given to pegnant women who were blieved at risk for miscarriage– Peak usage estimated as high as fiften percent of

prenant women • I958 randomized clinical trial (Universty of

Chicago), pregant women received DES or an inert placebo– No benefit shown in the prevetion of miscarriage

DES and Ovarian Cancer

• In the 1970s, a significant number of cases of vaginal cancer were reported

• A case-control study (Herbst, Ulfeder, Poskanzer – 1971) found that 7 out of 8 cases of vaginal cancer had been exposed to DES in utero.

• Connection confirmed by animal studies and a larger case control study.– New York State Tumor Registry confirmed more than

600 cases of vaginal cancer were linked to prenatal DES exposure

Over-the-Counter Drugs and Disease

• Although these illnesses are not strictly iatrogenic, epidemiological studies can be used to investigate illnesses arising from self-medication– Example: Natural food supplement containing

amino acid L-tryptophan

Over-the-Counter Drugs and Disease

• Cluster of individuals presented with:– Severe muscle aches– Skin rashes– Neurologic symptoms– Eosinophilia (increase in white blood cells)

• Most patients were young or middle-aged women

• Disease was sudden onset, clustering in time (late 1989) and place (New Mexico)

Cases of this disease appeared in late 1989, with the majority of the cases appearing in September and October. Doctors struggled to identify this bizarre new illness as well as determine the contributing factors to the development of disease. Doctors began to associate the appearance of disease with exposure to specific over-the-counter medications.

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Over-the-Counter Drugs and Disease• Physicians reviewed drug records

– Most women reported use of natural product for depression and insomnia

• Link confirmed by a case-control study– All cases had ingested L-tryptophan pills

• Epidemic of this disease, eosinophilia mylagia syndrome (EMS), traced to a single Japanese manufacturer

Conclusions

• Most advanced industrial nations have strict laws to ensure safety and efficacy of both prescription and OTC drugs.– Does the medication do what it is supposed to?– Does the medication have harmful side effects?

• Epidemiologic surveillance of drugs and other therapies provides a safeguard for doctors and patients.

References

• Stolley, D. Lasky, T. 1995. Investigating Disease Patterns: The Science of Epidemiology. New York: W.H. Freeman and Company.

2. Gordis. L. 2008. Epidemiology. Philadelphia, PA. W.B. Saunders Company.

Questions?

THE END!!!